Datasets:

hippocrates

/

HoC_1shot_train

like 0

[ { "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: Cellular senescence , an irreversible cell cycle arrest induced by a diversity of stimuli , has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy . Using a targeted proteomics approach , we show that fibroblasts induced into senescence by expression of oncogenic Ras exhibit a decrease of global acetylation on all core histones , consistent with formation of senescence-associated heterochromatic foci . We also detected clear increases in repressive markers ( e.g. >50% elevation of H3K27me2/3 ) along with decreases in histone marks associated with increased transcriptional expression/elongation ( e.g . H3K36me2/3 ) . Despite the increases in repressive marks of chromatin , 179 loci ( of 2206 total ) were found to be upregulated by global quantitative proteomics . The changes in the cytosolic proteome indicated an upregulation of mitochondrial proteins and downregulation of proteins involved in glycolysis . These alterations in primary metabolism are opposite to the well-known Warburg effect observed in cancer cells . This study significantly improves our understanding of stress-induced senescence and provides a potential application for triggering it in antiproliferative strategies that target the primary metabolism in cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;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: Although the expression of extracellular matrix protein-1 ( ECM1 ) has been documented in several tumor models , the function of ECM1 has remained unclear . In this study , expression of ECM1 was detected by real time PCR and immunohistochemistry . The role and mechanism of ECM1 overexpression in cholangiocarcinoma ( CCA ) cells were assessed by wound-healing , matrigel invasion assay and Western blotting . Expression of ECM1 was significantly elevated in CCA tissues than that in adjacent noncancerous , cholangitis and normal bile duct tissues . Its overexpression was associated with poor differentiation , lymph node metastasis , poor prognosis , and the level of CA199 , MMP-9 , estrogen receptor . Knockdown of ECM1 suppressed migration and invasion of CCA cells . Using PI3K or IKK inhibitor reduced the level of phospho-Akt or phospho-IκBα as well as ECM1 . Taken together , overexpression of ECM1 may contribute to CCA initiation and progression through promoting migration and invasion of CCA cells , its overexpression was associated with Akt/NF-κB signaling axis .\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: Elevated insulin-like growth factor binding protein-related protein 1 ( IGFBP-rP1 ) mRNA in senescent human mammary epithelial cells suggested that the IGFBP-3 gene product may inhibit cell proliferation . To test this hypothesis , we used a retroviral vector to express IGFBP-rP1 cDNA in the IGFBP-rP1-deficient MCF-7 breast cancer cell line . Compared with control vector-transduced cells , cumulative cell numbers for IGFBP-rP1-transduced polyclonal or clonal cell cultures were reduced by 39 and 74% , respectively , after 1 week . Medium conditioned by IGFBP-rP1-producing cultures reduced cumulative cell numbers in parental MCF-7 cultures by 20% compared with medium from cultures of a control vector-transduced cell line . Nuclear fragmentation analysis and cell proliferation assays completed in the presence of the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone excluded apoptosis as the responsible mechanism . The percentage of cells containing senescence-associated beta-galactosidase activity was doubled compared with control cell cultures . Flow cytometry analysis indicated that twice as many noncycling cells were present in the IGFBP-rP1-transduced MCF-7 cell cultures compared with controls . These findings indicate that IGFBP-rP1 is an inhibitor of MCF-7 breast cancer cell proliferation and may act via a cellular senescence-like mechanism .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Liver resection is now widely accepted as a potentially curative treatment for colorectal liver metastasis . However , the efficacy of surgical resection for gastric cancer liver metastasis(GLM)remains unclear . Based on our 18-year experience with 64 patients who underwent curative hepatectomy for GLM , we discuss the indication and efficacy of surgical resection for GLM . From January 1993 to January 2011 , 73 patients underwent hepatectomy for GLM in the Department of Gastroenterological Surgery , Cancer Institute Ariake Hospital(Japanese Foundation for Cancer Research ) , Japan . The actuarial1 - , 3- , and 5-year overall survival rates and 1- , 3- , and 5-year recurrence-free survival rates of those 64 patients who achieved curative resections were 84 , 50 , and 37% , and 42 , 27 , and 27% , respectively . By multivariate analysis , serosal invasion of the primary gastric cancer and larger hepatic tumor(>5 cm in diameter)were found to be independent indicators of poor prognosis . Based on the multivariate analysis results , all patients were divided into three groups no poor prognostic factor(n=38) , one poor prognostic factor(n=24) , and two poor prognostic factors(n=2) . The actuarial overall survival rates of each group were 63 , 36 , and 0% at 3 years , and 53 , 15 , and 0% at 5 years . GLM patients having hepatic tumors with the maximum diameter of <5 cm , and without serosalinvasion of the primary gastric cancer , are the best candidates for hepatectomy .\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: Cancer cells typically display altered glucose metabolism characterized by a preference of aerobic glycolysis , known as the Warburg effect , which facilitates cell proliferation . Hypoxia-inducible factor ( HIF ) and oncoprotein Myc are two prominent transcription factors that drive glycolysis . Previously , we reported that the estrogen-related receptors ( ERRs ) act as cofactors of HIF and enhance HIF-dependent transcription of glycolytic genes under hypoxia . ERRs are orphan nuclear receptors and key regulators of energy metabolism by orchestrating mitochondrial biogenesis , fatty acid oxidation ( FAO ) and oxidative phosphorylation . Here , we show that ERRs also stimulate glycolysis under normoxia . ERRs directly bind to and activate promoters of many genes encoding glycolytic enzymes , and the ERR-binding sites in such promoters are essential for ERR-mediated transcriptional activation . ERRs interact with Myc , and the two factors synergistically activate transcription of glycolytic genes . Furthermore , overexpression of ERRs increases glycolytic gene expression and lactate production . Conversely , depletion of ERRs in cancer cells reduces expression of glycolytic genes and glucose uptake , resulting in decreased aerobic glycolysis and cell growth . Taken together , these results suggest that ERRs are important transcriptional activators of the glycolytic pathway and contribute to the Warburg effect in cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Although interleukin-28A ( IL-28A ) is believed to have an antiviral effect , its role in tumor migration requires further examination . The present study was intended to verify the effect of IL-28A on the migration of UMUC-3 bladder cancer cells . IL-28A and its receptor IL-28AR1 mRNA were detected in UMUC-3 cells . Although exogenous IL-28A showed no effect on cell proliferation , a wound-healing migration assay showed that the migration of UMUC-3 cells was induced by IL-28A . Furthermore , treatment of the cells with IL-28A significantly promoted MMP-9 expression via binding activities of NF-κB and AP-1 . IL-28A also induced the activation of p38MAPK and Jak2-Stat2 signaling . Using the p38MAPK inhibitor SB203580 and the dominant-negative plasmid DN-p38 , we found evidence that the inhibition of p38MAPK signaling suppressed the effects of IL-28A including wound-healing migration and MMP-9 expression by activation of NF-κB and AP-1 binding in UMUC-3 cells . However , Jak-2 inhibition by AG490 did not affect IL-28A-induced migration of UMUC-3 cells . Collectively , we suggest for the first time that the p38MAPK pathway mediates IL-28A-induced cell migration through MMP-9 expression by activating NF-κB and AP-1 binding motifs .\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: BACKGROUND Epidemiologic data have shown that obesity independently increases colorectal cancer ( CRC ) risk , but the mechanisms are poorly understood . Obesity is an inflammatory state , and chronic colonic inflammation induces CRC . OBJECTIVE We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss . DESIGN We measured inflammatory cytokines , gene arrays , and macrophage infiltration in rectosigmoid mucosal biopsies of 10 obese premenopausal women [ mean ± SD body mass index ( in kg/m(2) ) : 35 ± 3.5 ] before and after weight loss induced by a very-low-calorie diet . RESULTS Subjects lost a mean ( ±SD ) of 10.1 ± 1% of their initial weight . Weight loss significantly reduced fasting blood glucose , total cholesterol , triglycerides , LDL , tumor necrosis factor-α ( TNF-α ) , and interleukin ( IL)-8 concentrations ( P &lt ; 0.05 ) . After weight loss , rectosigmoid biopsies showed a 25-57% reduction in TNF-α , IL-1β , IL-8 , and monocyte chemotactic protein 1 concentrations ( P &lt ; 0.05 ) . T cell and macrophage counts decreased by 28% and 42% , respectively ( P &lt ; 0.05 ) . Gene arrays showed dramatic down-regulation of proinflammatory cytokine and chemokine pathways , prostaglandin metabolism , and the transcription factors STAT3 ( signal transducer and activator of transcription 3 ) and nuclear transcription factor κB . Weight loss reduced expression of FOS and JUN genes and down-regulated oxidative stress pathways and the transcription factors ATF ( activating transcription factor ) and CREB ( cyclic AMP response element-binding ) . CONCLUSIONS Our data show that diet-induced weight loss in obese individuals reduces colorectal inflammation and greatly modulates inflammatory and cancer-related gene pathways . These data imply that obesity is accompanied by inflammation in the colorectal mucosa and that diet-induced weight loss reduces this inflammatory state and may thereby lower CRC risk .\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: Breast cancer is the malignant neoplasia with the highest incidence in women worldwide . Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression . Human studies have not considered the complexity of tumor biology during the stages of cancer advance , limiting their clinical application . The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early ( ED ; TNM I and II ) and advanced disease ( AD ; TNM III and IV ) of patients diagnosed with infiltrative ductal carcinoma breast cancer . Oxidative stress parameters were evaluated by plasmatic lipoperoxidation , carbonyl content , thiobarbituric reactive substances ( TBARS ) , nitric oxide levels ( NO ) , total radical antioxidant parameter ( TRAP ) , superoxide dismutase , and catalase activities and GSH levels . Immune evaluation was determined by TNF-α , IL-1β , IL-12 , and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence . Tissue damage analysis included heart ( total CK and CKMB ) , liver ( AST , ALT , GGT ) , and renal ( creatinine , urea , and uric acid ) plasmatic markers . C-reactive protein ( CRP ) and iron metabolism were also evaluated . Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages . ED was characterized by reduction in catalase , 8-isoprostanes , and GSH levels , with enhanced lipid peroxidation and TBARS levels . AD exhibited more pronounced oxidative status , with reduction in catalase activity and TRAP , intense lipid peroxidation and high levels of NO , TBARs , and carbonyl content . ED patients presented a Th2 immune pattern , while AD exhibited Th1 status . CRP levels and ferritin were increased in both stages of disease . Leukocytes burst impairment was observed in both the groups . Plasma iron levels were significantly elevated in AD . The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators .\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: Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors . When two cells touch , an adhesion link is created between them by means of transmembrane E-cadherin proteins . Simultaneously , their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links . Here , we propose a detailed quantitative model of the role of cytoplasmic beta-catenin and alpha-catenin proteins in this process , treated as a reaction-diffusion system . Upon cell-cell contact the concentration in alpha-catenin dimers increases , inhibiting actin branching and thereby reducing cellular motility and expansion pressure . This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin , beta-catenin , and alpha-catenin in the cellular phenotype and in tumorigenesis . In particular , we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene . Potential direct tests of our model are discussed .\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: Although the etiology of primary brain tumors is largely unknown , prior studies suggest that DNA repair polymorphisms may influence risk of glioma . Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma , but these tumors have not been well studied . We estimated the risk of glioma ( n = 362 ) , meningioma ( n = 134 ) , and acoustic neuroma ( n = 69 ) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based , case-control study conducted by the National Cancer Institute . We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 ( OR(CT/TT) = 3.5 ; 95% confidence interval : 1.8-6.9 ; P(trend) .0006 ) , which persisted after controlling for multiple comparisons ( P = .019 ) . Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 ( P(trend) .01 ) ; MUTYH rs3219466 ( P(trend) .02 ) , and PCNA rs25406 ( P(trend) .03 ) . The NBN rs1805794 minor allele variant was associated with decreased meningioma risk ( P(trend) .006 ) . Risk of acoustic neuroma was increased for the ERCC2 rs1799793 ( P(trend) .03 ) and ERCC5 rs17655 ( P(trend) .05 ) variants and decreased for the PARP1 rs1136410 ( P(trend) .03 ) . Decreased glioma risk was observed with the XRCC1 rs1799782 variant ( P(trend) .04 ) . Our results suggest that common DNA repair variants may affect the risk of adult brain tumors , especially meningioma .\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: This study is to investigate the effects of bortezomib on the angiogenesis of mesenchymal stem cells ( MSCs ) . We examined the effects of bortezomib on the cellular proliferation , migration , and capillary network formation of HUVECs cocultured with CMs of MSCs . We found that Bortezomib inhibited the cellular proliferation and tube formation of HUVECs cocultured with CMs in a dose-dependent fashion . Bortezomib also prevented the migration of HUVECs cocultured with CMs . In addition , bortezomib dose-dependently inhibited the growth of MSCs and prevented the production of angiogenic factors including VEGF ( vascular endothelial growth factor ) , HGF ( hepatocyte growth factor ) , and bFGF ( basic fibroblast growth factor ) in MSCs . In conclusion , bortezomib prevented the angiogenesis mediated by MSCs .\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: Glycol ethers are known reproductive and developmental toxins in laboratory animals , but little is known about their genotoxic effects in humans . In the current article , the authors tested the hypothesis that human in utero exposure to ethylene glycol monomethyl ether ( EGME ) is associated with the development of specific congenital anomalies and elevated levels of chromosome aberrations . The authors conducted a clinical and cytogenetic evaluation of 41 offspring of 28 females occupationally exposed to EGME for an average duration of 4.6 yr . Six offspring of 5 women who were occupationally exposed to EGME during pregnancy exhibited characteristic dysmorphic features that were not observed in 35 offspring of 23 women who worked in the same facility , but who were not pregnant at the time of exposure . Persistent cytogenetic damage was observed exclusively in all 6 in-utero-exposed offspring , but not in their 12 match non-in-utero-exposed controls . The study characterizes EGME as a human teratogen , as indicated by the prevalence of characteristic dysmorphic features and persistent cytogenetic damage in individuals exposed in utero to this chemical .\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: Alteration of the oxidative stress of hepatocellular carcinoma ( HCC ) cells can influence the expressions of genes favored angiogenesis . Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3 . Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3 . This study was to investigate the influence of therapeutic concentrations of prazosin ( 0.01 and 0.1μM ) on cell proliferation and differential expressions of CCL2 , CCL20 , CXCL6 , CXCL10 , IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines . Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress ( cell line A ; HCC24/KMUH ) and one with this effect ( cell line B ; HCC38/KMUH ) were investigated by 0.01 and 0.1μM prazosin . The premixed WST-1 cell proliferation reagent was applied for proliferation assay . Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction . Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines . Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes . However , 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion , high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress . Clinical application of prazosin in patients with HCC should consider this possibility .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;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: To characterize the impact of increased production of TGF-beta in a xenograft model of human breast cancer , TGF-beta-responsive MDA-231 cells were genetically modified by stable transfection so as to increase their production of active TGF-beta1 . Compared with control cells , cells that produced increased amounts of TGF-beta proliferated in vitro more slowly . In vivo , however , tumors derived from these cells exhibited increased proliferation and grew at an accelerated pace . To evaluate the role of autocrine TGF-beta signaling , cells were also transfected with a dominant-negative truncated type II TGF-beta receptor ( TbetaRII ) . Disruption of autocrine TGF-beta signaling in the TGF-beta-overexpressing cells reduced their in vivo growth rate . Co-inoculation of Matrigel with the TGF-beta-overexpressing cells expressing the truncated TbetaRII compensated for their diminished in vivo growth capacity , compared with the TGF-beta-overexpressing cells with an intact autocrine loop . Tissue invasion by the tumor was a distinctive feature of the TGF-beta-overexpressing cells , whether or not the autocrine loop was intact . Furthermore , tumors derived from TGF-beta-overexpressing cells , irrespective of the status of the autocrine TGF-beta-signaling pathway , had a higher incidence of lung metastasis . Consistent with the suggestion that TGF-beta's enhancement of invasion and metastasis is paracrine-based , we observed no significant differences among the cell clones in an in vitro invasion assay . Thus , in this experimental model system in vitro assays of cell proliferation and invasion do not accurately reflect in vivo observations , perhaps due to autocrine and paracrine effects of TGF-beta that influence the important in vivo-based phenomena of tumor growth , invasion , and metastasis .\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: BACKGROUND &amp ; AIMS Hepatocytes are considered an exception of the paradigmatic inverse correlation between cell proliferation and terminal differentiation . In fact , hepatic vital functions are guaranteed by proliferating parenchymal cells during liver regeneration . However , a fine molecular characterization of the relationship between proliferation and differentiation in hepatocytes has been hampered by the lack of reliable in vivo or in vitro models . METHODS The hepatocyte terminal differentiation program was characterized in the immortalized , untransformed and differentiated hepatocytic cell line MMH , using several techniques . Particularly , two-dimensional difference gel electrophoresis combined to tandem mass spectrometry proteomic approach was used . Cell cycle and cell adhesion properties of MMH have been altered using either myc-overexpression and MEK1/2 inhibition or a constitutive active beta-catenin mutant , respectively . RESULTS The hepatocyte terminal differentiation program is stimulated by the exit from the cell cycle induced by cell-cell contact . Comparative proteomic analysis of proliferating versus quiescent hepatocytes validated the importance of contact inhibition , identifying 68 differently expressed gene products , representing 49 unique proteins . Notably , enzymes involved in important liver functions such as detoxification processes , lipid metabolism , iron and vitamin A storage and secretion , anti-inflammatory response and exocytosis were found significantly up-regulated in quiescent hepatocytes . Finally , we found that : ( i ) cell cycle arrest induced by MEK1/2 inhibition is not sufficient to induce hepatic product expression ; ( ii ) constitutive activation of beta-catenin counteracts the contact inhibition-induced terminal differentiation . CONCLUSION The hepatocyte terminal differentiation program requires a quiescent state maintained by cell-cell contact through the E-cadherin/beta-catenin pathway , rather than the inhibition of proliferation .\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: To assess the immune function of microglia and macrophages in brain tumors , the expression of MHC class II and B7 costimulatory molecules in three rodent glioma models was examined . Microglia and macrophages , which accounted for 5-12% of total cells , expressed B7.1 and MHC class II molecules in the C6 and 9L tumors , but not RG2 gliomas . Interestingly , the expression of B7.1 and MHC class II molecules by microglia and macrophage was associated with an increase in the number of tumor-infiltrating lymphocytes in C6 and 9L tumors . B7.2 expression , which was present at low levels on microglia and macrophages in normal brain , did not significantly change in tumors . Interestingly , the expression of all three surface antigens increased after microglia were isolated from intracranial C6 tumors and cultured for a short period of time . We conclude that microglia immune activity may be suppressed in gliomas and directly correlates to the immunogenecity of experimental brain tumors .\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: A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system . However , immune responses to such antigens are often muted or lacking due to the antigens being recognized as \" self \" , and further complicated by the tumour environment and regulation of immune cells within . In an effort to circumvent the lack of immune responses to tumour antigens , we have devised a strategy to develop potential synthetic immunogens . The strategy , termed mirror image phage display , is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system . Here as ' proof of principle ' we have selected molecular mimics of the well-characterised tumour associated antigen , the human mucin1 protein ( MUC1 ) from two different peptide phage display libraries . The putative mimics were compared in structure and function to that of the native antigen . Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells . The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells . The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides .\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: AMPK is a metabolic sensor that helps maintain cellular energy homeostasis . Despite evidence linking AMPK with tumor suppressor functions , the role of AMPK in tumorigenesis and tumor metabolism isunknown . Here we show that AMPK negatively regulates aerobic glycolysis ( the Warburg effect ) in cancer cells and suppresses tumor growth invivo . Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis . Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis , increased allocation of glucose carbon into lipids , and biomass accumulation . These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α ( HIF-1α ) , as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling . Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation .\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: Despite an increasing incidence of human breast cancer , its etiology remains unknown . Since some environmental chemicals are stored in human breast fat and are rodent mammary carcinogens , determining the genotoxic potential of environmental agents in this key target tissue is important . An assay was developed for detecting genotoxic activity , as unscheduled DNA synthesis ( UDS ) , induced by chemicals and UV radiation in early passage cultures of normal human mammary epithelial cells ( HMEC ) derived from 5 different women . In order to measure UDS in culture , reduction in the percentage of cells in S-phase was accomplished either by depriving the cells of epidermal growth factor and bovine pituitary extract or by contact inhibition of growth . Cultures were incubated with test chemicals for 24 h in the presence of [ 3H]-thymidine . UDS was quantitated autoradiographically as net grains per nucleus ( nuclear grains minus cytoplasmic background , population average ) with &gt ; or = 6 net nuclear grains considered in repair for any individual cell . A positive response was observed with UV radiation , benzo(a)-pyrene , aflatoxin B1 , ethylmethanesulfonate , 1,6-dinitropyrene , 2-acetylaminofluorene , and tobacco smoke condensate but not 7,12-dimethylbenz(a)anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin . These results demonstrate that HMEC from all 5 women examined have the ability to metabolize a variety of environmental chemicals to DNA-reactive forms . Furthermore , some chemicals known either to cause mammary cancer in rodents or to be contaminants in human breast tissue are genotoxic in HMEC . A positive response in passage 9 cultures was observed only with direct acting agents , suggesting that HMEC may lose their metabolic capabilities in longer-term cultures . The HMEC UDS assay may be used to address the role of environmental agents in human breast cancer by determining whether chemicals are DNA reactive or metabolized to DNA reactive species in this critical target tissue .\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: Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2 , but clinical trials with Src inhibitors have shown little activity . The present study evaluated preclinical efficacy of a novel peptidomimetic compound , KX-01 ( KX2-391 ) , that exhibits dual action as an Src and pretubulin inhibitor . KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231 , MDA-MB-157 , and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells . Treatments were evaluated by growth/apoptosis , isobologram analysis , migration/invasion assays , tumor xenograft volume , metastasis , and measurement of Src , focal adhesion kinase ( FAK ) , microtubules , Ki67 , and microvessel density . KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition . KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts ( 1 and 5 mg/kg , twice daily ) . KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis . KX01 also resulted in microtubule disruption in tumors . Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver . KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis . As ER/PR/HER2-negative patients are candidates for paclitaxel therapy , combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype .\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: An efficent antitumor and antiviral cellular immune response requires optimal interferon-gamma ( IFN-gamma ) secretion and perforin expression in CD8(+) T cells . The aim of this study was to define whether CD4(+) and CD8(+) T cells from patients with undifferentiated carcinoma of nasopharyngeal type ( UCNT ) , a tumor regularly associated with the Epstein-Barr virus ( EBV ) , have abnormal phenotype profiles , cytokine production , perforin and CD3-zeta expressions . Our data showed that CD4 and CD8 subset distribution was not grossly altered in the peripheral blood of UCNT patients , while tumor biopsies contained an increased proportion of CD8(+) T cells . The analysis of the CD4(+) subset showed a defect in interleukin-2 ( IL-2 ) production and a moderate increase of IL-10 production , a situation consistent with a Th1/Th2 imbalance . We have also demonstrated that CD8(+) lymphocytes from UCNT patients had a marked impairment of IFN-gamma secretion and perforin expression . This impairment was not related to the presence of detectable EBV DNA in the plasma . In UCNT patients , the blockade of the perforin pathway and of IFN-gamma production may constitute important mechanisms for immune escape by the tumor and for impaired control of EBV replication .\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: Bcl-2/E1B 19-kDa interacting protein 3 ( BNIP3 ) is a proapoptotic protein whose expression level is often low in colorectal cancer ( CRC ) cells due to the BNIP3 gene promoter DNA methylation by DNA methyltransferase ( DNMT ) . It is known that chemotherapy and radiotherapy suppress CRC through inducing tumor apoptosis . However , the molecular mechanisms underlying chemotherapy and radiotherapy-induced apoptosis of CRC cells are not well defined . In this study , we observed that the expression level of BNIP3 in colon cancer cells was significantly increased by treatment with therapeutic agents and radiation in vitro . The BNIP3 protein level in CRC tissues from patients who received preoperative concurrent chemotherapy was significantly higher than in those who received surgery alone . Furthermore , treatment with chemotherapeutic agents and radiation significantly decreased the DNMT1 expression level and enzymatic activity . Both expression level and activity of DNMT1 were inversely correlated with the expression level of BNIP3 in colon carcinoma cells after treatment with chemotherapeutic agents and radiation . Consistent with increased BNIP3 expression , chemotherapeutic agents and radiation induced colon carcinoma cell apoptosis in a dose-dependent manner . Based on these observations , we conclude that chemotherapy and radiotherapy inhibit DNMT1 expression to upregulate BNIP3 expression to promote CRC cell apoptosis . And , BNIP3 may play a role in the caspase-dependent apoptosis pathways , mainly during treatment with chemotherapy and radiotherapy .\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: Keratinocyte growth factor ( KGF , fibroblast growth factor-7 ) is a fibroblast-derived mitogen , which stimulates proliferation of epithelial cells . The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair . However , the role of KGF in cutaneous carcinogenesis and cancer progression is not known . We have examined the role of KGF in progression of squamous cell carcinoma ( SCC ) of the skin . The expression of KGF receptor ( KGFR ) mRNA was lower in cutaneous SCCs ( n = 6 ) than in normal skin samples ( n = 6 ) . Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF . KGF did not stimulate SCC cell proliferation , but it reduced invasion of SCC cells through collagen . Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes , including genes with tumor suppressing properties ( SPRY4 , DUSP4 , DUSP6 , LRIG1 , PHLDA1 ) . KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes , including genes associated with tumor progression ( MMP13 , MATN2 , CXCL10 , and IGFBP3 ) . Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2 . Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression . These results provide evidence , that KGF does not promote progression of cutaneous SCC , but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells , as compared to normal keratinocytes .\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: OBJECTIVES To investigate the effects of serotonin and melatonin ( MLT ) on the regulation of malignant growth and the activity of serotonin receptors ( 5HTR1a/-1b ) in prostate cancer ( PCa ) cell lines . MATERIALS AND METHODS In four PCa cell lines ( LNCaP , 22RV1 , PC3 , DU145 ) and two reference cell lines 5HTR1a and -1b , relative mRNA expression levels were assessed . Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments . RESULTS mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines . Serotonin showed a significant growth stimulatory effect in all PCa lines . The 5HTR1a and -1b agonists/antagonists did not significantly affect viability . MLT inhibited viability only in PC3 cells . Similarly , the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10(-4)M , while the 5HTR1b antagonist induced necrosis at 10(-4)M in all cell lines . Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist . CONCLUSIONS Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations . In contrast to other reports , our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth .\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 effect of polychlorinated biphenyls ( PCBs ) on Vero cell proliferation was investigated , with the attempts to assess the possible hormetic dose-response and to compare their structure-dependent toxicity . Both PCB congeners revealed low doses stimulation in our experiment . However , significant cytotoxicity was only observed in PCB 52 concentrations larger than 0.1 microg ml(-1) , while there was no significant inhibition in PCB 77-treated cells at concentrations selected . Furthermore , the time-dependent cytotoxic trends were different . The comparison between PCB 52 and PCB 77 indicated that the cytotoxic mechanisms involved in coplanar or non-coplanar PCB congener exposure were different , and this difference might be associated with individual genotoxicity and the release of contact inhibition , respectively .\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: 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) is the most potent tumor promoter ever tested in rodents . Although it is known that most of TCDD actions are mediated by binding to the aryl hydrocarbon receptor ( AhR ) , the mechanisms leading to tumor promotion still remain to be elucidated . Loss of contact inhibition is one characteristic hallmark in tumorigenesis . In rat liver epithelial WB-F344 cells , TCDD induces a release from contact inhibition , which is manifested by a twofold increase in cell number when TCDD ( 1 nM for 48 h ) is added to confluent cells in the presence of serum , but not when given to exponentially growing or subconfluent , serum-deprived WB-F344 cells . Loss of G1 arrest was also shown by flow cytometric analysis . We demonstrate that TCDD treatment significantly increases cyclin D2 and cyclin A protein levels and show by immunofluorescence that these proteins accumulate in the nucleus . Although TCDD treatment leads to a strong increase in cyclin D2/cdk4 and cyclin A/cdk2 complex formation , we could only detect an elevation of cyclin A/cdk2 activity . In accordance with a lack of elevated cdk4 activity , no decrease in the amount of hypophosphorylated retinoblastoma protein could be shown after TCDD treatment . The importance of increased cyclin A/cdk2 activity for TCDD-dependent release from contact inhibition was shown by the fact that the cdk2/cdc2-specific inhibitor olomoucine ( 25 microM ) abolished TCDD response . These data indicate cyclin A-dependent loss of G1 arrest after TCDD treatment mainly downstream of the retinoblastoma protein .\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: BACKGROUND Hesperidin , a flavanone present in citrus fruits , has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells . However , the precise mechanisms of action are not entirely understood . AIM The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma ( PPARγ ) in hesperidin's anticancer actions in human pre-B NALM-6 cells , which expresses wild-type p53 . METHODS The effects of hesperidin on cell-cycle distribution , proliferation , and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662 . The expression of peroxisome proliferator-activated receptor-gamma ( PPARγ ) , p53 , phospho-IκB , Bcl-2 , Bax , and XIAP proteins were focused on using the immunoblotting assay . The transcriptional activities of PPARγ and nuclear factor-kappaB ( NF-κB ) were analyzed by the transcription factor assay kits . The expression of PPARγ and p53 was analyzed using the RT-PCR method . RESULTS Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner . The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin . CONCLUSIONS The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells . These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies .\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: Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease ( GVHD ) . However , optimal dosage is still under debate . Thirty-one consecutive children , mainly with haematological malignancies , were transplanted in a single institution with such donors , selected by HLA-A -B compatibility by serology and DRB1* by DNA typing . Antithymocyte globulin ( Thymoglobuline ; Sangstat ) was infused at days -3 , -2 , -1 . Total dosage varied : 16 patients received a median of 7.5 mg/kg ( 2.5 to 10.5 : low-dose group ) , and 15 a median of 15.5 mg/kg ( 14.4 to 19.4 : high-dose group ) . Post-transplant GVHD prophylaxis consisted of cyclosporine , short-course methotrexate and steroids . CD3(+) , CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group . Median time to reach 100 CD4(+) cells was 8 months vs 4 months ( P = 0.03 ) . Median time to normal CD19(+) cells was 16 months vs 8 months ( P = 0.01 ) . CD16(+)CD56(+) and CD8(+) cell reconstitution was similar . Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections ( P = 0.009 ) . Although obtained from a limited number of patients , our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution .\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: Capsaicin , one of the major pungent ingredients found in red peppers , has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism . In this study , the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated . The results of a Cell Counting Kit-8 ( CCK-8 ) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner . Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment . Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment . Furthermore , we revealed that phospho-PI3 Kinase p85 ( Tyr458 ) and phospho-Akt ( Ser473 ) in PANC-1 cells were downregulated in response to capsaicin . Moreover , capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice . An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice . In vivo , capsaicin downregulated the expression of phospho-PI3 Kinase p85 ( Tyr458 ) and phospho-Akt ( Ser473 ) . In conclusion , we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells , and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 ( PFKFB3 ) . Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cells to generate ATP . A series of analogues was synthesized to study structure-activity relationships key to enzyme inhibition . Changes to the triazolo or pyridazinone rings were not favoured , but limited-size substitutions on the aryl ring provided modest increases in potency against the enzyme . Selected analogues and literature-described inhibitors were evaluated for their ability to suppress the glycolytic pathway , as detected by a decrease in lactate production , but none of these compounds demonstrated such suppression at non-cytotoxic concentrations .\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: OBJECTIVES Epiphyseal cartilage is a barrier to osteosarcoma invasion , however the mechanisms behind this resistance remain unclear . The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage . METHODS We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression . We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis ; proangiogenic vascular endothelial growth factor ( VEGF ) and antiangiogenic pigment epithelium-derived factor ( PEDF ) . RESULTS Epiphyseal cartilage remained intact across its entire length in all sections examined , despite increasing tumor size as well as intra- and extraosseous destruction . In the most advanced cases , only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded . This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF . In contrast , the resting , proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases . This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF . CONCLUSION Epiphyseal cartilage is resistant to local invasion by osteosarcoma . The balance of angiogenesis , influenced by pro- and antiangiogenic factors , is likely to play an important role in this resistance .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;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 order to determine the in vivo immune response in glioblastoma , monoclonal and polyclonal antibodies specific for inflammatory leukocytes and immunoregulatory products were utilized to stain tissue from four surgical specimens . The more activated the inflammatory cells , the more activated the tumors appeared to be . In the tumor with the largest infiltration ( Case 3 ) , inflammatory cells were stained for interferon-gamma , interleukin-2 , interleukin-1 beta , lymphotoxin , tumor necrosis factor-alpha , and transforming growth factor-beta . The tumor cells also expressed interleukin-1 beta , interleukin-6 , transforming growth factor-beta , tumor necrosis factor-alpha , and prostaglandin E. In contrast , in the tumor with the least inflammatory response ( Case 1 ) , the tumor cells did not express any cytokines . Expression of cytokines by glioma cells was modest in the two cases with modest inflammatory responses . Cellular inflammation , primarily consisting of T cells and macrophages with few or no B cells or natural killer cells , was two- to 15-fold greater outside the tumor than within . In contrast to leukocytes outside the tumor , which were activated and expressing class II major histocompatibility antigens , leukocytes within the tumor parenchyma or at the tumor's edge were negative for these antigens . In the four specimens studied here , the tumor cells themselves were also negative for class II major histocompatibility antigens . These findings , although preliminary , suggest that inflammatory cells within gliomas are inactivated and that glioma cells may increase the expression of immunosuppressive cytokines in response to an increased lymphocyte infiltrate . This observation , if corroborated by more extensive studies , may help to explain the failure of immune treatments in glioblastoma multiforme .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;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: In response to genotoxic stress , a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint ( DDC ) signalling pathway positively contributes to genome maintenance . Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest , cells must tightly regulate the activity of the kinases involved in this pathway . Despite their importance , the mechanisms for monitoring and modulating DDC signalling are not fully understood . Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae . On replication stress , cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53 , whereas activation of the upstream DDC kinase Mec1 remains normal . An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A , two positive regulators of Rad9-dependent Rad53 activation . A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107 . We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions . Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors .\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 It has been proven that metastasis-associated in colon cancer 1 ( MACC1 ) is a new gene that is related to the invasion and metastasis of tumors . MACC1 also regulates c-met expression . The aim of this study is to explore the expressions of MACC1 and hepatocyte growth factor receptor ( c-met ) , and its relationship with invasion , metastasis , and prognosis of non-small cell lung cancer ( NSCLC ) . METHODS MACC1 and c-met expressions were detected in 103 cases of NSCLC and 40 cases of neighboring normal lung cancer tissue using immunohistochemistry . RESULTS MACC1 and c-met expressions were significantly higher in lung cancer tissues than that in neighboring normal tissue ( P<0.001 ) . MACC1 and c-met expressions were associated with poor differentiation , advanced T stages , lymph node metastasis , and advanced TNM stages ( P<0.05 ) of NSCLC , but not with sex , age , smoking , and histological classification ( P>0.05 ) . In addition , a positive correlation between MACC1 and c-met expressions was observed ( r=0.403 , P<0.001 ) . The result from the Kaplan-Meier survival analysis showed that the five-year survival rate in patients with positive MACC1 and c-met expressions was remarkanly lower than that in patients with negative expressions ( P<0.05 ) . The result from the Cox regression analysis showed that MACC1 expression was an independent prognostic factor for NSCLC ( P=0.026 ) . CONCLUSIONS MACC1 and c-met have an important function in the differentiation , invasion , and metastasis of NSCLC . MACC1 and c-met have poor prognosis in patients with NSCLC . Moreover , MACC1 expression is an independent prognostic factor for NSCLC .\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 Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics , although only coronin 3 has been shown to be related to cancer cell migration . In glioblastoma cells , the knockdown of coronin 3 inhibits cell proliferation and invasion . Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma . In this paper , we analyze the migration , invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3 , and explore the mechanism of coronin 3 in the process of gastric cancer metastasis . RESULTS The expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M , which we established in our laboratory . We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues , and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis . Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines . Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells . In contrast , up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells . In addition , knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells . The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3 , and the results suggested that , following the knockdown of coronin 3 , the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K. CONCLUSION Coronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells , including their migration and 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: Twelve postmenopausal women ( 54-93 years ) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery . Seven premenopausal patients ( 32-50 years ) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma . Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis , hormone receptor determination and analysis of proliferation fraction . Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy . Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells . A decreased proliferation fraction was observed in two tumors responding to tamoxifen . Eight patients , all with estrogen receptor positive tumors , had stable disease . Progressive disease was observed in two patients with less than 25% receptor positive cells . In these tumors the percentage of proliferating cells remained high during therapy . Objective response was recorded for six patients treated with chemotherapy . The clinical response was reflected in a decreased proliferation fraction . No correlation was observed between response and percentage of proliferating cells in the untreated tumor . The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas .\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: Electronic properties of DNA are believed to play a crucial role in many phenomena in living organisms , for example the location of DNA lesions by base excision repair ( BER ) glycosylases and the regulation of tumor-suppressor genes such as p53 by detection of oxidative damage . However , the reproducible measurement and modelling of charge migration through DNA molecules at the nanometer scale remains a challenging and controversial subject even after more than a decade of intense efforts . Here we show , by analysing 162 disease-related genes from a variety of medical databases with a total of almost 20,000 observed pathogenic mutations , a significant difference in the electronic properties of the population of observed mutations compared to the set of all possible mutations . Our results have implications for the role of the electronic properties of DNA in cellular processes , and hint at the possibility of prediction , early diagnosis and detection of mutation hotspots .\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: The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians . The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival . This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread . In this study , we used one- and two-dimensional gel electrophoresis , mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas . Using a refinement for classifying oral carcinomas in regard to prognosis , we analyzed small but lymph node metastasis-positive versus large , lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination . Specific protein patterns favoring metastasis were observed in the \" more-aggressive \" group defined by the present study . This group displayed upregulation of proteins involved in migration , adhesion , angiogenesis , cell cycle regulation , anti-apoptosis and epithelial to mesenchymal transition , whereas the \" less-aggressive \" group was engaged in keratinocyte differentiation , epidermis development , inflammation and immune response . Besides the identification of several proteins not yet described as deregulated in oral carcinomas , the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death;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: BACKGROUND Elevated levels of air pollution are associated with increased risk of lung cancer . Particulate matter ( PM ) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation , a lung cancer risk factor . Vanadium pentoxide ( V2O5 ) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans . In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage ( initiation-promotion ) model of pulmonary neoplasia in mice . RESULTS A/J , BALB/cJ ( BALB ) , and C57BL/6J ( B6 ) mice were treated either with the initiator 3-methylcholanthrene ( MCA ; 10 microg/g ; i.p. ) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment . Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid ( BALF ) , and chemokines , transcription factor activity , and MAPK signaling were quantified in lung homogenates . We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J ( 10.3 +/- 0.9 tumors/mouse ) and BALB ( 2.2 +/- 0.36 ) mice significantly above that observed with MCA/PBS or V2O5 alone ( P &lt ; 0.05 ) . No tumors were observed in the B6 mice in any of the experimental groups . Mice sensitive to tumor promotion by V2O5 were also found to be more susceptible to V2O5-induced pulmonary inflammation and hyperpermeability ( A/J>BALB>B6 ) . Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1 , higher NFkappaB and c-Fos binding activity , as well as sustained ERK1/2 activation in lung tissue . CONCLUSIONS In this study we demonstrate that V2O5 , an occupational and environmentally relevant metal oxide , functions as an in vivo lung tumor promoter among different inbred strains of mice . Further , we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation . These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways .\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: The DNA mismatch repair ( MMR ) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity . The genes of the MMR pathway are highly conserved across different organisms . Likewise , defective MMR function universally results in microsatellite instability ( MSI ) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer . ( Lynch syndrome ) . To identify previously unrecognized deleted genes or loci that can lead to MSI , we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae . This pool represents a collection of non-essential homozygous yeast diploid ( 2N ) mutants in which there are deletions for over four thousand yeast open reading frames ( ORFs ) . From our screen , we identified a deletion mutant strain of the PAU24 gene that leads to MSI . In a series of validation experiments , we determined that this PAU24 mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain , other deletion mutants and comparable to a MMR mutant involving the MLH1 gene . Likewise , in yeast strains with a deletion of PAU24 , we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen .\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: Comparative mutagenesis studies of N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene ( dG-AAF ) and N-(2'-deoxyguanosin-8-yl)-2-aminofluorene ( dG-AF ) adducts positioned in the Nar I restriction enzyme site were performed using Escherichia coli ( E. coli ) and simian kidney ( COS-7 ) cells . Oligodeoxynucleotides ( (5)(')TCCTCG(1)G(2)CG(3)CCTCTC ) containing a recognition sequence for the Nar I restriction enzyme were modified site-specifically with dG-AAF or dG-AF . Modified and unmodified oligomers inserted into single-stranded phagemid shuttle vectors were used to transform E. coli or to transfect COS-7 cells . Following replication in host cells , progeny plasmids were recovered and analyzed for mutations . In SOS-induced E. coli , dG-AAF primarily induced one- and two-base deletions . The mutational frequency varied , depending on the position modified in the Nar I site ; 91% two-base deletions were observed at G(3) , while 8.4% and 2.8% deletions were detected at G(2) and G(1) , respectively . In contrast , dG-AF at any position in the Nar I site failed to produce deletions , generating primarily G --&gt ; T transversions ( mutational frequency , 7.6-8.4% ) . In COS-7 cells , both dG-AAF and dG-AF primarily induced G --&gt ; T transversions . Mutation frequencies for dG-AAF were 9.4-24% , the highest values being at G(1) and G(3) . Mutation frequencies for dG-AF were 9.3-21% , the higher value at G(2) . We conclude from this study that the mutation potential of dG-AAF and dG-AF depends on the structure of the adduct , the sequence context of the lesion , and the host cell used for the experiment .\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 investigate whether luteolin , a highly prevalent flavonoid , reverses the effects of epithelial-mesenchymal transition ( EMT ) in vitro and in vivo and to determine the mechanisms underlying this reversal . METHODS Murine malignant melanoma B16F10 cells were exposed to 1% O(2) for 24 h . Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay , respectively . EMT-related proteins , such as E-cadherin and N-cadherin , were examined using Western blotting . Female C57BL/6 mice ( 6 to 8 weeks old ) were injected with B16F10 cells ( 1�10(6) cells in 0.2 mL per mouse ) via the lateral tail vein . The mice were treated with luteolin ( 10 or 20 mg/kg , ip ) daily for 23 d . On the 23rd day after tumor injection , the mice were sacrificed , and the lungs were collected , and metastatic foci in the lung surfaces were photographed . Tissue sections were analyzed with immunohistochemistry and HE staining . RESULTS Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips , which was accompanied by increased cellular adhesion and invasion . Luteolin ( 5-50 μmol/L ) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner . Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells ( indicating the occurrence of EMT-like transformation ) , which was reversed by luteolin ( 5 μmol/L ) . In B16F10 cells , luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway . In experimental metastasis model mice , treatment with luteolin ( 10 or 20 mg/kg ) reduced metastatic colonization in the lungs by 50% . Furthermore , the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues . CONCLUSION Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin , suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent .\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: Metastasis is the most lethal attribute of human malignancy . High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer . Previous studies indicate that a mutation of the threonine residue at position 34 ( Thr34Ala ) of survivin generates a dominant-negative mutant that induces apoptosis , inhibits angiogenesis , and suppresses highly metastatic breast carcinoma in mouse models . We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis . The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages . We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A ( Lip-mS ) , Lip-plasmid ( Lip-P ) , or normal saline ( NS ) . Eight days after the last dose , five randomly chosen mice from each group were sacrificed . We detected the apoptotic index , microvessel density ( MVD ) , lymphatic microvessel density ( LMVD ) , and the expression of VEGF-D with immunohistochemistry . After the remaining animals were sacrificed , we compared the tumor-infiltrated lymph nodes in each group . Administration of mSurvivinT34A plasmid complexed with cationic liposome ( DOTAP/chol ) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model . These responses were associated with tumor cell apoptosis , and angiogenesis and lymphangiogenesis inhibition . Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis , thus suppressing tumor growth and lymphatic metastasis . The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Reactive or activated stroma characterizes many malignancies including breast cancers . Recently , we isolated a reactive mouse mammary gland stromal cell line called BJ3Z . These cells express alpha-smooth muscle actin and stromal cell-derived factor 1 ( SDF-1 ) and are tumorigenic when injected into mice . Here we show that , in vivo , BJ3Z cells influence the angiogenesis and proliferation of xenografted estrogen receptor ( ER)-positive MCF-7 human breast cancer cell-derived solid tumors . The growth-promoting effects of BJ3Z cells are equivalent to those of estradiol ( E(2) ) . BJ3Z cells also increase the proliferation of normal mouse mammary luminal cells adjacent to tumors . In vitro , BJ3Z cells reorganize and increase the proliferation of cocultured malignant MCF-7 and normal human breast MCF10A cells grown as organoids in three-dimensional culture . The effects of BJ3Z cells on MCF-7 cells are equivalent to those of E(2) . In contrast , BJ3Z cells do not alter the growth of highly aggressive ER-negative MDA-MB-231 human breast cancer cells . We show that BJ3Z cells secrete vascular endothelial growth factor ( VEGF ) . The growth of MCF-7 organoids induced by BJ3Z can be inhibited by antagonists of VEGF and SDF-1 . Conversely , recombinant VEGF stimulates the proliferation of MCF-7 , but not MDA-MB-231 , organoids . We conclude that , in addition to angiogenesis , VEGF released by activated stroma increases the growth of ER-positive malignant epithelial cells and of adjacent normal epithelium . Because activated stroma can substitute for E(2) and fosters hormone-independent growth of ER-positive tumors , we suggest that breast cancers exhibiting intrinsic hormone resistance may respond to antiangiogenic therapies .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Ceramide is a sphingolipid metabolite that induces cancer cell death . When C6-ceramide is encapsulated in a nanoliposome bilayer formulation , cell death is selectively induced in tumor models . However , the mechanism underlying this selectivity is unknown . As most tumors exhibit a preferential switch to glycolysis , as described in the \" Warburg effect \" , we hypothesize that ceramide nanoliposomes selectively target this glycolytic pathway in cancer . We utilize chronic lymphocytic leukemia ( CLL ) as a cancer model , which has an increased dependency on glycolysis . In CLL cells , we demonstrate that C6-ceramide nanoliposomes , but not control nanoliposomes , induce caspase 3/7-independent necrotic cell death . Nanoliposomal ceramide inhibits both the RNA and protein expression of GAPDH , an enzyme in the glycolytic pathway , which is overexpressed in CLL . To confirm that ceramide targets GAPDH , we demonstrate that downregulation of GAPDH potentiates the decrease in ATP after ceramide treatment and exogenous pyruvate treatment as well as GAPDH overexpression partially rescues ceramide-induced necrosis . Finally , an in vivo murine model of CLL shows that nanoliposomal C6-ceramide treatment elicits tumor regression , concomitant with GAPDH downregulation . We conclude that selective inhibition of the glycolytic pathway in CLL cells with nanoliposomal C6-ceramide could potentially be an effective therapy for leukemia by targeting the Warburg effect .\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 telomerase activity and the senescence profile of cultured breast fibroblasts from normal human interstitial and malignant stromal tissue were studied in comparison with their proliferation and differentiation pattern . Fibroblasts were grown either in the presence or absence of a conditioned medium ( CM ) obtained from cultures of the oestrogen receptor-positive breast cancer MCF-7 cell line . At different passages ( from the 2nd up to the 48th ) , fibroblasts were examined for the telomerase activity by the Telomerase Repeats Amplification Protocol ( TRAP ) assay , for proliferation profile by Ki-67 antigen expression , and the myofibroblast or smooth muscle cell-like differentiation pattern by immunofluorescence with monoclonal antibodies specific for smooth muscle markers . Serial passages of fibroblasts from normal or tumour breast reveal that the relationship between the levels of telomerase activity and phenotypic/proliferation profile changes with cell subcultivation in a different manner in the two cell populations . The fibroblasts from normal tissue completed 12 passages in a CM-independent way prior to senescence whereas fibroblasts from tumour stroma senescence were attained after 48 passages . These cells showed a marked decrease of telomerase activity , growth rate and smooth muscle alpha-actin expressing myofibroblasts after the 32nd passage . CM treatment of this fibroblast population induces a decline in the myofibroblast content , which precedes the changes in telomerase activity . Passaged fibroblasts from normal breast tissue can be converted to myofibroblasts upon CM treatment whereas those from tumour stroma were CM-insensitive . Taken together our data suggest that a heterogeneous fibroblast population with different life span is activated/recruited in the breast interstitium and poses the problem of a unique activation/recruitment of fibroblasts in neoplastic conditions .\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: OBJECTIVE To design and develop a novel , sensitive and versatile method for in vivo foot printing and studies of DNA damage , such as DNA adducts and strand breaks . METHODS Starting with mammalian genomic DNA , single-stranded products were made by repeated primer extension , these products were ligated to a double-stranded linker having a randomized 3 ' overhang , and used for PCR . DNA breaks in p53 gene produced by restriction endonuclease AfaI were detected by using this new method followed by Southern hybridization with DIG-labeled probe . RESULTS This randomized terminal linker-dependent PCR ( RDPCR ) method could generate band signals many-fold stronger than conventional ligation-mediated PCR ( LMPCR ) , and it was more rapid , convenient and accurate than the terminal transferase-dependent PCR ( TDPCR ) . CONCLUSION DNA strand breakage can be detected sensitively in the gene level by RDPCR . Any lesion that blocks primer extension should be detectable .\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 elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib . METHODS The cell lines A549 , HeLa , and HepG2 were tested . The enzyme activity was examined under cell-free conditions using 384-well microplate assays . Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay . Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system . Protein expression analysis was performed using Western blotting . RESULTS Sorafenib potently suppressed the activities of cRAF , VEGFR2 , and RET with IC(50) values of 20.9 , 4 and 0.4 nmol/L , respectively . Sorafenib inhibited cRAF , VEGFR2 , and RET via non-ATP-competitive , ATP-competitive and mixed-type modes , respectively . In contrast , sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines . The IC(50) values for inhibition of A549 , HeLa , and HepG2 cells were 8572 , 4163 , and 8338 nmol/L , respectively . In the 3 cell lines , sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level , which in turn regulated related gene expression via a feed-back mechanism . CONCLUSION This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib .\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: PURPOSE Astrocytoma arises in the central nervous system as a tumor of great lethality , in part because of the invasive potential of the neoplastic cells that are able to release extracellular matrix-degrading enzymes . Furin convertase activates several precursor matrix metalloproteases involved in the breakdown of the extracellular matrix . In the present study inhibition of furin was achieved by gene transfer of alpha(1)-antitrypsin Portland ( PDX ) cDNA . EXPERIMENTAL DESIGN This furin inhibitor was transfected into two tumorigenic astrocytoma cell lines . The inhibitory effect was evaluated using in vivo tumorigenicity , invasion , and proliferation assays , as well as by investigating impairment of furin substrate processing . RESULTS Expression of PDX prevented the s.c. growth of the transfected cells . Invasion assays demonstrated that PDX-transfected cells exhibited a reduced invasive ability in vitro and in vivo . Furthermore , s.c. growth of PDX transfectant xenotransplants showed a significant reduction in size that coincided with a significant decrease of the in vitro doubling time and of the in vivo cell proliferation ability . Additional studies showed that the furin substrates insulin-like growth factor IR , transforming growth factor beta and membrane type 1-matrix metalloprotease were not activated in PDX-expressing astrocytoma cells . CONCLUSIONS PDX expression in astrocytoma cells demonstrated a direct mechanistic link between furin inhibition , and decreased astrocytoma proliferation and invasive ability . Because furin inhibition inhibits both invasiveness and cell growth in astrocytoma , furin should be considered a promising target for glioblastoma therapy .\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: Genomic instability has long been recognized as the main feature of neoplasia and a factor modulating individual cancer susceptibility . There are attempts to find effective assays of both individual DNA repair capacity and genetic instability , and their relation to the cancer risk . Genetic predisposition plays an important role in the etiology and development of head and neck squamous cell carcinoma ( HNSCC ) . The aim of our study was to search for a correlation between chromosomal instability and DNA repair capacity in HNSCC patients and healthy controls . The chromosomal instability was measured by the number of bleomycin ( BLM)-induced chromosomal aberrations and diepoxybutane ( DEB)-induced sister chromatid exchanges . The DNA repair capacity was assessed using the DEB-induced adaptive response ( AR ) . The HNSCC patients in our study showed a significant increase in chromosomal instability after a preterminal exposure of their lymphocytes to either BLM for the last 5 h or DEB for the last 24 h of incubation . However , the AR was higher in HNSCC patients than in the control group , suggesting an increase in the DNA repair capacity in the cancer patients as compared to the control . There is no correlation between the DNA repair capacity estimated on the basis of preterminal exposures to BLM and DEB and the DNA repair capacity estimated on the basis of the adaptive response to DEB . The preterminal exposure and the adaptive response test may activate different DNA repair mechanisms .\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: Hepatocellular carcinoma ( HCC ) , one of the most frequent and deadliest cancers , has been increasing considerably in the United States . In the absence of a proven effective therapy for HCC , novel chemopreventive strategies are urgently needed to lower the current morbidity and mortality of HCC . Recently , we have reported that resveratrol , a compound present in grapes and red wine , significantly prevents diethylnitrosamine ( DENA)-induced liver tumorigenesis in rats , although the mechanism of action is not completely understood . In the present study , we have examined the underlying mechanisms of resveratrol chemoprevention of hepatocarcinogenesis by investigating the effects of resveratrol on oxidative damage and inflammatory markers during DENA-initiated rat liver carcinogenesis . There was a significant increase in hepatic lipid peroxidation and protein oxidation in carcinogen control animals compared with their normal counterparts at the end of the study ( 20 weeks ) . Elevated expressions of inducible nitric oxide synthase and 3-nitrotyrosine were noticed in the livers of the same animals . Dietary resveratrol ( 50-300 mg/kg ) administered throughout the study reversed all the aforementioned markers in a dose-responsive fashion in rats challenged with DENA . Resveratrol also elevated the protein and mRNA expression of hepatic nuclear factor E2-related factor 2 ( Nrf2 ) . Results of the present investigation provide evidence that attenuation of oxidative stress and suppression of inflammatory response mediated by Nrf2 could be implicated , at least in part , in the chemopreventive effects of this dietary agent against chemically induced hepatic tumorigenesis in rats . The outcome of this study may benefit the development of resveratrol in the prevention and intervention of human HCC .\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: The epidemiologic association between asbestos exposure and human malignant mesothelioma is well established . However , the molecular mechanisms linking asbestos exposure of humans and the subsequent mesothelioma formation is not well understood . The most frequent genetic changes found so far in human malignant mesothelioma ( HMM ) are deletions and point mutations in the tumor suppressor genes p16INK4a and NF2 . Whereas homozygous deletions appear to be the predominant mechanism leading to p16/CDKN2A inactivation , inactivating point mutations coupled with allelic loss mainly occur at the NF2 locus . In the present study , asbestos-treated human mesothelial cells ( HMC ) , SV40-transformed human mesothelial cells ( MeT-5A ) and a human mesothelioma cell line ( COLO ) were investigated for genetic changes of cell cycle genes ( cyclin D1 , p16INK4a , RB1 , CDK2 ) using multicolor fluorescence in situ hybridization ( mFISH ) in interphase cells . The results show that cyclin D1 is unaffected in all investigated cells . The p16INK4a gene locus was shown to be mutated in COLO cells but not in HMC . After labeling of CDK2 and RB1 , hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells . Our data indicate that disarrangement of the RB1 dependent pathway seems to be involved in mesothelioma formation .\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: OBJECTIVE : Emerging evidences implicate long noncoding RNAs ( lncRNAs ) are deregulated in cancer development . The purpose of the current study is to investigate the role of new lncRNA , named PlncRNA-1 , in prostate cancer ( CaP ) pathogenesis . MATERIALS AND METHODS : In this study , real-time q-PCR was used to demonstrate the expression of PlncRNA-1 in 16 pairs CaP tissues and matched normal tissues , 14 pairs CaP tissues and BPH tissues , 4 CaP cell lines , including LNCaP , LNCaP-AI , PC3 , and C4-2 , and 2 normal prostate epithelial cell lines RWPE-1 and PWR-1E . After PlncRNA-1 was suppressed by siRNA in LNCaP and LNCaP-AI cell lines , cell proliferation and apoptosis were assessed using CCK-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) . After PlncRNA-1 and AR was suppressed by siRNA in LNCaP and LNCaP-AI cell lines , real-time q-PCR and Western blotting were used to measure reciprocal regulation of PlncRNA-1 and AR . RESULTS : We showed that expression PlncRNA-1 , was significantly higher in CaP cells relative to normal prostate epithelial cells , as well as higher in human CaPs compared with normal tissues and benign prostatic hyperplasia ( BPH ) . Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI . Mechanistically , PlncRNA-1 suppression by siRNA resulted in a decrease of androgen receptor ( AR ) mRNA , protein and AR downstream target . Of note , blockade of AR signaling with siRNA also resulted in a suppression of PlncRNA-1 expression in CaP cell lines . CONCLUSIONS : Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target .\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: Autophagy is one of the survival processes of cancer cells , especially in stressful conditions such as starvation , hypoxia and chemotherapeutic agents . However , its roles in tumor survival have not yet been fully elucidated . Here , we found for the first time that JAK2/STAT3 was activated in HeLa cells when they were starved or treated with rapamycin . STAT3 activation was associated with autophagic processes , because it was completely inhibited by 3-methyladenine , partially inhibited by knockdown of molecules associated with autophagic processes and blocked by antioxidants , DPI , a Nox inhibitor and knockdown of p22 phox , indicating that ROS generated by Nox that was activated during autophagic processes activated JAK2/STAT3 pathway . Activated STAT3 directly bound to IL6 promoter and increased IL6 mRNA and protein secretion . Finally , the conditioned media , which included IL6 , from starved HeLa cells promoted cancer cell survival in both normal and starved conditions , confirmed by clonogenic , proliferation and cell death assays . These data together indicate that the autophagic process in cancer cells can contribute to their survival by JAk2/STAT3 activation and subsequent secretion of growth factors .\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: We have examined the effect of FK506 on the Adriamycin sensitivity of the multidrug resistant human chronic myelocytic leukemia cell line ( K562/ADM ) . In K562/ADM cells , 1.0 microgram/ml FK506 reversed the resistance of Adriamycin , and increased the IC50 value for Adriamycin up to 17 fold . However , IC50 value for the parent cells ( K562 ) increased only 1.5 fold . By cell cycle analysis , the accumulation in late S-G2M phase was confirmed on K562/ADM cells , treated with 1.0 microgram/ml FK506 and low-dose of Adriamycin . Cyclosporin A ( CsA ) could also restored the Adriamycin sensitivity in the K562/ADM cells , as previously reported. 1.0 microgram/ml FK506 as well as CsA significantly increased radioactive Adriamycin accumulation in K562/ADM cells and blocked [ 3H]azidopien photoaffinity labeling of P-glycoprotein . These results suggest that 1.0 microgram/ml FK506 could reverse the Adriamycin resistance in a MDR human leukemia cells through the interaction with P-glycoprotein .\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: Evaluation of immune dysfunction during the tumor-bearing state is a critical issue in combating cancer . In this study , we initially found that IL-6 , one of the cachectic factors , suppressed CD4(+) T cell-mediated immunity through downregulation of MHC class II by enhanced arginase activity of dendritic cells ( DC ) in tumor-bearing mice . We demonstrated that administration of Ab against IL-6R ( anti-IL-6R mAb ) greatly enhanced T cell responses and inhibited the growth of tumor in vivo . We also found that IL-6 upregulated the expression of arginase-1 and arginase activity of DC in vitro . Tumor-infiltrating CD11c(+) DC exhibited upregulated mRNA expression of arginase-1 but reduced expression of MHC class II in parallel with the increase in serum IL-6 levels at the late stage in tumor-bearing hosts . However , the administration of anti-IL-6R mAb into tumor-bearing mice inhibited both the downmodulation of MHC class II and the upregulation of arginase-1 mRNA levels in DC . Furthermore , we noted that N(ω)-hydroxy-L-arginine or L-arginine , an arginase-1 inhibitor , blocked the reduction in MHC class II levels on CD11c(+) DC during the tumor-bearing state . Finally , we demonstrated that the administration of N(ω)-hydroxy-L-arginine at the peritumor site significantly enhanced CD4(+) T cell responses and inhibited tumor growth . Thus , IL-6-mediated arginase activation and the subsequent reduction in MHC class II expression on DC appeared to be critical mechanisms for inducing dysfunction of the immune system in the tumor-bearing state . Blockade of the IL-6-arginase cascade is a promising tool to overcome the dysfunction of antitumor immunity in tumor-bearing hosts .\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: The knowledge of alterations in regulation of autophagy during tumorigenesis may also help our understanding of its normal control . We established an experimental system and reported recently that autophagic capacity , measured as the cell's capability of increasing segregation ( formation of autophagosomes ) and subsequent degradation of cytoplasmic quanta were highly increased in premalignant nodule cells 6 months after initiation by azaserine in the rat pancreas in vivo . In the present study , we followed changes of these autophagic functions throughout the tumour progression . We carried out electron-microscopic morphometrical analysis of the expansion of autophagic vacuole compartment and subcompartments induced by vinblastine ( an in vivo segregation enhancer ) , as well as their regression upon segregation-inhibitor cycloheximide post-treatment . Premalignant tumour samples were taken at month 5 , month 8 ( nodules ) , month 10 and month 15 ( adenomas ) after initiation . In all these stages , a highly increased and varying autophagic capacity was found compared with the host tissue . The basal ( non-stimulated ) autophagic compartment was measurable only at month 5 and month 15 , and its regression upon cycloheximide was consistent with increased basal autophagic activity . Compared with the host tissue , autophagic capacity profoundly decreased in the differentiated and anaplastic adenocarcinomas at month 20 , when , surprisingly , cycloheximide was unable to inhibit segregation . Our conclusion is that down-regulation of the cycloheximide sensitive segregation and a partly compensatory up-regulation of an alternative pathway of segregation might occur along with malignant transformation .\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: IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy . Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality . This study tested the ability of IL-15 to block apoptosis , prevent immunosuppression , and improve survival in sepsis . Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia . The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle . In addition to survival studies , splenic cellularity , canonical markers of activation and proliferation , intracellular pro- and antiapoptotic Bcl-2 family protein expression , and markers of immune cell apoptosis were evaluated by flow cytometry . Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo . IL-15 blocked sepsis-induced apoptosis of NK cells , dendritic cells , and CD8 T cells . IL-15 also decreased sepsis-induced gut epithelial apoptosis . IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA . IL-15 increased both circulating IFN-gamma , as well as the percentage of NK cells that produced IFN-gamma . Finally , IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia . In conclusion , IL-15 prevents two immunopathologic hallmarks of sepsis , namely , apoptosis and immunosuppression , and improves survival in two different models of sepsis . IL-15 represents a potentially novel therapy of this highly lethal disorder .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: Ulcerative colitis ( UC ) is a major form of chronic inflammation that can frequently progress to colon cancer . Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis . Macrophages contribute to the development of colitis-associated colon cancer ( CAC ) . However , the role of neutrophils is not well understood . To better understand the involvement of tumor-associated neutrophils ( TANs ) in the regulation of CAC , we used a mouse CAC model produced by administering azoxymethane ( AOM ) , followed by repeated dextran sulfate sodium ( DSS ) ingestion . This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon . We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment . Macrophages infiltrated the lamina propria and submucosa , together with a marked increase in neutrophil infiltration . The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice , together with the infiltration of neutrophils expressing CXCR2 , a specific receptor for CXCL2 . This process was followed by neoplastic transformation . After AOM and DSS treatment , the mice showed enhanced production of metalloproteinase ( MMP)-9 and neutrophil elastase ( NE ) , accompanied by excessive vessel generation and cell proliferation . Moreover , CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro . Furthermore , administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2 , CXCL2 , MMP-9 , and NE . These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The purpose of this study was to combine a three-dimensional NMR-compatible bioreactor with hyperpolarized ( 13)C NMR spectroscopy in order to probe cellular metabolism in real time . JM1 ( immortalized rat hepatoma ) cells were cultured in a three-dimensional NMR-compatible fluidized bioreactor . ( 31)P spectra were acquired before and after each injection of hyperpolarized [ 1-(13)C ] pyruvate and subsequent ( 13)C spectroscopy at 11.7 T . ( 1)H and two-dimensional ( 1)H-(1)H-total correlation spectroscopy spectra were acquired from extracts of cells grown in uniformly labeled ( 13)C-glucose , on a 16.4 T , to determine ( 13)C fractional enrichment and distribution of ( 13)C label . JM1 cells were found to have a high rate of aerobic glycolysis in both two-dimensional culture and in the bioreactor , with 85% of the ( 13)C label from uniformly labeled ( 13)C-glucose being present as either lactate or alanine after 23 h . Flux measurements of pyruvate through lactate dehydrogenase and alanine aminotransferase in the bioreactor system were 12.18 +/- 0.49 nmols/sec/10(8) cells and 2.39 +/- 0.30 nmols/sec/10(8) cells , respectively , were reproducible in the same bioreactor , and were not significantly different over the course of 2 days . Although this preliminary study involved immortalized cells , this combination of technologies can be extended to the real-time metabolic exploration of primary benign and cancerous cells and tissues prior to and after therapy .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Hormone-independent tumor growth and metastasis are associated with increased mortality in human prostate cancer . In this study , we evaluate a potential role for ligand-mediated activation of HER2 receptor tyrosine kinase in androgen-independent prostate cancers . HER2 , HER3 , and epidermal growth factor receptor were detected in the androgen-independent cell line 22Rv1 . Heregulin stimulation results in receptor phosphorylation and cell proliferation that is inhibited by increasing concentrations of anti-HER2 recombinant humanized monoclonal antibody ( rhuMAb ) 2C4 . Furthermore , inhibition of tumor growth was observed in xenografts derived from 22Rv1 cells when treated with rhuMAb 2C4 in a dose-dependent manner . These studies provide a framework , both in vitro and in vivo , to examine the molecular mechanisms of ligand-driven HER2 activation in androgen-independent tumorigenesis .\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: Free radical-induced cellular stress contributes to cancer during chronic inflammation . Here , we investigated mechanisms of p53 activation by the free radical , NO . NO from donor drugs induced both ataxia-telangiectasia mutated ( ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications , leading to an increase in p53 transcriptional targets and a G(2)M cell cycle checkpoint . Such modifications were also identified in cells cocultured with NO-releasing macrophages . In noncancerous colon tissues from patients with ulcerative colitis ( a cancer-prone chronic inflammatory disease ) , inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels . Immunostaining of HDM-2 and p21(WAF1) was consistent with transcriptionally active p53 . Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Intra-arterial infusion with cisplatin ( CDDP ) and bleomycin ( BLM ) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone . Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM . Two to four courses of the infusion therapy were given to each patient , and the response rate , the tumor and serum drug concentrations , and the cell kinetics in tumor tissue were evaluated . The response rate ( CR+PR ) was 71.4% according to the WHO criteria . There was no difference , in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders . Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment , both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors . These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy .\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: Histone deacetylase inhibitors ( HDACi ) are promising epigenetic cancer chemotherapeutics rapidly approaching clinical use . In this study , we tested using in vitro and in vivo models the differential biological effects of a novel HDAC inhibitor [ belinostat ( PXD101) ] , in a wide panel of androgen-sensitive and androgen-independent tumor cells . Belinostat significantly increased acetylation of histones H3 and H4 . Belinostat potently inhibited the growth of prostate cancer cell lines ( IC50 range from 0.5 to 2.5 �M ) with cytotoxic activity preferentially against tumor cells . This agent induced G2/M arrest and increased significantly the percentage of apoptosis mainly in androgen-sensitive tumor cells confirming its growth-inhibitory effects . The cell death mechanisms were studied in three different prostate cancer cell lines with different androgen dependence and expression of androgen receptor ; LAPC-4 and 22rv1 ( androgen-dependent and expressing androgen receptor ) and PC3 ( androgen-independent not expressing androgen receptor ) . Belinostat induced the expression of p21 and p27 , acetylation of p53 and G2/M arrest associated with Bcl2 and Bcl-Xl downmodulation and significant reduction of survivin , IAPs and Akt/pAkt and increased caspase-8 and -9 expression/activity . Belinostat effectiveness was dependent on the androgen receptor ( AR ) , since the stable transfection of AR greatly increased the efficacy of this HDAC inhibitor . These observations were correlated using in vivo models . We demonstrated that belinostat preferentially resulted in antitumor effect in androgen-dependent tumor cells expressing AR . Our findings provide evidence that belinostat may be a promising anticancer drug for prostate cancer expressing AR , supporting its clinical role in prostate cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The HT29 adenocarcinoma is a common model of epithelial cell differentiation and colorectal cancer and its death is an oft-analyzed response to TNF family receptor signaling . The death event itself remains poorly characterized and here we have examined the involvement of caspases using pan-caspase inhibitors. zVAD-fmk did not block death of HT29 cells in response to activation of the Fas , TRAIL , TNF , TWEAK and LTbeta receptors . The secondary induction of TNF or the other known bona fide death inducing ligands did not account for death following LTbeta receptor activation indicating that TNF family receptors can trigger a caspase-independent death pathway regardless of the presence of canonical death domains in the receptor . To provide a frame of reference , the phenotype of HT29 death was compared to four other TNF family receptor triggered death events ; Fas induced Jurkat cell apoptosis , TNF/zVAD induced L929 fibroblast necrosis , TNF induced death of WEHI 164 fibroblastoid cells and TNF/zVAD induced U937 death . The death of HT29 and U937 cells under these conditions is an intermediate form with both necrotic and apoptotic features . The efficient coupling of TNF receptors to a caspase-independent death event in an epithelial cell suggests an alternative approach to cancer therapy .\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 Hepatocellular carcinoma ( HCC ) is the most common liver cancer . Therapeutic results are usually unsatisfactory because liver tumors recur often . Immunologic factors may be related to the recurrence of HCC ; however , this possibility is mentioned only rarely . METHODS Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs : group A ( n = 8 ) , diameter ≤3 cm ; group B ( n = 8 ) , diameter >3 cm and ≤5 cm ; and group C ( n = 14 ) , diameter >5 cm . T-lymphocytes from peripheral blood , nontumor liver tissue , and the HCC were analyzed . RESULTS The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups . CD25+ cells were increased in the tumor tissue in group C patients ( range , 6-41% ; median , 22.9% ; P = .003 ) , compared to group A patients . The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes ( r = 0.556 ) . These CD4+ CD25+ lymphocytes produced transforming growth factor-β and interferon-γ but not interleukin-10 , and were anergic to plate-coated monoclonal antibodies ( anti-CD3/anti-CD28 ) . The characteristics of these antibodies were comparable to those of regulatory T cells . When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells , the proliferation of lymphocytes was inhibited . CONCLUSION The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes . These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells .\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: Multivitamin preparation ( MVP ) is part of total parenteral nutrition given to premature infants . Photoactivated MVP carries an important load in peroxides , but their cellular effects have not yet been determined . We hypothesized that these peroxides may elicit a DNA-damage response . We found that photoactivation of MVP and the resulting peroxide production were time-dependent and required the simultaneous presence of ascorbic acid and riboflavin . Cells treated with photoactivated MVP showed strongly stimulated poly(ADP-ribosyl)ation , an early DNA-damage response in mammals . Poly(ADP-ribosyl)ation stimulation was dependent on the presence of ascorbic acid and riboflavin in the photoactivated MVP . It did not occur in the presence of a specific PARP inhibitor nor in mouse fibroblasts deficient in PARP-1 . Photoactivated MVP was able to induce single- and double-strand breaks in DNA , with a predominance of single-stand breaks . The presence of double-strand breaks was further confirmed using a 53PB1 focus analysis . Finally , photoactivated MVP was shown to be toxic to human cells and induced caspase-independent cell death . These results suggest that photoactivated MVP carries an important toxic load able to damage DNA and induce cell death . This study also emphasizes the importance of protecting MVP solution from light before use in preterm infants .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Anal canal cancer is a rare tumor without clear treatment evidence in the metastatic setting . In terms of the bad prognosis of patients with metastatic anal cancer , further therapeutic options are urgently needed . In this paper we present the case of a 64-year-old man suffering from undifferentiated squamous cell carcinoma with liver metastases . After progression on cisplatin and fluorouracil , tumor tissue was analyzed with respect to anti-EGFR therapy with cetuximab . There was no KRAS mutation and the EGFR expression level in the tumor tissue was 2+ ; ideal conditions for the immunotherapy . Encouraged by these results we started a therapy using FOLFIRI in combination with cetuximab . Fortunately the patient showed a partial response after 6 cycles . On patient's preference we did a therapy break of 6 weeks . Within this time period the disease was progressive indicating its aggressiveness . However , the same immunotherapy was able to stabilize the disease for a further 3 months . The patient died 21 months after diagnosis because of liver failure . Nevertheless , from our perspective the combination of FOLFIRI and cetuximab is quite a promising therapeutic option for patients with metastatic anal cancer . Potential predictive factors of the immunochemotherapy are discussed in this paper .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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 morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time . The apoptotic cancer cell contracted , became rounder and divorced from adjacent cells ; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane ; the endoplasmic reticulums ( ER ) expanded and fused with the cellular membrane ; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma . Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediatedin situ nick end labeling ( TUNEL ) . It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample . The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency ( ULF ) pulsed gradient magnetic field ; the nuclei DNA contents decreased , indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells . It was suggested that magnetic field could inhibit the metabolism of cancer cell , lower its malignancy , and restrain its rapid and heteromorphic growth . Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour , it could be used as a new method to treat cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: This study aimed to investigate the mechanism by which the human lung cancer drug resistance-related gene BC006151 regulates chemosensitivity by down-regulating BC006151 expression via antisense gene transfer in H446/(C)DDP cells . A retroviral vector containing the antisense BC006151 sequence was constructed and transfected into H446/(C)DDP cells . Transfection of the empty vector served as a negative control . The two groups of transfected cells were treated with various chemotherapeutic agents , after which morphological changes in cell ultrastructure were compared by transmission electron microscopy , cell proliferation and chemosensitivity to particular chemotherapeutic agents were compared by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method , the effects of chemotherapy on cell cycle and apoptosis were compared by flow cytometry , and Bcl-2 was evaluated by immunohistochemistry and Western blot analysis . Results showed that apoptotic body-like structures were identified by transmission electron microscopy in the antisense gene-transfected cells . MTT founded that these cells exhibited a significantly lower level of proliferation than the control cells ( p<0.01 ) , together with a markedly increased sensitivity to various chemotherapeutic agents ( p<0.01 ) . Flow cytometry analysis revealed that a G1 phase arrest accounted for the reduction in proliferation in the antisense gene-transfected cells ; increased apoptosis was also detected ( p<0.01 ) . Both immunohistochemistry and western blot analysis confirmed that Bcl-2 expression was significantly down-regulated in the antisense gene-transfected cells compared to controls . In a word , down-regulation of BC006151 can significantly inhibit proliferation and increase apoptosis of H446/(C)DDP cells after chemotherapy , and this gene may play an important role in the development of multidrug resistance in lung cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: Angiogenesis is increased in hematologic malignancies , including non-Hodgkin lymphoma ( NHL ) . Elevated serum levels of two important angiogenic factors , vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) , are associated with a poor prognosis . Immunohistochemistry was used to evaluate 27 patients with NHL and bone marrow involvement ( 17 with low-grade B-cell NHL , including 7 with higher grade transformation ; 6 with intermediate-grade B-cell NHL ; and 4 with T-cell lymphoma ) . Among the 17 patients with low-grade B-cell NHL , results for 7 were positive for VEGF stain ( 41.2% ) , and results were negative for all other stains for VEGF receptors , bFGF , and bFGF receptors . In the 10 patients with intermediate-grade B-cell NHL and T-cell lymphoma , all VEGF staining was positive ( 100% ) , but bFGF staining was only weakly positive in 2 . Staining results for seven patients who had low-grade B-cell NHL with higher grade transformation showed that VEGF staining was positive in large lymphoid cells of 5 patients and in small lymphoid cells of one patient . Staining for the receptors VEGFR-1 and VEGFR-2 was positive in large lymphoid cells in four and two cases , respectively . Staining for bFGF was positive in two cases of large lymphoid cells . We concluded that VEGF , but not bFGF , was associated with higher tumor grading of NHL and high-grade transformation of low-grade lymphoma .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The ARF locus is frequently inactivated in human cancer . The oncosuppressor ARF has indeed been described as a general sensor for different situation of cellular stress . We have previously demonstrated that ARF deficiency severely impairs inflammatory responses in vitro and in vivo , establishing a role for ARF in the regulation of innate immunity . The aim of the present work was to get further insights into the immune functions of ARF and to evaluate its possible contribution to the polarization of macrophages toward the M1 or M2 phenotype . Our results demonstrate that resting Arf(-/-) macrophages express high levels of Ym1 and Fizz-1 , two typical markers of alternatively-activated macrophages ( M2 ) . Additionally , Arf(-/-) peritoneal macrophages showed an impaired response to lipopolysaccharide ( a classical inducer of M1 polaryzation ) and a reduced production of pro-inflammatory cytokines/chemokines . Moreover , upon stimulation with interleukin-4 ( IL-4 ) , an inducer of the M2 phenotype , well established M2 markers such as Fizz-1 , Ym1 and arginase-1 were upregulated in Arf(-/-) as compared with wild type macrophages . Accordingly , the cytokine and chemokine profile associated with the M2 phenotype was significantly overexpressed in Arf(-/-) macrophages responding to IL-4 . In addition , multiple pro-angiogenic factors such as VEGF and MMP-9 were also increased . In summary , these results indicate that ARF contributes to the polarization and functional plasticity of macrophages .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;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: PURPOSE The cytotoxic effect of the combination treatment of TNF-alpha and hyperthermia on L929 and TNF-alpha-resistant L929 ( rL929 ) cells was investigated . MATERIALS AND METHODS L929 cells were treated with TNF-alpha ( 5 ng/mL ) , heating at 43 degrees C or the combination of TNF-alpha and heating . The cells were harvested at different time within the 24-hour period . The viability and the type of cell death of the harvested cells were examined . RESULTS When L929 cells were treated with a combination of TNF-alpha and heating the cells died quickly and apoptosis increased to an overwhelming extent , especially in the group pre-treated with TNF-alpha for 1 h prior to heating . Although rL929 cells were resistant to TNF-alpha alone , the cells became sensitive to TNF-alpha treatment when combined with heating . Similar to the L929 cell , the cells also died rapidly and exhibited apoptosis to a higher extent . Using an Annexin-V-FITC kit and flow cytometer , we found that both necrosis and apoptosis occurred . Agarose gel electrophoresis of DNA extracted from treated cells showed that the DNA fragments were multiples of approximately 200 bp . Furthermore , by studying the kinetics of cell death and apoptosis , we found that the loss of cell membrane integrity preceded the DNA fragmentation in both L929 and rL929 cells . CONCLUSION The results suggested that hyperthermia may enhance the necrotic and apoptotic effects of TNF-alpha on some tumour cells and overcome the resistance of some tumour cells to TNF-alpha .\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: Although tumor-associated macrophages ( TAMs ) are involved in tumor growth and metastasis , the mechanisms controlling their pro-tumoral activities remain largely unknown . The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors . In this study , we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice , which lack c-Myc in macrophages , to investigate the role of macrophage c-MYC expression in cancer . Under steady-state conditions , immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal , including the abundance of different subsets of bone marrow hematopoietic stem cells , precursors and circulating cells , macrophage density , and immune organ structure . In a model of melanoma , however , TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions ( e.g. , reduced expression of VEGF , MMP9 , and HIF1α ) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice . Macrophage c-Myc deletion also diminished fibrosarcoma growth . These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy .\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 HER2 and estrogen receptor ( ER ) are important in breast cancer and are therapeutic targets of trastuzumab ( Herceptin ) and tamoxifen , respectively . Retinoids inhibit breast cancer growth , and modulate signaling by HER2 and ER . We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects . METHODS The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture , BT474 and SKBR3 . Assays of proliferation , apoptosis , differentiation , cell cycle distribution , and receptor signaling were performed . RESULTS In HER2-overexpressing/ER-positive BT474 cells , combining all-trans retinoic acid ( atRA ) with tamoxifen or trastuzumab synergistically inhibited cell growth , and altered cell differentiation and cell cycle . Only atRA/trastuzumab-containing combinations induced apoptosis . BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids ( atRA , 9-cis-retinoic acid , 13-cis-retinoic acid , or N-(4-hydroxyphenyl) retinamide ( fenretinide ) ( 4-HPR) ) combined with trastuzumab . In BT474 cells , none of the single agents except 4-HPR induced apoptosis , but again combinations of each retinoid with trastuzumab did induce apoptosis . In contrast , the single retinoid agents did cause apoptosis in SKBR3 cells ; this was only modestly enhanced by addition of trastuzumab . The retinoid drug combinations altered signaling by HER2 and ER . Retinoids were inactive in trastuzumab-resistant BT474 cells . CONCLUSIONS Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells . Treatment with such combinations may have benefit for breast cancer patients .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The colon carcinoma cell line CC531 is metastatic to liver after splenic injection in syngeneic rats . After repeated in vivo passages , a subline was selected that produced liver metastases at a considerably higher rate than the original cell line . These cells were characterized by increased intracellular glutathione , proliferation and ability to restore glutathione after exposure to oxidative stress , thus indicating an elevated resistance to oxidative stress . Furthermore , the increased metastatic ability was also accompanied by increased proliferation rate , adhesion to extracellular matrix proteins and endothelial cells , and secretion of a 60 kD matrix metalloproteinase . When cultured in vitro for a prolonged time ( more than 30 trypsinizations ) , the cells showed a reduced in vivo metastatic ability , reduced secretion of three metalloproteinases including the 60 kD proteinase , and reduced intracellular glutathione . These results indicate that metastatic ability can be influenced through several adaptive mechanisms , and that the cell's ability to resist oxidative stress and maintain intracellular glutathione are of central importance .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Our purpose in this randomized , double blind , placebo controlled study was to find out the possible effect of a polyphenolic pine bark extract , Pycnogenol® ( Pyc ) on the level of 8-oxo-7,8-dihydroguanine ( 8-oxoG ) as representative of oxidative damage to DNA and on the DNA repair ability of elderly people . According to our results , three months of Pyc administration had no effect on the level of oxidative damage to DNA or on repair ability , but we found a relationship between the level of 8-oxoG and repair ability of DNA in this group . To conclude , even if the positive effect of Pyc was not confirmed in the case of elderly people it is important to highlight the necessity of further investigations about the mechanisms of Pyc acting on different age groups .\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: ABSTRACT : BACKGROUND : The ubiquitin-proteasome system and macroautophagy ( hereafter referred to autophagy ) are two complementary pathways for protein degradation . Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy . Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired . METHOD : Autophagy activation was measured using acridine orange staining and LC3 transition . Cell viability and apoptosis were measured using MTT assay and flow cytometry , respectively . Beclin 1 expression vectors or shRNA against Beclin 1 ( shBeclin 1 ) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors . RESULTS : Proteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells . Neither phosphoinositide 3-kinase ( PI3K ) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors . Moreover , Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells . CONCLUSIONS : For the first time , the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells . In addition , this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Bisphosphonates ( BPs ) are the current standard of care for bone lesions in patients with multiple myeloma ( MM ) but they are associated with a number of side effects such as osteonecrosis of the jaw . The exact mechanisms of osteonecrosis are not elucidated , and its physiopathology is based on several hypotheses such as a decrease in bone remodeling or an inhibitory effect on angiogenesis . The aim of our study was to investigate the mechanism involved in the pathogenesis of osteonecrosis . We examined the apoptosis of circulating endothelial progenitor cells in MM subjects before and after BP treatment and in osteonecrosis patients using a flow-cytometric analysis . Our data showed an increase in endothelial cell apoptosis in MM patients after BP administration and in osteonecrosis subjects . Our study seems in agreement with the hypothesis that BPs can inhibit angiogenesis interfering with endothelial cell proliferation and survival , leading to loss of blood vessels and avascular necrosis .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors , including cellular immunity . We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms . However , how metastasis susceptibility genes interact with the tumor stroma is incompletely understood . Here , we employ a complex genetic screen to identify Cadm1 as a novel modifier of metastasis . We demonstrate that Cadm1 can specifically suppress metastasis without affecting primary tumor growth . Unexpectedly , Cadm1 did not alter tumor-cell-autonomous properties such as proliferation or invasion , but required the host's adaptive immune system to affect metastasis . The metastasis-suppressing effect of Cadm1 was lost in mice lacking T cell-mediated immunity , which was partially phenocopied by depleting CD8(+) T cells in immune-competent mice . Our data show a novel function for Cadm1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms , and this is the first report of a heritable metastasis susceptibility gene engaging tumor non-autonomous factors .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: Interleukin-23 ( IL-23 ) plays an essential role in the mucosal immune system . It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells . However , neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed . The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells . We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry . Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer . ELISA and real-time PCR were used to evaluate the transforming growth factor ( TGF)-β production due to IL-23 stimulation . All of the TNM stage IV patients were positive for IL-23R . IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases . The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation , whereas no change was observed in the activities of MIP101 and KM12c cells . IL-23 directly enhanced the malignancy of the colon carcinoma cells . An autocrine mechanism via TGF-β production may underlie these effects . IL-23 is therefore a potential target for cancer immunotherapy . However , the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered .\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: Histopathological features of the lymph node involvement were studied in 104 patients with thoracic esophageal cancer who underwent subtotal esophagectomy combined with extended radical lymph adenectomy in cervicothoracoabdominal region . Metastatic involvement was found in a total number of 503 lymph nodes from 73 patients by histologic examination . The mean of long and short diameter was found to be less than 5mm in 125 ( 24.9% ) of these 503 nodes . The involved area on the section was less than one third in 149 nodes ( 29.6% ) , and was significantly smaller in mediastinal lymph nodes than those in cervical or abdominal ones . Sixty-seven ( 13.3% ) of 503 nodes were partially invaded by micrometastasis of 1mm or less in diameter . Micrometastasis also more frequently occurred in mediastinal nodes with a statistically significant difference . Extranodal proliferation ( ENP ) of cancer cells was found in 106 nodes ( 21.1% ) , and extranodal lymphatic and/or blood vessel invasion ( ENly , v ) was also recognized in 60 nodes ( 11.9% ) . Micrometastasis and ENP with or without ENly , v were found in 24 ( 32.9% ) and 29 ( 39.7% ) of 73 patients with positive lymph node metastasis , respectively . Postoperative survival rate in patients with micrometastasis and/or ENP with or without ENly , v was inferior to that in patients with neither of them .\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: This research aims to give a new insight to the relationship between host local immune response and the biological behaviour of the tumor by evaluating of intratumoral natural killer ( NK ) cells and tumor necrosis factor-alpha ( TNFalpha ) expressions in oral squamous cell carcinomas . New paraffin sections of the deepest parts of the 46 cases of oral squamous cell carcinomas were immunohistochemically treated by CD57 , selected as NK cell indicator , and TNFalpha monoclonal antibodies . The tumors were graded according to histopathologic grading scores of invasive margins and categorized into 2 groups as \" good \" and \" poor \" prognostic groups . Fifteen cases , from which could be obtained full clinical data , were clinically staged and because of the scarcity of the cases in each group were divided , again , two groups as group 1 : stage I+stage II and group 2 : stage III+stage IV . The expression levels of CD57 and TNFalpha were evaluated according to histopathologic grading groups and clinical staging groups . The results showed that the density of CD57+cells ( NK cells ) was statistically lower in tumors graded as poor prognostic group compared to the cases in good prognostic group . On the contrary , expression level of TNFalpha was statistically higher in poor prognostic group . These findings suggested that increased secretion of TNFalpha in the tumors , which show high invasive potential , may be one of the facilitating factors for tumor invasion and be responsible from suppression of NK cells . Withdrawal of NK cells in the high invasive tumor areas also reminds the necessity of certain shared genetic rearrangements in tumor cells for getting protected from NK cell attacks and moving ahead within the extracellular matrix .\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: Prohibiting angiogenesis is an important therapeutic approach for fighting cancer and other angiogenic related diseases . Research focused on proteins that regulate abnormal angiogenesis has attracted intense interest in both academia and industry . Such proteins are able to target several angiogenic factors concurrently , thereby increasing the possibility of therapeutic success . Aquaporin-1 ( AQP1 ) is a water channel membrane protein that promotes tumour angiogenesis by allowing faster endothelial cell migration . In this study we test the hypothesis that AQP1 inhibition impairs tumour growth in a mouse model of melanoma . After validating the inhibitor efficacy of two different AQP1 specific siRNAs in cell cultures , RNA interference experiments were performed by intratumoural injections of AQP1 siRNAs in mice . After 6 days of treatment , AQP1 siRNA treated tumours showed a 75 % reduction in volume when compared to controls . AQP1 protein level , in AQP1 knockdown tumours , was around 75 % that of the controls and was associated with a significant 40 % reduced expression of the endothelial marker , Factor VIII . Immunofluorescence analysis of AQP1 siRNA treated tumours showed a significantly lower microvessel density . Time course experiments demonstrated that repeated injections of AQP1 siRNA over time are effective in sustaining the inhibition of tumour growth . Finally , we have confirmed the role of AQP1 in sustaining an active endothelium during angiogenesis and we have shown that AQP1 reduction causes an increase in VEGF levels . In conclusion , this study validates AQP1 as a pro-angiogenic protein , relevant for the therapy of cancer and other angiogenic-related diseases such as psoriasis , endometriosis , arthritis and atherosclerosis .\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: INTRODUCTION Various agents used in breast cancer chemotherapy provoke DNA double-strand breaks ( DSBs ) . DSB repair competence determines the sensitivity of cells to these agents whereby aberrations in the repair machinery leads to apoptosis . Proteins required for this pathway can be detected as nuclear foci at sites of DNA damage when the pathway is intact . Here we investigate whether focus formation of repair proteins can predict chemosensitivity of breast cancer . METHODS Core needle biopsy specimens were obtained from sixty cases of primary breast cancer before and 18-24 hours after the first cycle of neoadjuvant epirubicin plus cyclophosphamide ( EC ) treatment . Nuclear focus formation of DNA damage repair proteins was immunohistochemically analyzed and compared with tumor response to chemotherapy . RESULTS EC treatment induced nuclear foci of gammaH2AX , conjugated ubiquitin , and Rad51 in a substantial amount of cases . In contrast , BRCA1 foci were observed before treatment in the majority of the cases and only decreased after EC in thirteen cases . The presence of BRCA1- , gammaH2AX- , or Rad51-foci before treatment or the presence of Rad51-foci after treatment was inversely correlated with tumor response to chemotherapy . DNA damage response ( DDR ) competence was further evaluated by considering all four repair indicators together . A high DDR score significantly correlated with low tumor response to EC and EC + docetaxel whereas other clinicopathological factors analyzed did not . CONCLUSIONS High performing DDR focus formation resulted in tumor resistance to DNA damage-inducing chemotherapy . Our results suggested an importance of evaluation of DDR competence to predict breast cancer chemosensitivity , and merits further studying into its usefulness in exclusion of non-responder patients .\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: The effect of transforming growth factor-beta 1 ( TGF-beta 1 ) and interleukin-1 beta ( IL-1 beta ) on LDL receptor in Hep G2 cells was investigated . A greater than two-fold stimulation of the binding and internalisation of [ 125I]-labelled LDL at 37 degrees C was observed after an 18-h incubation of the cells with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml compared with control cells . Scatchard analysis of the binding of [ 125I]-labelled LDL at 4 degrees C after an 18-h incubation of the cells with 1170 units/ml IL-1 beta and 5 ng/ml TGF-beta 1 showed that they were both acting primarily by increasing LDL receptor number . The increase in LDL receptor activity could not be attributed to an increase in cell proliferation as TGF-beta 1 at concentrations from 0.05 ng/ml to 50 ng/ml had no significant effect on either cell number or [ 3H]thymidine incorporation into DNA whilst IL-1 beta inhibited DNA synthesis by more than 80% at a concentration of 11,700 units/ml but had significant effect on cell number . Cholesterol biosynthesis from [ 14C]acetate , in contrast to the stimulation of LDL receptor activity , was inhibited by approximately two-fold by incubation with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml .\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: PURPOSE This study aims to investigate the role of the aberrant expression of Transkelolase-like 1 ( TKTL1 ) in head and neck squamous cell carcinoma ( HNSCC ) tumorigenesis and to characterize TKTL1 contribution to HNSCC tumorigenesis through aerobic glycolysis and HIF1alpha stabilization . EXPERIMENTAL DESIGN TKTL1 promoter hypomethylation and mRNA/protein aberrant expression were studied in human HNSCC tumor samples and normal mucosas . Oncogenic functions of TKTL1 were examined in HNSCC cell line panels and tumor xenograft models with TKTL1 expression construct . The metabolite levels of fructose-6-phosphate , glyceraldehydes-3-phosphate , pyruvate , lactate , and the levels of HIF1alpha protein and its downsteam glycolytic targets were compared between the TKTL1-expressing and vehicle-expressing HNSCC cells . Meanwhile , the effects of HIF1alpha/glycolytic inhibitors were evaluated on the TKTL1 transfectants . RESULTS TKTL1 exhibits high frequency of promoter hypomethylation in HNSCC tumors compared with the normal mucosas , correlating with its overexpression in HNSCC . Overexpression of TKTL1 in HNSCC cells promoted cellular proliferation and enhanced tumor growth in vitro and in vivo . Overexpression of TKTL1 increased the production of fructose-6-phosphate and glyceraldehyde-3-phosphate , in turn elevating the production of pyruvate and lactate , resulting in the normoxic stabilization of the malignancy-promoting transcription factor HIF1alpha and the upregulation of downstream glycolytic enzymes . Notably , the reduction of TKTL1 expression decreased HIF1alpha accumulation and inhibition with HIF1alpha and/or the glycolysis inhibitor could abrogate the growth effects mediated by TKTL1 overexpression . CONCLUSION TKTL1 is a novel candidate oncogene that is epigenetically activated by aberrant hypomethlation and contributes to a malignant phenotype through altered glycolytic metabolism and HIF1alpha accumulation .\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: Proline- , glutamic acid- and leucine-rich protein-1/modulator of non-genomic activity of estrogen receptor ( ER ) ( PELP1/MNAR ) is a novel nuclear receptor ( NR ) co-activator that plays an essential role in the actions of ER . Emerging findings suggest that PELP1/MNAR is a novel proto-oncogene , whose expression is deregulated in several hormone-responsive cancers , including endometrial cancer . In this study , we demonstrate that PELP1/MNAR is widely expressed in endometrial carcinoma cell lines . To investigate its possible role in endometrial carcinoma progression , we adopted an RNA interference technology to downregulate PELP1/MNAR expression in Ishikawa endometrial carcinoma cells . PELP1/MNAR downregulation substantially reduced cell proliferation , and the cells in which PELP1/MNAR expression was knocked down also exhibited a decreased migration and invasion ability , as shown by Boyden chamber and invasion assays . The results showed that the expression of MMP-2 and MMP-9 was also decreased . These results suggest that PELP1/MNAR plays a role in endometrial cancer progression and metastasis , and that PELP1/MNAR may be a potential therapeutic target for endometrial cancer .\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: Lewis y ( LeY ) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface . Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis . However , the effects of LeY on ovarian cancer are not yet clear . Previously , we transfected the ovarian cancer cell line RMG-I with the α1,2-fucosyltransferase gene to obtain stable transfectants , RMG-I-H , that highly express LeY . In the present study , we examined the proliferation , tumorigenesis , adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody ( mAb ) . Additionally , we examined the expression of TGF-β1 , VEGF and b-FGF in xenograft tumors . The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb . When subcutaneously inoculated in nude mice , RMG-I-H cells produced large tumors , while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors . Moreover , the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb . Notably , the expression of TGF-β1 , VEGF and b-FGF all increased in RMG-I-H cells . In conclusion , LeY plays an important role in promoting cell proliferation , tumorigenecity and adhesion , and these effects may be related to increased levels of growth factors . The LeY antibody shows potential application in the treatment of LeY-positive tumors .\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: High concentrations of lactic acid ( LA ) are found under various pathophysiological conditions and are accompanied by an acidification of the environment . To study the impact of LA on TNF secretion , human LPS-stimulated monocytes were cultured with or without LA or the corresponding pH control . TNF secretion was significantly suppressed by low concentrations of LA ( &lt ; or = 10 mM ) , whereas only strong acidification had a similar effect . This result was confirmed in a coculture model of human monocytes with multicellular tumor spheroids . Blocking synthesis of tumor-derived lactate by oxamic acid , an inhibitor of lactate dehydrogenase , reversed the suppression of TNF secretion in this coculture model . We then investigated possible mechanisms underlying the suppression . Uptake of [ 3-(13)C]lactate by monocytes was shown by hyphenated mass spectrometry . As lactate might interfere with glycolysis , the glycolytic flux of monocytes was determined . We added [ 1,2-(13)C(2)]glucose to the culture medium and measured glucose uptake and conversion into [ 2,3-(13)C(2)]lactate . Activation of monocytes increased the glycolytic flux and the secretion of lactate , whereas oxygen consumption was decreased . Addition of unlabeled LA resulted in a highly significant decrease in [ 2,3-(13)C(2)]lactate secretion , whereas a mere corresponding decrease in pH exerted a less pronounced effect . Both treatments increased intracellular [ 2,3-(13)C(2)]lactate levels . Blocking of glycolysis by 2-deoxyglucose strongly inhibited TNF secretion , whereas suppression of oxidative phosphorylation by rotenone had little effect . These results support the hypothesis that TNF secretion by human monocytes depends on glycolysis and suggest that LA and acidification may be involved in the suppression of TNF secretion in the tumor environment .\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: Premature senescence , a key strategy used to suppress carcinogenesis , can be driven by p53/p21 proteins in response to various stresses . Here , we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability . Wig1 controls the association of Argonaute2 ( Ago2 ) , a central component of the RNA-induced silencing complex ( RISC ) , with target p21 mRNA via binding of the stem-loop structure near the microRNA ( miRNA ) target site . Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence . Wig1 plays an essential role in cell proliferation , as demonstrated in tumour xenografts in mice , and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues . Together , our data indicate a novel role of Wig1 in RISC target accessibility , which is a key step in RNA-mediated gene silencing . In addition , these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence .\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: FMS-like tyrosine kinase 3 ( FLT3 ) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells , but its constitutive activation by internal tandem duplication ( ITD ) mutations correlates with a poor prognosis in AML . The development of FLT3 tyrosine kinase inhibitors ( TKI ) is a promising strategy , but resistance that arises during the course of treatment caused by secondary mutations within the mutated gene itself poses a significant challenge . In an effort to predict FLT3 resistance mutations that might develop in patients , we used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI . We identified F621L , A627P , F691L and Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI . Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3 autophosphorylation and signaling through MAP kinase , STAT5 and AKT in some mutants . Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed resistance to sorafenib in vivo but not to lestaurtinib . These results indicate a growing number of FLT3 mutations that are likely to be encountered in patients . Such knowledge , combined with known remaining sensitivity to other FLT3 TKI , will be important to establish as secondary drug treatments that can be substituted when these mutants are encountered .\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: OBJECTIVE To study the effects of angiostatin(AS) gene mediated by liposome on human pancreatic cancer cell line SW1990 . METHODS Angiostatin gene was cloned into the eukaryotic expression vector pRC/CMV . The recombinant of pRC/CMV-AS was introduced into the pancreatic cancer cell line , SW1990 . The mechanism of anti-tumor was studied and tested . RESULTS The eukaryotic expression vector pRC/CMV-AS was identified by the restriction digest. pRC/CMV-AS was stably integrated into the target cells and expressed by Western blot and drug-sensitivity tests , and inhibited the vascular endothelial cells proliferation in vitro . In addition , the effects of the angiostatin vector on reducing the volume of tumors implanted in nude mouse models were also noted . CONCLUSION This study demonstrated that the recombinant pRC/CMV-AS mediated by liposome may play a potential role in the treatment of pancreatic cancer in the future .\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: We previously reported that hepatic stellate cells ( HSCs ) activated by angiotensin II ( AngII ) facilitate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma ( ICC ) . AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition ( EMT ) in renal epithelial cells , alveolar epithelial cells and peritoneal mesothelial cells . However , in the past , the relationship between AngII and stromal cell-derived factor-1 ( SDF-1 ) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail . SDF-1 and its specific receptor , CXCR4 , are now receiving attention as a mechanism of cell progression and metastasis . In this study , we examined whether activated HSCs promote tumor fibrogenesis , tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor ( AT-1 ) and the SDF-1/CXCR4 axis . Two human ICC cell lines and a human HSC line , LI-90 , express CXCR4 . Significantly higher concentration of SDF-1α was released into the supernatant of LI-90 cells to which AngII had been added . SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor . Furthermore , addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression , reduced E-cadherin expression , and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells . Co-culture with HSCs also enhanced the migratory capability of ICC cells . These findings suggest that SDF-1α , released from activated HSCs and AngII , play important roles in cancer progression , tumor fibrogenesis , and migration in autocrine and paracrine fashion by mediating EMT . Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma , tumor progression and meta-stasis of tumor cells expressing AT-1 and CXCR4 .\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: Aberrant expression and polymorphism of fibroblast growth factor receptor 4 ( FGFR4 ) has been linked to tumor progression and anticancer drug resistance . We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase ( MT1-MMP , MMP-14 ) induction at the edge of tumors expressing the FGFR4-R388 risk variant . Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas , where they were partially coexpressed at the tumor/stroma border and tumor invasion front . The strongest overall coexpression was found in prostate carcinoma . Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant , which has previously been associated with poor cancer prognosis , increased MT1-MMP-dependent collagen invasion . In this experimental model , knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen . This was coupled with impaired phosphorylation of FGFR substrate 2 and Src , upregulation of E-cadherin , and suppression of cadherin-11 and N-cadherin . These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing . In contrast , knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen . These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors .\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: This study examined the possible role of p120ctn in the pathogenesis and development of pancreatic cancer . PANC-1 cells , a kind of human pancreatic carcinoma cell line , were cultured in this study. p120ctn was immunocytochemically detected in PANC-1 cells . The recombinant lentivirus vector was constructed to knock down the p120ctn expression of PANC-1 cells . Real-time quantitative PCR ( RQ-PCR ) and Western blotting were used to determine the expression of p120ctn and E-cadherin in PANC-1 cells after p120ctn knockdown . The adhesion , invasion and migration capacity of PANC-1 cells after p120ctn knockdown was detected by cell adhesion , invasion and migration assays . Cell growth was measured by the MTT method . Cell cycle and apoptosis were analyzed by fluorescence-activated cell sorting . The results showed that p120ctn knockdown led to significantly down-regulated E-cadherin and a reduced cell-to-cell adhesion ability in PANC-1 cells. shRNA-mediated knockdown of p120ctn reduced invasion and migration capacity of PANC-1 cells , inhibited cell growth , caused a significant decrease in the percentage of cells in G(1) , an increase in S , and promoted apoptosis of PANC-1 cells . It was concluded that p120ctn plays a pivotal role in the proliferation and metastasis of pancreatic carcinoma , suggesting that p120ctn is a novel target for pancreatic carcinoma treatment .\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: Multiple myeloma ( MM ) is classically illustrated by a desynchronized cytokine system with rise in inflammatory cytokines . There are recent reports which emphasized the potential role of angiogenesis in the development of MM. Role of cyclooxygenase 2 ( COX-2 ) is well documented in the pathogenesis of solid tumors , but little is known about its occurrence and function in hematologic neoplasms . Involvement of neoangiogenesis is reported in the progression of MM , and angiopoietins probably contribute to this progression by enhancing neovascularization . Circulatory and mRNA levels of angiogenic factors and cyclooxygenase were determined in 125 subjects ( 75 MM patients and 50 healthy controls ) by using enzyme-linked immunosorbent assay and quantitative PCR . We observed significant increase for angiogenic factors ( Ang-1 , Ang-2 , hepatocyte growth factor , and vascular endothelial growth factor ) and cyclooxygenase at circulatory level , as well as at mRNA level , as compared to healthy controls except insignificant increase for Ang-1 at circulatory level . We have also observed the significant positive correlation of all angiogenic factors with cyclooxygenase . The strong association found between angiogenic factors and COX-2 in this study may lead to the development of combination therapeutic strategy to treat MM. Therefore , targeting COX-2 by using its effective inhibitors demonstrating antiangiogenic and antitumor effects could be used as a new therapeutic approach for treatment of MM .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;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 tumor suppressors Lats1 and Lats2 are mediators of the Hippo pathway that regulates tissue growth and proliferation . Their N-terminal non-kinase regions are distinct except for Lats conserved domains 1 and 2 ( LCD1 and LCD2 ) , which may be important for Lats1/2-specific functions . Lats1 knockout mice were generated by disrupting the N-terminal region containing LCD1 ( Lats1(ΔN/ΔN) ) . Some Lats1(ΔN/ΔN) mice were born safely and grew normally . However , mouse embryonic fibroblasts ( MEFs ) from Lats1(ΔN/ΔN) mice displayed mitotic defects , centrosomal overduplication , chromosomal misalignment , multipolar spindle formation , chromosomal bridging and cytokinesis failure . They also showed anchorage-independent growth and continued cell cycles and cell growth , bypassing cell-cell contact inhibition similar to tumor cells . Lats1(ΔN/ΔN) MEFs produced tumors in nude mice after subcutaneous injection , although the tumor growth rate was much slower than that of ordinary cancer cells . Yap , a key transcriptional coactivator of the Hippo pathway , was overexpressed and stably retained in Lats1(ΔN/ΔN) MEFs in a cell density independent manner , and Lats2 mRNA expression was downregulated . In conclusion , N-terminally truncated Lats1 induced Lats2 downregulation and Yap protein accumulation , leading to chromosomal instability and tumorigenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;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: Progression to malignancy requires that cells overcome senescence and switch to an immortal phenotype . Thus , exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation . In the present study , we have globally profiled DNA methylation in relation to gene expression in primary , senescent and immortalized mouse embryonic fibroblasts . Using a high-resolution genome-wide mapping technique , followed by extensive locus-specific validation assays , we have identified 24 CpG islands that display significantly higher levels of CpG methylation in immortalized cell lines as compared to primary murine fibroblasts . Several of these hypermethylated CpG islands are associated with genes involved in the MEK-ERK pathway , one of the most frequently disrupted pathways in cancer . Approximately half of the hypermethylated targets are developmental regulators , and bind to the repressive Polycomb group ( PcG ) proteins , often in the context of bivalent chromatin in mouse embryonic stem cells . Because PcG-associated aberrant DNA methylation is a hallmark of several human malignancies , our methylation data suggest that epigenetic reprogramming of pluripotency genes may initiate cell immortalization . Consistent with methylome alterations , global gene expression analysis reveals that the vast majority of genes dysregulated during cell immortalization belongs to gene families that converge into the MEK-ERK pathway . Additionally , several dysregulated members of the MAP kinase network show concomitant hypermethylation of CpG islands . Unlocking alternative epigenetic routes for cell immortalization will be paramount for understanding crucial events leading to cell transformation . Unlike genetic alterations , epigenetic changes are reversible events , and as such , can be amenable to pharmacological interventions , which makes them appealing targets for cancer therapy when genetic approaches prove inadequate .\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: In traditional biochemical experiments , the behavior of individual proteins is obscured by ensemble averaging . To better understand the behavior of proteins that bind to and/or translocate on DNA , we have developed instrumentation that uses optical trapping , microfluidic solution delivery , and fluorescent microscopy to visualize either individual proteins or assemblies of proteins acting on single molecules of DNA . The general experimental design involves attaching a single DNA molecule to a polystyrene microsphere that is then used as a microscopic handle to manipulate individual DNA molecules with a laser trap . Visualization is achieved by fluorescently labeling either the DNA or the protein of interest , followed by direct imaging using high-sensitivity fluorescence microscopy . We describe the sample preparation and instrumentation used to visualize the interaction of individual proteins with single molecules of DNA . As examples , we describe the application of these methods to the study of proteins involved in recombination-mediated DNA repair , a process essential for the maintenance of genomic integrity .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]