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hippocrates

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HoC_1shot_train

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[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with β(2)-adrenergic receptor ( β(2)-AR ) stimulation . However , the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear . Here , we compare the effect of the β(2)-AR agonists ( R,R')-fenoterol ( Fen ) and ( R,R')-4-methoxy-1-naphthylfenoterol ( MNF ) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [ (3)H]thymidine incorporation assays . Despite the expression of β(2)-AR , no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen , although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation . Unexpectedly , isoproterenol and Fen promoted HepG2 cell growth , but MNF reduced proliferation together with increased apoptosis . The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol ( ICI 118,551 ) , a β(2)-AR antagonist , whereas those of MNF were unaffected . Because of the coexpression of β(2)-AR and cannabinoid receptors ( CBRs ) and their impact on HepG2 cell proliferation , these Gα(i)/Gα(o)-linked receptors may be implicated in MNF signaling . Cell treatment with ( R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone ( WIN 55,212-2 ) , a synthetic agonist of CB(1)R and CB(2)R , led to growth inhibition , whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling . MNF responses were sensitive to pertussis toxin . The β(2)-AR-deficient U87MG cells were refractory to Fen , but responsive to the antiproliferative actions of MNF and WIN 55,212-2 . The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway , providing one of the first examples of a dually acting β(2)-AR-CBR ligand .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Context:The ubiquitin-proteasome system and macroautophagy are two major pathways for intracellular protein degradation . Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system by proteasome inhibitors activates macroautophagy.Objective:The purpose of this study was to determine the involvement of autophagy essential gene Beclin 1 in cytotoxicity of thyroid cancer cells mediated by proteasome inhibitors.Design:Autophagy was measured by acidic-trophic dye staining and EGF-LC3 distribution using fluorescence microscopy , as well as LC3-II transition using Western blot . To ascertain the effect of Beclin 1 , cells were transfected with Beclin 1 plasmid or shRNA against Beclin 1 . Cell viability and apoptotic cells were measured using MTT assay and flow cytometry , respectively.Results:Proteasome inhibitors decreased Beclin 1 expression . In addition , treatment with PI3K inhibitors 3-MA or wortmannin , as well as knockdown of Beclin 1 expression , was unable to affect autophagic responses mediated by proteasome inhibitors . Overexpression of Beclin 1 enhanced proteasome inhibitor-mediated cytotoxicity of thyroid cancer cells via suppression of survivin.Conclusions:Proteasome inhibitors cause Beclin 1-independent macroautophagic responses of thyroid cancer cells in a Beclin 1-independent manner . Beclin 1 possesses autophagy-independent antitumoral effects upon exposure of thyroid cancer cells to proteasome inhibitors .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: SCOPE In this study , we evaluated the efficacy of lycopene against the growth of prostate cancer in vivo . METHODS AND RESULTS Athymic nude mice were implanted subcutaneously with human androgen-independent prostate carcinoma PC-3 cells . They were supplemented with a low or a high dose of lycopene ( 4 and 16 mg/kg ) and a single dose of β-carotene ( 16 mg/kg ) twice a week for 7 wk . At the end of the experiment , both lycopene and β-carotene strongly inhibited the tumor growth , as evidenced by the decrease in tumor volume and tumor weight . High-dosage lycopene and β-carotene significantly decreased the expression of proliferating cell nuclear antigen in tumor tissues and increased the levels of insulin-like growth factor-binding protein-3 in plasma . In addition , high-dosage lycopene supplementation significantly decreased the vascular endothelial growth factor ( VEGF ) levels in plasma . In contrast , β-carotene supplementation significantly increased the VEGF levels , as compared with tumor control group . CONCLUSION Lycopene and β-carotene supplementation suppressed the growth of prostate tumor cells , and the effects are likely associated with reduction of proliferation ( attenuation of proliferating cell nuclear antigen expression ) and with interference of the insulin-like growth factor 1 signaling ( increased plasma insulin-like growth factor-binding protein-3 levels ) . Furthermore , the inhibition of VEGF by lycopene suggests that the antitumor mechanisms of lycopene also involve anti-angiogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process , methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M . All transformants examined revealed an alteration in DNA methylation in some of the genes , although these changes were variable among them . A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes , whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes . Resultant data indicate that the alteration of DNA methylation is closely related to transformation process , yet how this involvement occurs is complex and remains unclear .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells ( MECs ) . One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence . However , the precise genetic changes that are responsible for this event in MECs is largely unknown . Here , we report that Bmi-1 , originally identified as a c-Myc cooperating oncoprotein , can bypass senescence , extend the replicative life span , and immortalize MECs . Furthermore , Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines . Overexpression of Bmi-1 in MECs led to activation of human telomerase reverse transcriptase ( hTERT ) transcription and induction of telomerase activity . Telomerase induction by Bmi-1 was an early event in the extension of the replicative life span and immortalization . Bmi-1 was not overexpressed in hTERT-immortalized MECs , suggesting that Bmi-1 functions upstream of hTERT . Although , c-Myc has been reported to induce telomerase in MECs , Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT promoter . Deletion analysis of the Bmi-1 protein suggested that the RING finger , as well as a conserved helix-turn-helix-turn domain , were required for its ability to induce telomerase and immortalize MECs . These data suggest that Bmi-1 regulates telomerase expression in MECs and plays a role in the development of human breast cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils . More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer . METHODS In the present study , we used microarrays in order to obtain a global view of the transcriptional responses of the lung to LPS in mice , which mimics an acute lung inflammation . To investigate the influence of neutrophils in this process , we depleted mice from circulating neutrophils by treatment with anti-PMN antibodies prior to LPS exposure . RESULTS A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes , such as cytokine/chemokine activity and signalling . Down regulated genes represented nonimmune processes , such as development , metabolism and transport . Notably , the number of genes and pathways that were differentially expressed , was reduced when animals were depleted from circulating neutrophils , confirming the central role of neutrophils in the inflammatory response . Furthermore , there was a significant correlation between the differentially expressed gene list and the promutagenic DNA lesion M1dG , suggesting that it is the extent of the immune response which drives genetic instability in the inflamed lung . Several genes that were specifically regulated by the presence of activated neutrophils could be identified and these were mostly involved in interferon signalling , oxidative stress response and cell cycle progression . The latter possibly refers to a higher rate of cell turnover in the inflamed lung with neutrophils , suggesting that the neutrophil influx is associated with a higher risk for the accumulation and fixation of mutations . CONCLUSION Gene expression profiling identified specific genes and pathways that are related to neutrophilic inflammation and could be associated to cancer development and indicate an active role of neutrophils in mediating the LPS induced inflammatory response in the mouse lung .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo . Although it is generally accepted that contact inhibition plays a pivotal role in maintaining tissue homeostasis , the molecular mechanisms of contact inhibition are still not fully understood . FoxM1 is known as a proliferation-associated transcription factor and is upregulated in many cancer types . Vice versa , anti-proliferative signals , such as TGF-β and differentiation signals decrease FoxM1 expression . Here we investigated the role of FoxM1 in contact inhibition in fibroblasts . We show that protein expression of FoxM1 is severely and rapidly downregulated upon contact inhibition , probably by inhibition of ERK activity , which then leads to decreased expression of cyclin A and polo-like kinase 1 . Vice versa , ectopic expression of FoxM1 prevents the decrease in cyclin A and polo-like kinase 1 and causes a two-fold increase in saturation density indicating loss of contact inhibition . Hence , we show that downregulation of FoxM1 is required for contact inhibition by regulating expression of cyclin A and polo-like kinase 1 .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Breast cancer constitutes a major health problem for women worldwide . However , its incidence varies between populations and geographical locations . These variations could be diet-related , since there are several carcinogenic compounds in the modern diet , while natural products contain various anti-cancer elements . Several lines of evidence indicate that , in addition to their clear preventive effect , these compounds could also be used as therapeutic agents . In the present report we have shown that oleuropein , a pharmacologically safe natural product of olive leaf , has potent anti-breast cancer properties . Indeed , oleuropein exhibits specific cytotoxicity against breast cancer cells , with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells . This effect is mediated through the induction of apoptosis via the mitochondrial pathway . Moreover , oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21 . Furthermore , oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-κB and its main oncogenic target cyclin D1 . This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells . Therefore , oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer , especially the less-responsive basal-like type .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We have constructed plasmids pS3G-1 and pSG4 that contain single acetylaminofluorene adducts within contiguous runs of three ( 5'-CCCG1G2G3-3' ) and four ( 5'-CG1GGG4T-3' ) guanine residues , respectively . In Escherichia coli , the frequency of induced -1 frameshift mutations was strongly dependent on the position of modification : pS3G-G3 was approximately 100-fold and 10-fold more mutagenic than pS3G-G1 and pS3G-G2 , respectively ; pSG4-G4 was approximately 600-fold more mutagenic than pSG4-G1 . Mutagenesis was SOS-dependent and was markedly reduced in bacteria that were proficient in nucleotide excision repair as compared to a repair-deficient uvrA6 mutant . DNA sequencing showed that -1 frameshift events in pS3G-1 consisted of either targeted mutations ( greater than 90% of induced mutations ) within the guanine sequence or semitargeted mutations ( greater than 10% ) in the 5 ' flanking repetitive cytosine sequence . Semitargeted events , which were observed when acetylaminofluorene modification was at G1 and G2 , show that a lesion can reduce the fidelity of replication at positions 5 ' to its location on the template strand . No semitargeted frameshifts were observed in plasmid pSG4 , which lacks a repetitive sequence 5 ' to the adduct . Our results are consistent with a model for frameshift mutagenesis in which the acetylaminofluorene adduct ( i ) allows accurate incorporation of cytosine opposite the bulky lesion during DNA synthesis and ( ii ) impedes elongation of primer/template termini formed opposite the adduct or 5 ' to the adduct on the template strand , providing increased opportunity for the formation of slipped frameshift intermediates .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Myxoid leiomyosarcoma is an extremely rare variant of leiomyosarcoma , masquerading almost to perfection as a benign lesion . For , indeed , the tumor lacks the defining features of high mitotic activity , cellular atypia or necrosis , and the microscopic picture is dominated by abundant myxoid stroma containing sparse spindle cells . We report here such a case occurring in the uterus and discuss the differential diagnosis . The relevant literature is reviewed .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Most ovarian cancers are estrogen-positive and hormonal treatments using anti-estrogens or aromatase inhibitors are under investigation for treating the tumors that are resistant to conventional therapies . In this study , the long-term effects of two anti-estrogens , namely 4-hydroxytamoxifen and fulvestrant ( or ICI182,780 ) , were investigated in ERα-positive BG1 epithelial ovarian cancer cells . To this aim , cells were grown in the presence of anti-estrogen concentrations that were sufficient to saturate the estrogen receptors , but were neither cytotoxic nor cytostatic as indicated by the absence of inhibition of cell proliferation . In these conditions and despite the lack of cytostatic effect of the drugs , long-term treatment ( 3 months ) with the pure anti-estrogen fulvestrant induced a specific , reproducible and irreversible inhibition of ERα expression . This inhibition was accompanied by loss of estrogen-induced cell proliferation and gene expression as indicated by the analysis of several estrogen-responsive genes . ERα down-regulation was not linked to deregulated expression of transcription factors which drive ERα transcription and did not involve DNA methylation or histone deacetylation . Altogether , these results demonstrate that non-cytotoxic concentrations of pure anti-estrogens affect estrogen signaling and might be relevant for the treatment for ovarian cancers .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The secretin receptor ( SR ) , a G protein-coupled receptor , mediates the effects of the gastrointestinal hormone secretin on digestion and water homeostasis . Recently , high SR expression has been observed in pancreatic ductal adenocarcinomas , cholangiocellular carcinomas , gastrinomas , and bronchopulmonary carcinoid tumors . Receptor overexpression associates with enhanced secretin-mediated signaling , but whether this molecule plays an independent role in tumorigenesis is currently unknown . We recently discovered that pheochromocytomas developing in rats affected by the MENX ( multiple endocrine neoplasia-like ) syndrome express at very high-level Sctr , encoding SR . We here report that SR are also highly abundant on the membranes of rat adrenal and extraadrenal pheochromocytoma , starting from early stages of tumor development , and are functional . PC12 cells , the best characterized in vitro pheochromocytoma model , also express Sctr at high level . Thus , we used them as model to study the role of SR in neoplastic transformation . Small interfering RNA-mediated knockdown of Sctr decreases PC12 cells proliferation and increases p27 levels . The proproliferative effect of SR in PC12 cells is mediated , in part , by the phosphatidylinositol 3 kinase ( PI3K)/serine-threonine protein kinase ( AKT ) pathway . Transfection of Sctr in Y1 adrenocortical carcinoma cells , expressing low endogenous levels of Sctr , stimulates cell proliferation also , in part , via the PI3K/AKT signaling cascade . Because of the link between SR and PI3K/AKT signaling , tumor cells expressing high levels of the receptor ( MENX-associated primary pheochromocytoma and NCI-H727 human bronchopulmonary carcinoid cells ) respond well and in a SR-dependent manner to PI3K inhibitors , such as NVP-BEZ235 . The association between SR levels and response to PI3K inhibition might open new avenues for the treatment of tumors overexpressing this receptor .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Many cells in mammals exist in the state of quiescence , which is characterized by reversible exit from the cell cycle . Quiescent cells are widely reported to exhibit reduced size , nucleotide synthesis , and metabolic activity . Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes . In contrast , we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition . By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data , we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells , with greater overflow flux from the pentose phosphate pathway back to glycolysis . Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts . By feeding the cells labeled glutamine , we also detected a \" backwards \" flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts ; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis . The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid , and in part toward excretion of extracellular matrix proteins . Thus , reduced metabolic activity is not a hallmark of the quiescent state . Quiescent fibroblasts , relieved of the biosynthetic requirements associated with generating progeny , direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVES/HYPOTHESIS Head and neck squamous cell carcinoma ( HNSCC ) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells . We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor ( FGFR ) . STUDY DESIGN Preclinical investigation . METHODS HNSCC cell lines ( FADU , OSC19 , Cal27 , SCC1 , SCC5 , SCC22A ) , fibroblast ( HS27 ) , and endothelial cells ( human umbilical vascular endothelial cell ) were cultured individually or in coculture . Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074 . Mice bearing established HNSCC xenografts were treated with PD173074 ( 12 mg/kg ) , and tumor histology was analyzed for stromal composition , proliferation ( Ki67 staining ) , and apoptosis ( TUNEL [ terminal deoxynucleotidyl transferase dUTP nick end labeling ] staining ) . RESULTS In vitro , inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls . However , HNSCC cell proliferation was not affected by inhibition of FGFR . When cocultured with fibroblasts , HNSCC cells proliferation increased by 15% to 80% ( P &lt ; .01 ) . Furthermore , this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition . Additionally , treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition ( P &lt ; .001 ) . Additionally , those tumors from mice treated with PD173074 had a smaller stromal component , decreased proliferation , and increased apoptosis . CONCLUSIONS Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment ( as well as their accumulation in human adipose tissue ) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity . A variety of musk fragrances were tested using the E-screen assay . A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks ( musk xylene , musk ketone ) , a major metabolite of musk xylene ( p-amino-musk xylene ) , and the polycyclic musk fragrance AHTN . This indicates that these substances do , in fact , demonstrate estrogenic activity . Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated . It must be noted , however , that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol . The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances , a group of substances that have not yet been well characterized in respect to their toxicological properties , has also been shown to be weakly estrogenically active in vitro . E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK , the macrocyclic musk fragrances ethylene brassylate , ethylene dodecandioate , and cyclopentadecanolide , are not estrogenically active .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Extensive biochemical and structural analyses have been performed on the putative DNA repair proteins of hyperthermophilic archaea , in contrast to the few genetic analyses of the genes encoding these proteins . Accordingly , little is known about the repair pathways used by archaeal cells at high temperature . Here , we attempted to disrupt the genes encoding the potential repair proteins in the genome of the hyperthermophilic archaeon Thermococcus kodakaraensis . We succeeded in isolating null mutants of the hjc , hef , hjm , xpb , and xpd genes , but not the radA , rad50 , mre11 , herA , nurA , and xpg/fen1 genes . Phenotypic analyses of the gene-disrupted strains showed that the xpb and xpd null mutants are only slightly sensitive to ultraviolet ( UV ) irradiation , methyl methanesulfonate ( MMS ) and mitomycin C ( MMC ) , as compared with the wild-type strain . The hjm null mutant showed sensitivity specifically to mitomycin C. On the other hand , the null mutants of the hjc gene lacked increasing sensitivity to any type of DNA damage . The Hef protein is particularly important for maintaining genome homeostasis , by functioning in the repair of a wide variety of DNA damage in T. kodakaraensis cells . Deletion of the entire hef gene or of the segments encoding either its nuclease or helicase domain produced similar phenotypes . The high sensitivity of the Δhef mutants to MMC suggests that Hef performs a critical function in the repair process of DNA interstrand cross-links . These damage-sensitivity profiles suggest that the archaeal DNA repair system has processes depending on repair-related proteins different from those of eukaryotic and bacterial DNA repair systems using homologous repair proteins analyzed here .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Bone marrow transplantation ( BMT ) , used to treat severe hematological malignancies , often leads to potentially fatal acute graft-versus-host disease ( GVHD ) , despite attempts for better matching and/or use of immune suppressive agents . We reported that embryo-derived PreImplantation-Factor plays a determining role in developing maternal/host tolerance towards the semi/allogenic embryo and regulating systemic immune response . Synthetic PIF ( PIF ) treatment is effective preventing immune attack in non-pregnant models of autoimmunity . Herein , we test PIF ability to prevent acute GVHD development in semi or totally allogenic murine models . We examine PIF's regulatory effect in vivo and in vitro , to control deleterious GVHD while maintaining its ability to preserve beneficial graft vs. leukemia ( GVL effect ) . Bone marrow and spleen cells from C57BL/6 donors were transplanted to semi-allogenic ( C57BL/6�BALB/c ) F1 or allogenic ( BALB/c ) recipients , and then treated with PIF1mg/kg/day/2weeks . Short-term PIF administration reduced acute GVHD in both models and increased survival for up to four months after semi-(or totally ) allogenic BMT . The obtained effect was coupled with lessened skin ( semi-allogenic ) and decreased liver inflammation ( both models ) as well as reduced colon ulceration ( allogenic ) . Both GVHD associated cytokines and chemokines gene expression were decreased in the liver . PIF further lowered circulating interleukin-17 , but not interferon-γ levels . PIF treatment was demonstrated in vivo and in vitro to lead to decreased iNOS expression and in LPS-activated macrophages to lower nitric oxide secretion . Significantly , PIF did not impair the beneficial GVL effect in the B-cell leukemia model . PIF primarily acts by inducing regulatory phenotype on monocytes/APC , which controls T-cell proliferation . Overall our data demonstrates that PIF protects against semi/allogenic GVHD long-term by reducing both target organ and systemic inflammation and by lowering oxidative stress , all while preserving the beneficial GVL effect .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone ( DHC ) , a novel synthetic flavonoid , and fisetin , a naturally occurring flavonol-in prostate cancer cells . In this study , we further examine the mechanisms of these compounds on survival and proliferation pathways . DHC and fisetin ( 1-50 microM ) caused a dose-dependent reduction in viability , a concomitant increase in apoptosis in PC3 cells at 72 h , and a decrease in clonogenic survival at 24 h treatment . DHC was considerably more potent than fisetin in these cytotoxicity assays . The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate ( LNCaP ) cells . Gene expression alterations in PC3 and LNCaP cells treated with 15 muM DHC and 25 microM fisetin for 6 to 24 h were determined by oligonucleotide array . Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category . In total , 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds . Other functional categories altered included chromosome organization , apoptosis , and stress response . These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Helicobacter hepaticus-infected Rag2(-/-) mice emulate many aspects of human inflammatory bowel disease , including the development of colitis and colon cancer . To elucidate mechanisms of inflammation-induced carcinogenesis , we undertook a comprehensive analysis of histopathology , molecular damage , and gene expression changes during disease progression in these mice . Infected mice developed severe colitis and hepatitis by 10wk post-infection , progressing into colon carcinoma by 20wk post-infection , with pronounced pathology in the cecum and proximal colon marked by infiltration of neutrophils and macrophages . Transcriptional profiling revealed decreased expression of DNA repair and oxidative stress response genes in colon , but not in liver . Mass spectrometric analysis revealed higher levels of DNA and RNA damage products in liver compared to colon and infection-induced increases in 5-chlorocytosine in DNA and RNA and hypoxanthine in DNA . Paradoxically , infection was associated with decreased levels of DNA etheno adducts . Levels of nucleic acid damage from the same chemical class were strongly correlated in both liver and colon . The results support a model of inflammation-mediated carcinogenesis involving infiltration of phagocytes and generation of reactive species that cause local molecular damage leading to cell dysfunction , mutation , and cell death . There are strong correlations among histopathology , phagocyte infiltration , and damage chemistry that suggest a major role for neutrophils in inflammation-associated cancer progression . Further , paradoxical changes in nucleic acid damage were observed in tissue- and chemistry-specific patterns . The results also reveal features of cell stress response that point to microbial pathophysiology and mechanisms of cell senescence as important mechanistic links to cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Recent data indicate the Signal Transducer and Activator of Transcription 3 ( STAT3 ) pathway is required for VEGF production and angiogenesis in various types of cancers . STAT3 inhibitors have been shown to reduce tumor microvessel density in tumors but a direct anti-angiogenic activity has not been described . METHODOLOGY/PRINCIPAL FINDINGS We investigated the direct action of a small molecule inhibitor of STAT3 ( LLL12 ) in human umbilical cord vascular endothelial cells ( HUVECs ) in vitro , in a Matrigel model for angiogenesis in vivo , and its antitumor activity in a xenograft model of osteosarcoma . LLL12 ( 100 nM ) significantly inhibited VEGF-stimulated STAT3 phosphorylation in HUVECs , reduced their proliferation/migration and inhibited VEGF-induced tube formation . Morphologic analysis of LLL12 treated HUVECs demonstrated marked changes in actin/tubulin distribution and bundling . In scid mice , LLL12 reduced microvessel invasion into VEGF-infused Matrigel plugs by ∼90% at a dose of 5 mg/kg daily . Following a period of tumor progression ( 2 weeks ) , LLL12 completely suppressed further growth of established OS-1 osteosarcoma xenografts . Pharmacodynamic studies showed robust phosphorylated STAT3 in control tumors , whereas phospho-STAT3 was not detected in LLL12-treated OS-1 tumors . Treated tumors demonstrated decreased proliferation ( Ki67 staining ) , and decreased microvessel density ( CD34 staining ) , but no significant increase in apoptosis ( TUNEL staining ) , relative to controls . Assay of angiogenic factors , using an antibody array , showed VEGF , MMP-9 , Angiopoietin1/2 , Tissue Factor and FGF-1 expression were dramatically reduced in LLL12-treated tumors compared to control tumors . CONCLUSIONS These findings provide the first evidence that LLL12 effectively inhibits tumor angiogenesis both in vitro and in vivo .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Dentin matrix protein 1 ( DMP1 ) is a member of the small integrin-binding ligand N-linked glycoprotein ( SIBLING ) family , a group of proteins initially described as mineralized extracellular matrices components . More recently , SIBLINGs have been implicated in several key steps of cancer progression , including angiogenesis . Although proangiogenic activities have been demonstrated for 2 SIBLINGs , the role of DMP1 in angiogenesis has not yet been addressed . We demonstrate that this extracellular matrix protein induced the expression of vascular endothelial cadherin ( VE-cadherin ) , a key regulator of intercellular junctions and contact inhibition of growth of endothelial cells that is also known to modulate vascular endothelial growth factor receptor 2 ( VEGFR-2 ) activity , the major high-affinity receptor for VEGF . DMP1 induced VE-cadherin and p27(Kip1) expression followed by cell-cycle arrest in human umbilical vein endothelial cells ( HUVECs ) in a CD44-dependent manner . VEGF-induced proliferation , migration , and tubulogenesis responses were specifically blocked on DMP1 pretreatment of HUVECs . Indeed , after VE-cadherin induction , DMP1 inhibited VEGFR-2 phosphorylation and Src-mediated signaling . However , DMP1 did not interfere with basic fibroblast growth factor-induced angiogenesis . In vivo , DMP1 significantly reduced laser-induced choroidal neovascularization lesions and tumor-associated angiogenesis . These data enable us to put DMP1 on the angiogenic chessboard for the first time and to identify this protein as a new specific inhibitor of VEGF-induced angiogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: CEACAM1 , CEA/CEACAM5 , and CEACAM6 are cell adhesion molecules ( CAMs ) of the carcinoembryonic antigen ( CEA ) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers . However , little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression . Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated , contact-inhibited cell growth . Interestingly , CEACAM1-L , but not CEACAM1-S , negatively regulates proliferation via its ITIM domain , while in proliferating cells no CEACAM expression is detectable . Furthermore , we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells , likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L , leading to undifferentiated anchorage-independent cell growth . We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6 , representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients . Taken together , our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L , but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Maintaining the integrity of the cell cycle is critical for ensuring that cells only undergo DNA replication and proliferation under controlled conditions in response to discrete stimuli . One mechanism by which the fidelity of this process is guaranteed is through the activation of cell cycle checkpoints . The mitotic spindle checkpoint , which is regulated by Aurora B kinase , ensures proper kinetochore attachment to chromosomes leading to equal distribution of chromosomes to daughter cells . We demonstrated that the mitogen-activated protein kinase ( MAPK ) cascade regulates mitotic progression and the spindle checkpoint . As demonstrated by immunofluorescence at kinetochores , depletion of Raf Kinase Inhibitory Protein ( RKIP ) , an inhibitor of Raf/MEK/ERK signaling , causes an increase in MAPK activity that inhibits Aurora B kinase activity . By monitoring mitotic index and transit time from nuclear envelope breakdown to anaphase , we demonstrated that RKIP depletion leads to a defective spindle checkpoint and genomic instability , particularly in response to drugs that disrupt microtubule function .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The role of estrogen receptor beta ( ERβ ) in breast cancer is unclear . ERβ is considered to have a protective role in breast cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer cells . We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells . To study the mechanisms of the ERβ-mediated G2 cell cycle arrest , we investigated its effects on the regulatory pathways responsible for the G2/M phase transition . We found that ERβ inhibits CDK1 activity , which is the critical determinant of the G2/M progression . CDK1 activity is modulated by both stimulatory and inhibitory factors . Cyclin B1 is the major activator of CDK1 . ERβ inhibited the cell cycle-dependent stimulation of cyclin B1 mRNA and protein . GADD45A and BTG2 are two major inhibitors of CDK1 , which have been implicated in breast tumor formation . Based on these findings , we explored if the expression pattern of GADD45A and BTG2 is affected by ERβ . We found that ERβ stimulates GADD45A and BTG2 mRNA levels . The induction of these two genes is caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2 . Our findings demonstrated that unliganded ERβ causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2 expression . These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new therapies to prevent breast cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND The pTalpha/preTCR regulates the beta-selection , a crucial T-cell developmental checkpoint , providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck) . METHODS To define the relevance of pTalpha in human T-cell lymphoblastic leukemia ( T-ALL ) , we analyzed in T-ALL cell lines ( n=14 ) pTalpha and p56(Lck) mRNA and protein expression as also the tyrosine-phosphorylation . The p56(Lck) specific src-protein-tyrosine kinase inhibitor ( PTK-I ) PP1 was used in growth inhibition assays . IC(50) value determination , cell cycle- and apoptosis analyses were performed in T-ALL- , non-T-ALL- and murine transgenic cell lines . RESULTS pTalpha expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts . PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G(1/0) phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2 , respectively . PP1 sensitive cell lines expressed the target protein p56(Lck) and showed a corresponding P-Tyr signal . CONCLUSION Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTalpha mediated proliferation in this leukemic sub-type . In addition , p56(Lck) represents also independently of pTalpha a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Increasing evidence shows that estrogens are involved in lung cancer proliferation and progression , and most human lung tumors express estrogen receptor β ( ERβ ) as well as aromatase . To determine if the aromatase inhibitor anastrozole prevents development of lung tumors induced by a tobacco carcinogen , alone or in combination with the ER antagonist fulvestrant , ovariectomized female mice received treatments with the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone ( NNK ) along with daily supplements of androstenedione , the substrate for aromatase . Placebo , anastrozole and/or fulvestrant were administered in both an initiation and a promotion protocol of lung tumorigenesis . The combination of fulvestrant and anastrozole given during NNK exposure resulted in significantly fewer NNK-induced lung tumors ( mean = 0.5 ) compared with placebo ( mean = 4.6 , P &lt ; 0.001 ) , fulvestrant alone ( mean = 3.4 , P &lt ; 0.001 ) or anastrozole alone ( mean = 2.8 , P = 0.002 ) . A significantly lower Ki67 cell proliferation index was also observed compared with single agent and control treatment groups . Beginning antiestrogen treatment after NNK exposure , when preneoplastic lesions had already formed , also yielded maximum antitumor effects with the combination . Aromatase expression was found mainly in macrophages infiltrating preneoplastic and tumorous areas of the lungs , whereas ERβ was found in both macrophages and tumor cells . Antiestrogens , especially in combination , effectively inhibited tobacco carcinogen-induced murine lung tumorigenesis and may have application for lung cancer prevention . An important source of estrogen synthesis may be inflammatory cells that infiltrate the lungs in response to carcinogens , beginning early in the carcinogenesis process . ERβ expressed by inflammatory and neoplastic epithelial cells in the lung may signal in response to local estrogen production .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Von Hippel-Lindau ( VHL ) is a tumor suppressor that negatively regulates the production of angiogenic factors . Mutations in the VHL gene cause VHL syndrome , which is characterized by highly vascularized tumors . Here we report a c.464T>A mutation of the VHL gene in three patients with hemangioblastoma from a Chinese family . This mutation was not reported previously and was absent in the unaffected family members . The mutation is predicted to cause Val to Glu substitution at VHL protein residue 155 in a conserved region . Previous biochemical studies demonstrated that residue Val-155 was critical for VHL protein binding to chaperonin TRiC/CCT , an essential step for proper VHL protein folding . Our finding of naturally occurring VHL V155E mutation in patients with VHL syndrome supports the functional importance of Val-155 residue in VHL protein and illustrates the diversity of VHL gene defects underlying VHL syndrome .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Autophagy is activated in response to cellular stressors and mediates lysosomal degradation and recycling of cytoplasmic material and organelles as a temporary cell survival mechanism . Defective autophagy is implicated in human pathology , as disruption of protein and organelle homeostasis enables disease-promoting mechanisms such as toxic protein aggregation , oxidative stress , genomic damage , and inflammation . We previously showed that autophagy-defective immortalized mouse mammary epithelial cells are susceptible to metabolic stress , DNA damage , and genomic instability . We now report that autophagy deficiency is associated with endoplasmic reticulum ( ER ) and oxidative stress , and with deregulation of p62-mediated keratin homeostasis in mammary cells , allograft tumors , and mammary tissues from genetically engineered mice . In human breast tumors , high phospho(Ser73)-K8 levels are inversely correlated with Beclin 1 expression . Thus , autophagy preserves cellular fitness by limiting ER and oxidative stress , a function potentially important in autophagy-mediated suppression of mammary tumorigenesis . Furthermore , autophagy regulates keratin homeostasis in the mammary gland via a p62-dependent mechanism . High phospho(Ser73)-K8 expression may be a marker of autophagy functional status in breast tumors and , as such , could have therapeutic implications for breast cancer patients .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The multi-kinase inhibitor dasatinib induced a variable but significant decrease of viability in both p53(wild-type) ( EHEB , JVM-2 , JVM-3 ) and p53(mutated) ( MEC-1 , MEC-2 , BJAB ) prolymphocytic B leukemic cells , due to a combination of cell cycle block in G1 and apoptosis . Antibody phospho-kinase array analysis revealed that dasatinib inhibited the phosphorylation of various kinases , including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors , in both p53(wild-type) and p53(mutated) cells . Therefore , dasatinib might offer a novel therapeutic strategy not only for p53(wild-type) , but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: To investigate whether the Bcl-2 gene family is involved in modulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60 cell line and primary acute myelogenous leukemic cells , the Bcl-2 family member Mcl-1 , Bax and Bak and cell cycle proteins including P27kipl , P21wafl , cyclin D3 and pRbp- were selected and their expression detected by SABC immuno-histochemical stain method . The attitude of sub-G1 peak in DNA histogram was determined by FCM . The TUNEL positive cell percentage was identified by terminal deoxynucleotidyl transferase ( TdT)-mediated Biotin dUNP end labeling technique . It was found that when HL-60 cells were treated with 25 mumol/L curcumin for 24 h , the expression level of Mcl-1 was down-regulated , but that of Bax and Bak up-regulated time-dependently . There was significant difference in the expression level of Mcl-1 , Bax and Bak between the curcumin-treated groups and control group ( P &lt ; 0.05-0.01 ) . At the same time , curcumin had no effect on progress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis , but could increase the peak of Sub-G1 ( P &lt ; 0.05 ) , and down-regulate the expression of Mcl-1 and up-regulate the expression of Bax and Bak with the difference being statistically significant . The expression of P27kipl , P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin . These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process of apoptosis induced by curcumin in HL-60 cells and AML cells . Curcumin can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells . The mechanism appeared to be mediated by perturbing G0/G1 phases checkpoints which associated with up-regulation of P27kipl , P21wafl and pRbp- expression , and down-regulation of cyclin D3 .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE To evaluate the risk factors for sentinel lymph node metastasis and validate the value of the Memorial Sloan-Kettering Cancer Center nomogram for the prediction of sentinel lymph node metastasis in breast cancer patients . METHODS A sentinel lymph node biopsy database containing 1227 consecutive breast cancer patients ( 416 patients with at least one positive sentinel lymph node ) was retrospectively analyzed . The predictive value of the Memorial Sloan-Kettering Cancer Center nomogram was calculated by the trend line and the area under the receiver-operator characteristic curve . Meanwhile , predictors for sentinel lymph node metastasis were also evaluated . RESULTS Tumor size , histological grade , lymphovascular invasion , mulifocality , estrogen receptor and progesterone receptor status were significant independent predictors for sentinel lymph node metastasis ( all P<0.01 ) . The Memorial Sloan-Kettering Cancer Center nomogram presented an area under the receiver-operator characteristic curve value of 0.730 . Patients with predictive value<16% had a frequency of sentinel lymph node metastasis of 0.9% . Those with values larger than 70% had a frequency of 96.2% . CONCLUSIONS The risk factors for sentinel lymph node metastasis in our study were consistent with those in the Memorial Sloan-Kettering Cancer Center nomogram . The Memorial Sloan-Kettering Cancer Center nomogram is a useful tool that could accurately predict the probability of sentinel lymph node metastasis in our breast cancer patients . Axillary surgical staging might be avoided in patients with a predictive value of <16% and axillary lymph node dissection might be done directly in those with a predictive value >70% , while other patients should still accept sentinel lymph node biopsy .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Epirubicin was developed as a semi-synthetic anthracycline derivative to circumvent the cardiotoxic limitations associated with the use of doxorubicin in the clinic . Anthracycline compounds have been demonstrated to form covalent drug-DNA adducts utilising endogenous and exogenous sources of formaldehyde ; however , previous investigations of the formation of epirubicin-DNA adducts provide conflicting evidence for adduct formation . This work provides evidence that epirubicin acts to form drug-DNA adducts at physiologically relevant concentrations and demonstrates that the rate of formation of epirubicin-DNA adducts is slower than that observed for other anthracycline compounds , explaining why they are only detectable under defined experimental conditions . Formation of covalent epirubicin-DNA adducts improves the apoptotic profile of epirubicin and provides opportunities to overcome drug resistance and cardiotoxic limitations .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Acetyl-11-keto-beta-boswellic acid ( AKBA ) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata ( frankincense ) . AKBA has been recently identified as a novel , orally active , non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro . Because natural pentacyclic triterpenes have an antiproliferative effect against different tumor types , we investigated the effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas , common central nervous system tumors . Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2-8 microM . At similar , physiologically achievable concentrations , AKBA rapidly ( within minutes ) and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 ( Erk-1 and Erk-2 ) in meningioma cells stimulated with platelet-derived growth factor BB . High expression level of 5-LO was detected in primary meningioma cells and surgical specimens by immunoblotting analysis , suggesting the possible role of 5-LO in meningioma tumorigenesis . Considering the critical importance of the Erk-1/2 signal transduction pathway not only in meningiomas but in other human neoplasms , the interruption of signaling through this evolutionarily conserved pathway might be one of the mechanisms by which AKBA induces suppression of proliferation and apoptosis of different tumor types .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Many reports have emphasized the role of gastrin as a growth factor for normal gastrointestinal mucosa and gastrointestinal cancers . Recent studies have pointed out that this peptide acts also as a growth factor for the pancreatic cancer cell line AR42J . This effect is mediated by gastrin [ cholecystokinin ( CCK)-B ] receptors . In the present study , we investigated gastrin ( CCK-B ) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6 , comparing it to normal rat pancreas , and we also characterized CCK receptor subtypes in this tumor . The results showed that there is extensive gastrin binding to the DSL-6 pancreatic carcinoma . No evidence of specific gastrin binding to normal pancreas was found . Analysis of the ability of gastrin-17-I to inhibit 125I-gastrin-I binding demonstrated that gastrin bound to a single class of receptors with a Kd of 0.21 +/- 0.04 nM and a binding capacity of 184 +/- 29 fmol/mg protein. 125I-Gastrin-I binding was inhibited by the specific CCK-B receptor antagonist L365,260 approximately 40 times more effectively than by the specific CCK-A receptor antagonist L364,718 . Analysis of the ability of cholecystokinin octapeptide ( CCK-8 ) to inhibit 125I-Bolton-Hunter-CCK-8 binding revealed two CCK binding sites , i.e. , a high affinity site and a low affinity site . The observed binding affinities of CCK-8 were then introduced into the computer analysis of the dose-inhibition curve of the ability of gastrin-17-I to inhibit binding of 125I-Bolton-Hunter-CCK-8 , which was significantly better fit by a three-site model than by a two-site model . The three sites meet the criteria for CCK-B , high affinity CCK-A , and low affinity CCK-A receptors . The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites . This study demonstrated that DSL-6 pancreatic carcinoma expresses three subtypes of CCK receptors . Gastrin ( CCK-B ) receptors , which were not detected in normal rat pancreas , constitute about one third of the total high affinity CCK receptors . We suggest that novel expression of gastrin ( CCK-B ) receptors may be generated by gene mutation or amplification during carcinogenesis and may play an important role in promoting tumor growth .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND &amp ; AIMS GUCY2C is the intestinal receptor for the paracrine hormones guanylin and uroguanylin that converts guanosine-5'-triphosphate to cyclic guanosine monophosphate ( cGMP ) . It functions as a tumor suppressor ; its loss disrupts intestinal homeostasis and promotes tumorigenesis . We investigated the effects of GUCY2C loss on intestinal cell proliferation , metabolism , signaling , and tumorigenesis in mice . METHODS Intestinal cell proliferation and metabolism were examined in Gucy2c(-/-) and colon cancer cells by microscopy , immunoblot , and functional analyses . Microarray analyses compared gene expression profiles of intestine cell from Gucy2c(-/-) and wild-type mice. v akt murine thymoma viral oncogene homolog ( AKT ) regulation and signaling were examined , and the role of AKT in GUCY2C-dependent tumorigenesis was defined in Gucy2c(-/-)Akt1(-/-) mice . RESULTS The size and number of intestinal crypts increased in Gucy2c(-/-) mice ; the associated epithelial cells showed accelerated proliferation , increased glycolysis , and reduced oxidative phosphorylation , which was reversed by oral administration of cGMP . Conversely , activating guanylyl cyclase C in human colon cancer cells delayed cell-cycle progression , decreased DNA synthesis and colony formation , reduced glycolysis , and increased mitochondrial adenosine triphosphate production . AKT signaling pathways were activated in intestines of Gucy2c(-/-) mice , associated with increased AKT phosphorylation . Disruption of AKT activity , pharmacologically or genetically , reduced DNA synthesis , proliferation , and glycolysis , and increased mitochondrial biogenesis . Intestinal tumorigenesis increased after administration of azoxymethane to Gucy2c(-/-) mice , compared with wild-type mice , but was eliminated in Gucy2c(-/-)Akt1(-/-) mice . CONCLUSIONS GUCY2C is a tumor suppressor that controls proliferation and metabolism of intestinal epithelial cells by inactivating AKT signaling . This receptor and its ligands , which are paracrine hormones , might be novel candidates for anticolorectal cancer therapy .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer ( NSCLC ) patients was studied . Furthermore , transferrin receptors 1 ( TfR1 ) and ferritin expression in tumor tissue , tumor stroma , and normal lung tissue were analyzed . Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis . TfR1 and ferritin expression were determined by immuno-histochemical methods . About 50% of patients survived 12 months only . At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin . Iron content of serum ferritin ( ICF ) was below the reference values in 90% of patients . Furthermore , ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR . The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients , respectively . Tumor stroma was TfR1 negative and sporadically ferritin positive . Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit ( Ht ) , and positive correlation with ferritin , erythrocyte sedimentation rate ( ESR ) , alpha-1 globulin , and alpha-2 globulin . Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin . The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed . Therefore , we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload . Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Overexpression of cyclin D1 is believed to endow mammary epithelial cells ( MEC ) with a proliferative advantage by virtue of its contribution to pRB inactivation . Accordingly , abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2 . Here , we report that mouse cyclin D1(KE/KE) MECs ( deficient in cyclin D1 activity ) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo . In addition , immortalized cyclin D1(KE/KE) MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro . However , highlighting its dual role during tumorigenesis , downregulation of autophagy led to an increase in senescence in cyclin D1(KE/KE) MECs . Autophagy upregulation was also confirmed in human mammary epithelial cells ( HMEC ) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and , similar to our murine system , simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response . Collectively , our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium . Cancer Res ; 72(24) ; 6477-89. �2012 AACR .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Senescence limits the proliferative capacity of primary cells in culture . We describe here a genetic screen to identify genes that allow bypass of this checkpoint . Using retroviral cDNA expression libraries , we identify BCL6 as a potent inhibitor of senescence . BCL6 is frequently activated in non-Hodgkin's lymphoma , but its mechanism of action has remained unclear . BCL6 efficiently immortalizes primary mouse embryonic fibroblasts and cooperates with RAS in oncogenic transformation . BCL6 overrides the senescence response downstream of p53 through a process that requires induction of cyclin D1 expression , as cyclin D1 knockout fibroblasts are specifically resistant to BCL6 immortalization . We show that BCL6 expression also dramatically extends the replicative lifespan of primary human B cells in culture and induces cyclin D1 expression , indicating that BCL6 has a similar activity in lymphoid cells . Our results suggest that BCL6 contributes to oncogenesis by rendering cells unresponsive to antiproliferative signals from the p19(ARF)-p53 pathway .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Therapy-induced cellular senescence ( TCS ) , characterized by prolonged cell cycle arrest , is an in vivo response of human cancers to chemotherapy and radiation . Unfortunately , TCS is reversible for a subset of senescent cells , leading to cellular reproliferation and ultimately tumor progression . This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer . We report the findings of a clinicopathological study in patients with locally advanced non-small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome . In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape , we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry . We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS . These polyploid senescent cells represent important transition states through which escape preferentially occurs . The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin-dependent kinase inhibitor family during TCS . Altogether , these studies underscore the importance of TCS in cancer therapeutics .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Recently , the use of gold nanoparticles as potential tumor selective radiosensitizers has been proposed as a breakthrough in radiotherapy . Experiments in living cells and in vivo have demonstrated the efficiency of the metal nanoparticles when combined with low energy x-ray radiations ( below conventional 1 MeV Linac radiation ) . Further studies on DNA have been performed in order to better understand the fundamental processes of sensitization and to further improve the method . In this work , we propose a new strategy based on the combination of platinum nanoparticles with irradiation by fast ions effectively used in hadron therapy . It is observed in particular that nanoparticles enhance strongly lethal damage in DNA , with an efficiency factor close to 2 for double strand breaks . In order to disentangle the effect of the nano-design architecture , a comparison with the effects of dispersed metal atoms at the same concentration has been performed . It is thus shown that the sensitization in nanoparticles is enhanced due to auto-amplified electronic cascades inside the nanoparticles , which reinforces the energy deposition in the close vicinity of the metal . Finally , the combination of fast ion radiation ( hadron therapy ) with platinum nanoparticles should strongly improve cancer therapy protocols .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks ( DSBs ) in genomic DNA in cycling cells . These DSBs are often covalently bound with polypeptides at the 3 ' and 5 ' ends . Such modifications must be eliminated before DSB repair can take place , but it remains elusive which nucleases are involved in this process . Previous studies show that CtIP plays a critical role in the generation of 3 ' single-strand overhang at \" clean \" DSBs , thus initiating homologous recombination ( HR)-dependent DSB repair . To analyze the function of CtIP in detail , we conditionally disrupted the CtIP gene in the chicken DT40 cell line . We found that CtIP is essential for cellular proliferation as well as for the formation of 3 ' single-strand overhang , similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex . We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332 , which is required for interaction with BRCA1 . Although the resulting CtIP(S332A/-/-) cells exhibited accumulation of RPA and Rad51 upon DNA damage , and were proficient in HR , they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP(+/-/-) cells . Finally , CtIP(S332A/-/-)BRCA1(-/-) and CtIP(+/-/-)BRCA1(-/-) showed similar sensitivities to these reagents . Taken together , our data indicate that , in addition to its function in HR , CtIP plays a role in cellular tolerance to topoisomerase inhibitors . We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs , thereby facilitating subsequent DSB repair .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PURPOSE Although the adrenal gland is a common site of extrahepatic metastasis from hepatocellular carcinoma ( HCC ) , there are no definitive guidelines for the treatment of adrenal metastasis . This study examines the effectiveness of various treatments for this disease . METHODS We retrospectively analyzed 20 patients treated for adrenal metastasis of HCC by adrenalectomy ( n = 13 ) , transarterial chemoembolization ( TACE ) , or percutaneous ethanol injection therapy ( PEIT ) ( n = 7 ) . RESULTS There were no significant differences in cumulative survival rates between patients given adrenalectomy and those given TACE or PEIT , either after completing treatment for primary HCC or after the first treatment for adrenal metastasis . Six of seven patients with tumor thrombi in the inferior vena cava ( IVC ) from adrenal metastasis underwent adrenalectomy combined with intracaval thrombectomy , five of whom survived for more than 1 year after surgery , and two of whom are still alive without any recurrence more than 3 years after surgery . PEIT showed good results for small adrenal metastasis . CONCLUSION These findings suggest that therapeutic modalities should be chosen according to the clinical features of each individual , including the size of the metastatic tumor , whether there is invasion into the IVC , the function of the remaining liver , and the existence of intra- and/or nonadrenal extrahepatic lesions . Furthermore , intracaval tumor thrombectomy could be indicated for patients with IVC thrombus if they are suitable candidates for surgery .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: It is still difficult to decide on the treatment modalities for advanced esophageal carcinoma when the prognostic factors of T4 esophageal cancer are not fully understood . In this article , we report that among 71 patients with T4 thoracic esophageal cancer , 49 underwent esophagectomy , 9 had curative resection ( R0 group ) , and 40 had palliative resection ( R1/2 group ) . A total of 22 patients had palliative treatments : bypass in 5 ( bypass group ) , gastrostomy or jejunostomy in 6 ( stoma group ) , and radiochemotherapy alone in 11 ( nonoperation group ) . Clinicopathologic characteristics were retrospectively investigated . Treatment-related deaths occurred in 7 ( 10% ) : none in R0 , 3 ( 8% ) in R1/2 , 3 ( 60% ) in bypass , and 1 ( 17% ) in stoma group . Swallowing was improved in 50 ( 70% ) patients : 9 ( 100% ) in R0 , 30 ( 75% ) in R1/2 , 1 ( 20% ) in bypass , 3 ( 50% ) in stoma , and 7 ( 64% ) in the nonoperation group . One- , two- , and three-year overall survival rates were 56% , 22% , and 22% in the R0 group and 35% , 19% and 6% in the R1/2 group , respectively ( p = 0.19 ) . In the bypass , stoma , and nonoperation groups , none survived 1.6 years . The factors influencing the survival rate of the 49 patients undergoing esophagectomy were grade of lymph node metastasis , amount of perioperative blood transfusion , lymph vessel , and blood vessel invasion . Among these , independent prognostic factors for survival were amount of blood transfusion ( -6 units vs. -7 units , p <0.0001 ) and grade of lymph node metastasis [ none- or peritumoral [ lymph nodes adjacent to the main tumor or at a nearby location ( <3 cm ) from the tumor ] metastasis vs. more distant metastasis [ lymph nodes at a distant location ( &gt ; 3 cm) ] , p = 0.016 ] . Bypass and stoma operation neither prolonged the survival nor improved the difficulty of swallowing compared with radiochemotherapy alone . Esophagectomy can achieve the best improvement of swallowing and the longest survival with an acceptable mortality rate . Esophageal carcinoma patients with T4 disease and distinct metastasis in the lymph nodes at a distant location ( >3 cm ) from the primary tumor may not benefit from an esophageal resection .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Urokinase plasminogen activator receptor ( uPAR ) activates alpha5beta1 integrin and ERK signaling , inducing in vivo proliferation of HEp3 human carcinoma . Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin ( FN ) induced growth pathway . Its activation is ligand-independent and does not require high EGFR , but does require high uPAR expression . Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated . Domain 1 of uPAR is crucial for EGFR activation , and FAK links integrin and EGFR signaling . Inhibition of EGFR kinase blocks uPAR induced signal to ERK , implicating EGFR as an important effector of the pathway . Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo . These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling , providing cancer cells with proliferative advantage .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Silver nanoparticles ( Ag-np ) have been used in medicine and commercially due to their anti-microbial properties . Therapeutic potentials of these nanoparticles are being explored extensively despite the lack of information on their mechanism of action at molecular and cellular level . Here , we have investigated the DNA damage response and repair following Ag-np treatment in mammalian cells . Studies have shown that Ag-np exerts genotoxicity through double-strand breaks ( DSBs ) . DNA-PKcs , the catalytic subunit of DNA dependent protein kinase , is an important caretaker of the genome which is known to be the main player mediating Non-homologous End-Joining ( NHEJ ) repair pathway . We hypothesize that DNA-PKcs is responsible for the repair of Ag-np induced DNA damage . In vitro studies have been carried out to investigate both cytotoxicity and genotoxicity induced by Ag-np in normal human cells , DNA-PKcs proficient , and deficient mammalian cells . Chemical inhibition of DNA-PKcs activity with NU7026 , an ATP-competitive inhibitor of DNA-PKcs , has been performed to further validate the role of DNA-PKcs in this model . Our results suggest that Ag-np induced more prominent dose-dependent decrease in cell viability in DNA-PKcs deficient or inhibited cells . The deficiency or inhibition of DNA-PKcs renders the cells with higher susceptibility to DNA damage and genome instability which in turn contributed to greater cell cycle arrest/cell death . These findings support the fact that DNA-PKcs is involved in the repair of Ag-np induced genotoxicity and NHEJ repair pathway and DNA-PKcs particularly is activated to safeguard the genome upon Ag-np exposure .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Exposure to benzo[a]pyrene ( BaP ) can induce inflammatory skin diseases and skin cancer , which are both associated to oxidative stress . BaP is known to bind with high specificity to the aryl hydrocarbon receptor ( AhR ) , modifying the expression of CYP1A1 , involved both in cancer and inflammation . While the current knowledge is based on murine skin and cell culture data , in this study human healthy skin has been treated with 5muM BaP in conditions simulating occupational and environmental exposure . AhR and CYP1A1 expression was evaluated by Western blotting , which revealed their presence even in control untreated skin ; both enzyme and receptor increased more than twofold after exposure to BaP . AhR expression level was lower than CYP1A1 in basal conditions and following induction . Oxidative stress was evaluated in terms of MTT reduction , protein peroxidation and reactive oxygen species ( ROS ) formation . A significant increase in ROS and carbonyl compound production , as well as reduced tissue viability have been determined by BaP . The results of this experiment indicate that BaP , an AhR agonist , can significantly increase receptor and CYP1A1 expression and induce oxidative stress in human skin , confirming the involvement of this pathway in the pathogenesis of tissue damage due to polycyclic aromatic hydrocarbons .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Jaceosidin , a flavonoid derived from Artemisia princeps ( Japanese mugwort ) , has been shown to inhibit the growth of several human cancer cells , However , the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood . In this study , we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells . We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells . In contrast , jaceosidin-induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin . Jaceosidin induced G2/M phase cell cycle arrest and modulated the levels of cyclin B and p-Cdc2 in Hec1A cells . Knockdown of p21 using specific siRNAs partially abrogated jaceosidin-induced cell growth inhibition . Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM-Chk1/2 . Ku55933 , an ATM inhibitor , reversed jaceosidin-induced cell growth inhibition , in part . Moreover , jaceosidin treatment resulted in phosphorylation of ERK , and pretreatment with the ERK inhibitor , PD98059 , attenuated cell growth inhibition by jaceosidin . These data suggest that jaceosidin , isolated from Japanese mugwort , modulates the ERK/ATM/Chk1/2 pathway , leading to inactivation of the Cdc2-cyclin B1 complex , followed by G2/M cell cycle arrest in endometrial cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The neurofibromatosis type 2 ( NF2 ) tumor suppressor gene encodes merlin , a membrane/cytoskeleton protein necessary for the maintenance of contact inhibition of growth in cells . Bi-allelic inactivation of NF2 is known to cause multiple cancers in both humans and mice . However , the mechanism through which merlin exerts its tumor-suppressive function remains obscure . In this report , we show that NF2 knockout mouse embryonic fibroblasts lost contact inhibition of cell proliferation and contained significantly increased canonical Wnt signaling . Inhibition of Rac1 , the activity of which is inversely regulated by NF2 , through the use of a dominant-negative mutant , small hairpin RNA or a small molecule inhibitor in NF2-deficient cells , was able to suppress elevated Wnt signals as shown by reduced activity of the T-cell factor 4 ( TCF4 ) transcription factor . Dominant-negative TCF4 or Rac1 mutant , as well as a small molecule inhibition of Wnt , were able to curb NF2 deficiency-elicited cell proliferation at the confluent state . Thus , Rac1-mediated canonical Wnt signaling is essential for the loss of contact inhibition in NF2-deficient cells .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Nonmelanoma skin cancer ( NMSC ) is by far the most frequent type of cancer in humans . NMSC includes several types of malignancies with different clinical outcomes , the most frequent being basal and squamous cell carcinomas . We have used the Sleeping Beauty transposon/transposase system to identify somatic mutations associated with NMSC . Transgenic mice bearing multiple copies of a mutagenic Sleeping Beauty transposon T2Onc2 and expressing the SB11 transposase under the transcriptional control of regulatory elements from the keratin K5 promoter were treated with TPA , either in wild-type or Ha-ras mutated backgrounds . After several weeks of treatment , mice with transposition developed more malignant tumors with decreased latency compared with control mice . Transposon/transposase animals also developed basal cell carcinomas . Genetic analysis of the transposon integration sites in the tumors identified several genes recurrently mutated in different tumor samples , which may represent novel candidate cancer genes . We observed alterations in the expression levels of some of these genes in human tumors . Our results show that inactivating mutations in Notch1 and Nsd1 , among others , may have an important role in skin carcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Olfactomedin 4 ( OLFM4 ) is highly expressed in gastrointestinal cancers and has an anti-apoptotic function . The roles of OLFM4 in tumor growth and metastasis and how it functions in these processes remain elusive . We investigated the function of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an experimental system . Our results showed that OLFM4 had no positive effect on cell viability or cell cycle progression in B16F10 cells . However , it significantly suppressed the tumorigenicity of B16F10 cells , i.e. , intradermal primary tumor growth and lung metastasis . OLFM4 also suppressed the migration and invasion of B16F10 cells in vitro . For further insight into the mechanisms underlying OLFM4-mediated suppression of tumor progression , we examined the effect of OLFM4 on the expression of integrin and matrix metalloproteinase ( MMP ) , both of which are involved in tumor progression . Overexpression of OLFM4 clearly reduced the expression levels of integrin α1 , integrin α4 , integrin α5 , integrin α6 , and MMP9 . Moreover , forced expression of MMP9 attenuated the inhibitory activity of OLFM4 on migration and invasiveness . Our findings provide the experimental evidence that OLFM4 may function as a tumor suppressor and an anti-metastatic gene during tumor progression .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Chromosomal instability and the subsequent genetic mutations are considered to be critical factors in the development of the majority of solid tumors , but the mechanisms by which a stable diploid cell loses the ability to maintain genomic integrity are not well characterized . We have approached this critical issue through the use of high-throughput screens in untransformed diploid epithelial cells . In a screen of a cDNA library , we identified 13 kinases whose overexpression leads to increased ploidy . In a series of shRNA screens , we identified 16 kinases whose loss leads to increased ploidy . In both cDNA and shRNA screens , the majority of hits have not been linked previously to genomic stability . We further show that sustained loss of the shRNA screening hits leads to multipolar spindles and heterogeneous chromosome content , two characteristics of chromosomal instability . Loss of several of the kinases leads to loss of contact inhibition and to anchorage-independent growth , vital traits acquired during tumor development . We anticipate that this work will serve as a template for the comprehensive identification of pathways whose dysregulation can drive tumorigenesis through impaired karyotypic maintenance .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Although the p16(INK4a) and p21Waf1/Cip1 cyclin-dependent kinase ( CDK ) inhibitors are known to play key roles in cellular senescence in vitro , their roles in senescence remain rather poorly understood in vivo . This situation is partly due to the possibility of compensatory effect(s) between p16INK4a and p21Waf1/Cip1 or to the upregulation of functionally related CDK inhibitors . To directly address the cooperative roles of p16INK4a and p21Waf1/Cip1 in senescence in vivo , we generated a mouse line simply lacking both p16INK4a and p21Waf1/Cip1 genes [ double-knockout ( DKO) ] . Mouse embryonic fibroblasts ( MEF ) derived from DKO mice displayed no evidence of cellular senescence when cultured serially in vitro . Moreover , DKO MEFs readily escaped Ras-induced senescence and overrode contact inhibition in culture . This was not the case in MEFs lacking either p16INK4a or p21Waf1/Cip1 , indicating that p16(INK4a) and p21Waf1/Cip1 play cooperative roles in cellular senescence and contact inhibition in vitro . Notably , we found the DKO mice to be extremely susceptible to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis that involves oncogenic mutation of the H-ras gene . Mechanistic investigations suggested that the high incidence of cancer in DKO mice likely reflected a cooperative effect of increased benign skin tumor formation caused by p21Waf1/Cip1 loss , with increased malignant conversion of benign skin tumors caused by p16(INK4a) loss . Our findings establish an intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines , A2780 and CP70 , induced by a novel curcumin analogue , B19 . The proliferation of cells was detected with methyl thiazolyl tetrazolium ( MTT ) assay and apoptosis was examined by flow cytometry . Reactive oxygen species ( ROS ) were assessed by the fluorescent indicator DCF-DA . The protein expression of the endoplasmic reticulum ( ER ) stress pathways , GRP78 , XBP-1 , ATF-4 and CHOP , was examined with Western blotting . A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin . At 20 �M , B19 induced significant apoptosis in CP70 cells . Furthermore , B19 induced the ER stress response , while curcumin had no effect on ER stress . These results suggest that B19 has more effective antitumor properties than curcumin , and is associated with the activation of ER stress and ROS in ovarian cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Inflammatory events have been associated with senile plaques , one of the pathological hallmarks of Alzheimer's disease ( AD ) . It is believed that aggregated beta-amyloid ( betaA ) proteins , which form the core of these plaques , may be responsible for triggering the inflammatory reaction . In the present study , the ability of aluminum ( Al ) to initiate similar inflammatory events was investigated in a human glioblastoma cell line . A 6-day exposure to either lipopolysaccharide ( LPS ) or aluminum sulfate caused a significant increase in the rate of proliferation of the glioblastoma cells . Both treatments also caused activation of the immune-responsive transcription factor NF-kappaB although there were time-related differences . The levels of secreted cytokines , interleukin-6 ( IL-6 ) and tumor necrosis factor alpha ( TNF-alpha ) were both increased by the LPS treatment although exposure to Al decreased the secretion of the former while elevating the levels of the latter . These events may be due to the activation of glial cells and subsequent stress response to either Al complexes or LPS . Although exposure to either stress factor caused a stimulation of inflammatory markers , there were time-dependent differences in the response . This may reflect the ability of the cells to discern different stress factors and thus orchestrate an innate immune response profile distinct to each immunogen .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Annexin II is secreted into the extracellular environment , where , via interactions with specific proteases and extracellular matrix proteins , it participates in plasminogen activation , cell adhesion , and tumor metastasis and invasion . However , mechanisms regulating annexin II transport across the cellular membrane are unknown . In this study , we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 ( IGF-1 ) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin ( NIH-3T3(IR) ) or IGF-1 receptor ( NIH-3T3(IGF-1R) ) . Stimulation of insulin and IGF-1 receptors by insulin caused a temporary dissociation of annexin II from these receptors , which was accompanied by an increased amount of extracellular annexin II detected in the media of PC12 , NIH-3T3(IR) , and NIH-3T3(IGF-1R) cells but not in that of untransfected NIH-3T3 cells . Activation of a different growth factor receptor , the platelet-derived growth factor receptor , did not produce such results . Tyrphostin AG1024 , a tyrosine kinase inhibitor of insulin and IGF-1 receptor , was shown to inhibit annexin II secretion along with reduced receptor phosphorylation . Inhibitors of a few downstream signaling enzymes including phosphatidylinositol 3-kinase , pp60c-Src , and protein kinase C had no effect on insulin-induced annexin II secretion , suggesting a possible direct link between receptor activation and annexin II secretion . Immunocytochemistry revealed that insulin also induced transport of the membrane-bound form of annexin II to the outside layer of the cell membrane and appeared to promote cell aggregation . These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The involvement of signal transduction systems in the initial attachment of two murine B16 melanoma clones of differing metastatic potential to extracellular matrix components was examined to learn more of the early events in cell-matrix interaction . Clones of high and low metastatic capacity attached similarly in the absence of any stimulators , exhibiting a two phase time course of attachment with 100% attachment by 60 min . A slight difference in attachment characteristics between the clones was seen in response to phorbol ester stimulation , which significantly inhibited attachment of the low metastatic clone but which had no effect on the highly metastatic clone . Total protein kinase C activity and distribution was similar for both clones . Attachment of both clones was severely reduced , however , if intracellular calcium was elevated or intracellular calmodulin inhibited . This study suggests that signal transduction mechanisms are involved in melanoma cell attachment to matrix proteins and offers an approach to pharmacological manipulation of these cell-matrix interactions which may be relevant to reducing metastatic spread .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Most hepatocellular carcinomas ( HCC ) develop in the context of severe liver fibrosis and cirrhosis caused by chronic liver inflammation , which also results in accumulation of reactive oxygen species ( ROS ) . In this study , we examined whether the stress-activated protein kinase p38α ( Mapk14 ) controls ROS metabolism and development of fibrosis and cancer in mice given thioacetamide to induce chronic liver injury . Liver-specific p38α ablation was found to enhance ROS accumulation , which appears to be exerted through the reduced expression of antioxidant protein HSP25 ( Hspb1 ) , a mouse homolog of HSP27 . Its reexpression in p38α-deficient liver prevents ROS accumulation and thioacetamide-induced fibrosis. p38α deficiency increased expression of SOX2 , a marker for cancer stem cells and the liver oncoproteins c-Jun ( Jun ) and Gankyrin ( Psmd10 ) and led to enhanced thioacetamide-induced hepatocarcinogenesis . The upregulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole . Intriguingly , the risk of human HCC recurrence is positively correlated with ROS accumulation in liver . Thus , p38α and its target HSP25/HSP27 appear to play a conserved and critical hepatoprotective function by curtailing ROS accumulation in liver parenchymal cells engaged in oxidative metabolism of exogenous chemicals . Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Paragangliomas are relatively uncommon neoplasms that arise in adrenal and extra-adrenal paraganglia of the autonomic nervous system . Parasympathetic paraganglioma develop predominantly in the head and neck . It is exceedingly uncommon to develop a primary intraparathyroid paraganglioma . There is only a single case report in the English literature . The information from the single previous case report ( Medline 1960-2009 ) was combined with this case report . Our patient was a 69 year old woman who presented with a thyroid gland mass , with extension into the substernal space . The patient had a history of renal cell carcinoma removed 18 months before . At surgery , a thyroid lobectomy and a parathyroidectomy were performed . The parathyroid tissue showed a very well defined zellballen arrangement of paraganglion cells within the parenchyma of the parathyroid gland . The cells had ample basophilic , granular cytoplasm . The nuclei were generally round to oval with ' salt-and-pepper ' nuclear chromatin distribution . There was a richly vascularized stroma . Mitotic figures , necrosis , invasive growth , and profound nuclear pleomorphism were absent . The neoplastic cells were strongly and diffusely immunoreactive with chromogranin , synaptophysin , CD56 , and focally with cyclin-D1 . The paraganglioma showed a delicate S-100 protein positive supporting sustentacular framework . Keratin , CD10 , PTH , calcitonin and RCC markers were negative . The patient showed no stigmata of Multiple Endocrine Neoplasia ( MEN ) and has no paraganglioma in any other anatomic site . She is alive without any additional findings 12 months after surgery . Isolated paraganglioma within the parathyroid is rare , and should be separated from parathyroid adenoma , hyperplasia or metastatic disease to assure appropriate management .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE To study the clinicopathologic features , immunophenotype and ultrastructural features of sinonasal inflammatory myofibroblastic tumors ( IMT ) . METHODS The clinical and histologic features of 5 cases of sinonasal IMT were reviewed . Immunohistochemical study for vimentin , MSA , SMA , calponin , h-caldesmon , desmin , ALK , fibronectin , CK , S-100 and Ki-67 was carried out . Ultrastructural examination was also performed in two of the cases . RESULTS The patients age ranged from 28 to 62 years ( mean = 43 years ) . The male-to-female ratio was 2:3 . The clinical presentation included nasal obstruction , nasal discharge , nasal bleeding , facial pain , facial swelling , toothache and tear overflow . All of the 5 patients suffered from disease relapses ; and 4 of them had recurrences for more than 5 times . One patient had lymph node metastasis and 3 patients died of the disease . Histologically , the tumor cells were arranged in interlacing fascicles and sometimes haphazard in fashion . They were spindly in shape , cytoplasm eosinophilic with mild nuclear atypia and a low mitotic activity . The intervening stroma was myxoid in appearance accompanied by lymphocyte and plasma cell infiltration , abundant blood vessels and focal collagenized areas . In 3 of the recurrent cases , the tumor cells displayed increased nuclear atypia and mitotic activity ( average about 5 to 6 per 10 high-power fields ) , accompanied by patchy necrosis , less inflammatory cell infiltration and focal sarcomatous changes . Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin . SMA , MSA , calponin and fibronectin were variably expressed . Desmin was weakly positive in 1 case . The staining for h-caldesmon , ALK , S-100 and CK was negative . The Ki-67 proliferation index increased with tumor recurrences . Electron microscopy revealed abundant rough endoplasmic reticulum and dense body formation in the cytoplasm . There were an increased amount of collagen fibers in the stroma . CONCLUSIONS IMT rarely occurs in nasal cavity and paranasal sinuses . The tumor is prone to local invasion and recurrences , with subsequent progression to frank malignancy and distant metastasis , resulting in high mortality and poor prognosis . Complete surgical resection remains the main modality of treatment .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;resisting cell death;tumor promoting inflammation;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The aim of this study was to determine whether isorhamnetin , an immediate 3'-O-methylated metabolite of quercetin , affects proliferation , cell death , and the cell cycle of human colon carcinoma ( HCT-116 ) cells . Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner , with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay . Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis . Isorhamnetin also increased the number of cells in G2/M phase . Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase . These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells , leading to apoptotic and necrotic death . These antiproliferative , apoptotic , necrotic , and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities . To our knowledge , this is the first report of the effect of isorhamnetin on human colon cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Candida albicans infections are very frequent in cancer patients , whose immune system is often compromised , but whether this fungal pathogen affects cancer progression is unknown . C. albicans infection involves endogenous production of inflammatory cytokines such as tumour necrosis factor alpha ( TNF-alpha ) and interleukin-18 ( IL-18 ) . Increased levels of these cytokines have already been correlated with metastasis of most common cancer types . In this study , a well-established model of IL-18-dependent hepatic melanoma metastasis was used to study whether C. albicans can alter the ability of murine B16 melanoma ( B16M ) cells to colonize the liver . First , we determined the ability of intrasplenically ( IS ) injected B16M cells to metastasize into the liver of mice challenged with 5 x 10(4) C. albicans cells by three different routes ( intravenous , IV ; intrasplenic , IS ; or intraperitoneal , IP ) 12 h prior to injection of B16M cells . We demonstrated that C. albicans significantly increased metastasis of B16M cells with all three fungal injection routes . Pro-metastatic effects occurred when hepatic colonization with B16M cells place after the peak of TNF-alpha and IL-18 levels had been reached in the hepatic blood of fungal challenged mice . In a second set of experiments , mice were fungal challenged 4 days after injection of B16M cells . In these mice , C. albicans also potentiated the growth of established micro-metastases . Significantly , the fungal challenge had pro-metastatic effects without the C. albicans being able to reach the liver , suggesting that soluble factors can promote metastasis in remote sites . Mouse treatment with antifungal ketoconazol abrogated hepatic TNF-alpha stimulation by C. albicans and prevented the enhancement of hepatic metastasis in fungal challenged-mice . Therefore , the pro-inflammatory microenvironment generated by the host's systemic response to C. albicans stimulates circulating cancer cells to metastasize in the liver .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Aberrant expression of mucins is likely associated with cancer biology as alterations in the expression and/or glycosylation patterns of various mucins have been noted . Expression of the mucin family in gastric cancers has been reported in numerous studies , but the results are conflicting . Therefore , we investigated the potential use of mucin ( MUC)1 and 4 as prognostic markers in gastric cancer according to histological subtype . Three-hundred and sixty-five gastric adenocarcinoma patients who underwent surgical resection were selected for this study . Among the 365 gastric cancer samples tested here , 34% consisted of early gastric cancer and 66% were advanced . In terms of location , 68.7% of the cohort had intestinal-type cancer and 30.7% had diffuse-type . We constructed tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using monoclonal antibodies . Two-hundred and ninety-two patients ( 92.7% ) were positive for MUC1 and 216 ( 60.5% ) were positive for MUC4 . MUC1 expression was not correlated with any other clinicopathological variables such as age , gender , depth of invasion , lymph node metastasis , Lauren classification or recurrence . However , loss of MUC4 expression was significantly correlated with recurrence ( p=0.033 ) . MUC4 expression was also significantly correlated with better disease-free survival ( p=0.049 ) and particularly in the intestinal-type ( p=0.018 ) . Our present findings demonstrated that loss of MUC4 expression can be used as a prognostic marker in gastric cancer . Loss of MUC4 expression is a prognostic indicator of increased recurrence and poor disease-free survival in patients with gastric cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Bilateral spontaneous pneumothorax is a rare occurrence in patients with both primary and metastatic lung cancer . Pneumothorax occurring as a complication of vascular endothelial growth factor receptor ( VEGFR ) inhibitor therapy has not been previously described in the medical literature . Sunitinib malate is a VEGFR inhibitor approved for the treatment of advanced renal cell carcinoma . We present a patient with metastatic renal cell carcinoma manifested as bilateral pulmonary nodules who developed a bilateral spontaneous pneumothorax 3 weeks after initiation of sunitinib therapy . We believe that sunitinib therapy resulted in necrosis of multiple pleural-based pulmonary nodules with central cavernization and ultimately rupture with bronchopleural fistula formation . Based on this experience , we advise that practitioners exercise caution when prescribing anti-VEGFR therapy in patients with pleural-based pulmonary metastases and recognize that the efficacy and toxicity of these agents may be closely linked .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Human diploid fibroblasts have a limited life span in vitro , and spontaneous immortalization is an extremely rare event . We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization . Comparison of a preimmortal transformant ( SVtsA/HF-A ) with its uncloned and cloned immortalized derivatives ( AR5 and HAL ) has failed to reveal any major alteration involving the simian virus 40 genome . Karyotypic analysis , however , demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21 . The karyotypic analysis was corroborated by DNA analyses . Southern analysis demonstrated that only one copy of three proto-oncogene loci ( ros1 , c-myb , and mas1 ) on 6q was retained in immortal cells . Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 ( D6S87 ) showed loss of heterozygosity . In addition , elevated expression of c-myb ( 6q22-23 ) was observed . We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization , consistent with the presence of a growth suppressor gene .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: A glycolytic profile unifies a group of pheochromocytomas and paragangliomas ( PHEOs/PGLs ) with distinct underlying gene defects , including von Hippel-Lindau ( VHL ) and succinate dehydrogenase B ( SDHB ) mutations . Nevertheless , their tumor aggressiveness is distinct : PHEOs/PGLs metastasize rarely in VHL- , but frequently in SDHB-patients . To date , the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown . Recently , however , an excellent model to study aggressive PHEOs ( mouse tumor tissue ( MTT ) cells ) has been developed from mouse PHEO cells ( MPC ) . We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness , which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs . The increase of glucose transporter 1 in VHL , and of hexokinase 2 in VHL and SDHB , confirmed their glycolytic profile . In agreement with the cell model and in support of decoupling of glycolysis , the Krebs cycle and oxidative phosphorylation ( OXPHOS ) , SDHB tumors showed increased lactate dehydrogenase levels . In SDHB-PGLs OXPHOS complex activity was increased at complex III and , as expected , decreased at complex II . Moreover , protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors . Although there was no direct evidence for increased reactive oxygen species production , elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs . For the first time , we show that despite dysfunction in complex II and evidence for a glycolytic phenotype , the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS . In addition , we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs , proteins that have been proposed as promising therapeutic targets in other cancers . This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs , which may lead to identifying new diagnostic and prognostic markers in the near future .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Proliferator-activated receptor gamma ( PPARgamma ) is a nuclear receptor , which mainly associates with adipogenesis , but also appears to facilitate cell differentiation or apoptosis in certain malignant cells . This apoptosis induction by PPARgamma is increased by co-stimulation with tumor necrosis factor ( TNF)-alpha-related apoptosis-inducing ligand ( TRAIL ) , a member of the TNF family . In this study , we investigated the effect of PPARgamma on Fas-mediated apoptosis in hepatocellular carcinoma ( HCC ) cell lines . PPARgamma was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-Delta-12,14-prostaglandin J2 ( 15d- PGJ2 ) , a PPARgamma ligand , inhibited cellular proliferation in HepG2 , SK-Hep1 or HLE cells , unlike pioglitazone , another PPARgamma ligand , which did not have a significant influence on proliferation of these cells . However , 15d-PGJ2 facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone . These results suggest that PPARgamma can augment TNF-family-induced apoptosis .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The effects of tea polyphenols and tea pigments on cell cycle of hepatic cancer cells were studied . HepG2 cells were incubated with 50 and 100 mg/L tea polyphenols and tea pigments for 48 h respectively . Flow cytometry , Western blot and RT-PCR analysis were used . Flow cytometry analysis showed that tea polyphenols and tea pigments induced G1 arrest . Western blot analysis showed tea polyphenols and tea pigments significantly inhibited the expression of cyclin D1 protein and induced higher expression of P21WAFI/CIPI protein . The result of RT-PCR analysis demonstrated that Cdk4 was significantly inhibited by tea polyphenols and tea pigments . It is concluded that the induction of cell cycle arrest may be an important mechanism of tea on cancer prevention .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Methyleugenol ( MEG ) , a constituent of plants used in the human diet , is hepatocarcinogenic in rodents . In an experiment to elucidate its mode of action in rat liver , male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase , after which half the rats were fed 500 ppm phenobarbital ( PB ) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks . At 8 and 16 week interim terminations , ( 32)P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups . The hepatocellular replicating fractions , measured by proliferating cell nuclear antigen immunohistochemistry , were doubled or more in all MEG groups . Hepatocellular altered foci , detected by glutathione S-transferase-placental type ( π ) immunohistochemistry , were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks . At the end of maintenance/promotion phase , the incidences , multiplicity and size of foci was similar between control and low dose groups , while those of mid and high dose groups were increased . Hepatocellular adenomas occurred in the mid and high dose groups , attaining higher multiplicity and size with PB . Thus , MEG had rapid initiating activity , reflecting the formation of DNA adducts and possibly cell proliferation .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: In response to DNA double strand breaks , the histone variant H2AX at the break site is phosphorylated at serine 139 by DNA damage sensor kinases such as ataxia telangiectasia-mutated , forming gamma-H2AX . This phosphorylation event is critical for sustained recruitment of other proteins to repair the break . After repair , restoration of the cell to a prestress state is associated with gamma-H2AX dephosphorylation and dissolution of gamma-H2AX-associated damage foci . The phosphatases PP2A and PP4 have previously been shown to dephosphorylate gamma-H2AX . Here , we demonstrate that the wild-type p53-induced phosphatase 1 ( WIP1 ) also dephosphorylates gamma-H2AX at serine 139 in vitro and in vivo . Overexpression of WIP1 reduces formation of gamma-H2AX foci in response to ionizing and ultraviolet radiation and blocks recruitment of MDC1 ( mediator of DNA damage checkpoint 1 ) and 53BP1 ( p53 binding protein 1 ) to DNA damage foci . Finally , these inhibitory effects of WIP1 on gamma-H2AX are accompanied by WIP1 suppression of DNA double strand break repair . Thus , WIP1 has a homeostatic role in reversing the effects of ataxia telangiectasia-mutated phosphorylation of H2AX .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: DNA single-strand breaks and associated growth inhibition induced by the thymidylate synthase inhibitor N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazoline-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid ( ICI D1694 ) were quantitated using the human ileocecal adenocarcinoma cell line , HCT-8 . The effects of different concentrations and schedules of [ 6R,S]-5-formyltetrahydrofolate ( [ 6RS]LV ) and 2'-deoxy-thymidine ( dThd ) on drug growth inhibition and DNA damage were also evaluated . The drug concentrations for 50% inhibition of cell growth in culture following 2-h and 72-h exposures were 0.073 and 0.003 microM , respectively . After a 2-h drug exposure , the occurrence of DNA single-strand breaks ( SSBs ) was time dependent . It was detectable at 8 h and reached a maximum at about 24 h , 34 +/- 3 ( SD ) and 305 +/- 34 rad equivalents with 0.1 microM ( 50% inhibition concentration ) and 1.0 microM ( 90% inhibition concentration ) ICI D1694 , respectively . A significant level of DNA SSBs ( 101 +/- 13 rad equivalents ) was still detectable at 72 h after the 2-h treatment with 1 microM ICI D1694 . No significant level of DNA SSBs was detected when cells were exposed simultaneously to ICI D1694 and 20 microM [ 6RS]LV . Complete rescue of drug-induced DNA SSBs could be achieved when cells were exposed to 10 microM dThd starting no later than 4 h after drug treatment . The growth inhibition of ICI D1694 was abrogated by [ 6RS]LV in a concentration-dependent manner . Complete protection was achieved when cells were exposed simultaneously to 1 microM ICI D1694 and 5 microMs [ 6RS]LV or to 3 microMs dThd immediately after drug treatment . The results demonstrate that : ( a ) the growth inhibition of ICI D1694 is a function of time and schedule ; ( b ) the growth inhibition is accompanied by extensive DNA single-strand breaks and slow repair ; ( c ) at 1 microM ICI D1694 , 3 microMs dThd and 5 microMs [ 6RS]LV can completely rescue cells from drug effects when dThd is added up to 4 h following drug treatment or when [ 6RS]LV is given in combination with the drug ; ( d ) interference of [ 6RS]LV with ICI D1694 action may be occurring at the level of drug uptake and at intracellular targets , while dThd interferes with the drug action at intracellular targets .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: In the course of a medicinal chemistry program aimed at discovering novel tumour-active rebeccamycin derivatives targeting DNA and/or topoisomerase I , a series of analogues with the sugar residue linked to the two indole nitrogens was recently developed . Two promising drug candidates in this staurosporine-rebeccamycin hybrid series were selected for a DNA-binding study reported here . The DNA interaction of the cationic indolocarbazole glycosides MP059 bearing a N,N-diethylaminoethyl side chain and MP072 containing a sugar bearing an amino group was compared with that of the uncharged analogue MP024 . The results show that the addition of a cationic substituent , either directly on the indolocarbazole chromophore or on the carbohydrate residue , significantly reinforces the interaction of the drugs with nucleic acids . The two cationic molecules MP059 and MP072 recognise preferentially sequences containing GpT.ApC and TpG.CpA steps but they do not inhibit topoisomerase I , in contrast to the parent uncharged derivative MP024 which stimulates DNA single strand breaks by topoisomerase I. The cytotoxic activity of the indolocarbazole derivatives bearing positively charged groups is one order of magnitude higher than that of the neutral compound MP024 . The high cytotoxic potential can be attributed to the enhanced DNA binding and sequence recognition capacity of the cationic compounds . The study provides useful information for further structure-activity relationship studies in the indolocarbazole series .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Peritoneal transport status is important not only for prescription , but also as a prognostic index . Flt-1 and Flk-1 , the major vascular endothelial growth factor receptors involved in angiogenesis and hyperpermeability , may play a potent role in determining peritoneal transport characteristics . However , the relationship between them has not been studied to date . We hypothesized that Flt-1 and Flk-1 expression in the peritoneal vasculature of uremic patients could be closely related to baseline peritoneal transport status . METHODS Thirty-six new patients without a previous history of peritonitis were enrolled . Clinical parameters such as age , sex , height , weight , causes of renal failure , and residual renal function were assessed . Parietal peritoneal biopsies were obtained during implantation of peritoneal dialytic catheters . Flt-1 and Flk-1 were semi-quantitatively evaluated by immunohistochemical staining . Peritoneal microvascular density ( MVD ) was counted . Within 6 weeks after commencing peritoneal dialysis , a standard peritoneal equilibration test was performed , and the dialysate-to-plasma concentration ratio for creatinine at 4 h ( D4/P Cr ) was determined . The patients were divided into two groups based on the D4/P Cr : more than 0.65 ( Group H , n = 22 ) and less than or equal to 0.65 ( Group L , n = 14 ) . The 24-h peritoneal protein excretion ( PPE ) was assayed . Flt-1 and Flk-1 were correlated with peritoneal MVD , D4/P Cr , and PPE . RESULTS Flt-1 and Flk-1 were detected in the peritoneal vasculature of uremic patients . Flt-1 expression was similar between the two groups , but Flk-1 expression in Group H was significantly higher than that in Group L ( p = 0.001 ) . Flt-1 expression did not show significant correlations with peritoneal MVD , D4/P Cr , and PPE . However , Flk-1 expression showed significant correlations with the above three parameters ( p &lt ; 0.001 for all ) . CONCLUSIONS For the first time , the expressions of Flt-1 and Flk-1 in peritoneal vasculature of uremic patients were detected . Flk-1 expression in peritoneal vasculature of uremic patients is closely correlated with the number of peritoneal microvessels , peritoneal small solute transport rate , and PPE . Our findings strongly suggest that Flk-1 may be a crucial determinant of baseline peritoneal transport characteristics . Further interventional studies are needed .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The triterpenoid fraction ( 100 and 200 mg/kg ) of the fruit bodies of Ganoderma lucidum inhibited primary solid-tumor growth in the spleen , liver metastasis and secondary metastatic tumor growth in the liver in intrasplenic Lewis lung carcinoma ( LLC)-implanted mice . In addition , the triterpenoid fraction ( 800 micrograms/mL ) inhibited angiogenesis induced by Matrigel ( a soluble basement membrane extract of the Engelbreth-Holm-Swam ( EHS ) tumor ) supplemented with vascular endothelial growth factor ( VEGF ) and heparin in an in vivo model . This suggested that the antitumor and antimetastatic activities of the triterpenoid fraction of G. lucidum might be due to the inhibition of tumor-induced angiogenesis . Next , we attempted to isolate the active substance(s) using the in vivo assay system of Matrigel-induced angiogenesis . The acidic fraction of the triterpenoid fraction inhibited the Matrigel-induced angiogenesis . Compound I was isolated from the acidic fraction as an active substance that inhibited the Martigel-induced angiogenesis . Compound I was identified as ganoderic acid F based on the data of IR , 1H- and 13C-NMR and MS analyses .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Novel photosensitizers Hypocrellin A ( HA ) and Hypocrellin B ( HB ) , lipid soluble perylquinone derivatives of the genus Hypericum have a strong photodynamic effect on tumors and viruses . However , the mechanisms of tumor cell death induced by HA and HB are still unclear . In this study , we attempt to elucidate the photodynamic effects of HA and HB compounds in poorly differentiated ( CNE2 ) and moderately differentiated ( TW0-1 ) human nasopharyngeal carcinoma ( NPC ) cells as well as human mucosal colon ( CCL-220.1 ) and bladder ( SD ) cells . Using these cell lines we investigated few hall marks of apoptotic commitments in a drug and light dose dependent manner . Tumor cells photoactivated with HA and HB showed cell size shrinkage and an increase in the sub-diploid DNA content . A loss of membrane phospholipid asymmetry associated with apoptosis was induced by all tumor cell lines as evidenced by the externalization of phosphatidylserine . Western blot analysis of poly ( ADP-ribose ) polymerase , a caspases substrate , showed the classical cleavage pattern ( 116 to 85kDa ) associated with apoptosis in HA and HB-treated cell lysates . In addition , PARP cleavage was blocked by using tetrapepdide caspases inhibitors such as DEVD or z-VAD . These results demonstrate that tumor cell death induced by HB and HA is mediated by caspase proteases . This study also identifies both colon and bladder cells were more sensitive cell lines than NPC ( CNE2 and TWO-1 ) cell lines .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone . The use of a tissue-selective estrogen complex ( TSEC ) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen . Combination of bazedoxifene ( BZA ) with conjugated estrogens ( CEs ) , the first TSEC , has shown beneficial effects . Whether it would exert antiestrogenic effects on breast cancer is not clear . To address this issue , we compared estradiol ( E(2) ) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells . CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E(2) . Both CE and E(2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK , Akt , and p70S6K and up-regulation of antiapoptotic factors survivin , Bcl-2 , and X-linked inhibitor of apoptosis protein , These effects could be completely blocked by BZA . Gene expression studies demonstrated that CE and E(2) were equally potent on expression of cMyc , pS2 , and WNT1 inducible signaling pathway protein 2 , whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E(2) . BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone . Our results indicate that the stimulatory effects of E(2) or CE on breast cancer cells could be completely abrogated by BZA . These studies imply that the CE/BZA , TSEC , exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women , resulting in an overall reduction in tumor incidence .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The contribution that mitochondrial bioenergetics could have in cancer development is debated . Here , we have generated HCT116-derived colocarcinoma cell lines expressing different levels of the beta catalytic subunit of the mitochondrial H+-adenosine triphosphate synthase to assess the contribution of mitochondrial bioenergetics in colon cancer progression . The generated cells exhibit large ultrastructural , transcriptomic , proteomic and functional differences in their mitochondria and in their in vivo tumor forming capacity . We show that the activity of oxidative phosphorylation defines the rate of glucose utilization by aerobic glycolysis . The aggressive cellular phenotype , which is highly glycolytic , is bound to the deregulated expression of genes involved in metabolic processes , the regulation of the cell cycle , apoptosis , angiogenesis and cell adhesion . Remarkably , the molecular and ultrastructural analysis of the tumors derived from the three HCT116 cell lines under study highlight that tumor promotion inevitably requires the selection of cancer cells with a repressed biogenesis and functional activity of mitochondria , i.e. the highly glycolytic phenotype is selected for tumor development . The tumor forming potential of the cells is a non-genetically acquired condition that provides the cancer cell with a cell-death resistant phenotype . An abrogated mitochondrial respiration contributes to a diminished potential for reactive oxygen species signaling in response to 5-fluorouracil treatment . Treatment of cancer cells with dichloroacetate partially restores the functional differentiation of mitochondria and promotes tumor regression , emphasizing the reversible nature of the metabolic trait of cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We compared gadolinium diethylenetriaminepentaacetic acid ( Gd-DTPA ) enhanced T1-weighted images ( T1-Gd ) with the histopathological findings in 13 patients with bone or soft tissue sarcomas . Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients . The necrotic or cystic areas in the tumor were not enhanced , rendering them distinctly . The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients . Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced . Thus , the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd . Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Mitochondrial biogenesis , which depends on nuclear as well as mitochondrial genes , occurs in response to increased cellular ATP demand . The nuclear transcriptional factors , estrogen-related receptor alpha ( ERRalpha ) and nuclear respiratory factors 1 and 2 , are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis , whereas coactivators of the peroxisome proliferator-activated receptor gamma coactivator-1 ( PGC-1 ) family serve as mediators between the environment and this machinery . In the context of proliferating cells , PGC-1-related coactivator ( PRC ) is a member of the PGC-1 family , which is known to act in partnership with nuclear respiratory factors , but no functional interference between PRC and ERRalpha has been described so far . We explored three thyroid cell lines , FTC-133 , XTC.UC1 and RO 82 W-1 , each characterized by a different mitochondrial content , and studied their behavior towards PRC and ERRalpha in terms of respiratory efficiency . Overexpression of PRC and ERRalpha led to increased respiratory chain capacity and mitochondrial mass . The inhibition of ERRalpha decreased cell growth and respiratory chain capacity in all three cell lines . However , the inhibition of PRC and ERRalpha produced a greater effect in the oxidative cell model , decreasing the mitochondrial mass and the phosphorylating respiration , whereas the nonphosphorylating respiration remained unchanged . We therefore hypothesize that the ERRalpha-PRC complex plays a role in arresting the cell cycle through the regulation of oxidative phosphorylation in oxidative cells , and through some other pathway in glycolytic cells .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The published results on nanoparticles cytotoxicity and genotoxicity such as titanium dioxide nanoparticles ( TiO(2) NPs ) are inconsistent , and often conflicting and insufficient . Since different parameters may have impact on the toxicity results , there is need to lay stress on detailed characterization of NPs and the use of different testing conditions for assessment of NPs toxicity . In order to investigate whether dispersion procedures influence NP cytotoxicity and genotoxicity , we compared two protocols giving TiO(2) NP dispersions with different stability and agglomeration states . Detailed primary and secondary characteristics of both TiO(2) NP dispersions in culture media were carried out before toxicological testing ; TK6 human lymphoblast cells , EUE human embryonic epithelial cells and Cos-1 monkey kidney fibroblasts were used to assess cytotoxicity ( by trypan blue exclusion , proliferation activity and plating efficiency assays ) and genotoxicity ( by the comet assay ) . DNA strand breaks were detected by the alkaline comet assay . DNA oxidation lesions ( especially 8-oxo-7,8-dihydroguanine , 8-oxoG ) were measured with a modified comet assay including incubation with specific repair enzyme formamidopyrimidine DNA glycosylase ( FPG ) . The TiO(2) NPs dispersion with large agglomerates ( 3 min sonication and no serum in stock solution ) induced DNA damage in all three cell lines , while the TiO(2) NPs dispersed with agglomerates less than 200 nm ( foetal serum in stock solution and sonication 15 min ) had no effect on genotoxicity . An increased level of DNA oxidation lesions detected in Cos-1 and TK6 cells indicates that the leading mechanism by which TiO(2) NPs trigger genotoxicity is most likely oxidative stress . Our results show that the dispersion method used can influence the results of toxicity studies . Therefore at least two different dispersion procedures should be incorporated into assessment of cyto- and genotoxic effects of NPs . It is important , when assessing the hazard associated with NPs , to establish standard testing procedures and thorough strategies to consider the diverse conditions relevant to possible exposures .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE Expression of N-myc downstream-regulated gene 1 ( NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs . We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer ( NSCLC ) in vivo using an animal experimental model , and also how it could affect tumor angiogenesis and prognosis in NSCLC patients . METHODS AND RESULTS Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells , but decreased tumor growth rates in vivo markedly . Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor ( EGFR ) family proteins and c-Met in two human lung cancer cell lines in vitro . However , cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8 . Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis . Using immunohistochemistry , we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis . High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma ( p = 0.003 ) and squamous cell carcinoma ( p=0.041 ) . For both adenocarcinoma ( p = 0.031 ) and squamous cell carcinoma ( p=0.034 ) , the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive . CONCLUSION Therefore , the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Glioblastoma multiforme ( GBM ) and oxidative stress are closely linked . Oxidative stress affects many signaling pathways and may cause the induction of autophagy . The NF-E2-related factor 2 ( Nrf2)/Kelch-like ECH-associated protein 1 ( Keap1 ) signaling pathway is the main pathway responsible for cell defense against oxidative stress and Nrf2 is a critical transcription factor related with cancer multidrug resistance . However , the relation between Nrf2 and regulation of autophagy is not well understood . In this study , we used temozolomide ( TMZ ) , which inhibited the viability of GBM cells mainly by inducing autophagic cell death and explored the role of Nrf2 downregulation on autophagy induced by TMZ in GBM cells . In U251-Si-Nrf2 48h after transfection the protein levels of Nrf2 were significantly downregulated , while the protein levels of LC3B-II increased by western blot analysis . Knockdown of Nrf2 also led to a significant increase of autophagic vacuoles and acidic vesicular organelles ( AVOs ) , revealed by trans-mission electron microscopy ( TEM ) and acridine orange ( AO ) staining using flow cytometry . Collectively , these findings demonstrate that knockdown of Nrf2 can enhance the basal level of autophagy in the U251 glioma cell line . Furthermore , after the treatment with TMZ ( 100µM ) for 3 days , the U251-Si-Nrf2 transfected cells showed less viability rate by cell counting kit-8 ( CCK-8 ) assay and the levels of autophagy increased obviously through analysis of western blot and AO staining using flow cytometry . Taken together , our results suggest that knockdown of Nrf2 may enhance autophagy induced by TMZ in the U251 glioma cell line , which should be further evaluated for novel anticancer activity .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND/AIMS Adenocarcinoma of the gallbladder is a highly malignant neoplasm. p16 is a tumor suppressor gene protein , which is a cyclin-dependent kinase inhibitor that regulates the G1-S phase of the cell cycle . The purpose of the present study was to investigate the expression of p16 in gallbladder carcinoma and its precancerous conditions and to examine the relationship between p16 expression and clinicopathological parameters . METHODOLOGY Formalin-fixed , paraffin-embedded tissue sections from 20 cases of normal gallbladder , 20 cases of chronic cholecystitis , 20 cases of gallbladder adenoma , 20 cases of dysplasia , and 58 cases of adenocarcinoma were examined . The expression of p16 was evaluated by immunohistochemical analysis . RESULTS In normal gallbladder , no expression of p16 was found . In chronic cholecystitis , expression of p16 was not found . In gallbladder adenomas , expression of p16 was found in 20% ( 4/20 ) . In low grade dyspalsias , expression of p16 was not found . In high grade dysplasias , p16 expression was present in 45.0% ( 9/20 ) . In gallbladder adenocarcinomas , p16 expression was found in 27.6% ( 16/58 ) . Expression of p16 correlated significantly with histologic grade ( p &lt ; 0.05 ) . No correlation was found between p16 expression and age , gender , tumor size , gross type , location , vascular invasion , lymph node metastasis , and TNM stage , respectively . CONCLUSIONS P16 protein overexpression is an early and relatively common event in carcinogenesis of gallbladder carcinoma . Expression of p16 protein is absent in normal or chronic cholecystitis . Expression of p16 may be an ancillary diagnostic marker of gallbladder carcinoma and its precancerous conditions .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Chronic inflammation is a critical component in breast cancer progression . Pro-inflammatory mediators along with growth/survival factors within the tumor microenvironment potentiate the expression of pro-inflammatory cytokines ( IL-1 , IL-6 , TNF-α ) , chemotactic cytokines and their receptors ( CXCR4 , CXCL12 , CXCL8 ) and angiogenic factors ( VEGF ) that often overcome the effect of anti-inflammatory molecules ( IL-4 , IL-10 ) thus evading the host's antitumor immunity . Detailed knowledge , therefore , of the regulatory mechanisms determining cytokine levels is essential to understand the pathogenesis of breast cancer . HIF-1α and NF-κB transcription factors are important players for the establishment of a pro-inflammatory and potentially oncogenic environment . HIF-1α is the key mediator of the cellular response to oxygen deprivation and induces the expression of genes involved in survival and angiogenesis within solid hypoxic tumors . The expression of these genes is often modulated by the p53 tumor suppressor protein that induces apoptosis or cell cycle arrest in neoplastic cells . Functional crosstalk between HIF-1α and p53 pathways mediated by modulators shared between the two transcription factors such as SRC-1 and SIRT-1 differentially regulate the expression of distinct subsets of their target genes under variable stress conditions . In an attempt to shed light on the complex regulatory mechanisms involved in cancer-related inflammation , we investigated the role of the two common p53 and HIF-1α co-regulators SRC-1 and SIRT-1 , in the expression of the highly potent metastatic chemokine receptor CXCR4 . Both SRC-1 and SIRT-1 overexpression in DSFX-treated MCF-7 cells reduced CXCR4 cellular levels implying that both co-regulators are crucial factors in the determination of the metastatic potential of breast cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer . However , whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown . Here , we show that exposure of non-malignant prostate epithelial cells ( HPr-1AR ) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence . Notably , knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2 : ERG rearrangement , a prostate-specific chromosome translocation frequently found in prostate cancer cells . Intriguingly , unlike the non-malignant prostate epithelial cells , the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells , since androgen treatment only induced a partial activation of the DNA damage response . This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX , lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway . Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Limited options for the treatment of prostate cancer have spurred the search for new therapies . One innovative approach is the use of targeted alpha therapy ( TAT ) to inhibit cancer growth , using an alpha particle emitting radioisotope such as ( 213)Bi . Because of its short range and high linear energy transfer ( LET ) , alpha-particles may be particularly effective in the treatment of cancer , especially in inhibiting the development of metastatic tumors from micro-metastases . Prostate-specific membrane antigen ( PSMA ) is expressed in prostate cancer cells and the neovasculature of a wide variety of malignant neoplasms including lung , colon , breast and others , but not in normal vascular endothelium . The expression is further increased in higher-grade cancers , metastatic disease and hormone-refractory prostate cancer ( PCA ) . J591 is one of several monoclonal antibodies ( mabs ) to the extracellular domain of PSMA . Chelation of J591 mab with ( 213)Bi forms the alpha-radioimmunoconjugate ( AIC ) . The objective of this preclinical study was to design an injectable AIC to treat human prostate tumors growing subcutaneously in mice . The anti-proliferative effects of AIC against prostate cancer were tested in vitro using the MTS assay and in vivo with the nude mice model . Apoptosis was documented using terminal deoxynucleotidyl transferase [ TdT]-mediated deoxyuridinetriphosphate [ dUTP ] nick end-labeling ( TUNEL ) assay , while proliferative index was assessed using the Ki-67 marker . We show that a very high density of PSMA is expressed in an androgen-dependent human PCA cell line ( LNCaP-LN3 ) and in tumor xenografts from nude mice . We also demonstrate that the AIC extensively inhibits the growth of LN3 cells in vitro in a concentration-dependent fashion , causing the cells to undergo apoptosis . Our in vivo studies showed that a local AIC injection of 50 microCi at 2 days post-cell inoculation gave complete inhibition of tumor growth , whereas results for a non-specific AIC were similar to those for untreated mice . Further , after 1 and 3 weeks post-tumor appearance , a single ( 100 microCi/100 microl ) intra-lesional injection of AIC can inhibit the growth of LN3 tumor xenografts ( volume<100 mm(3) ) in nude mice . Tumors treated with AIC decreased in volume from a mean 46+/-14 mm(3) in the first week or 71+/-15 mm(3) in the third week to non-palpable , while in control mice treated with a non-specific AIC using the same dose , tumor volume increased from 42 to 590 mm(3) . There were no observed side effects of the treatment . Because of its in vitro cytotoxicity and these anti-proliferative properties in vivo , the ( 213)Bi-J591 conjugate has considerable potential as a new therapeutic agent for the treatment of prostate cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The aryl hydrocarbon receptor ( AHR ) is a ligand-activated transcription factor that mediates the effects of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) . Recently , AHR has emerged as a potential therapeutic target for breast cancer by virtue of its ability to modulate estrogen receptor-α ( ERα ) signalling and/or its ability to block cell proliferation . Our previous studies identified cyclin G2 ( CCNG2 ) , an inhibitor of cell-cycle progression , as an AHR target gene ; however , the mechanism of this regulation is unknown . Chromatin immunoprecipitation assays in T-47D human breast cancer cells revealed a TCDD-dependent recruitment of AHR , nuclear co-activator 3 ( NCoA3 ) and the transcription factor forkhead box A1 ( FOXA1 ) , a key regulator of breast cancer cell signaling , to CCNG2 resulting in increases in CCNG2 mRNA and protein levels . Mutation of the AHR response element ( AHRE ) and forkhead-binding sites abolished TCDD-induced CCNG2-regulated reporter gene activity . RNA interference-mediated knockdown of FOXA1 prevented the TCDD-dependent recruitment of AHR and NCoA3 to CCNG2 and reduced CCNG2 mRNA levels . Interestingly , knockdown of FOXA1 also caused a marked decrease in ERα , but not AHR protein levels . However , RNA interference-mediated knockdown of ERα , a negative regulator of CCNG2 , had no effect on TCDD-dependent AHR or NCoA3 recruitment to or expression of CCNG2 . These findings show that FOXA1 , but not ERα , is essential for AHR-dependent regulation of CCNG2 , assigning a role for FOXA1 in AHR action .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The ASPP2 ( also known as 53BP2L ) tumor suppressor is a proapoptotic member of a family of p53 binding proteins that functions in part by enhancing p53-dependent apoptosis via its C-terminal p53-binding domain . Mounting evidence also suggests that ASPP2 harbors important nonapoptotic p53-independent functions . Structural studies identify a small G protein Ras-association domain in the ASPP2 N terminus . Because Ras-induced senescence is a barrier to tumor formation in normal cells , we investigated whether ASPP2 could bind Ras and stimulate the protein kinase Raf/MEK/ERK signaling cascade . We now show that ASPP2 binds to Ras-GTP at the plasma membrane and stimulates Ras-induced signaling and pERK1/2 levels via promoting Ras-GTP loading , B-Raf/C-Raf dimerization , and C-Raf phosphorylation . These functions require the ASPP2 N terminus because BBP ( also known as 53BP2S ) , an alternatively spliced ASPP2 isoform lacking the N terminus , was defective in binding Ras-GTP and stimulating Raf/MEK/ERK signaling . Decreased ASPP2 levels attenuated H-RasV12-induced senescence in normal human fibroblasts and neonatal human epidermal keratinocytes . Together , our results reveal a mechanism for ASPP2 tumor suppressor function via direct interaction with Ras-GTP to stimulate Ras-induced senescence in nontransformed human cells .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Low-dose cyclophosphamide ( CP ) therapy induces immunogenic tumor cell death and decreases regulatory T cell ( Treg ) numbers in mice with transplantable tumors . Using the ret transgenic murine melanoma model that resembles human melanoma , we detected no beneficial antitumor effects with such treatment , despite a decrease in Tregs . On the contrary , low-dose CP enhanced the production of chronic inflammatory mediators in melanoma lesions associated with increased accumulation of Gr1(+)CD11b(+) myeloid-derived suppressor cells ( MDSCs ) , which exhibit elevated suppressive activity and nitric oxide ( NO ) production as well as inhibition of T-cell proliferation . Moreover , the frequencies of CD8(+) T cells in the tumors and their ability to produce perforin were decreased . To study whether the observed CP-induced MDSC expansion and activation also occurs under chronic inflammatory tumor-free conditions , mice exhibiting chronic inflammation were treated with CP . Similar to tumor-bearing mice , CP-treated inflamed mice displayed elevated levels of MDSCs with enhanced production of NO , reactive oxygen species , and a suppressed in vivo natural killer ( NK ) cell cytotoxic activity indicating CP effects on the host immune system independent of the tumor . We suggest that melanoma therapy with low-dose CP could be efficient only when combined with the neutralization of MDSC immunosuppressive function and chronic inflammatory microenvironment.Journal of Investigative Dermatology advance online publication , 6 December 2012 ; doi:10.1038/jid.2012.444 .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Both the deregulation of microRNAs and epidermal growth factor receptor ( EGFR ) are emerging as important factors in non-small-cell lung cancer ( NSCLC ) . Here , miR-133b was found to be associated with tumor stage , the extent of regional lymph node involvement , stage , visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC . Bioinformatic analysis and luciferase reporter assay revealed that miR-133b can interact specifically with the 3'-UTR of EGFR mRNA . Functionally , miR-133b transfection showed regulatory activity in translationally repressing EGFR mRNA . Moreover , miR-133b transfection may modulate apoptosis , invasion and sensitivity to EGFR-TKI through the EGFR signaling pathways , especially in EGFR-addicted NSCLC cells . Taken together , our findings show that miR-133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway . This finding has important implications for the development of targeted therapeutics for a number of EGFR-addicted cancers .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis;resisting cell death" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: MicroRNAs ( miRNAs ) are considered to be regulators of various biological processes in cancers , including the epithelial to mesenchymal transition ( EMT ) , which is a key factor in cancer metastasis . In this study , we aimed to clarify the potential roles of miR-490-3p in hepatocellular carcinoma ( HCC ) cells . Using real-time quantitative RT-PCR , we discovered that miR-490-3p was up-regulated in HCC tissues and cells compared with the adjacent non-tumor tissues and normal cells . We also found that overexpression of miR-490-3p led to an increase in cell proliferation , migration , and invasion abilities and that it contributed to EMT . The inhibition of miR-490-3p had the opposite effect on the cells . We identified ERGIC3 ( endoplasmic reticulum-Golgi intermediate compartment protein 3 ) as a direct target gene for miR-490-3p . Unlike most miRNA-mRNA interactions , miR-490-3p increased ERGIC3 mRNA and protein levels as well as the intensity of expression of the EGFP reporter gene controlled by the 3'-UTR of ERGIC3 mRNA . The up-regulation by miR-490-3p also required the participation of Ago2 . The inhibition of miR-490-3p reduced the expression of ERGIC3 . Overexpression of ERGIC3 led to the same effect on HCC cells as miR-490-3p overexpression , including EMT . Importantly , silencing ERGIC3 reversed the cellular responses mediated by miR-490-3p overexpression . In conclusion , our study indicated for the first time that miR-490-3p functioned like an oncogenic miRNA in HCC cells and that the inhibition of miR-490-3p might provide an potential treatment approach for HCC patients .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Progression of breast cancer is associated with remodeling of the extracellular matrix , often involving a switch from estrogen dependence to a dependence on EGF receptor ( EGFR)/HER-2 and is accompanied by increased expression of the main binding protein for insulin-like growth factors ( IGFBP-3 ) . We have examined the effects of IGFBP-3 on EGF responses of breast epithelial cells in the context of changes in the extracellular matrix . On plastic and laminin with MCF-10A normal breast epithelial cells , EGF and IGFBP-3 each increased cell growth and together produced a synergistic response , whereas with T47D breast cancer cells IGFBP-3 alone had no effect , but the ability of EGF to increase cell proliferation was markedly inhibited in the presence of IGFBP-3 . In contrast on fibronectin with MCF-10A cells , IGFBP-3 alone inhibited cell growth and blocked EGF-induced proliferation . With the cancer cells , IGFBP-3 alone had no effect but enhanced the EGF-induced increase in cell growth . The insulin-like growth factor-independent effects of IGFBP-3 alone on cell proliferation were completely abrogated in the presence of an EGFR , tyrosine kinase inhibitor , Iressa . Although IGFBP-3 did not affect EGFR phosphorylation [ Tyr(1068) ] , it was found to modulate receptor internalization and was associated with activation of Rho and subsequent changes in MAPK phosphorylation . The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "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.\n ###\n 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.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n 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 .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]