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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: c-myc , c-erbB-2 , and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas . The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues . Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors , while the level of expression in normal breast tissue was much less than that in breast cancer . Membrane staining of the c-erbB-2 protein was demonstrated in 29% ( 4 of 14 ) of noninvasive ductal carcinomas and in 45% ( 19 of 42 ) of invasive breast carcinomas . None of the 11 normal breast tissue samples was positive . The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue , 4.57 +/- 1.36% for noninvasive ductal carcinoma , and 12.76 +/- 2.18% for invasive breast cancer . In 42 invasive breast carcinomas , the expression of c-myc , c-erbB-2 , and Ki-67 proliferation marker were compared with lymph node status , estrogen receptor status , progesterone receptor status , and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status . We concluded that they might be additional prognostic factors for breast carcinoma .\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 AND AIM The importance of glycolysis in cancer cells is well documented . The effects of inhibiting glycolysis using metabolic inhibitors iodoacetate ( IAA ) , an inhibitor of GAPDHase , and 3-bromopyruvate ( 3BP ) , an inhibitor of hexokinase-II , on survival and signaling of pancreatic cancer cells ( Panc-1 ) were investigated . MATERIALS AND METHODS Cellular survival was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay . Lactate dehydrogenase ( LDH ) assay was used to analyze the induced necrosis and protein levels were evaluated using Western blot analysis . RESULTS The results show that the inhibitors lowered cellular survival and increased cellular necrosis . Mitogenic signaling pathways were affected by 3BP but not by IAA . CONCLUSION We conclude that there may be a cross-talk between signaling pathways and glycolysis in regulating pancreatic cancer cell survival and signaling . Thus , a combination of agents that inhibit both energy production and cell signaling may provide a novel and effective approach to target pancreatic cancer effectively .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The aim of this study was to determine whether caffeine enhanced radiosensitivity of normal liver tissue in a rat radiation-induced liver disease model . Buffalo rat McA-RH7777 hepatocellular cancer cells and BRL3A normal liver cells were irradiated , and cell cycle distribution and apoptosis rates were analyzed . A rat model of radiation-induced liver disease was established , rats were randomized into four groups : control ; caffeine alone ; irradiation ( IR ) alone ; and caffeine plus IR ( Caff + IR ) group . Apoptosis rates in normal rat liver tissue after IR were evaluated by TUNEL staining and caspase-3 Western blot . Transaminase activity was measured and histopathological examination was done after IR . Caffeine abrogated IR-induced G2 phase arrest ( Caff + IR vs. IR : 40.9 ± 4.0 vs. 60.7 ± 5.5% , at 12 h after IR ) and increased apoptosis rates ( Caff + IR vs. IR : 56.1 ± 6.8 vs. 35.5 ± 4.0% , at 72 h after IR ) in McA-RH7777 cells , but did not affect IR-induced G2 phase arrest and apoptosis rates at any time point after IR in BRL3A cells . Caffeine did not enhance apoptosis , transaminase activity , or histopathological injury of normal rat liver tissue at any time points after IR . This study suggests that caffeine might not enhance radiosensitivity of normal liver tissue in vivo . In an earlier study , we reported that caffeine enhanced radiosensitivity of human hepatocellular cancer in a nude mice model . Together , these results offer feasibility of clinical application .\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: Diphenyl ditelluride ( DPDT ) is a potential prototype for the development of novel biologically active molecules . Thus , it is important to evaluate the toxic effects of this compound . In the present study , we evaluated the cytotoxic , genotoxic and mutagenic properties of DPDT in Chinese hamster fibroblast ( V79 ) cells , in strains of the yeast Saccharomyces cerevisiae both proficient and deficient in several DNA repair pathways and in Salmonella typhimurium . DPDT induced frameshift mutations in both S.typhimurium and a haploid wild-type strain of S.cerevisiae . Mutants of S.cerevisiae defective in base excision repair and recombinational repair were more sensitive to DPDT . The results of a lactate dehydrogenase leakage assay suggest that DPDT is cytotoxic to V79 cells . At cytotoxic concentrations , this compound increased thiobarbituric reactive species levels and decreased the glutathione:GSSH ratio in yeast and V79 cells . DPDT generated single- and double-strand DNA breaks in V79 cells , both with and without metabolic activation , as revealed by alkaline and neutral comet assays . Moreover , an induction of oxidative DNA base damage was indicated by a modified comet assay using formamidopyrimidine DNA glycosylase and endonuclease III . Treatment with DPDT also induced micronucleus formation in V79 cells . Pre-incubation with N-acetylcysteine reduced DPDT's oxidative , genotoxic and mutagenic effects in yeast and V79 cells . Our results suggest that the toxic and mutagenic properties of DPDT may stem from its ability to disturb the redox balance of the cell , which leads to oxidative stress and the induction of DNA damage .\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: Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia . Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells , it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors . More than a metabolic waste , the lactate anion is known to participate to cancer aggressiveness , in part through activation of the hypoxia-inducible factor-1 ( HIF-1 ) pathway in tumor cells . Whether lactate may also directly favor HIF-1 activation in endothelial cells ( ECs ) thereby offering a new druggable option to block angiogenesis is however an unanswered question . In this study , we therefore focused on the role in ECs of monocarboxylate transporter 1 ( MCT1 ) that we previously identified to be the main facilitator of lactate uptake in cancer cells . We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis . Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 ( VEGFR2 ) and basic fibroblast growth factor ( bFGF ) expression . Furthermore , using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry , we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects . Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells , the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities .\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: SET and MYND domain-containing protein 3 ( SMYD3 ) is a histone methyltransferase that plays an important role in transcriptional regulation in human carcinogenesis . It can specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes , including several oncogenes ( e.g. , N-myc , CrkL , Wnt10b , RIZ and hTERT ) and genes involved in the control of cell cycle ( e.g. , CyclinG1 and CDK2 ) and signal transduction ( e.g. , STAT1 , MAP3K11 and PIK3CB ) . To determine the effects of SMYD3 over-expression on cell proliferation , we transfected SMYD3 into MDA-MB-231 cells and found that these cells showed several transformed phenotypes as demonstrated by colony growth in soft agar . Besides , we show here that down-regulation of SMYD3 could induce G1-phase cell cycle arrest , indicating the potent induction of apoptosis by SMYD3 knockdown . These results suggest the regulatory mechanisms of SMYD3 on the acceleration of cell cycle and facilitate the development of strategies that may inhibit the progression of cell cycle in breast cancer cells .\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: Tumor cells are elusive targets for immunotherapy due to their heterogeneity and genetic instability . Here we describe a novel , oral DNA vaccine that targets stable , proliferating endothelial cells in the tumor vasculature rather than tumor cells . Targeting occurs through upregulated vascular-endothelial growth factor receptor 2 ( FLK-1 ) of proliferating endothelial cells in the tumor vasculature . This vaccine effectively protected mice from lethal challenges with melanoma , colon carcinoma and lung carcinoma cells and reduced growth of established metastases in a therapeutic setting . CTL-mediated killing of endothelial cells indicated breaking of peripheral immune tolerance against this self antigen , resulting in markedly reduced dissemination of spontaneous and experimental pulmonary metastases . Angiogenesis in the tumor vasculature was suppressed without impairment of fertility , neuromuscular performance or hematopoiesis , albeit with a slight delay in wound healing . Our strategy circumvents problems in targeting of genetically unstable tumor cells . This approach may provide a new strategy for the rational design of cancer therapies .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction;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: Therapy-induced senescence ( TIS ) , a cytostatic stress response in cancer cells , is induced inefficiently by current anticancer agents and radiation . The mechanisms that mediate TIS in cancer cells are not well defined . Herein , we characterize a robust senescence response both in vitro and in vivo to the quinone diaziquone ( AZQ ) , previously identified in a high-throughput senescence-induction small-molecule screen . Using AZQ and several other agents that induce senescence , we screened a series of cyclin-dependent kinase inhibitors and found that p27(Kip1) was induced in all investigated prostate cancer cell lines . The ubiquitin-ligase Skp2 negatively regulates p27(Kip1) and , during TIS , is translocated to the cytoplasm before its expression is decreased in senescent cells . Overexpression of Skp2 blocks the effects of AZQ on senescence and p27(Kip1) induction . We also find that stable long-term short hairpin RNA knockdown of Skp2 decreases proliferation but does not generate the complete senescence phenotype . We conclude that Skp2 participates in regulating TIS but , alone , is insufficient to induce senescence in cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]