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HoC_1shot800 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: AIM To assess the prognostic significance of nuclear factor-κB ( NF-κB ) and its target genes in gastric cancer . METHODS The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA . Preoperative serum levels of vascular endothelial growth factor ( VEGF ) , interleukin-6 ( IL-6 ) were assessed via enzyme-linked immuno-sorbent assay . C-reactive protein ( CRP ) and serum amyloid A ( SAA ) were measured via immunotrubidimetry . RESULTS Positive rate of NF-κB RelA was 42.6% . NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 ( P = 0.044 ) and CRP ( P = 0.010 ) . IL-6 , SAA , CRP were related to depth of invasion , VEGF and SAA were correlated with lymph node metastasis . IL-6 , VEGF , SAA and CRP were related to the stage . Univariate analysis demonstrated that immunostaining of NF-κB RelA , levels of IL-6 , VEGF , SAA were significantly related with both disease free survival and overall survival ( OS ) . Multivariate analysis verified that NF-κB RelA [ hazard ratio ( HR ) : 3.40 , P = 0.024 ] and SAA ( HR : 3.39 , P = 0.045 ) were independently associated with OS . CONCLUSION Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot801 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The suppression of MAPK and oxidative stress could be an important anti-inflammatory mechanism . Fucoidan regulates MAPK activity in several cell lines . However , the mechanism for the anti-inflammatory and oxidative stress effect of low molecular weight fucoidan ( LMWF ) is poorly understood in RAW264.7 cells . The objective of this study was to examine the critical role of LMWF during LPS-induced inflammation in RAW264.7 cells . To determine the potential role of LMWF , we analysed pro-inflammatory cytokine , transcription factor , inflammation-related and oxidative stress related protein expression in vitro during LPS-induced inflammation in RAW264.7 cells . In this study , we demonstrated the anti-inflammatory effects of LMWF on LPS-induced inflammation in macrophages through the regulation of signalling pathways , including its effect on the attenuation of inflammatory cytokines , such as IL-1β , IL-1 and TNF-α , and the degradation of phosphorylated p38 MAPK , ERK1/2 and JNK . This study also demonstrates that LMWF might block NO as well as the expression of reactive oxygen species ( ROS ) , which subsequently inhibits the iNOS and COX-2 expression induced by LPS . Based on these findings , we suggest that LMWF might have great potential as an external pathogen prevention and intervention agent for inflammatory diseases .
OUTPUT:
| tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot802 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance . Here we report the novel finding that Tph-1 ( tryptophan hydroxylase-1 ) , a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan , is a potent regulator of immunity . In models of skin allograft tolerance , tumor growth , and experimental autoimmune encephalomyelitis , Tph-1 deficiency breaks allograft tolerance , induces tumor remission , and intensifies neuroinflammation , respectively . All of these effects of Tph-1 deficiency are independent of its downstream product serotonin . Because mast cells ( MCs ) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect , these experiments introduce a fundamentally new mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot803 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: This study is to investigate the effects of bortezomib on the angiogenesis of mesenchymal stem cells ( MSCs ) . We examined the effects of bortezomib on the cellular proliferation , migration , and capillary network formation of HUVECs cocultured with CMs of MSCs . We found that Bortezomib inhibited the cellular proliferation and tube formation of HUVECs cocultured with CMs in a dose-dependent fashion . Bortezomib also prevented the migration of HUVECs cocultured with CMs . In addition , bortezomib dose-dependently inhibited the growth of MSCs and prevented the production of angiogenic factors including VEGF ( vascular endothelial growth factor ) , HGF ( hepatocyte growth factor ) , and bFGF ( basic fibroblast growth factor ) in MSCs . In conclusion , bortezomib prevented the angiogenesis mediated by MSCs .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot804 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Retinoic acid ( RA)-induced differentiation therapy is partially successful in neuroblastoma treatment . We found that a novel combination of vanadium-based PTP inhibitors with RA induced extensive differentiation in neuroblastoma cells . In contrast to RA alone , this led to either permanent differentiation or senescence after 14days of combined treatment followed by chemical removal . Senescence was dependent in part on synergistic AKT and ERK activation. p21 was also strongly induced , but in contrast to oncogene-induced senescence , p53 was not activated . Vanadium-based inhibitors thus serve strongly to enhance RA's ability to drive differentiation and a novel form of senescence in neuroblastoma cells .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot805 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Chronic inflammation is a critical component in breast cancer progression . Pro-inflammatory mediators along with growth/survival factors within the tumor microenvironment potentiate the expression of pro-inflammatory cytokines ( IL-1 , IL-6 , TNF-α ) , chemotactic cytokines and their receptors ( CXCR4 , CXCL12 , CXCL8 ) and angiogenic factors ( VEGF ) that often overcome the effect of anti-inflammatory molecules ( IL-4 , IL-10 ) thus evading the host's antitumor immunity . Detailed knowledge , therefore , of the regulatory mechanisms determining cytokine levels is essential to understand the pathogenesis of breast cancer . HIF-1α and NF-κB transcription factors are important players for the establishment of a pro-inflammatory and potentially oncogenic environment . HIF-1α is the key mediator of the cellular response to oxygen deprivation and induces the expression of genes involved in survival and angiogenesis within solid hypoxic tumors . The expression of these genes is often modulated by the p53 tumor suppressor protein that induces apoptosis or cell cycle arrest in neoplastic cells . Functional crosstalk between HIF-1α and p53 pathways mediated by modulators shared between the two transcription factors such as SRC-1 and SIRT-1 differentially regulate the expression of distinct subsets of their target genes under variable stress conditions . In an attempt to shed light on the complex regulatory mechanisms involved in cancer-related inflammation , we investigated the role of the two common p53 and HIF-1α co-regulators SRC-1 and SIRT-1 , in the expression of the highly potent metastatic chemokine receptor CXCR4 . Both SRC-1 and SIRT-1 overexpression in DSFX-treated MCF-7 cells reduced CXCR4 cellular levels implying that both co-regulators are crucial factors in the determination of the metastatic potential of breast cancer cells .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot806 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Given the important role of CXCR4 in cancer metastasis , microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion . Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior . CXCR4 is upregulated in several cancer cells under hypoxic conditions , suggesting a relationship between tumor hypoxia and CXCR4 . However , the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood . KATO III gastric cancer cells were exposed to hypoxia or normoxia . CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry . Wound healing , migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12 , a major CXCR4 ligand . CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATOIII cells following exposure to hypoxia . This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses ( migration and invasion ) to CXCL12 treatment in vitro . The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA . Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner , and that upregulation of CXCR4 plays a role in cancer cell migration and invasion . Thus , disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot807 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Advanced or metastatic prostate cancer is treated by androgen deprivation ; however , patients inevitably relapse with castration-resistant prostate cancer ( CRPC ) . CRPC remains dependent on androgen receptor ( AR ) signaling , which may include constitutive , ligand-independent action of naturally occurring AR splice variants . For example , the AR splice variant AR3 ( also termed AR-V7 ) is expressed in CRPC and is linked to poor prognosis . Vav3 , a Rho GTPase guanine nucleotide exchange factor , is an AR coactivator that is up-regulated in human prostate cancer compared with benign tissue and in preclinical models of CRPC . Vav3 confers castration-resistant growth to androgen-dependent human prostate cancer cells . Despite the importance of AR coactivators in promoting CRPC , the potential role of these regulatory proteins in modulating AR splice variant activity is unknown . We examined the contributions of Vav3 to AR activity in two CRPC cell lines that naturally express relatively high levels of Vav3 and AR3 . Vav3 or AR3 knockdown greatly attenuated cell proliferation , soft agar growth , and ligand-independent AR activity . Vav3 potently enhanced the transcriptional activity of AR3 and another clinically relevant AR splice variant , ARv567es . Vav3 knockdown resulted in lowered nuclear AR3 levels , whereas total AR3 levels remained similar . Conversely , overexpression of Vav3 resulted in increased nuclear AR3 . Coimmunoprecipitation revealed that AR3 and Vav3 interact . These novel data demonstrating physical and functional interactions between Vav3 , a unique AR coactivator , and an AR splice variant provide insights into the mechanisms by which Vav3 exploits and enhances AR signaling in the progression to CRPC .
OUTPUT:
| sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot808 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Tumor cells trigger angiogenesis through overexpression of various angiogenic factors including vascular endothelial growth factor ( VEGF ) and angiopoietin 1 ( Ang1 ) . Therefore , inhibition of the expression of both VEGF and Ang1 , the initial step of tumor angiogenesis , is a promising strategy for cancer chemoprevention and therapy . Grape seed proanthocyanidins ( GSPs ) are widely consumed dietary supplements that have antitumor activity . Due to their polymeric structure , GSPs are poorly absorbed along the gastrointestinal tract and can reach the colon at high concentrations , allowing these chemicals to act as chemopreventive agents for colon cancer . In the present study , we found that GSPs inhibited colon tumor-induced angiogenesis and , thus , the growth of colon tumor xenografts on the chick chorioallantoic membranes . The mechanisms of their action were related to inhibiting the expression of both VEGF and Ang1 through scavenging reactive oxygen species . Previous studies have demonstrated that the chemopreventive effects of GSPs on colon cancer are associated with their growth inhibitory and apoptosis-inducing effects . Our results demonstrate another mechanism by which GSPs inhibit colon tumor growth , which will be helpful for developing GSPs as a pharmacologically safe angiopreventive agent against colorectal cancer .
OUTPUT:
| inducing angiogenesis;tumor promoting inflammation;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot809 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Protein tyrosine kinase 6 ( PTK6 ) is a non-receptor tyrosine kinase expressed in epithelial cancers . Disruption of Ptk6 decreases azoxymethane-induced colon tumorigenesis in mice by preventing signal transducer and activator of transcription 3 activation . Relocalization of PTK6 in prostate cancers contributes to increased growth . Although not expressed in normal breast or ovary , PTK6 promotes anchorage-independent survival of breast and ovarian tumor cells . We identified several potential PTK6 substrates in the human SW620 colon cancer cell line using mass spectrometry , including FAK ( focal adhesion kinase ) . We show that FAK is a direct substrate of PTK6 in vitro and in vivo . Expression of membrane-targeted active PTK6 ( Palm-PTK6-YF ) induces constitutive activation of FAK and cell morphology changes , which are independent of SRC family kinases in Src-/- , Yes-/- , Fyn-/- ( SYF ) mouse embryonic fibroblasts ( MEFs ) . Palm-PTK6-YF expressing SYF cells are transformed and overcome contact inhibition , form colonies in transformation assays , proliferate in suspension and form tumors in a xenograft model . Expression of FAK and Palm-PTK6-YF in Fak-/- MEFs synergistically activates AKT and protects cells against anoikis . However , expression of Palm-PTK6-YF in Akt1/2-/- MEFs fails to protect cells from anoikis , indicating AKT is critical in PTK6 and FAK-mediated survival signaling . In a conditional Pten knockout murine prostate cancer model , we identify prostate epithelial cells with enhanced activation of endogenous PTK6 and FAK at the plasma membrane . Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis , which can be rescued by exogenous expression of FAK . Our data reveal important roles for a PTK6-FAK-AKT signaling axis in promoting anchorage-independent cell survival .
OUTPUT:
| evading growth suppressors | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot810 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors , including cellular immunity . We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms . However , how metastasis susceptibility genes interact with the tumor stroma is incompletely understood . Here , we employ a complex genetic screen to identify Cadm1 as a novel modifier of metastasis . We demonstrate that Cadm1 can specifically suppress metastasis without affecting primary tumor growth . Unexpectedly , Cadm1 did not alter tumor-cell-autonomous properties such as proliferation or invasion , but required the host's adaptive immune system to affect metastasis . The metastasis-suppressing effect of Cadm1 was lost in mice lacking T cell-mediated immunity , which was partially phenocopied by depleting CD8(+) T cells in immune-competent mice . Our data show a novel function for Cadm1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms , and this is the first report of a heritable metastasis susceptibility gene engaging tumor non-autonomous factors .
OUTPUT:
| activating invasion and metastasis;avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot811 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: It is known that sperm samples from recurrent pregnancy loss ( RPL ) couples have an increase in their sperm DNA fragmentation ( SDF ) , but no studies have been performed in order to identify differences between single stranded SDF ( ssSDF ) and double stranded SDF ( dsSDF ) in these patients . This could be relevant because the type of DNA damage could have different effects . Semen samples were classified attending their clinical status : 25 fertile donors and 20 RPL patients with at least two unexplained first trimester miscarriages . SDF was analysed using alkaline and neutral Comet assay , SCD test and pulsed-field gel electrophoresis ( PFGE ) , and ROC analysis including data from 105 more infertile patients ( n = 150 ) was performed to establish predictive threshold values . SDF for alkaline and neutral Comet , and the SCD test was analysed in these categories of individuals . Data revealed the presence of two subgroups within fertile donors . The values obtained were 21.10±9.13 , 23.35±10.45 and 12.31±4.31 , respectively , for fertile donors with low values for both ssSDF and dsSDF ; 27.86±12.64 , 80.69±12.67 and 12.43±5.22 , for fertile donors with low ssSDF and high dsSDF ; and 33.61±15.50 , 84.64±11.28 and 19.28±6.05 , for unexplained RPL patients , also showing a low ssSDF and high dsSDF profile . This latter profile was seen in 85% of unexplained RPL and 33% of fertile donors , suggesting that it may be associated to a male risk factor for undergoing RPL . ROC analysis regarding recurrent miscarriage set the cut-off value at 77.50% of dsDNA SDF . PFGE for low ssSDF and high dsSDF profile samples and positive controls treated with DNase , to induce dsDNA breaks , showed a more intense band of about 48 kb , which fits the toroid model of DNA compaction in sperm , pointing out that some nuclease activity may be affecting their sperm DNA in RPL patients . This work identifies a very specific SDF profile related to the paternal risk of having RPL .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot812 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Perlecan Domain V ( DV ) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells ( BECs ) following stroke . In this study , we define the specific mechanism of DV interaction with the α(5)β(1) integrin , identify the downstream signal transduction pathway , and further investigate the functional significance of resultant VEGF release . Interestingly , we found that the LG3 portion of DV , which has been suggested to possess most of DV's angio-modulatory activity outside of the brain , binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV . Additionally , we implicate DV's DGR sequence as an important element for the interaction of DV with α(5)β(1) . Furthermore , we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion . We show that DV increases the phosphorylation of ERK , which leads to subsequent activation and stabilization of eIF4E and HIF-1α . Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs . While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors , LY294002 and Akt IV . Lastly , we demonstrate that VEGF activity is critical for DV increases in BEC proliferation , as well as angiogenesis in a BEC-neuronal co-culture system . Collectively , our findings expand our understanding of DV's mechanism of action on BECs , and further support its potential as a novel stroke therapy .
OUTPUT:
| inducing angiogenesis;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot813 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Although tumor-associated macrophages ( TAMs ) are involved in tumor growth and metastasis , the mechanisms controlling their pro-tumoral activities remain largely unknown . The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors . In this study , we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice , which lack c-Myc in macrophages , to investigate the role of macrophage c-MYC expression in cancer . Under steady-state conditions , immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal , including the abundance of different subsets of bone marrow hematopoietic stem cells , precursors and circulating cells , macrophage density , and immune organ structure . In a model of melanoma , however , TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions ( e.g. , reduced expression of VEGF , MMP9 , and HIF1α ) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice . Macrophage c-Myc deletion also diminished fibrosarcoma growth . These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot814 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The SR/CR mouse phenotype , first described in 1999 in BALB/c and later bred into C57BL/6 mice , is resistant to cancer formation following high doses of cancer cells administered intraperitoneally . The tumor cell targeting and destruction mechanisms have not been identified . By fluorescence-activated cell sorting analysis , the immune response of SR/CR mice after intraperitoneal injection of cancer cells was investigated and compared with parent strain mice . A massive influx of leukocytes into the peritoneal cavity was found . A large fraction of these leukocytes were polymorphonuclear granulocytes , macrophages and natural killer cells . A relative decrease in influx of B-cells compared with controls was demonstrated . Increased proportions of leukocytes belonging to the innate immune system were also demonstrated in splenocytes of SR/CR mice . Cytospins of peritoneal fluid from SR/CR mice after cancer cell injection showed formations of immune cells morphologically resembling polymorphonuclear granulocytes and macrophages adjoining the cancer cells . The results point to the potential involvement of innate immune cells in cancer immunology . Our data support migration of polymorphonuclear granulocytes , macrophages and NK cells into the peritoneum of the SR/CR mouse in response to intraperitoneal injection of S180 cancer cells . The cell composition of spleens of SR/CR mice reflected the differential regulation of the innate immune cells in peritoneal exudates . Both peritoneal exudates and the spleens of SR/CR mice contained decreased proportions of B-cells compared with BALB/c and C57BL/6 mice . We reproduce important aspects of previous published data and further extend them by showing differentially regulated populations of splenocytes including B-lymphocytes in SR/CR mice compared with parent strain controls . Importantly , this differentially regulated immune response of SR/CR mice could not be found in response to challenge with the lymphoma cell line EL-4 .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot815 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Glioblastoma is the most common and most aggressive form of malignant glioma and is very difficult to treat . Controlling tumour cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients . Since constitutive activation of nuclear factor-κB ( NF-κB ) is necessary for tumour progression , NF-κB may be an important pharmacological target for this disease . Our study aimed to evaluate the antitumour effects of parthenolide , a NF-κB inhibitor , in two human glioblastoma cell lines ( U87MG and U373 ) and in glioblastoma xenografts . Furthermore , we aimed to investigate the molecular mechanisms underlying these effects . METHODS The anti-invasive and anti-angiogenic effects of parthenolide were analysed using in vitro invasion and angiogenesis assays . Parthenolide-induced growth inhibition of glioblastoma cells in vitro was determined using the MTT ( methyl thiazolyl tetrazolium ) assay . In addition , the effect of parthenolide on orthotropic implantation in vivo was evaluated using an intracerebral human glioblastoma xenograft model . RESULTS We found that parthenolide suppresses proliferation , invasion , and tumour- induced angiogenesis of glioblastoma cells . Molecular studies demonstrated that parthenolide suppresses gene and protein expression of angiogenic factors . Furthermore , parthenolide reduced Akt phosphorylation and activated mitochondrial signalling , suggesting that the antitumour function of parthenolide may be mediated not only by the inhibition of NF-κB but also by the inhibition of Akt signalling and the activation of apoptotic proteins . Parthenolide suppressed neovascularity and tumour growth in glioblastoma xenografts . CONCLUSION The present study identified parthenolide as a new therapeutic agent for glioblastomas .
OUTPUT:
| activating invasion and metastasis;inducing angiogenesis;sustaining proliferative signaling;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot816 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Overexpression of cyclin D1 is believed to endow mammary epithelial cells ( MEC ) with a proliferative advantage by virtue of its contribution to pRB inactivation . Accordingly , abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2 . Here , we report that mouse cyclin D1(KE/KE) MECs ( deficient in cyclin D1 activity ) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo . In addition , immortalized cyclin D1(KE/KE) MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro . However , highlighting its dual role during tumorigenesis , downregulation of autophagy led to an increase in senescence in cyclin D1(KE/KE) MECs . Autophagy upregulation was also confirmed in human mammary epithelial cells ( HMEC ) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and , similar to our murine system , simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response . Collectively , our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium . Cancer Res ; 72(24) ; 6477-89. �2012 AACR .
OUTPUT:
| enabling replicative immortality;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot817 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The orphan receptor TR3 is an important regulator of cell proliferation and apoptosis . However , whether TR3 is involved in regulating the stem-like properties of cancer cells remains unknown . The present study shows that TR3 expression is increased in gastric tumorsphere cells and is positively correlated with cancer stem cell ( CSC ) characteristics . Knocking down TR3 leads to the suppression of its stem-like properties in both gastric cancer cells and tumorsphere cells . This process involves the decreased expression of the stemness-related genes Oct-4 and Nanog and the invasion-related gene MMP-9 . We further identify Nanog as a new target for the transcription factor TR3 . Together , these data demonstrate for the first time that TR3 is essential for the maintenance of stem-like properties in human gastric cancer cells and implicate TR3 as a new therapeutic target for gastric cancer .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot818 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The recent approval of a prostate cancer vaccine has renewed hope for anticancer immunotherapies . However , the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies . Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy , but they often are used at high doses in the clinic to prune tumor vessels and paradoxically may compromise various therapies . Here , we demonstrate that targeting tumor vasculature with lower vascular-normalizing doses , but not high antivascular/antiangiogenic doses , of an anti-VEGF receptor 2 ( VEGFR2 ) antibody results in a more homogeneous distribution of functional tumor vessels . Furthermore , lower doses are superior to the high doses in polarizing tumor-associated macrophages from an immune inhibitory M2-like phenotype toward an immune stimulatory M1-like phenotype and in facilitating CD4(+) and CD8(+) T-cell tumor infiltration . Based on this mechanism , scheduling lower-dose anti-VEGFR2 therapy with T-cell activation induced by a whole cancer cell vaccine therapy enhanced anticancer efficacy in a CD8(+) T-cell-dependent manner in both immune-tolerant and immunogenic murine breast cancer models . These findings indicate that vascular-normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies . Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients , our study suggests a strategy to use antiangiogenic agents in breast cancer more effectively with active immunotherapy and potentially other anticancer therapies .
OUTPUT:
| inducing angiogenesis;avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
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"avoiding immune destruction"
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HoC_1shot819 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Neural stem cells ( NSCs ) are considered to be the cell of origin of glioblastoma multiforme ( GBM ) . However , the genetic alterations that transform NSCs into glioma-initiating cells remain elusive . Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture , followed by additional rounds of mutagenesis to generate tumors in vivo , we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells . Mobilization of Sleeping Beauty transposons in NSCs induced the immortalization of astroglial-like cells , which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation , consistent with a potential astroglial origin for mesenchymal GBM . Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes , including human GBM-associated genes , such as Met and Nf1 , and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development . We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method . Finally , we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development , suggesting that tumor formation in this model system involves competition among genetically variant cells , which is similar to the Darwinian evolutionary processes now thought to generate many human cancers . This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro .
OUTPUT:
| enabling replicative immortality;genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot820 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND : The immune system has been shown to play an important role in gastrointestinal stromal tumor ( GIST ) . The neutrophil-to-lymphocyte ratio ( NLR ) in blood is an easily assessable parameter of systemic inflammatory response . The aim of this study was to determine whether the NLR is prognostic in GIST . METHODS : A total of 339 previously untreated patients with primary , localized GIST operated at our institution between 1995 and 2010 were identified from a prospectively collected sarcoma database . NLR was assessed preoperatively . Patients who received adjuvant imatinib treatment were excluded from the analysis ( n=64 ) . Cox regression models were calculated and correlation analyses were performed . RESULTS : On univariate analysis , NLR was associated with recurrence-free survival ( RFS ) ( P=0.003 , hazard ratio 3.3 , 95% confidence interval 1.5-7.4 ) . Patients with a low NLR had a 1- and 5-year RFS of 98 and 91% , compared with 89 and 76% in those with a high NLR . The median RFS was not reached . Positive correlations were found between NLR and mitotic rate ( Pearson correlation coefficient [ r]=0.15 , P=0.03 ) , and NLR and tumor size ( r=0.36 , P=0.0001 ) . RFS in patients with a GIST>5cm with low NLR was significantly longer compared to patients with high NLR ( P=0.002 ) . Flow cytometry analysis of freshly obtained GISTs revealed that neutrophils constituted a minimal percentage of intratumoral immune cells . CONCLUSIONS : NLR is a surrogate for high-risk tumor features . Elevated blood NLR appears to represent systemic inflammation in patients with high-risk GIST .
OUTPUT:
| avoiding immune destruction;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot821 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The epithelial-mesenchymal transition ( EMT ) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis . Besides their therapeutic effects , accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells ; however , the mechanism(s) still remains unclear . Here , we investigated the role of β-catenin signaling in doxorubicin ( Dox)-induced EMT in human gastric cancer cell line BGC-823 . We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells . We also found that β-catenin signaling was activated upon Dox treatment . Inhibition of β-catenin by indomethacin ( Indo ) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability . Our results showed that β-catenin signaling was critical to Dox-induced EMT . Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot822 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Growth Regulation by Estrogen in Breast cancer ( GREB1 ) was an estrogen receptor ( ER ) target gene , and GREB1 expression inversely correlated with HER2 status , possibly as a surrogate marker for ER status and a predictor for tamoxifen resistance in breast cancer patients . In the present study , we examine the function and regulation of GREB1 in breast cancer , with the goal to develop GREB1 as a biomarker in breast cancer with de novo and acquired tamoxifen resistance . METHODS We overexpressed GREB1 using adenovirus containing the full length GREB1 cDNA ( Ad-GREB1 ) in breast cancer cell lines . The soft agar assay was used as a measure of anchorage independent growth . The effects of GREB1 on cell proliferation in MCF-7 cells transduced with Ad-GREB1 were also measured by the me olic activity using AlamarBlue assay . We tested whether there was interaction between STAT3 and ER , which could repress GREB1 expression by immunoprecipitation assay . The effects of IL-6/JAK/STAT3 cascade activation on estrogen-induced GREB1 promoter activity were determined by luciferase assay and those on gene expression were measured by real time reverse transcription polymerase chain reaction ( qRT-PCR ) . RESULTS We found that the ability of breast cancer cells to grow in soft agar is enhanced following GREB1 transfection . In MCF-7 cells transduced with Ad-GREB1 or transfected with siRNA GREB1 , the metabolic activity was increased or completely abolished , suggesting that GREB1 may function as a growth promoter in breast cancer . E2 treatment increased GREB1 promoter luciferase activity . IL-6 inhibited E2-induced GREB1 transcription activity and GREB1 mRNA expression . Constitutively expressing active STAT3 construct ( STAT3-C ) dramatically decreased GREB1 transcription . CONCLUSIONS These data indicate that overexpression of GREB1 promotes cell proliferation and increases the clonogenic ability in breast cancer cells . Moreover , Il6/STAT3 modulates estrogen-induced GREB1 transcriptional activity in breast cancer cells .
OUTPUT:
| sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot823 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Widespread changes in gene expression drive tumorigenesis , yet our knowledge of how aberrant epigenomic and transcriptome profiles arise in cancer cells is poorly understood . Here , we demonstrate that metabolic transformation plays an important role . Butyrate is the primary energy source of normal colonocytes and is metabolized to acetyl-CoA , which was shown to be important not only for energetics but also for HAT activity . Due to the Warburg effect , cancerous colonocytes rely on glucose as their primary energy source , so butyrate accumulated and functioned as an HDAC inhibitor . Although both mechanisms increased histone acetylation , different target genes were upregulated . Consequently , butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring , whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect . These findings link a common metabolite to epigenetic mechanisms that are differentially utilized by normal and cancerous cells because of their inherent metabolic differences .
OUTPUT:
| cellular energetics | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot824 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: TNF , an inflammatory cytokine that is enriched in the tumor microenvironment , promotes tumor growth and subverts innate immune responses to cancer cells . We previously reported that tumors implanted in TNF receptor-deficient ( Tnfr-/- ) mice are spontaneously rejected ; however , the molecular mechanisms underlying this rejection are unclear . Here we report that TNF signaling drives the peripheral accumulation of myeloid-derived suppressor cells ( MDSCs ) . MDSCs expand extensively during inflammation and tumor progression in mice and humans and can enhance tumor growth by repressing T cell-mediated antitumor responses . Peripheral accumulation of MDSCs was drastically impaired in Tnfr-/- mice . Signaling of TNFR-2 , but not TNFR-1 , promoted MDSC survival through upregulation of cellular FLICE-inhibitory protein ( c-FLIP ) and inhibition of caspase-8 activity . Loss of TNFRs impaired the induction of MDSCs from bone marrow cells , but this could be reversed by treatment with caspase inhibitors . These results demonstrate that TNFR-2 signaling promotes MDSC survival and accumulation and helps tumor cells evade the immune system .
OUTPUT:
| tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot825 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: This study intended to investigate the expression of the ZEB1 and E-cadherin proteins in lung squamous cell carcinoma ( LSCC ) tissues and to examine the clinicopathological correlation between protein levels and LSCC . RT-PCR and Western blot were used to examine the expression of ZEB1 and E-cadherin mRNAs and proteins in LSCC tissues as well as in adjacent normal tissues , and then analyze the relationship between the clinicopathological characteristics and the expression changes of ZEB1 and E-cadherin mRNAs in LSCC . In addition , RNAi was used to knockdown the expression of the ZEB1 gene in Human HCC827 cells ; subsequently , changes in the invasive ability of the resultant cells were studied . The positive rates of ZEB1 and E-cadherin mRNAs in LSCC tissues were 69.2 and 38.5% , respectively . They differed significantly from the corresponding positive rates in the adjacent normal lung tissues ( 15.4 and 80.8% , p<0.05 ) . There was a negative correlation between the protein levels of ZEB1 and E-cadherin in LSCC tissues ( r=-0.714 , p<0.001 ) ; in addition , it was found that ZEB1 protein expression in LSCC tissues was significantly higher than that in the neighboring normal lung tissues ( p<0.05 ) , and its expression was also significantly higher in patients with lymph node metastases and distant metastases compared to those patients without metastatic disease ( p<0.05 ) . On the contrary , E-cadherin expression was significantly lower in LSCC tissues than that in the neighboring normal tissue ( p<0.05 ) . It was lower in patients with lymph node metastasis and distant metastasis compared to patients without metastatic disease ( p<0.05 ) . However , the expression of ZEB1 and E-cadherin was independent of gender , age , tumor size , or tumor differentiation level ( p>0.05 ) . Transfection of ZEB1 siRNA into HCC827 cells significantly reduced the ZEB1 protein level ( p<0.01 ) and significantly elevated E-cadherin levels ( p<0.01 ) . Moreover , significantly less ZEB1 siRNA-transfected cells migrated through Transwell chambers in the LSCC tissue than that in the control groups ( untransfected or transfected with control siRNA , p<0.01 ) . The expression of the ZEB1 gene in LSCC tissues is downregulated with the expression of E-cadherin . On the other hand , the expression of siRNA against ZEB1 promotes E-cadherin expression and suppresses the invasive ability conferred by E-cadherin . In conclusion , our data suggested that overexpression of the ZEB1 gene is possibly associated with the occurrence , development , invasion of LSCC .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot826 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: This study examined the possible role of p120ctn in the pathogenesis and development of pancreatic cancer . PANC-1 cells , a kind of human pancreatic carcinoma cell line , were cultured in this study. p120ctn was immunocytochemically detected in PANC-1 cells . The recombinant lentivirus vector was constructed to knock down the p120ctn expression of PANC-1 cells . Real-time quantitative PCR ( RQ-PCR ) and Western blotting were used to determine the expression of p120ctn and E-cadherin in PANC-1 cells after p120ctn knockdown . The adhesion , invasion and migration capacity of PANC-1 cells after p120ctn knockdown was detected by cell adhesion , invasion and migration assays . Cell growth was measured by the MTT method . Cell cycle and apoptosis were analyzed by fluorescence-activated cell sorting . The results showed that p120ctn knockdown led to significantly down-regulated E-cadherin and a reduced cell-to-cell adhesion ability in PANC-1 cells. shRNA-mediated knockdown of p120ctn reduced invasion and migration capacity of PANC-1 cells , inhibited cell growth , caused a significant decrease in the percentage of cells in G(1) , an increase in S , and promoted apoptosis of PANC-1 cells . It was concluded that p120ctn plays a pivotal role in the proliferation and metastasis of pancreatic carcinoma , suggesting that p120ctn is a novel target for pancreatic carcinoma treatment .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot827 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Cancer can be envisioned as a metabolic disease driven by pressure selection and intercellular cooperativeness . Together with anaerobic glycolysis , the Warburg effect , formally corresponding to uncoupling glycolysis from oxidative phosphorylation , directly participates in cancer aggressiveness , supporting both tumor progression and dissemination . The transcription factor hypoxia-inducible factor-1 ( HIF-1 ) is a key contributor to glycolysis . It stimulates the expression of glycolytic transporters and enzymes supporting high rate of glycolysis . In this study , we addressed the reverse possibility of a metabolic control of HIF-1 in tumor cells . We report that lactate , the end-product of glycolysis , inhibits prolylhydroxylase 2 activity and activates HIF-1 in normoxic oxidative tumor cells but not in Warburg-phenotype tumor cells which also expressed lower basal levels of HIF-1α . These data were confirmed using genotypically matched oxidative and mitochondria-depleted glycolytic tumor cells as well as several different wild-type human tumor cell lines of either metabolic phenotype . Lactate activates HIF-1 and triggers tumor angiogenesis and tumor growth in vivo , an activity that we found to be under the specific upstream control of the lactate transporter monocarboxylate transporter 1 ( MCT1 ) expressed in tumor cells . Because MCT1 also gates lactate-fueled tumor cell respiration and mediates pro-angiogenic lactate signaling in endothelial cells , MCT1 inhibition is confirmed as an attractive anticancer strategy in which a single drug may target multiple tumor-promoting pathways .
OUTPUT:
| cellular energetics;inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot828 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: A metaphase chromosome analysis method was used to evaluate the mutagenic activity of volatile petroleum fractions in chronically intoxicated rats . The findings indicate that chronic inhalation exposure of the rats to volatile petroleum fractions at different concentrations results in a significant ( 2.5-fold ) increase , compared to the spontaneous level , in the occurrence of chromosomal aberrations in the bone marrow cells in a number of generations . In addition to chromosomal structural abnormalities , there are genomic changes ( aneuploidy , polyploidy ) . There is a tendency towards an increased rate of petroleum-induced chromosomal aberrations in a number of generations ( P , F1 , and F2 ) in the rat bone marrow cells . The maximum mutagenic effect of volatile petroleum fractions was found when used at concentrations of 10 and 100 mg/l upon long-term chronic exposure during three generations ( P1 , F1 , and F2 ) . The findings are indicative of the mutagenic activity of volatile petroleum fractions , which is likely to pose a potential risk from environmental pollution to biota and population health in the area of intensive oil extraction and refining .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot829 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Patients with invasive breast ductal carcinoma ( IBDC ) with metastasis have a very poor prognosis . Little is known about the synergistic action of growth and inflammatory factors in IBDC metastases . METHODS The expression of activated extracellular signal-regulated kinase1/2 ( phosphorylated or p-ERK1/2 ) was analyzed by immunohistochemistry in IBDC tissue samples from 80 cases . BT474 IBDC cell migration and invasion were quantified using the Transwell assay . Matrix metalloproteinase ( MMP)-9 expression and activity were analyzed by RT-PCR , Western blotting and zymography . Activator protein ( AP)-1 activity was measured with a luciferase reporter gene assay . The Wilcoxon signed-rank test , Chi-square test , the partition of Chi-square test , independent t-test , and Spearman's method were used for the statistical analysis . RESULTS Phosphorylated ERK1/2 was detected in 58/80 ( 72.5% ) IBDC tissues , and was associated with higher TNM stage and lymph node metastasis , but not patient age or tumor size . Individually , epidermal growth factor ( EGF ) , and interleukin ( IL)-1β activated ERK1/2 , increased cell migration and invasion , MMP-9 expression and activity , AP-1 activation in vitro and the expression of p-ERK1/2 was positively correlated with EGF expression levels , as well as IL-1β , MMP-9 and c-fos in IBDC tissue samples . Co-stimulation with EGF and IL-1β synergistically increased ERK1/2 and AP-1 activation , cell migration and invasion , and MMP-9 expression and activity . Inhibition of ERK1/2 using U0126 or siRNA abolished EGF and/or IL-1β-induced cell migration and invasion in a dose-dependent manner . CONCLUSION Activated ERK1/2 was associated with higher TNM stage and lymph node metastasis in IBDC . Both in vitro and in vivo studies indicated that ERK-1/2 activation may increase the metastatic ability of IBDC cells . Growth and inflammatory factors synergistically induced IBDC cell migration and invasion via ERK1/2 signaling , AP-1 activation and MMP-9 upregulation .
OUTPUT:
| activating invasion and metastasis;sustaining proliferative signaling;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot830 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: PURPOSE Recently , a new renal cell cancer syndrome has been linked to germline mutation of multiple subunits ( SDHB/C/D ) of the Krebs cycle enzyme , succinate dehydrogenase . We report our experience with the diagnosis , evaluation and treatment of this novel form of hereditary kidney cancer . MATERIALS AND METHODS Patients with suspected hereditary kidney cancer were enrolled on a National Cancer Institute institutional review board approved protocol to study inherited forms of kidney cancer . Individuals from families with germline SDHB , SDHC and SDHD mutations , and kidney cancer underwent comprehensive clinical and genetic evaluation . RESULTS A total of 14 patients from 12 SDHB mutation families were evaluated . Patients presented with renal cell cancer at an early age ( 33 years , range 15 to 62 ) , metastatic kidney cancer developed in 4 and some families had no manifestation other than kidney tumors . An additional family with 6 individuals found to have clear cell renal cell cancer that presented at a young average age ( 47 years , range 40 to 53 ) was identified with a germline SDHC mutation ( R133X ) Metastatic disease developed in 2 of these family members . A patient with a history of carotid body paragangliomas and an aggressive form of kidney cancer was evaluated from a family with a germline SDHD mutation . CONCLUSIONS SDH mutation associated renal cell carcinoma can be an aggressive type of kidney cancer , especially in younger individuals . Although detection and management of early tumors is most often associated with a good outcome , based on our initial experience with these patients and our long-term experience with hereditary leiomyomatosis and renal cell carcinoma , we recommend careful surveillance of patients at risk for SDH mutation associated renal cell carcinoma and wide surgical excision of renal tumors .
OUTPUT:
| activating invasion and metastasis;genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot831 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Premature senescence , a key strategy used to suppress carcinogenesis , can be driven by p53/p21 proteins in response to various stresses . Here , we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability . Wig1 controls the association of Argonaute2 ( Ago2 ) , a central component of the RNA-induced silencing complex ( RISC ) , with target p21 mRNA via binding of the stem-loop structure near the microRNA ( miRNA ) target site . Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence . Wig1 plays an essential role in cell proliferation , as demonstrated in tumour xenografts in mice , and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues . Together , our data indicate a novel role of Wig1 in RISC target accessibility , which is a key step in RNA-mediated gene silencing . In addition , these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot832 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Alteration of the oxidative stress of hepatocellular carcinoma ( HCC ) cells can influence the expressions of genes favored angiogenesis . Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3 . Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3 . This study was to investigate the influence of therapeutic concentrations of prazosin ( 0.01 and 0.1μM ) on cell proliferation and differential expressions of CCL2 , CCL20 , CXCL6 , CXCL10 , IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines . Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress ( cell line A ; HCC24/KMUH ) and one with this effect ( cell line B ; HCC38/KMUH ) were investigated by 0.01 and 0.1μM prazosin . The premixed WST-1 cell proliferation reagent was applied for proliferation assay . Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction . Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines . Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes . However , 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion , high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress . Clinical application of prazosin in patients with HCC should consider this possibility .
OUTPUT:
| inducing angiogenesis;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot833 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Centrosome overduplication or amplification has been observed in many human cancers and in premalignant tissue , but the mechanisms leading to such centrosome aberrations are not fully understood . We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human fibroblasts , especially in a polyploid subpopulation . This study examines localization of p53 protein at centrosomes in mitotic cells , which is often observed in association with DNA damage response , to investigate a possible association between p53 localization and numerical centrosome aberrations induced by cellular senescence . Cultures at later passages or the 4th day after exposure to H(2)O(2) showed increased frequencies of mitotic cells with supernumerary centrosomes , especially in a polyploid subpopulation . Immunohistochemical analysis frequently showed p53-positive foci in mitotic cells , and some were localized at centrosomes . The number of p53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence . Supernumerary centrosomes showed higher frequencies of p53 localization compared to normally duplicated centrosomes . Centrosome-associated p53 protein was phosphorylated at Ser15 . These data suggest a possible association between localization of p53 protein and numerical centrosome aberrations in replicatively or prematurely senescent cells .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot834 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Purpose . The purpose of this paper is to evaluate a new PET tracer ( 64)Cu-NODAGA-c(RGDyK ) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans . Procedures . Nude mice with human neuroendocrine tumor xenografts ( H727 ) were administered ( 64)Cu-NODAGA-c(RGDyK ) i.v. for study of biodistribution as well as for dynamic PET . Gene expression of angiogenesis markers integrin α(V) , integrin β(3) , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors ( %ID/g ) . From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM . Results . Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake , for integrin α(V)âR = 0.76 , integrin β(3)âR = 0.75 and VEGF-A R = 0.81 ( all P < ; 0.05 ) . The whole body effective dose for humans was estimated to be 0.038 and 0.029âmSv/MBq for females and males , respectively , with highest absorbed dose in bladder wall . Conclusion . ( 64)Cu-NODAGA-c(RGDyK ) is a promising new angiogenesis PET tracer with potential for human use .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot835 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Cytokine-dependent cell lines have been used to analyze the cytokine-induced cellular signaling and the mechanism of oncogenesis . In the current study , we analyzed MOTN-1 and PLT-2 cell lines established from different stages of a T-cell large granular lymphocyte leukemia patient ( Daibata et al. 2004 ) . MOTN-1 is IL-2-dependent derived from the chronic phase , whereas IL-2-independent PLT-2 is from the aggressive and terminal stage . They shared considerable chromosome abnormalities and the pattern of T-cell receptor rearrangement , presuming that the cytokine independence of PLT-2 was due to the additive genetic abnormality . Besides IL-2 , IL-15 supported MOTN-1 cell growth , because these receptors share beta- and gamma-subunits . IL-2 activated ERK , AKT and STAT pathway of MOTN-1 . STAT3 pathway of PLT-2 was also activated by IL-2 , suggesting intact IL-2 induces signal transduction of PLT-2 . However , ERK1/2 but not AKT , was continuously activated in PLT-2 , consistent with the increased Ras-activity of PLT-2 . Sequence analysis revealed KRAS G12A mutation but not NRAS and HRAS mutation of PLT-2 but not MOTN-1 . Another signaling molecule affecting Ras-signaling pathway , SHP2 , which has been frequently mutated in juvenile myelomonocytic leukemia ( JMML ) , did not show mutation . Moreover , MEK inhibitor , PD98059 , as well as farnesylation inhibitor inhibited PLT-2 cell growth . Using NIH3T3 and MOTN-1 , ERK activation , increased cell proliferation and survival by KRAS G12A were shown , suggesting the important role of KRAS G12A in IL-2-independent growth of PLT-2 . Taken together , KRAS G12A is important for IL-2-independent growth of PLT-2 cells and suggests the possibility of involvement of KRAS mutation with disease progression .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot836 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Angiotensin II type 1 receptor ( AT1R ) promotes tumor invasion , migration , metastasis and angiogenesis . We explored the potential antitumor effects of AT1R antagonists in breast cancer . We found that angiotensin II promoted cell proliferation and upregulated the expression of vascular endothelial growth factor A ( VEGF-A ) in MCF-7 cells . Losartan downregulated the expression of VEGF-A in MCF-7 cells treated with angiotensin II . Candesartan downregulated the expression of VEGF-A in mice bearing MCF-7 xenografts and inhibited tumor growth and angiogenesis . AT1R and VEGF-A expression correlated with increased microvascular density in 102 breast cancer patients . Our data suggest that AT1R antagonists might be useful to suppress breast cancer by inhibiting the angiotensin II .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot837 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The CD4+CD25+ regulatory T cell ( Treg ) is a special kind of T cell subset . Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases , transplantation tolerance and cancer . Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance . The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma ( HCC ) . A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods . Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status . The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ( 18.8% � 1.26% ) was found to be significantly higher than that in normal mice ( 9.99% � 1.90% ) ( P<0.01 ) . Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice , while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed . Anti-tumour immunity was suppressed , and this might be associated with the increase of Tregs . Our observations suggest that the CD4+CD25+Treg/ CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot838 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: OBJECTIVE To evaluate the risk factors for sentinel lymph node metastasis and validate the value of the Memorial Sloan-Kettering Cancer Center nomogram for the prediction of sentinel lymph node metastasis in breast cancer patients . METHODS A sentinel lymph node biopsy database containing 1227 consecutive breast cancer patients ( 416 patients with at least one positive sentinel lymph node ) was retrospectively analyzed . The predictive value of the Memorial Sloan-Kettering Cancer Center nomogram was calculated by the trend line and the area under the receiver-operator characteristic curve . Meanwhile , predictors for sentinel lymph node metastasis were also evaluated . RESULTS Tumor size , histological grade , lymphovascular invasion , mulifocality , estrogen receptor and progesterone receptor status were significant independent predictors for sentinel lymph node metastasis ( all P<0.01 ) . The Memorial Sloan-Kettering Cancer Center nomogram presented an area under the receiver-operator characteristic curve value of 0.730 . Patients with predictive value<16% had a frequency of sentinel lymph node metastasis of 0.9% . Those with values larger than 70% had a frequency of 96.2% . CONCLUSIONS The risk factors for sentinel lymph node metastasis in our study were consistent with those in the Memorial Sloan-Kettering Cancer Center nomogram . The Memorial Sloan-Kettering Cancer Center nomogram is a useful tool that could accurately predict the probability of sentinel lymph node metastasis in our breast cancer patients . Axillary surgical staging might be avoided in patients with a predictive value of <16% and axillary lymph node dissection might be done directly in those with a predictive value >70% , while other patients should still accept sentinel lymph node biopsy .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot839 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The topoisomerase II ( topo II ) DNA incision-and-ligation cycle can be poisoned ( for example following treatment with cancer chemotherapeutics ) to generate cytotoxic DNA double-strand breaks ( DSBs ) with topo II covalently conjugated to DNA . Tyrosyl-DNA phosphodiesterase 2 ( Tdp2 ) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts . Here , X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 β-2-helix-β DNA damage-binding ' grasp ' , helical ' cap ' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove . The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing . Structural , mutational and functional analyses support a single-metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase ( EEP ) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot840 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The relevance of many BRCA2 variants of uncertain significance ( VUS ) to breast cancer has not been determined due to limited genetic information from families carrying these alterations . Here , we classified six new variants as pathogenic or nonpathogenic by analysis of genetic information from families carrying 64 individual BRCA2 DNA binding domain ( DBD ) missense mutations using a multifactorial likelihood model of cancer causality . Next , we evaluated the use of a homology-directed DNA break repair ( HDR ) functional assay as a method for inferring the clinical relevance of VUS in the DBD of BRCA2 using 18 established nonpathogenic missense variants and all 13 established pathogenic missense mutations from the BRCA2 DBD . Compared with the known status of these variants based on the multifactorial likelihood model , the sensitivity of the HDR assay for pathogenic mutations was estimated at 100% [ 95% confidence interval ( CI ) : 75.3%-100% ] and specificity was estimated at 100% ( 95% CI : 81.5%-100% ) . A statistical classifier for predicting the probability of pathogenicity of BRCA2 DBD variants was developed using these functional results . When applied to 33 additional VUS , the classifier identified eight with 99% or more probability of nonpathogenicity and 18 with 99% or more probability of pathogenicity . Thus , in the absence of genetic evidence , a cell-based HDR assay can provide a probability of pathogenicity for all VUS in the BRCA2 DBD , suggesting that the assay can be used in combination with other information to determine the cancer relevance of BRCA2 VUS .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot841 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Blockage of the metastasis process remains a significant clinical challenge , requiring innovative therapeutic approaches . For this purpose , molecules that inhibit matrix metalloproteinases activity or induce the expression of their natural inhibitor , the tissue inhibitor of metalloproteinases ( TIMPs ) , are potentially interesting . In a previous study , we have shown that synthetic ligands binding to cell surface nucleolin/nucleophosmin and known as HB 19 for the lead compound and NucAnt 6L ( N6L ) for the most potent analog , inhibit both tumor growth and angiogenesis . Furthermore , they prevent metastasis in a RET transgenic mice model which develops melanoma . Here , we investigated the effect of N6L on the invasion capacity of MDA-MB-435 melanoma cells . Our results show that the multivalent pseudopeptide N6L inhibited Matrigel invasion of MDA-MB-435 cells in a modified Boyden chamber model . This was associated with an increase in TIMP-3 in the cell culture medium without a change in TIMP-3 mRNA expression suggesting its release from cell surface and/or extracellular matrix . This may be explained by our demonstrated N6L interaction with sulfated glycosaminoglycans and consequently the controlled bioavailability of glycosaminoglycan-bound TIMP-3 . The implication of TIMP-3 in N6L-induced inhibition of cell invasion was evidenced by siRNA silencing experiments showing that the loss of TIMP-3 expression abrogated the effect of N6L . The inhibition of tumor cell invasion by N6L demonstrated in this study , in addition to its previously established inhibitory effect on tumor growth and angiogenesis , suggests that N6L represents a promising anticancer drug candidate warranting further investigation .
OUTPUT:
| activating invasion and metastasis;inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot842 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Melittin ( 1 ) is a major polypeptide in honey bee venom that has been used traditionally against chronic inflammation and cancer . However , its molecular mechanism has not been determined . In this study , the antitumor effect of 1 was compared with that of NS398 , a cyclooxygenase-2 ( COX-2 ) inhibitor , in vivo and in vitro . Subcutaneous injection of 1 at 0.5 and 5 mg/kg suppressed significantly vascular endothelial growth factor ( VEGF)-A-transfected highly metastatic Lewis lung cancer ( VEGF-A-hm LLC ) tumor growth by 25% and 57% , respectively . Also , 1 inhibited significantly the number of vessels around VEGF-A-hm LLC cells . The results were superior to those obtained in the mice treated with NS398 . Compound 1 dose-dependently inhibited proliferation and tube formation in human umbilical vein endothelial cells ( VEGF-A-HUVECs ) , without affecting cell viability in native HUVECs . In addition , 1 decreased the expression of VEGF receptor-2 ( VEGFR-2 ) , COX-2 , and prostaglandin E(2) ( PGE(2) ) in VEGF-A-transfected HUVECs . These effects were accompanied by a reduction of the phosphorylation of extracellular signal-regulated kinase 1/2 and c-jun N-terminal kinase , whereas it increased the phosphorylation of p38 mitogen-activated protein kinase ( MAPK ) . SB203580 abolished the downregulation of COX-2 and VEGFR-2 and the inhibition of cell proliferation by 1 . The antitumor activity of 1 may be associated with antiangiogenic actions via inhibiting VEGFR-2 and inflammatory mediators involved in the MAPK signaling pathway .
OUTPUT:
| inducing angiogenesis;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot843 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Although regulatory T cells ( T(regs) ) are known to suppress self-reactive autoimmune responses , their role during T cell responses to nonself antigens is not well understood . We show that T(regs) play a critical role during the priming of immune responses in mice . T(reg) depletion induced the activation and expansion of a population of low-avidity CD8(+) T cells because of overproduction of CCL-3/4/5 chemokines , which stabilized the interactions between antigen-presenting dendritic cells and low-avidity T cells . In the absence of T(regs) , the avidity of the primary immune response was impaired , which resulted in reduced memory to Listeria monocytogenes . These results suggest that T(regs) are important regulators of the homeostasis of CD8(+) T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot844 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Trabecular meshwork ( TM ) cells have widely been used as an invitro model for glaucoma research . However , primary TM cells suffer the disadvantages of limited cell numbers and slow rates of proliferation . We discovered a spontaneously transformed bovine TM ( BTM ) cell line , BTM-28T . This cell line proliferated rapidly in low-glucose culture medium but also demonstrated contact inhibition in high-glucose culture medium . BTM-28T cells expressed key TM cell markers including α-smooth muscle actin ( α-SMA ) , laminin and collagen IV ( col IV ) . Also , 100nM dexamethasone ( DEX ) enhanced the formation of cross-linked actin networks ( CLANs ) in confluent BTM-28T cell cultures . Transforming growth factor beta 2 ( TGFβ2 ) induced the expression of fibronectin ( FN ) , plasminogen activator inhibitor-1 ( PAI-1 ) , and connective tissue growth factor ( CTGF ) in our cell cultures . This cell line will be helpful to better understand the aqueous humor outflow pathway as related to the pathophysiology of glaucoma .
OUTPUT:
| evading growth suppressors | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot845 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Investigations concerned the mechanism of HT-29 cells radiosensitization by cis-9,trans-11-conjugated linoleic acid ( c9,t11-CLA ) , a natural component of human diet with proven antitumor activity . METHODS The cells were incubated for 24h with 70μM c9,t11-CLA and then X-irradiated . The following methods were used : gas chromatography ( incorporation of the CLA isomer ) , flow cytometry ( cell cycle ) , cloning ( survival ) , Western blotting ( protein distribution in membrane fractions ) , and pulse-field gel electrophoresis ( rejoining of DNA double-strand breaks ) . In parallel , DNA-PK activity , γ-H2AX foci numbers and chromatid fragmentation were estimated . Gene expression was analysed by RT-PCR and chromosomal aberrations by the mFISH method . Nuclear accumulation of the EGF receptor ( EGFR ) was monitored by ELISA . RESULTS AND CONCLUSIONS C9,t11-CLA sensitized HT-29 cells to X-radiation . This effect was not due to changes in cell cycle progression or DNA-repair-related gene expression . Post-irradiation DSB rejoining was delayed , corresponding with the insufficient DNA-PK activation , although chromosomal aberration frequencies did not increase . Distributions of cholesterol and caveolin-1 in cellular membrane fractions changed . The nuclear EGFR translocation , necessary to increase the DNA-PK activity in response to oxidative stress , was blocked . We suppose that c9,t11-CLA modified the membrane structure , thus disturbing the intracellular EGFR transport and the EGFR-dependent pro-survival signalling , both functionally associated with lipid raft properties . GENERAL SIGNIFICANCE The results point to the importance of the cell membrane interactions with the nucleus after injury inflicted by X -rays . Compounds like c9,t11-CLA , that specifically alter membrane properties , could be used to develop new anticancer strategies .
OUTPUT:
| genomic instability and mutation;sustaining proliferative signaling;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot846 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Lung cancer is primarily caused by exposure to tobacco smoke . Tobacco smoke contains numerous carcinogens , including polycyclic aromatic hydrocarbons ( PAH ) . The most common PAH studied is benzo[a]pyrene ( B[a]P ) . B[a]P is metabolically activated through multiple routes , one of which is catalyzed by aldo-keto reductase ( AKR ) to B[a]P-7,8-dione ( BPQ ) . BPQ undergoes a futile redox cycle in the presence of NADPH to generate reactive oxygen species ( ROS ) . ROS , in turn , damages DNA . Studies with a yeast p53 mutagenesis system found that the generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because of similarities between the patterns ( types of mutations ) and spectra ( location of mutations ) and those seen in lung cancer . The patterns were dominated by G to T transversions , and the spectra in the experimental system have mutations at lung cancer hotspots . To address repair mechanisms that are responsible for BPQ induced damage we observed the effect of mutating two DNA repair genes OGG1 and APE1 ( APN1 in yeast ) and tested them in a yeast reporter system for p53 mutagenesis . There was an increase in both the mutant frequency and the number of G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1 yeast . Knocking out APN2 increased mutagenesis in the apn1 cells . In addition , we did not find a strand bias on p53 treated with BPQ in ogg1 yeast . These studies suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ , Apn1 and Apn2 have redundant functions and that the stand bias seen in lung cancer may not be due to impaired repair of oxidative lesions .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot847 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas ( ccRCCs ) are poorly understood . A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau ( VHL ) gene , which contributes to cancer progression and metastasis . We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells . VIP increased adhesion but decreased expression of metalloproteinases , MMP2 and MMP9 , as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells . VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells , suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma . VIP effects in A498 cells were blocked by the VPAC(1/2)-receptor antagonist JV-1-53 . In conclusion , present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease .
OUTPUT:
| activating invasion and metastasis;inducing angiogenesis;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot848 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Mitochondrial uncoupling protein 2 ( UCP2 ) can moderate oxidative stress by favoring the influx of protons into the mitochondrial matrix , thus reducing electron leakage from respiratory chain and mitochondrial superoxide production . Here , we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly increases reactive oxygen species ( ROS ) production inhibiting pancreatic adenocarcinoma cell growth . We also show that UCP2 inhibition triggers ROS-dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase ( GAPDH ) , formation of autophagosomes , and the expression of the autophagy marker LC3-II . Consistently , UCP2 over-expression significantly reduces basal autophagy confirming the anti-autophagic role of UCP2 . Furthermore , we demonstrate that autophagy induced by UCP2 inhibition determines a ROS-dependent cell death , as indicated by the apoptosis decrease in the presence of the autophagy inhibitors chloroquine ( CQ ) or 3-methyladenine ( 3-MA ) , or the radical scavenger NAC . Intriguingly , the autophagy induced by genipin is able to potentiate the autophagic cell death triggered by gemcitabine , the standard chemotherapeutic drug for pancreatic adenocarcinoma , supporting the development of an anti-cancer therapy based on UCP2 inhibition associated to standard chemotherapy . Our results demonstrate for the first time that UCP2 plays a role in autophagy regulation bringing new insights into mitochondrial uncoupling protein field .
OUTPUT:
| tumor promoting inflammation;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot849 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Acrolein ( Acr ) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust . It can also be produced endogenously by oxidation of polyunsaturated fatty acids . The Acr-derived 1,N(2)-propanodeoxyguanosine ( Acr-dG ) adducts in DNA are mutagenic lesions that are potentially involved in human cancers . In this study , monoclonal antibodies were raised against Acr-dG adducts and characterized using ELISA . They showed strong reactivity and specificity toward Acr-dG , weaker reactivity toward crotonaldehyde- and trans-4-hydroxy-2-nonenal-derived 1,N(2)-propanodeoxyguanosines , and weak or no reactivity toward 1,N(6)-ethenodeoxyadenosine and 8-oxo-deoxyguanosine . Using these antibodies , we developed assays to detect Acr-dG in vivo : first , a simple and quick FACS-based assay for detecting these adducts directly in cells ; second , a highly sensitive direct ELISA assay for measuring Acr-dG in cells and tissues using only 1 μg of DNA without DNA digestion and sample enrichment ; and third , a competitive ELISA for better quantitative measurement of Acr-dG levels in DNA samples . The assays were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA , and the results were confirmed by LC-MS/MS-MRM . An immunohistochemical assay was also developed to detect and visualize Acr-dG in HT29 cells as well as in human oral cells . These antibody-based methods provide useful tools for the studies of Acr-dG as a cancer biomarker and of the molecular mechanisms by which cells respond to Acr-dG as a ubiquitous DNA lesion .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot850 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The mammalian COP9 signalosome ( CSN ) complex is involved in cell transformation , but its molecular mechanism remains undetermined . Here we show that disruption of the fifth component ( CSN5 ) prevented the formation of tumors by p53-null cells transformed with an active form of Ras in subcutaneously injected mice . Depletion of CSN5 suppressed cell proliferation , and induced premature senescence characterized by upregulation of senescence-associated-β-galactosidase activity and increased expression of CDK inhibitors . CSN5-depleted cells exhibited enhanced activation of the PI3 kinase-Akt pathway , and chemical inhibition of this pathway reduced the level of senescence . Thus , CSN5 is suggested to be a novel target in cancer therapy and for drugs against tumor cells harboring mutated p53 .
OUTPUT:
| enabling replicative immortality;genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
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"avoiding immune destruction"
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HoC_1shot851 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Glioblastoma multiforme ( GBM ) and oxidative stress are closely linked . Oxidative stress affects many signaling pathways and may cause the induction of autophagy . The NF-E2-related factor 2 ( Nrf2)/Kelch-like ECH-associated protein 1 ( Keap1 ) signaling pathway is the main pathway responsible for cell defense against oxidative stress and Nrf2 is a critical transcription factor related with cancer multidrug resistance . However , the relation between Nrf2 and regulation of autophagy is not well understood . In this study , we used temozolomide ( TMZ ) , which inhibited the viability of GBM cells mainly by inducing autophagic cell death and explored the role of Nrf2 downregulation on autophagy induced by TMZ in GBM cells . In U251-Si-Nrf2 48h after transfection the protein levels of Nrf2 were significantly downregulated , while the protein levels of LC3B-II increased by western blot analysis . Knockdown of Nrf2 also led to a significant increase of autophagic vacuoles and acidic vesicular organelles ( AVOs ) , revealed by trans-mission electron microscopy ( TEM ) and acridine orange ( AO ) staining using flow cytometry . Collectively , these findings demonstrate that knockdown of Nrf2 can enhance the basal level of autophagy in the U251 glioma cell line . Furthermore , after the treatment with TMZ ( 100µM ) for 3 days , the U251-Si-Nrf2 transfected cells showed less viability rate by cell counting kit-8 ( CCK-8 ) assay and the levels of autophagy increased obviously through analysis of western blot and AO staining using flow cytometry . Taken together , our results suggest that knockdown of Nrf2 may enhance autophagy induced by TMZ in the U251 glioma cell line , which should be further evaluated for novel anticancer activity .
OUTPUT:
| resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot852 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: LewisY ( LeY ) antigen is an oligosaccharide that is highly expressed at the cell surface in various human cancers . Increased LeY expression activates epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2 ) and promotes cell proliferation in EGFR-overexpressing cells . However , the effect of downregulation of LeY expression on cell proliferation in HER2-overexpressing cells remains unknown . FUT1 encodes α1,2-fucosyltransferase , a key enzyme for LeY synthesis . We knocked down FUT1 by short interfering RNA ( siRNA ) in four HER2-overexpressing human cancer cell lines , including NCI-N87 , MKN7 , SKBr3 and BT474 . We investigated whether downregulation of LeY and alteration in the glycosylation status of these cells affect cell proliferation and HER2 activation . Knocking down FUT1 expression markedly inhibited proliferation of NCI-N87 , which highly expressed EGFR and was sensitive to EGFR deprivation . Furthermore , FUT1 siRNA downregulated the total amount of HER2 protein , phosphorylation of HER2 and EGFR , and phosphorylation of extracellular signal-regulated kinase ( ERK ) in this cell line . Moreover , the marked downregulation of phosphorylation of HER2 and ERK was observed following short-time EGF-stimulation . These effects were not observed in the other three cell lines . Our results suggest that knockdown of FUT1 downregulates HER2 signaling via EGFR downregulation . FUT1 may serve as a new molecular target for HER2-overexpressing human cancers with activated EGFR signaling .
OUTPUT:
| sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot853 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Blind mole rats Spalax ( BMR ) are small subterranean rodents common in the Middle East . BMR is distinguished by its adaptations to life underground , remarkable longevity ( with a maximum documented lifespan of 21 y ) , and resistance to cancer . Spontaneous tumors have never been observed in spalacids . To understand the mechanisms responsible for this resistance , we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani . BMR cells proliferated actively for 7-20 population doublings , after which the cells began secreting IFN-β , and the cultures underwent massive necrotic cell death within 3 d . The necrotic cell death phenomenon was independent of culture conditions or telomere shortening . Interestingly , this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat , Heterocephalus glaber , the naked mole rat in which cells display hypersensitivity to contact inhibition . Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death . Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways , and triggered by the release of IFN-β . Thus , we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground .
OUTPUT:
| resisting cell death;enabling replicative immortality;evading growth suppressors | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot854 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Chromosomal translocations typically impair cell differentiation and often require secondary mutations for malignant transformation . However , the role of a primary translocation in the development of collaborating mutations is debatable . To delineate the role of leukemic translocation NUP98-HOXD13 ( NHD13 ) in secondary mutagenesis , DNA break and repair mechanisms in stimulated mouse B lymphocytes expressing NHD13 were analyzed . Our results showed significantly reduced expression of non-homologous end joining ( NHEJ)-mediated DNA repair genes , DNA Pkcs , DNA ligase4 , and Xrcc4 leading to cell cycle arrest at G2/M phase . Our results showed that expression of NHD13 fusion gene resulted in impaired NHEJ-mediated DNA break repair .
OUTPUT:
| genomic instability and mutation;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot855 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: A prominent feature of inflammatory diseases is endothelial dysfunction . Factors associated with endothelial dysfunction include proinflammatory cytokines , adhesion molecules , and matrix degrading enzymes . At the transcriptional level , they are regulated by the histone deacetylase sirtuin ( SIRT ) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB ( NF-κB ) . The role of SIRT6 , also a histone deacetylase , in regulating inflammation in endothelial cells is not known . The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells ( HUVECs ) in the presence of lipopolysaccharide ( LPS ) . LPS decreased expression of SIRT6 in HUVECs . Knockdown of SIRT6 increased the expression of proinflammatory cytokines ( IL-1β , IL-6 , IL-8 ) , COX-prostaglandin system , ECM remodelling enzymes ( MMP-2 , MMP-9 and PAI-1 ) , the adhesion molecule ICAM-1 , and proangiogenic growth factors VEGF and FGF-2 ; cell migration ; cell adhesion to leukocytes . Loss of SIRT6 increased the expression of NF-κB , whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity . Taken together , these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation , vascular remodelling , and angiogenesis . SIRT6 may be a potential pharmacological target for inflammatory vascular diseases .
OUTPUT:
| activating invasion and metastasis;inducing angiogenesis;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot856 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: New molecularly targeted therapies are needed for childhood ependymoma . Angiogenesis and the PDGFR pathway could be potential therapeutic targets . This study aimed to screen ependymomas for the expression and clinicopathological correlates of angiogenic factors and potential therapeutic targets including VEGFR , endoglin ( CD105 ) , CD34 , CD31 , c-Kit , PDGFR-α and PDGFR-β . Immunohistochemistry for angiogenesis factors and PDGFR-α and β was performed in 24 archival tumor samples from children and adults treated for ependymoma at our institution . CD31 density , CD105 density and pericyte coverage index ( PCI ) were calculated . These findings were correlated with clinical outcome . VEGFR2 was overexpressed in tumor cells in only one out of 24 cases , but was found overexpressed in the vessels in 6 cases . PDGFR-α and β were found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases ( 29.2 % ) . CD31 density , CD105 density and PCI did not correlate with expression of PDGFRs . Overexpression of PDGFR-α and β in tumor cells and overexpression of PDGFR-α in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFR-α in tumor cells ( 2 year progression free survival was 16.7 ± 15.2 for cases with overexpression of PDGFR-α in the tumor vs. 74.5 ± 15.2 for those with low/no expression , hazard ratio = 5.78 , p = 0.04 ) . A number of angiogenic factors are expressed in ependymoma tumor cells and tumor endothelium . Preliminary evidence suggests that the expression of PDGFRs could have a prognostic significance in ependymoma . This data suggests that PDGFRs should be further evaluated as targets using novel PDGFR inhibitors .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot857 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Engineered zinc-finger nucleases ( ZFN ) represented an innovative method for the genome manipulation in vertebrates . ZFN introduced targeted DNA double strand breaks ( DSB ) and initiated non-homologous end joining ( NHEJ ) after pronuclear or cytoplasmatic microinjection into zygotes . Resulting frame shift mutations led to functional gene ablations in zebra fish , mice , pigs and also in laboratory rats . Therefore , we targeted the rat Rag1 gene essential for the V(D)J recombination within the immunoglobulin production process and for the differentiation of mature B and T lymphocytes to generate an immunodeficient rat model in the LEW/Ztm strain . RESULTS After microinjection of Rag1 specific ZFN mRNAs in 623 zygotes of inbred LEW/Ztm rats 59 offspring were born from which one carried a 4 bp deletion . This frame shift mutation led to a premature stop codon and a subsequently truncated Rag1 protein confirmed by the loss of the full-length protein in Western Blot analysis . Truncation of the Rag1 protein was characterized by the complete depletion of mature B cells . The remaining T cell population contained mature CD4+/CD3+/TCRαβ+ as well as CD8+/CD3+/TCRαβ+ positive lymphocytes accompanied by a compensatory increase of natural killer cells in the peripheral blood . Reduction of T cell development in Rag1 mutant rats was associated with a hypoplastic thymus that lacked follicular structures . Histological evaluation also revealed the near-complete absence of lymphocytes in spleen and lymph nodes in the immunodeficient Rag1 mutant rat . CONCLUSION The Rag1 mutant rat will serve as an important model for transplantation studies . Furthermore , it may be used as a model for reconstitution experiments related to the immune system , particularly with respect to different populations of human lymphocytes , natural killer cells and autoimmune phenomena .
OUTPUT:
| genomic instability and mutation;avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot858 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: We previously demonstrated that downregulation of protein kinase CKII induces cellular senescence in human colon cancer HCT116 cells . To investigate the role of microRNAs ( miRNAs ) in CKII downregulation during senescence , we employed computational algorithms . Four miRNAs ( miR-186 , miR-216b , miR-337-3p , and miR-760 ) were predicted to be miRNAs against CKIIα mRNA . Mimics of all four miRNAs jointly downregulated CKIIα expression in HCT116 cells . Reporter analysis and RT-PCR have suggested that these four miRNAs may stimulate degradation of CKIIα mRNA by targeting its 3 ' untranslated regions ( UTRs ) . The four miRNA mimics increased senescent-associated β-galactosidase ( SA-β-gal ) staining , p53 and p21(Cip1/WAF1) expression , and reactive oxygen species ( ROS ) production . In contrast , concomitant knockdown of the four miRNAs by antisense inhibitors increased the CKIIα protein level and suppressed CKII inhibition-mediated senescence . Finally , CKIIα overexpression antagonized senescence induced by the four miRNA mimics . Therefore , the present results show that miR-186 , miR-216b , miR-337-3p , and miR-760 cooperatively promote cellular senescence through the p53-p21(Cip1/WAF1) pathway by CKII downregulation-mediated ROS production in HCT116 cells .
OUTPUT:
| enabling replicative immortality;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot859 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Aberrant expression of mucins is likely associated with cancer biology as alterations in the expression and/or glycosylation patterns of various mucins have been noted . Expression of the mucin family in gastric cancers has been reported in numerous studies , but the results are conflicting . Therefore , we investigated the potential use of mucin ( MUC)1 and 4 as prognostic markers in gastric cancer according to histological subtype . Three-hundred and sixty-five gastric adenocarcinoma patients who underwent surgical resection were selected for this study . Among the 365 gastric cancer samples tested here , 34% consisted of early gastric cancer and 66% were advanced . In terms of location , 68.7% of the cohort had intestinal-type cancer and 30.7% had diffuse-type . We constructed tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using monoclonal antibodies . Two-hundred and ninety-two patients ( 92.7% ) were positive for MUC1 and 216 ( 60.5% ) were positive for MUC4 . MUC1 expression was not correlated with any other clinicopathological variables such as age , gender , depth of invasion , lymph node metastasis , Lauren classification or recurrence . However , loss of MUC4 expression was significantly correlated with recurrence ( p=0.033 ) . MUC4 expression was also significantly correlated with better disease-free survival ( p=0.049 ) and particularly in the intestinal-type ( p=0.018 ) . Our present findings demonstrated that loss of MUC4 expression can be used as a prognostic marker in gastric cancer . Loss of MUC4 expression is a prognostic indicator of increased recurrence and poor disease-free survival in patients with gastric cancer .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot860 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: To investigate whether altered energy metabolism induces the Warburg effect and results in tumor malignancy , the respiratory enzyme citrate synthase ( CS ) was examined , silenced , and the effects analyzed . In human cervical carcinoma cells , RNAi-mediated CS knockdown induced morphological changes characteristic of the epithelial-mesenchymal transition ( EMT ) . This switch accelerated cancer cell metastasis and proliferation in in vitro assays and in vivo tumor xenograft models . Notably , CS knockdown cells exhibited severe defects in respiratory activity and marked decreases in ATP production , but great increases in glycolytic metabolism . This malignant progression was due to activation of EMT-related regulators ; altered energy metabolism resulted from deregulation of the p53/TIGAR and SCO2 pathways . This phenotypic change was completely reversed by p53 reactivation via treatment with proteasome inhibitor MG132 or co-knockdown of E3 ligase HDM2 and partially suppressed by ATP treatment . This study directly links the Warburg effect to tumor malignancy via induction of the EMT phenotype .
OUTPUT:
| activating invasion and metastasis;cellular energetics | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot861 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: When the prostate cancer cells become unresponsive to androgen therapy , resistance to chemotherapy becomes imminent , resulting in high mortality . To combat this situation , lycopodine , a pharmacologically important bioactive component derived from Lycopodium clavatum spores , was tested against hormone sensitive ( LnCaP ) and refractory ( PC3 ) prostate cancer cells in vitro . This study aims to check if lycopodine has demonstrable anti-cancer effects and if it has , to find out the possible mechanism of its action . The MTT assay was performed to evaluate the cytotoxic effect . Depolarization of mitochondrial membrane potential , cell cycle , EGF receptor activity and apoptosis were recorded by FACS ; profiles of different anti- and pro-apoptotic genes and their products were studied by semi-quantitative RT-PCR , indirect-ELISA , western blotting . Drug-DNA interaction was determined by CD spectroscopy . Administration of lycopodine down-regulated the expression of 5-lipoxygenase and the 5-oxo-ETE receptor ( OXE receptor1 ) and EGF receptor , and caused up-regulation of cytochrome c with depolarization of mitochondrial inner membrane potential , without palpable change in p53 activity , resulting in apoptosis , cell arrest at G0/G1 stage and ultimately reduced proliferation of cancer cells ; concomitantly , there was externalization of phosphotidyl serine residues . CD spectroscopic analysis revealed intercalating property of lycopodine with DNA molecule , implicating its ability to block cellular DNA synthesis . The overall results suggest that lycopodine is a promising candidate suitable for therapeutic use as an anti-cancer drug .
OUTPUT:
| resisting cell death;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot862 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND AND AIMS : Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity . We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism ( SNPs ) like TLR2 ( -196 to-174del ) , TLR3 ( C1377T ) , TLR4 ( Thr399Ile ) and TLR9 ( G2848A ) genes in patients with bladder cancer in a North Indian population . METHODS : SNPs were comprised of TLR2 ( -196 to -174 Del ) , TLR3(C1377T) , TLR4 ( Thr399Ile ) and TLR9 ( G2848A ) genes . Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer ( n=200 ) and unrelated healthy controls of similar ethnicity ( n=200 ) were genotyped by polymerase chain reaction restriction fragment length polymorphism ( PCR-RFLP ) analysis . RESULTS : In TLR2 I/D gene polymorphism , the combination of ID+DD showed a significant 3-fold increased risk ( p=0.001 ) . TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype ( ID+DD ) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer . The other genotypes of TLR3 , 4 and 9 did not exhibit any significant association with bladder cancer risk . CONCLUSIONS : Our results suggested the involvement of TLR2 ( -196 to-174 del ) in bladder cancer susceptibility ; however , TLR3 , 4 and 9 genes were not associated with risk of bladder cancer , implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer . Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot863 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: DNA mismatch repair ( MMR ) of simple base mismatches and small insertion-deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 ( MSH2)-MSH6 heterodimer to mismatched DNA . Cadmium ( Cd ) is a genotoxic heavy metal that has been recognized as a human carcinogen . Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity . Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish ( Danio rerio ) embryos . This study was undertaken to explore if Cd-induced oxidative stress down-regulated MSH gene activities . Following the exposure of zebrafish embryos at 1 h post fertilization ( hpf ) to sublethal concentrations of Cd at 3-5 μM for 4 or 9 h , a parallel down-regulation of MSH2 , MSH6 and Cu/Zn superoxide dismutase ( Cu/Zn-SOD ) gene expression was detected by real-time RT-PCR and the expression levels were 40-50% of control after a 9-h exposure . Cd exposure also induced oxidative stress , yet no inhibition of catalase gene activity was observed . Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene ( BHT ) , d-mannitol or N-acetylcysteine ( NAC ) at 1-10 μM restored Cd-suppressed msh6 expression . QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6 mRNA production . Down-regulated MSH gene activities reaching about 50% of control were also induced in embryos exposed to paraquat , a reactive oxygen species ( ROS)-generating herbicide , or hydrogen peroxide at 200 μM . Hence , Cd at sublethal levels down-regulates msh2/msh6 expression primarily via ROS as signaling molecules . The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 ( Sp1 ) . Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay , therefore excluding the involvement of Sp1 inactivation in Cd-induced MSH gene inhibition in zebrafish embryos .
OUTPUT:
| tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot864 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Progression to malignancy requires that cells overcome senescence and switch to an immortal phenotype . Thus , exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation . In the present study , we have globally profiled DNA methylation in relation to gene expression in primary , senescent and immortalized mouse embryonic fibroblasts . Using a high-resolution genome-wide mapping technique , followed by extensive locus-specific validation assays , we have identified 24 CpG islands that display significantly higher levels of CpG methylation in immortalized cell lines as compared to primary murine fibroblasts . Several of these hypermethylated CpG islands are associated with genes involved in the MEK-ERK pathway , one of the most frequently disrupted pathways in cancer . Approximately half of the hypermethylated targets are developmental regulators , and bind to the repressive Polycomb group ( PcG ) proteins , often in the context of bivalent chromatin in mouse embryonic stem cells . Because PcG-associated aberrant DNA methylation is a hallmark of several human malignancies , our methylation data suggest that epigenetic reprogramming of pluripotency genes may initiate cell immortalization . Consistent with methylome alterations , global gene expression analysis reveals that the vast majority of genes dysregulated during cell immortalization belongs to gene families that converge into the MEK-ERK pathway . Additionally , several dysregulated members of the MAP kinase network show concomitant hypermethylation of CpG islands . Unlocking alternative epigenetic routes for cell immortalization will be paramount for understanding crucial events leading to cell transformation . Unlike genetic alterations , epigenetic changes are reversible events , and as such , can be amenable to pharmacological interventions , which makes them appealing targets for cancer therapy when genetic approaches prove inadequate .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot865 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The number of renal cancers has increased over the last ten years and patient survival in advanced stages remains very poor . Therefore , new therapeutic approaches for renal cancer are essential . Englerin A is a natural product with a very potent and selective cytotoxicity against renal cancer cells . This makes it a promising drug candidate that may improve current treatment standards for patients with renal cancers in all stages . However , little is known about englerin A's mode of action in targeting specifically renal cancer cells . Our study is the first to investigate the biological mechanism of englerin A action in detail . We report that englerin A is specific for renal tumor cells and does not affect normal kidney cells . We find that englerin A treatment induces necrotic cell death in renal cancer cells but not in normal kidney cells . We further show that autophagic and pyroptotic proteins are unaffected by the compound and that necrotic signaling in these cells coincided with production of reactive oxygen species and calcium influx into the cytoplasm . As the first study to analyze the biological effects of englerin A , our work provides an important basis for the evaluation and validation of the compound's use as an anti-tumor drug . It also provides a context in which to identify the specific target or targets of englerin A in renal cancer cells .
OUTPUT:
| resisting cell death;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot866 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Regulation of poly(ADP-ribose) ( PAR ) synthesis and turnover is critical to determining cell fate after genotoxic stress . Hyperactivation of PAR synthesis by poly(ADP-ribose) polymerase-1 ( PARP-1 ) occurs when cells deficient in DNA repair are exposed to genotoxic agents ; however , the function of this hyperactivation has not been adequately explained . Here , we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β ( pol β ) . The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent , methyl methanesulfonate ( MMS ) , or to low energy laser-induced DNA damage . There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells , but not in wild-type cells . In the case of MMS treatment , PAR synthesis did not lead to cell death in the pol β null cells , but instead resulted in increased PARylation of the nonhomologous end-joining ( NHEJ ) protein Ku70 and increased association of Ku70 with PARP-1 . Inhibition of the NHEJ factor DNA-PK , under conditions of MMS-induced PARP-1 hyperactivation , enhanced necrotic cell death . These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised .
OUTPUT:
| genomic instability and mutation;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot867 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Thrombospondin-1 is a matricellular protein with potent antitumour activities , the levels of which determine the fate of many different tumours , including renal carcinomas . However , the factors that regulate this protein remain unclear . In renal carcinomas , hypoxic conditions enhance the expression of angiogenic factors that help adapt tumour cells to their hostile environment . Therefore , we hypothesized that anti-angiogenic factors should correspondingly be dampened . Indeed , we found that hypoxia decreased the thrombospondin-1 protein in several clear cell renal carcinoma cell lines ( ccRCC ) , although no transcriptional regulation was observed . Furthermore , we proved that hypoxia stimulates multiple signals that independently contribute to diminish thrombospondin-1 in ccRCC , which include a decrease in the activity of oxygen-dependent prolylhydroxylases ( PHDs ) and activation of the PI3K/Akt signalling pathway . In addition , thrombospondin-1 regulation in hypoxia proved to be important for ccRCC cell migration and invasion .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot868 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: DNA damage induced by benzene and its metabolites is thought of as an important mechanism underlying benzene genotoxicity in chronic benzene poisoning ( CBP ) . Therefore , genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population . Since benzene-induced DNA damages include DNA adducts , we hypothesized that the polymorphisms of ERCC1 ( Excision repair cross complementation group 1 ) and ERCC2/XPD ( Excision repair cross complementation group 2/xeroderma pigmentosum group D ) are associated with the risk of CBP . A case-control study involving 102 benzene-poisoned patients and 204 none-benzene-poisoned controls occupationally exposed to benzene was carried out in the Northeast region of China . The polymorphisms of codon 118 ( rs11615 ) and C8092A ( rs3212986 ) of ERCC1 , codon 751 ( rs13181 ) , 312 ( rs1799793 ) and 156 ( rs238406 ) of ERCC2/XPD were genotyped by TaqMan(®) Real-time PCR . The results showed that individuals carrying the ERCC1 codon 118 TT genotype had an increased risk of CBP ( OR(adj)=3.390 ; 95%CI : 1.393-8.253 ; P=0.007 ) comparing with its CC genotype . After stratified by smoking , gender and exposure duration we found that the increased risk of CBP associated with the ERCC1 codon 118 TT genotype confined to nonsmokers ( OR=3.214 ; 95% CI : 1.359-7.601 ; P=0.006 ) , female ( OR=3.049 ; 95% CI : 1.235-7.529 ; P=0.013 ) and exposure duration> ; 12 years ( OR=3.750 ; 95% CI : 1.041-13.513 ; P=0.035 ) . Since ERCC1 and ERCC2/XPD are both located on chromosome 19q13.3 , haplotype analysis of all 5 SNPs was also conducted . However no correlations between the risks of CBP and other genotypes or haplotypes were found . Therefore , our findings suggest an important role of ERCC1 codon 118 polymorphisms for a biomarker to CBP in the Chinese occupational population .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot869 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The DNA repair protein Ku70 is a key player in chemoresistance to anticancer agents ( e.g. , etoposide ) or radioresistance . The responses of different organs to radiation vary widely and likely depend on the cell population in the organs . Previously , we established and characterized Ku70-deficient murine lung epithelial ( Ku70 -/- MLE ) cells and found that these cells are more sensitive than Ku70 +/- MLE cells ( control cells ) to X-irradiation , as determined by clonogenic survival assay ; however , the mechanism underlying this sensitivity remains unclear . In this study , we examined the mechanism by which X-irradiation triggers the death of Ku70 -/- MLE cells . Our results showed that Ku70 -/- MLE cells were more sensitive to radiation-induced apoptosis than control cells , although X-irradiation activated caspase-3 and caspase-7 , and cleaved PARP in both cell lines . We also examined the expression level of phosphorylated H2AX ( γH2AX ) , which is a marker of DSB , and observed the phosphorylation of H2AX and the elimination of γH2AX in both cell lines after X-irradiation . The elimination in Ku70 -/- MLE cells was slower than that in control cells , suggesting that DSB repair activity in the Ku70 -/- MLE cells is lower than that in control cells . These findings suggest that Ku70 might play a key role in the inhibition of apoptosis through the DSB repair pathway in lung epithelial cells . Our findings also suggest that these cell lines might be useful for the study of Ku70 functions and the Ku70-dependent DSB repair pathway in lung epithelial cells .
OUTPUT:
| resisting cell death;genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot870 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The main feedback loop driving circadian rhythm in mice is controlled , in part , by the genes encoding the cryptochromes Cry1 and Cry2 . Targeted mutation of both Cry1 and Cry2 delay the early onset of tumor formation in p53-null mutant mice . Furthermore , Ras-transformed p53- and Cry-null mouse skin fibroblasts are more sensitive than p53 mutants to apoptotic cell death initiated by agents that activate either the intrinsic or the extrinsic apoptosis pathways . Here , we investigated the effect of Cry1 and Cry2 mutations on cell death by other genotoxic agents that generate alkylated bases , interstrand crosslinks , DNA-protein crosslinks , and double-strand breaks . Both ultraviolet ( UV ) and the UV mimetic compound oxaliplatin and the radiomimetic compound doxorubicin promoted apoptosis by upregulating the tumor suppressor p73 . However , only the UV and oxaliplatin-induced upregulation of p73 mediated by the transcription factor Egr1 , but not the doxorubicin-induced upregulation mediated by the transcription factor E2F1 , was enhanced by Cry1/Cry2 double mutation . Accordingly , Egr1 downregulation reduced oxaliplatin-induced apoptosis , whereas E2F1 downregulation reduced doxorubicin-induced apoptosis . Our findings establish distinct roles for cryptochromes in intrinsic apoptosis induced by UV mimetic and radiomimetic agents .
OUTPUT:
| resisting cell death;genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot871 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: More effective treatments for metastatic lung cancer remain a pressing clinical need . In this study , we identified migration inducting gene-7 ( MIG-7 ) protein as critical for COX-2/prostaglandin E2 ( PGE2)- and Akt/GSK-3β-dependent tumor invasion/metastasis . COX-2/PGE2 activated EP4 to enhance Akt and GSK-3β phosphorylation and β-catenin/T-cell factor/lymphoid enhancer factor signaling leading to MIG-7 upregulation . RNAi-mediated attenuation of MIG-7 blocked COX-2/PGE2- and Akt/GSK-3β-mediated migration/invasion effects . Furthermore , MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK-3β phosphorylation and cancer-cell migration/invasion . Cancer cells overexpressing MIG-7 exhibited increased expression of ZEB-1 and Twist in parallel with epithelial-mesenchymal transition , metastasis and cancer lethality . MIG-7 protein level positively correlated with advanced stages of human lung cancers . MIG-7 thus offers a theranostic target for cancer metastases arising from aberrant activation of the cellular COX-2/PGE2 and Akt/GSK-3β signaling pathways .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot872 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Ophiopogonin B ( OP-B ) is a bioactive component of Radix Ophiopogon Japonicus , which is often used in Chinese traditional medicine to treat pulmonary disease . However , whether or not OP-B has any potential antitumor activity has not been reported . Here , we show that the non-small cell lung cancer ( NSCLC ) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells . Flow cytometric analysis showed that the cells were arrested in G0/G1 phase . Nuclear morphology , Annexin-V/PI staining , and expression of cleaved caspase-3 all confirm that OP-B does not induce apoptosis . Instead , based on results from both transmission electron microscopy ( TEM ) and the expression of microtubule-associated protein 1 light chain 3-II ( LC3-II ) , we determined that OP-B treatment induced autophagy in both cell lines . Next , we examined the PI3K/Akt/mTOR signaling pathway and found that OP-B inhibited phosphorylation of Akt(Ser473 , Thr308 ) in NCI-H157 cells and also inhibited several key components of the pathway in NCI-H460 cells , such as p-Akt(Ser473 , Thr308 ) , p-p70S6K ( Thr389 ) . Additionally , insulin-mediated activation of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway may correlate with induction of autophagy in H460 cells . Therefore , OP-B is a prospective inhibitor of PI3K/Akt and may be used as an alternative compound to treat NSCLC .
OUTPUT:
| sustaining proliferative signaling;resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot873 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels . It is a complex process , involving both pro- and anti-angiogenic factors , and plays a significant role in physiological and pathophysiological processes such as embryonic development , atherosclerosis , post-ischemic vascularization of the myocardium , tumor growth and metastasis , rheumatoid arthritis etc . This is the first report of zinc oxide ( ZnO ) nanoflowers that show significant pro-angiogenic properties ( formation of new capillaries from pre-existing blood vessels ) , observed by in vitro and in vivo angiogenesis assays . The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation . Additionally , it helps to promote endothelial cell ( EA.hy926 cells ) migration in wound healing assays . Formation of reactive oxygen species ( ROS ) , especially hydrogen peroxide ( H(2)O(2))-a redox signaling molecule , might be the plausible mechanism for nanoflower-based angiogenesis . Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases , where angiogenesis plays a significant role .
OUTPUT:
| inducing angiogenesis;tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot874 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Tumor development requires angiogenesis and anti-angiogenic therapies have been introduced in the treatment of cancer . In this context , heparan sulfate proteoglycans ( HSPGs ) emerge as interesting targets , owing to their function as co-receptors of major , pro-angiogenic factors . Accordingly , previous studies have suggested anti-tumor effects of heparin , i.e. over-sulfated HS , and various heparin mimetics ; however , a significant drawback is their unspecific mechanism of action and potentially serious side-effects related to their anticoagulant properties . Here , we have explored the use of human ScFv anti-HS antibodies ( αHS ) as a more rational approach to target HSPG function in endothelial cells ( ECs). αHS were initially selected for their recognition of HS epitopes localized preferentially to the vasculature of patient glioblastoma tumors , i.e. highly angiogenic brain tumors . Unexpectedly , we found that these αHS exhibited potent pro-angiogenic effects in primary human ECs. αHS were shown to stimulate EC differentiation , which was associated with increased EC tube formation and proliferation . Moreover , αHS supported EC survival under hypoxia and starvation , i.e. conditions typical of the tumor microenvironment . Importantly , αHS-mediated proliferation was efficiently counter-acted by heparin and was absent in HSPG-deficient mutant cells , confirming HS-specific effects . On a mechanistic level , binding of αHS to HSPGs of ECs as well as glioblastoma cells was found to trigger p38 MAPK-dependent signaling resulting in increased proliferation . We conclude that several αHS that recognize HS epitopes abundant in the tumor vasculature may elicit a pro-angiogenic response , which has implications for the development of antibody-based targeting of HSPGs in cancer .
OUTPUT:
| sustaining proliferative signaling;inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot875 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Metastasis is a major cause of death of patients with malignant tumors . Matrix metalloproteinases ( MMPs ) are important for the migration and invasion of various types of cancer cell . Propofol is a known anesthetic agent , widely used for short-term anesthesia and for longer-term sedation . Propofol inhibits the proliferation of a variety of tumor cells , but there is no available information regarding propofol-inhibited migration and invasion of tumor cells in vitro . In this study , we investigated the effects of propofol on the migration and invasion of human lung carcinoma A549 cells . Wound healing assay and Boyden chamber assays indicated that propofol inhibited the migration and invasion of A549 cells in vitro . Gelatin zymographic analysis showed the inhibitory effect of propofol on the activation of expression MMP-2 . Western blot analysis also indicated that propofol suppressed the protein expiration of growth factor receptor-bound protein 2 ( GRB2 ) , Jun N-terminal kinases 1/2 ( p-JNK1/2 ) , p-p38 , MMP-2 and MMP-9 in A549 cells . Results from real-time PCR assay also showed that propofol inhibited the mRNA gene expression of MMP-2 , -7 and -9 , and enhanced that of tissue inhibitor of metalloproteinase 1 ( TIMP1 ) and TIMP2 in A549 cells . Taken together , these data show that propofol inhibits MMP-2 and -9 mRNA and protein expressions , resulting in suppression of lung cancer cell invasion and migration in vitro .
OUTPUT:
| activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot876 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Adhesion to the extracellular matrix ( ECM ) is critical for epithelial tissue homeostasis and function . ECM detachment induces metabolic stress and programmed cell death via anoikis . ECM-detached mammary epithelial cells are able to rapidly activate autophagy allowing for survival and an opportunity for re-attachment . However , the mechanisms controlling detachment-induced autophagy remain unclear . Here we uncover that the kinase PERK rapidly promotes autophagy in ECM-detached cells by activating AMP-activated protein kinase ( AMPK ) , resulting in downstream inhibition of mTORC1-p70(S6K) signaling . LKB1 and TSC2 , but not TSC1 , are required for PERK-mediated inhibition of mammalian target of rapamycinin MCF10A cells and mouse embryo fibroblast cells . Importantly , this pathway shows fast kinetics , is transcription-independent and is exclusively activated during ECM detachment , but not by canonical endoplasmic reticulum stressors . Moreover , enforced PERK or AMPK activation upregulates autophagy and causes luminal filling during acinar morphogenesis by perpetuating a population of surviving autophagic luminal cells that resist anoikis . Hence , we identify a novel pathway in which suspension-activated PERK promotes the activation of LKB1 , AMPK and TSC2 , leading to the rapid induction of detachment-induced autophagy . We propose that increased autophagy , secondary to persistent PERK and LKB1-AMPK signaling , can robustly protect cells from anoikis and promote luminal filling during early carcinoma progression.Oncogene advance online publication , 19 November 2012 ; doi:10.1038/onc.2012.512 .
OUTPUT:
| resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot877 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: In response to genotoxic stress , a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint ( DDC ) signalling pathway positively contributes to genome maintenance . Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest , cells must tightly regulate the activity of the kinases involved in this pathway . Despite their importance , the mechanisms for monitoring and modulating DDC signalling are not fully understood . Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae . On replication stress , cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53 , whereas activation of the upstream DDC kinase Mec1 remains normal . An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A , two positive regulators of Rad9-dependent Rad53 activation . A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107 . We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions . Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
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"avoiding immune destruction"
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HoC_1shot878 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Thymidine phosphorylase ( TYMP ) is an angiogenic factor that has potent chemotactic activity for endothelial cells and is involved in 5-fluorouracil ( 5-FU ) metabolism . In colorectal cancer ( CRC ) , previous studies evaluating the relationship between TYMP expression and clinicopathological features have yielded inconsistent results . The aim of this study was to investigate the prognostic value of TYMP , its association with other angiogenic factors , proliferation markers and , to our knowledge , for the first time its relationship with extracellular matrix components . MATERIALS AND METHODS Formalin-fixed , paraffin-embedded specimens from 97 patients with CRC were immunostained for TYMP , vascular endothelial growth factor ( VEGF ) , microvascular density ( CD34 ) , proliferation marker ( Ki-67 ) , proliferating cell nuclear antigen ( PCNA ) , p53 oncoprotein and extracellular matrix components ( collagen type IV , fibronectin , tenascin and laminin ) . Survival curves were calculated with the Kaplan-Meier method . RESULTS Immunoreactivity was observed in the cytoplasm ( cyt ) and nucleus ( n ) of the tumor cells , as well in the stroma ( st ) , endothelium and tumor-associated macrophages . High TYMPcyt expression was observed in 7.2% of the cases , moderate in 22.7% and weak in 59.9% , while 10.3% were negative . High TYMPst expression was observed in 58.8% of the cases . TYMPcyt expression was correlated with the VEGF expression of tumor cells and VEGF expression of vessels ( p=0.014 and p=0.022 , respectively ) . TYMPst expression was correlated with VEGF expression and tenascin ( p=0.014 and p=0.011 , respectively ) . Patients with higher TYMPcyt expression had a more favorable overall survival ( p=0.041 ) in univariate analysis compared to patients without TYMP expression . CONCLUSION These findings suggest that TYMP plays an important role in angiogenesis , extracellular matrix remodeling and in the prognosis of patients with CRC , but further studies are needed to clearly define its role in CRC .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot879 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Olfactomedin 4 ( OLFM4 ) is highly expressed in gastrointestinal cancers and has an anti-apoptotic function . The roles of OLFM4 in tumor growth and metastasis and how it functions in these processes remain elusive . We investigated the function of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an experimental system . Our results showed that OLFM4 had no positive effect on cell viability or cell cycle progression in B16F10 cells . However , it significantly suppressed the tumorigenicity of B16F10 cells , i.e. , intradermal primary tumor growth and lung metastasis . OLFM4 also suppressed the migration and invasion of B16F10 cells in vitro . For further insight into the mechanisms underlying OLFM4-mediated suppression of tumor progression , we examined the effect of OLFM4 on the expression of integrin and matrix metalloproteinase ( MMP ) , both of which are involved in tumor progression . Overexpression of OLFM4 clearly reduced the expression levels of integrin α1 , integrin α4 , integrin α5 , integrin α6 , and MMP9 . Moreover , forced expression of MMP9 attenuated the inhibitory activity of OLFM4 on migration and invasiveness . Our findings provide the experimental evidence that OLFM4 may function as a tumor suppressor and an anti-metastatic gene during tumor progression .
OUTPUT:
| sustaining proliferative signaling;activating invasion and metastasis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot880 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Endothelial cells respond to hypoxic changes with resultant accumulation of several metabolites and switch over to angiogenic phenotype . Although certain intermediates of glycolytic and oxidative metabolic pathways have been known to affect angiogenesis , the effect of citrate , which accumulates in certain tumors , on angiogenesis is not known . Therefore , the effect of citrate on angiogenesis was studied using different model systems . Increased vascularization in chorioallantoic membrane assay , increased endothelial sprouting in rat aortic rings , and increased expression of CD31 , E-selectin in endothelial cells suggested a possible proangiogenic effect of citrate . Upregulation of angiogenic factors such as vascular endothelial growth factor and fibroblast growth factor suggested that the effect of citrate involves modulation of expression of angiogenic growth factors . LY 294002 , an inhibitor of PI3K-Akt pathway , and wortmannin , an inhibitor of Akt pathway , reversed the effect of citrate in human umbilical vein endothelial cells . Citrate induced significant upregulation and activation of Akt in endothelial cells . Rapamycin , an inhibitor of mTOR , also reversed the effect of citrate in human umbilical vein endothelial cells and sprouting of aortic rings suggesting that the angiogenic effect of citrate involves activation of PI3K-Akt-mTOR pathway .
OUTPUT:
| inducing angiogenesis;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot881 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system . However , immune responses to such antigens are often muted or lacking due to the antigens being recognized as " self " , and further complicated by the tumour environment and regulation of immune cells within . In an effort to circumvent the lack of immune responses to tumour antigens , we have devised a strategy to develop potential synthetic immunogens . The strategy , termed mirror image phage display , is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system . Here as ' proof of principle ' we have selected molecular mimics of the well-characterised tumour associated antigen , the human mucin1 protein ( MUC1 ) from two different peptide phage display libraries . The putative mimics were compared in structure and function to that of the native antigen . Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells . The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells . The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides .
OUTPUT:
| avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot882 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death , especially in western countries . The toxic environmental pollutant , 1 , 2-dimethylhydrazine ( DMH ) , is also a colon-specific carcinogen . Tannic acid ( TA ) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis . In the present study , we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model . Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities , lipid peroxidation , histopathological changes and expression of early molecular markers of inflammation and tumor promotion . DMH treatment induced oxidative stress enzymes ( p<0.001 ) and an early inflammatory and tumor promotion response in the colons of Wistar rats . TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2 , i-NOS , PCNA protein expression levels and TNF-α(p<0.001) release . It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant , anti-inflammatory and antiproliferative activities .
OUTPUT:
| tumor promoting inflammation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot883 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Senescence is a cellular response preventing tumorigenesis . The Ras oncogene is frequently activated or mutated in human cancers , but Ras activation is insufficient to transform primary cells . Ina search for cooperating oncogenes , we identify the lysine demethylase JMJD2A/KDM4A . We show that JMJD2A functions as a negative regulator of Ras-induced senescence and collaborates with oncogenic Ras to promote cellular transformation by negatively regulating the p53 pathway . We find CHD5 , a known tumor suppressor regulating p53 activity , as a target of JMJD2A . The expression of JMJD2A inhibits Ras-mediated CHD5 induction leading to a reduced activity of the p53 pathway . In addition , we show that JMJD2A is overexpressed inmouse and human lung cancers . Depletion of JMJD2A in the human lung cancer cell line A549 bearing an activated K-Ras allele triggers senescence . We propose that JMJD2A is an oncogene that represents a target for Ras-expressing tumors .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot884 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: The omega-3 long chain polyunsaturated fatty acids , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , elicit antiproliferative effects in cancer cell lines and in animal models . Dietary DHA and EPA can be converted to their ethanolamine derivatives , docosahexaenoyl ethanolamine ( DHEA ) and eicosapentaenoyl ethanolamine ( EPEA ) , respectively ; however , few studies are reported on their anticancer activities . Here , we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells . Since DHA and EPA are ligands of Peroxisome Proliferator-Activated Receptor ( PPAR ) γ , we sought to determine whether PPARγ may also mediate DHEA and EPEA actions . In MCF-7 cells , both compounds enhanced PPARγ expression , stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN , resulting in the inhibition of AKT-mTOR pathways . Besides , DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction . We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining . Finally , we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor . In summary , our data show that the two omega-3 ethanolamines exert antiproliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents . J. Cell . Physiol. © 2012 Wiley Periodicals , Inc .
OUTPUT:
| resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot885 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns ( DAMPs ) . However , how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions , in the absence of pathogen associated molecular patterns ( PAMPs ) , remains poorly understood . Here , we examined antigen-specific CD8(+) T-cell responses to primary sterile necrotic tumor cells both in vitro and in vivo . We found that primary necrotic cells alone fail to generate CD8(+) T cell-dependent immune responses toward cell-associated antigens . We show that necrotic cells trigger CD8(+) T-cell immunity only in the presence of PAMPs or analogs , such as p(dI-dC) and/or unmethylated CpG DNA . The electroporation of tumor cells with these PAMPs prior to necrosis induction triggered antigen-specific CD8(+) T-cell responses through a TLR9/MyD88-dependent pathway . In addition , we found that necrotic cells contain factors that can block the cross-priming of CD8(+) T cells even under non-sterile conditions and can serve as a possible mechanism of immunosuppression . These results suggest that antigen-specific CD8(+) T-cell responses to primary necrotic tumor cells can be induced in the presence of PAMPs and thus have a substantial impact on the development of antitumor vaccination strategies .
OUTPUT:
| resisting cell death;tumor promoting inflammation;avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot886 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: PURPOSE We did this retrospective study to explore the association between epidermal growth factor receptor ( EGFR ) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer ( NSCLC ) . MATERIALS AND METHODS We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007 . The start of tyrosine kinase inhibitor therapy was treated as a censoring event . Corresponding surgical specimens of primary tumors were used to test for EGFR mutations . RESULTS Thirty patients presented with local recurrence and distant recurrence was identified in 56 . Thirty-four of the 86 patients ( 40% ) harbored EGFR mutations . Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence ( 48% versus 23% ; P = 0.024 ) . On multivariate analysis , distant recurrence was associated with a high frequency of EGFR mutations ( OR , 3.3 ; P = 0.028 ) . Survival analysis showed poor survival of patients with mutated EGFR ( HR , 2.3 ; P = 0.017 ) or with non-adenocarcinoma histology ( HR , 3.3 ; P = 0.001 ) . CONCLUSION The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients . In addition , our data indicate unfavorable disease process of EGFR mutated tumors . Further studies need to be conducted to validate these findings .
OUTPUT:
| genomic instability and mutation;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot887 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Pyruvate kinase M2 ( PKM2 ) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms . Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 Ile429/Leu431 through the ERK2 docking groove and phosphorylates PKM2 at Ser37 , but does not phosphorylate PKM1 . Phosphorylated PKM2 Ser37 recruits PIN1 for cis-trans isomerization of PKM2 , which promotes PKM2 binding to importin α5 and translocating to the nucleus . Nuclear PKM2 acts as a coactivator of β-catenin to induce c-Myc expression , resulting in the upregulation of GLUT1 , LDHA and , in a positive feedback loop , PTB-dependent PKM2 expression . Replacement of wild-type PKM2 with a nuclear translocation-deficient mutant ( S37A ) blocks the EGFR-promoted Warburg effect and brain tumour development in mice . In addition , levels of PKM2 Ser37 phosphorylation correlate with EGFR and ERK1/2 activity in human glioblastoma specimens . Our findings highlight the importance of nuclear functions of PKM2 in the Warburg effect and tumorigenesis .
OUTPUT:
| cellular energetics;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot888 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Telomerase is a ribonucleoprotein consisting of a catalytic subunit , the telomerase reverse transcriptase , TERT , and an integrally associated RNA , TR , which contains a template for the synthesis of short repetitive G-rich DNA sequences at the ends of telomeres . Telomerase can repetitively reverse transcribe its short RNA template , acting processively to add multiple telomeric repeats onto the same DNA substrate . The contribution of enzyme processivity to telomere length regulation in human cells is not well characterized . In cancer cells , under homeostatic telomere length-maintenance conditions , telomerase acts processively , while under nonequilibrium conditions , telomerase acts distributively on the shortest telomeres . To investigate the role of increased telomerase processivity on telomere length regulation in human cells with limited lifespan that are dependent on human TERT ( hTERT ) for lifespan extension and immortalization , we mutated the leucine at position 866 in the reverse transcriptase C motif of hTERT to a tyrosine ( L866Y ) , which is the amino acid found at a similar position in HIV-1 reverse transcriptase . We report that , similar to the previously reported ' gain of function ' Tetrahymena telomerase mutant ( L813Y ) , the human telomerase variant displays increased processivity. hTERT-L866Y , like wild-type hTERT can immortalize and extend the lifespan of limited lifespan cells . Moreover , hTERT-L866Y expressing cells display heterogenous telomere lengths , telomere elongation , multiple telomeric signals indicative of fragile sites and replicative stress , and an increase in short telomeres , which is accompanied by telomere trimming events . Our results suggest that telomere length and homeostasis in human cells may be regulated by telomerase enzyme processivity .
OUTPUT:
| enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot889 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response . In the present study , we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma . METHODS Ninety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined . All patients underwent radical thoracic surgery of primary tumor ( lobectomy or pneumonectomy ) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry . Follow-up was available for all patients ; mean duration of follow-up was 27.50 ± 14.07 months ( range 0.2-57 months , median 24 months ) . RESULTS Sixty-three patients ( 65.2% ) died during the follow-up period . The mean survival time was 32.2 ± 1.9 months ( 95% confidence interval [ CI ] : 28.5-35.8 months ; median 30.0 months ) ; 1- , 2- and 3-year survival rates were 86.5% ± 3.5% , 57.3% ± 5.1% , and 37.1% ± 5.4% , respectively . Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression ( 35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression , P = 0.009 ; hazard ratio [ HR ] 1.95 , 95% CI : 1.15-3.30 ) . Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival ( HR 2.15 , 95% CI : 1.22-3.79 , P = 0.026 ) . A combined p53/γ-H2AX analysis was performed , and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes . CONCLUSION Our study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer . Further studies are needed to confirm our results .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot890 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Endoplasmic reticulum ( ER ) stress induces both autophagy and apoptosis yet the molecular mechanisms and pathways underlying the regulation of these two cellular processes in cells undergoing ER stress remain less clear . We report here that eukaryotic elongation factor-2 kinase ( EEF2K ) is a critical controller of the ER stress-induced autophagy and apoptosis in tumor cells . DDIT4 , a stress-induced protein , was required for transducing the signal for activation of EEF2K under ER stress . We further showed that phosphorylation of EEF2K at Ser398 was essential for induction of autophagy , while phosphorylation of the kinase at Ser366 and Ser78 exerted an inhibitory effect on autophagy . Suppression of the ER stress-activated autophagy via silencing of EEF2K aggravated ER stress and promoted apoptotic cell death in tumor cells . Moreover , inhibiting EEF2K by either RNAi or NH125 , a small molecule inhibitor of the enzyme , rendered tumor cells more sensitive to curcumin and velcade , two anticancer agents that possess ER stress-inducing action . Our study indicated that the DDIT4-EEF2K pathway was essential for inducing autophagy and for determining the fate of tumor cells under ER stress , and suggested that inhibiting the EEF2K-mediated autophagy can deteriorate ER stress and lead to a greater apoptotic response , thereby potentiating the efficacy of the ER stress-inducing agents against cancer .
OUTPUT:
| resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot891 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: That a knock-in mouse harboring a dominant-negative thyroid hormone receptor ( TR)-β ( Thrb ) mutation develops metastatic thyroid cancer strongly suggests the involvement of TRβ in carcinogenesis . Epigenetic silencing of the THRB gene is common in human cancers . The aim of the present study was to determine how DNA methylation affected the expression of the THRB gene in differentiated thyroid cancer ( DTC ) and how reexpression of the THRB gene attenuated the cancer phenotypes . We used methylation-specific PCR to examine the expression and promoter methylation of the THRB gene in DTC tissues . Thyroid cancer cells with hypermethylated THRB were treated with the demethylating agents 5'-aza-2'-deoxycytidine ( 5'-aza-CdR ) and zebularine to evaluate their impact on the cancer cell phenotypes . THRB mRNA expression in DTC was 90% lower than in normal controls , and this decrease was associated with a higher tumor/lymph node staging . The promoter methylation level of the THRB gene had a significant negative correlation with the expression level of the THRB gene . Treatment of FTC-236 cells with 5'-aza-CdR or zebularine induced reexpression of the THRB gene and inhibited cell proliferation and migration . FTC-236 cells stably expressing TRβ exhibited lower cell proliferation and migration through inhibition of β-catenin signaling pathways compared with FTC-236 without TRβ. 5'-Aza-CdR also led to suppression of tumor growth in an in vivo xenograft model using FTC-236 cells consistent with the cell-based studies . These finding indicate that TRβ is a tumor suppressor and could be tested as a potential therapeutic target .
OUTPUT:
| activating invasion and metastasis;sustaining proliferative signaling | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot892 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: This study aimed to analyze the role of endothelial progenitor cell ( EPC)-derived angiogenic factors and chemokines in the multistep process driving angiogenesis with a focus on the recently discovered macrophage migration inhibitory factor ( MIF)/chemokine receptor axis . Primary murine and murine embryonic EPCs ( eEPCs ) were analyzed for the expression of angiogenic/chemokines and components of the MIF/CXC chemokine receptor axis , focusing on the influence of hypoxic versus normoxic stimulation . Hypoxia induced an upregulation of CXCR2 and CXCR4 but not CD74 on EPCs and triggered the secretion of CXCL12 , CXCL1 , MIF , and vascular endothelial growth factor ( VEGF ) . These factors stimulated the transmigration activity and adhesive capacity of EPCs , with MIF and VEGF exhibiting the strongest effects under hypoxia . MIF- , VEGF- , CXCL12- , and CXCL1-stimulated EPCs enhanced tube formation , with MIF and VEGF exhibiting again the strongest effect following hypoxia . Tube formation following in vivo implantation utilizing angiogenic factor-loaded Matrigel plugs was only promoted by VEGF . Coloading of plugs with eEPCs led to enhanced tube formation only by CXCL12 , whereas MIF was the only factor which induced differentiation towards an endothelial and smooth muscle cell ( SMC ) phenotype , indicating an angiogenic and differentiation capacity in vivo . Surprisingly , CXCL12 , a chemoattractant for smooth muscle progenitor cells , inhibited SMC differentiation . We have identified a role for EPC-derived proangiogenic MIF , VEGF and MIF receptors in EPC recruitment following hypoxia , EPC differentiation and subsequent tube and vessel formation , whereas CXCL12 , a mediator of early EPC recruitment , does not contribute to the remodeling process . By discerning the contributions of key angiogenic chemokines and EPCs , these findings offer valuable mechanistic insight into mouse models of angiogenesis and help to define the intricate interplay between EPC-derived angiogenic cargo factors , EPCs , and the angiogenic target tissue .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot893 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells . To resolve these contradictory observations , we studied radiosensitivities by employing breast cancer stem cell ( CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells . CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [ 1 ] . These cells were exposed to γ-rays ( 1.25-8.75 Gy ) and survival curves were determined by colony formation . A final slope , D(0) , of the survival curve for each cell line was determined to measure radiosensitivity . The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy , respectively . Similar results were observed in MDA-MB-231 cells ( 0.94 Gy vs. 1.56 Gy ) . After determination of radiosensitivity , we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution , free-radical scavengers and DNA repair . We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity , differential DNA repair capacity may be a greater determinant of radiosensitivity . Unlike non-stem cells , CSC-like cells have little/no sublethal damage repair , a low intracellular level of ataxia telangiectasia mutated ( ATM ) and delay of γ-H2AX foci removal ( DNA strand break repair ) . These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot894 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model . It was suggested that the up-regulation of IL-10 production and IL-10 receptor ( IL-10R ) expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10 , besides its immunosuppressive activity , may act as a growth factor for metastatic L-TACB cells . The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production , reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth . Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells . Considering that cyclophosphamide is a prodrug , we used mafosfamide , a compound that yields in vitro the same active metabolites as cyclophosphamide does in vivo . Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and , concomitantly , inhibited metastatic cell proliferation . We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and , as a consequence , metastatic cell proliferation . These results may have a considerable impact on the design of new therapies for metastatic lymphomas .
OUTPUT:
| activating invasion and metastasis;avoiding immune destruction | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot895 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: When the cell cycle is arrested , even though growth-promoting pathways such as mTOR are still active , then cells senesce . For example , induction of either p21 or p16 arrests the cell cycle without inhibiting mTOR , which , in turn , converts p21/p16-induced arrest into senescence ( geroconversion ) . Here we show that geroconversion is accompanied by dramatic accumulation of cyclin D1 followed by cyclin E and replicative stress . When p21 was switched off , senescent cells ( despite their loss of proliferative potential ) progressed through S phase , and levels of cyclins D1 and E dropped . Most cells entered mitosis and then died , either during mitotic arrest or after mitotic slippage , or underwent endoreduplication . Next , we investigated whether inhibition of mTOR would prevent accumulation of cyclins and loss of mitotic competence in p21-arrested cells . Both nutlin-3 , which inhibits mTOR in these cells , and rapamycin suppressed geroconversion during p21-induced arrest , decelerated accumulation of cyclins D1 and E and decreased replicative stress . When p21 was switched off , cells successfully progressed through both S phase and mitosis . Also , senescent mouse embryonic fibroblasts ( MEFs ) overexpressed cyclin D1 . After release from cell cycle arrest , senescent MEFs entered S phase but could not undergo mitosis and did not proliferate . We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence .
OUTPUT:
| sustaining proliferative signaling;enabling replicative immortality | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot896 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Gastrointestinal stromal tumor ( GIST ) is a prototype of mutant KIT oncogene-driven tumor . Prolonged tyrosine kinase inhibitor ( TKI ) treatment may result in a resistant phenotype through acquired secondary KIT mutation . Heat shock protein 90 ( HSP90AA1 ) is a chaperone protein responsible for protein maturation and stability , and KIT is a known client protein of HSP90AA1 . Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway . In this study , we demonstrated that NVP-AUY922 ( AUY922 ) , a new class of HSP90AA1 inhibitor , is effective in inhibiting the growth of GIST cells expressing mutant KIT protein , the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells . The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines . Surprisingly , AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway . The blockade of autophagy alone led to the accumulation of the KIT protein , highlighting the role of autophagy in endogenous KIT turnover . The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B- , acridine orange- or SQSTM1-labeled autophagosome , and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity . Therefore , the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs , but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation .
OUTPUT:
| resisting cell death | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
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HoC_1shot897 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Prohibiting angiogenesis is an important therapeutic approach for fighting cancer and other angiogenic related diseases . Research focused on proteins that regulate abnormal angiogenesis has attracted intense interest in both academia and industry . Such proteins are able to target several angiogenic factors concurrently , thereby increasing the possibility of therapeutic success . Aquaporin-1 ( AQP1 ) is a water channel membrane protein that promotes tumour angiogenesis by allowing faster endothelial cell migration . In this study we test the hypothesis that AQP1 inhibition impairs tumour growth in a mouse model of melanoma . After validating the inhibitor efficacy of two different AQP1 specific siRNAs in cell cultures , RNA interference experiments were performed by intratumoural injections of AQP1 siRNAs in mice . After 6 days of treatment , AQP1 siRNA treated tumours showed a 75 % reduction in volume when compared to controls . AQP1 protein level , in AQP1 knockdown tumours , was around 75 % that of the controls and was associated with a significant 40 % reduced expression of the endothelial marker , Factor VIII . Immunofluorescence analysis of AQP1 siRNA treated tumours showed a significantly lower microvessel density . Time course experiments demonstrated that repeated injections of AQP1 siRNA over time are effective in sustaining the inhibition of tumour growth . Finally , we have confirmed the role of AQP1 in sustaining an active endothelium during angiogenesis and we have shown that AQP1 reduction causes an increase in VEGF levels . In conclusion , this study validates AQP1 as a pro-angiogenic protein , relevant for the therapy of cancer and other angiogenic-related diseases such as psoriasis , endometriosis , arthritis and atherosclerosis .
OUTPUT:
| inducing angiogenesis | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
] | [
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HoC_1shot898 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: Bisphenol A is a monomer used in the production of polycarbonate plastics , epoxy resins , and flame retardants . It is an endocrine disruptor with a variety of other effects , including genotoxicity . Oxidative metabolism of bisphenol A yields electophilic bisphenol A-3,4-quinone ( BPAQ ) , which may cause genotoxicity . To determine the genotoxic potential of bisphenol A , the mechanism of the reaction between the BPAQ and deoxyadenosine ( dA ) was studied in detail . The most probable reaction pathway was determined using quantum chemical methods . Our results demonstrate that the rate limiting step is Michael addition between BPAQ and dA , the main product being the unstable N7-modified adduct that rapidly undergoes depurination . In addition , our calculations provide strong evidence for protonation of the adducts prior to depurination , which indicates pH dependence of the reaction . The calculated activation barrier for Michael addition is 28.7 kcal/mol , indicating that the reaction with dA is very slow . Comparison with the activation energy of 23.1 kcal/mol for the corresponding deoxyguanosine reaction indicates that most of the DNA damage by BPAQ will occur at the guanine site . The detoxification reactions with glutathione compete with reactions between BPAQ and DNA . The calculated free energy of activation for the reaction with glutathione is significantly lower than that for the corresponding reaction with dA . This indicates that BPAQ will preferably react with glutathione and will only react with DNA when the level of glutathione in the cell is low .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
] | [
0,
0,
0,
0,
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0,
1,
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0
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HoC_1shot899 | The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
###
INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.
OUTPUT: sustaining proliferative signaling;resisting cell death
INPUT: BACKGROUND Cellular and clinical sensitivity to ionizing radiation ( IR ) is determined by DNA double-strand breaks ( DSB ) repair . Here , we investigate the molecular mechanism underlying the extreme response of a head and neck tumor case ( SKX ) to standard radiotherapy . METHODS Immunofluorescence ( IF ) was used for the assessment of DSB repair , Western blot and real-time PCR for protein and mRNA expression , respectively . RESULTS SKX cells exhibited a pronounced radiosensitivity associated with numerous residual γ-H2AX foci after IR . This was not associated with lacking canonical repair proteins . SKX cells did not express any ATM protein . Accordingly , immunoblotting revealed no ATM kinase activity toward substrates such as p-SMC1 , p-CHK2 and p-KAP1 . Sequencing of all 66 exons of ATM showed no mutation . ATM mRNA level was moderately reduced , which could be reverted by 5'-Aza-C treatment but without restoring protein levels . Importantly , we demonstrated a post-transcriptional regulation in SKX cells via 6-fold enhanced levels of miR-421 , which targets the 3'-UTR of ATM mRNA . Transfection of SKX cells with either anti-miR-421 inhibitor or a microRNA-insensitive ATM vector recovered ATM expression and abrogated the hyper-radiosensitivity . CONCLUSION This is the first report describing microRNA-mediated down-regulation of ATM leading to clinically manifest tumor radiosensitivity .
OUTPUT:
| genomic instability and mutation | [
"sustaining proliferative signaling",
"evading growth suppressors",
"resisting cell death",
"enabling replicative immortality",
"inducing angiogenesis",
"activating invasion and metastasis",
"genomic instability and mutation",
"tumor promoting inflammation",
"cellular energetics",
"avoiding immune destruction"
] | [
0,
0,
0,
0,
0,
0,
1,
0,
0,
0
] |