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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: Tumor necrosis factor related apoptosis-inducing ligand ( TRAIL ) and agonistic anti-DR4/TRAIL-R1 and anti-DR5/TRAIL-R2 antibodies are currently under clinical investigation for treatment of different malignancies . TRAIL activates DR4 and DR5 and thereby triggers apoptotic and non-apoptotic signaling pathways , but possible different roles of DR4 or DR5 in these responses has poorly been addressed so far . In the present work , we analyzed cell viability , DISC formation as well as IL-8 and NF-kappaB activation side by side in responses to TRAIL and agonistic antibodies against DR4 ( mapatumumab ) and against DR5 ( lexatumumab ) in pancreatic ductal adenocarcinoma cells . We found that all three reagents are able to activate cell death and pro-inflammatory signaling . Death-inducing signaling complex ( DISC ) analysis revealed that mapatumumab and lexatumumab induce formation of homocomplexes of either DR4 or DR5 , whereas TRAIL additionally stimulated the formation of heterocomplexes of both receptors . Notably , blocking of receptors using DR4- and DR5-specific Fab fragments indicated that TRAIL exerted its function predominantly via DR4 . Interestingly , inhibition of PKC by Goe6983 enabled DR5 to trigger apoptotic signaling in response to TRAIL and also strongly enhanced lexatumumab-mediated cell death . Our results suggest the existence of mechanisms that silence DR5 for TRAIL- but not for agonistic-antibody treatment .\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: The down-regulation of dominant oncogenes , including C-MYC , in tumor cells often leads to the induction of senescence via mechanisms that are not completely identified . In the current study , we demonstrate that MYC-depleted melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase ( TS ) and ribonucleotide reductase ( RR ) and subsequent depletion of deoxyribonucleoside triphosphate pools . Simultaneous genetic inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones caused by MYC-depletion . Reciprocally , overexpression of TS and RR in melanoma cells or addition of deoxyribo-nucleosides to culture media substantially inhibited DNA damage and senescence-associated phenotypes caused by C-MYC depletion . Our data demonstrate the essential role of TS and RR in C-MYC-dependent suppression of senescence in melanoma cells .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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: INTRODUCTION Cell-cell interaction is an essential component of atherosclerotic plaque development . Activated monocytes appear to play a central role in the development of atherosclerosis , not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development . Using serum free co-culture method , we determined the effect of monocytes on endothelial cell proliferation . METHODS Endothelial cell proliferation is determined by the amount of [ 3H]thymidine incorporated in to the DNA . Basic fibroblast growth factor ( b-FGF ) , vascular endothelial growth factor ( VEGF ) and interleukin-8 ( IL-8 ) levels in the conditioned medium were determined by ELISA . RESULTS Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation , whereas conditioned medium from activated monocytes promoted endothelial cell proliferation . The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF , VEGF and IL-8 . Neutralizing antibodies against b-FGF , VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes . When b-FGF , VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes , it is less mitogenic to endothelial cells . CONCLUSION Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors .\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: OBJECTIVE To clarify the relationship between the expression of pol beta and DNA damage /repair induced by Benzo(a)pyrene ( BaP ) . METHODS pol beta wild-type cells ( pol beta +/+ ) , pol beta null cells ( pol beta -/- ) and wild-type pol beta overexpressed cells ( pol beta oe ) which had the same genetic background were studied . Firstly , RT-PCR and Western blot targeting to pol beta were carried out to measure the expression of pol beta mRNA and protein in above three kinds of cells , then MTT test and single cell gel electrophoresis ( comet assay ) were used to compare cell viability and DNA damage/repair of the three kinds of cells when exposed to BaP . RESULTS There was pol beta deletion in pol beta -/- cells and the level of pol beta mRNA and protein in pol beta oe cells was twice higher than that in pol beta +/+ cells . BaP could induce DNA damage and reduce cell viability , when compared with pol beta +/+ cells , IC50 of pol beta -/- cells was remarkably lower , DNA was prone to damage and more difficult to be repaired , on the other hand , IC50 of pol beta oe cells was obviously higher and the damage effect on DNA was weaker and prone to be repaired . CONCLUSION Pol beta played an important role in the repair of DNA damage induced by BaP , deficiency of pol beta could decrease the DNA repair capability of cells , and overexpression of pol beta could help cells response to DNA damage and protect cells from death in a certain degree .\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: Elevated phosphorylation of estrogen receptor α ( ERα ) at serines 118 ( S118 ) and 167 ( S167 ) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer . It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling , resulting in aggressive ERα-independent breast cancer cells . To this end , MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα . The resulting cell line was stably transfected with wild-type ERα ( ER-AB cells ) , or ERα containing serine to alanine mutation at S118 or S167 ( S118A cells and S167A cells , respectively ) . These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth , morphology , migration/invasion , and ERα-regulated gene expression . S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro . Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size , and both S118A and S167A cells exhibited less cellular complexity . S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin , indicating retention of epithelial lineage markers . Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells . In summary , attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells , resulting in increased growth , migration/invasion , compromised expression of ERα target genes , and markedly altered gene expression patterns .\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: BACKGROUND Tissue factor ( TF ) , an initiator of blood coagulation , participates in cancer progression and metastasis . We recently found that inhibition of MAPK/ERK upregulated both full length TF ( flTF ) and soluble isoform TF ( asTF ) gene expression and cell-associated TF activity in breast cancer MDA-MB-231 cells . We explored the possible mechanisms , especially the possible interaction with EGFR and PI3K/Akt pathways . METHODS A plasmid containing TF promoter -2174  plus luciferase reporter gene was introduced into MDA-MB-231 cells to evaluate TF promoter activity . In order to study the interaction of these pathways , ERK inhibitor ( PD98059 ) , PI3K inhibitors ( LY294002 , wortmannin ) , Akt inhibitor ( A6730 ) , and EGFR inhibitor ( erlotinib ) as well as the corresponding siRNAs were used to treat MDA-MB-231 cells , and ovarian cancer OVCAR-3 and SKOV-3 cells . Quantitative PCR and western blot were used to determine TF expression . One stage clotting assays were used to measure pro-coagulation activity of the MDA-MB-231 cells . RESULTS We show that PI3K inhibitors LY294002 , wortmannin and A6730 significantly inhibited TF promoter activity , and reduced TF mRNA and protein levels due to the inhibition of Akt phosphorylation . In contrast , ERK inhibitor PD98059 and ERK siRNA enhanced TF promoter activity by 2.5 fold and induced an increase in TF mRNA and protein levels in a dose dependent manner in these cells . The PI3K/Akt pathway was shown to be involved in PD98059-induced TF expression because the induction was inhibited by PI3K/Akt inhibitors . Most interestingly , the EGFR inhibitor erlotinib and EGFR siRNA also significantly suppressed PD98059- or ERK siRNA-induced TF promoter activity and TF protein expression . Similar results were found with ovarian cancer cells SKOV-3 and OVCAR-3 . Furthermore , in MDA-MB-231 , mRNA levels of asTF were regulated in a similar way to that of TF in response to the cell treatment . CONCLUSIONS This study showed a regulatory mechanism in which MAPK/ERK signals inhibit EGFR/PI3K/Akt-mediated TF expression in breast cancer MDA-MB-231 cells . The same regulation was observed in ovarian cancer OVCAR-3 and SKOV-3 cells . Interestingly , we observed that both flTF and asTF could be regulated in a parallel manner in MDA-MB-231 . As the PI3K/Akt pathway and EGFR regulate TF expression in cancer cells , targeting these signaling components is expected to potentially inhibit TF expression-associated tumor progression .\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: Direct experimental evidence implicates telomere erosion as a primary cause of cellular senescence . Using a well characterized model system for breast cancer , we define here the molecular and cellular consequences of adriamycin treatment in breast tumor cells . Cells acutely exposed to adriamycin exhibited an increase in p53 activity , a decline in telomerase activity , and a dramatic increase in beta-galactosidase , a marker of senescence . Inactivation of wild-type p53 resulted in a transition of the cellular response to adriamycin treatment from replicative senescence to delayed apoptosis , demonstrating that p53 plays an integral role in the fate of breast tumor cells treated with DNA-damaging agents . Stable introduction of hTERT , the catalytic protein component of telomerase , into MCF-7 cells caused an increase in telomerase activity and telomere length . Treatment of MCF-7-hTERT cells with adriamycin produced an identical senescence response as controls without signs of telomere shortening , indicating that the senescence after treatment is telomere length-independent . However , we found that exposure to adriamycin resulted in an overrepresentation of cytogenetic changes involving telomeres , showing an altered telomere state induced by adriamycin is probably a causal factor leading to the senescence phenotype . To our knowledge , these data are the first to demonstrate that the mechanism of adriamycin-induced senescence is dependent on both functional p53 and telomere dysfunction rather than overall shortening .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;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: Radiotherapy is commonly used for cancer treatment . However , it often results in side effects due to radiation damage in normal tissue , such as bone marrow ( BM ) failure . Adult hematopoietic stem and progenitor cells ( HSPC ) reside in BM next to the endosteal bone surface , which is lined primarily by hematopoietic niche osteoblastic cells . Osteoblasts are relatively more radiation-resistant than HSPCs , but the mechanisms are not well understood . In the present study , we demonstrated that the stress response gene REDD1 ( regulated in development and DNA damage responses 1 ) was highly expressed in human osteoblast cell line ( hFOB ) cells after γ irradiation . Knockdown of REDD1 with siRNA resulted in a decrease in hFOB cell numbers , whereas transfection of PCMV6-AC-GFP-REDD1 plasmid DNA into hFOB cells inhibited mammalian target of rapamycin ( mTOR ) and p21 expression and protected these cells from radiation-induced premature senescence ( PS ) . The PS in irradiated hFOB cells were characterized by significant inhibition of clonogenicity , activation of senescence biomarker SA-β-gal , and the senescence-associated cytokine secretory phenotype ( SASP ) after 4 or 8 Gy irradiation . Immunoprecipitation assays demonstrated that the stress response proteins p53 and nuclear factor κ B ( NFkB ) interacted with REDD1 in hFOB cells . Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein expression in these cells , indicating that REDD1 was regulated by both factors . Our data demonstrated that REDD1 is a protective factor in radiation-induced osteoblast cell premature senescence .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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: We investigated the priming effect and mechanism of granulocyte colony-stimulating factor ( G-CSF ) in chemotherapy with low-dose Ara-C and VP-16 for acute myeloid leukemia . We analyzed cell proliferation , apoptosis , and cell cycle in vitro using leukemia cell lines 32Dcl3 , U937 , HL-60 , and Ba/F3 . Cell proliferation assays were performed using the Trypan Blue dye exclusion method . For detection of apoptosis , the Annexin V-binding capacity of treated cells was examined by flow cytometry . To evaluate the cell cycle , we used an FITC BrdU Flow kit and conducted analysis by flow cytometry . The combination of Ara-C and VP-16 significantly enhanced the observed effects compared with those of Ara-C or VP-16 alone . Concurrent administration of G-CSF further reduced the cell number and viability of 32Dcl3 and U937 cells , but not of HL-60 and Ba/F3 cells . Apoptotic cells were significantly increased in number by the addition of G-CSF to 32Dcl3 and U937 cells , while G-CSF had no significant effect on HL-60 and Ba/F3 cell lines . The addition of G-CSF significantly decreased the percentage of G0/G1-phase cells and significantly increased that of S-phase cells among 32Dcl3 and U937 cells . No significant effect was observed for HL-60 and Ba/F3 cells . An enhancement was confirmed for the combination of Ara-C , VP-16 , and G-CSF for 32Dcl3 and U937 cells but not for HL-60 and Ba/F3 cells . It was thought that this difference was a result of different responses to G-CSF . G-CSF potentiates Ara-C- and VP-16-induced cytotoxicities through apoptosis induction by mobilizing resting G0-G1-phase cells into S phase .\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: Telomerase activity , a cardinal requirement for immortalization , is a crucial step in the development of cancer and has been studied in many kinds of malignant tumours for clinical diagnostic and/or prognostic utilities . Using a PCR-based TRAP assay , we investigated telomerase activity in 8 adenomatous polyps , 9 dysplastic polyps , and in 36 paired cancer-normal mucosa specimens , one liver and one spleen metastasis from patients resected for sporadic colorectal cancer . Telomerase was absent or very low in normal mucosa and in adenomatous polyps . Dysplastic polyps and adenocarcinoma samples showed telomerase activity , with higher levels in cancer tissues compared to dysplastic lesions . A high telomerase activity was shown to be associated with late-staged cancers and metastasis , providing arguments supporting the role of telomerase not only in the development but also in the progression of colorectal carcinoma . Moreover , telomerase evaluation may help to confirm the malignant transformation in polypoid colorectal lesions with different levels of dysplastic alterations .\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: Epstein-Barr virus ( EBV ) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus . The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1 . However , the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression . Here , we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells . Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae . Using time-lapse microscopy , we found the fate of individual HeLa cells was determined by the expression level of BGLF4 . In addition to slight cell growth retardation , BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells . In Saos-2 cells , BGLF4 induced the hyperphosphorylation of co-transfected RB , while E2F1 was not released from RB-E2F1 complexes . The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner . Detection with phosphoamino acid specific antibodies revealed that , in addition to Ser780 , phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4 . Taken together , our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression .\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: Genetic immunotherapy with tumor antigen gene-modified dendritic cells ( DC ) generates robust immunity , although antitumor protection is not complete in all models . Previous experience in a model in which C57BL/6 mice immunized with DC transduced with adenoviral vectors expressing MART-1 demonstrated a 20-40% complete protection to a tumor challenge with B16 melanoma cells . Tumors that did develop in immunized mice had slower growth kinetics compared to tumors implanted in na�ve mice . In the present study , we wished to determine if the supraphysiological production of the Th1-skewing cytokine interleukin-12 ( IL-12 ) could enhance immune activation and antitumor protection in this model . In a series of experiments immunizing mice with DC cotransduced with MART-1 and IL-12 , antitumor protection and antigen-specific splenocyte cytotoxicity and interferon gamma production inversely correlated with the amount of IL-12 produced by DC . This adverse effect of IL-12 could not be explained by a direct cytotoxic effect of natural killer cells directed towards DC , nor the production of nitric oxide leading to down-regulation of the immune response - the two mechanisms previously recognized to explain immune-suppressive effects of IL-12-based vaccine therapy . In conclusion , in this animal model , IL-12 production by gene-modified DC leads to a cytokine-induced dose-dependent inhibition of antigen-specific antitumor protection .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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: Abstract Purpose : Cell death is one of the most important endpoints of radiosensitivity . The tumor suppressor p53 participates not only in regulation of apoptosis , but also in autophagy mechanism . In this study , H1299-P53 ( with wild-type p53 ) and H1299-175H ( with mutant 175H ) were used , and the effects of p53 on radiosensitivity were analyzed . Methods : Cell models with different p53 status were established by gene engineering , and cell viability was examined by colony formation assay , and cell counting kit-8 ( CCK-8 ) , 3-Methyladenine , and Z-VAD were used to block autophagy and apoptosis , respectively . Western blot was used to detect protein expression ; monodansylcadaverine ( MDC ) staining was used to analyze autophagy rate ; DAPI/Propidium Iodide ( PI ) staining and flow cytometry were used to assess apoptosis and necrosis . Results : In parental H1299 , H1299-P53 , and H1299-175H cells , radiosensitivity exhibited different by colony formation and CCK-8 assay ( D0 : 1.764 Gy , 1.407 Gy and 1.695 Gy ; Dq : 2.977 Gy , 1.199 Gy and 2.312 Gy in turn ) . The radiosensitization of p53 was associated with the increase of MDM2 and P21 expression . The ionizing radiation ( IR)-induced apoptosis was significant in H1299-P53 compared with in H1299 and H199-175H ( p<0.05 ) by flow cytometry , and the expression of cleaved-caspase3 was increased in H1299-P53 cells . While the IR-induced autophagy was significant in H1299 cells ( p<0.01 ) and decreased in H1299-P53 and H1299-175H cells ( p<0.01 ) by MDC staining , the expression of MAPLC3II and Beclin-1 increased in H1299 , but not in H1299-p53 and H199-175H cells . The IR-induced cell survival was significantly increased by Z-VAD-FMK and decreased by 3MA in H1299-P53 cells ; IR- induced autophagy was significantly increased by Z-VAD-FMK in H1299-P53 cells ( p<0.01 ) , but not changed in H1299 cells . Conclusion : p53 could regulate radiosensitivity by inhibiting autophagy and activating apoptosis ; autophagy provides a prosurvival mechanism , and p53 potently abrogated the IR-induced autophagy , while mutant 175H shown no effect on radiosensitivity , suggesting that individual treatment strategies should be based on p53 status in 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: BACKGROUND Epithelial mesenchymal transition ( EMT ) is known to be associated with chemoresistance as well as increased invasion/metastasis . However , the relationship between EMT and resistance to an epidermal growth factor receptor ( EGFR ) -targeting drug in head and neck squamous cell carcinoma ( HNSCC ) remains unknown . In this study , we investigated the acquisition of EMT by gefitinib in HNSCC cell line ( UMSCC81B ) . METHODS We isolated fibroblastoid variant ( 81B-Fb ) from gefitinib-resistant UMSCC81B-GR3 cells obtained after increasing the doses of gefitinib treatment in vitro and examined EMT and its underlying mechanism . RESULT 81B-Fb cells exhibited fibroblast-like morphology , increased motility , loss of E-cadherin , acquisition of vimentin and snail expression . In 81B-Fb cells , downregulation of EGFR , which is mediated by increased ubiquitination , and activation of downstream protein kinase B ( Akt ) , glycogen synthase kinase-beta ( GSK-3β ) signalling and upregulation of snail expression were observed compared with UMSCC81B cells . LY294002 , but not U0126 , suppressed foetal bovine serum or heregulin-β1-induced phosphorylation of Akt/GSK-3β and snail expression together with the inhibition of 81B-Fb cell motility . Furthermore , forced expression of EGFR resulted in partial restoration of gefitinib sensitivity and reversal of EMT . CONCLUSION These results suggest that EMT in the gefitinib-resistant cells is mediated by the downregulation of EGFR and compensatory activation of Akt/GSK-3β/snail pathway .\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: Many breast cancers are estrogen independent , and even in patients who initially respond to estrogen suppression therapy , the regression is often temporary . We have recently shown that antagonists of bombesin and gastrin-releasing peptide , including RC-3095 , inhibit the growth of pancreatic , colonic , and prostatic cancers in experimental animals . This effect was associated with a substantial decrease in epidermal growth factor ( EGF ) receptor levels in pancreatic and colon 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: E6-associated protein ( E6-AP ) is a dual function protein . It acts as an E3 ubiquitin-protein ligase enzyme and coactivator of steroid hormone receptors such as estrogen ( ERα ) and progesterone ( PR ) receptors . It promotes the degradation of ERα and PR through the ubiquitin-proteasome pathway . Furthermore , it has been shown that the levels of E6-AP are inversely associated with that of ERα in human breast tumors . But the role of wild-type human E6-AP and its ubiquitin-protein ligase activity in mammary tumorigenesis is still unknown . To investigate this role , the authors utilized transgenic mice lines that specifically overexpress either the wild-type human E6-AP ( E6-AP(WT) ) or the ubiquitin-protein ligase defective E6-AP that contains C833S mutation ( E6-AP(C833S) ) in the mammary gland . To further substantiate the role of E6-AP in the development of breast tumorigenesis , it was also examined the expression of E6-AP in a large cohort of human breast cancer samples . The transgenic mice that overexpress wild-type E6-AP ( E6-AP(WT) ) fail to develop mammary tumors . Unlike the E6-AP(WT) mice , the E6-AP(C833S) mice that overexpress ubiquitin-protein ligase defective E6-AP protein develop mammary hyperplasia with a median latency of 18months . These observations suggest that the inactivation of the ubiquitin-protein ligase function of E6-AP is sufficient to initiate the process of mammary tumor development . Furthermore , the data also suggests that E6-AP exerts its effects on target cells by modulating the protein levels and functions of ERα and PR . In addition , it was found in human breast cancer patients that the level of E6-AP is decreased in invasive breast tumors compared to normal breast tissue . Moreover , the authors also show that the survival patterns for E6-AP negative patients were worse compared to E6-AP positive patients . Taken together , these data suggests that E6-AP may act as a tumor suppressor in breast .\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: In mammalian cells more than 90% of double-strand breaks are repaired by NHEJ . Impairment of this pathway is associated with cell cycle arrest , cell death , genomic instability and cancer . Human diseases such as Nijmegen breakage syndrome , due to mutations in the NBS1 gene , produce defects in resection of double-strand breaks . NBS1 hypomorphic mutant mice are viable , and cells from these mice are defective in S phase and G2/M checkpoints . NBS1 polymorphisms have been associated with increased risk of breast cancer . We previously demonstrated that estradiol protected estrogen receptor ( ER)-positive ( + ) breast cancer cell lines against double-strand breaks and cell death . We now demonstrate that protection from double-strand break damage in ER+ cells is mediated via regulation by c-myc , p53 , CBP and SRC1 coactivators in intron 1 of the NBS1 gene . We concluded that NBS1 is responsible for estradiol-mediated protection from double-strand breaks in ER+ breast cancer cells .\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: Ghrelin was identified in the stomach as an endogenous ligand specific for the growth hormone secretagogue receptor ( GHS-R ) . GHS-R is found in various tissues , but its function is unknown . Here we show that GHS-R is found in hepatoma cells . Exposure of these cells to ghrelin caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1 ( IRS-1 ) , association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1 , mitogen-activated protein kinase activity , and cell proliferation . Unlike insulin , ghrelin inhibited Akt kinase activity as well as up-regulated gluconeogenesis . These findings raise the possibility that ghrelin modulates insulin activities in humans .\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: Genotoxic stress induces cell cycle arrest and DNA repair which may enable tumor cells to survive radiation therapy . Here , we defined the role of Ca(2+) signaling in the cell cycle control and survival of chronic myeloid leukemia ( CML ) cells subjected to ionizing radiation ( IR ) . To this end , K562 erythroid leukemia cells were irradiated ( 0-10 Gy ) . Tumor survival was analyzed by clonogenic survival assay and cell cycle progression via flow cytometry . Plasma membrane cation conductance was assessed by patch-clamp whole-cell recording and the cytosolic free Ca(2+) concentration ( [ Ca(2+)](i) ) was measured by fura-2 Ca(2+) imaging . Nuclear activity of Ca(2+)/calmodulin-dependent kinase II ( CaMKII ) was defined by Western blotting . In addition , the effect of IR ( 5 Gy ) on the cation conductance of primary CML cells was determined . The results indicated that IR ( 10 Gy ) induced a G(2)/M cell cycle arrest of K562 cells within 24 h post-irradiation ( p.i. ) and decreased the clonogenic survival to 0.5 % of that of the control cells . In K562 cells , G(2)/M cell cycle arrest was preceded by activation of TRPV5/6-like nonselective cation channels in the plasma membrane 1-5 h p.i. , resulting in an elevated Ca(2+) entry as evident from fura-2 Ca(2+) imaging . Similarly , IR stimulated a Ca(2+)-permeable nonselective cation conductance in primary CML cells within 2-4 h p.i. . Ca(2+) entry , into K562 cells was paralleled by an IR-induced activation of nuclear CaMKII . The IR-stimulated accumulation in G(2) phase was delayed upon buffering [ Ca(2+)](i) with the Ca(2+) chelator BAPTA-AM or inhibiting CaMKII with KN93 ( 1 nM ) . In addition , KN93 decreased the clonogenic survival of irradiated cells but not of control cells . In conclusion , the data suggest that IR-stimulated cation channel activation , Ca(2+) entry and CaMKII activity participate in control of cell cycle progression and survival of irradiated CML 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: One of the immunosuppressive effects of both ultraviolet ( UV ) light and chemical carcinogens is to deplete Langerhans cells ( LC ) from the epidermis , suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis . Retinoids such as all-trans-retinoic acid ( RA ) are natural or synthetic derivatives of vitamin A ; RA binds to nuclear receptors in the skin , effecting transcription of a wide range of genes . Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate ( TPA ) from depleting the density of LC in murine epidermis . In contrast , topical RA did not itself alter the normal LC density . RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer . Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells ( Thy-1+ dEC ) . However , the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation . The reasons for this are unclear , however , it is possible that RA does not inhibit some other immunosuppressive effect of UV light . Temarotene , a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis . Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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: Genetic and epigenetic changes in the von Hippel-Lindau ( VHL ) tumour suppressor gene are common in sporadic conventional ( clear cell ) renal cell carcinoma ( ccRCC ) . The effects on VHL expression are unknown but increased understanding may be relevant clinically , either in terms of prognosis or in therapy selection . We have examined the expression of VHL mutant RNA in 84 ccRCC tumours previously screened for mutations in genomic DNA , 56 of which contained 52 unique mutations or polymorphisms . Based on the predicted change to the primary amino acid sequence , 24 of the mutations were missense , 11 resulted in frameshifts with premature truncation , 9 resulted in immediate truncation at the site of the mutation and 2 were frameshifts which extended the reading frame beyond the normal stop codon . Nine tumours had intronic variants , including substitution of invariant residues at splice sites , deletion of nucleotides spanning the exon-intron junction , an intronic variant of unknown function and the polymorphism c.463+43A>G . Four variants were identified which were present in genomic DNA but not in mRNA . Three of these , all encoding apparent missense changes to the primary amino acid sequence , were located close to the ends of exons , reduced the strength of the splice site and function as null rather than missense variants . One nonsense variant was not detectable in mRNA but all other mutations resulting in premature truncation codons ( PTCs ) were , suggesting truncating VHL mutations may potentially generate truncated VHL protein . An intronic variant , c.341‑11T>A , previously regarded as of unknown function , is associated with an increased level of skipping of exon 2 and may , therefore , reduce production of pVHL . Our data show that the biological consequences of VHL mutations are not necessarily predictable from the sequence change of the mutation and that for the majority of VHL mutations , the potential for the generation of mutant protein exists .\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: Cancer cells preferentially metabolize glucose by aerobic glycolysis , characterized by increased lactate production . This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase , in contrast to the M1 isozyme normally expressed in differentiated cells , and it confers a proliferative advantage to tumor cells . The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons . We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues , tumor cell lines , and during terminal differentiation of muscle cells , and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms . We further show that the M1-specific exon is actively repressed in cancer-cell lines--although some M1 mRNA is expressed in cell lines derived from brain tumors--and demonstrate that the related splicing repressors hnRNP A1 and A2 , as well as the polypyrimidine-tract-binding protein PTB , contribute to this control . Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production . These findings extend the links between alternative splicing and cancer , and begin to define some of the factors responsible for the switch to aerobic glycolysis .\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: Ceramide induces cell cycle arrest and apoptotic cell death associated with increased levels of p27(kip1) . The aim of this study was to examine the effects of ceramide on p27(kip1) protein levels as a measure of cell cycle arrest and apoptosis . Results showed that ceramide increased p27(kip1) protein levels through activation of protein phosphatase 2A ( PP2A ) in PC-3 prostate cancer cells . Treatment of cells with the PP2A inhibitor okadaic acid or with PP2A-Cα siRNA inhibited ceramide-induced enhanced p27(kip1) protein expression and Akt dephosphorylation , and prevented Skp2 downregulation . Overexpression of constitutively active Akt attenuated ceramide-induced Skp2 downregulation and p27(kip1) upregulation . In addition , ceramide stimulated binding of the PP2A catalytic subunit PP2A-Cαβ to Akt as assessed by immunoprecipitation experiments , indicating that PP2A is involved in the induction of p27(kip1) via inhibition of Akt pathway . Finally , whether PP2A can regulate p27(kip1) expression independently of Akt pathway was determined . Knockdown of PP2A-Cα with siRNA reduced p27(kip1) levels in the presence of Akt inhibitor . These data reveal that PP2A is a regulator of ceramide-induced p27(kip1) expression via Akt-dependent and Akt-independent pathways .\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: DNA repair is an essential cellular process required to maintain genomic stability . Every cell is subjected to thousands of DNA lesions daily under normal physiological conditions . Ionizing radiation ( IR ) is a major DNA damaging agent that can be produced by both natural and man-made sources . A common source of radiation exposure is through its use in medical diagnostics or treatments such as for cancer radiotherapy where relatively high doses are received by patients . To understand the detailed DNA repair gene transcription response to high dose IR , gene expression exon array studies have been performed and the response to radiation in two divergent cell types , lymphoblastoid cell lines and primary fibroblasts , has been examined . These exon arrays detect expression levels across the entire gene , and have the advantage of high sensitivity and the ability to identify alternative transcripts . We found a selection of DNA repair genes , including some not previously reported , that are modulated in response to radiation . Detailed dose and time course kinetics of DNA repair transcription was conducted and results have been validated utilizing PCR methods . Alternative transcription products in response to IR were identified in several DNA repair genes including RRM2B and XPC where alternative initiation sites were found . These investigations have advanced the knowledge about the transcriptional response of DNA repair .\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 Anthracyclines have been widely used as antitumor agents , playing a crucial role in the successful treatment of many types of cancer , despite some side effects related to cardiotoxicity . New anthracyclines have been designed and tested , but the first ones discovered , doxorubicin and daunorubicin , continue to be the drugs of choice . Despite their extensive use in chemotherapy , little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines . The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis , characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene . METHODS We assessed the induction of apoptosis ( Sub-G1 ) by cosmomycin D in nucleotide excision repair-deficient fibroblasts ( XP-A and XP-C ) as well as the levels of DNA damage ( alkaline comet assay ) . RESULTS Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner , with highest apoptosis levels observed 96 h after treatment . The effects of cosmomycin D were equivalent to those obtained with doxorubicin . The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells , and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay . CONCLUSIONS Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts . Despite similar apoptosis levels , cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin . This may be related to differences in structure between cosmomycin D and doxorubicin .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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 effects of genomic changes in hepatitis B virus ( HBV ) on the occurrence of hepatocellular carcinoma ( HCC ) are still unclear , especially in relation to the genotype of HBV . In this study , we examined the effects of genomic changes in HBV of genotype C2 on the development of HCC . A total of 318 patients with HBV-associated HCC and 234 patients with chronic hepatitis B ( CHB ) were studied . All of HCC cases were diagnosed histologically and treated with surgical resection . The whole of the X , S , basal core promoter ( BCP ) and precore regions of the viral genome from sera or liver tissues were sequenced . All subjects had HBV of genotype C2 . The prevalence of the T1653 mutation in the X region and the A1896 mutation in the precore region of HBV was significantly higher in the HCC group than in the control CHB group ( 22% vs 11% , P = 0.003 ; 50% vs 23% , P &lt ; 0.001 , respectively ) . Moreover , the T1762/A1764 mutations in the BCP region in combination with either T1653 or A1896 were more common in the HCC compared with the CHB group ( BCP+X1653 : 18% vs 11% , P = 0.05 ; BCP+PC , 40% vs 15% , P &lt ; 0.001 , respectively ) . In multivariate analysis , T1653 and A1896 were revealed to be independent risk factors for HCC development . G1896A in the precore region and C1653T mutation in the X region of genotype C2 HBV are important risk factors for HCC development . Also , the A1762T/G1764A double mutation may act in synergy with C1653T to increase the risk of HCC in patients chronically infected with HBV genotype C2 .\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: Perlecan Domain V ( DV ) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells ( BECs ) following stroke . In this study , we define the specific mechanism of DV interaction with the α(5)β(1) integrin , identify the downstream signal transduction pathway , and further investigate the functional significance of resultant VEGF release . Interestingly , we found that the LG3 portion of DV , which has been suggested to possess most of DV's angio-modulatory activity outside of the brain , binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV . Additionally , we implicate DV's DGR sequence as an important element for the interaction of DV with α(5)β(1) . Furthermore , we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion . We show that DV increases the phosphorylation of ERK , which leads to subsequent activation and stabilization of eIF4E and HIF-1α . Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs . While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors , LY294002 and Akt IV . Lastly , we demonstrate that VEGF activity is critical for DV increases in BEC proliferation , as well as angiogenesis in a BEC-neuronal co-culture system . Collectively , our findings expand our understanding of DV's mechanism of action on BECs , and further support its potential as a novel stroke therapy .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;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: Arsenic trioxide ( ATO ) is a novel agent to treat acute promyelocytic leukemia ( APL ) . ATO can degrade chimeric PML-RAR proteins and induce apoptosis in various cancer cells . However , its effects on primary hematopoietic CD34+ have not been examined . In this study , we compared the effects of ATO on HL60 leukemic cells and primary umbilical cord blood ( UCB ) CD34+ cells . HL60 cells and UCB CD34+ cells were cultured with different concentrations of ATO for up to three weeks and examined for changes of cell cycle . We found that ATO ( &lt ; or = 5 microM ) caused prolongation of G1/S and G2/M phase in a dose-dependent manner . The percentage of cells in G2/M increased significantly ( from 8.6 to 53.8% ) . High-dose ATO ( &gt ; or = 25 microM ) caused non-specific cell death in HL60 cells without any changes in cell cycle . In contrast to HL60 cells , UCB CD34+ cells were more resistant to high-dose ATO and most ATO-resistant CD34+ cells remained in G0/G1 phase . Primary cells that were resistant to ATO were rich in CD34+ cells . We further show that the ATO resistance was not related to the expression of P-glycoprotein ( MDR-1 ) . Our results suggest that the resistance to ATO in primitive UCB CD34+ cells is most likely related to its cell-cycle status . These results could be useful to design treatments for non-APL malignancies and to enrich hematopoietic stem cells in clinically applicable settings .\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: MD-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa ( an oriental edible mushroom ) . Intraperitoneal ( i.p. ) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system . In this study , we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models . After oral administration , MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells ( DCs ) present in the Peyer's patch . The captured MD-Fraction was then transported to the spleen , thereby inducing the systemic immune response . Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway . The therapeutic response of orally administered MD-Fraction was associated with ( i ) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs , ( ii ) increased infiltration of the activated T cells into the tumor , and ( iii ) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells . Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer. � 2012 Wiley Periodicals , Inc .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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: INTRODUCTION A subpopulation of cancer cells , tumor-initiating cells , is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy . The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins , as well as a reduced propensity to undergo apoptosis or senescence . METHODS To test this hypothesis , we isolated CD24-/low/CD44+ tumor-initiating cells ( as mammospheres ) from MCF-7 breast cancer cells grown in adherent monolayer culture , and carried out a comprehensive comparison of cell death and DNA damage response pathways prior to and after exposure to ionizing radiation in mammospheres and monolayer MCF-7 cells . Single and double-strand break repair was measured by single-cell gel electrophoresis . The latter was also examined by phosphorylation of histone H2AX and formation of 53BP1 and Rad51 foci . Apoptosis was quantified by flow-cytometric analysis of annexin V-binding and senescence was analyzed on the basis of cellular beta-galactosidase activity . We employed the telomeric repeat amplification protocol to quantify telomerase activity . Expression of key DNA repair and cell cycle regulatory proteins was detected and quantified by western blot analysis . RESULTS Our data demonstrate that in comparison to the bulk population of MCF-7 cells ( predominantly CD24+/CD44+ ) , the MCF-7 mammosphere cells benefit from a multifaceted approach to cellular protection relative to that seen in monolayer cells , including a reduced level of reactive oxygen species , a more active DNA single-strand break repair ( SSBR ) pathway , possibly due to a higher level of expression of the key SSBR protein , human AP endonuclease 1 ( Ape1 ) , and a significantly reduced propensity to undergo senescence as a result of increased telomerase activity and a low level of p21 protein expression . No significant difference was seen in the rates of double-strand break repair ( DSBR ) between the two cell types , but DSBR in mammospheres appears to by-pass the need for H2AX phosphorylation . CONCLUSIONS Enhanced survival of MCF-7 tumor-initiating cells in response to ionizing radiation is primarily dependent on an inherent down-regulation of the senescence pathway . Since MCF-7 cells are representative of cancer cells that do not readily undergo apoptosis , consideration of senescence pathways may play a role in targeting stem cells from such tumors .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;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: p53 is a well-known transcription factor that controls cell cycle arrest and cell death in response to a wide range of stresses . Moreover , p53 regulates glucose metabolism and its mutation results in the metabolic switch to the Warburg effect found in cancer cells . Nucleotide biosynthesis is also critical for cell proliferation and the cell division cycle . Nonetheless , little is known about whether p53 regulates nucleotide biosynthesis . Here we demonstrated that p53-inducible microRNA-34a ( miR-34a ) repressed inosine 5'-monophosphate dehydrogenase ( IMPDH ) , a rate-limiting enzyme of de novo GTP biosynthesis . Treatment with anti-miR-34a inhibitor relieved the expression of IMPDH upon DNA damage . Ultimately , miR-34a-mediated inhibition of IMPDH resulted in repressed activation of the GTP-dependent Ras signaling pathway . In summary , we suggest that p53 has a novel function in regulating purine biosynthesis , aided by miR-34a-dependent IMPDH repression .\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: Pterostilbene , a polyphenolic compound present in grapes and other fruits , has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types . We found that pterostilbene at the IC90 concentration of 44 �M inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells . Treatment with pterostilbene resulted in a transient accumulation of cells in the G0/G1-cell cycle phase followed by the S-phase arrest . Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential , phosphatidylserine externalization and internucleosomal DNA fragmentation . Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia .\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: The polycomb group family protein BMI-1 is overexpressed by and functions as an oncogene in many different human cancers . We have previously shown that BMI-1 promotes the tumorigenicity of Ewing sarcoma family tumors ( ESFTs ) and that this is mediated independently of CDKN2A repression . In this study , we have discovered that high levels of BMI-1 confer resistance to contact inhibition in ESFT cells . Using stable retroviral transduction , we evaluated the consequences of BMI-1 knockdown on the growth of CDKN2A wild-type and mutant ESFT cells in subconfluent and confluent conditions . Although knockdown of BMI-1 had no effect on proliferation in low-density cultures , at high cell densities it resulted in cell cycle arrest and death . The normal cell contact inhibition response is mediated , in large part , by the recently described Hippo pathway which functions to inhibit cell proliferation and promote cell death by inactivating the Yes-Associated Protein ( YAP ) . Significantly , we found that YAP levels , activity and expression did not diminish in confluent ESFT cells that expressed high levels of BMI-1 . In contrast , YAP expression and nuclear localization were reduced in confluent BMI-1 knockdown cells suggesting that silencing of BMI-1 restored contact inhibition by restoring normal activation of the Hippo-YAP growth-suppressor pathway . Importantly , knockdown of YAP in ESFT cells resulted in profound inhibition of cell proliferation and anchorage-independent colony formation suggesting that stabilization and continued expression of YAP is critical for ESFT growth and tumorigenicity . Together , these studies reveal a previously unrecognized link between BMI-1 , contact inhibition and the Hippo-YAP pathway and suggest that resistance to contact inhibition in BMI-1 overexpressing cancer cells may be in part a result of Hippo inhibition and aberrant stabilization of YAP .\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 androgen receptor ( AR ) plays a central role in prostate cancer progression to the castration-resistant ( CR ) lethal state . L-Dopa decarboxylase ( DDC ) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells , where it may enhance AR activity . Here , we hypothesize that the DDC enzymatic inhibitor , carbidopa , can suppress DDC-coactivation of AR and retard prostate tumor growth . Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen ( PSA ) mRNA levels . Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays . The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells ( stably expressing AR ) . In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts , inducibly overexpressing DDC , were reverted to control levels with carbidopa administration . In castrated mice , treating LNCaP tumors , expressing endogenous DDC , with carbidopa delayed progression to the CR state from 6 to 10 weeks , while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold , respectively . Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors , decrease serum PSA , reduce tumor growth and delay CR progression . Since carbidopa is clinically approved , it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression .\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: BACKGROUND &amp ; OBJECTIVE Altered cell adhesion has a critical role in the development of epithelial cancers . E-cadherin act on the maintenance of cell-cell adhesion and its function was thought to be regulated by associated cytoplasmic proteins , such as alpha-catenin and beta-catenin . This study was designed to examine the expression of beta-catenin in gastric carcinoma and to determine the relationship between tumor characteristics and survival . METHODS Immunohistochemical staining of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was demonstrated in 43.2% and 44.6% of tumors respectively . Up to 63% of tumors stained abnormally for one or two components of the cadherin-catenin complex ( beta-catenin , E-cadherin ) . Abnormal beta-catenin and E-cadherin staining occurred more frequently in poor differentiated tumor than in good differentiated tumors ( P &lt ; 0.005 , respectively ) . There was a significant correlation between abnormal beta-catenin expression and depth of invasion(P &lt ; 0.025 ) . Moreover , abnormal beta-catenin expression was more frequent in tumors with positive lymph node metastasis ( 45/84 , 53.6% ) and distance metastasis(21/31 , 67.7% ) than in tumors without lymph node metastasis ( 19/64 , 29.7% ) ( P &lt ; 0.005 ) and distance metastasis ( 43/117 , 36.8% ) ( P &lt ; 0.005 ) . A survival advantage was noted in tumors retaining normal membranous expression of beta-catenin , independent of type , grade , or stage ( P &lt ; 0.005 ) . CONCLUSIONS Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma . The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker .\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: Colorectal tumors are continuously exposed to an inflammatory environment , which together with mitogenic signals sustain several cancer hallmarks . Nuclear factor-kappa B ( NFκB ) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with increased risk of colorectal cancer ( CRC ) development , and/or a rapidly progressing disease . In this study , 348 CRC cases and 806 randomly selected healthy individuals from southeastern Sweden were examined with regard to seven polymorphisms in NFκB pathway-associated genes . Log-rank-tests and Cox proportional hazard regression analysis examined the association between the polymorphisms and CRC-specific survival , whereas chi-square tests and logistic regression analysis were used to test for associations between the polymorphisms and CRC susceptibility . Gene expression and loss of heterozygosity analyses of TNFAIP3 were carried out in a subset of tumors to assess its role as a tumor suppressor in CRC . Heterozygous and polymorphic TNFAIP3 ( rs6920220 ) , heterozygous NLRP3 ( Q705K ) and polymorphic NFκB -94 ATTG ins/del genotypes were found to be associated with poorer survival in patients diagnosed with invasive CRC ( aHR = 5.2 , 95% CI : 2.5-10.9 , P &lt ; 0.001 ) . TNFAIP3 mRNA levels were significantly decreased in tumors compared with adjacent non-neoplastic mucosa ( P &lt ; 0.0001 ) and loss of heterozygosity of 6q23.3 ( TNFAIP3 ) was detected in 17% of cases , whereas only 2.5% of the investigated specimens displayed TNFAIP3 gene mutations . We propose that TNFAIP3 ( rs6920220 ) , NLRP3 ( Q705K ) and NFκB -94 ATTG ins/del polymorphisms are associated with poor survival in patients with advanced CRC and may be used as prognostic markers . Experimental results indicate that TNFAIP3 may act as a tumor suppressor in CRC .\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: AIM : To explore the inhibitory effect of sulfated polysaccharide from Masson pine ( Pinus massoniana ) pollen ( SPPM60 ) on G(2)/M phase of human liver cancer HepG2 cells and its mechanism . METHODS : The proliferation rate of HepG2 cells was evaluated by methyl thiazolyl tetrazolium ( MTT ) colorimetric assay . The cycles of HepG2 cells were measured by flow cytometry when 200μg/ml concentration of SPPM60 was adopted , the expression of the genes related to cell cycle was detected by real-time PCR . RESULTS : SPPM60 inhibited the proliferation of HepG2 cells and the inhibition rate was elevated with increase of SPPM60 concentration . After treatment with 200μg/ml of SPPM60 , the percentage of S phase cells was decreased , but that of G(2)/M phase was significantly increased ( 72h vs control : 32.96�0.33% vs 18.59�0.04% , 3.44�0.05% vs 18.30�0.08% , P<0.01 ) . The results of real-time PCR showed that SPPM60 could down-regulate the mRNA levels of CDK1 and CyclinB ( P<0.01 ) , and up-regulate the expression of p53 and p21 ( P<0.05 ) . CONCLUSION : SPPM60 causes arrest of HepG2 cells at G(2)/M phase , and the mechanism is related to the down-regulation of CDK1 and CyclinB and up-regulation of p53 and p21 expression .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;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 effect of peptides released during the fermentation of milk on the humoral immune system and on fibrosarcoma growth was studied . Lactobacillus helveticus was able to release peptidic compounds during milk fermentation due to its high proteolytic activity , as was shown by the degree of proteolysis and size-exclusion HPLC elution profiles . Three fractions of these compounds were separated and fed to mice during different periods ( 2 , 5 , and 7 d ) . The humoral immune response was assessed by following the number of IgA-secreting cells , and the antitumor activity was monitored by studying the regression of subcutaneously implanted fibrosarcomas . Feeding during 2 and 7 d with the medium-sized fraction ( Fraction II ) significantly increased the IgA-producing cells in the intestines , whereas feeding with the large compound fraction ( Fraction I ) during 5 d and the small compound fraction ( Fraction III ) during all three feeding periods provided similar increases . A double dose of Fraction II showed the highest IgA-producing cell count . The increase by Fraction III was shown to be caused by the presence of L-Tryptophan . Fraction II significantly decreased the size of fibrosarcoma when previously fed during 7 d , and feeding with Fraction I during 5 d decreased significantly its size after 35 d of growth . Although the mechanisms by which lactic acid bacteria enhance the immune system are not clear , this study clearly shows that bioactive compounds released in fermented milks contribute to the immunoenhancing and antitumor properties of these products . The release of bioactive peptides by lactic acid bacteria can have important implications on the modulation of the cellular immune response .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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: Onions ( Allium cepa L. ) are widely used in the food industry for its nutritional and aromatic properties . Our studies showed that ethyl acetate extract of onion ( EEO ) had potent inhibitory effects on animal fatty acid synthase ( FAS ) , and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells . Furthermore , this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids , the final product of FAS catalyzed synthesis . These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS . We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes , which was also related to its inhibition of intracellular FAS activity . Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers , these findings suggested that onion might be useful for preventing obesity-related malignancy .\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: Clear cell renal cell carcinoma ( ccRCC ) is the most common pathological subtype of kidney cancer . Here , we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease . One of the most potent survival regulators , the monocarboxylate transporter MCT4 ( SLC16A3 ) , impaired ccRCC viability in all eight ccRCC lines tested and was the seventh most overexpressed gene in a meta-analysis of five ccRCC expression datasets . MCT4 silencing impaired secretion of lactate generated through glycolysis and induced cell cycle arrest and apoptosis . Silencing MCT4 resulted in intracellular acidosis , and reduction in intracellular ATP production together with partial reversion of the Warburg effect in ccRCC cell lines . Intra-tumoural heterogeneity in the intensity of MCT4 protein expression was observed in primary ccRCCs . MCT4 protein expression analysis based on the highest intensity of expression in primary ccRCCs was associated with poorer relapse-free survival , whereas modal intensity correlated with Fuhrman nuclear grade . Consistent with the potential selection of subclones enriched for MCT4 expression during disease progression , MCT4 expression was greater at sites of metastatic disease . These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;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: BACKGROUND The presence of distant metastases from colorectal cancer ( CRC ) does not preclude curative treatment . Early detection of pulmonary metastases at a potentially curable stage could improve survival . The aim of the present study was to assess the prognostic significance of commonly reported clinicopathologic features to identify high-risk patients who would likely benefit from more intensive chest surveillance for pulmonary metastases . MATERIAL AND METHOD A total of 351 consecutive patients , with surgical stages I-III colorectal cancer , who underwent curative resection at Phramongkutklao hospital from 1999 to 2005 , were followed regularly according to the established guidelines with routine physical examination , serum carcinoembryonic antigen ( CEA ) and colonoscopic surveillance . Imaging studies for detecting metastases were computed tomography ( CT ) , plain film radiography , and ultrasonograpy . Clinical and pathologic features were analyzed for their association with pulmonary metastasis . RESULTS There were 145 patients who had been operated for longer than five years after curative intent surgery . Of these , nineteen patients were lost to follow-up or died from other causes that were unrelated to colorectal cancer . Pulmonary metastases were detected in 26 patients by either CXR or CT scan . Median time to pulmonary metastasis was 19 months ( 95 percent CI , 12-35 ) . According to an univariate analysis , with log-rank test , identified four factors associated with pulmonary metastasis : Tumor stage T4 , Nodal stage N2 , elevation of serum CEA &gt ; 3.4 ng/ml and presence of lymphovascular invasion(LVI) . According to a multivariate analysis , with Cox regression , found an elevation of serum CEA &gt ; 3.4 ng/ml which was an independent factor that was significantly associated with pulmonary metastasis ( Hazard ratio ( HR ) , 8.9 ; 95 percent CI , 3.6-22 ; p &lt ; 0.01 ) . The present study revealed that 50 percent of patients who had more than one of these risk factors would eventually develop pulmonary metastases . CONCLUSION An elevation of serum CEA &gt ; or = 3.4 ng/ml was found as an independent factor that was significantly associated with pulmonary metastasis whereas tumor stage T4 , nodal stage N2 and presence of lymphovascular invasion ( LVI ) were not independent clinicopathologic features associated with subsequent pulmonary metastases . Chest CT scan has greater sensitivity than chest radiography in detection of pulmonary metastasis and should be considered as an imaging study of choice for intensive chest surveillance for patients who had more than one of these risk factors .\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: Gastrin stimulates the growth of pancreatic cancer cells through the activation of the cholecystokinin-B receptor ( CCK-BR ) , which has been found to be overexpressed in pancreatic cancer . In this study , we proposed that the CCK-BR drives growth of pancreatic cancer ; hence , interruption of CCK-BR activity could potentially be an ideal target for cancer therapeutics . The effect of CCK-BR downregulation in the human pancreatic adenocarcinoma cells was examined by utilizing specific CCK-BR-targeted RNA interference reagents . The CCK-BR receptor expression was both transiently and stably downregulated by transfection with selective CCK-BR small-interfering RNA or short-hairpin RNA , respectively , and the effects on cell growth and apoptosis were assessed . CCK-BR downregulation resulted in reduced cancer cell proliferation , decreased DNA synthesis , and cell cycle arrest as demonstrated by an inhibition of G(1) to S phase progression . Furthermore , CCK-BR downregulation increased caspase-3 activity , TUNEL-positive cells , and decreased X-linked inhibitor of apoptosis protein expression , suggesting apoptotic activity . Pancreatic cancer cell mobility was decreased when the CCK-BR was downregulated , as assessed by a migration assay . These results show the importance of the CCK-BR in regulation of growth and apoptosis in pancreatic cancer . Strategies to decrease the CCK-BR expression and activity may be beneficial for the development of new methods to improve the treatment for patients with pancreatic cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;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: It is well established that hyperplasia and decreased apoptosis of airway smooth muscle cells ( ASMCs ) play an important role in the asthmatic airway remodeling . Tumor suppressor PTEN gene with phosphatase activity plays an important regulatory role in embryonic development , cell proliferation , and apoptosis , cell cycle regulation , migration ( invasion ) of the cytoskeleton . We hypotheses that PTEN gene could affect the growth and viability of ASMCs through the regulation of PI3K/Akt , MAPK , and cell cycle-related gene expression . We constructed a recombinant adenovirus to transfect ASMCs . Cells were divided into the overexpression of PTEN gene group ( Ad-PTEN-GFP ) , negative control group ( Ad-GFP ) , and blank control group ( DMEM ) . The cell apoptosis of ASMCs were evaluated by Hoechst-33342 staining and PE-7AAD double-labeled flow cytometry . The cell cycle distribution was observed by flow cytometry with PI staining . The expression of PTEN , p-Akt , total-Akt , p-ERK1/2 , total-ERK1/2 , cleaved-Caspases-3 , Caspases-9 , p21 , and Cyclin D1 were tested by the Western blotting . Our study revealed that overexpression of PTEN gene did not induce apoptosis of human ASMCs cultured in vitro . However , overexpression of PTEN inhibited proliferation of human ASMCs cultured in vitro and was associated with downregulation of Akt phosphorylation levels , while did not affect ERK1/2 phosphorylation levels . Moreover , overexpression of PTEN could induce ASMCs arrested in the G0/G1 phase through the downregulation of Cyclin D1 and upregulation of p21 expressions .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;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: Triggering tumor necrosis factor receptor-1 ( TNFR1 ) induces apoptosis in various cell lines . In contrast , stimulation of TNFR1 in L929sA leads to necrosis . Inhibition of HSP90 , a chaperone for many kinases , by geldanamycin or radicicol shifted the response of L929sA cells to TNF from necrosis to apoptosis . This shift was blocked by CrmA but not by BCL-2 overexpression , suggesting that it occurred through activation of procaspase-8 . Geldanamycin pretreatment led to a proteasome-dependent decrease in the levels of several TNFR1-interacting proteins including the kinases receptor-interacting protein , inhibitor of kappa B kinase-alpha , inhibitor of kappa B kinase-beta , and to a lesser extent the adaptors NF-kappaB essential modulator and tumor necrosis factor receptor-associated factor 2 . As a consequence , NF-kappa B , p38MAPK , and JNK activation were abolished . No significant decrease in the levels of mitogen-activated protein kinases , adaptor proteins TNFR-associated death domain and Fas-associated death domain , or caspase-3 , -8 , and -9 could be detected . These results suggest that HSP90 client proteins play a crucial role in necrotic signaling . We conclude that inhibition of HSP90 may alter the composition of the TNFR1 complex , favoring the caspase-8-dependent apoptotic pathway . In the absence of geldanamycin , certain HSP90 client proteins may be preferentially recruited to the TNFR1 complex , promoting necrosis . Thus , the availability of proteins such as receptor-interacting protein , Fas-associated death domain , and caspase-8 can determine whether TNFR1 activation will lead to apoptosis or to necrosis .\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: XRCC4 , in association with DNA ligase IV , is thought to play a critical role in the ligation of two DNA ends in DNA double-strand break ( DSB ) repair through non-homologous end-joining ( NHEJ ) pathway . In the present study , we captured radiation-induced chromatin-recruitment of XRCC4 by biochemical fractionation using detergent Nonidet P-40 . A subpopulation of XRCC4 changed into a form that is resistant to the extraction with 0.5% Nonidet P-40-containing buffer after irradiation . This form of XRCC4 was liberated by micrococcal nuclease treatment , indicating that it had been tethered to chromatin DNA . This chromatin-recruitment of XRCC4 could be seen immediately ( &lt ; 0.1 hr ) after irradiation and remained up to 4 hr after 20 Gy irradiation . It was seen even after irradiation of small doses , i.e. , 2 Gy , but the residence of XRCC4 on chromatin was very transient after 2 Gy irradiation , returning to near normal level in 0.2-0.5 hr after irradiation . The chromatin-bound XRCC4 represented only approximately 1% of total XRCC4 molecules even after 20 Gy irradiation and the quantitative analysis using purified protein as the reference suggested that only a few XRCC4-DNA ligase IV complexes were recruited to each DNA end . We further show that the chromatin-recruitment of XRCC4 was not attenuated by wortmannin , an inhibitor of DNA-PK , or siRNA-mediated knockdown of the DNA-PK catalytic subunit ( DNA-PKcs ) , indicating that this process does not require DNA-PKcs . These results would provide us with useful experimental tools and important insights to understand the DNA repair process through NHEJ pathway .\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: Mutations in the Nf2 tumor suppressor gene lead to tumor formation in humans and mice and cellular overproliferation phenotypes in Drosophila . The Nf2 encoded protein , merlin , shares close sequence similarity in its amino terminus to members of the band 4.1 family of membrane-cytoskeletal linkers . Similarities between merlin and this family suggest a role for merlin in regulating cytoskeletal function . However , the mechanism of the tumor suppressing activity of merlin is not yet understood . Mutational analysis of Nf2 in flies has led to the identification of a dominant-negative allele , which harbors mutations in the amino terminus of the protein . Here , we report that expression of a murine analog of this amino-terminal mutant of Nf2 leads to complete transformation of NIH3T3 fibroblasts in culture . Cells that express this Nf2 mutant allele display disruptions of the actin cytoskeleton , lack of contact inhibition of growth , and anchorage-independent growth . Finally , fibroblasts that express this mutant Nf2 allele form tumors when injected into nude mice .\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: MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion . The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined . Previous reports have suggested that MDSC may contribute to Treg induction in cancer . Herein , we provide evidence that tumor-induced gr-MDSCs , endowed with the potential of suppressing conventional T Lc , surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs . Furthermore , gr-MDSCs impede the proliferation of nTregs without , however , affecting FoxP3 expression . Suppression of iTreg differentiation from na�ve CD4(+) cells by gr-MDSC occurs early in the polarization process , requires inhibition of early T cell activation , and depends on ROS and IDO but does not require arginase 1 , iNOS , NO , cystine/cysteine depletion , PD-1 and PD-L1 signaling , or COX-2 . These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;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: Cigarette smoking is implicated in numerous diseases , including emphysema and lung cancer . The clinical expression of lung disease in smokers is not well explained by currently defined variations in gene expression or simple differences in smoking exposure . Alveolar macrophages play a critical role in the inflammation and remodeling of the lung parenchyma in smoking-related lung disease . Significant gene expression changes in alveolar macrophages from smokers have been identified . However , the mechanism for these changes remains unknown . One potential mechanism for smoking-altered gene expression is via changes in cytosine methylation in DNA regions proximal to gene-coding sequences . In this study , alveolar macrophage DNA from heavy smokers and never smokers was isolated and methylation status at 25,000 loci determined . We found differential methylation in genes from immune-system and inflammatory pathways . Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune-system and inflammatory pathways . A significant number of genes with smoking-altered mRNA expression had inverse changes in methylation status . One gene highlighted by this data was the FLT1 , and further studies found particular up-regulation of a splice variant encoding a soluble inhibitory form of the receptor . In conclusion , chronic cigarette smoke exposure altered DNA methylation in specific gene promoter regions in human alveolar macrophages .\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: Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment . This study investigates the hypothesis that manganese superoxide dismutase ( MnSOD ) regulates cellular redox flux and glucose consumption during the cell cycle . A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts , which was absent in MnSOD homozygous knockout fibroblasts . Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells , which was associated with an increase in glucose and oxygen consumption , and a decrease in MnSOD activity . Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine ( 68 , 89 , 122 , and 202 ) and arginine ( 197 and 216 ) residues . MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD . Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site . Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide , a negatively charged substrate . These results support the hypothesis that MnSOD regulates a \" metabolic switch \" during progression from quiescent through the proliferative cycle . We propose MnSOD as a new molecular player contributing to the Warburg effect .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;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: Bulky DNA adducts are considered a potential biomarker of cancer risk . In this study , the association between various lifestyle , environmental , and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort . At enrollment , blood samples were collected and information on lifestyle , including dietary and smoking habits , obtained . Previously , bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort . Of these 500 individuals , data on 375 individuals were included in this study , excluding 125 cases , which developed lung cancer within the first 3 yr after blood sampling . Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined . Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses . Women tended to have higher adduct levels than men . Living in central Copenhagen and surface darkness of fried meat and fish were associated with quantitative higher adduct levels . No significant associations were found between dietary factors or smoking and DNA adduct levels . Further , the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels . Overall , our study showed only few associations between dietary , environmental , and genetic factors and levels of bulky DNA adducts measured in peripheral leukocytes in a general Danish population .\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 Prostate cancer ( PCa ) progression is often associated with transactivation of the androgen receptor ( AR ) by endogenous hormones/growth factors . One such factor affecting growth , proliferation , and apoptostis ( pro-/anti- ) in various cancers is the adipokine leptin . This research studied leptin-induced signaling and apoptosis in androgen sensitive ( LNCaP , PC3/AR ) and insensitive ( PC3 , DU145 ) PCa cell lines . METHODS Signaling was studied by immunoblotting in cells overexpressing leptin receptors ( LRb ) , Janus kinase 2 ( JAK2 ) , and kinase negative-HER2-YFP cDNAs . Apoptosis was measured by immunoblotting of apoptotic proteins and by Hoechst staining of condensed DNA . RESULTS Leptin rapidly induced activation of JAK2 , STAT3 , and MAPK ( ERK1/2 ) signaling cascades ; it may also induce HER2 transactivation via leptin-induced phospho-JAK2 . Leptin was then shown to exert clear pro-apoptotic effects , increasing levels of caspase 3 , cleavage of its substrate , poly ( ADP-ribose ) polymerase ( PARP ) to cleaved PARP(89) , levels of CK 18 , a cytoskeletal protein formed during apoptosis , and DNA condensation . Kinase inhibitors indicated that leptin-induced apoptosis is probably mediated by balanced activation of JAK2/STAT3 , p38 MAPK , and PKC pathways in PCa cells . A human leptin mutein LRb antagonist , L39A/D40A/F41A , fully inhibited leptin-induced phosphorylation of JAK2 , ERK1/2 , and Akt/PKB , and partially abrogated effects on apoptotic proteins . In LNCaP and PC3/AR cells , leptin increased AR protein levels in correlation with raised apoptotic markers . Thus , AR may mediate , at least partly , the leptin-induced apoptotic response . CONCLUSIONS Leptin can clearly induce apoptosis in human PCa cell lines . These findings could lead to development of new leptin agonists with enhanced pro-apoptotic effects and targeted for use in human PCa .\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: Food-derived heterocyclic aromatic amines ( HCAs ) have proved to be carcinogenic in both rodents and nonhuman primates . Two different metabolic pathways are suggested for the metabolic activation of HCA . The hepatic pathway proceeds via a two-step process involving N-hydroxylation by cytochrome P4501A2 and subsequent O-acetylation by N-acetyltransferase-2 . An alternative pathway may be of particular interest in extrahepatic tissues and proceeds via one-electron oxidation catalyzed by prostaglandin H synthase ( PHS ) , rendering free-radical metabolites . In this study , we investigated the metabolic activation of two HCAs , 2-amino-3-methylimidazo[4,5-f]quinoline ( IQ ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , by two different enzyme systems in vitro , generating different primary and secondary reactive metabolites . Rat liver S9 mix and PHS were used as the activating system and represent the hepatic and extrahepatic pathways , respectively . Electron-spin resonance spectroscopy showed that both IQ and PhIP exerted inhibiting effects on PHS-mediated formation of hydroxyl radicals during the conversion of arachidonic acid to prostaglandins . Evidence for the formation of HCA free radicals was presented in an indirect way by the formation of glutathione-derived thiyl radicals , with purified PHS as the activating system . Activation by S9 mix did not result in the formation of detectable radical metabolites , showing that the two metabolic routes primarily led to the formation of different metabolites . In all electron-spin resonance experiments , IQ appeared to be more effective than PhIP . In contrasts , DNA adduct analysis by means of ( 32)P-postlabeling showed similar adduct patterns for S9 and PHS in single-stranded and double-stranded salmon testes DNA after incubation with PhIP , indicating the ultimate formation of a common reactive intermediate . For IQ , activation by PHS led to an additional adduct spot that was not present after S9 activation . Furthermore , activation of IQ resulted in higher adduct levels compared with PhIP for both activation pathways . Overall , adduct levels were higher in single-stranded DNA than double-stranded DNA . Our results showed that the hepatic and extrahepatic pathways resulted in different primary metabolites , while the ultimate formation of a similar reactive intermediate for PhIP , possibly an arylnitrenium ion , suggested that both pathways could play an important role in the onset of 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: Construction industry workers are exposed to many known carcinogens in their complex occupational environment . Since there are no past studies on genotoxicity among this group in the Indian subcontinent , workers engaged in different construction sites at Coimbatore , Tamil Nadu , India , were assessed here . We enrolled 96 workers and 68 control subjects with similar mean age , smoking , tobacco chewing prevalence and alcohol consumption , for analysis of DNA damage in blood leucocytes by micronucleus ( MN ) and comet assays . DNA repair inhibition was also analyzed by assessing the XPD gene . Construction workers showed a significant increase in MN and comet tail length compared to controls with adjustment for smoking habits , tobacco chewing , alcohol consumption and years of exposure ( P<0.05 ) . The results indicated that chronic occupational exposure to cement during construction work could lead to increased levels of DNA damage and repair inhibition .\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 damage checkpoints arrest cell cycle progression to facilitate DNA repair . The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance . While activation of DNA damage checkpoints has been studied extensively , molecular mechanisms involved in sustaining and ultimately inactivating cell cycle checkpoints are largely unknown . Here , we explored feedback mechanisms that control the maintenance and termination of checkpoint function by computationally identifying an evolutionary conserved mitotic phosphorylation network within the DNA damage response . We demonstrate that the non-enzymatic checkpoint adaptor protein 53BP1 is an in vivo target of the cell cycle kinases Cyclin-dependent kinase-1 and Polo-like kinase-1 ( Plk1 ) . We show that Plk1 binds 53BP1 during mitosis and that this interaction is required for proper inactivation of the DNA damage checkpoint. 53BP1 mutants that are unable to bind Plk1 fail to restart the cell cycle after ionizing radiation-mediated cell cycle arrest . Importantly , we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells . Thus , a mitotic kinase-mediated negative feedback loop regulates the ATM-Chk2 branch of the DNA damage signaling network by phosphorylating conserved sites in 53BP1 and Chk2 to inactivate checkpoint signaling and control checkpoint duration .\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 pancreatic stellate cells ( PSCs ) have complex roles in pancreas , including tissue repair and fibrosis . PSCs surround ATP releasing exocrine cells , but little is known about purinergic receptors and their function in PSCs . Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability . The number of PSCs isolated from wild type ( WT ) mice was 50% higher than those from the Pfizer P2X7 receptor knock out ( KO ) mice . The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs , while KO PSCs only expressed truncated versions of the receptor . In culture , the proliferation rate of the KO PSCs was significantly lower . Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs , indicating importance of endogenous ATP . Exogenous ATP had a two-sided effect . Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM . At high ATP concentration ( 5 mM ) , WT PSCs , but not the KO PSCs died . The intracellular Ca(2+) signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120 . The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations . This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death , and therefore might be potential targets for treatments of pancreatic fibrosis and cancer .\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: A comparative study was undertaken between cancer of the uterine cervix ( n = 50 ) and female breast cancer ( n = 50 ) with reference to the expression of c-erbB-2 oncoprotein ( HER-2/neu ) and that of epidermal growth factor receptor ( EGF-R ) , both being highly homologous structurally . Expressions of EGF-R and c-erbB-2 oncoprotein were viewed in breast and cervical cancer tissues by immunochemical staining . Cervical cancer cases showed much higher expression of EGF-R which also revealed significant association with the expression of c-erbB-2 oncoprotein and tumour grading . Among breast cancer cases , over-expression of EGF-R correlated significantly with metastasis of lymph node ; and expression of c-erbB-2 oncoprotein showed a significant relationship with histological grading of the tumour . Moreover , an association was noticed between the tumour grade and the concomitant immuno positive expression of EGF-R and c-erbB-2 . Our study revealed an existence of a conflicting pattern in the expression of EGF-R and c-erbB-2 oncoprotein between carcinomas of the breast and uterine cervix .\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: A new cell line of human ovarian clear cell adenocarcinoma ( CCC ) , TU-OC-1 , was established and characterized . The cells showed a polygonal-shaped morphology and grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle . The chromosome numbers ranged from 64 to 90 . A low rate of proliferation was observed , similar to other CCC cell lines tested ( OVTOKO , RMG-I , and OVAS ) , and the doubling time was 38.4h . The respective IC50 values of cisplatin and paclitaxel were 12.2μM and 58.3nM . Mutational analysis revealed that TU-OC-1 cells harbored a PIK3CA mutation at codon 542 ( E542K ) in exon 9 , which is a mutation hot spot on this gene . We observed that phosphorylated Akt protein was overexpressed in TU-OC-1 cells by western blot analysis . Heterotransplantation to nude mice produced tumors that reflected the original . This cell line may be useful to study the chemoresistant mechanisms of CCC and contribute to novel treatment strategies .\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: Glioblastoma is one of the most lethal and common malignant human brain tumors , with aggressive proliferation and highly invasive properties . Honokiol derived from Magnolia officinalis is able to cross the blood-brain barrier ( BBB ) and the blood-cerebrospinal fluid barrier ( BCSFB ) , suggesting a strong possibility that it could be an effective drug for the treatment of brain tumors , including glioblastoma . Thus , we investigated the effects of honokiol on the expression of adhesion molecules in TNF-α-stimulated endothelial cells , and cancer growth and invasion were determined in T98G human glioblastoma cells . Honokiol dose-dependently inhibited the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) in human umbilical vein endothelial cells ( HUVECs ) stimulated with TNF-α for 6 h . Pretreatment with honokiol significantly reduced the adhesion of T98G cells to HUVECs . Moreover , honokiol inhibited the invasion of T98G cells , suggesting that honokiol has an anti-metastatic effect . In addition , honokiol increased the cytotoxicity of T98G cells in a dose- and time-dependent manner as assayed by MTT . TUNEL assay showed that honokiol significantly induced apoptosis in T98G cells at doses of 10 �M or more . The induction of apoptotic cell death was mediated by the downregulation of the anti-apoptotic protein Bcl-2 and the upregulation of the pro-apoptotic protein Bax . Taken together , the results of this study suggest that honokiol exerts an anticancer effect by preventing metastasis and inducing apoptotic cell death of brain tumor cells .\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: Retinoic acid ( RA ) has been believed to be an anticancer drug for a long history . However , the molecular mechanisms of RA actions on cancer cells remain diverse . In this study , the dose-dependent inhibition of RA on DU145 cell proliferation was identified . Interestingly , RA treatment triggered p35 cleavage ( p25 formation ) and Cdk5 overactivation , and all could be blocked by Calpain inhibitor , Calpeptin ( CP ) . Subsequently , RA-triggered DU145 apoptosis detected by sub-G1 phase accumulation and Annexin V staining could also be blocked by CP treatment . Furthermore , RA-triggered caspase 3 activation and following Cdk5 over-activation were destroyed by treatments of both CP and Cdk5 knockdown . In conclusion , we report a new mechanism in which RA could cause apoptosis of androgen-independent prostate cancer cells through p35 cleavage and Cdk5 over-activation . This finding may contribute to constructing a clearer image of RA function and bring RA as a valuable chemoprevention agent for prostate cancer patients .\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 aberrant activation of sonic hedgehog ( SHH ) pathway contributes to initiation and progression of various malignancies . However , the roles and underlying mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer have not been well understood . In this study , we found that SHH signaling was activated and correlated with invasion and metastasis in hepatocellular carcinoma ( HCC ) . Enhanced SHH signaling by recombinant human SHH N-terminal peptide ( rSHH-N ) promoted hepatoma cell adhesion , migration and invasion , whereas blockade of SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma cell adhesion , migration and invasion . Furthermore , matrix metalloproteinase ( MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated by rSHH-N and SHH signaling inhibitor , respectively . The rSHH-N-mediated hepatoma cell migration and invasion was blocked by MMP-specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9 . In addition , phosphorylations of AKT and focal adhesion kinase ( FAK ) were increased and decreased by rSHH-N and SHH signaling inhibitor , respectively . Further investigations showed that activation of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9 , cell migration and invasion . Finally , we found that SHH protein expression was positively correlated with phosphorylatd FAK Tyr397 , phosphorylatd AKT Ser473 , MMP-2 and MMP-9 protein expressions in HCC samples . Taken together , our findings suggest that SHH pathway induces cell migration and invasion through FAK/AKT signaling-mediated MMP-2 and MMP-9 production and activation in liver 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: The omega-3 long chain polyunsaturated fatty acids , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , elicit antiproliferative effects in cancer cell lines and in animal models . Dietary DHA and EPA can be converted to their ethanolamine derivatives , docosahexaenoyl ethanolamine ( DHEA ) and eicosapentaenoyl ethanolamine ( EPEA ) , respectively ; however , few studies are reported on their anticancer activities . Here , we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells . Since DHA and EPA are ligands of Peroxisome Proliferator-Activated Receptor ( PPAR ) γ , we sought to determine whether PPARγ may also mediate DHEA and EPEA actions . In MCF-7 cells , both compounds enhanced PPARγ expression , stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN , resulting in the inhibition of AKT-mTOR pathways . Besides , DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction . We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining . Finally , we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor . In summary , our data show that the two omega-3 ethanolamines exert antiproliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents . J. Cell . Physiol. © 2012 Wiley Periodicals , Inc .\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: We examined how well the human papillomavirus ( HPV ) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer : the Asian-American E6 variant ( AAE6 ) . This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant , as evidenced by independent epidemiological data . Using cell culture and cell-based functional assays , we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant . The ability to immortalize and transform primary human foreskin keratinocytes ( PHFKs ) to acquire resilient phenotypes and the ability to promote cell migration were evaluated . The immortalization capability was assayed based on population doublings , number of passages , surpassing mortality stages 1 and 2 , human telomerase reverse transcriptase ( hTERT ) expression , and the ability to overcome G(1) arrest via p53 degradation . Transformation and migration efficiency were analyzed using a combination of functional cell-based assays . We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs , although AAE6 was more potent in doing so . The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype . Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer , as evidenced by a superior immortalization , transformation , and metastatic potential .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;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: To determine the threshold dose of β-Naphthoflavone ( BNF ) that induces hepatocellular tumor promoting effects , reactive oxygen species ( ROS ) generation and thiobarbituric acid-reactive substance ( TBARS ) formation , and drug-metabolizing enzymes that protect against ROS generation , two-stage liver carcinogenesis model was used . Partial hepatectomized rats ( n = 11 to 12 ) were fed diets containing 0 , 0.03 , 0.06 , 0.125 or 0.25% BNF for 6 weeks after an intraperitoneal injection of N-diethylnitrosamine ( DEN ) to initiate hepatocarcinogenesis . Histopathologically , glutathione S-transferase placental form ( GST-P)-positive foci significantly increased in rats given 0.25% BNF . No marked changes in ROS production and TBARS contents were observed between the BNF treated and DEN alone groups . Real-time RT-PCR showed that the expression of Cyp1a1 , Cyp1a2 , Cyp1b1 and Nqo1 significantly increased in the groups given 0.03% BNF or more , but Ugt1a6 , Akr7a3 and Gstm1 significantly increased in the groups given 0.125% BNF or more . Gpx2 and Yc2 significantly increased in the groups given 0.06% BNF or more and 0.25% BNF , respectively . Inflammation-related genes such as Ccl2 , Mmp12 , Serpine1 and Cox-2 significantly increased in the 0.25% BNF group . In immunohistochemistry , the number of cyclooxygenase-2 ( COX-2)-positive cells increased in rats given 0.25% BNF . These results suggest that 0.25% BNF is the threshold dose for liver tumor promotion , and the fact that inflammation-related genes and COX-2 protein increased in the 0.25% BNF group strongly suggests that inflammation is involved in the liver tumor promoting effect of BNF in rats .\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: A rat colonic adenocarcinoma was implanted subcutaneously ( s.c. ) in nude mice . After 7 days , the animals were divided into different groups . Two groups received subcutaneous injections twice daily with 3 or 6 micro g/kg body weight octreotide , galanin and serotonin . Three groups were respectively treated with 20 , 30 , and 40 micro g/kg body weight of the previously mentioned bioactive substances . Control group received only saline solution in the same fashion as treated animals . The treatment lasted for 5 days . The tumour volume and weight , the relative density of blood vessels , of tumour necrotic tissue , of apoptotic nuclei and of proliferating nuclei were measured . Apoptosis was detected by in situ labelling of nuclear DNA fragmentation according to TUNEL method , and proliferation by immunocytochemistry . Morphometry was done with the classical stereological point-counting method . Food consumption , animal weight , faeces weight and its water content were measured for 3 days before and after treatment . Triple therapy with 3 and 6 micro g/kg body weight had no effect on any of the parameters measured , except in reducing the relative volume density of tumour blood vessels . Treatment with 20 , 30 and 40 micro g/kg body weight of the previously mentioned bioactive substances reduced the tumour volume , the relative volume density of blood vessels and increased the relative volume density of necrotic tissue and of apoptotic nuclei ( in the 20 micro g group ) . However , there was no difference between treated mice and controls regarding the relative volume density of proliferating nuclei . There was no statistical difference between treated animals regarding food consumption , body weight , faeces weight and its water content before and during treatment . The present study confirms that triple therapy with octreotide , galanin and serotonin causes regression of a rat colon carcinoma . It further showed that optimum treatment dose is 20 micro g/kg body weight of each bioactive substance . Moreover , this therapy regime does not show apparent side effects in the experiments carried out on mice .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: Peroxisome proliferator activated receptor γ ( PPARγ ) , a subgroup of ligand-activated nuclear receptors , plays critical roles in cell cycle regulation , differentiation , apoptosis and invasion . PPARγ is involved in tumorigenesis and is a potent target for cancer therapy . PPARγ transactivation of KLF4 has been demonstrated in various studies ; however , how PPARγ regulates KLF4 expression is not clear . In this study , we revealed that PPARγ regulates the expression of KLF4 by binding directly to the PPAR response element ( PPRE ) within the KLF4 promoter . The PPRE resided at -1657bp to -1669bp upstream of the KLF4 ATG codon , which is essential for the transactivation of TGZ-induced KLF4 expression . Furthermore , we found that stable silencing of KLF4 obviously suppressed the G1/S arrest and anti-proliferation effects induced by PPARγ ligands . Taken together , our data indicated that upregulating KLF4 upon PPARγ activation is mediated through PPRE in KLF4 promoter , thus providing further insights into PPARγ signal transduction pathway as well as a novel cancer therapeutic strategy .\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: Monoclonal antibodies ( mAbs ) to HER2 are currently used to treat breast cancer , but low clinical efficacy , along with primary and acquired resistance to therapy , commonly limit clinical applications . We previously reported that combinations of antibodies directed at non-overlapping epitopes of HER2 are endowed with enhanced antitumor effects , probably due to accelerated receptor degradation . Here , we extend these observations to three-dimensional mammary cell models , and compare the effects of single mAbs with the effects of antibody combinations . Collectively , our in vitro assays and computational image analyses indicate that combining mAbs against different epitopes of HER2 better inhibits invasive growth . Importantly , while growth factors are able to reduce intraluminal apoptosis and induce an invasive phenotype , combinations of mAbs better than single mAbs can reverse the growth factor-induced phenotypes of HER2-overexpressing spheroids . In conclusion , our studies propose that mAb combinations negate the biological effects of growth factors on invasive growth of HER2-overexpressing cells . Hence , combining mAbs offers a therapeutic strategy , potentially able to enhance clinical efficacy of existing antireceptor immunotherapeutics .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: Previously we have found deregulation of collagen metabolism in human pancreatitis and pancreatic cancer tissues . Insulin-like growth factor-I ( IGF-I ) is known to stimulate collagen biosynthesis through interaction with IGF-I receptor . IGF-I binding proteins ( BPs ) regulate the activity of IGF-I . We investigated whether serum and tissue IGF-I and IGF-BPs as well as tissue IGF-I receptor expression may reflect disturbances of collagen metabolism in patients with pancreatitis and pancreatic cancer . In pancreatitis tissue , a significant increase in IGF-I and IGFBP-3 content was accompanied by a distinct increase in IGF-I receptor expression , compared to control pancreas tissue . In contrast , serum from patients with pancreatitis did not show significant increases in IGF-I and IGFBP-3 levels , however , significant increases in IGFBP-1 level ( 2.5 fold ) . Moreover , a distinct decrease in radioactive IGF-binding to the BPs , compared to control serum , was found . Pancreatic cancer tissue and serum of patients with pancreatic cancer showed significant increases in IGF-I , IGFBP-3 and IGFBP-1 content , accompanied by dramatic increases in IGF-I tissue receptor expression , compared to controls . In serum of patients with pancreatic cancer distinct increases in radioactive IGF-binding to 46 kDa BP , compared to control serum , were observed . The data suggest that disturbances in tissue collagen metabolism during pancreatic diseases may result from deregulation of IGF-I homeostasis and that elevated serum levels of IGF-I , IGFBP-3 and IGFBP-1 may serve as markers of pancreatic 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: Pegylated Interferon-α2b ( pIFN-α ) is an integral part of the drug regimen currently employed against melanoma . Interferon Regulatory Factor-1 ( IRF-1 ) plays an important role in the transcriptional regulation of the IFN response , cell cycle and apoptosis . We have studied pIFN-α induced responses when combined with the chemotherapy agent , vinblastine in tumor and endothelial cell lines and the connection to IRF-1 signaling . Levels of IRF-1/IRF-2 protein expression were found to be decreased in tumor versus normal tissues. pIFN-α induced IRF-1 signaling in human melanoma ( M14 ) and endothelial ( EA.hy926 ) cells and enhanced cell death when combined with vinblastine . Upon combined IFN-α and vinblastine treatment , p21 expression , PARP cleavage and activated Bak levels were increased in M14 cells . An increase in p21 and cyclin D1 expression occurred in EA.hy926 cells after 6 h of treatment with pIFN-α which dissipated by 24 h . This biphasic response , characteristic of cellular senescence , was more pronounced upon combined treatment . Exposure of the EA.hy926 cells to pIFN-α was associated with an enlarged , multinucleated , β-galactosidase-positive senescent phenotype . The overall therapeutic mechanism of IFN-α combined with chemotherapy may be due to both direct tumor cell death via IRF-1 signaling and by premature senescence of endothelial cells and subsequent effects on angiogenesis in the tumor microenvironment .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;enabling replicative immortality;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: Prostaglandin E(2) ( PGE(2) ) receptor subtype EP(2) , which is coupled to cAMP metabolism , is known to mediate proliferation of primary human keratinocytes in vitro . The effect of gain or loss of EP(2) receptors in immortalized human keratinocytes ( HaCat cells ) was examined . HaCat keratinocytes were transfected with sense or anti-sense constructs of the EP(2) receptor . Loss or gain of EP(2) expression was documented by immunoblot and associated changes in agonist-stimulated cAMP production . Loss or gain of EP(2) receptor expression correlated with alterations in plating efficiencies but with modest affects on growth . When cell lines were studied in an organ culture model , anti-sense clones were highly invasive compared with vector controls and sense transfectants . A marked increase in prostaglandin production is commonly seen in malignant lesions . Because prostaglandin receptors are known to undergo ligand-induced receptor down-regulation , we sought to determine whether EP(2) receptor down-regulation results in increased invasiveness . In vector controls , invasiveness was reproduced by ligand-dependent EP(2) receptor down-regulation as assessed by immunohistochemistry . In addition , loss of EP(2) receptor expression was associated with decreased paxillin expression , a critical component of focal adhesion assembly . Thus , down-regulation of EP(2) receptors represents a potential mechanism for neoplastic progression to an invasive phenotype .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: It has been demonstrated that growth factors produced by breast cancer cells stimulate aromatase expression in both breast cancer and adjacent adipose fibroblasts and stromal cells . However , whether these growth factors affect aromatase activity by other mechanisms still remain unclear . In the current study , MCF-7aro and T47Daro aromatase transfected breast carcinoma cells were used to explore the mechanisms of post-transcriptional regulation of aromatase activity by growth factor pathways . Our study reveals that PI3K/Akt and MAPK inhibitors suppressed aromatase activity in MCF-7aro cells . However , PI3K/Akt pathway inhibitors stimulated aromatase activity in T47Daro cells . This is due to enhanced MAPK phosphorylation as compensation after the PI3K/Akt pathway has been blocked . IGF-1 treatment increased aromatase activity in both breast cancer cell lines . In addition , LTEDaro cells ( long-term estrogen deprived MCF-7aro cells ) which have enhanced MAPK activity , show higher aromatase activity compared to parental MCF-7aro cells , but the aromatase protein level remains the same . These results suggest that aromatase activity could be enhanced by growth factor signaling pathways via post-transcriptional mechanisms .\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 Colorectal cancer is one of the main cancers in the Western world . About 90% of the deaths arise from formation of distant metastasis . The expression of the newly identified gene metastasis associated in colon cancer 1 ( MACC1 ) is a prognostic indicator for colon cancer metastasis . Here , we analyzed for the first time the impact of single nucleotide polymorphisms ( SNPs ) in the coding region of MACC1 for clinical outcome of colorectal cancer patients . Additionally , we screened met proto-oncogene ( Met ) , the transcriptional target gene of MACC1 , for mutations . METHODS We sequenced the coding exons of MACC1 in 154 colorectal tumors ( stages I , II and III ) and the crucial exons of Met in 60 colorectal tumors ( stages I , II and III ) . We analyzed the association of MACC1 polymorphisms with clinical data , including metachronous metastasis , UICC stages , tumor invasion , lymph node metastasis and patients ' survival ( n = 154 , stages I , II and III ) . Furthermore , we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells . RESULTS We genotyped three MACC1 SNPs in the coding region . Thirteen % of the tumors had the genotype cg ( rs4721888 , L31V ) , 48% a ct genotype ( rs975263 , S515L ) and 84% a gc or cc genotype ( rs3735615 , R804T ) . We found no association of these SNPs with clinicopathological parameters or with patients ' survival , when analyzing the entire patients ' cohort . An increased risk for a shorter metastasis-free survival of patients with a ct genotype ( rs975263 ) was observed in younger colon cancer patients with stage I or II ( P = 0.041 , n = 18 ) . In cell culture , MACC1 SNPs did not affect MACC1-induced cell motility and proliferation . CONCLUSION In summary , the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients ' survival compared to MACC1 expression analysis alone . The ct genotype ( rs975263 ) might be associated with a reduced survival for younger colon cancer patients in early stages . However , further studies with larger sample sizes are needed .\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: Past studies have shown that amplified insulin-like growth factor 1 ( IGF1)/IGF1 receptor ( IGF1-R ) signalling has an important role in colorectal cancer ( CRC ) development , progression and resistance to treatment . In this report , we demonstrate that downregulation of microRNA-497 ( miR-497 ) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells . MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3 ' untranslated region ( 3'UTR ) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa . However , only overexpression of miR-497 led to suppression of the IGF1-R 3'UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells . This was associated with inhibition of cell survival , proliferation and invasion , and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil , and the death ligand tumour necrosis factor-related apoptosis-inducing ligand . The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling , as overexpression of an active form of Akt reversed its impact on cell survival and proliferation , recapitulating the effect of overexpression of IGF1-R . Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1 , where these miRs are located at proximity . Similarly to miR-195 , the members of the same miR family , miR-424 that was upregulated , and miR-15a , miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa , did not appear to have a role in regulating the expression of IGF1-R . Taken together , these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.Oncogene advance online publication , 18 June 2012 ; doi:10.1038/onc.2012.214 .\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: The DNA repair protein Ku70 is a key player in chemoresistance to anticancer agents ( e.g. , etoposide ) or radioresistance . The responses of different organs to radiation vary widely and likely depend on the cell population in the organs . Previously , we established and characterized Ku70-deficient murine lung epithelial ( Ku70 -/- MLE ) cells and found that these cells are more sensitive than Ku70 +/- MLE cells ( control cells ) to X-irradiation , as determined by clonogenic survival assay ; however , the mechanism underlying this sensitivity remains unclear . In this study , we examined the mechanism by which X-irradiation triggers the death of Ku70 -/- MLE cells . Our results showed that Ku70 -/- MLE cells were more sensitive to radiation-induced apoptosis than control cells , although X-irradiation activated caspase-3 and caspase-7 , and cleaved PARP in both cell lines . We also examined the expression level of phosphorylated H2AX ( γH2AX ) , which is a marker of DSB , and observed the phosphorylation of H2AX and the elimination of γH2AX in both cell lines after X-irradiation . The elimination in Ku70 -/- MLE cells was slower than that in control cells , suggesting that DSB repair activity in the Ku70 -/- MLE cells is lower than that in control cells . These findings suggest that Ku70 might play a key role in the inhibition of apoptosis through the DSB repair pathway in lung epithelial cells . Our findings also suggest that these cell lines might be useful for the study of Ku70 functions and the Ku70-dependent DSB repair pathway in lung epithelial cells .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: Immunosenescence , the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections , cancer and autoimmune conditions in the elderly . Senescence-accelerated mouse ( SAM ) was used to study the protective effects of Pu-erh tea in the elderly . The senile-prone sub-strain , SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125 , 250 or 500mg/kg . The results showed that Pu-erh tea significantly increased the fractions of na�ve T lymphocytes , CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood , but decreased the levels of IL-6 in aged mice . These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine . Thus , long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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 papillomavirus type 16 ( HPV16 ) E6 and E7 are selectively retained and expressed in HPV16-associated human genital tumors . E6 is active in several cell culture assays , including transformation of NIH 3T3 cells , trans activation of the adenovirus E2 promoter , and cooperation with E7 to immortalize normal human keratinocytes . Biochemically , the HPV16 E6 protein has been shown to bind to tumor suppressor protein p53 in vitro and induce its degradation in a rabbit reticulocyte lysate . To examine the relationship between the various biological activities of E6 and inactivation of p53 , we tested the abilities of dominant negative mutants of p53 to substitute functionally for E6 in the three cell culture assays . While wild-type p53 inhibited keratinocyte proliferation , both mouse and human mutant p53s , in conjunction with E7 , increased proliferation of the keratinocytes , resulting in generation of immortalized lines . However , in contrast to E6 , mutant p53 was unable to induce transformation or trans activate the adenovirus E2 promoter in NIH 3T3 cells . These results suggest that inactivation of wild-type p53 is necessary for HPV-induced immortalization of human keratinocytes and that different or additional activities are required for E6-dependent transformation and trans activation of NIH 3T3 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: High-grade prostate cancers express high levels of matrix metalloproteinases ( MMPs ) , major enzymes involved in tumor invasion and metastasis . However , the tumor cell lines commonly employed for prostate cancer research express only small amounts of MMPs when cultivated as monolayer cultures , in common culture media . The present study was conducted to ascertain whether culture conditions that include fibronectin can alter MMP2 and MMP9 expression by the human prostatic epithelial cell lines RWPE-1 , LNCaP and PC-3 . These cells were individually seeded at 2×10(4) cells/cm(2) , cultivated until they reached 80% confluence , and then exposed for 4h to fibronectin , after which the conditioned medium was analyzed by gelatin zymography . Untreated cells were given common medium . Only RWPE-1 cells express detectable amounts of MMP9 when cultivated in common medium , whereas the addition of fibronectin induced high expression levels of pro and active forms of MMP2 in all tested cell lines . Our findings demonstrate that normal and tumor prostate cell lines express MMP2 activity when in contact with extracellular matrix components or blood plasma proteins such as fibronectin . Future studies of transcriptomes and proteomes in prostate cancer research using these cell lines should not neglect these important conclusions .\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: Ovarian steroids are one of the strongest risk factors for breast cancer . Sex hormone-binding globulin ( SHBG ) binds and transports sex steroids in the blood , regulating their bioavailable fraction and access to target cells . It can also inhibit the estradiol-induced proliferation of breast cancer cells through its membrane receptor . Three coding-region polymorphisms , which lead to an amino acid change , have been reported . We studied the influence of these three polymorphisms on breast cancer risk in three different populations : Polish familial breast cancer cases , 27% of them carrying a BRCA1/BRCA2 mutation , Nordic familial and sporadic breast cancer cases . The reported G to A polymorphism in exon 1 was not found in the 423 analyzed samples . Instead , we found a C to T transition causing an arg to cys amino acid change within the same codon in one Polish breast cancer patient and her daughter . Both of them were heterozygotes for the exon 8 G to A polymorphism as well . They were diagnosed for bilateral breast cancer and carried a BRCA1 mutation ( 5382insC ) . Analysis of the tumor samples showed that they had lost the wild-type allele both at exons 1 and 8 of the SHBG gene . Analysis of the other Polish samples showed no correlation of the exon 8 polymorphism to breast cancer , bilateral breast cancer , BRCA1/BRCA2 mutations or age at diagnosis . No association of the exon 8 polymorphism with breast cancer in the Nordic familial or sporadic cases was found . The C to T polymorphism located in exon 4 was rare in all the studied populations ( overall allele frequency 0.011 ) . However , in each of the study populations there was a trend for a lower variant allele frequency in cancer cases than in controls . Variant allele frequency in all the breast cancer cases was significantly lower than in all the controls ( chi(2) = 5.27 , P-value 0.02 ; odds ratio = 0.23 , 95% confidence interval 0.05-0.84 ) .\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: Epithelial-mesenchymal transition ( EMT ) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites . Recently , EMT was shown to be associated with the cancer stem cell ( CSC ) phenotype in breast cancer . Snail is a transcription factor that mediates EMT in a number of tumor types , including colorectal cancer ( CRC ) . Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC . Human CRC specimens were stained for Snail expression , and human CRC cell lines were transduced with a retroviral Snail construct or vector control . Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT ( colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) assay . Migration and invasion were determined in vitro using modified Boyden chamber assays . EMT and putative CSC markers were analyzed using Western blotting . Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice . Snail was overexpressed in human CRC surgical specimens . This overexpression induced EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration and invasion ( P &lt ; 0.002 vs. control ) . Snail overexpression also led to an increase in metastasis formation in vivo ( P &lt ; 0.002 vs. control ) . Furthermore , the Snail-overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells . Increased Snail expression induces EMT and the CSC-like phenotype in CRC cells , which enhance cancer cell invasion and chemoresistance . Thus , Snail is a potential therapeutic target in metastatic CRC .\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: A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol . MCF-7 cells were treated with growth factors in the presence and absence of oestradiol . Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF-alpha ) and basic fibroblast growth factor ( bFGF ) . Platelet derived growth factor ( PDGF ) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol . In the absence of oestradiol , there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive . In the presence of oestradiol , the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist . Overall , bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin . The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression .\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: Metastases in the sellar region are rare and are frequently found incidentally or in necropsies . Only 7% are reported to be symptomatic . Diabetes insipidus , anterior pituitary dysfunction , visual field defects , headache/pain and ophthalmoplegia are the most commonly reported symptoms . We present the cases of two male patients with a small-cell lung carcinoma whose first clinical symptoms were due to pituitary metastasis . One case presented with symptoms of cavernous sinus invasion and panhypopituitarism and the other case with diabetes insipidus . Both patients had a rapid progression of their disease despite chemotherapy and died after a few months . Pituitary metastases occur most commonly with breast cancer in women and lung cancer in men . The presence of polyuria and polydipsia in an oncologic patient should alert the physician for diabetes insipidus and , if confirmed , an imaging procedure of the pituitary gland is mandatory . Treatment for these tumors is often multimodal and includes surgery , radiation therapy , chemotherapy and hormone replacement . Although surgical series have not shown any significant survival benefits given by tumor resection , the patient's quality of life may be improved .\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: Curcumin , a well-known chemopreventive agent from turmeric , inhibits the expression of several oncogenes and cell proliferation genes in tumor cells . This study aims to understand the precise molecular mechanism by which curcumin exerts its effects on retinoblastoma cells , by performing whole genome microarray analysis to determine the gene expression profiles altered by curcumin treatment . Curcumin suppressed cell viability and altered the cell cycle of retinoblastoma cells . We identified 903 downregulated genes and 1,319 upregulated genes when compared with the control cells after treatment with 20 μM curcumin concentration for 48 h . These genes were grouped into respective functional categories according to their biological function . We found that curcumin regulated the expression of genes that are involved in the regulation of apoptosis , tumor suppressor , cell-cycle arrest , transcription factor , and angiogenesis . Quantitative real-time polymerase chain reaction ( qRT-PCR ) analysis was used to validate the results of genome array , and the results were consistent with the obtained data . In conclusion , treatment of curcumin affects the expression of genes involved in various cellular functions and plays an important role in tumor metastasis and apoptosis . Thus , curcumin might be an effective chemopreventive agent for retinoblastoma cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death;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: BACKGROUND To assess the potential mechanisms that may underlie increased local failure in triple negative ( TN ) breast cancers , an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors , including molecular phenotype . METHODS A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision . Data were collected on age ; tumor size , grade , and nodal stage ; estrogen receptor , progesterone receptor , and human endothelial growth factor receptor 2 ( Her2 ) ; extensive intraductal component ; lymphovascular invasion ; margins ; and reexcision findings . Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings . Molecular phenotypes were defined by conventionally used immunohistochemical pattern . RESULTS Data were collected on 369 patients with breast cancer . The median age was 57 years , median tumor size was 1.5 cm , 36% had positive margins , 32% had positive lymph nodes , 73.5% had the luminal A subtype , 9.5% had the luminal B subtype , 4.5% were Her2-enriched , and 12.5% were TN . Overall , 32% of patients had invasive cancer in their reexcision specimens , and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes . On univariate analysis , age , tumor size , margin status , lymphovascular invasion , nodal status , and TN subtype were associated with elevated risk of residual invasive cancer . On multivariate analysis using a forward stepwise model , TN subtype maintained significance , with an odds ratio of 3.28 ( P = .002 ) . CONCLUSION TN subtype has a statistically significant association with an increased risk of residual tumor . This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden .\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: Estrogen receptor ( ER ) and NF-κB are transcription factors with profound effects on breast cancer cell proliferation and survival . While many studies demonstrate that ER and NF-κB can repress each other , we previously identified a gene signature that is synergistically upregulated by these two factors in more aggressive luminal B breast tumors . Herein , we examine a novel mechanism of cross talk between ER and NF-κB that results in the upregulation of the antiapoptotic gene BIRC3 ( also known as cIAP2 ) . We demonstrate that NF-κB , acting through two response elements , is required for ER recruitment to an adjacent estrogen response element ( ERE ) in the BIRC3 promoter . This effect is accompanied by a major increase in NF-κB-dependent histone acetylation around the ERE . Interestingly , CBP , a histone acetyltransferase previously implicated in repressive interactions between ER and NF-κB , plays a permissive role by promoting histone acetylation and ER recruitment , as well as enhanced expression of BIRC3 . These findings suggest a new gene regulatory mechanism by which inflammation and NF-κB activation can influence ER recruitment to inherently inactive ER binding sites . This fine-tuning mechanism may explain how two factors that generally repress each other's activity may work together on certain genes to promote breast cancer cell survival and tumor progression .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;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: Νuclear factor-κB ( NF-κB ) and activator protein-1 ( AP-1 ) are major transcription factors that have been associated with breast cancer metastasis by inducing matrix metalloproteinase-9 ( MMP-9 ) expression . In this study , we investigated the inhibitory effects of guggulsterone isomers ( cis or trans ) on 12-O-tetradecanoylpho-bol-13-acetate ( TPA)-induced MMP-9 expression . Cis-guggulsterone inhibited TPA-induced MMP expression by blocking IκB kinase ( IKK)/NF-κB signaling , whereas trans-guggulsterone blocked mitogen-activated protein kinase ( MAPK)/AP-1 signaling . Cis-guggulsterone was more potent than trans-guggulsterone in the inhibition of TPA-induced MMP-9 expression and invasion of MCF-7 cells . Furthermore , we found that the combination of these isomers exerted an additive effect on the inhibition of MCF-7 cell invasion . These results suggest that guggulsterone isomers downregulate MMP-9 expression and tumor cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1 activation . In addition , the suppression of MMP-9 expression correlated well with the inhibition of cell invasion .\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: Notch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages . In addition , truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and , when introduced into mouse bone marrow stem cells , cause T-cell neoplasms . However , functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking . Here we show that Notch1 is highly expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large cell lymphoma . We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro . We further provide evidence that in Hodgkin and anaplastic large cell lymphoma , Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells . Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions , and it seems likely that these interactions contribute to lymphomagenesis in vivo . Thus , our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment .\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: Immunosuppressive oligodeoxynucleotides ( SupODNs ) containing repetitive TTAGGG motifs reduce inflammation and , thus , may have an impact on inflammation‑related tumor growth . In this study , we found a significant antiproliferative effect of Sup ODNs on the A549 non‑small cell lung cancer ( NSCLC ) cell line compared to those treated with control ODNs ( p<0.05 ) . Sup-ODN-mediated G1 phase cell cycle arrest was achieved via inhibition of Akt and extracellular signal-regulated kinase 1/2 phosphorylation and the p15INK4b and p27KIP1/retinoblastoma protein pathway . In addition , Sup ODNs induced apoptosis and enhanced apoptosis when combined with vinorelbine . In a setting similar to clinical use of multidrug chemotherapy for advanced NSCLC , these effects were investigated by using Sup ODNs in combination with conventional anticancer drugs . Sup ODNs had a significant synergistic effect with 5-fluorouracil , vinorelbine , gemcitabine , paclitaxel and irinotecan , with a mean combination index of 0.43-0.78 ( <1.0 indicates synergism ) in the A549 NSCLC cell line . In conclusion , our results showed that Sup ODNs have an anticancer effect and increase the sensitivity of NSCLC cells to conventional anticancer drugs by modifying Akt and the extracellular signal-regulated kinase 1/2 pathway . Thus , Sup ODNs may serve as a novel therapeutic strategy for NSCLC patients .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;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: To explore the possibility of a new therapeutic strategy for leukemia by intervening in the DNA methylation to re-express p15 suppressor gene , methylation inhibitors , 5-Aza-2'-deoxycytidine ( 5-Aza-CdR ) and cell differentiation agent ( CDAII ) were used to treat myelogenous leukemia cell line KG1a in which p15 gene expression was suppressed due to DNA hypermethylation . The biological characteristics of KG1a cells untreated or treated with the agents were investigated and analyzed using morphology , methylation specific-PCR ( MSP ) , ( 3)H-labeled microassay technique , restriction endonuclease reaction , flow cytometry and immunofluorescence methods . The results indicated that both agents showed concentration-dependent and time-dependent inhibition of cell proliferation. 5-Aza-CdR and CDAII induced apoptosis and cell differentiation with G(2) and G(0)/G(1) arrest respectively . Furthermore , DNA methyltransferase activity and level of methylation in genomic DNA were decreased and p15 protein was re-expressed partially . It is concluded that it is possible to treat leukemia by intervening in the DNA methylation using methyltransferase inhibitors and it is worth to make a thorough study on mechanism of the new strategy .\n OUTPUT:\n " }, { "from": "agent", "value": "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: The role of energy deregulation and altered/adapted metabolism in tumor cells is an increasingly important issue in understanding cancer . Hereditary leiomyomatosis and renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of fumarate hydratase ( FH ) , followed by somatic loss of the remaining wild-type allele and known to be a highly metastatic and lethal malignancy compared to other RCCs . The intrinsic loss of normal tricarboxylic acid ( TCA ) cycle presumably aids tumorigenesis due to the necessary metabolic alterations required and the enforced dependence on glycolysis derived energy , mimicking the Warburg effect . Thus , there is considerable utility in establishing a preclinical cell model from these tumors to study energy metabolism deregulation , as well as developing new targeted therapeutic approaches for TCA cycle enzyme-deficient cancers . Here , we describe a new immortalized cell line , UOK268 , derived from a patient's primary HLRCC-associated kidney cancer . This represents the first primary renal cell line to model TCA cycle gene loss and provides a perfect partner cell line to our previously described metastasis-derived HLRCC-associated cell line , UOK262 . We identified a novel germline FH missense mutation , p.His192Asp , and the subsequent loss of heterozygosity in UOK268 . The UOK268 cell line expressed mutant FH protein , which localized to the mitochondria , but with loss of almost all catalytic activity . The UOK268 cells had severely compromised oxidative phosphorylation and increased glycolytic flux . Ingenuity pathways analysis of human mitochondria-focused cDNA microarray ( hMitChip3 ) gene chip data confirmed the altered mRNA expression patterns of genes involved in several important pathways , such as lipid metabolism , apoptosis , and energy production/glycolysis . UOK268 provides a unique model of a primary cell line demonstrating an enforced , irreversible Warburg effect and , combined with UOK262 , provides a unique invitro preclinical model for studying the bioenergetics of the Warburg effect in human cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;cellular energetics;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: A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication . Simultaneously , however , it may also enhance antitumor therapy through initiation of proinflammatory , antiviral cytokine responses at the tumor site . The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus . In this respect , injection of oncolytic vesicular stomatitis virus ( VSV ) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression , but it is not associated with viral replicative burst in the tumor . In contrast , intratumoral delivery of VSV induces an acute proinflammatory reaction , which quickly resolves concomitantly with virus clearance . Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication , a single-cycle VSV is equally effective as a fully replication-competent VSV , whereas inactivated viruses do not generate therapy . Even though therapy is dependent on host CD8+ and natural killer cells , these effects are not associated with interferon-gamma-dependent responses against either the virus or tumor . There is , however , a strong correlation between viral gene expression , induction of proinflammatory reaction in the tumor and in vivo therapy . Overall , our results suggest that acute innate antiviral immune response , which rapidly clears VSV from B16ova tumors , is associated with the therapy observed in this model . Therefore , the antiviral immune response to an oncolytic virus mediates an intricate balance between safety , restriction of oncolysis and , potentially , significant immune-mediated antitumor therapy .\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: Trinucleotide repeat ( TNR ) expansions and deletions are associated with human neurodegenerative diseases and prostate cancer . Recent studies have pointed to a linkage between oxidative DNA damage , base excision repair ( BER ) and TNR expansion , which is demonstrated by the observation that DNA polymerase β ( pol β ) gap-filling synthesis acts in concert with alternate flap cleavage by flap endonuclease 1 ( FEN1 ) to mediate CAG repeat expansions . In this study , we provide the first evidence that the repair of a DNA base lesion can also contribute to CAG repeat deletions that were initiated by the formation of hairpins on both the template and the damaged strand of a continuous run of ( CAG)(20 ) or ( CAG)(25 ) repeats . Most important , we found that pol β not only bypassed one part of the large template hairpin but also managed to pass through almost the entire length of small hairpin . The unique hairpin bypass of pol β resulted in large and small deletions in coordination with FEN1 alternate flap cleavage . Our results provide new insight into the role of BER in modulating genome stability that is associated with human diseases .\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: Focal adhesion kinase ( FAK ) is an important mediator of extracellular matrix integrin signaling , cell motility , cell proliferation and cell survival . Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis . Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients . Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells . The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples . Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation , anchorage independent growth , three-dimensional growth in Matrigel , migration and invasion . Conversely , inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth . Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development , local invasion and metastatic colonization of breast cancer xenografts . Thus , miR-7 expression is decreased in metastatic breast cancer , correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression .\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 aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene ( DMBA)-induced rat mammary tumors , by simultaneously investigating the expression of estrogen receptor-alpha ( ERalpha ) , estrogen receptor-beta ( ERbeta ) , progesterone receptor ( PR ) , apoptosis , neu , and markers of cell proliferation , such as proliferating cell nuclear antigen ( PCNA ) by immunohistochemistry . The percentage of ERalpha positive tumors was 65.8% in masses from control animals , and significantly dropped to 36.8% in tumors from soy treated rats ( P=0.010 ) . The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals ( P=0.066 ) . Moreover , the percentage of cases which were both ERalpha and ERbeta positive was significantly lower ( 17.6% ) in soy treated than in control animals ( 51.3% ) ( P=0.006 ) . The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats ( P=0.0006 ) . There were no statistically significant differences in the percentage of tumors positively stained for neu , apoptosis , or PCNA , in control vs. soy treated rats . However , when analyzing the reciprocal correlation among the different biochemical parameters we showed that , in treated animals , the majority of ERalpha positive tumors ( 91.7% ) were also PCNA positive ( P=0.036 ) . The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors ( 25 vs. 5% ) ( P=0.0031 ) . Moreover , an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive ( P=0.011 ) .\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: Neurofibromatosis type 2 patients develop schwannomas , meningiomas and ependymomas resulting from mutations in the tumor suppressor gene , NF2 , encoding a membrane-cytoskeleton adapter protein called merlin . Merlin regulates contact inhibition of growth and controls the availability of growth factor receptors at the cell surface . We tested if microtubule-based vesicular trafficking might be a mechanism by which merlin acts . We found that schwannoma cells , containing merlin mutations and constitutive activation of the Rho/Rac family of GTPases , had decreased intracellular vesicular trafficking relative to normal human Schwann cells . In Nf2-/- mouse Schwann ( SC4 ) cells , re-expression of merlin as well as inhibition of Rac or its effector kinases , MLK and p38(SAPK) , each increased the velocity of Rab6 positive exocytic vesicles . Conversely , an activated Rac mutant decreased Rab6 vesicle velocity . Vesicle motility assays in isolated squid axoplasm further demonstrated that both mutant merlin and active Rac specifically reduce anterograde microtubule-based transport of vesicles dependent upon the activity of p38(SAPK) kinase . Taken together , our data suggest loss of merlin results in the Rac-dependent decrease of anterograde trafficking of exocytic vesicles , representing a possible mechanism controlling the concentration of growth factor receptors at the cell surface .\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: Biallelic mutations in MCPH1 cause primary microcephaly ( MCPH ) with the cellular phenotype of defective chromosome condensation . MCPH1 encodes a multifunctional protein that notably is involved in brain development , regulation of chromosome condensation , and DNA damage response . In the present studies , we detected that MCPH1 encodes several distinct transcripts , including two major forms : full-length MCPH1 ( MCPH1-FL ) and a second transcript lacking the six 3 ' exons ( MCPH1Δe9-14 ) . Both variants show comparable tissue-specific expression patterns , demonstrate nuclear localization that is mediated independently via separate NLS motifs , and are more abundant in certain fetal than adult organs . In addition , the expression of either isoform complements the chromosome condensation defect found in genetically MCPH1-deficient or MCPH1 siRNA-depleted cells , demonstrating a redundancy of both MCPH1 isoforms for the regulation of chromosome condensation . Strikingly however , both transcripts are regulated antagonistically during cell-cycle progression and there are functional differences between the isoforms with regard to the DNA damage response ; MCPH1-FL localizes to phosphorylated H2AX repair foci following ionizing irradiation , while MCPH1Δe9-14 was evenly distributed in the nucleus . In summary , our results demonstrate here that MCPH1 encodes different isoforms that are differentially regulated at the transcript level and have different functions at the protein level .\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: Transforming growth factor-beta1 ( TGF-beta1 ) exerts potent immunosuppressive effects . In this study , we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma ( HCC ) cell lines in immunosuppression mechanisms . Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay ( ELISA ) , we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5 , Hep3B , and HepG2 . To determine the biological activity of TGF-beta1 in the supernatants , we examined the effects of the culture supernatants on the production of interferon ( IFN)-gamma induced during the culture of peripheral blood mononuclear cells ( PBMCs ) stimulated with interleukin ( IL)-12 . IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5 , Hep3B , and HepG2 reduced to 14.7 +/- 0.8 , 17.3 +/- 9.0 , and 35.9 +/- 14.6% , respectively , compared with the value in the culture with control medium ( complete culture medium ) . These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes ( CTL ) and natural killer ( NK ) cells , and thus could enhance their ability to escape immune-mediated surveillance .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "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: Solar ultraviolet radiation is considered to be injurious rather than necessary for most organisms living on the earth . It is reported that the risk of skin cancer in humans increases by the depletion of the ozone layer . We have examined the genotoxicity of solar ultraviolet , especially the longer wavelength light , using Drosophila . Recently , we have demonstrated that light of wavelength up to 340 nm is mutagenic on Drosophila larvae . Using an excision repair-deficient Drosophila strain ( mus201 ) , we have obtained results suggesting that the lesion caused in larvae by the 320 nm-light irradiation may be similar to the damage induced by irradiation at 310 nm , and that light of 330 and 340 nm may induce damage different from that induced by 310 and 320 nm-light . To examine the difference in DNA damage induced by light of a particular wavelength , we performed monochromatic irradiation on larvae of two Drosophila strains ; one excision repair-deficient ( mei-9 ) and another postreplication repair-deficient ( mei-41). 310 and 320 nm-light was more mutagenic in the mei-9 strain than in mei-41 , whereas 330 and 340 nm-light was more mutagenic in mei-41 than in mei-9 . It is demonstrated that the mei-41 gene is a homologue of the human atm gene which is responsible for a cell cycle checkpoint . This result suggests that 310-320 nm-light induces DNA damage that is subject to nucleotide excision repair ( NER ) and that 330-360 nm-light causes damage to be recognized by the cell cycle checkpoint but it is not repairable by NER .\n OUTPUT:\n " }, { "from": "agent", "value": "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: We present a novel gain-of-function mutation of TGF-β receptor II ( TβRII ) found in human oral squamous cell carcinoma ( OSCC ) . Expression of E221V/N238I mutant TβRII enhanced TGF-β signaling . Mutation of TβRII conferred cells higher migratory and invasive capabilities and MMP-2 activity . In mouse tumor model , mutant tumors exhibited poor differentiation and E-cadherin relocalization to the cytosol . Lipid-raft-dependent endocytosis of TβRII was attenuated in mutant TβRII , suggesting that enhancement of TGF-β signaling by this mutation is due to delayed TβRII internalization . Taken together , our results show a novel gain-of-function TβRII mutation , which enhances TGF-β signaling leading to more invasive phenotypic changes in human OSCC .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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: There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells . To resolve these contradictory observations , we studied radiosensitivities by employing breast cancer stem cell ( CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells . CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [ 1 ] . These cells were exposed to γ-rays ( 1.25-8.75 Gy ) and survival curves were determined by colony formation . A final slope , D(0) , of the survival curve for each cell line was determined to measure radiosensitivity . The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy , respectively . Similar results were observed in MDA-MB-231 cells ( 0.94 Gy vs. 1.56 Gy ) . After determination of radiosensitivity , we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution , free-radical scavengers and DNA repair . We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity , differential DNA repair capacity may be a greater determinant of radiosensitivity . Unlike non-stem cells , CSC-like cells have little/no sublethal damage repair , a low intracellular level of ataxia telangiectasia mutated ( ATM ) and delay of γ-H2AX foci removal ( DNA strand break repair ) . These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells .\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: Results generated by the immunohistochemical staining with PC10 , a new monoclonal antibody recognizing PCNA ( a nuclear protein associated with cell proliferation ) in formalin-fixed and paraffin-embedded tissue were compared with those of Ki-67 labeling and DNA flow cytometry in 47 consecutive non-small cell lung cancer ( NSCLC ) . PCNA reactivity was observed in all samples and confined to the nuclei of cancer cells . Its frequency ranged from 0 to 80% ( 37.7 +/- 23.6 ) and larger sized , early-staged and DNA aneuploid tumors expressed a significant higher number of PCNA-reactive cells . The PCNA and Ki-67 labeling rates were closely correlated ( r = 0.383 , P = 0.009 ) . By flow cytometry , we observed a good correlation among PCNA labeling and S-phase fraction ( r = 0.422 , P = .0093 ) and G1 phase ( r = 0.303 , P = .051 ) of the cell cycle . Results indicate that PCNA labeling with PC10 is a simple method for assessing the proliferative activity in formalin-fixed , paraffin-embedded tissue of NSCLC and correlates well with Ki-67 labeling and S-phase fraction of the cell cycle .\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: Mutations in the tumor suppressor tuberin ( TSC2 ) are a common factor in the development of lymphangioleiomyomatosis ( LAM ) . LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma . The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated , although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells . Here we show that tuberin-null cells become nonadherent and invasive . These nonadherent cells express cleaved forms of β-catenin . In reporter assays , the β-catenin products are transcriptionally active and promote MMP7 expression . Invasion by the tuberin-null cells is mediated by MMP7 . Examination of LAM tissues shows the expression of cleaved β-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a β-catenin-dependent mechanism , which may underlie the development of LAM .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]