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clinicalnlplab

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HoC_1shot_test

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HoC_1shot1000

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: AMPK is a metabolic sensor that helps maintain cellular energy homeostasis . Despite evidence linking AMPK with tumor suppressor functions , the role of AMPK in tumorigenesis and tumor metabolism isunknown . Here we show that AMPK negatively regulates aerobic glycolysis ( the Warburg effect ) in cancer cells and suppresses tumor growth invivo . Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis . Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis , increased allocation of glucose carbon into lipids , and biomass accumulation . These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α ( HIF-1α ) , as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling . Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation . OUTPUT:

cellular energetics

HoC_1shot1001

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: Indolylmaleimides display a broad spectrum of biological activity and offer great opportunity to influence several aspects of cell fate , as proliferation and differentiation . In this study we describe the effect of PDA-66 , a newly synthesised indolylmaleimide , showing a strong dose dependent anti-proliferative effect on immortalised human progenitor and cancer cells . We demonstrated a highly depolymerizing effect on in vitro tubulin assembly and conclude that PDA-66 acts as microtubule destabilising agent . In addition we found that PDA-66 induces mitotic arrest of cells in the G(2)/M phase of the cell cycle . Subsequently cells undergo apoptosis , indicating the major mechanism of the anti-proliferative effect . To prove a potential anti-cancer activity of PDA-66 we examined the effect of PDA-66 on human SH-SY5Y neuroblastoma and A-459 lung cancer cells , showing a significant reduction in cancer cell proliferation in a dose dependent manner . Thus PDA-66 is a new anti-mitotic compound with an indole-core with the potential to be used for cancer therapy . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot1002

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 human epithelial cancers , the microRNA ( miRNA ) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis , apoptosis , proliferation , and differentiation . Autophagy , a degradation pathway for long-lived protein and organelles , regulates the survival and death of many cell types . Increasing evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression . Using a combined bioinformatics approach , gene set enrichment analysis and miRNA target prediction , we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1 , BNIP3L , ATG12 , ATG5 , ATG2 . Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells . Finally , we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II . Taken together , our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway . This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy . OUTPUT:

resisting cell death

HoC_1shot1003

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: Compound C , a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase ( AMPK ) , has been reported to cause apoptotic cell death in myeloma , breast cancer cells and glioma cells . In this study , we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells . Compound C can induce upregulation , phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma ( BCC ) cells . The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species ( ROS ) generation and associated with activated ataxia-telangiectasia mutated ( ATM ) protein . Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines , we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy . The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression . Overall , our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status . OUTPUT:

resisting cell death;genomic instability and mutation;tumor promoting inflammation;evading growth suppressors;sustaining proliferative signaling

HoC_1shot1004

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 ( BPA ) is one of the most prevalent chemicals in daily-use materials , therefore , human exposure to BPA is ubiquitous . We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 ( GPR30)-mediated epidermal growth factor receptor ( EGFR)-extracellular regulated kinase ( ERK)-c-Fos pathway . However , through the same pathway GPR30 expression has been shown to be induced by EGF , an EGFR ligand . Thus , we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells . By transient transfection with expression plasmids , 10(-9)M BPA significantly transactivates the Gpr30-5'-flanking region through activating the GPR30 , cGMP-dependent protein kinase ( PKG ) , estrogen receptor-α ( ER-α ) , and EFGR-ERK pathways . Furthermore , an activator protein-1 ( AP-1 ) site located within this region is found to be responsible for the transactivation of BPA . Expectedly , through the same pathways , BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30 , p-ERK1/2 , p-Ser118-ER-α and cell proliferation by BPA . Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos , ER-α , and PKG pathways , presumably boosting the cells proliferation via a regulatory loop . The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA . OUTPUT:

sustaining proliferative signaling

HoC_1shot1005

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: Nitric oxide ( NO)-releasing non-steroidal anti-inflammatory drugs ( NO-NSAIDs ) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs , possess anti-proliferative , pro-apoptotic and anti-cancer activities . Here , we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice . Topical application of NO-sulindac reduced tumor incidence , number ( p<0.05 ) and volume ( p<0.005 ) as compared to UVB ( alone)-irradiated vehicle-treated mice . An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio . The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced . However , proliferation was identified as the major target of NO-sulindac in this study . A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed . The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway . UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2 , p38 and JNK1/2 . In this regard , NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2 , the direct NFκB transcription target proteins . NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial-mesenchymal transition . A marked decrease in the expression of mesenchymal markers such as Fibronectin , N-cadherin , SNAI , Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors . Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways . OUTPUT:

resisting cell death;sustaining proliferative signaling;tumor promoting inflammation;activating invasion and metastasis

HoC_1shot1006

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: Cells undergoing malignant transformation often exhibit a shift in cellular metabolism from oxidative phosphorylation to glycolysis . This glycolytic shift , called the Warburg effect , provides a mechanistic basis for targeting glycolysis to suppress carcinogenesis through the use of dietary caloric restriction and energy restriction-mimetic agents ( ERMA ) . We recently reported the development of a novel class of ERMAs that exhibits high potency in eliciting starvation-associated cellular responses and epigenetic changes in cancer cells though glucose uptake inhibition . The lead ERMA in this class , OSU-CG5 , decreases the production of ATP and NADH in LNCaP prostate cancer cells . In this study , we examined the effect of OSU-CG5 on the severity of preneoplastic lesions in male transgenic adenocarcinoma of the mouse prostate ( TRAMP ) mice . Daily oral treatment with OSU-CG5 at 100 mg/kg from 6 to 10 weeks of age resulted in a statistically significant decrease in the weight of urogenital tract and microdissected dorsal , lateral , and anterior prostatic lobes relative to vehicle controls . The suppressive effect of OSU-CG5 was evidenced by marked decreases in Ki67 immunostaining and proliferating cell nuclear antigen ( PCNA ) expression in the prostate . OSU-CG5 treatment was not associated with evidence of systemic toxicity . Microarray analysis indicated a central role for Akt , and Western blot analysis showed reduced phosphorylation and/or expression levels of Akt , Src , androgen receptor , and insulin-like growth factor-1 receptor in prostate lobes . These findings support further investigation of OSU-CG5 as a potential chemopreventive agent . OUTPUT:

sustaining proliferative signaling

HoC_1shot1007

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 hyperplasia and decreased apoptosis of airway smooth muscle cells ( ASMCs ) play an important role in the asthmatic airway remodeling . Tumor suppressor PTEN gene with phosphatase activity plays an important regulatory role in embryonic development , cell proliferation , and apoptosis , cell cycle regulation , migration ( invasion ) of the cytoskeleton . We hypotheses that PTEN gene could affect the growth and viability of ASMCs through the regulation of PI3K/Akt , MAPK , and cell cycle-related gene expression . We constructed a recombinant adenovirus to transfect ASMCs . Cells were divided into the overexpression of PTEN gene group ( Ad-PTEN-GFP ) , negative control group ( Ad-GFP ) , and blank control group ( DMEM ) . The cell apoptosis of ASMCs were evaluated by Hoechst-33342 staining and PE-7AAD double-labeled flow cytometry . The cell cycle distribution was observed by flow cytometry with PI staining . The expression of PTEN , p-Akt , total-Akt , p-ERK1/2 , total-ERK1/2 , cleaved-Caspases-3 , Caspases-9 , p21 , and Cyclin D1 were tested by the Western blotting . Our study revealed that overexpression of PTEN gene did not induce apoptosis of human ASMCs cultured in vitro . However , overexpression of PTEN inhibited proliferation of human ASMCs cultured in vitro and was associated with downregulation of Akt phosphorylation levels , while did not affect ERK1/2 phosphorylation levels . Moreover , overexpression of PTEN could induce ASMCs arrested in the G0/G1 phase through the downregulation of Cyclin D1 and upregulation of p21 expressions . OUTPUT:

resisting cell death;sustaining proliferative signaling;evading growth suppressors

HoC_1shot1008

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 the present study , the question was addressed whether anthocyanins interfere with the topoisomerase I poison irinotecan in vivo . In vivo complexes of enzyme to DNA bioassay was used to detect irinotecan-induced stabilization of topoisomerase I/DNA complexes and single cell gel electrophoresis to determine DNA-strand-break induction in the colon of male Wistar rats . Furthermore , analysis of anthocyanin concentrations in rat plasma and rat colon was included in the testing , demonstrating that anthocyanins reach the colon and the concentrations do not differ between rats that only received anthocyanins and the anthocyanin/irinotecan group . Blackberry extract was found to significantly reduce irinotecan-mediated topoisomerase I/DNA cleavable complex formation . Overall , anthocyanins did not notably increase cleavable complex formation . However , a significant increase of DNA damage was shown after a single dose of irinotecan as well as the single compounds cyanidin ( cy ) and cyanidin-3-glucoside ( cy-3-g ) . Furthermore , a significant reduction of irinotecan-induced DNA-strand breaks after a pretreatment with cy , cy-3-g and blackberry extract was observed . Thus , the question arises whether anthocyanin-rich preparations might interfere with chemotherapy or whether , due to low systemic bioavailability , the preparations might provide protective potential in the gastrointestinal tract . OUTPUT:

genomic instability and mutation

HoC_1shot1009

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: Peroxisome proliferator activated receptor γ ( PPARγ ) , a subgroup of ligand-activated nuclear receptors , plays critical roles in cell cycle regulation , differentiation , apoptosis and invasion . PPARγ is involved in tumorigenesis and is a potent target for cancer therapy . PPARγ transactivation of KLF4 has been demonstrated in various studies ; however , how PPARγ regulates KLF4 expression is not clear . In this study , we revealed that PPARγ regulates the expression of KLF4 by binding directly to the PPAR response element ( PPRE ) within the KLF4 promoter . The PPRE resided at -1657bp to -1669bp upstream of the KLF4 ATG codon , which is essential for the transactivation of TGZ-induced KLF4 expression . Furthermore , we found that stable silencing of KLF4 obviously suppressed the G1/S arrest and anti-proliferation effects induced by PPARγ ligands . Taken together , our data indicated that upregulating KLF4 upon PPARγ activation is mediated through PPRE in KLF4 promoter , thus providing further insights into PPARγ signal transduction pathway as well as a novel cancer therapeutic strategy . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1010

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: Splenic haemangiosarcomas ( HSAs ) from 122 dogs were characterized and classified according to their patterns of growth , survival time post splenectomy , metastases and chemotherapy . The most common pattern of growth was a mixture of cavernous , capillary and solid tumour tissue . Survival time post splenectomy was independent of the growth pattern ; however , it was influenced by chemotherapy and metastases . Immunohistochemical assessment of the expression of angiogenic factors ( fetal liver kinase-1 , angiopoietin-2 , angiopoietin receptor-2 and vascular endothelial growth factor A ) and conventional endothelial markers ( CD31 , factor VIII-related antigen ) revealed variable expression , particularly in undifferentiated HSAs . Therefore , a combination of endothelial markers should be used to confirm the endothelial origin of splenic tumours . OUTPUT:

activating invasion and metastasis;inducing angiogenesis

HoC_1shot1011

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: AMP-activated protein kinase ( AMPK ) has been implicated in anti-proliferative actions in a range of cell systems . Recently , it was observed that Compound C , an inhibitor of AMPK , also reduced the cell viability in human diploid fibroblasts ( HDFs ) . Compound C-induced growth arrest was associated with a decrease in the cell cycle regulatory proteins , such as proliferating cell nuclear antigen , phosphorylated pRB , cyclin-dependent protein kinases ( Cdk 2 and 4 ) , cyclins ( D and E ) , and the Cdk inhibitors ( p21 , p16 , and p27 ) . Therefore , the present study examined the molecular mechanism of the antiproliferative effects of Compound C. Although Compound C inhibited serum-induced phosphorylation of Akt and its substrate , glycogen synthase kinase-3β , it did not affect the Akt activity in vitro . Compound C significantly inhibited the receptor tyrosine phosphorylation and the activity of downstream signaling molecules , such as p85 phosphoinositide 3-kinase , phospholipase C-γ1 , and extracellular signal-regulated kinase 1/2 , induced by platelet-derived growth factor ( PDGF ) but not by epidermal growth factor- and insulin-like growth factor . In vitro growth factor receptor tyrosine kinase activity profiling revealed the IC(50) for PDGF receptor-β ( PDGFRβ ) to be 5.07 μM , whereas the IC(50) for the epidermal growth factor receptor and insulin-like growth factor receptor was ≥100 μM . The inhibitory effect of Compound C on PDGFRβ and Akt was also observed in AMPKα(1)/α(2)-knockout mouse embryonic fibroblasts , indicating that its inhibitory effect is independent of the AMPK activity . The inhibitory effect of Compound C on cell proliferation and PDGFRβ tyrosine phosphorylation was also demonstrated in various PDGFR-expressing cells , including MRC-5 , BEAS-2B , rat aortic vascular smooth muscle cells , and A172 glioblastoma cells . These results indicate that Compound C can be used as a potential antiproliferative agent for PDGF- or PDGFR-associated diseases , such as cancer , atherosclerosis , and fibrosis . OUTPUT:

sustaining proliferative signaling

HoC_1shot1012

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 O(6) -methylguanine-DNA methyltransferase ( MGMT ) is a DNA repair enzyme that can protect cells from carcinogenic effects of alkylating agents by removing adducts from the O(6) position of guanine . Evidences indicated that areca quid chewing may increase the risk of oral squamous cell carcinoma ( OSCC ) . This study was to investigate the role of MGMT expression in OSCCs and the normal oral tissues . METHODS Thirty-two OSCCs from areca quid chewers and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by the immunohistochemistry for MGMT . Primary human oral keratinocytes ( HOKs ) were challenged with arecoline , the major alkaloid of areca nut , by Western blot . Nicotine , an important component of cigarette smoke , was added to find the possible regulatory mechanisms . RESULTS Significant association was observed between low MGMT expression and advanced clinical stage of OSCCs and lymph node metastasis ( P=0.03 ) . MGMT expression was significantly higher in patients only chewing areca quid than patients both chewing areca quid and smoking ( P=0.028 ) . Arecoline was found to elevate MGMT expression in a dose- and time-dependent manner . The addition of nicotine was found to enhance arecoline-induced MGMT expression . CONCLUSION Our results indicate that MGMT could be used clinically as a predictive marker for tumor processing , the potential for lymph node metastasis as well as advanced clinical stage . MGMT expression was significantly upregulated by arecoline in HOKs . Nicotine has a synergistic effect of arecoline-induced MGMT expression . The cigarette smoking may act synergistically in the pathogenesis of OSCC in areca quid chewers via the upregulation of MGMT . OUTPUT:

activating invasion and metastasis;genomic instability and mutation

HoC_1shot1013

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 ALKBH family of proteins are highly expressed in various types of human cancer where they are involved in tumor growth and progression . However , multiple isoforms of ALKBH exist and the effect of individual isoforms on the development of urinary bladder cancer is unknown , particularly the molecular mechanisms involved in the progression from a noninvasive to invasive phenotype . We examined the role and function of ALKBH2 in human bladder cancer development in vitro and provide the first report that suppression of ALKBH2 in a human urothelial carcinoma cell line , KU7 , reduced the expression of the transmembrane mucin protein , MUC1 , and induced G1 cell cycle arrest . Moreover , reduction of ALKBH2 suppressed epithelial to mesenchymal transition ( EMT ) via increasing E-cadherin and decreasing vimentin expression . Transfection of MUC1 siRNA inhibited cell proliferation and EMT to the same extent as ALKBH2 gene silencing in vitro . ALKBH2 knockdown significantly suppressed MUC1 expression and tumor volume of bladder cancers in vivo as assessed in an orthotopic mouse model using ALKBH2 shRNA transfected KU7 cells . Immunohistochemical examination showed high expression levels of ALKBH2 in human urothelial carcinoma samples , especially in high-grade , superficially and deeply invasive carcinomas ( pT(1) and >pT(2) ) , and in carcinoma in situ but not in normal urothelium . This study demonstrates that ALKBH2 is an upstream molecule of the oncoprotein , MUC1 , and regulates cell cycle and EMT , resulting in progression of urothelial carcinomas . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot1014

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: Sonodynamic therapy ( SDT ) has shown great potential in target cancer therapy , but it induced cell death modes hasn't been fully investigated . This study was to examine autophagic and apoptotic responses to protoporphyrin IX ( PpIX ) mediated SDT in murine leukemia L1210 cells . After SDT , the occurrence of autophagy was identified by morphological observation and biochemical analysis . Meanwhile , the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death . The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies , which indicated that impairment of autophagy enhanced the anti-tumor effect of SDT through induction of apoptosis and necrosis , while caspase inhibition didn't affect autophagic vacuoles formation or protect SDT induced cytotoxicity . The findings supported that autophagic vacuoles formed upstream and independently from caspase-dependent cell death . Additionally , the possible mechanism of SDT-induced autophagy was evaluated by measurement of ROS ( reactive oxygen species ) formation . Result suggested ROS play important role in initiating autophagy , possibly through the sono-damaged mitochondria being enclosed by autophagic vacuoles . All together , these data indicate that autophagy may be cytoprotective in our experimental system , and point to an important insight into how autophagy inhibitors , in combination with SDT may contribute a regimen for cancer therapy . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot1015

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: Colorectal cancer ( CRC ) is one of the leading causes of cancer deaths in Western countries . A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease . MicroRNAs ( miRNAs ) are aberrantly expressed in cancers and appear to have both diagnostic and prognostic significance . In this study , we identified novel miRNAs associated with recurrence of CRC , and their possible mechanism of action . TaqMan� Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosas and 46 microsatellite stable CRC tumors . Four miRNAs ( miR-362-3p , miR-570 , miR-148a* and miR-944 ) were expressed at a higher level in tumors from patients with no recurrence ( p &lt ; 0.015 ) , compared to tumors from patients with recurrence . A significant association with increased disease free survival was confirmed for miR-362-3p in a second independent cohort of 43 CRC patients , using single TaqMan� microRNA assays . In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability , and proliferation mainly due to cell cycle arrest . E2F1 , USF2 and PTPN1 were identified as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p . Subsequently , these genes were confirmed as direct targets by Luciferase reporter assays . Their knockdown in vitro phenocopied the effects of miR-362-3p over-expression . We conclude that miR-362-3p may be a novel prognostic marker in CRC , and hypothesize that the positive effects of augmented miR-362-3p expression may in part be mediated through the targets E2F1 , USF2 and PTPN1. � 2012 Wiley Periodicals , Inc . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1016

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: Dichlorvos , an organophosphate ( OP ) , is known to cause oxidative stress in the central nervous system ( CNS ) . Previously we have shown that dichlorvos treatment promoted the levels of proinflammatory molecules and ultimately induced apoptotic cell death in primary microglial cells . Here we studied the effect of dichlorvos on crucial cell cycle regulatory proteins and the DNA damage sensor ataxia-telangiectasia mutated ( ATM ) . We found a significant increase in p53 and its downstream target , p21 , levels in dichlorvos-treated microglial cells compared with control cells . Moreover , dichlorvos exposure promoted the levels of different cell cycle regulatory proteins . These results along with flow cytometry results suggested that primary microglial cells were arrested at G1 and G2/M phase after dichlorvos exposure . We have shown in a previous study that dichlorvos can induce DNA damage in microglia ; here we found that microglial cells also tried to repair this damage by inducing a DNA repair enzyme , i.e. , ATM . We observed a significant increase in the levels of ATM after dichlorvos treatment compared with control . OUTPUT:

evading growth suppressors

HoC_1shot1017

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: MD-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa ( an oriental edible mushroom ) . Intraperitoneal ( i.p. ) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system . In this study , we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models . After oral administration , MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells ( DCs ) present in the Peyer's patch . The captured MD-Fraction was then transported to the spleen , thereby inducing the systemic immune response . Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway . The therapeutic response of orally administered MD-Fraction was associated with ( i ) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs , ( ii ) increased infiltration of the activated T cells into the tumor , and ( iii ) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells . Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer. � 2012 Wiley Periodicals , Inc . OUTPUT:

avoiding immune destruction

HoC_1shot1018

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 anti-tumor antibiotic salinomycin ( Sal ) was recently identified as a selective inhibitor of breast cancer stem cells ; however , the effect of Sal on hepatocellular carcinoma ( HCC ) is not clear . This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC . HCC cell lines ( HepG2 , SMMC-7721 , and BEL-7402 ) were treated with Sal . Cell doubling time was determinated by drawing growth curve , cell viability was evaluated using the Cell Counting Kit 8 . The fraction of CD133(+) cell subpopulations was assessed by flow cytometry . We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+)cell subpopulations in HCC cells . Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases . Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining . Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio . Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays . Compared to control , β-catenin expression is significantly down-regulated upon Sal addition . The Ca(2+) concentration in HCC cells was examined by flow cytometry and higher Ca(2+) concentrations were observed in Sal treatment groups . The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls . Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo . Finally , the role of Sal on in vivo Wnt/β-catenin signaling was evaluated by Western blot and immunohistochemistry . This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/β-catenin signaling via increased intracellular Ca(2+) levels . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot1019

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 pancreatic stellate cells ( PSCs ) have complex roles in pancreas , including tissue repair and fibrosis . PSCs surround ATP releasing exocrine cells , but little is known about purinergic receptors and their function in PSCs . Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability . The number of PSCs isolated from wild type ( WT ) mice was 50% higher than those from the Pfizer P2X7 receptor knock out ( KO ) mice . The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs , while KO PSCs only expressed truncated versions of the receptor . In culture , the proliferation rate of the KO PSCs was significantly lower . Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs , indicating importance of endogenous ATP . Exogenous ATP had a two-sided effect . Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM . At high ATP concentration ( 5 mM ) , WT PSCs , but not the KO PSCs died . The intracellular Ca(2+) signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120 . The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations . This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death , and therefore might be potential targets for treatments of pancreatic fibrosis and cancer . OUTPUT:

sustaining proliferative signaling

HoC_1shot1020

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: Hepatocellular carcinoma ( HCC ) is the most prevalent liver tumor and a deadly disease with limited therapeutic options . Dysregulation of cell signaling pathways is a common denominator in tumorigenesis , including hepatocarcinogenesis . The epidermal growth factor receptor ( EGFR ) signaling system is commonly activated in HCC , and is currently being evaluated as a therapeutic target in combination therapies . We and others have identified a central role for the EGFR ligand amphiregulin ( AR ) in the proliferation , survival and drug resistance of HCC cells . AR expression is frequently up-regulated in HCC tissues and cells through mechanisms not completely known . Here we identify the β-catenin signaling pathway as a novel mechanism leading to transcriptional activation of the AR gene in human HCC cells . Activation of β-catenin signaling , or expression of the T41A β-catenin active mutant , led to the induction of AR expression involving three specific β-catenin-Tcf responsive elements in its proximal promoter . We demonstrate that HCC cells expressing the T41A β-catenin active mutant show enhanced proliferation that is dependent in part on AR expression and EGFR signaling . We also demonstrate here a novel cross-talk of the EGFR system with fibroblast growth factor 19 ( FGF19 ) . FGF19 is a recently identified driver gene in hepatocarcinogenesis and an activator of β-catenin signaling in HCC and colon cancer cells . We show that FGF19 induced AR gene expression through the β-catenin pathway in human HCC cells . Importantly , AR up-regulation and EGFR signaling participated in the induction of cyclin D1 and cell proliferation elicited by FGF19 . Finally , we demonstrate a positive correlation between FGF19 and AR expression in human HCC tissues , therefore supporting in clinical samples our experimental observations . These findings identify the AR/EGFR system as a key mediator of FGF19 responses in HCC cells involving β-catenin signaling , and suggest that combined targeting of FGF19 and AR/EGFR may enhance therapeutic efficacy . OUTPUT:

sustaining proliferative signaling

HoC_1shot1021

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 cancers express the cholinergic autocrine loop , which facilitates the progression of cancer cells . The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers ( SCLCs ) . In this study we intended to investigate the growth inhibitory effect of R2HBJJ , a novel muscarinic antagonist , on non-small cell lung cancer ( NSCLC ) cells and the possible mechanisms . The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs . R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea . R2HBJJ markedly suppressed the growth of NSCLC cells , such as H1299 , H460 and H157 . In H1299 cells , both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin . Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition . Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection , respectively . Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb . Therefore , the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells . R2HBJJ , as a novel mAChRs antagonist , can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth , which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1022

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 repair is an essential cellular process required to maintain genomic stability . Every cell is subjected to thousands of DNA lesions daily under normal physiological conditions . Ionizing radiation ( IR ) is a major DNA damaging agent that can be produced by both natural and man-made sources . A common source of radiation exposure is through its use in medical diagnostics or treatments such as for cancer radiotherapy where relatively high doses are received by patients . To understand the detailed DNA repair gene transcription response to high dose IR , gene expression exon array studies have been performed and the response to radiation in two divergent cell types , lymphoblastoid cell lines and primary fibroblasts , has been examined . These exon arrays detect expression levels across the entire gene , and have the advantage of high sensitivity and the ability to identify alternative transcripts . We found a selection of DNA repair genes , including some not previously reported , that are modulated in response to radiation . Detailed dose and time course kinetics of DNA repair transcription was conducted and results have been validated utilizing PCR methods . Alternative transcription products in response to IR were identified in several DNA repair genes including RRM2B and XPC where alternative initiation sites were found . These investigations have advanced the knowledge about the transcriptional response of DNA repair . OUTPUT:

genomic instability and mutation

HoC_1shot1023

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: Prostate cancer is the second most common cancer in elderly men worldwide and its incidence rate is rising continuously . Agents capable of inducing apoptosis in prostate cancer cells seem a promising approach to treat this malignancy . In this study we describe the synthesis of a number of novel N- and N,N'-substituted S-2,3,4,5,6-pentabromobenzylisothiouronium bromides and their activity against the human prostate adenocarcinoma PC3 cell line . All the compounds produced changes in mitochondrial transmembrane potential and cell cycle progression , showed a cytostatic effect and induced apoptosis in the tested cancer line in a concentration- and time-dependent manner . The most effective compounds ZKK-3 , ZKK-9 and ZKK-13 produced , at 20 microM concentration , apoptosis in 42 , 46 , and 66% of the cells , respectively , after 48 h incubation . Two selected S-2,3,4,5,6-pentabromobenzylisothiouronium bromides ( ZKK-3 , ZKK-9 ) showed also a synergic proapoptotic effect with the new casein kinase II inhibitor 2-(4-methylpiperazin-1-yl)-4,5,6,7-tetrabromo-1H-benzimidazole ( TBIPIP ) in the PC3 cell line . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot1024

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 investigate the effect of bufalin on nucleus-mitochondria localization of human telomerase reverse transcriptase(hTERT) by exploring its effect on proliferation and apoptosis in human esophageal squamous carcinoma EC9706 cells . Methods EC9706 cells were treated with bufalin at various concentrations , and then the cell growth inhibition of EC9706 cells was examined by CCK-8 assay and the 50% inhibitory concentration ( IC(50) ) was calculated.Cell cycle analysis was performed by flow cytometry with PI staining , and nucleus morphology of apoptosis were observed by fluorescence microscopy with Hoechst 33342 staining . The apoptotic index was measured by flow cytometry with Annexin V-FITC/PI double staining. hTERT subcellular localization and protein expression were determined by Western blotting and multiple immunofluorescence labling combined with laser confocal scanning microscopy . Results The proliferation of EC 9706 cells was significantly inhibited by bufalin along with the increase of processing time and concentrations ( p<0.01 ) . After the EC9706 cells were exposed to 100 nmol/L bufalin,the number of cells gradually decreased in G(1) phase and increased in S and G(2)/M phases(p<0.05) . The typical nucleus morphological changes of apoptosis were observed and the apoptotic index was increased(p<0.01) . The expression of hTERT decreased in nucleus but increased in mitochondria(p<0.05) . Conclusions Bufalin can inhibit the proliferation of human esophageal squamous carcinoma EC9706 cells in a time- and dose-dependent manner . It can arrest cell cycle in S and G(2)/M phases and induce the apoptosis of EC 9706 cells. hTERT is localized in both nucleus and mitochondria,and can be partially translocated from nucleus to mitochondria during the bufalin-induced apoptosis . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot1025

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: Induced pluripotent stem ( iPS ) cells share some basic properties , such as self-renewal and pluripotency , with cancer cells , and they also appear to share several metabolic alterations that are commonly observed in human tumors . The cancer cells ' glycolytic phenotype , first reported by Otto Warburg , is necessary for the optimal routing of somatic cells to pluripotency . However , how iPS cells establish a Warburg-like metabolic phenotype and whether the metabolic pathways that support the bioenergetics of iPS cells are produced by the same mechanisms that are selected during the tumorigenic process remain largely unexplored . We recently investigated whether the reprogramming-competent metabotype of iPS cells involves changes in the activation/expression status of the H ( + ) -ATPase , which is a core component of mitochondrial oxidative phosphorylation that is repressed at both the activity and protein levels in human carcinomas , and of the lipogenic switch , which refers to a marked overexpression and hyperactivity of the acetyl-CoA carboxylase ( ACACA ) and fatty acid synthase ( FASN ) lipogenic enzymes that has been observed in nearly all examined cancer types . A comparison of a starting population of mouse embryonic fibroblasts and their iPS cell progeny revealed that somatic cell reprogramming involves a significant increase in the expression of ATPase inhibitor factor 1 ( IF1 ) , accompanied by extremely low expression levels of the catalytic β-F1-ATPase subunit . The pharmacological inhibition of ACACA and FASN activities markedly decreases reprogramming efficiency , and ACACA and FASN expression are notably upregulated in iPS cells . Importantly , iPS cells exhibited a significant intracellular accumulation of neutral lipid bodies ; however , these bodies may be a reflection of intense lysosomal/autophagocytic activity rather than bona fide lipid droplet formation in iPS cells , as they were largely unresponsive to pharmacological modulation of PPARgamma and FASN activities . The AMPK agonist metformin , which endows somatic cells with a bioenergetic infrastructure that is protected against reprogramming , was found to drastically elongate fibroblast mitochondria , fully reverse the high IF1/β-F1-ATPase ratio and downregulate the ACACA/FASN lipogenic enzymes in iPS cells . The mitochondrial H ( + ) -ATP synthase and the ACACA/FASN-driven lipogenic switch are newly characterized as instrumental metabolic events that , by coupling the Warburg effect to anabolic metabolism , enable de-differentiation during the reprogramming of somatic cells to iPS cells . OUTPUT:

cellular energetics

HoC_1shot1026

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: Filamin-A cross-links actin filaments into dynamic orthogonal networks , and interacts with an array of proteins of diverse cellular functions . Because several filamin-A interaction partners are implicated in signaling of cell mobility regulation , we tested the hypothesis that filamin-A plays a role in cancer metastasis . Using four pairs of filamin-A proficient and deficient isogenic cell lines , we found that filamin-A deficiency in cancer cells significantly reduces their migration and invasion . Using a xenograft tumor model with subcutaneous and intracardiac injections of tumor cells , we found that the filamin-A deficiency causes significant reduction of lung , splenic and systemic metastasis in nude mice . We evaluated the expression of filamin-A in breast cancer tissues by immunohistochemical staining , and found that low levels of filamin-A expression in cancer cells of the tumor tissues are associated with a better distant metastasis-free survival than those with normal levels of filamin-A . These data not only validate filamin-A as a prognostic marker for cancer metastasis , but also suggest that inhibition of filamin-A in cancer cells may reduce metastasis and that filamin-A can be used as a therapeutic target for filamin-A positive cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot1027

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 increasing evidence supported the role of Enhancer of Zeste Homolog 2 ( EZH2 ) in the cancer development and progression . However , its precise role in the tumorigenesis of Nasopharyngeal Carcinoma ( NPC ) remains to be elucidated . EZH2 was depleted by retroviral infection in the NPC cells ( HK-1 , CNE-2 , CNE-1 and C666-1 ) . The degree of EZH2 knockdown was then assessed by real-time quantitative PCR and Western Blot analysis . Cell proliferation was assessed using the soluble tetrazolium salt ( MTS ) cell proliferation assay , and cell cycle was measured by FACS test . The methylation status of p16(INK4a )was determined by bisulphate treatment of the DNA , followed by MSP . EZH2 was over-expressed in NPC cells , and the expression in undifferentiated-derived NPC cells ( CNE-1 , C666-1 ) was more significant than differentiated-derived NPC cells ( HK-1 , CNE-2 ) . EZH2 was successfully depleted after retroviral infection in C666-1 cells , and the EZH2 depletion could inhibit the proliferation and arrested G1/S phase of NPC cells . In addition , both mRNA and protein levels of p16(INK4a) increased significantly in presence of EZH2 depletion . The further Methylation-Specific Polymerase Chain Reaction ( MSP ) assay suggested that over-expressed EZH2 may contribute to the reduction of p16(INK4a) expression by hyper methylating its promoter . EZH2 is overexpressed in NPC and reduces expression of p16(INK4a) by influencing methylation , opening therapeutic options . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1028

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: Immunosuppressive oligodeoxynucleotides ( SupODNs ) containing repetitive TTAGGG motifs reduce inflammation and , thus , may have an impact on inflammation‑related tumor growth . In this study , we found a significant antiproliferative effect of Sup ODNs on the A549 non‑small cell lung cancer ( NSCLC ) cell line compared to those treated with control ODNs ( p<0.05 ) . Sup-ODN-mediated G1 phase cell cycle arrest was achieved via inhibition of Akt and extracellular signal-regulated kinase 1/2 phosphorylation and the p15INK4b and p27KIP1/retinoblastoma protein pathway . In addition , Sup ODNs induced apoptosis and enhanced apoptosis when combined with vinorelbine . In a setting similar to clinical use of multidrug chemotherapy for advanced NSCLC , these effects were investigated by using Sup ODNs in combination with conventional anticancer drugs . Sup ODNs had a significant synergistic effect with 5-fluorouracil , vinorelbine , gemcitabine , paclitaxel and irinotecan , with a mean combination index of 0.43-0.78 ( <1.0 indicates synergism ) in the A549 NSCLC cell line . In conclusion , our results showed that Sup ODNs have an anticancer effect and increase the sensitivity of NSCLC cells to conventional anticancer drugs by modifying Akt and the extracellular signal-regulated kinase 1/2 pathway . Thus , Sup ODNs may serve as a novel therapeutic strategy for NSCLC patients . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot1029

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 mammalian cells more than 90% of double-strand breaks are repaired by NHEJ . Impairment of this pathway is associated with cell cycle arrest , cell death , genomic instability and cancer . Human diseases such as Nijmegen breakage syndrome , due to mutations in the NBS1 gene , produce defects in resection of double-strand breaks . NBS1 hypomorphic mutant mice are viable , and cells from these mice are defective in S phase and G2/M checkpoints . NBS1 polymorphisms have been associated with increased risk of breast cancer . We previously demonstrated that estradiol protected estrogen receptor ( ER)-positive ( + ) breast cancer cell lines against double-strand breaks and cell death . We now demonstrate that protection from double-strand break damage in ER+ cells is mediated via regulation by c-myc , p53 , CBP and SRC1 coactivators in intron 1 of the NBS1 gene . We concluded that NBS1 is responsible for estradiol-mediated protection from double-strand breaks in ER+ breast cancer cells . OUTPUT:

genomic instability and mutation

HoC_1shot1030

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: Diarylquinoline compounds are newly synthesized derivatives of the new anti-tuberculosis drug , TMC207 . In this study , nine diarylquinoline compounds were screened for cytotoxic activity against human tumor cells , and their mechanisms of action were investigated . Among the nine compounds , STM-57 [ N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methl)-N-(3,4-dichlorophenyl)-3-(4 -methylpiperazin-1-yl)propanamide ] showed potent cytotoxic activity . STM-57 induced caspase-independent cell death in the human nasopharyngeal carcinoma cell line , CNE-2 . Further investigation showed that STM-57 induced autophagy , as determined with the increased expression of green fluorescent protein-light chain3 ( GFP-LC3 ) and increased LC3-II levels . STM-57 inhibited the phosphorylation of Akt and the mammalian target of rapamycin ( mTOR ) in CNE-2 cells . The intracellular calcium concentration and reactive oxygen species levels were increased in CNE-2 cells following treatment with STM-57 , whereas the mitochondrial transmembrane potential ( ΔΨm ) and ATP concentrations were decreased . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot1031

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: Here , we provide the necessary proof of concept , that it is possible to metabolically create a non-permissive or " hostile " stromal microenvironment , which actively prevents tumor engraftment in vivo . We developed a novel genetically engineered fibroblast cell line that completely prevents tumor formation in mice , with a 100% protection rate . No host side effects were apparent.This could represent a viable cellular strategy for preventing and treating a variety of human cancers . More specifically , we examined the autocrine and paracrine effects of the cellular delivery of TNF-alpha on breast cancer tumor growth and cancer metabolism . For this purpose , we recombinantly overexpressed TNF-alpha in human breast cancer cells ( MDA-MB-231 ) or human immortalized fibroblasts ( hTERT-BJ1 ) . Our results directly show that TNF-alpha functions as a potent tumor suppressor . Remarkably , TNF-alpha-expressing breast cancer cells were viable , without any significant increases in their basal apoptotic rate . However , after 4 weeks post-implantation , TNF-alpha-expressing breast cancer cells failed to form any tumors in xenografted mice ( 0 tumors/10 injections ) , ultimately conferring 100% protection against tumorigenesis . Similarly , TNF-alpha-overexpressing fibroblasts were also viable , without any increases in apoptosis . Significantly , complete tumor suppression was obtained by co-injecting TNF-alpha expressing stromal fibroblasts with human breast cancer cells , indicating that paracrine cell-mediated delivery of TNF-alpha can also prevent tumor engraftment and growth ( 0 tumors/10 injections ) . Mechanistically , TNF-alpha induced autophagy and mitochondrial dysfunction in both epithelial cancer cells and stromal fibroblasts , preventing energy transfer from the tumor microenvironment , likely " starving " the cancer cells to death . In addition , via qRT-PCR analysis of MDA-MB-231 cells , we observed that TNF-alpha mediated the up-regulation of gene transcripts associated with inflammation and senescence [ IL-1-beta , IL-6 , IL-8 , MCP-1 , COX-2 , p21(WAF1/CIP1) ] and downregulated known tumor-promoting genes ( collagen VI and MMP2 ) . Recombinant overexpression of TNF-alpha receptor(s) in MDA-MB-231 cells also significantly reduced tumor growth , but was not as effective as the TNF-alpha ligand itself in preventing tumor growth . Thus , we propose that stromal cell-mediated delivery of TNF-alpha to human tumors [ using transfected fibroblasts or mesenchymal stem cells ( hMSCs) ] may be a novel and effective strategy for the prevention and treatment of human cancers . OUTPUT:

resisting cell death;enabling replicative immortality;tumor promoting inflammation

HoC_1shot1032

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 aberrant expression of human epidermal growth factor receptor-2 ( HER-2 ) has been detected in ovarian cancer . However , the role of HER-2 in the development of ovarian cancer has not been sufficiently elucidated . The objective of this study was to determine the role of HER-2 in the apoptosis and metastasis of SKOV-3 ovarian cancer cells . SKOV-3 cells were transfected with three double‑stranded small interfering RNA ( siRNA ) molecules that target HER-2 . Various sequences were synthesized by T7 transcription invitro to select the most effective HER-2‑silencing siRNA . SKOV-3 cells were examined for growth inhibition using the MTT proliferation assay and apoptosis was assessed using flow cytometry and TUNEL assay . The Matrigel basement memebrane matrix was used to assess invasion and chemotactic mobility , as a model of tumor cell metastasis . Western blot analysis was used to detect the expression of matrix metallopeptidase-9 ( MMP-9 ) , E-cadherin , N-cadherin and vimentin. siRNA interference in HER-2 resulted in decreased cell proliferation and invasion and increased apoptosis . Western blot analysis demonstrated a marked increase in E-cadherin and MMP-9 and a reduction in N-cadherin and vimentin protein levels in the SKOV-3 cells . The suppression of HER-2 expression resulted in apoptosis and the inhibition of metastasis of SKOV-3 cells . Therefore , the overexpression of the HER-2 gene can enhance the metastatic potential of SKOV-3 cells by increasing the protein levels of MMP-9 . Epithelial-mesenchymal transition may be involved in the HER-2 siRNA-induced invasion and migration of SKOV-3 cells . Taken together , these results suggest that HER-2 functions as an oncogene and may thus be an attractive therapeutic target in SKOV-3 ovarian cancer cells . OUTPUT:

activating invasion and metastasis;resisting cell death;sustaining proliferative signaling

HoC_1shot1033

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: Cell invasion is required for neoplastic metastasis . Matrix metalloproteinase-9 ( MMP-9 ) , which degrades the extracellular matrix , is a major component in the process of cancer cell invasion . Sulfuretin is one of the major flavonoids isolated from Rhus verniciflua . Sulfuretin has been used to reduce oxidative stress , platelet aggregation , the inflammatory response and mutagenesis . However , the effect of sulfuretin on breast cancer metastasis is unknown . In this study , we investigated the inhibitory effect of sulfuretin on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells . Sulfuretin inhibited TPA-induced transcriptional activation of nuclear factor-κB ( NF-κB ) . We demonstrated that sulfuretin mediated the inhibition of TPA-induced MMP-9 expression and that cell invasion in MCF-7 cells involved suppression of the NF-κB pathway . Therefore , inhibiting MMP-9 expression by sulfuretin may have therapeutic potential for controlling breast cancer invasiveness . OUTPUT:

activating invasion and metastasis

HoC_1shot1034

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: Prostate cancer is responsible for major deaths globally after lung cancer . However , etiology of prostate cancer is still unknown . Individual risk and incidence of prostate cancer may result from the interaction of genetic susceptibility with exposure to environmental factors such as infectious agents , tobacco , occupational exposure , dietary carcinogens , and/or hormonal imbalances leading to injury of the prostate and to the development of chronic inflammation . About 30% of all human cancers are caused by tobacco smoking and inhaled pollutants . Inflammation is now regarded as an important hallmark of cancer . The present study has been aimed to explore the pro-inflammatory levels in prostate carcinoma patients by examining the serum levels of novel cytokine interleukin-18 ( IL-18 ) expression in tobacco exposed population . A total of 578 ( n = 284 biopsy proven prostate cancer patients , n = 294 controls with and without tobacco exposed population ) were recruited . Serum IL-18 ( Interleukin-18 ) level was done by ELISA . The IL-18 levels between cancer patients and controls within same mode tobacco exposure as tobacco smoking ( overall ) showed significant difference ( P &lt ; 0.0001 ) and further we compared within stratified group , it significantly differ ( P &lt ; 0.0001 ) in bidi and cigarette smoking than control non users . Furthermore , IL-18 levels in tobacco chewers ( overall ) with gutkha and khaini chewers showed significant difference ( P &lt ; 0.01 ) than controls non users . Moreover , the IL-18 levels between cancer patients and controls with in of combined mode chewers smokers and alcohol ( CSA ) , smokers with alcohol showed significant difference ( P &lt ; 0.01 ) than controls . The IL-18 levels also differed significantly ( P &lt ; 0.05 ) with smokers and chewers in higher stages of III and IV , and showed non significant with in lower stages . Tobacco exposure enhance the inflammation in prostate carcinoma patients in stratified group as it have been represented as a risk factors in various cancers , but this study provide further its role that seems to influence inflammation especially in prostate carcinoma . OUTPUT:

tumor promoting inflammation

HoC_1shot1035

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 In addition to its effects on cholesterol levels , apoE3 has lipid-independent effects that contribute to cardiovascular protection ; one of these effects is the ability to inhibit cell cycling in VSMCs . The goal of this study was to identify and characterize cell cycle-regulatory mechanisms responsible for the anti-mitogenic effect of apoE . METHODS AND RESULTS Primary VSMCs were stimulated with serum in the absence or presence of apoE3. apoE3 upregulated expression of the cdk inhibitor , p27(kip1) , in primary VSMCs , and this effect required Cox2 and activation of PGI(2)-IP signaling . The microRNA family , miR221/222 has recently been identified as a post-translational regulator of p27 , and apoE3 inhibited miR221/222 expression in a Cox2- and PGI(2)/IP-dependent manner . Moreover , reconstituted miR222 expression was sufficient to override the effects of apoE on p27 expression and S phase entry . The ability to repress expression of miR221/222 is shared by apoE3-containing HDL but is absent from apoA-1 , LDL and apoE-depleted HDL . All three apoE isoforms regulate miR221/222 , and the effect is independent of the C-terminal lipid-binding domain. miR221/222 levels are increased in the aortae of apoE3-null mice and reduced when apoE3 expression is reconstituted by adeno-associated virus infection . Thus , regulation of miR221/222 by apoE3 occurs invivo as well as invitro . CONCLUSIONS ApoE inhibits VSMC proliferation by regulating p27 through miR221/222 . Control of cell cycle-regulatory microRNAs adds a new dimension to the spectrum of cardiovascular protective effects afforded by apoE and apoE-HDL . OUTPUT:

evading growth suppressors

HoC_1shot1036

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 kinase B ( AKT)/mammalian target of rapamycin ( mTOR ) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors , and has been shown to be important therapeutic targets for cancer . The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma ( HA ) . Twenty-five cases of human HA tissues were collected . The expression of AKT , mTOR and proliferating cell nuclear antigen ( PCNA ) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA . AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR ( rAd5-Am ) , used for infecting proliferating phase HA-derived endothelial cells ( HDEC ) . The expression of AKT , mTOR and PCNA was detected by Real-time PCR and Western blot assays . Cell proliferative activities were determined by MTT assay , and cell cycle distribution and apoptosis were analyzed by flow cytometry . As a consequence , the expression of AKT , mTOR and PCNA was significantly increased in proliferative phase HA , while that was decreased in involutive phase . Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities , and induced cell apoptosis and cycle arrest with the decreased expression of AKT , mTOR and PCNA in proliferative phase HDEC . In conclusion , the activity of AKT/mTOR pathway was increased in proliferative phase HA , while it was decreased in involutive phase . Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression , and induce apoptosis and cycle arrest in proliferative phase HDEC , suggesting that AKT/mTOR pathway might represent the important therapeutic targets for human HA . OUTPUT:

resisting cell death;sustaining proliferative signaling;evading growth suppressors

HoC_1shot1037

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: Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy . Therefore , there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response . Recently , several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer . In order to explore the predictive value of inflammation in breast cancer patients , we measured the inflammatory biomarkers serum ferritin and C-reactive protein ( CRP ) in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival . The elevation in pre-treatment serum ferritin ( >250 ng/ml ) or CRP ( >7.25 mg/l ) was a significant predictor of reduced progression-free survival and shorter overall survival . When patients were stratified based on their serum ferritin and CRP levels , patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy . Therefore , the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy . Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics . OUTPUT:

tumor promoting inflammation

HoC_1shot1038

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: Nuclear factor kappa-B ( NF-κB ) activates multiple genes with overlapping roles in cell proliferation , inflammation and cancer . Using an unbiased approach we identified human CDK6 as a novel kinase phosphorylating NF-κB p65 at serine 536 . Purified and reconstituted CDK6/cyclin complexes phosphorylated p65 in vitro and in transfected cells . The physiological role of CDK6 for basal as well as cytokine-induced p65 phosphorylation or NF-κB activation was revealed upon RNAi-mediated suppression of CDK6 . Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-κB and TNF-induced gene expression . In complex with a constitutively active viral cyclin CDK6 stimulated NF-κB p65-mediated transcription in a target gene specific manner and this effect was partially dependent on its ability to phosphorylate p65 at serine 536 . Tumor formation in thymi and spleens of v-cyclin transgenic mice correlated with increased levels of p65 Ser536 phosphorylation , increased expression of CDK6 and upregulaton of the NF-κB target cyclin D3 . These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-κB to chronic inflammation and neoplasia . OUTPUT:

tumor promoting inflammation

HoC_1shot1039

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: Angiogenesis , the formation of new blood vessels from pre-existing vascular beds , is essential for tumor growth , invasion , and metastasis . Luteolin is a common dietary flavonoid found in fruits and vegetables . We studied the antiangiogenic activity of luteolin using in vitro , ex vivo , and in vivo models . In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation , migration , invasion and tube formation of endothelial cells , which are key events in the process of angiogenesis . Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay ( CAM ) and matrigel plug assay . Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9 . Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 in HUVECs . Proinflammatory cytokines such as IL-1β , IL-6 , IL-8 , and TNF-α level were significantly reduced by the treatment of luteolin in PC-3 cells . Luteolin ( 10 mg/kg/d ) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model , indicating that luteolin inhibited tumorigenesis by targeting angiogenesis . CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin . Moreover , luteolin reduced cell viability and induced apoptosis in prostate cancer cells , which were correlated with the downregulation of AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 expressions . Taken together , our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis . OUTPUT:

inducing angiogenesis;resisting cell death

HoC_1shot1040

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: Tumors are infiltrated by macrophages , T and B-lymphocytes , which may favor tumor development by promoting angiogenesis , growth and invasion . The aim of this study was to investigate the clinical relevance of the relative amount of macrophages ( CD68⁺ ) , T-cells ( CD3⁺ and B-cells ( CD20⁺ ) at the invasive front of breast carcinomas , and the expression of matrix metalloproteases ( MMPs ) and their inhibitors ( TIMPs ) either at the invasive front or at the tumor center . We performed an immunohistochemical study counting CD3 , CD20 and CD68 positive cells at the invasive front , in 102 breast carcinomas . Also , tissue sections were stained with MMP-2 , -9 , -11 , -14 and TIMP-2 antibodies , and immunoreactivity location , percentage of reactive area and intensity were determined at the invasive front and at the tumor center . The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center ( p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio , respectively for MMP-11 and TIMP-2 ) . In addition , a high CD68/(CD3+CD20) ratio ( >0.05 ) was directly associated with a higher probability of shortened relapse-free survival . Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival ( RR : 2.54 , CI : ( 1.23-5.24 ) , p<0.01 ) . Therefore , CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot1041

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 the leading cause of cancer-related deaths in the world . Achaete-scute complex homolog-1 ( Ascl1 ) is a member of the basic helix-loop-helix ( bHLH ) transcription factor family that has multiple functions in the normal and neoplastic lung such as the regulation of neuroendocrine differentiation , prevention of apoptosis and promotion of tumor-initiating cells . We now show that Ascl1 directly regulates matrix metalloproteinase-7 ( MMP-7 ) and O(6)-methylguanine-DNA methyltransferase ( MGMT ) . Loss- and gain-of-function experiments in human bronchial epithelial and lung carcinoma cell lines revealed that Ascl1 , MMP-7 and MGMT are able to protect cells from the tobacco-specific nitrosamine NNK-induced DNA damage and the alkylating agent cisplatin-induced apoptosis . We also examined the role of Ascl1 in NNK-induced lung tumorigenesis in vivo . Using transgenic mice which constitutively expressed human Ascl1 in airway lining cells , we found that there was a delay in lung tumorigenesis . We conclude that Ascl1 potentially enhances DNA repair through activation of MMP-7 and MGMT which may impact lung carcinogenesis and chemoresistance . The study has uncovered a novel and unexpected function of Ascl1 which will contribute to better understanding of lung carcinogenesis and the broad implications of transcription factors in tobacco-related carcinogenesis . OUTPUT:

genomic instability and mutation;resisting cell death

HoC_1shot1042

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: Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer . Here , we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger ( SDGE ) are potent inhibitors of proliferation of endometrial cancer cells . SDGE , isolated from six different batches of ginger rhizomes , consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50) of 1.25 �g/ml . SDGE also enhanced the anti-proliferative effect of radiation and cisplatin . Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3 . GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE , with the isomers neral and geranial constituting 30-40% . Citral , a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50) 10 �M ( 2.3 �g/ml ) . Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells . SDGE was more effective in inducing cancer cell death than citral , suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death . SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential . Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE . This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax . Inhibitor of p53 , pifithrin-α , attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg) SKOV-3 cells . Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer . OUTPUT:

resisting cell death

HoC_1shot1043

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 ) has been believed to be an anticancer drug for a long history . However , the molecular mechanisms of RA actions on cancer cells remain diverse . In this study , the dose-dependent inhibition of RA on DU145 cell proliferation was identified . Interestingly , RA treatment triggered p35 cleavage ( p25 formation ) and Cdk5 overactivation , and all could be blocked by Calpain inhibitor , Calpeptin ( CP ) . Subsequently , RA-triggered DU145 apoptosis detected by sub-G1 phase accumulation and Annexin V staining could also be blocked by CP treatment . Furthermore , RA-triggered caspase 3 activation and following Cdk5 over-activation were destroyed by treatments of both CP and Cdk5 knockdown . In conclusion , we report a new mechanism in which RA could cause apoptosis of androgen-independent prostate cancer cells through p35 cleavage and Cdk5 over-activation . This finding may contribute to constructing a clearer image of RA function and bring RA as a valuable chemoprevention agent for prostate cancer patients . OUTPUT:

resisting cell death

HoC_1shot1044

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 . Multiple myeloma ( MM ) , an almost incurable disease , is the second most common blood cancer . Initial chemotherapeutic treatment could be successful ; however , resistance development urges the use of higher toxic doses accompanied by hematopoietic stem cell transplantation . The establishment of more effective treatments that can overcome or circumvent chemoresistance has become a priority . We recently demonstrated that venom extracted from Walterinnesia aegyptia ( WEV ) either alone or in combination with silica nanoparticles ( WEV+NPs ) mediated the growth arrest and apoptosis of prostate cancer cells . In the present study , we evaluated the impact of WEV alone and WEV+NP on proliferation and apoptosis of MM cells . Methods . The impacts of WEV alone and WEV+NP were monitored in MM cells from 70 diagnosed patients . The influences of WEV and WEV+NP were assessed with flow cytometry analysis . Results . WEV alone and WEV+NP decreased the viability of MM cells . Using a CFSE proliferation assay , we found that WEV+NP strongly inhibited MM cell proliferation . Furthermore , analysis of the cell cycle using the propidium iodide ( PI ) staining method indicated that WEV+NP strongly altered the cell cycle of MM cells and enhanced the induction of apoptosis . Conclusions . Our data reveal the biological effects of WEV and WEV+NP on MM cells that enable these compounds to function as effective treatments for MM . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot1045

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 Objective . The cell cycle is regulated by proteins at different checkpoints , and dysregulation of this cycle plays a role in carcinogenesis . Matrix metalloproteinases ( MMPs ) are enzymes that degrade collagen and promote tumour infiltration . The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder ( UCB ) . Patients and Methods . This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder . Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs . Results . Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence . Also , normal p16 expression was related to a lower risk of tumour progression . MMP2 , p21 , cyclin D1 , and pRb showed no significant results that could estimate progression or recurrence . Conclusions . Normal p16 expression is associated with a lower risk of tumour progression , but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1046

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 expression of the angiogenic phenotype is regulated by a balance of pro-angiogenic and anti-angiogenic factors released into the tumor microenvironment . Nuclear protein 7 ( NOL7 ) , a novel tumor suppressor , acts as a master regulator of angiogenesis by downregulating pro-angiogenic factors and upregulating anti-angiogenic factors . Using cervical cancer as a model of investigation , we have previously shown that loss of NOL7 mRNA and protein expression is observed as early as the premalignant phase . Analysis of the gene failed to identify tumor-specific promoter methylation or coding region mutations , suggesting that NOL7 loss may be mediated by aberrant expression of its upstream regulators . In this study , we show that the RB tumor suppressor gene ( RB ) positively regulates NOL7 at the transcriptional level by recruiting transcription factors and transcription machinery proteins to its promoter region . Conversely , the loss of RB represses NOL7 transcription by inhibiting assembly of these proteins . This loss of NOL7 expression is also observed in RB-deficient human malignancies . Together , this work further characterizes the transcriptional activator function of RB and defines a potential role for RB in regulating angiogenesis through activation of NOL7 . Current anti-angiogenic therapies lack long-term efficacy , as they are unable to target the diverse angiogenic signals generated by tumors . Our data provide evidence to support the hypothesis that reactivation of pRB can potentially modulate the expression of the angiogenic phenotype through regulation of NOL7 . Therefore , this knowledge may be employed to design more comprehensive and effective therapies . OUTPUT:

inducing angiogenesis

HoC_1shot1047

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 The aim of this retrospective study is to analyze the clinical and pathological factors related to the prognosis of Chinese patients with stage Ib to IIb cervical cancer . METHODS AND RESULTS 13 clinical pathological factors in 255 patients with stage Ib to IIb cervical cancer undergoing radical hysterectomy and systematic lymphadenectomy were analyzed to screen for factors related to prognosis . The cumulative 5-year survival of the 255 patients was 75.7% . The result of the univariate analysis suggested that clinical stage , cell differentiation , depth of cervical stromal invasion , parametrial tissue involvement , and lymph node metastasis were prognostic factors for patients with stage Ib to IIb cervical cancer ( P<0.05 ) . Compared with cases with involvement of iliac nodes , obturator nodes , or inguinal lymph nodes , cases with metastasis to the common iliac lymph nodes had a poorer prognosis ( P<0.05 ) . Cases with involvement of four or more lymph nodes had a poorer prognosis than those with involvement of three or fewer lymph nodes ( P<0.05 ) . Using multivariate Cox proportional hazards model regression analysis , non-squamous histological type , poor differentiation , parametrial tissue involvement , and outer 1/3 stromal invasion were found to be independently related to patients poor prognosis ( P<0.05 ) . CONCLUSION Non-squamous histological type , poor cell differentiation , parametrial tissue involvement , and outer 1/3 stromal invasion are the independent poor prognostic factors for patients with stage Ib to IIb cervical cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot1048

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: Onions ( Allium cepa L. ) are widely used in the food industry for its nutritional and aromatic properties . Our studies showed that ethyl acetate extract of onion ( EEO ) had potent inhibitory effects on animal fatty acid synthase ( FAS ) , and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells . Furthermore , this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids , the final product of FAS catalyzed synthesis . These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS . We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes , which was also related to its inhibition of intracellular FAS activity . Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers , these findings suggested that onion might be useful for preventing obesity-related malignancy . OUTPUT:

resisting cell death

HoC_1shot1049

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: Family with sequence similarity 189 , member B ( FAM189B ) , alias COTE1 , a putative oncogene selected by microarray , for the first time was here found to be significantly up-regulated in hepatocellular carcinoma ( HCC ) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction ( RT-PCR ) and real-time PCR , while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry . In addition , invasion of HCC cells was observed after overexpressing or silencing COTE1 . In the total of 48 paired HCC specimens , compared with the adjacent non-cancer tissues , the expression of COTE1 was up-regulated in 31 ( p<0.01 ) . In HCC cell lines , COTE1 expression was significantly higher than in normal human adult liver ( p<0.01 ) . Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro . In contrast , COTE1 knockdown via RNAi markedly suppressed these phenotypes , as documented in LM3 and MHCC-H HCC cells . Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase ( WWOX ) , a tumor suppressor . COTE1 may be closely correlated with invasion of hepatocellular carcinoma ( HCC ) cells and thus may serve as an effective target for gene therapy . OUTPUT:

activating invasion and metastasis

HoC_1shot1050

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: 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

HoC_1shot1051

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: Momordica charantia has been found to exhibit anticancer activity , in addition to its well-known therapeutic functions . We have demonstrated that the leaf extract of Momordica charantia ( MCME ) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways . In this study , a different susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability , leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells . MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities . We proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt , β-catenin , and MMPs . OUTPUT:

activating invasion and metastasis

HoC_1shot1052

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 The signalling molecule protein kinase B ( Akt ) modulates many cellular processes . Phosphatidylinositol 3-kinase ( PI3K)/Akt signalling pathways play important roles in tumour angiogenesis . The aim of this study was to determine the role of phosphorylated Akt ( pAkt ) in angiogenesis and its correlation with vascular endothelial growth factor ( VEGF)-A in gastric adenocarcinoma . METHODS Tumour tissue and matched healthy gastric mucosa were obtained from patients undergoing surgical resection of gastric adenocarcinoma . Akt and pAkt were detected via Western blotting . VEGF-A , pAkt and CD34 were examined by immunohistochemistry . RESULTS Akt and pAkt protein levels were significantly higher in gastric cancer tissue than in normal tissue ( n = 48 patients ) . Positive VEGF-A immunostaining was significantly associated with pAkt immunostaining . Microvessel density was correlated with both VEGF-A and pAkt positivity . CONCLUSIONS Phosphorylated Akt and VEGF-A are involved in angiogenesis of gastric adenocarcinoma , and Akt activation may contribute to angiogenesis via VEGF-A upregulation . The PI3K/Akt/VEGF signalling pathway may be involved in gastric adeno carcinoma . OUTPUT:

inducing angiogenesis;sustaining proliferative signaling

HoC_1shot1053

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 observe the effects of octreotide ( OCT ) on cisplatin resistance reversal of cancer cells in vitro and in nude mice in vivo . MTT method and flow cytometry were used to investigate the effect of cisplatin , OCT or the combination of these two compounds on the proliferation and apoptosis of SKOV3-DDP cells . The size and weight of xenograft tumors from the nude mice model were measured . Real-time PCR was used to detect the mRNA expression of SSTR2 , MDR1 , MRP2 , GST-pi and EGFR in SKOV3/DDP cells following the different treatment . At the concentration of 2.5-20 g/ml , OCT significantly reduced IC50 ( p &lt ; 0.05 ) and promoted apoptosis ( p &lt ; 0.05 ) of SKOV3-DDP cells ' response to cisplatin . Unchanged expression was found in SSTR2 on the SKOV3/DDP cell in vitro after OCT treatment , but increased expression in vivo ( p &lt ; 0.05 ) . OCT increased GST-pi expression ( p &lt ; 0.05 ) and reduced MRP2 and EGFR expression ( p &lt ; 0.05 ) in a dose-dependent manner . The similar results were obtained in mice in vivo experiment , except the reduced expression of GST-pi . It is suggested that OCT could inhibit ovarian cancer proliferation and promote apoptosis , via the cell surface SSTR2 , and reverse cisplatin resistance through inhibition of MRP2 , EGFR , and even GST-pi expressions . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot1054

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: Epithelial-mesenchymal transition ( EMT ) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites . Recently , EMT was shown to be associated with the cancer stem cell ( CSC ) phenotype in breast cancer . Snail is a transcription factor that mediates EMT in a number of tumor types , including colorectal cancer ( CRC ) . Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC . Human CRC specimens were stained for Snail expression , and human CRC cell lines were transduced with a retroviral Snail construct or vector control . Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT ( colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) assay . Migration and invasion were determined in vitro using modified Boyden chamber assays . EMT and putative CSC markers were analyzed using Western blotting . Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice . Snail was overexpressed in human CRC surgical specimens . This overexpression induced EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration and invasion ( P &lt ; 0.002 vs. control ) . Snail overexpression also led to an increase in metastasis formation in vivo ( P &lt ; 0.002 vs. control ) . Furthermore , the Snail-overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells . Increased Snail expression induces EMT and the CSC-like phenotype in CRC cells , which enhance cancer cell invasion and chemoresistance . Thus , Snail is a potential therapeutic target in metastatic CRC . OUTPUT:

activating invasion and metastasis

HoC_1shot1055

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 purpose of the study was to evaluate Sorafenib ( BAY 43-9006 ) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors . Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors . Rip1Tag2 mice were treated in two different groups according to the model of tumor progression : the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death . Tumor surface , tumor cell proliferation , and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib . Survival was recorded for the late treatment group . In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group . Apoptosis was significantly augmented and cell proliferation was inhibited . As a single therapy Sorafenib significantly improved survival in the late treatment group . Conclusion . Sorafenib may provide a new paradigm for the therapy of islet cell tumors . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot1056

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 Hippo signaling pathway inhibits cell growth and regulates organ size through a kinase cascade that leads to the phosphorylation and nuclear exclusion of the growth-promoting transcriptional coactivator Yes-associated protein ( YAP)/Yorkie . It mediates contact inhibition of cell growth downstream of cadherin adhesion molecules and other cell surface proteins . Contact inhibition is often antagonized by mitogenic growth factor signaling . We report an important mechanism for this antagonism , inhibition of Hippo pathway signaling by mitogenic growth factors . EGF treatment of immortalized mammary cells triggers the rapid translocation of YAP into the nucleus along with YAP dephosphorylation , both of which depend on Lats , the terminal kinase in the Hippo pathway . A small-molecule inhibitor screen of downstream effector pathways shows that EGF receptor inhibits the Hippo pathway through activation of PI3-kinase ( PI3K ) and phosphoinositide-dependent kinase ( PDK1 ) , but independent of AKT activity . The PI3K-PDK1 pathway also mediates YAP nuclear translocation downstream of lysophosphatidic acid and serum as a result of constitutive oncogenic activation of PI3K . PDK1 associates with the core Hippo pathway-kinase complex through the scaffold protein Salvador . The entire Hippo core complex dissociates in response to EGF signaling in a PI3K-PDK1-dependent manner , leading to inactivation of Lats , dephosphorylation of YAP , and YAP nuclear accumulation and transcriptional activation of its target gene , CTGF . These findings show that an important activity of mitogenic signaling pathways is to inactivate the growth-inhibitory Hippo pathway and provide a mechanism for antagonism between contact inhibition and growth factor action . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot1057

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 observe the anti-tumor recurrent and metastatic efficacy of Ru'ai Shuhou Recipe ( RSR ) on HER2 positive breast cancer , to evaluate the effects of RSR on the expressions of matrix metalloproteinases ( MMPs ) and the tissue inhibitor of metalloproteinases ( TIMPs ) in the recurrence and metastasis of HER2 positive breast cancer , thus revealing its anti-tumor recurrent and metastatic mechanisms . METHODS Selected were 30-week-old HER2/neu transgenic spontaneous breast cancer mice FVB/neu . The primary tumor resection was carried out . After surgery they were randomly divided into the blank control group , the RSR group , the Herceptin group , and the combination group ( RSR + Herceptin group ) . The treatment lasted for 4 months . The inhibition rate of the recurrent tumor volume and the inhibition rate of the lung metastasis were evaluated . The expressions of matrix metalloproteinase-2 ( MMP-2 ) , matrix metalloproteinase-9 ( MMP-9 ) , tissue inhibitor of metalloproteinase ( TIMP-1 ) , and TIMP-2 in the recurrent tumor tissue were detected using Western blot . RESULTS By the end of the treatment the average recurrent tumor volume was 11.11 +/- 8.71 cm3 in the blank control group and 5.56 +/- 5.55 cm3 of the RSR group , showing statistical difference between the two groups ( P = 0.037 ) . The average lung metastatic nodule was 16 in the blank control group and 10 in the RSR group . The inhibition rate of lung metastasis was 37. 85% in the RSR group , but with no statistical significance . The expression level of activated MMP-2 in the RSR group was down-regulated when compared with the blank control group , the Herceptin group , and the combination group ( P &lt ; 0.05 ) . The expression of MMP-9 of the RSR group , the Herceptin group , and the combination group was significantly down-regulated when compared with the blank control group ( P &lt ; 0.05 ) . The expression of MMP-9 of the RSR group and the combination group was further down-regulated when compared with the Herceptin group ( P &lt ; 0.05 ) . The expressions of both TIMP-1 and TIMP-2 of the RSR group , the Herceptin group , and the combination group were all up-regulated when compared with the blank control group ( P &lt ; 0.05 ) . The increased expression of TIMP-1 was more significantly in the RSR group and the combination group when compared with the Herceptin group ( P &lt ; 0.05 ) . It was higher in the combination group than in the RSR group ( P &lt ; 0.05 ) . CONCLUSIONS RSR could inhibit the tumor recurrence of FVB/neu mice . It could reduce the degradation of extracellular matrix and increase the protective effects of extracellular matrix . It might achieve its anti-tumor effect through effecting the invasive and metastatic capabilities of breast tumor cells . OUTPUT:

activating invasion and metastasis

HoC_1shot1058

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: Bcl-2/E1B 19-kDa interacting protein 3 ( BNIP3 ) is a proapoptotic protein whose expression level is often low in colorectal cancer ( CRC ) cells due to the BNIP3 gene promoter DNA methylation by DNA methyltransferase ( DNMT ) . It is known that chemotherapy and radiotherapy suppress CRC through inducing tumor apoptosis . However , the molecular mechanisms underlying chemotherapy and radiotherapy-induced apoptosis of CRC cells are not well defined . In this study , we observed that the expression level of BNIP3 in colon cancer cells was significantly increased by treatment with therapeutic agents and radiation in vitro . The BNIP3 protein level in CRC tissues from patients who received preoperative concurrent chemotherapy was significantly higher than in those who received surgery alone . Furthermore , treatment with chemotherapeutic agents and radiation significantly decreased the DNMT1 expression level and enzymatic activity . Both expression level and activity of DNMT1 were inversely correlated with the expression level of BNIP3 in colon carcinoma cells after treatment with chemotherapeutic agents and radiation . Consistent with increased BNIP3 expression , chemotherapeutic agents and radiation induced colon carcinoma cell apoptosis in a dose-dependent manner . Based on these observations , we conclude that chemotherapy and radiotherapy inhibit DNMT1 expression to upregulate BNIP3 expression to promote CRC cell apoptosis . And , BNIP3 may play a role in the caspase-dependent apoptosis pathways , mainly during treatment with chemotherapy and radiotherapy . OUTPUT:

resisting cell death

HoC_1shot1059

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 new concept of keeping primary tumor under control in situ to suppress distant foci sheds light on the novel treatment of metastatic tumor . Hyperthermia is considered as one of the means for controlling tumor growth . In this study , a novel thermal modality was built to introduce hyperthermia effect on tumor to suppress its growth and progression using 4T1 murine mammary carcinoma , a common animal model of metastatic breast cancer . A mildly raised temperature ( i.e.39�C ) was imposed on the skin surface of the implanted tumor using a thermal heating pad . Periodic heating ( 12 hours per day ) was carried out for 3 days , 7 days , 14 days , and 21 days , respectively . The tumor growth rate was found significantly decreased in comparison to the control without hyperthermia . Biological evidences associated with tumor angiogenesis and metastasis were examined using histological analyses . Accordingly , the effect of mild hyperthermia on immune cell infiltration into tumors was also investigated . It was demonstrated that a delayed tumor growth and malignancy progression was achieved by mediating tumor cell apoptosis , vascular injury , degrading metastasis potential and as well as inhibiting the immunosuppressive cell myeloid derived suppressor cells ( MDSCs ) recruitment . Further mechanistic studies will be performed to explore the quantitative relationship between tumor progression and thermal dose in the near future . OUTPUT:

activating invasion and metastasis;avoiding immune destruction;resisting cell death

HoC_1shot1060

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: UNLABELLED BACKGROUND Cell lines are very useful for clinical and basic research . Thus far , only 11 reports have documented the characteristics of ovarian endometrioid adenocarcinoma cell lines in the literature . Due to the scarcity of information , the establishment of an ovarian malignant tumor cell line with distinctive characteristics is particularly important to study this disease . Thus , this study was undertaken to establish and characterize a new human endometrioid adenocarcinoma cell line of the ovary . METHODS The cell line NOMH-1 was established from an ovarian tumor of a 44-year-old woman . Features of the cell line studied included morphology , chromosome analysis , heterotransplantation , tumor markers , and chemosensitivity . RESULTS This cell line has been growing well for 232 months and subcultured more than 50 times . Monolayer cultured cells were polygonal in shape , showing a pavement-like arrangement and a tendency to stack without contact inhibition . They exhibited a human karyotype with a modal chromosomal number in the hypertriploid range . The cells could be transplanted into the subcutis of nude mice and produced tumors resembling the original tumor . NOMH-1 cells expressed both CEA and CA19-9 which were identified immunohistochemically in the original tumor and the heterotransplanted tumor . The cells were sensitive to paclitaxel , an agent commonly used in the treatment of gynecological cancers . CONCLUSIONS NOMH-1 is the first ovarian endometrioid adenocarcinoma cell line in which CEA and CA19-9 expression have been defined . This newly established cell line should be useful for investigating the characteristics of ovarian endometrioid adenocarcinoma . OUTPUT:

evading growth suppressors

HoC_1shot1061

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 effects of genomic changes in hepatitis B virus ( HBV ) on the occurrence of hepatocellular carcinoma ( HCC ) are still unclear , especially in relation to the genotype of HBV . In this study , we examined the effects of genomic changes in HBV of genotype C2 on the development of HCC . A total of 318 patients with HBV-associated HCC and 234 patients with chronic hepatitis B ( CHB ) were studied . All of HCC cases were diagnosed histologically and treated with surgical resection . The whole of the X , S , basal core promoter ( BCP ) and precore regions of the viral genome from sera or liver tissues were sequenced . All subjects had HBV of genotype C2 . The prevalence of the T1653 mutation in the X region and the A1896 mutation in the precore region of HBV was significantly higher in the HCC group than in the control CHB group ( 22% vs 11% , P = 0.003 ; 50% vs 23% , P &lt ; 0.001 , respectively ) . Moreover , the T1762/A1764 mutations in the BCP region in combination with either T1653 or A1896 were more common in the HCC compared with the CHB group ( BCP+X1653 : 18% vs 11% , P = 0.05 ; BCP+PC , 40% vs 15% , P &lt ; 0.001 , respectively ) . In multivariate analysis , T1653 and A1896 were revealed to be independent risk factors for HCC development . G1896A in the precore region and C1653T mutation in the X region of genotype C2 HBV are important risk factors for HCC development . Also , the A1762T/G1764A double mutation may act in synergy with C1653T to increase the risk of HCC in patients chronically infected with HBV genotype C2 . OUTPUT:

genomic instability and mutation

HoC_1shot1062

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 This study describes a new method used in the clinical laboratory at Hospital Israelita Albert Einstein to detect mutations in exons 8 and 17 of the KIT gene in patients with acute myeloid leukemia . METHODS Genomic DNA extraction was performed on 54 samples of peripheral blood or bone marrow from patients with acute myeloid leukemia . The extracted DNA was amplified by polymerase chain reaction and sequenced , and the fragments were analyzed . RESULTS Within the analyzed samples , we detected four mutations in exon 8 , two mutations in exon 17 , and mutations or a double mutation in one sample . CONCLUSION The tests detecting mutations in exon 8 and 17 on the KIT gene were successfully standardized . The test is now included among the routine diagnostics employed for patients at Hospital Israelita Albert Einstein clinical laboratory . OUTPUT:

genomic instability and mutation

HoC_1shot1063

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 the present study , post-treatment effects of dietary turmeric on markers related to apoptosis , cell proliferation , and inflammation in 7,12-dimethylbenz(a)anthracene ( DMBA)-induced hamster buccal pouch ( HBP ) tumors were investigated . Tumors were induced by applying 0.5% DMBA topically to the HBP three times per week for 12 weeks . After tumor development , half of the animals continued on the control diet and the other half were shifted to a 1% turmeric diet for 4 weeks . To rule out DMBA discontinuation as a cause of inhibition in tumor growth , DMBA treatment was continued during dietary exposure of turmeric in another set of animals until the end of the experiment . The turmeric diet inhibited tumor growth in animals with or without DMBA carcinogen treatment compared to the animals on the control diet . When compared to hamsters bearing tumors that remained on the control diet , the buccal pouches of hamsters bearing tumors receiving turmeric showed the following results : ( 1 ) decreased cell proliferation ( diminished PCNA , cyclin D1 , and Bcl-2 ) and PCNA labelling index , ( 2 ) enhanced apoptosis ( increased Bax , caspase-3 , caspase-9 , and cytochrome c , and decreased survivin ) and apoptotic index , ( 3 ) decreased inflammation ( decreased Cox-2 ) , and ( 4 ) decreased MAPK activation ( p-ERK and p-p38 ) . These data indicate that tumor growth decreased due to the modulation of cellular pathways associated with cell proliferation and apoptosis . OUTPUT:

resisting cell death;sustaining proliferative signaling;tumor promoting inflammation

HoC_1shot1064

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 sort and identify side population ( SP ) cancer stem cells ( CSC ) in human prostate cancer ( PCa ) cell lines . METHODS Stem-like cells were isolated from five PCa cell lines Du145 , IA8 , LNCaP , TSU-Pr and PC-3 using FACS based on CD133+ CD44+ immunophenotype and SP in Hoechst staining . The in vitro growth pattern and tumorigenicity of SP stem cells were verified by soft agar colony-formation trial . LNCaP/SP cells were selected for further identification of stem cell properties using immunostaining , proliferation and invasion assay . Eventually , tumorigenicity and metastasis ability of LNCaP/SP were confirmed by xenograft experiments . RESULTS The percentages of CSCs of the CD133 CD44 + immunophenotype were extremely low in the five PCa cell lines . On the contrary , the percentages of the isolated SP cells were significantly higher in Du145 ( [ 0.15 +/- 0.02]% ) , IA8 ( [ 0.60 +/- 0.07 ]% ) , LNCaP ( [ 0.8 +/- 0.1]% ) and TSU-PrL ( [ 2.0 +/- 0.4]% ) , but none was detected in PC-3 . Besides , IA8/SP , LNCaP/SP and TSU-PrL/SP cells showed a significantly greater colony-forming efficiency than non-side population ( NSP ) cells ( P &lt ; 0.05 ) . Compared with LNCaP/NSP cells , LNCaP/SP cells exhibited high expressions of integrin alpha2 , Nanog , CD44 , OCT4 and ABCG2 , remarkably enhanced invasive and proliferative potentials in vitro , and markedly increased tumorigenicity and metastasis ( P &lt ; 0.01 ) . CONCLUSION SP sorting is more suitable than CD133+ CD44+ selection for enriching CSCs from PCa cell lines , and LNCaP/ SP represents a typical CSC population . OUTPUT:

activating invasion and metastasis

HoC_1shot1065

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: HM781-36B is an orally administered pan-human epidermal growth factor receptor ( HER ) inhibitor . To explore the role of pan-HER inhibitor in breast cancer , we investigated the antitumor effect and mechanisms of HM781-36B in breast cancer cell lines . Six breast cancer cell lines ( BT474 , MDA-MB-453 , SK-BR-3 , T47D , MCF-7 , and MDA-MB-231 ) were tested . The growth inhibitory effect was assessed using the tetrazolium bromide [ 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide ] assay . The cell cycle at various concentrations of HM781-36B was analyzed by flow cytometry , and analysis of downstream molecules was performed by western blot analysis . Interaction of HM781-36B with cytotoxic chemotherapeutic agents was analyzed by combination index using CalcuSyn . The HER2-amplified cells ( SK-BR-3 , BT474 , and MDA-MB-453 ) were sensitive to HM781-36B ( IC50=0.001 μmol/l , 0.0012 μmol/l , and 0.0095 μmol/l , respectively ) . HM781-36B induced G1 arrest and resulted in apoptosis . It reduced the level of p-HER2 , p-AKT , p-ERK , and p-STAT3 . HM781-36B combined with 5-fluorouracil , cisplatin , paclitaxel , or gemcitabine showed a synergistic inhibitory effect on the HER2-amplified and on some of the HER2-nonamplified breast cancer cells . HM781-36B could be a promising treatment for HER2-amplified breast cancer as a single agent or in combination with cytotoxic agents and can be a candidate for treatment of HER2-nonamplified breast cancer in combination with cytotoxic agents . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot1066

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: Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle , which then stops when confluence is reached again . Although the events involved in cell cycle entry have been widely documented , those managing cell cycle exit have remained so far ill defined . We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p , which acts as a mandatory signal triggering cell cycle arrest when confluence is reached . Blocking miR-483-3p accumulation strongly delays cell cycle exit , maintains cells into a proliferative state and retards their differentiation program . Using two models of cell cycle synchronization ( i.e. mechanical injury and serum addition ) , we show that an ectopic upregulation of miR-483-3p blocks cell cycle progression in early G1 phase . This arrest results from a direct targeting of the CDC25A phosphatase by miR-483-3p , which can be impeded using an anti-miRNA against miR-483-3p or a protector that blocks the complex formation between miR-483-3p and the 3'-untranslated region ( UTR ) of CDC25A transcript . We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which , in turn , abolishes CDK4/6 capacity to associate with D-type cyclins . This prevents CDK4/6 kinases ' activation , impairs downstream events such as cyclin E stimulation and sequesters cells in early G1 . We propose this new regulatory process of cyclin-CDK association as a general mechanism coupling miRNA-mediated CDC25A invalidation to CDK post-transcriptional modifications and cell cycle control . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1067

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 new cell line of human ovarian clear cell adenocarcinoma ( CCC ) , TU-OC-1 , was established and characterized . The cells showed a polygonal-shaped morphology and grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle . The chromosome numbers ranged from 64 to 90 . A low rate of proliferation was observed , similar to other CCC cell lines tested ( OVTOKO , RMG-I , and OVAS ) , and the doubling time was 38.4h . The respective IC50 values of cisplatin and paclitaxel were 12.2μM and 58.3nM . Mutational analysis revealed that TU-OC-1 cells harbored a PIK3CA mutation at codon 542 ( E542K ) in exon 9 , which is a mutation hot spot on this gene . We observed that phosphorylated Akt protein was overexpressed in TU-OC-1 cells by western blot analysis . Heterotransplantation to nude mice produced tumors that reflected the original . This cell line may be useful to study the chemoresistant mechanisms of CCC and contribute to novel treatment strategies . OUTPUT:

genomic instability and mutation

HoC_1shot1068

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 recently reported that chronic myeloid leukaemia ( CML ) patients harbour high levels of STAT5 when they progress to advanced phases of disease . Advanced disease is characterized by an increased incidence of BCR-ABL1 mutations . We now describe a highly significant correlation between STAT5 expression and the incidence of BCR-ABL1 mutations in primary CML . Forced expression of STAT5 in murine BCR-ABL1 transformed cells sufficed to enhance the production of reactive oxygen species ( ROS ) and to trigger DNA damage . STAT5-mediated ROS production is independent of JAK2 but requires concomitant BCR-ABL1 signalling as forced STAT5 expression in untransformed BCR-ABL1 negative cells has no impact on ROS levels . Only within the context of a BCR-ABL1 positive cell does STAT5 transcriptionally regulate a target gene or set of genes that causes the enhanced ROS production . Our study suggests the existence of a feed-forward loop accelerating disease progression , in which BCR-ABL1 enhances its own mutation rate in a STAT5-ROS dependent manner . This model explains the increased occurrence of inhibitor-resistant BCR-ABL1 mutations in advanced disease stages driven and characterized by high STAT5 expression . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot1069

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: Transforming growth factor beta ( TGF-β ) signaling has been implicated in driving tumor progression and metastasis by inducing stem cell-like features in some human cancer cell lines . In this study , we have utilized a novel murine cell line NMuMG-ST , which acquired cancer stem cell ( CSC ) phenotypes during spontaneous transformation of the untransformed murine mammary cell line NMuMG , to investigate the role of autocrine TGF-β signaling in regulating their survival , metastatic ability , and the maintenance of cancer stem cell characteristics . We have retrovirally transduced a dominant-negative TGF-β type II receptor ( DNRII ) into the NMuMG-ST cell to abrogate autocrine TGF-β signaling . The expression of DNRII reduced TGF-β sensitivity of the NMuMG-ST cells in various cell-based assays . The blockade of autocrine TGF-β signaling reduced the ability of the cell to grow anchorage-independently and to resist serum deprivation-induced apoptosis . These phenotypes were associated with reduced levels of active and phosphorylated AKT and ERK , and Gli1 expression suggesting that these pathways contribute to the growth and survival of this model system . More interestingly , the abrogation of autocrine TGF-β signaling also led to the attenuation of several features associated with mammary stem cells including epithelial-mesenchymal transition , mammosphere formation , and expression of stem cell markers . When xenografted in athymic nude mice , the DNRII cells were also found to undergo apoptosis and induced significantly lower lung metastasis burden than the control cells even though they formed similar size of xenograft tumors . Thus , our results indicate that autocrine TGF-β signaling is involved in the maintenance and survival of stem-like cell population resulting in the enhanced metastatic ability of the murine breast cancer cells . OUTPUT:

resisting cell death;activating invasion and metastasis

HoC_1shot1070

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: Systemic oxidative stress is associated with a wide range of pathological conditions . Oxidative DNA damage is frequently measured in circulating lymphocytes . Mitochondrial DNA ( mtDNA ) is known to be more sensitive to oxidative damage than nuclear DNA but is rarely used for direct measurement of DNA damage in clinical studies . Based on the supercoiling-sensitive real-time PCR method , we propose a new approach for the noninvasive monitoring of systemic oxidative stress by quantifying the mtDNA structural damage and copy number change in isolated lymphocytes in a single test . We show that lymphocytes have significantly less mtDNA content and relatively lower baseline levels of damage than cancer cell lines . In an ex vivo challenge experiment , we demonstrate , for the first time , that exogenous H2O2 induces a significant increase in mtDNA damage in lymphocytes from healthy individuals , but no repair activity is observed after 1 h recovery . We further demonstrate that whole blood may serve as a convenient alternative to the isolated lymphocytes in mtDNA analysis . Thus , the blood analysis with the multiple mtDNA end-points proposed in the current study may provide a simple and sensitive test to interrogate the nature and extent of systemic oxidative stress for a broad spectrum of clinical investigations . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot1071

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: Metastases in the sellar region are rare and are frequently found incidentally or in necropsies . Only 7% are reported to be symptomatic . Diabetes insipidus , anterior pituitary dysfunction , visual field defects , headache/pain and ophthalmoplegia are the most commonly reported symptoms . We present the cases of two male patients with a small-cell lung carcinoma whose first clinical symptoms were due to pituitary metastasis . One case presented with symptoms of cavernous sinus invasion and panhypopituitarism and the other case with diabetes insipidus . Both patients had a rapid progression of their disease despite chemotherapy and died after a few months . Pituitary metastases occur most commonly with breast cancer in women and lung cancer in men . The presence of polyuria and polydipsia in an oncologic patient should alert the physician for diabetes insipidus and , if confirmed , an imaging procedure of the pituitary gland is mandatory . Treatment for these tumors is often multimodal and includes surgery , radiation therapy , chemotherapy and hormone replacement . Although surgical series have not shown any significant survival benefits given by tumor resection , the patient's quality of life may be improved . OUTPUT:

activating invasion and metastasis

HoC_1shot1072

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: Within the family of protein kinase C ( PKC ) molecules , the novel isoform PRKCE ( PKCɛ ) acts as a bona fide oncogene in in vitro and in vivo models of tumorigenesis . Previous studies have reported expression of PKCɛ in breast , prostate and lung tumors above that of normal adjacent tissue . Data from the cancer genome atlas suggest increased copy number of PRKCE in triple negative breast cancer ( TNBC ) . We find that overexpression of PKCɛ in a non-tumorigenic breast epithelial cell line is sufficient to overcome contact inhibition and results in the formation of cellular foci . Correspondingly , inhibition of PKCɛ in a TNBC cell model results in growth defects in two-dimensional ( 2D ) and three-dimensional ( 3D ) culture conditions and orthotopic xenografts . Using stable isotope labeling of amino acids in a cell culture phosphoproteomic approach , we find that CTNND1/p120ctn phosphorylation at serine 268 ( P-S268 ) occurs in a strictly PKCɛ-dependent manner , and that loss of PKCɛ signaling in TNBC cells leads to reversal of mesenchymal morphology and signaling . In a model of Ras activation , inhibition of PKCɛ is sufficient to block mesenchymal cell morphology . Finally , treatment with a PKCɛ ATP mimetic inhibitor , PF-5263555 , recapitulates genetic loss of function experiments impairing p120ctn phosphorylation as well as compromising TNBC cell growth in vitro and in vivo . We demonstrate PKCɛ as a tractable therapeutic target for TNBC , where p120ctn phosphorylation may serve as a readout for monitoring patient response.Oncogene advance online publication , 1 April 2013 ; doi:10.1038/onc.2013.91 . OUTPUT:

evading growth suppressors

HoC_1shot1073

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: Cell migration plays important roles in natural processes involving embryonic development , inflammation , wound healing , cancer metastasis and angiogenesis . Cell migration on various biomaterials is also believed to improve the rate of wound healing and implant therapies in the tissue-engineering field . This study measured the distance traversed , or mileage , of mouse fibroblasts on a silk fibroin surface . Fibroblasts on the fibroin surface moved with better progress during 24 h than cells on collagen or fibronectin surfaces . Results obtained by quantitative real-time reverse transcription-polymerase chain reaction ( qRT-PCR ) revealed that fibroblasts on the fibroin surface expressed transforming growth factor β-induced protein ( TGFBI ) , which is an extracellular matrix ( ECM ) protein , stronger than on other surfaces in the early cell-culture stages . These results demonstrate that the fibroin surface shows higher potential to enhance cell migration and the production of ECM than a collagen or fibronectin surface . OUTPUT:

activating invasion and metastasis

HoC_1shot1074

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 Angiogenesis is an essential process in cancer growth maintenance , and metastasis . Angiopoietin-2 promotes tumor angiogenesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization . Enhanced expression of angiopoietin-2 has been reported in lung cancer tissue . Survivin is one of the inhibitors of apoptosis protein that has been shown to play a key role in cancer progression , and in tumor angiogenesis . Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation . AIM To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance . PATIENTS AND METHODS Patients with lung cancer as NSCLC ( n=70 ) and healthy volunteers ( n=10 ) were enrolled . Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay ( ELIZA ) . RESULTS Median serum angiopoietin-2 levels with lung cancer ( 2730pg/mL ) ranged from 1171 to 6541pg/mL was higher than the median of the control group ( 1795pg/mL ) ranged from 1076 to 2730/mL , p<0.001 . Median serum survivin levels were also higher in patients with lung cancer ( 53.0pg/mL ) ranged from 39.3 to 96.3pg/mL than the median of the control group ( 48.8pg/mL ) ranged from 38.0 to 74.6pg/mL , but did not reach statistical significance p=0.206 . In all patients with lung cancer , serum angiopoietin-2 was not significantly correlated with survivin ( r=0.073 , p=0.657 ) . Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types , stage progression , and metastasis among the patients with NSCLC . CONCLUSIONS Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique . OUTPUT:

inducing angiogenesis

HoC_1shot1075

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: Understanding how arsenic exacts its diverse , global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis . A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic , and manifest as diverse diseases . Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells , the report here shows that low level exposure to arsenite ( 75ppb ) is sufficient to induce aerobic glycolysis ( the Warburg effect ) as a generalized phenomenon in cultured human primary cells and cell lines . Expanded studies in one such cell line , the non-malignant pulmonary epithelial line , BEAS-2B , established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate , an increased rate of extracellular acidification , and inhibition by the non-metabolized glucose analog , 2-deoxy-D-glucose . Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression , as well as protein accumulation of an established glycolysis master-regulator , hypoxia-inducible factor 1A . Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases . OUTPUT:

cellular energetics

HoC_1shot1076

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 mismatch repair ( MMR ) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity . The genes of the MMR pathway are highly conserved across different organisms . Likewise , defective MMR function universally results in microsatellite instability ( MSI ) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer . ( Lynch syndrome ) . To identify previously unrecognized deleted genes or loci that can lead to MSI , we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae . This pool represents a collection of non-essential homozygous yeast diploid ( 2N ) mutants in which there are deletions for over four thousand yeast open reading frames ( ORFs ) . From our screen , we identified a deletion mutant strain of the PAU24 gene that leads to MSI . In a series of validation experiments , we determined that this PAU24 mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain , other deletion mutants and comparable to a MMR mutant involving the MLH1 gene . Likewise , in yeast strains with a deletion of PAU24 , we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen . OUTPUT:

genomic instability and mutation

HoC_1shot1077

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 current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues . This was done to mimic the clinical setting where in , normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation . The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretreatment with macerated extract of Nigella sativa seeds ( 100 mg/kg ) , using alkaline comet assay , and also estimating biochemical and blood parameters such as levels of antioxidant enzymes superoxide dismutase and catalase , thiobarbituric acid reactive substances and protein oxidation in organs such as spleen , liver , brain and intestine haemoglobin and total leucocyte count , respectively . The results showed that the macerated extract of Nigella sativa seeds protected the liver , spleen , brain and intestines both in normal as well as tumour bearing mice . This study concludes that macerated extract of Nigella sativa seeds has protective effects against radiation-induced damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties . Hence macerated extract of Nigella sativa seeds , could be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating unwanted side effects of radiation in normal tissues . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot1078

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 In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis , whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells . We show that this may result in cancer via mitotic failure , recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer , to a biophysical defect that may contribute to cancer initiation . MODEL Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance , disrupted microtubule dynamics , and finally , genomic instability , from which cancers can arise . Specifically , we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer . CONCLUSIONS A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell . Contrary to current understanding , this effect may precipitate cancer development , rather than follow from it , providing new insights into carcinogenesis , cancer treatment , and prevention . OUTPUT:

cellular energetics

HoC_1shot1079

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 green fluorescent protein ( GFP ) is the most commonly used reporter protein for monitoring gene expression and protein localization in a variety of living and fixed cells , including not only prokaryotes , but also eukaryotes , e.g. , yeasts , mammals , plants and fish . In general , it is thought that GFP is nontoxic to cells , although there are some reports on the side effect of GFP . Further , details of the molecular mechanism concerning the side effect of GFP remain unclear . Here we show that Ku80 , but not XRCC4 , plays an important role in the mechanism of the resistance to cytotoxicity induced by enhanced GFP ( EGFP ) . EGFP inhibited both cell proliferation and colony formation , and induced cell death in Ku80-deficient hamster cells , i.e. , xrs-6 cells . In addition , Ku80 attenuated EGFP-induced cytotoxicity in the xrs-6 cells . No EGFP-induced cytotoxicity was observed in the NHEJ core protein XRCC4-deficient hamster cells , i.e. , XR-1 cells . Furthermore , EGFP markedly enhanced X-ray-induced cytotoxicity in the xrs-6 cells . These results suggest that Ku80 plays a key role in the novel NHEJ-independent defense mechanism against EGFP-induced cytotoxicity . Caution should be taken in considering of the potential influence by the stress response mechanism , namely , the Ku80-dependent elimination mechanism of EGFP-induced cytotoxicity , being activated , even when using EGFP-expressing cells in which Ku80 functions normally . OUTPUT:

genomic instability and mutation

HoC_1shot1080

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: As a member of peroxiredoxin ( Prx ) family , PrxIII is predominantly located in mitochondria and plays an important role as a scavenger of reactive oxygen species ( ROS ) . Since previous reports demonstrated over-expression of PrxIII in cervical cancer , we conducted the present study to investigate the significance of PrxIII in cervical cancer development and/or progression . Cervical cancer cells were cultured from tissues derived from cervical cancer patients . After successful knockdown of PrxIII expression by small interfering RNA , we evaluated ROS level , viable cell number , and apoptosis of cervical cancer cells along with the culture time . The production of ROS was increased in cervical cancer cells as compared with normal cervical epithelia . Knockdown of PrxIII expression induced up-regulation of other Prx members including PrxI , PrxII , and PrxV . ROS level was higher in down-regulated cervical cancer cells than in controls and the difference was increasing with culture time . We also observed increased apoptosis and decreased viable cell number in down-regulated cervical cancer cells . Our results suggest that PrxIII is an indispensable ROS scavenger , which protects tumor cells against oxidative damage and subsequent apoptosis . OUTPUT:

tumor promoting inflammation;resisting cell death

HoC_1shot1081

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: Cellular senescence , an irreversible cell cycle arrest induced by a diversity of stimuli , has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy . Using a targeted proteomics approach , we show that fibroblasts induced into senescence by expression of oncogenic Ras exhibit a decrease of global acetylation on all core histones , consistent with formation of senescence-associated heterochromatic foci . We also detected clear increases in repressive markers ( e.g. >50% elevation of H3K27me2/3 ) along with decreases in histone marks associated with increased transcriptional expression/elongation ( e.g . H3K36me2/3 ) . Despite the increases in repressive marks of chromatin , 179 loci ( of 2206 total ) were found to be upregulated by global quantitative proteomics . The changes in the cytosolic proteome indicated an upregulation of mitochondrial proteins and downregulation of proteins involved in glycolysis . These alterations in primary metabolism are opposite to the well-known Warburg effect observed in cancer cells . This study significantly improves our understanding of stress-induced senescence and provides a potential application for triggering it in antiproliferative strategies that target the primary metabolism in cancer cells . OUTPUT:

enabling replicative immortality;cellular energetics

HoC_1shot1082

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: Hypoxia-inducible factor-1 ( HIF-1 ) plays a critical role in reprogramming cancer metabolism toward aerobic glycolysis ( i.e. , the Warburg effect ) , which is critical to supplying cancer cells with the biomass needed for proliferation . Previous studies have shown that cetuximab , an EGF receptor-blocking monoclonal antibody , downregulates the alpha subunit of HIF-1 ( HIF-1α ) through the inhibition of EGF receptor downstream cell signaling and that downregulation of HIF-1α is required for cetuximab-induced antiproliferative effects . However , the mechanism underlying these actions has yet to be identified . In this study , we used the Seahorse XF96 extracellular flux analyzer to assess the effect of cetuximab treatment on changes in glycolysis and mitochondrial respiration , the two major energy-producing pathways , in live cells . We found that cetuximab downregulated lactate dehydrogenase A ( LDH-A ) and inhibited glycolysis in cetuximab-sensitive head and neck squamous cell carcinoma ( HNSCC ) cells in an HIF-1α downregulation-dependent manner . HNSCC cells with acquired cetuximab resistance expressed a high level of HIF-1α and were highly glycolytic . Overexpression of a HIF-1α mutant ( HIF-1α/ΔODD ) conferred resistance to cetuximab-induced G1 phase cell-cycle arrest , which could be overcome by knockdown of LDH-A expression . Inhibition of LDH-A activity with oxamate enhanced the response of cetuximab-resistant cells to cetuximab . Cetuximab had no noticeable inhibitory effect on glycolysis in nontransformed cells . These findings provide novel mechanistic insights into cetuximab-induced cell-cycle arrest from the perspective of cancer metabolism and suggest novel strategies for enhancing cetuximab response . OUTPUT:

cellular energetics;sustaining proliferative signaling

HoC_1shot1083

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: Oncogene-induced senescence is now recognized as being an important mechanism in protecting against cancer . The phenotypic consequences , i.e. , the inhibition of cell proliferation , are well described in model systems and specific events/key players defined . However , there is still the need to understand , at a more global level , the network of events involved both in terms of cause and consequence . This paper shows the power of systematic proteomic analyses , both targeted and global , in addressing such biological questions , highlighting the widespread nature of histone acetylation changes , and the opposite metabolic changes to those seen in the Warburg effect . OUTPUT:

cellular energetics

HoC_1shot1084

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: CONTEXT Papillary thyroid carcinoma ( PTC ) is the most frequent thyroid tumor and is responsible for the overall increase in thyroid cancer incidence . S100A11 ( calgizzarin ) , a member of the S100 Ca(2+)-binding protein family , is involved in several different biological processes . S100A11 has been found up-regulated in PTC , both at the mRNA and protein levels . OBJECTIVE Through a combination of expression analysis and functional in vitro and in vivo studies , we have attempted to gain insight into the relevance of S100A11 overexpression in PTC biology . DESIGN The expression of the S100A11 gene in PTC was investigated in several gene expression data sets . The effect of S100A11 silencing on the hallmarks of the malignant phenotype of several PTC-derived cell lines was investigated . In NIH3T3 cells , the cooperation of S100A11 with the different PTC-specific oncogenes was assessed . RESULTS We found that the S100A11 gene expression is frequently up-regulated in PTC , anaplastic thyroid carcinoma , but not in follicular thyroid carcinoma . S100A11 overexpression was also detected in PTC-derived cell lines , which were then used for functional studies . S100A11 silencing in PTC-derived cell lines did not affect cell proliferation , whereas it reduced the loss of contact inhibition , anchorage-independent growth , and resistance to anoikis . Cotransfection experiments in NIH3T3 cells showed that overexpression of the S100A11 gene was able to enhance the transforming capabilities of the different PTC-associated oncogenes by affecting the loss of contact inhibition , anchorage-independent growth , and in vivo tumor formation . CONCLUSION Our data indicate that S100A11 overexpression exerts a protumoral functional role in PTC pathogenesis . OUTPUT:

evading growth suppressors

HoC_1shot1085

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 Yes Associated Protein ( YAP ) has been implicated in the control of organ size by regulating cell proliferation and survival . YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus , while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol . YAP overexpression has been associated with different types of cancer , such as lung , skin , prostate , ovary and liver cancer . Recently , YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells . RESULTS In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression . We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP ( p < 0.001 ) . Nuclear YAP expression did not associate with other variables such as lymph node involvement , tumor grade , tumor size , mitotic activity or the molecular sub-types of invasive breast cancer . We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC ( p < 0.001 ) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer . CONCLUSIONS Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions , it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot1086

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 aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide ( H2O2 ) in murine Hepa-1c1c7 cells . Oxidative DNA damage was estimated by nuclear condensation assessment , fluorescence-activated cell sorting analysis , and Comet assay . Rutaecarpine inhibited cell death induced by 500 μM H2O2 , as assessed by 4',6-diamidino-2-phenylindole ( DAPI ) staining . Treatment with rutaecarpine reduced the number of DNA strand breaks induced by H2O2 , as assessed by DAPI staining and Comet assay , and increased quinone reductase , phosphatidylinositol 3-kinase , and pAkt protein levels , as assessed by western blotting . OUTPUT:

resisting cell death;genomic instability and mutation

HoC_1shot1087

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 the immense efforts have been made for cancer prevention , early diagnosis , and treatment , cancer morbidity and mortality has not been decreased during last forty years . Especially , lung cancer is top-ranked in cancer-associated human death . Therefore , effective strategy is strongly required for the management of lung cancer . In the present study , we found that novel daphnane diterpenoids , yuanhualine ( YL ) , yuanhuahine ( YH ) and yuanhuagine ( YG ) isolated from the flower of Daphne genkwa ( Thymelaeaceae ) , exhibited potent anti-proliferative activities against human lung A549 cells with the IC50 values of 7.0 , 15.2 and 24.7 nM , respectively . Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells . The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A , cyclin B1 , cyclin E , cyclin dependent kinase 4 , cdc2 , phosphorylation of Rb and cMyc expression . In the analysis of signal transduction molecules , the daphnane diterpenoids suppressed the activation of Akt , STAT3 and Src in human lung cancer cells . The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549 , gefitinib- , erlotinib-resistant H292 cells . Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine , gefitinib or erlotinib in A549 cells . Taken together , these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot1088

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: Epidermal growth factor receptor ( EGFR ) gene amplification and overexpression are commonly present in glioblastoma , and confer advantages of growth , invasiveness and radio/chemotherapy-resistance for tumour cells . Here , we assessed the role of EGFR activation for downstream mitogenic signalling in the commonly used glioblastoma cell line U251 . Despite the high expression level , activation of EGFR under standard culture conditions was low . Intact EGFR function was verified by the rapid phosphorylation of EGFR and downstream mitogen-activated protein(MAP) kinase ERK1/2 upon addition of exogenous EGF to serum-starved cells . By contrast , addition of fetal bovine serum ( FBS ) activated downstream ERK1/2 via the MAP kinase kinase without phosphorylating EGFR . A phosphoreceptor tyrosine kinase array showed FBS-induced activation of insulin-like growth factor-1 receptor ( IGF-1R),and the IGF-1R inhibitor AG1024 inhibited FBS-induced phosphorylation of ERK1/2 , implying IGF-1R as the major driver of FBS-associated mitogenic signalling in the absence of exogenous EGF . These findings have important implications for in vitro drug testing in glioblastoma . Moreover , activation of ERK1/2 was also strongly influenced by growth state and cell density of U251 cultures . Re-seeding exponentially growing cultures at high cell density induced p27/CDKN1B expression and suppressed P-ERK1/2 indicating a certain regulation of proliferation by contact inhibition . Strikingly , highly activated ERK1/2 signalling and cell cycle progression occurred when cells were released from plateau phase regardless of high seeding density . This phenomenon might implicate a proliferation response in the early recurrence observed after clinical therapy in glioblastoma patients . However , whether it will recapitulate in vivo remains to be demonstrated . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot1089

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: Accumulating data suggest arsenic may be an endocrine disruptor and tentatively linked to breast cancer by some studies . Therefore , we tested the effects of chronic inorganic arsenic exposure on the normal estrogen receptor ( ER)-negative breast epithelial cell line , MCF-10A . Cells were chronically exposed to a low-level arsenite ( 500nM ) for up to 24weeks . Markers of cancer cell phenotype and the expression of critical genes relevant to breast cancer or stem cells ( SCs ) were examined . After 24weeks , chronic arsenic-exposed breast epithelial ( CABE ) cells showed increases in secreted MMP activity , colony formation , invasion , and proliferation rate , indicating an acquired cancer cell phenotype . These CABE cells presented with basal-like breast cancer characteristics , including ER-α , HER-2 , and progesterone receptor negativity , and overexpression of K5 and p63 . Putative CD44(+)/CD24(-/low) breast SCs were increased to 80% over control in CABE cells . CABE cells also formed multilayer cell mounds , indicative of loss of contact inhibition . These mounds showed high levels of K5 and p63 , indicating the potential presence of cancer stem cells ( CSCs ) . Epithelial-to-mesenchymal transition occurred during arsenic exposure . Overexpression of aromatase , a key rate-limiting enzyme in estrogen synthesis , occurred with arsenic starting early on in exposure . Levels of 17β-estradiol increased in CABE cells and their conditioned medium . The aromatase inhibitor letrozole abolished arsenic-induced increases in 17β-estradiol production and reversed cancer cell phenotype . Thus , chronic arsenic exposure drives human breast epithelia into a cancer cell phenotype with an apparent overabundance of putative CSCs . Arsenic appears to transform breast epithelia through overexpression of aromatase , thereby activating oncogenic processes independent of ER . OUTPUT:

activating invasion and metastasis;sustaining proliferative signaling;evading growth suppressors

HoC_1shot1090

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: Metabolic reprogramming in cancer is manifested by persistent aerobic glycolysis and suppression of mitochondrial function and is known as the Warburg effect . The Warburg effect contributes to cancer progression and is considered to be a promising therapeutic target . Understanding the mechanisms used by cancer cells to suppress their mitochondria may lead to development of new approaches to reverse metabolic reprogramming . We have evaluated mitochondrial function and morphology in poorly respiring LM7 and 143B osteosarcoma ( OS ) cell lines showing the Warburg effect in comparison with actively respiring Saos2 and HOS OS cells and noncancerous osteoblastic hFOB cells . In LM7 and 143B cells , we detected markers of the mitochondrial permeability transition ( MPT ) , such as mitochondrial swelling , depolarization , and membrane permeabilization . In addition , we detected mitochondrial swelling in human OS xenografts in mice and archival human OS specimens using electron microscopy . The MPT inhibitor sanglifehrin A reversed MPT markers and increased respiration in LM7 and 143B cells . Our data suggest that the MPT may play a role in suppression of mitochondrial function , contributing to the Warburg effect in cancer . OUTPUT:

cellular energetics

HoC_1shot1091

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 cells require glucose to support their rapid growth through a process known as aerobic glycolysis , or the Warburg effect . As in ovarian cancer cells , increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer . However , it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis . In the present research , we found that EF24 , a HIF-1α inhibitor , could significantly block glucose uptake , the rate of glycolysis , and lactate production compared with vehicle treatment in SKOV-3 , A2780 and OVCAR-3 cells . These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays . Furthermore , as an important mediator of glucose metabolism , glucose transporter 1 ( Glut1 ) was found to contribute to the function of EF24 in both energy metabolism and metastasis . To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model , intraperitoneal metastasis and lung metastasis model were introduced . Our results indicated that EF24 treatment could inhibit tumor growth , intraperitoneal metastasis and lung metastasis of SKOV-3 cells , and Glut1 is a possible mediator for the role of EF24 . In conclusion , our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis , and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer . OUTPUT:

cellular energetics;activating invasion and metastasis

HoC_1shot1092

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: One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype . Carbon monoxide ( CO ) , one of the products of the cytoprotective molecule heme oxygenase-1 ( HO-1 ) in cancer cells , has been implicated in carcinogenesis and therapeutic resistance . However , the functional contributions of CO and HO-1 to these processes are poorly defined . In human prostate cancers , we found that HO-1 was nuclear localized in malignant cells , with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes . Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy , with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe . CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption , free radical generation , and mitochondrial collapse . Collectively , our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics , ultimately resulting in metabolic exhaustion . OUTPUT:

resisting cell death;cellular energetics

HoC_1shot1093

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 the most lethal attribute of human malignancy . High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer . Previous studies indicate that a mutation of the threonine residue at position 34 ( Thr34Ala ) of survivin generates a dominant-negative mutant that induces apoptosis , inhibits angiogenesis , and suppresses highly metastatic breast carcinoma in mouse models . We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis . The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages . We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A ( Lip-mS ) , Lip-plasmid ( Lip-P ) , or normal saline ( NS ) . Eight days after the last dose , five randomly chosen mice from each group were sacrificed . We detected the apoptotic index , microvessel density ( MVD ) , lymphatic microvessel density ( LMVD ) , and the expression of VEGF-D with immunohistochemistry . After the remaining animals were sacrificed , we compared the tumor-infiltrated lymph nodes in each group . Administration of mSurvivinT34A plasmid complexed with cationic liposome ( DOTAP/chol ) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model . These responses were associated with tumor cell apoptosis , and angiogenesis and lymphangiogenesis inhibition . Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis , thus suppressing tumor growth and lymphatic metastasis . The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis . OUTPUT:

activating invasion and metastasis;inducing angiogenesis;resisting cell death

HoC_1shot1094

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 a key player in the Warburg effect of cancer cells . However , the mechanisms of regulating PKM2 are not fully elucidated . Here , we identified the protein-serine/threonine kinase PIM2 , a known oncogene , as a novel binding partner of PKM2 . The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells . Importantly , we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue , resulting in an increase of PKM2 protein levels . Compared with wild type , PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis , co-activating HIF-1α and β-catenin , and cell proliferation , while enhancing mitochondrial respiration of cancer cells . These findings demonstrate that PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer , highlighting PIM2 as a potential therapeutic target . OUTPUT:

cellular energetics;genomic instability and mutation

HoC_1shot1095

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 is the most aggressive primary brain tumor in adults . Overexpression of the EGF receptor ( EGFR ) is recognized as a widespread oncogenic signature in glioblastoma multiforme , but the complexity of its contributions is not fully understood , nor the most effective ways to leverage anti-EGFR therapy in this setting . Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria ( OXPHOS ) , a phenomenon termed the Warburg effect , which is a general feature of oncogenesis . In this study , we report that hypoxia drives expression of the pyruvate dehydrogenase kinase ( PDK1 ) and EGFR along with the hypoxia-inducing factor ( HIF)-1α in human glioblastoma multiforme cells . PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation , initiating a feed-forward loop that can sustain malignant progression . RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1α expression , shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation . In clinical specimens of glioblastoma multiforme , we found that immunohistochemical expression of PDK1 , EGFR , and HIF-1α were elevated in glioblastoma multiforme specimens when compared with normal brain tissues . Collectively , our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme . OUTPUT:

sustaining proliferative signaling;cellular energetics

HoC_1shot1096

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 Anti-angiogenic treatment of glioblastoma characteristically results in therapy resistance and tumor progression via diffuse infiltration . Monitoring tumor progression in these patients is thwarted because therapy results in tumor invisibility in contrast-enhanced ( CE ) MRI . To address this problem , we examined whether tumor progression could be monitored by metabolic mapping using ( 1)H MR spectroscopic imaging ( MRSI ) . METHODS We treated groups of BALB/c nu/nu mice carrying different orthotopic diffuse-infiltrative glioblastoma xenografts with bevacizumab ( anti-vascular endothelial growth factor [ VEGF ] antibody , n = 13 ) , cabozantinib ( combined VEGF receptor 2/c-Met tyrosine kinase inhibitor , n = 11 ) , or placebo ( n = 15 ) and compared CE-MRI with MRS-derived metabolic maps before , during , and after treatment . Metabolic maps and CE-MRIs were subsequently correlated to histology and immunohistochemistry . RESULTS In vivo imaging of choline/n-acetyl aspartate ratios via multivoxel MRS is better able to evaluate response to therapy than CE-MRI . Lactate imaging revealed that diffuse infiltrative areas in glioblastoma xenografts did not present with excessive glycolysis . In contrast , glycolysis was observed in hypoxic areas in angiogenesis-dependent compact regions of glioma only , especially after anti-angiogenic treatment . CONCLUSION Our data present MRSI as a powerful and feasible approach that is superior to CE-MRI and may provide handles for optimizing treatment of glioma . Furthermore , we show that glycolysis is more prominent in hypoxic areas than in areas of diffuse infiltrative growth . The Warburg hypothesis of persisting glycolysis in tumors under normoxic conditions may thus not be valid for diffuse glioma . OUTPUT:

cellular energetics;inducing angiogenesis

HoC_1shot1097

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: Metastatic breast tumors undergo epithelial-to-mesenchymal transition ( EMT ) , which renders them resistant to therapies targeted to the primary cancers . The mechanistic link between mtDNA ( mitochondrial DNA ) reduction , often seen in breast cancer patients , and EMT is unknown . We demonstrate that reducing mtDNA content in human mammary epithelial cells ( hMECs ) activates Calcineurin ( Cn)-dependent mitochondrial retrograde signaling pathway , which induces EMT-like reprogramming to fibroblastic morphology , loss of cell polarity , contact inhibition and acquired migratory and invasive phenotype . Notably , mtDNA reduction generates breast cancer stem cells . In addition to retrograde signaling markers , there is an induction of mesenchymal genes but loss of epithelial markers in these cells . The changes are reversed by either restoring the mtDNA content or knockdown of CnAα mRNA , indicating the causal role of retrograde signaling in EMT . Our results point to a new therapeutic strategy for metastatic breast cancers targeted to the mitochondrial retrograde signaling pathway for abrogating EMT and attenuating cancer stem cells , which evade conventional therapies . We report a novel regulatory mechanism by which low mtDNA content generates EMT and cancer stem cells in hMECs.Oncogene advance online publication , 4 November 2013 ; doi:10.1038/onc.2013.467 . OUTPUT:

activating invasion and metastasis;evading growth suppressors

HoC_1shot1098

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 normal tissues , strict control of tissue size is achieved by regulating cell numbers . The mechanism that controls total cell number is known as contact inhibition of growth and it depends on the NF2/Merlin pathway . Negative regulation of this pathway by deleterious mutations or by oncogenes results in cell transformation and tumor progression . Here we provide evidence that the CD43 sialomucin cooperates with oncogenic signals to promote cell transformation by abrogating the contact inhibition of growth through a molecular mechanism that involves AKT-dependent Merlin phosphorylation and degradation . Accordingly , inhibition of endogenous CD43 expression by RNA interference in lung , cervix and colon human cancer cells impaired tumor growth in vivo . These data underscore a previously unidentified role for CD43 in non-hematopoietic tumor progression . OUTPUT:

evading growth suppressors

HoC_1shot1099

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 Multiple myeloma ( MM ) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype ( i.e. , the Warburg effect ) . We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane ( PM ) localization of GLUT4 , consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates , proliferative capacity , and viability . The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells . FINDINGS We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect . AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation , known to be required for inactivation of AS160 Rab-GAP activity . Importantly , we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines . Furthermore , we demonstrate that ectopic expression of a full-length , phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence , which is characteristic of MM cells . CONCLUSIONS This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer . Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease . OUTPUT:

cellular energetics