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HoC_1shot_test

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HoC_1shot300

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer ( NSCLC ) patients was studied . Furthermore , transferrin receptors 1 ( TfR1 ) and ferritin expression in tumor tissue , tumor stroma , and normal lung tissue were analyzed . Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis . TfR1 and ferritin expression were determined by immuno-histochemical methods . About 50% of patients survived 12 months only . At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin . Iron content of serum ferritin ( ICF ) was below the reference values in 90% of patients . Furthermore , ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR . The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients , respectively . Tumor stroma was TfR1 negative and sporadically ferritin positive . Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit ( Ht ) , and positive correlation with ferritin , erythrocyte sedimentation rate ( ESR ) , alpha-1 globulin , and alpha-2 globulin . Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin . The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed . Therefore , we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload . Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors . OUTPUT:

tumor promoting inflammation

HoC_1shot301

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Ferric nitrilotriacetate ( Fe-NTA ) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress . The present study was undertaken to explore protective effect of silymarin , a flavonolignan from milk thistle ( Silybum marianum ) , against Fe-NTA mediated renal oxidative stress , inflammation and tumor promotion response along with elucidation of the implicated mechanism(s) . Administration of Fe-NTA ( 10 mg/kg bd wt , i.p. ) to Swiss albino mice induced marked oxidative stress in kidney , evident from augmentation in renal metallothionein ( MT ) expression , depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes , and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal . Fe-NTA also significantly activated nuclear factor kappa B ( NFkappaB ) and upregulated the expression of downstream genes : cyclooxygenase 2 and inducible nitric oxide synthase and enhancing the production of proinflammatory cytokines : tumor necrosis factor alpha ( TNF-alpha ) and interleukin-6 ( IL-6 ) . However , feeding of 0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA induced oxidative stress and inflammation . It further augmented MT expression , restored the antioxidant armory , ameliorated NFkappaB activation and decreased the expression of proinflammatory mediators . Silymarin also suppressed Fe-NTA induced hyperproliferation in kidney , ameliorating renal ornithine decarboxylase activity and DNA synthesis . From these results , it could be concluded that silymarin markedly protects against chemically induced renal cancer and acts plausibly by virtue of its antioxidant , anti-inflammatory and antiproliferative activities . OUTPUT:

tumor promoting inflammation

HoC_1shot302

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Nucling is a stress-inducible protein associated with apoptosomes . The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis . We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well . Here we show that hepatocellular carcinoma ( HCC ) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout ( KO ) mice than wild-type ( WT ) mice . Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males . In the background of Nucling-KO mice , we observed the up-regulation of TNFalpha , spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver . In addition , we observed a decrease in the number of Kupffer cells ( KCs ) in the KO mice . KCs are important for the hepatic immune system , acting as phagocytes or antigen-presenting cells ( APCs ) . We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha . These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver . We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development . OUTPUT:

avoiding immune destruction;resisting cell death

HoC_1shot303

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Metabolic dependence on glucose utilisation has been described for different tumours characterised by activation of Akt , upregulation of GLUT1 , M2PK and TKTL1 . To date , however , little is known about glucose metabolism in breast cancer tissue . METHODS We analysed 55 breast cancer specimens , 26 adjacent ductal carcinomas in situ ( DCIS ) and 23 adjacent normal breast tissues for expression of glycolytic markers by immunohistochemistry . RESULTS We found expression of pAkt in 49% , GLUT1 in 25% , M2PK in 68% and TKTL1 in 31% of the tumours investigated . Expression of pAkt and Her2neu are positively correlated with borderline significance ( P = 0.055 ) . Expression of pAkt , GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue . Surprisingly , M2PK expression was highest in normal breast tissue . CONCLUSIONS We found a glycolytic phenotype in a high percentage of breast cancer samples . Inhibition of glycolysis might evolve as a future option for breast cancer therapy . OUTPUT:

cellular energetics

HoC_1shot304

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND &amp ; AIMS Hepatocellular carcinoma ( HCC ) is an aggressive malignancy with few treatment options . As the status of the tumour immune microenvironment can affect progression of established tumours , we evaluated potential immune mechanisms associated with survival in HCC . METHODS Immune gene expression profiles were analyzed in tumour and non-tumour liver tissues from resected HCC patients using quantitative PCR and immunohistochemistry . Tumour-infiltrating leukocytes ( TILs ) were isolated to verify the expression of immune genes and to identify proliferating TILs . These parameters were analyzed statistically in relation with patient survival and tumour phenotype ( apoptosis and proliferation ) . RESULTS The immune microenvironment within tumours was found to be heterogeneous , although globally more inert compared to the adjacent non-tumour liver tissue . Univariate analysis in 61 patients identified a group of innate immune genes whose expression within tumours is positively associated with patient survival . TNF , IL6 and CCL2 are the most significant genes , with TNF being an independent predictor of survival in multivariate analysis . The gene set includes macrophage and NK-associated molecules such as TLR4 , TLR3 , CCR2 , NCR3 . Most of these molecules are expressed by TILs . Importantly , proliferating immune cells , predominantly NK and T cells , are present in tumours of patients with longer survival , and exclusively in areas devoid of proliferating tumour cells . NK and CD8(+) T cell densities are correlated positively with tumour apoptosis , and negatively with tumour proliferation . CONCLUSIONS Hence , an inflammatory immune microenvironment within HCC tumours could be an important means to control tumour progression via TIL activation and proliferation . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot305

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND &amp ; AIMS GUCY2C is the intestinal receptor for the paracrine hormones guanylin and uroguanylin that converts guanosine-5'-triphosphate to cyclic guanosine monophosphate ( cGMP ) . It functions as a tumor suppressor ; its loss disrupts intestinal homeostasis and promotes tumorigenesis . We investigated the effects of GUCY2C loss on intestinal cell proliferation , metabolism , signaling , and tumorigenesis in mice . METHODS Intestinal cell proliferation and metabolism were examined in Gucy2c(-/-) and colon cancer cells by microscopy , immunoblot , and functional analyses . Microarray analyses compared gene expression profiles of intestine cell from Gucy2c(-/-) and wild-type mice. v akt murine thymoma viral oncogene homolog ( AKT ) regulation and signaling were examined , and the role of AKT in GUCY2C-dependent tumorigenesis was defined in Gucy2c(-/-)Akt1(-/-) mice . RESULTS The size and number of intestinal crypts increased in Gucy2c(-/-) mice ; the associated epithelial cells showed accelerated proliferation , increased glycolysis , and reduced oxidative phosphorylation , which was reversed by oral administration of cGMP . Conversely , activating guanylyl cyclase C in human colon cancer cells delayed cell-cycle progression , decreased DNA synthesis and colony formation , reduced glycolysis , and increased mitochondrial adenosine triphosphate production . AKT signaling pathways were activated in intestines of Gucy2c(-/-) mice , associated with increased AKT phosphorylation . Disruption of AKT activity , pharmacologically or genetically , reduced DNA synthesis , proliferation , and glycolysis , and increased mitochondrial biogenesis . Intestinal tumorigenesis increased after administration of azoxymethane to Gucy2c(-/-) mice , compared with wild-type mice , but was eliminated in Gucy2c(-/-)Akt1(-/-) mice . CONCLUSIONS GUCY2C is a tumor suppressor that controls proliferation and metabolism of intestinal epithelial cells by inactivating AKT signaling . This receptor and its ligands , which are paracrine hormones , might be novel candidates for anticolorectal cancer therapy . OUTPUT:

cellular energetics

HoC_1shot306

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers . As chronic inflammations are associated with malignancies , it is important to prevent inflammation-mediated neoplastic formation , promotion and/or progression . One possible intervention will be using cancer chemopreventive agents such as curcumin ( CUR ) , a potent anti-inflammatory and anti-oxidative stress compound . Polyunsaturated fatty acids ( PUFA ) such as docosahexaenoic acid ( DHA ) or eicosapentaenoic acid ( EPA ) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids , cytokines , and reactive oxygen species ( ROS ) . The present study aims at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory effects in RAW 264.7 cells . Non-toxic concentrations of single and combination of the compounds were investigated at 6 , 12 and 24h . The nitric oxide ( NO ) suppression effects were most prominent at 24h . All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 microM and 25 microM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels . Importantly , very low doses of CUR 2.5 microM and DHA or EPA of 0.78 microM could synergistically suppress the LPS-induced prostaglandin E(2) ( PGE(2) ) . The combinations were also found to suppress iNOS , COX-2 , 5-lipoxygenase ( 5-LOX ) and cPLA(2) but induce HO-1 . Taken together , the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA . OUTPUT:

tumor promoting inflammation

HoC_1shot307

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PTEN loss of function enhances proliferation , but effects on cellular energy metabolism are less well characterized . We used an inducible PTEN expression vector in a PTEN-null glioma cell line to examine this issue . While proliferation of PTEN-positive cells was insensitive to increases in glucose concentration beyond 2.5mM , PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to approximately 10mM , coinciding with a shift to glycolysis and " glucose addiction " . This demonstrates that the impact of loss of function of PTEN is modified by glucose concentration , and may be relevant to epidemiologic results linking hyperglycemia to cancer risk and cancer mortality . OUTPUT:

cellular energetics

HoC_1shot308

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Earlier studies indicated that density-arrested cancer cells released an unidentified growth inhibitor whose secretion was prevented by overexpression of the lysosomal protease cathepsin D ( cath D ) . In this study , this growth inhibitor was purified by affinity chromatography and identified as the heat shock cognate 70 protein ( hsc70 ) based on its peptide microsequencing and specific antibody recognition . Among intracellular proteins , including other heat shock proteins , only constitutive hsc70 was secreted in response to the high-cell density . Moreover , hsc70 secretion from cancer cells was generated by serum deprivation , whereas its cellular concentration did not change . Prevention of Hsc70 secretion by cath D overexpression was associated with the formation of multilayer cell cultures , thus indicating a loss of contact inhibition . In addition , we showed that supplementing the culture medium with purified hsc70 inhibited cell proliferation in the nanomolar range . Conversely , removal of this extracellular hsc70 from the medium by either retention on ADP-agarose or competition at the Hsc70 binding site restored cell proliferation . Hsc70 appears active in human breast cancer cells and hypersecreted by direct cath D inhibition . These results suggest a new role of this secreted hsc70 chaperone in cell proliferation that might account for the higher tumor growth of cancer cells overexpressing cath D . OUTPUT:

evading growth suppressors

HoC_1shot309

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Manganese , an essential trace nutrient in human beings , has been widely used in the steel industry to improve hardness , stiffness , and strength . With the increased applications of manganese compounds , discharge into the environment has rapidly increased and may exert adverse effects on human health . In this study , manganese toxicity was investigated using cultured T98G cells , which are derived from human glioblasts with the ability to differentiate into several different types of neuroglia . Cytotoxicity was shown in manganese-treated groups ( 100 , 200 , 400 , and 800microM of MnCl(2) ) , and cell viability was decreased to 58.8% of the control group at 2days after treatment with 800microM of MnCl(2) . When cells were treated with manganese for 24h , ROS dose-dependently increased while antioxidant intracellular GSH decreased . With the generation of ROS , the increased activity of caspase-3 was shown , and was followed by chromatin condensation and breakage , which is an indication of the cellular apoptotic process . ROS also triggered pro-inflammatory responses in cultured T98G cells , which were demonstrated by the increased gene expression and protein levels of IL-6 and IL-8 . OUTPUT:

tumor promoting inflammation;resisting cell death

HoC_1shot310

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Gliomas are aggressive and almost incurable glial brain tumors which frequently display abnormal platelet-derived growth factor ( PDGF ) signaling . Evidence gained from studies on several in vivo animal models has firmly established a causal connection between aberrant PDGF signaling and the formation of some gliomas . However , only recently has significant knowledge been gained regarding crucial issues such as the glioma cell of origin and the relationship between the transforming stimulus and the cellular characteristics of the resulting tumor . Based on recent evidence , we propose that PDGF can bias cell-fate decisions , driving the acquisition of cell type-specific features by the progeny of multipotent neural progenitors , thus determining the shape and direction of the transformation path . Furthermore , recent data about the cellular mechanisms of PDGF-driven glioma progression and maintenance indicate that PDGF may be required , unexpectedly , to override cell contact inhibition and promote glioma cell infiltration rather than to stimulate cell proliferation . OUTPUT:

evading growth suppressors

HoC_1shot311

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Inflammation which is an indispensable participant in tumor progression is intricately linked with redox modulation . The pro-inflammatory cytokine Tumor Necrosis Factor ( TNFalpha ) elevates reactive oxygen species ( ROS ) in glioblastoma multiforme ( GBM ) . As both TNFalpha and oxidative stress independently play role in regulating cytoskeletal organization and cell survival pathways we investigated whether TNFalpha mediated oxidative stress regulates responses that offer survival advantages to glioblastoma cells . Treatment with TNFalpha elevated Akt phosphorylation in glioma cells . Increased in Akt phosphorylation was concurrent with the decrease in ROS scavenger SOD-1 levels . TNFalpha mediated increase in Akt phosphorylation was dependent on oxidative stress as Akt phosphorylation was abrogated in the presence of ROS inhibitor and elevated in cells transfected with SOD-1 siRNA . TNFalpha altered actin cytoskeletal organization and increased Cdc42 levels . This increase in Cdc42 was concomitant with its increased interaction with scaffold protein IQGAP-1 . Also , we report for the first time a ROS dependent interaction between pAkt and IQGAP-1 in TNFalpha treated cells . Importantly , Akt inhibition not only reversed TNFalpha mediated changes in actin cytoskeletal organization but also abrogated anchorage independent growth . Together , these results suggest that TNFalpha induced oxidative stress affects Akt activation to regulate actin organization and growth of glioma cells . OUTPUT:

tumor promoting inflammation

HoC_1shot312

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Tumor endothelial marker ( TEM ) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis . So far , the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified . Here , we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel , during capillary morphogenesis in a three-dimensional collagen I matrix , and upon confluence on a two-dimensional matrix . TEM5 expression was not induced by a variety of soluble angiogenic factors , including VEGF and bFGF , in subconfluent endothelial cells . TEM5 upregulation was blocked by toxin B from Clostridium difficile , an inhibitor of the small GTPases Rho , Rac , and Cdc42 . The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression , whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation . An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation . Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells . OUTPUT:

inducing angiogenesis;evading growth suppressors

HoC_1shot313

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: In cancer cells , glucose is often converted into lactic acid , which is known as the ' Warburg effect ' . The reason that cancer cells have a higher rate of aerobic glycolysis , but not oxidative phosphorylation , remains largely unclear . Herein , we proposed an epigenetic mechanism of the Warburg effect . Fructose-1,6-bisphosphatase-1 ( FBP1 ) , which functions to antagonize glycolysis was downregulated through NF-kappaB pathway in Ras-transformed NIH3T3 cells . Restoration of FBP1 expression suppressed anchorage-independent growth , indicating the relevance of FBP1 downregulation in carcinogenesis . Indeed , FBP1 was downregulated in gastric carcinomas ( P<0.01 , n=22 ) and gastric cancer cell lines ( 57% , 4/7 ) . Restoration of FBP1 expression reduced growth and glycolysis in gastric cancer cells . Moreover , FBP1 downregulation was reversed by pharmacological demethylation . Its promoter was hypermethylated in gastric cancer cell lines ( 57% , 4/7 ) and gastric carcinomas ( 33% , 33/101 ) . Inhibition of NF-kappaB restored FBP1 expression , partially through demethylation of FBP1 promoter . Notably , Cox regression analysis revealed FBP1 promoter methylation as an independent prognosis predicator for gastric cancer ( hazard ratio : 3.60 , P=0.010 ) . In summary , we found that NF-kappaB functions downstream of Ras to promote epigenetic downregulation of FBP1 . Promoter methylation of FBP1 can be used as a new biomarker for prognosis prediction of gastric cancer . Such an important epigenetic link between glycolysis and carcinogenesis partly explains the Warburg effect . OUTPUT:

cellular energetics

HoC_1shot314

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES Recently , it was revealed that carnosine inhibits growth of cells isolated from human malignant glioma . In order to understand how this effect is mediated , experiments were performed that addressed a possible influence of carnosine on energy metabolism . METHODS Cells from the glioma line T98G and primary cultured cells from human malignant glioma were cultivated in the presence of carnosine and inhibitors of cellular energy metabolism . As a specific inhibitor for anaerobic glycolysis , oxamate , and as an inhibitor for mitochondrial oxidative phosphorylation , potassium cyanide , were used , and the influence on ATP production was determined using cell-based assays . RESULTS The experiments identified glycolysis as crucial for ATP production in gliomas . In addition , ATP production by mitochondrial activity did not significantly contribute to ATP production and carnosine was identified to be an inhibitor of the vital anaerobic glycolysis . DISCUSSION Carnosine might be considered as a potential drug for the treatment of malignant glioma or other tumors since it inhibits the glycolytic energy metabolism that is crucial for cancer cells and malignant gliomas as shown in the current study . This is especially interesting since the dipeptide is a naturally occurring substance that should be well tolerated . OUTPUT:

cellular energetics

HoC_1shot315

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The aim of the present study was to evaluate immunomodulator ginsan , a polysaccharide extracted from Panax ginseng , on carbon tetrachloride ( CCl(4))-induced liver injury . BALB/c mice were injected i.p. with ginsan 24 h prior to CCl(4) administration . Serum liver enzyme levels , histology , expression of antioxidant enzymes , and several cytokines/chemokines were subsequently evaluated . Ginsan treatment markedly suppressed the serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels , and hepatic histological necrosis increased by CCl(4) treatment . Ginsan inhibited CCl(4) induced lipid peroxidation through the cytochrome P450 2E1 ( CYP2E1 ) downregulation . The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents , such as superoxide dismutase ( SOD ) , catalase , and glutathione peroxidase ( GPX ) as well as restoration of the hepatic glutathione ( GSH ) concentration . The marked increase of proinflammatory cytokines ( IL-1beta , IFN-gamma ) and chemokines ( MCP-1 , MIP-2beta , KC ) in CCl(4) treated mice was additionally attenuated by ginsan , thereby preventing leukocyte infiltration and local inflammation . Our results suggest that ginsan effectively prevent liver injury , mainly through downregulation of oxidative stress and inflammatory response . OUTPUT:

tumor promoting inflammation

HoC_1shot316

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: A common metabolic change in cancer is the acquisition of glycolytic phenotypes . Increased expression of glycolytic enzymes is considered as one contributing factor . The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial . Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-Ras(Q61L) transformation , even though the mitochondrial contents or mass was not reduced in the transformed cells . First , mitochondrial respiration , as measured by mitochondrial oxygen consumption , was suppressed in NIH-3T3 cells transformed with H-Ras(Q61L) . Second , oligomycin or rotenone did not reduce the cellular ATP levels in the H-Ras(Q61L) transformed cells , suggesting a diminished role of mitochondrial respiration in the cellular energy metabolism . Third , inhibition of glycolysis with iodoacetic acid reduced ATP levels at a much faster rate in H-Ras(Q61L) transformed cells than in the vector control cells . The reduction of cellular ATP levels was reversed by exogenously added pyruvate in the vector control cells but not in H-Ras(Q61L) transformed cells . Finally when compared to the HRas(Q61L) transformed cells , the vector control cells had increased resistance toward glucose deprivation . The increased resistance was dependent on mitochondrial oxidative phosphorylation since rotenone or oligomycin abolished the increased survival of the vector control cells under glucose deprivation . The results also suggest an inability of the H-Ras(Q61L) transformed cells to reactivate mitochondrial respiration under glucose deprivation . Taken together , the data suggest that mitochondrial respiration can be impaired during transformation of NIH-3T3 cells by oncogeneic H-Ras(Q61L) . OUTPUT:

cellular energetics

HoC_1shot317

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Inhibition of Notch signaling is effective in inhibiting colon tumorigenesis , but targeting specific components of the pathway may provide more effective strategies . Here we show that the expression of Jagged1 , a ligand for canonical Notch signaling , was restricted to enteroendocrine cells or undetectable in the mucosa of the human small and large intestine , respectively . In contrast , increased expression characterized half of human colon tumors , although not all tumors with elevated Wnt signaling displayed elevated Jagged1 . Increased Jagged1 was also present in intestinal tumors of Apc(1638N/+) and Apc(Min/+) mice , but to a higher level and more frequently in the former , and in 90% of mouse tumors Notch signaling was elevated when Jagged1 was elevated . In the human HT29Cl16E colonic carcinoma cell line , induction of goblet cell differentiation by contact inhibition of growth depended on the loss of Jagged1-mediated Notch activation , with signaling through Notch1 and Notch2 acting redundantly . Therefore , targeting of Jagged1 could be effective in downregulating Notch signaling in a subset of tumors , but may avoid the limiting gastrointestinal toxicity caused by pharmacological inhibition of Notch signaling . OUTPUT:

evading growth suppressors

HoC_1shot318

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Reactive oxygen species ( ROS ) such as hydrogen peroxide ( H(2)O(2) ) , O(*-)(2) and OH(*) participate in the pathogenesis of ischemia/reperfusion injury , inflammation and atherosclerosis . Our previous studies have suggested that increased angiotensin II ( Ang II)-forming chymase may be involved in the development of atherosclerosis . However , the regulatory mechanism of chymase expression has not yet been clarified . In this study , we tested whether oxidative stress upregulates mouse mast cell proteinase chymase , mouse mast cell proteinase ( MMCP)-5 or MMCP-4 . We also examined the expression and activity of these proteins after treatment . Cultured mouse mastocytoma cells ( MMC ) displaying chymase-dependent Ang II-forming activity were treated with H(2)O(2) and several aminothiols with or without anti-oxidants . The levels of MMCP-5 and MMCP-4 expression were determined by quantitative RT-PCR ; the level of chymase-dependent Ang II-forming activity was measured by high performance liquid chromatography using Ang I as a substrate . Treatment of MMC with homocysteine ( 0.1-3 mmol l(-1) ) significantly increased MMCP-5 and MMCP-4 expression , as well as Ang II-forming activity . These effects were significantly inhibited by the addition of catalase and further suppressed by the combination of catalase and superoxide dismutase . Incubation with hydrogen peroxide alone caused a significant increase in Ang II-forming activity , which was completely suppressed by co-treatment with catalase . Furthermore , MMCP-5 and MMCP-4 expression levels were drastically suppressed and chymase induction by homocysteine was diminished under the GATA-inhibited condition . Homocysteine increased mast cell chymase expression and activity through the mechanism of oxidative stress . Our results suggest that there is a biochemical link between oxidative stress and the local Ang II-forming system . OUTPUT:

tumor promoting inflammation

HoC_1shot319

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Energy deregulation and abnormalities of tumor cell metabolism are critical issues in understanding cancer . Hereditary leiomyomatosis renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme fumarate hydratase ( FH ) , and one known to be highly metastatic and unusually lethal . There is considerable utility in establishing preclinical cell and xenograft models for study of disorders of energy metabolism , as well as in development of new therapeutic approaches targeting of tricarboxylic acid ( TCA ) cycle enzyme-deficient human cancers . Here we describe a new immortalized cell line , UOK 262 , derived from a patient having aggressive HLRCC-associated recurring kidney cancer . We investigated gene expression , chromosome profiles , efflux bioenergetic analysis , mitochondrial ultrastructure , FH catabolic activity , invasiveness , and optimal glucose requirements for in vitro growth . UOK 262 cells have an isochromosome 1q recurring chromosome abnormality , i(1)(q10) , and exhibit compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC . The cells also display glucose-dependent growth , an elevated rate of lactate efflux , and overexpression of the glucose transporter GLUT1 and of lactate dehydrogenase A ( LDHA ) . Mutant FH protein was present primarily in edematous mitochondria , but with catalytic activity nearly undetectable . UOK 262 xenografts retain the characteristics of HLRCC histopathology . Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme-deficient form of kidney cancer . This tumor model is the embodiment of the Warburg effect . UOK 262 provides a unique in vitro and in vivo preclinical model for studying the bioenergetics of the Warburg effect in human cancer . OUTPUT:

cellular energetics

HoC_1shot320

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Depleted uranium ( DU ) is commonly used in military armor and munitions , and thus , exposure of soldiers and noncombatants is frequent and widespread . Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion . However , there is limited research information on the potential carcinogenicity of DU in human bronchial cells . Accordingly , we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells ( BEP2D ) . We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h . We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU . Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype . These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype . OUTPUT:

evading growth suppressors

HoC_1shot321

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication . Simultaneously , however , it may also enhance antitumor therapy through initiation of proinflammatory , antiviral cytokine responses at the tumor site . The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus . In this respect , injection of oncolytic vesicular stomatitis virus ( VSV ) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression , but it is not associated with viral replicative burst in the tumor . In contrast , intratumoral delivery of VSV induces an acute proinflammatory reaction , which quickly resolves concomitantly with virus clearance . Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication , a single-cycle VSV is equally effective as a fully replication-competent VSV , whereas inactivated viruses do not generate therapy . Even though therapy is dependent on host CD8+ and natural killer cells , these effects are not associated with interferon-gamma-dependent responses against either the virus or tumor . There is , however , a strong correlation between viral gene expression , induction of proinflammatory reaction in the tumor and in vivo therapy . Overall , our results suggest that acute innate antiviral immune response , which rapidly clears VSV from B16ova tumors , is associated with the therapy observed in this model . Therefore , the antiviral immune response to an oncolytic virus mediates an intricate balance between safety , restriction of oncolysis and , potentially , significant immune-mediated antitumor therapy . OUTPUT:

tumor promoting inflammation

HoC_1shot322

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The high glucose consumption of tumor cells even in an oxygen-rich environment , referred to as the Warburg effect , has been noted as a nearly universal biochemical characteristic of cancer cells . Targeting the glycolysis pathway has been explored as an anti-cancer therapeutic strategy to eradicate cancer based on this fundamental biochemical property of cancer cells . Oncoproteins such as Akt and c-Myc regulate cell metabolism . Accumulating studies have uncovered various molecular mechanisms by which oncoproteins affect cellular metabolism , raising a concern as to whether targeting glycolysis will be equally effective in treating cancers arising from different oncogenic activities . Here , we established a dual-regulatable FL5.12 pre-B cell line in which myristoylated Akt is expressed under the control of doxycycline , and c-Myc , fused to the hormone-binding domain of the human estrogen receptor , is activated by 4-hydroxytamoxifen . Using this system , we directly compared the effect of these oncoproteins on cell metabolism in an isogenic background . Activation of either Akt or c-Myc leads to the Warburg effect as indicated by increased cellular glucose uptake , glycolysis , and lactate generation . When cells are treated with glycolysis inhibitors , Akt sensitizes cells to apoptosis , whereas c-Myc does not . In contrast , c-Myc but not Akt sensitizes cells to the inhibition of mitochondrial function . This is correlated with enhanced mitochondrial activities in c-Myc cells . Hence , although both Akt and c-Myc promote aerobic glycolysis , they differentially affect mitochondrial functions and render cells susceptible to the perturbation of cellular metabolic programs . OUTPUT:

cellular energetics

HoC_1shot323

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

resisting cell death;avoiding immune destruction

HoC_1shot324

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

cellular energetics

HoC_1shot325

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND &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 . OUTPUT:

evading growth suppressors

HoC_1shot326

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Candida albicans infections are very frequent in cancer patients , whose immune system is often compromised , but whether this fungal pathogen affects cancer progression is unknown . C. albicans infection involves endogenous production of inflammatory cytokines such as tumour necrosis factor alpha ( TNF-alpha ) and interleukin-18 ( IL-18 ) . Increased levels of these cytokines have already been correlated with metastasis of most common cancer types . In this study , a well-established model of IL-18-dependent hepatic melanoma metastasis was used to study whether C. albicans can alter the ability of murine B16 melanoma ( B16M ) cells to colonize the liver . First , we determined the ability of intrasplenically ( IS ) injected B16M cells to metastasize into the liver of mice challenged with 5 x 10(4) C. albicans cells by three different routes ( intravenous , IV ; intrasplenic , IS ; or intraperitoneal , IP ) 12 h prior to injection of B16M cells . We demonstrated that C. albicans significantly increased metastasis of B16M cells with all three fungal injection routes . Pro-metastatic effects occurred when hepatic colonization with B16M cells place after the peak of TNF-alpha and IL-18 levels had been reached in the hepatic blood of fungal challenged mice . In a second set of experiments , mice were fungal challenged 4 days after injection of B16M cells . In these mice , C. albicans also potentiated the growth of established micro-metastases . Significantly , the fungal challenge had pro-metastatic effects without the C. albicans being able to reach the liver , suggesting that soluble factors can promote metastasis in remote sites . Mouse treatment with antifungal ketoconazol abrogated hepatic TNF-alpha stimulation by C. albicans and prevented the enhancement of hepatic metastasis in fungal challenged-mice . Therefore , the pro-inflammatory microenvironment generated by the host's systemic response to C. albicans stimulates circulating cancer cells to metastasize in the liver . OUTPUT:

activating invasion and metastasis;tumor promoting inflammation

HoC_1shot327

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Mutations in the tumor suppressor tuberin ( TSC2 ) are a common factor in the development of lymphangioleiomyomatosis ( LAM ) . LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma . The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated , although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells . Here we show that tuberin-null cells become nonadherent and invasive . These nonadherent cells express cleaved forms of β-catenin . In reporter assays , the β-catenin products are transcriptionally active and promote MMP7 expression . Invasion by the tuberin-null cells is mediated by MMP7 . Examination of LAM tissues shows the expression of cleaved β-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a β-catenin-dependent mechanism , which may underlie the development of LAM . OUTPUT:

activating invasion and metastasis

HoC_1shot328

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects . Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk . All mice developed tumors by 13 wk of promotion . However , in mice pretreated with 30 microL eugenol , no tumors were detected until 8 wk ( following anti-initiation protocol ) and until 14 wk ( following antipromotion protocol ) of tumor promotion . PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively . The effect of eugenol was assessed on specific stages of carcinogenesis . Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA . However , pretreatment with eugenol led to overexpression of these genes , which probably helped stimulate apoptosis of the initiated cells . To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol , its effect was investigated on markers of tumor promotion and inflammation : ODC activity and iNOS and COX-2 expression , and on levels of proinflammatory cytokines ( IL-6 , TNF-alpha , and PGE(2) ) . Eugenol markedly inhibited all . Eugenol also inhibited the upstream signaling molecule : NF-kappaB , which regulates the expression of these genes . TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol . From these results , it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative , anti-inflammatory , and antioxidant activities . OUTPUT:

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

HoC_1shot329

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Polycyclic aromatic hydrocarbons ( PAHs ) are widely distributed immunotoxic and carcinogenic environmental contaminants , known to affect macrophages . In order to identify their molecular targets in such cells , we have analyzed gene expression profile of primary human macrophages treated by the prototypical PAH benzo(a)pyrene ( BaP ) , using pangenomic oligonucleotides microarrays . Exposure of macrophages to BaP for 8 and 24 h resulted in 96 and 1100 genes , differentially expressed by at least a twofold change factor , respectively . Some of these targets , including the chemokine receptor CXCR5 , the G protein-coupled receptor 35 ( GPR35 ) , and the Ras regulator RASAL1 , have not been previously shown to be affected by PAHs , in contrast to others , such as interleukin-1beta and the aryl hydrocarbon receptor ( AhR ) repressor . These BaP-mediated gene regulations were fully validated by reverse transcription-quantitative polymerase chain reaction assays for some selected genes . Their bioinformatic analysis indicated that biological functions linked to immunity , inflammation , and cell death were among the most affected by BaP in human macrophages and that the AhR and p53 signaling pathways were the most significant canonical pathways activated by the PAH . AhR and p53 implications were moreover fully confirmed by the prevention of BaP-related upregulation of some selected target genes by AhR silencing or the use of pifithrin-alpha , an inhibitor of PAH bioactivation-related DNA damage/p53 pathways . Overall , these data , through identifying genes and signaling pathways targeted by PAHs in human macrophages , may contribute to better understand the molecular basis of the immunotoxicity of these environmental contaminants . OUTPUT:

tumor promoting inflammation;genomic instability and mutation;avoiding immune destruction

HoC_1shot330

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Mitochondrial biogenesis , which depends on nuclear as well as mitochondrial genes , occurs in response to increased cellular ATP demand . The nuclear transcriptional factors , estrogen-related receptor alpha ( ERRalpha ) and nuclear respiratory factors 1 and 2 , are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis , whereas coactivators of the peroxisome proliferator-activated receptor gamma coactivator-1 ( PGC-1 ) family serve as mediators between the environment and this machinery . In the context of proliferating cells , PGC-1-related coactivator ( PRC ) is a member of the PGC-1 family , which is known to act in partnership with nuclear respiratory factors , but no functional interference between PRC and ERRalpha has been described so far . We explored three thyroid cell lines , FTC-133 , XTC.UC1 and RO 82 W-1 , each characterized by a different mitochondrial content , and studied their behavior towards PRC and ERRalpha in terms of respiratory efficiency . Overexpression of PRC and ERRalpha led to increased respiratory chain capacity and mitochondrial mass . The inhibition of ERRalpha decreased cell growth and respiratory chain capacity in all three cell lines . However , the inhibition of PRC and ERRalpha produced a greater effect in the oxidative cell model , decreasing the mitochondrial mass and the phosphorylating respiration , whereas the nonphosphorylating respiration remained unchanged . We therefore hypothesize that the ERRalpha-PRC complex plays a role in arresting the cell cycle through the regulation of oxidative phosphorylation in oxidative cells , and through some other pathway in glycolytic cells . OUTPUT:

cellular energetics

HoC_1shot331

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: RAD51 is a key enzyme of homologous recombination and repair of DNA double-strand breaks . RAD51 mRNA expression levels are significantly increased in laser-microdissected mammary simple carcinomas and their lymph node metastases when compared to adenomas or nonneoplastic mammary gland of the same dog . Here , RAD51 protein expression was analyzed by immunohistochemistry in paraffin-embedded mammary carcinomas and their lymph node metastases of 40 dogs , adenomas of 48 dogs , and nonneoplastic mammary gland of 88 dogs . Number of cells with nuclear RAD51 expression was significantly ( P &lt ; or = .05 ) increased in carcinomas when compared to adenomas and metastases . In contrast , no significant differences in the number of RAD51-expressing cells were detected when metastases were compared with adenomas and nonneoplastic gland . RAD51 expression in carcinomas was correlated with expression in metastases but not with histologic grade . In conclusion , the increased number of RAD51-expressing cells in carcinomas might indicate genomic instability in these cells . Nevertheless , the increased RAD51 mRNA expression in metastases could not be confirmed by immunohistochemistry . OUTPUT:

activating invasion and metastasis;genomic instability and mutation

HoC_1shot332

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cell proliferation is known to be accompanied by activation of glycolysis . We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase , isoform 3 ( PFKFB3 ) , is degraded by the E3 ubiquitin ligase APC/C-Cdh1 , which also degrades cell-cycle proteins . We now show in two different cell types ( neoplastic and nonneoplastic ) that both proliferation and aerobic glycolysis are prevented by overexpression of Cdh1 and enhanced by its silencing . Furthermore , we have coexpressed Cdh1 with PFKFB3--either wild-type or a mutant form resistant to ubiquitylation by APC/C-Cdh1--or with the glycolytic enzyme 6-phosphofructo-1-kinase and demonstrated that whereas glycolysis is essential for cell proliferation , its initiation in the presence of active Cdh1 does not result in proliferation . Our experiments indicate that the proliferative response , regardless of whether it occurs in normal or neoplastic cells , is dependent on a decrease in the activity of APC/C-Cdh1 , which activates both proliferation and glycolysis . These observations have implications for cell proliferation , neoplastic transformation , and the prevention and treatment of cancer . OUTPUT:

cellular energetics

HoC_1shot333

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The contribution that mitochondrial bioenergetics could have in cancer development is debated . Here , we have generated HCT116-derived colocarcinoma cell lines expressing different levels of the beta catalytic subunit of the mitochondrial H+-adenosine triphosphate synthase to assess the contribution of mitochondrial bioenergetics in colon cancer progression . The generated cells exhibit large ultrastructural , transcriptomic , proteomic and functional differences in their mitochondria and in their in vivo tumor forming capacity . We show that the activity of oxidative phosphorylation defines the rate of glucose utilization by aerobic glycolysis . The aggressive cellular phenotype , which is highly glycolytic , is bound to the deregulated expression of genes involved in metabolic processes , the regulation of the cell cycle , apoptosis , angiogenesis and cell adhesion . Remarkably , the molecular and ultrastructural analysis of the tumors derived from the three HCT116 cell lines under study highlight that tumor promotion inevitably requires the selection of cancer cells with a repressed biogenesis and functional activity of mitochondria , i.e. the highly glycolytic phenotype is selected for tumor development . The tumor forming potential of the cells is a non-genetically acquired condition that provides the cancer cell with a cell-death resistant phenotype . An abrogated mitochondrial respiration contributes to a diminished potential for reactive oxygen species signaling in response to 5-fluorouracil treatment . Treatment of cancer cells with dichloroacetate partially restores the functional differentiation of mitochondria and promotes tumor regression , emphasizing the reversible nature of the metabolic trait of cancer . OUTPUT:

cellular energetics

HoC_1shot334

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Diets rich in fruits and vegetables are associated with lower risk of cancer which may be conferred in part by the antioxidant properties of these foods . However , antioxidant supplementation or increased consumption of antioxidant-rich foods has been reported to have inconsistent effects on DNA damage . The present work ( the DART study ) investigated the extent of inter-individual variation in DNA damage , the capacity for base excision repair ( BER ) and the responses of both variables to supplementation with an antioxidant supplement for 6 weeks . There was a wide inter-individual variation in endogenous lymphocyte DNA strand breaks ( 8-fold variation ) , in damage after a challenge with H2O2 ( 16-fold variation ) and in DNA repair ( 41-fold variation ) measured using the comet assay . When stratified into tertiles according to the pre-supplementation level of endogenous DNA damage , there was a statistically significant decrease in DNA damage after supplementation in the tertile with the highest pre-supplementation level of damage . There was no effect of supplementation on BER . Endogenous DNA damage level before supplementation was significantly different ( P = 0.037 ) between the three genotypes for the Val16Ala single nucleotide polymorphism in manganese superoxide dismutase ( rs4880 ) with individuals homozygous/wild type showing less damage than those carrying the alanine variant . OUTPUT:

genomic instability and mutation

HoC_1shot335

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Genomic complexity is present in approximately 15% to 30% of all chronic lymphocytic leukemia ( CLL ) and has emerged as a strong independent predictor of rapid disease progression and short remission duration in CLL . We conducted this study to advance our understanding of the causes of genomic complexity in CLL . EXPERIMENTAL DESIGN We have obtained quantitative measurements of radiation-induced apoptosis and radiation-induced ATM autophosphorylation in purified CLL cells from 158 and 140 patients , respectively , and have used multivariate analysis to identify independent contributions of various biological variables on genomic complexity in CLL . RESULTS Here , we identify a strong independent effect of radiation resistance on elevated genomic complexity in CLL and describe radiation resistance as a predictor for shortened CLL survival . Furthermore , using multivariate analysis , we identify del17p/p53 aberrations , del11q , del13q14 type II ( invariably resulting in Rb loss ) , and CD38 expression as independent predictors of genomic complexity in CLL , with aberrant p53 as a predictor of approximately 50% of genomic complexity in CLL . Focusing on del11q , we determined that normalized ATM activity was a modest predictor of genomic complexity but was not independent of del11q . Through single nucleotide polymorphism array-based fine mapping of del11q , we identified frequent monoallelic loss of Mre11 and H2AFX in addition to ATM , indicative of compound del11q-resident gene defects in the DNA double-strand break response . CONCLUSIONS Our quantitative analysis links multiple molecular defects , including for the first time del11q and large 13q14 deletions ( type II ) , to elevated genomic complexity in CLL , thereby suggesting mechanisms for the observed clinical aggressiveness of CLL in patients with unstable genomes . OUTPUT:

genomic instability and mutation

HoC_1shot336

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Acute endothelial cell apoptosis and microvascular compromise couple gastrointestinal tract irradiation to reproductive death of intestinal crypt stem cell clonogens ( SCCs ) following high-dose radiation . Genetic or pharmacologic inhibition of endothelial apoptosis prevents intestinal damage , but as the radiation dose is escalated , SCCs become directly susceptible to an alternate cell death mechanism , mediated via ceramide synthase ( CS)-stimulated de novo synthesis of the proapoptotic sphingolipid ceramide , and p53-independent apoptosis of crypt SCCs . We previously reported that ataxia-telangiectasia mutated deficiency resets the primary radiation lethal pathway , allowing CS-mediated apoptosis at the low-dose range of radiation . The mechanism for this event , termed target reordering , remains unknown . Here , we show that inactivation of DNA damage repair pathways signals CS-mediated apoptosis in crypt SCCs , presumably via persistent unrepaired DNA double-strand breaks ( DSBs ) . Genetic loss of function of sensors and transducers of DNA DSB repair confers the CS-mediated lethal pathway in intestines of sv129/B6Mre11(ATLD1/ATLD1) and C57BL/6(Prkdc/SCID) ( severe combined immunodeficient ) mice exposed to low-dose radiation . In contrast , CS-mediated SCC lethality was mitigated in irradiated gain-of-function Rad50(s/s) mice , and epistasis studies order Rad50 upstream of Mre11 . These studies suggest unrepaired DNA DSBs as causative in target reordering in intestinal SCCs . As such , we provide an in vivo model of DNA damage repair that is standardized , can be exploited to understand allele-specific regulation in intact tissue , and is pharmacologically tractable . OUTPUT:

genomic instability and mutation

HoC_1shot337

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: CEACAM1 , CEA/CEACAM5 , and CEACAM6 are cell adhesion molecules ( CAMs ) of the carcinoembryonic antigen ( CEA ) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers . However , little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression . Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated , contact-inhibited cell growth . Interestingly , CEACAM1-L , but not CEACAM1-S , negatively regulates proliferation via its ITIM domain , while in proliferating cells no CEACAM expression is detectable . Furthermore , we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells , likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L , leading to undifferentiated anchorage-independent cell growth . We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6 , representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients . Taken together , our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L , but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation . OUTPUT:

evading growth suppressors

HoC_1shot338

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Folate ( vitamin B9 ) is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate ( dTMP ) and s-adenosylmethionine ( AdoMet ) . The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance , but still unclear . We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis , which is prominent in prostate cells . We , therefore , hypothesized that prostate cells might be highly susceptible to genetic , epigenetic and phenotypic changes consequent to folate restriction . RESULTS We studied the consequences of long-term , mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate ( TRAMP ) model , recapitulating different stages of prostate cancer ; benign , transformed and metastatic . High-performance liquid chromatography analysis demonstrated that mild folate depletion ( 100 nM ) sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines . Random oligonucleotide-primed synthesis ( ROPS ) revealed a significant increase in uracil misincorporation and DNA single strand breaks , while spectral karyotype analysis ( SKY ) identified five novel chromosomal rearrangements in cells grown with mild folate depletion . Using global approaches , we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine , indicating a broad effect of folate depletion on epigenetic regulation . These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion . CONCLUSIONS This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with supraphysiological amounts of folate ( 2 microM ) routinely used in tissue culture . In addition , we elucidate for the first time the contribution of these aspects to consequent phenotype changes in epithelial cells . These results provide a strong rationale for studying the effects of folate manipulation on the prostate in vivo , where cells might be more sensitive to changes in folate status resulting from folate supplementation or antifolate therapeutic approaches . OUTPUT:

genomic instability and mutation

HoC_1shot339

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Radiation therapy appears to kill cells mainly by inducing DNA double-strand breaks . We investigated whether the DNA repair gene expression status might influence the risk of locoregional recurrence ( LRR ) in breast cancer patients . METHODS AND MATERIALS We used a quantitative reverse transcriptase PCR-based approach to measure messenger RNA levels of 20 selected DNA repair genes in tumor samples from 97 breast cancer patients enrolled in a phase III trial ( Centre René Huguenin cohort ) . Normalized mRNA levels were tested for an association with LRR-free survival ( LRR-FS ) and overall survival ( OS ) . The findings were validated in comparison with those of an independent cohort ( Netherlands Cancer Institute ( NKI ) cohort ) . Multivariate analysis encompassing known prognostic factors was used to assess the association between DNA repair gene expression and patient outcome . RESULTS RAD51 was the only gene associated with LRR in both cohorts . With a median follow-up of 126 months in the CRH cohort , the 5-year LRR-FS and OS rates were 100% and 95% in the 61 patients with low RAD51 expression , compared with 70% and 69% in the 36 patients with high RAD51 expression , respectively ( p &lt ; 0.001 ) . RAD51 overexpression was associated with a higher risk of LRR ( hazard ratio [ HR ] , 12.83 ; 95% confidence interval [ CI ] , 3.6-45.6 ) and death ( HR , 4.10 ; 95% CI , 1.7-9.7 ) . RAD51 overexpression was also significantly associated with shorter LRR-FS and OS in the NKI cohort . CONCLUSIONS Overexpression of RAD51 , a key component of the homologous DNA repair pathway , is associated with poor breast cancer outcome . This finding warrants prospective studies of RAD51 as a prognosticator and therapeutic target . OUTPUT:

genomic instability and mutation

HoC_1shot340

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: ATM(Tel1) and ATR(Rad3) checkpoint kinases phosphorylate the C-terminus of histone H2AX ( H2A in yeasts ) in chromatin flanking DNA damage , establishing a recruitment platform for checkpoint and repair proteins . Phospho-H2A/X ( gammaH2A/X)-binding proteins at double-strand breaks ( DSBs ) have been characterized , but those required for replication stress responses are unknown . Here , we present genetic , biochemical , small angle X-ray scattering ( SAXS ) , and X-ray structural studies of the Schizosaccharomyces pombe Brc1 , a 6-BRCT-domain protein that is structurally related to Saccharomyces cerevisiae Rtt107 and mammalian PTIP . Brc1 binds gammaH2A to form spontaneous and DNA damage-induced nuclear foci . Spontaneous Brc1 foci colocalize with ribosomal DNA repeats , a region prone to fork pausing and genomic instability , whereas DNA damage-induced Brc1 foci colocalize with DSB response factors. gammaH2A binding is critical for Brc1 function . The 1.45 A resolution crystal structure of Brc1-gammaH2A complex shows how variable BRCT insertion loops sculpt tandem-BRCT phosphoprotein-binding pockets to facilitate unique phosphoprotein-interaction specificities , and unveils an acidic DNA-mimicking Brc1 surface . From these results , Brc1 docking to gammaH2A emerges as a critical chromatin-specific response to replication-associated DNA damage . OUTPUT:

genomic instability and mutation

HoC_1shot341

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Epidemiological studies exploring the connection between hypertension and cancer incidence find a higher cancer mortality in hypertensive patients , particularly elevated in hypertension associated with a stimulation of the renin-angiotensin-aldosterone system . Primary aldosteronism , with plasma aldosterone levels between 0.5 and 1 nM ( 18-36 ng/dL ) and local aldosterone levels up to 500 nM ( 18,000 ng/dL ) , is now recognised as a more common cause for hypertension . We recently found angiotensin II to be genotoxic due to its induction of oxidative stress . Since aldosterone in higher concentrations also has oxidative effects , its potential genotoxic action in pig LLC-PK1 cells with properties of proximal tubules was analysed . DNA damage was evaluated by two test systems : the comet assay , and the micronucleus frequency test . The results showed that aldosterone concentrations starting from 10 nM ( 360 ng/dL ) caused a significant increase of DNA damage monitored with the comet assay in LLC-PK1 , while there was no change in cell vitality and proliferation . The micronucleus frequency test revealed that 10 nM aldosterone also leads to the formation of micronuclei . Furthermore , the formation of superoxide radicals in the cells by this aldosterone concentration could be detected with the superoxide-specific stain dihydroethidium . Further evidence for oxidative stress-induced DNA damage was its reversibility by the antioxidants tempol and catalase . Addition of the steroidal mineralocorticoid receptor antagonist spironolactone or the novel selective nonsteroidal antagonist ( R)-BR-4628 reduced the DNA damage and the amount of superoxide radicals indicating a receptor-dependent process . OUTPUT:

genomic instability and mutation

HoC_1shot342

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The purpose of 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 . OUTPUT:

cellular energetics

HoC_1shot343

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

genomic instability and mutation;resisting cell death

HoC_1shot344

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: It is thought that high linear energy transfer ( LET ) radiation induces more complex DNA damage than low-LET particles , specifically clustered DNA damage that causes cells to repair DNA double strand breaks ( DSB ) more slowly and leads to severe biological consequences . The present study aimed to investigate the role of exogenously added glutathione ( GSH ) on ( 12)C-beam ( 287keV/mum ) and ( 7)Li-beam ( 60keV/mum ) induced chromosome aberration ( CA ) formation , particularly on exchange aberration formation . In order to characterize the role of GSH in the joining of DNA DSBs , we induced DNA lesions with bleomycin ( Blem ) in conjunction with either high- or low-LET radiation ( X-rays ) since the chemistry of the free DNA ends created by Blem and X-rays is similar . CHO cells were exposed to reduced GSH at a concentration of 2mM for 3h before radiation . Treatment with Blem ( 20mug/ml ) was carried out for 2h before the cells were exposed to radiation . Our results show that the frequency of chromosomal aberration increases with increased LET . Heavy ion exposed cells show a higher frequency of CA over time than do X-irradiated cells . An analysis of the first post-irradiation mitosis of exposed CHO cells shows that high-LET radiation induces more breaks than exchange-type aberrations and exogenous GSH has no influence on high-LET radiation-induced DNA damage . The DNA lesions induced by low-LET radiation interact relatively strongly with Blem-induced lesions whereas interaction between Blem and high-LET radiations was poor . This could be attributed to differences in repair kinetics and qualitative differences in the DNA lesions induced by Blem and high-LET radiation . OUTPUT:

genomic instability and mutation

HoC_1shot345

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Recently , the use of gold nanoparticles as potential tumor selective radiosensitizers has been proposed as a breakthrough in radiotherapy . Experiments in living cells and in vivo have demonstrated the efficiency of the metal nanoparticles when combined with low energy x-ray radiations ( below conventional 1 MeV Linac radiation ) . Further studies on DNA have been performed in order to better understand the fundamental processes of sensitization and to further improve the method . In this work , we propose a new strategy based on the combination of platinum nanoparticles with irradiation by fast ions effectively used in hadron therapy . It is observed in particular that nanoparticles enhance strongly lethal damage in DNA , with an efficiency factor close to 2 for double strand breaks . In order to disentangle the effect of the nano-design architecture , a comparison with the effects of dispersed metal atoms at the same concentration has been performed . It is thus shown that the sensitization in nanoparticles is enhanced due to auto-amplified electronic cascades inside the nanoparticles , which reinforces the energy deposition in the close vicinity of the metal . Finally , the combination of fast ion radiation ( hadron therapy ) with platinum nanoparticles should strongly improve cancer therapy protocols . OUTPUT:

genomic instability and mutation

HoC_1shot346

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

cellular energetics

HoC_1shot347

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BRIT1 protein ( also known as MCPH1 ) contains 3 BRCT domains which are conserved in BRCA1 , BRCA2 , and other important molecules involved in DNA damage signaling , DNA repair , and tumor suppression . BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients . Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways . To investigate its physiological role and dissect the underlying mechanisms , we generated BRIT1(-/-) mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability . Both BRIT1(-/-) mice and mouse embryonic fibroblasts ( MEFs ) were hypersensitive to gamma-irradiation . BRIT1(-/-) MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation . Notably , BRIT1(-/-) mice were infertile and meiotic homologous recombination was impaired . BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis , and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis . In mutant spermatocytes , DNA double-strand breaks ( DSBs ) were formed , but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired . In addition , we found that BRIT1 could bind to RAD51/BRCA2 complexes and that , in the absence of BRIT1 , recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered , indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site . Collectively , our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages , and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice . OUTPUT:

genomic instability and mutation

HoC_1shot348

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks ( DSBs ) in genomic DNA in cycling cells . These DSBs are often covalently bound with polypeptides at the 3 ' and 5 ' ends . Such modifications must be eliminated before DSB repair can take place , but it remains elusive which nucleases are involved in this process . Previous studies show that CtIP plays a critical role in the generation of 3 ' single-strand overhang at " clean " DSBs , thus initiating homologous recombination ( HR)-dependent DSB repair . To analyze the function of CtIP in detail , we conditionally disrupted the CtIP gene in the chicken DT40 cell line . We found that CtIP is essential for cellular proliferation as well as for the formation of 3 ' single-strand overhang , similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex . We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332 , which is required for interaction with BRCA1 . Although the resulting CtIP(S332A/-/-) cells exhibited accumulation of RPA and Rad51 upon DNA damage , and were proficient in HR , they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP(+/-/-) cells . Finally , CtIP(S332A/-/-)BRCA1(-/-) and CtIP(+/-/-)BRCA1(-/-) showed similar sensitivities to these reagents . Taken together , our data indicate that , in addition to its function in HR , CtIP plays a role in cellular tolerance to topoisomerase inhibitors . We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs , thereby facilitating subsequent DSB repair . OUTPUT:

genomic instability and mutation

HoC_1shot349

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative ( gemtuzumab ozogamicin , GO ) are a novel therapy option for acute myeloid leukaemia ( AML ) . Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies , including drug efflux or other mechanisms decreasing apoptosis . Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks ( DSBs ) accompanied by decreased DNA repair . METHODS We labelled anti-CD33 antibodies with the alpha-emitter ( 211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the ( 211)At-labelled antibodies , GO or unlabelled antibodies as controls . We also measured caspase-3/7 activity , DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free ( 211)At . RESULTS The mean labelling ratio of ( 211)At-labelled antibodies was 1:1,090 +/- 364 ( range : 1:738-1:1,722 ) in comparison to 2-3:1 for GO . Tumour cell binding of ( 211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33 . ( 211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution ( 1:1,000 ) . No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after ( 211)At-anti-CD33 ( 1:1,090 ) versus GO ( 1:1 ) treatment . CONCLUSION Our results suggest that ( 211)At is a promising , highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody . Labelling techniques leading to higher chemical yield and specific activities must be developed to increase ( 211)At-anti-CD33 therapeutic effects . OUTPUT:

genomic instability and mutation;resisting cell death

HoC_1shot350

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Anthracyclines have been widely used as antitumor agents , playing a crucial role in the successful treatment of many types of cancer , despite some side effects related to cardiotoxicity . New anthracyclines have been designed and tested , but the first ones discovered , doxorubicin and daunorubicin , continue to be the drugs of choice . Despite their extensive use in chemotherapy , little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines . The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis , characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene . METHODS We assessed the induction of apoptosis ( Sub-G1 ) by cosmomycin D in nucleotide excision repair-deficient fibroblasts ( XP-A and XP-C ) as well as the levels of DNA damage ( alkaline comet assay ) . RESULTS Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner , with highest apoptosis levels observed 96 h after treatment . The effects of cosmomycin D were equivalent to those obtained with doxorubicin . The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells , and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay . CONCLUSIONS Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts . Despite similar apoptosis levels , cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin . This may be related to differences in structure between cosmomycin D and doxorubicin . OUTPUT:

resisting cell death;genomic instability and mutation

HoC_1shot351

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We have developed fluorescent probes for the detection of strand scission in the excision repair of oxidatively damaged bases . They were hairpin-shaped oligonucleotides , each containing an isomer of thymine glycol or 5,6-dihydrothymine as a damaged base in the center , with a fluorophore and a quencher at the 5'- and 3'-ends , respectively . Fluorescence was detected when the phosphodiester linkage at the damage site was cleaved by the enzyme , because the short fragment bearing the fluorophore could not remain in a duplex form hybridized to the rest of the molecule at the incubation temperature . The substrate specificities of Escherichia coli endonuclease III and its human homolog , NTH1 , determined by using these probes agreed with those determined previously by gel electrophoresis using ( 32)P-labeled substrates . Kinetic parameters have also been determined by this method . Since different fluorophores were attached to the oligonucleotides containing each lesion , reactions with two types of substrates were analyzed separately in a single tube , by changing the excitation and detection wavelengths . These probes were degraded during an incubation with a cell extract . Therefore , phosphorothioate linkages were incorporated to protect the probes from nonspecific nucleases , and the base excision repair activity was successfully detected in HeLa cells . OUTPUT:

genomic instability and mutation

HoC_1shot352

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cancer cells constantly adapt to oxidative phosphorylation ( OXPHOS ) suppression resulting from hypoxia or mitochondria defects . Under the OXPHOS suppression , AMP-activated protein kinase ( AMPK ) regulates global metabolism adjustments , but its activation has been found to be transient . Whether cells can maintain cellular ATP homeostasis and survive beyond the transient AMPK activation is not known . Here , we study the bioenergetic adaptation to the OXPHOS inhibitor oligomycin in a group of cancer cells . We found that oligomycin at 100 ng/ml completely inhibits OXPHOS activity in 1 h and induces various levels of glycolysis gains by 6 h , from which we calculate the bioenergetic organizations of cancer cells . In glycolysis-dominant cells , oligomycin does not induce much energy stress as measured by glycolysis acceleration , ATP imbalance , AMPK activation , AMPK substrate acetyl-CoA carboxylase phosphorylation at Ser(79) , and cell growth inhibition . In OXPHOS-dependent LKB1 wild type cells , oligomycin induces 5-8% ATP drops and transient AMPK activation during the initial 1-2 h . After AMPK activation is completed , oligomycin-induced increase of acetyl-CoA carboxylase phosphorylation at Ser(79) is still detected , and cellular ATP is back at preoligomycin treatment levels by sustained elevation of glycolysis . Cell growth , however , is inhibited without an increase in cell death and alteration in cell cycle distribution . In OXPHOS-dependent LKB1-null cells , no AMPK activation by oligomycin is detected , yet cells still show a similar adaptation . We also demonstrate that the adaptation to oligomycin does not invoke activation of hypoxia-induced factor . Our data suggest that cancer cells may grow and survive persistent OXPHOS suppression through an as yet unidentified regulatory mechanism . OUTPUT:

cellular energetics

HoC_1shot353

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: It is commonly believed that neurons remain in G(0) phase of the cell cycle indefinitely . Cell-cycle re-entry , however , is known to contribute to neuronal apoptosis . Moreover , recent evidence demonstrates the expression of cell-cycle proteins in differentiated neurons under physiological conditions . The functional roles of such expression remain unclear . Since DNA repair is generally attenuated by differentiation in most cell types , the cell-cycle-associated events in postmitotic cells may reflect the need to re-enter the cell cycle to activate DNA repair . We show that cyclin-C-directed , pRb-dependent G(0) exit activates the non-homologous end joining pathway of DNA repair ( NHEJ ) in postmitotic neurons . Using RNA interference , we found that abrogation of cyclin-C-mediated exit from G(0) compromised DNA repair but did not initiate apoptosis . Forced G(1) entry combined with prevention of G(1) --&gt ; S progression triggered NHEJ activation even in the absence of DNA lesions , but did not induce apoptosis in contrast to unrestricted progression through G(1) --&gt ; S. We conclude that G(0) --&gt ; G(1) transition is functionally significant for NHEJ repair in postmitotic neurons . These findings reveal the importance of cell-cycle activation for controlling both DNA repair and apoptosis in postmitotic neurons , and underline the particular role of G(1) --&gt ; S progression in apoptotic signaling , providing new insights into the mechanisms of DNA damage response ( DDR ) in postmitotic neurons . OUTPUT:

genomic instability and mutation

HoC_1shot354

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: In response to DNA double strand breaks , the histone variant H2AX at the break site is phosphorylated at serine 139 by DNA damage sensor kinases such as ataxia telangiectasia-mutated , forming gamma-H2AX . This phosphorylation event is critical for sustained recruitment of other proteins to repair the break . After repair , restoration of the cell to a prestress state is associated with gamma-H2AX dephosphorylation and dissolution of gamma-H2AX-associated damage foci . The phosphatases PP2A and PP4 have previously been shown to dephosphorylate gamma-H2AX . Here , we demonstrate that the wild-type p53-induced phosphatase 1 ( WIP1 ) also dephosphorylates gamma-H2AX at serine 139 in vitro and in vivo . Overexpression of WIP1 reduces formation of gamma-H2AX foci in response to ionizing and ultraviolet radiation and blocks recruitment of MDC1 ( mediator of DNA damage checkpoint 1 ) and 53BP1 ( p53 binding protein 1 ) to DNA damage foci . Finally , these inhibitory effects of WIP1 on gamma-H2AX are accompanied by WIP1 suppression of DNA double strand break repair . Thus , WIP1 has a homeostatic role in reversing the effects of ataxia telangiectasia-mutated phosphorylation of H2AX . OUTPUT:

genomic instability and mutation

HoC_1shot355

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The anti-apoptotic protein , BAX inhibitor-1 ( BI-1 ) , has a role in cancer/tumor progression . BI-1-overexpressing HT1080 and B16F10 cells produced higher lung weights and tumor volumes after injection into the tail veins of mice . Transfection of BI-1 siRNA into cells before injection blocked lung metastasis. in vitro , the overexpression of BI-1 increased cell mobility and invasiveness , with highly increased glucose consumption and cytosolic accumulation of lactate and pyruvate , but decreased mitochondrial O(2) consumption and ATP production . Glucose metabolism-associated extracellular pH also decreased as cells excreted more H(+) , and sodium hydrogen exchanger ( NHE ) activity increased , probably as a homeostatic mechanism for intracellular pH . These alterations activated MMP 2/9 and cell mobility and invasiveness , which were reversed by the NHE inhibitor , 5-(N-ethyl-N-isopropyl) amiloride ( EIPA ) , suggesting a role for NHE in cancer metastasis . In both in vitro and in vivo experiments , C-terminal deleted ( CDeltaBI-1 ) cells showed similar results to control cells , suggesting that the C-terminal motif is required for BI-1-associated alterations of glucose metabolism , NHE activation and cancer metastasis . These findings strongly suggest that BI-1 reduces extracellular pH and regulates metastasis by altering glucose metabolism and activating NHE , with the C-terminal tail having a pivotal role in these processes . OUTPUT:

activating invasion and metastasis;cellular energetics

HoC_1shot356

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We investigated the mechanisms of DNA exit during single-cell gel electrophoresis ( the comet assay ) by measuring the kinetics of the comet tail formation . In the neutral comet assay , the rate of DNA exit was found to be dependent on the topological state of DNA , which was influenced by either ethidium bromide or a low radiation dose . The results clearly show that the comet tail is formed by extended DNA loops : the loop extension , being reversible when the DNA torsional constraint remains in the loops , is favored when the constraint is relaxed . The kinetics of the comet formation in the case of a high radiation dose points out that accumulation of the single-strand breaks causes DNA fragmentation . In contrast to the neutral comet assay , the alkaline comet assay is not related to the chromatin loops . Our results imply that the alkaline treatment induces detachment of the loops from the nuclear matrix , and the comet tail is formed by ssDNA fragments , the ends of which are pulled out from the comet head by electric force . We suggest that the kinetic approach can be considered as an important improvement of the comet assay . OUTPUT:

genomic instability and mutation

HoC_1shot357

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Homologous recombination ( HR ) is essential for repair of meiotic DNA double-strand breaks ( DSBs ) . Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized , the subsequent steps of HR are less well defined . Here , we describe a synthetic lethal interaction between the C. elegans helicase helq-1 and RAD-51 paralog rfs-1 , which results in a block to meiotic DSB repair after strand invasion . Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics in helq-1 , rfs-1 double mutants , persistence of RAD-51 foci and genetic interactions with rtel-1 suggest a failure to disassemble RAD-51 from strand invasion intermediates . Indeed , purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from double-stranded , but not single-stranded , DNA filaments via distinct mechanisms in vitro . These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly , which are collectively essential for completion of meiotic DSB repair . OUTPUT:

genomic instability and mutation

HoC_1shot358

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Diphenyl ditelluride ( DPDT ) is a potential prototype for the development of novel biologically active molecules . Thus , it is important to evaluate the toxic effects of this compound . In the present study , we evaluated the cytotoxic , genotoxic and mutagenic properties of DPDT in Chinese hamster fibroblast ( V79 ) cells , in strains of the yeast Saccharomyces cerevisiae both proficient and deficient in several DNA repair pathways and in Salmonella typhimurium . DPDT induced frameshift mutations in both S.typhimurium and a haploid wild-type strain of S.cerevisiae . Mutants of S.cerevisiae defective in base excision repair and recombinational repair were more sensitive to DPDT . The results of a lactate dehydrogenase leakage assay suggest that DPDT is cytotoxic to V79 cells . At cytotoxic concentrations , this compound increased thiobarbituric reactive species levels and decreased the glutathione:GSSH ratio in yeast and V79 cells . DPDT generated single- and double-strand DNA breaks in V79 cells , both with and without metabolic activation , as revealed by alkaline and neutral comet assays . Moreover , an induction of oxidative DNA base damage was indicated by a modified comet assay using formamidopyrimidine DNA glycosylase and endonuclease III . Treatment with DPDT also induced micronucleus formation in V79 cells . Pre-incubation with N-acetylcysteine reduced DPDT's oxidative , genotoxic and mutagenic effects in yeast and V79 cells . Our results suggest that the toxic and mutagenic properties of DPDT may stem from its ability to disturb the redox balance of the cell , which leads to oxidative stress and the induction of DNA damage . OUTPUT:

genomic instability and mutation

HoC_1shot359

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair . The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance . While activation of DNA damage checkpoints has been studied extensively , molecular mechanisms involved in sustaining and ultimately inactivating cell cycle checkpoints are largely unknown . Here , we explored feedback mechanisms that control the maintenance and termination of checkpoint function by computationally identifying an evolutionary conserved mitotic phosphorylation network within the DNA damage response . We demonstrate that the non-enzymatic checkpoint adaptor protein 53BP1 is an in vivo target of the cell cycle kinases Cyclin-dependent kinase-1 and Polo-like kinase-1 ( Plk1 ) . We show that Plk1 binds 53BP1 during mitosis and that this interaction is required for proper inactivation of the DNA damage checkpoint. 53BP1 mutants that are unable to bind Plk1 fail to restart the cell cycle after ionizing radiation-mediated cell cycle arrest . Importantly , we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells . Thus , a mitotic kinase-mediated negative feedback loop regulates the ATM-Chk2 branch of the DNA damage signaling network by phosphorylating conserved sites in 53BP1 and Chk2 to inactivate checkpoint signaling and control checkpoint duration . OUTPUT:

evading growth suppressors

HoC_1shot360

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Class switch recombination ( CSR ) in B lymphocytes is initiated by introduction of multiple DNA double-strand breaks ( DSBs ) into switch ( S ) regions that flank immunoglobulin heavy chain ( IgH ) constant region exons . CSR is completed by joining a DSB in the donor S mu to a DSB in a downstream acceptor S region ( e.g. , S gamma1 ) by end-joining . In normal cells , many CSR junctions are mediated by classical nonhomologous end-joining ( C-NHEJ ) , which employs the Ku70/80 complex for DSB recognition and XRCC4/DNA ligase 4 for ligation . Alternative end-joining ( A-EJ ) mediates CSR , at reduced levels , in the absence of C-NHEJ , even in combined absence of Ku70 and ligase 4 , demonstrating an A-EJ pathway totally distinct from C-NHEJ . Multiple DSBs are introduced into S mu during CSR , with some being rejoined or joined to each other to generate internal switch deletions ( ISDs ) . In addition , S-region DSBs can be joined to other chromosomes to generate translocations , the level of which is increased by absence of a single C-NHEJ component ( e.g. , XRCC4 ) . We asked whether ISD and S-region translocations occur in the complete absence of C-NHEJ ( e.g. , in Ku70/ligase 4 double-deficient B cells ) . We found , unexpectedly , that B-cell activation for CSR generates substantial ISD in both S mu and S gamma1 and that ISD in both is greatly increased by the absence of C-NHEJ . IgH chromosomal translocations to the c-myc oncogene also are augmented in the combined absence of Ku70 and ligase 4 . We discuss the implications of these findings for A-EJ in normal and abnormal DSB repair . OUTPUT:

genomic instability and mutation

HoC_1shot361

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cancer cells preferentially metabolize glucose by aerobic glycolysis , characterized by increased lactate production . This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase , in contrast to the M1 isozyme normally expressed in differentiated cells , and it confers a proliferative advantage to tumor cells . The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons . We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues , tumor cell lines , and during terminal differentiation of muscle cells , and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms . We further show that the M1-specific exon is actively repressed in cancer-cell lines--although some M1 mRNA is expressed in cell lines derived from brain tumors--and demonstrate that the related splicing repressors hnRNP A1 and A2 , as well as the polypyrimidine-tract-binding protein PTB , contribute to this control . Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production . These findings extend the links between alternative splicing and cancer , and begin to define some of the factors responsible for the switch to aerobic glycolysis . OUTPUT:

cellular energetics

HoC_1shot362

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth . We observed promoter methylation and loss of expression in neurofilament heavy polypeptide ( NEFH ) in a significant proportion of primary esophageal squamous cell carcinoma ( ESCC ) samples that were of a high tumor grade and advanced stage . RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo , whereas forced expression of NEFH significantly inhibited cell growth and colony formation . Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase , via activation of the Akt/beta-catenin pathway , resulting in enhanced aerobic glycolysis and mitochondrial dysfunction . The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of beta-catenin expression , and was decreased by the treatment of 2-Deoxyglucose , a glycolytic inhibitor , or API-2 , an Akt inhibitor . Loss of NEFH activates the Akt/beta-catenin pathway and increases glycolysis and mitochondrial dysfunction . Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways . OUTPUT:

cellular energetics

HoC_1shot363

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The relationship between DNA damage and repair of peripheral blood leukocytes , liver , kidney and brain cells was investigated in Swiss albino mice ( Mus musculus L. ) after exposure to sevoflurane ( 2.4 vol% for 2 h daily , for 3 days ) . Genetic damage of mouse cells was investigated by the comet assay and micronucleus test . To perform the comet assay , mice were divided into a control group and 4 groups of exposed mice sacrificed on day 3 of the experiment , at 0 , 2 , 6 or 24 h after the last exposure to sevoflurane . Mean tail length ( TL ) , tail moment ( TM ) , and tail intensity ( TI ) values were significantly higher in exposed mice ( all examined organs ) than in the control group . Significant DNA damage immediately after exposure to sevoflurane was observed in leukocytes . Damage induction in the liver , kidney , and brain occurred 6 h later than in leukocytes , as expected according to the toxicokinetics of the drug , where blood is the first compartment to absorb sevoflurane . However , none of the tested tissues revealed signs of repair until 24 h after the exposure . To distinguish the unrepaired genome damage in vivo , the micronucleus test was applied . Number of micronuclei in reticulocytes showed a statistically significant increase , as compared with the control group at all observed times after the treatment . OUTPUT:

genomic instability and mutation

HoC_1shot364

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Colorectal cancer ( CRC ) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor , and thus is an useful model for studying metabolic shift . In the present study , we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry ( GC/MS ) and liquid chromatography tandem mass spectrometry ( LC/MS/MS ) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC . Colonic tissues including tumor , polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study . The metabolic profiles were obtained using GC/MS and LC/MS/MS . Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues . Various amino acids and lipids in the polyps and tumors were elevated , suggesting higher energy needs for increased cellular proliferation . In contrast , significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis . In addition , the accumulation of hypoxanthine and xanthine , and the decrease of uric acid concentration , suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC . Further , there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors . It appears that to gain a growth advantage , cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment . OUTPUT:

cellular energetics

HoC_1shot365

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Although the 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 . OUTPUT:

genomic instability and mutation

HoC_1shot366

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The neurofibromatosis type 2 ( NF2 ) tumor suppressor gene encodes merlin , a membrane/cytoskeleton protein necessary for the maintenance of contact inhibition of growth in cells . Bi-allelic inactivation of NF2 is known to cause multiple cancers in both humans and mice . However , the mechanism through which merlin exerts its tumor-suppressive function remains obscure . In this report , we show that NF2 knockout mouse embryonic fibroblasts lost contact inhibition of cell proliferation and contained significantly increased canonical Wnt signaling . Inhibition of Rac1 , the activity of which is inversely regulated by NF2 , through the use of a dominant-negative mutant , small hairpin RNA or a small molecule inhibitor in NF2-deficient cells , was able to suppress elevated Wnt signals as shown by reduced activity of the T-cell factor 4 ( TCF4 ) transcription factor . Dominant-negative TCF4 or Rac1 mutant , as well as a small molecule inhibition of Wnt , were able to curb NF2 deficiency-elicited cell proliferation at the confluent state . Thus , Rac1-mediated canonical Wnt signaling is essential for the loss of contact inhibition in NF2-deficient cells . OUTPUT:

evading growth suppressors

HoC_1shot367

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The phosphatidylinositol-3-kinase ( PI3K)/Akt oncogenic pathway is critical in glioblastomas . Loss of PTEN , a negative regulator of the PI3K pathway or activated PI3K/Akt pathway that drive increased proliferation , survival , neovascularization , glycolysis , and invasion is found in 70%-80% of malignant gliomas . Thus , PI3K is an attractive therapeutic target for malignant glioma . We report that a new irreversible PI3K inhibitor , PX-866 , shows potent inhibitory effects on the PI3K/Akt signaling pathway in glioblastoma . PX-866 did not induce any apoptosis in glioma cells ; however , an increase in autophagy was observed . PX-866 inhibited the invasive and angiogenic capabilities of cultured glioblastoma cells . In vivo , PX-866 inhibited subcutaneous tumor growth and increased the median survival time of animals with intracranial tumors . We also assessed the potential of proton magnetic resonance spectroscopy ( MRS ) as a noninvasive method to monitor response to PX-866 . Our findings show that PX-866 treatment causes a drop in the MRS-detectable choline-to-NAA , ratio and identify this partial normalization of the tumor metabolic profile as a biomarker of molecular drug action . Our studies affirm that the PI3K pathway is a highly specific molecular target for therapies for glioblastoma and other cancers with aberrant PI3K/PTEN expression . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot368

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers ; however , therapies targeting this gene have not proved to be as effective as was initially hoped . Transcriptional profiling meta-analyses have shown that there are approximately 150 genes co-overexpressed with ERBB2 , suggesting that these genes may represent alternative factors influencing ERBB2-positive tumors . Here we describe an RNA interference-based analysis of these genes that identifies transcriptional regulators of fat synthesis and storage as being critical for the survival of these cells . These transcription factors , nuclear receptor subfamily 1 , group D , member 1 ( NR1D1 ) and peroxisome proliferator activated receptor gamma binding protein ( PBP ) , both reside on ERBB2-containing 17q12-21 amplicons and are part of the ERBB2 expression signature . We show that NR1D1 and PBP act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network , which is highly active in ERBB2-positive breast cancer cells . Malate dehydrogenase 1 and malic enzyme 1 , enzymes that link glycolysis and fatty acid synthesis , are also regulated by NR1D1 . The resulting high-level fat production from increased expression of these genes likely contributes to an abnormal cellular energy metabolism based on aerobic glycolysis . Together , these results show that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival . OUTPUT:

cellular energetics

HoC_1shot369

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Ataxia-telangiectasia mutated ( ATM ) is a cellular damage sensor that coordinates the cell cycle with damage-response checkpoints and DNA repair to preserve genomic integrity . However , ATM also has been implicated in metabolic regulation , and ATM deficiency is associated with elevated reactive oxygen species ( ROS ) . ROS has a central role in many physiological and pathophysiological processes including inflammation and chronic diseases such as atherosclerosis and cancer , underscoring the importance of cellular pathways involved in redox homeostasis . We have identified a cytoplasmic function for ATM that participates in the cellular damage response to ROS . We show that in response to elevated ROS , ATM activates the TSC2 tumor suppressor via the LKB1/AMPK metabolic pathway in the cytoplasm to repress mTORC1 and induce autophagy . Importantly , elevated ROS and dysregulation of mTORC1 in ATM-deficient cells is inhibited by rapamycin , which also rescues lymphomagenesis in Atm-deficient mice . Our results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy , identifying an integration node for the cellular damage response with key pathways involved in metabolism , protein synthesis , and cell survival . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot370

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND &amp ; OBJECTIVE Hereditary non-polyposis colorectal cancer ( HNPCC or Lynch syndrome ) , is a genetically heterogeneous disorder that is believed to account for 2-10 per cent of all the colorectal cancer cases . The disease follows autosomal dominant inheritance pattern with high penetrance ( 85% ) and younger age of onset when compared to patients with sporadic tumours . HNPCC is associated with germ-line mutations in the DNA mismatch repair ( MMR ) genes namely MLH1 , MSH2 , MSH6 , and PMS2 . The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria , and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed . METHODS A total 12 members of the HNPCC family were studied for genetic investigation . Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/polymorphisms at population level . RESULTS The analysis resulted in identification of a 1975C>T mutation in exon 17 , resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed , resulting in replacement of isoleucine with valine at codon 219 . Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation , while I219V variant was found in 9.8 per cent of the controls . INTERPRETATION &amp ; CONCLUSION R659X mutation correlates with disease phenotype , and 655A>G locus is highly polymorphic . Our study suggested that R659X substitution was prime cause for the disease phenotype in this family . I219V substitution is a polymorphism having no association with the disease onset or segregation . The family members harbouring this mutation were advised to be under regular medical surveillance . OUTPUT:

genomic instability and mutation

HoC_1shot371

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils . More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer . METHODS In the present study , we used microarrays in order to obtain a global view of the transcriptional responses of the lung to LPS in mice , which mimics an acute lung inflammation . To investigate the influence of neutrophils in this process , we depleted mice from circulating neutrophils by treatment with anti-PMN antibodies prior to LPS exposure . RESULTS A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes , such as cytokine/chemokine activity and signalling . Down regulated genes represented nonimmune processes , such as development , metabolism and transport . Notably , the number of genes and pathways that were differentially expressed , was reduced when animals were depleted from circulating neutrophils , confirming the central role of neutrophils in the inflammatory response . Furthermore , there was a significant correlation between the differentially expressed gene list and the promutagenic DNA lesion M1dG , suggesting that it is the extent of the immune response which drives genetic instability in the inflamed lung . Several genes that were specifically regulated by the presence of activated neutrophils could be identified and these were mostly involved in interferon signalling , oxidative stress response and cell cycle progression . The latter possibly refers to a higher rate of cell turnover in the inflamed lung with neutrophils , suggesting that the neutrophil influx is associated with a higher risk for the accumulation and fixation of mutations . CONCLUSION Gene expression profiling identified specific genes and pathways that are related to neutrophilic inflammation and could be associated to cancer development and indicate an active role of neutrophils in mediating the LPS induced inflammatory response in the mouse lung . OUTPUT:

tumor promoting inflammation;genomic instability and mutation

HoC_1shot372

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: AIM Colorectal cancer is the third most common form of cancer in the industrial countries . Due to advances regarding the treatments , primarily development of improved surgical methods and the ability to make the earlier diagnosis , the mortality has remained constant during the past decades even though the incidence in fact has increased . To improve chemotherapy and enable personalised treatment , the need of biomarkers is of great significance . In this study , we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38 , the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis . MATERIAL AND METHODS The study included 3 colon cancer cell lines : KM12C , KM12SM and KM12l4a . The 3 cell lines were treated with SN-38 , and samples were obtained after 24 and 48 hour treatments . The gene expression analyses were performed using oligonucleotide microarrays comprising of approximately 27,000 spots where the untreated controls were compared to the SN-38-treated samples . RESULTS Unsupervised clustering clearly distinguished the treated cell lines from the untreated . Supervised analysis identified 3,974 significant genes ( p = 0.05 ) differentiating the treated samples from the untreated , majority of which were down-regulated after treatment . The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity , signal transduction , apoptosis , RNA processing , protein metabolism and transport , cell cycle and transcription . A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis , transcription , development and differentiation . CONCLUSIONS These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA , DNA and protein metabolism were affected by SN-38 . The impact of certain genes on colorectal cancer development needs to be further evaluated ; however , these results could serve as a basis for further studies in order to find targets for irinotecan treatment . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot373

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hypoxia is widespread in solid tumors as a consequence of poorly structured tumor-derived neovasculature , which is recognized to play a role in the resistance of cancer cells to chemotherapy . Etoposide ( VP-16 ) , a drug commonly used in chemotherapy , leads to enhanced accumulation of cell populations in G2/M phase and increases levels of apoptosis as a topoisomerase II inhibitor . We evaluated the effects of hypoxia on the response of the neuroblastoma cell line CHP126 to VP-16 , in order to delineate the mechanisms responsible for the hypoxia-induced chemoresistance of this clinically conventional anti-cancer agent , with an insight to determining potential indications in neuroblastoma therapy . In this study , physiological hypoxia was shown to attenuate G2/M arrest and apoptosis induced in CHP126 cells by VP-16 . It suppressed drug-related Cdk1 activity with a less elevation of regulator proteins such as cyclin B1 , Cdk7 and reduced caspase activation and PARP cleavage compared to the efficiency observed in normoxic condition , which were significantly relative with hypoxia-driven inhibition of p53 and p-ERK1/2 activation . These results clearly demonstrated that hypoxia had a protective effect against VP-16-induced cytotoxicity , which is likely to provide a further therapeutic knowledge in neuroblastomas . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot374

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The aryl hydrocarbon receptor ( AhR ) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds . Several reports have shown that the AhR plays an important role in the control of cell-cycle progression , and this function is thought to be partly associated with the tumor promotion activity of dioxin . However , the underling mechanisms are not fully understood . We have previously shown that overexpression of AhR , as well as AhR ligand treatment , stimulates cell proliferation of human lung cancer A549 cells . In AhR-activated cells , the expression levels of DNA synthesis-related genes such as proliferating cell nuclear antigen ( PCNA ) and RFC38 are notably increased . Expression of these genes is mainly regulated by E2F1 , a transcription factor that is crucial for transition of the cell cycle from G1 to S phase . We show here that the transcriptional activity of E2F1 is increased by the AhR agonist treatment and that this effect depends on the presence of AhR . Functional mapping of AhR showed that the Per-Arnt-Sim ( PAS ) B domain is required for promotion of E2F1 activity . The mechanism involves formation of a complex of AhR and E2F1 on the regulatory region in the E2F1 target gene , followed by recruitment of coactivator activator for thyroid hormone and retinoid receptors ( ACTR ) . Consequently , the results in this study indicate the physiological function of AhR as a potent transcriptional coactivator of E2F1-dependent transcription and implicate the AhR-E2F1 interaction as a part of the mechanism by which AhR/Arnt promotes cell proliferation . OUTPUT:

sustaining proliferative signaling

HoC_1shot375

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Although anticancer effect of gambogic acid ( GA ) and its potential mechanisms were well documented in past decades , limited information is available on the anticancer effect of gambogenic acid ( GNA ) , another major active component of Gamboge . Here we performed a study to determine whether GNA possesses anticancer effect and find its potential mechanisms . The results suggested that GNA significantly inhibited the proliferation of several tumor cell lines in vitro and in vivo . Treatment with GNA dose and time dependently induced A549 cells apoptosis , arrested the cells to G0/G1 phase in vitro and down-regulated the expression of cyclin D1 and cyclooxygenase ( COX)-2 in mRNA level . In addition , anticancer effect was further demonstrated by applying xenografts in nude mice coupled with the characteristic of apoptosis in the GNA treated group . Taken together , these observations might suggest that GNA inhibits tumor cell proliferation via apoptosis-induction and cell cycle arrest . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling;tumor promoting inflammation

HoC_1shot376

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cancer cells upregulate glycolysis , increasing glucose uptake to meet energy needs . A small fraction of a cell's glucose enters the hexosamine biosynthetic pathway ( HBP ) , which regulates levels of O-linked beta-N-acetylglucosamine ( O-GlcNAc ) , a carbohydrate posttranslational modification of diverse nuclear and cytosolic proteins . We discovered that breast cancer cells upregulate the HBP , including increased O-GlcNAcation and elevated expression of O-GlcNAc transferase ( OGT ) , which is the enzyme catalyzing the addition of O-GlcNAc to proteins . Reduction of O-GlcNAcation through RNA interference of OGT in breast cancer cells leads to inhibition of tumor growth both in vitro and in vivo and is associated with decreased cell-cycle progression and increased expression of the cell-cycle inhibitor p27(Kip1) . Elevation of p27(Kip1) was associated with decreased expression and activity of the oncogenic transcription factor FoxM1 , a known regulator of p27(Kip1) stability through transcriptional control of Skp2 . Reducing O-GlcNAc levels in breast cancer cells decreased levels of FoxM1 protein and caused a decrease in multiple FoxM1-specific targets , including Skp2 . Moreover , reducing O-GlcNAcation decreased cancer cell invasion and was associated with the downregulation of matrix metalloproteinase-2 , a known FoxM1 target . Finally , pharmacological inhibition of OGT in breast cancer cells had similar anti-growth and anti-invasion effects . These findings identify O-GlcNAc as a novel mechanism through which alterations in glucose metabolism regulate cancer growth and invasion and suggest that OGT may represent novel therapeutic targets for breast cancer . OUTPUT:

evading growth suppressors;cellular energetics

HoC_1shot377

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Ataxia telangiectasia ( AT ) cells , with their defective double-strand break ( DSB ) repair processes , exhibit high sensitivity to low-LET radiation such as X-rays irradiation and gamma beams . Since heavy ion beam treatment for cancer is becoming increasingly common in Japan and elsewhere , it is important to also determine their sensitivity to high-LET radiation . For this purpose we irradiated AT and normal human cells immortalized with the human telomerase gene using high- ( 24-60 keV/microm carbon and 200 keV/microm iron ions ) or low-LET ( X-rays ) radiation in non-proliferative conditions . In normal cells the RBE ( relative biological effectiveness ) of carbon and iron ions increased from 1.19 to 1.81 in proportion to LET . In contrast , their RBE in AT cells increased from 1.32 at 24 keV/microm to 1.59 at 40 keV/microm , and exhibited a plateau at over 40 keV/microm . In normal cells most gamma-H2AX foci induced by both carbon- and iron-ion beams had disappeared at 40 h . In AT cells , however , a significant number of gamma-H2AX foci were still observed at 40 h . The RBEs found in the AT cells after heavy-ion irradiation were consistent with the effects predicted from the presence of non-homologous end joining defects . The DSBs remaining after heavy-ion irradiation suggested defects in the AT cells ' DSB repair ability . OUTPUT:

genomic instability and mutation

HoC_1shot378

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk , but these studies produced inconsistent results . In this pilot , randomized , double-blind , placebo-controlled clinical trial ( n = 47 ) , we assessed the effects of an antioxidant micronutrient combination ( 800 mg dl-alpha-tocopherol acetate , 24 mg beta-carotene , 1.0 g vitamin C , 200 microg l-selenomethionine , 7.2 mg riboflavin , 80 mg niacin , 60 mg zinc , 5 mg manganese ) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma . Plasma tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 , and F2-isoprostane concentrations were measured using ELISAs , and cystine ( CySS ) was measured using high-performance liquid chromatography . Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group ( P = 0.002 ) , and CySS decreased by 19% ( P = 0.03 ) ; however , interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers , although these findings were not statistically significant . The decreases of TNF-alpha and CySS were more pronounced in nonsmokers . These data suggest that ( a ) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and ( b ) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status . OUTPUT:

tumor promoting inflammation

HoC_1shot379

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The tumor suppressor p27(Kip1) is an inhibitor of cyclin/cyclin-dependent kinase ( CDK ) complexes and plays a crucial role in cell cycle regulation . Nevertheless , p27 function in the tumorigenesis of the uterine cervix has been poorly defined . Some phenomenon hints that HPV E7 protein can enhance p27 expression , which is contradictory to HPV E7's property of increasing cell proliferation rate . So , in the present study , we have examined the effect of E7 on p27 expression . Though the levels of p27 are increased after HPV E7 expression , most of the p27 protein localized in the cytoplasm and have no function on cell cycle arrest and contact inhibition . The cell migration rate is elevated when p27 is high expression and located in cytoplasm . The results indicated that E7-p27 interaction not only abolished the p27's cell cycle inhibitory function by sequestering it to the cytoplasm , but also endow the cell with invasive property which is the feature of malignant cells . OUTPUT:

evading growth suppressors

HoC_1shot380

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Bilateral spontaneous pneumothorax is a rare occurrence in patients with both primary and metastatic lung cancer . Pneumothorax occurring as a complication of vascular endothelial growth factor receptor ( VEGFR ) inhibitor therapy has not been previously described in the medical literature . Sunitinib malate is a VEGFR inhibitor approved for the treatment of advanced renal cell carcinoma . We present a patient with metastatic renal cell carcinoma manifested as bilateral pulmonary nodules who developed a bilateral spontaneous pneumothorax 3 weeks after initiation of sunitinib therapy . We believe that sunitinib therapy resulted in necrosis of multiple pleural-based pulmonary nodules with central cavernization and ultimately rupture with bronchopleural fistula formation . Based on this experience , we advise that practitioners exercise caution when prescribing anti-VEGFR therapy in patients with pleural-based pulmonary metastases and recognize that the efficacy and toxicity of these agents may be closely linked . OUTPUT:

resisting cell death

HoC_1shot381

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

genomic instability and mutation

HoC_1shot382

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Astaxanthin modulates immune response , inhibits cancer cell growth , reduces bacterial load and gastric inflammation , and protects against UVA-induced oxidative stress in in vitro and rodent models . Similar clinical studies in humans are unavailable . Our objective is to study the action of dietary astaxanthin in modulating immune response , oxidative status and inflammation in young healthy adult female human subjects . METHODS Participants ( averaged 21.5 yr ) received 0 , 2 , or 8 mg astaxanthin ( n = 14/diet ) daily for 8 wk in a randomized double-blind , placebo-controlled study . Immune response was assessed on wk 0 , 4 and 8 , and tuberculin test performed on wk 8 . RESULTS Plasma astaxanthin increased ( P &lt ; 0.01 ) dose-dependently after 4 or 8 wk of supplementation . Astaxanthin decreased a DNA damage biomarker after 4 wk but did not affect lipid peroxidation . Plasma C-reactive protein concentration was lower ( P &lt ; 0.05 ) on wk 8 in subjects given 2 mg astaxanthin . Dietary astaxanthin stimulated mitogen-induced lymphoproliferation , increased natural killer cell cytotoxic activity , and increased total T and B cell subpopulations , but did not influence populations of Thelper , Tcytotoxic or natural killer cells . A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8 . Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects . There was no difference in TNF and IL-2 concentrations , but plasma IFN-gamma and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin . CONCLUSION Therefore , dietary astaxanthin decreases a DNA damage biomarker and acute phase protein , and enhances immune response in young healthy females . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot383

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND The pTalpha/preTCR regulates the beta-selection , a crucial T-cell developmental checkpoint , providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck) . METHODS To define the relevance of pTalpha in human T-cell lymphoblastic leukemia ( T-ALL ) , we analyzed in T-ALL cell lines ( n=14 ) pTalpha and p56(Lck) mRNA and protein expression as also the tyrosine-phosphorylation . The p56(Lck) specific src-protein-tyrosine kinase inhibitor ( PTK-I ) PP1 was used in growth inhibition assays . IC(50) value determination , cell cycle- and apoptosis analyses were performed in T-ALL- , non-T-ALL- and murine transgenic cell lines . RESULTS pTalpha expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts . PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G(1/0) phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2 , respectively . PP1 sensitive cell lines expressed the target protein p56(Lck) and showed a corresponding P-Tyr signal . CONCLUSION Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTalpha mediated proliferation in this leukemic sub-type . In addition , p56(Lck) represents also independently of pTalpha a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot384

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Prostate cancer ( PCA ) is the most common invasive malignancy and the second leading cause of cancer-related death in males . The present study investigated the effects of fangchinoline ( Fan ) , an important compound in Stephania Tetradra S. Moore ( Fenfangji ) with pain-relieving , blood pressure-depressing , and antibiotic activities , on human PCA . It was found that Fan inhibited human prostate cancer cell lines ( PC3 ) cell proliferation in a dose- and time-dependent manner . Studies of cell-cycle progression showed that the anti-proliferative effect of Fan was associated with an increase in the G1/S phase of PC3 cells . Western blot results indicated that Fan-induced G1/S phase arrest was mediated through inhibition of cyclin-regulated signaling pathways . Fan induced p27 expression and inhibited cyclin D and proliferating cell nuclear antigen ( PCNA ) expression in PC3 cells . Increased exposure time to Fan caused apoptosis of PC3 cells , which was associated with up-regulation of pro-apoptotic proteins Bax and caspase 3 , and down-regulation of anti-apoptotic protein Bcl-2 . Furthermore , Fan had anti-tumorigenic activity in vivo , including reduction of tumor volume and pro-apoptotic and anti-proliferative effects in a PC3 nude mouse xenograft . Taking all this together , it can be concluded that Fan is an effective anti-proliferative agent that modulates cell growth regulators in prostate cancer cells . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot385

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To study the effects of genistein on the proliferation , apoptosis induction and expression of related gene proteins of human colon cancer cells in vitro and in vivo , and its mechanisms of action . METHODS MTT colorimetric assay was used to detect the effects of genistein on the proliferation of human colon adenocarcinoma SW480 cells . Light and transmission electron microscopy were used to study the histological and ultrastructural changes . Flow cytometry was used to determine the effects of genistein on cell cycle and apoptosis . Flow cytometry and immunohistochemistry were used to determine the effects of genistein on apoptosis induction and expression of related gene proteins of colon cancer cells . RESULTS The MTT colorimetric assay showed that genistein inhibited the proliferation of SW480 cells in a dose-dependent and time-dependent manner , and the highest inhibition rate was 60.2% after 80 microg/ml genistein treatment for 72 h . The light microscopy revealed that many genistein-treated cancer cells were shrunken , disrupted , or showing cytoplasmic vacuolization . The electron microscopic examination showed cell shrinkage , nuclear fragmentation and pronounced chromatin condensation , sometimes formed crescent chromatin condensation attached to the nuclear membrane . The results of flow cytometry showed that : after SW480 cells were treated with 0 , 20 , 40 , 80 microg/ml genistein for 48 h , the FI values of PCNA were 1.49 +/- 0.02 , 1.28 +/- 0.04 , 1.14 +/- 0.03 , and 0.93 +/- 0.08 ; the FI values of VEGF were 1.75 +/- 0.02 , 1.34 +/- 0.06 , 1.32 +/- 0.04 , and 1.23 +/- 0.04 ; the fluorescence index ( FI ) values of p21 were 1.26 +/- 0.05 , 1.36 +/- 0.06 , 1.61 +/- 0.03 , and 1.73 +/- 0.03 , respectively . There were statistically significant differences between the control group and each treatment group ( P &lt ; 0.05 or P &lt ; 0.01 ) . The scores of immunohistochemical staining of PCNA and VEGF proteins were decreased , while p21 increased . There were statistically significant differences between the control group and each treatment group ( P &lt ; 0.05 or P &lt ; 0.01 ) . CONCLUSION Genistein can inhibit the growth of colon cancer cells via apoptosis induction and cell cycle arrest at G(2)/M phase . The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA , and up-regulation of the expression of p21 . OUTPUT:

resisting cell death;evading growth suppressors;sustaining proliferative signaling;inducing angiogenesis

HoC_1shot386

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Dendritic cells ( DCs ) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system . Ductal pancreatic adenocarcinoma ( PDAC ) , the most common pancreatic cancer , is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence . METHODS We examined the systemic influence ductal pancreatic adenocarcinoma ( PDAC ) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors , chronic pancreatitis , and age-matched controls . RESULTS All groups examined , including PDAC , had decreased levels of myeloid DCs ( MDC ) and plasmacytoid DCs ( PDC ) and enhanced apoptosis in these cells as compared to controls . We found elevated levels of PGE2 and CXCL8 in subjects with PDAC , and chronic pancreatitis . Levels of these inflammatory factors were in part restored in PDAC after tumor resection , whereas the levels of DCs were impaired in the majority of these patients approximately 12 weeks after tumor removal . Our results prove that solid pancreatic tumors , including PDAC , systemically affect blood DCs . The impairments do not seem to be tumor-specific , since similar results were obtained in subjects with chronic pancreatitis . Furthermore , we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival . CONCLUSIONS Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs . Furthermore , the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival . OUTPUT:

tumor promoting inflammation

HoC_1shot387

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Targeting cancer cell metabolism is a new promising strategy to fight cancer . Metformin , a widely used antidiabetic agent , exerts antitumoral and antiproliferative action . In this study , the addition of metformin to 2-deoxyglucose ( 2DG ) inhibited mitochondrial respiration and glycolysis in prostate cancer cells leading to a severe depletion in ATP . The combination of the two drugs was much more harmful for cancer cells than the treatment with metformin or 2DG alone , leading to 96% inhibition of cell viability in LNCaP prostate cancer cells . In contrast , a moderate effect on cell viability was observed in normal prostate epithelial cells . At the cellular level , the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase , and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity . In addition to apoptosis , the combination of metformin and 2DG arrested prostate cancer cells in G(2)-M . This G(2)-M arrest was independent of p53 and correlated with a stronger decrease in cell viability than obtained with either drug . Finally , metformin inhibited 2DG-induced autophagy , decreased beclin 1 expression , and triggered a switch from a survival process to cell death . Our study reinforces the growing interest of metabolic perturbators in cancer therapy and highlights the potential use of the combination of metformin and 2DG as an anticancerous treatment . OUTPUT:

cellular energetics;resisting cell death

HoC_1shot388

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To analyze histological factors not routinely assessed as potential prognostic factors in renal cell carcinoma , such as tumor necrosis , microscopic vascular invasion , and sinus fat invasion . MATERIALS AND METHODS A retrospective , analytical study was conducted of surgical specimens from 139 patients with localized renal cell carcinoma who underwent nephrectomy from 1993 to 2005 . Tumor necrosis , microscopic vascular invasion , and sinus fat invasion were analyzed and compared to the classical factors : TNM classification , Fuhrman grade , and tumor size . For statistical analysis , variables analyzed were categorized as pT1 , 2 vs pT3 , 4 ; Fuhrman grade 1 , 2 vs 3 , 4 ; tumor size &lt ; 7 cm vs >or= 7cm ; tumor necrosis vs no tumor necrosis ; microvascular invasion of sinus fat vs no invasion . Cancer-specific survival probability and disease-free survival were calculated . A descriptive and analytical statistical analysis was performed using logistic regression for univariate and multivariate analyses . Dependent variables were used to analyze cancer-specific survival rates . Disease-free survival was estimated using a Cox regression model and Kaplan-Meier curves . RESULTS In the univariate analysis , all variables analyzed had a significant influence on death for renal cell carcinoma . In the multivariate analysis , the variable having the greatest influence was Fuhrman grade ( p = 0,032 ) . The variables significantly influencing disease-free survival , estimated by the Cox method , were the pT stage ( p = 0.038 ) and Fuhrman grade ( p = 0.048 ) . CONCLUSIONS In patients with clinically localized renal cell carcinoma undergoing nephrectomy , pT stage and Fuhrman grade are the most important prognostic factors for survival and disease-free survival . Tumor necrosis , microscopic vascular invasion , and sinus fat invasion are prognostic factors for death from renal carcinoma which are associated to TNM classification , Fuhrman grade , and tumor size . OUTPUT:

activating invasion and metastasis;resisting cell death

HoC_1shot389

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Adenoid cystic carcinoma ( ACC ) of the Breast is a rare tumour ( less than 1 % of all breast carcinomas ) . The aim of this study was to determine the clinical , histological and immunohistochemical characteristics of these tumours . METHODS From the database of the Bergonié Institute of Bordeaux , 30 cases of ACC were identified . The clinical and histological features of these carcinomas were characterized . An immunohistochemical study was performed with the following antibodies : ER , PR , HER-2-neu , Vimentin , EGFR , P63 , SMA , CK5/6 , CK8/18 , CK14 , cKIT , MIB1 , CD44 and CD24 . RESULTS Thirty patients were included ( median age 60.7 years ) . The 10 axillary lymph node dissections and two sentinel lymph procedures were negative . The architecture was frequently of a mixed type ( 26/30 ) and less often solid ( 4/30 ) . Among the 23 patients for whom follow up was available ( median follow-up : 84 months [ 2-288] ) , there were three local recurrences and three metastatic events . The tumors with recurrence and metastasis showed more necrosis , a mitotic count greater than 4/10hpf , and in one case perineural infiltration . All the tumours were ER , PR and Her-2-neu negative . Morphological and immunophenotypical analysis disclosed in each tumor , a basaloid and a luminal cell population with divergent immunophenotypical patterns . CONCLUSIONS The mammary ACC is made of two cell types and is of good prognosis despite its triple negative phenotype , similar to the basal-like infiltrating carcinoma NOS . Axillary lymph node dissection is not recommended . Good local control by at least large lumpectomy with long-term follow-up is necessary . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot390

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES To evaluate the impact of the category of unclassified renal cell carcinoma ( URCC ) on survival following nephrectomy . METHODS Patients with clear cell RCC ( ccRCC , n = 3048 ) and URCC ( n = 38 ) were identified . Patients with URCC were matched 4:1 with ccRCC patients based on year of surgery , symptoms at presentation , tumor size , stage , regional lymph node involvement , metastases , grade , coagulative tumor necrosis , and sarcomatoid differentiation . Survival was estimated using the Kaplan-Meier method and compared between ccRCC and URCC patients using log-rank tests . RESULTS Patients with URCC were more likely to have regional lymph node involvement ( P <.001 ) , higher grade ( P <.001 ) , tumor necrosis ( P <.001 ) , and sarcomatoid differentiation ( P <.001 ) as compared to patients with ccRCC . Overall survival was not significantly different between URCC and ccRCC patients in either the unmatched ( P = .337 ) or matched ( P = .345 ) cohorts . Cancer-specific survival was significantly worse for URCC patients compared with unmatched ccRCC patients ( P = .020 ) . However , this difference was not statistically significant when the URCC patients were compared with the matched cohort ( P = .688 ) . Distant metastases-free survival was somewhat worse for M0 URCC patients compared with unmatched M0 ccRCC patients ( P = .063 ) , but not in the matched cohort ( P = .788 ) . CONCLUSIONS Although URCC is more likely to present with advanced clinicopathologic features compared with ccRCC , no statistically significant differences in outcome were noted after adjusting for these features in a matched analysis . OUTPUT:

resisting cell death

HoC_1shot391

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Pilocytic astrocytoma is commonly viewed as a benign lesion . However , disease onset is most prevalent in the first two decades of life , and children are often left with residual or recurrent disease and significant morbidity . The Hedgehog ( Hh ) pathway regulates the growth of higher WHO grade gliomas , and in this study , we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas . Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed ( ages 1-22 years ) and correlated inversely with patient age . Evaluation of a tissue array revealed oligodendroglioma-like features , pilomyxoid features , infiltration , and necrosis more commonly in specimens from younger patients ( below the median patient age of 10 years ) . Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10 . A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured , and 86% of Ki67-positive cells also expressed PTCH . The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism . Taken together , these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot392

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The BLM helicase is a member of the RecQ DNA helicase family and is mutated in the cancer-prone disorder Bloom syndrome . BLM plays a role in a number of cellular processes including DNA double-strand break repair , Holliday junction dissolution , and chromosome segregation . In Drosophila melanogaster , the BLM ortholog ( DmBlm ) is encoded by the mus309 gene . To study the role of DmBlm in double-strand break repair , we utilized a genetic assay in which a targeted DNA double-strand gap is created through excision of a P transposable element . By recovering and molecularly analyzing individual repair products from wild-type and mus309 male pre-meiotic germline cells , we demonstrated that the DmBlm helicase is involved in homologous recombination downstream of strand invasion . This assay can be adapted to test the roles of numerous DNA metabolic factors in DNA double-strand gap repair . OUTPUT:

genomic instability and mutation

HoC_1shot393

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

resisting cell death

HoC_1shot394

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Paragangliomas are relatively uncommon neoplasms that arise in adrenal and extra-adrenal paraganglia of the autonomic nervous system . Parasympathetic paraganglioma develop predominantly in the head and neck . It is exceedingly uncommon to develop a primary intraparathyroid paraganglioma . There is only a single case report in the English literature . The information from the single previous case report ( Medline 1960-2009 ) was combined with this case report . Our patient was a 69 year old woman who presented with a thyroid gland mass , with extension into the substernal space . The patient had a history of renal cell carcinoma removed 18 months before . At surgery , a thyroid lobectomy and a parathyroidectomy were performed . The parathyroid tissue showed a very well defined zellballen arrangement of paraganglion cells within the parenchyma of the parathyroid gland . The cells had ample basophilic , granular cytoplasm . The nuclei were generally round to oval with ' salt-and-pepper ' nuclear chromatin distribution . There was a richly vascularized stroma . Mitotic figures , necrosis , invasive growth , and profound nuclear pleomorphism were absent . The neoplastic cells were strongly and diffusely immunoreactive with chromogranin , synaptophysin , CD56 , and focally with cyclin-D1 . The paraganglioma showed a delicate S-100 protein positive supporting sustentacular framework . Keratin , CD10 , PTH , calcitonin and RCC markers were negative . The patient showed no stigmata of Multiple Endocrine Neoplasia ( MEN ) and has no paraganglioma in any other anatomic site . She is alive without any additional findings 12 months after surgery . Isolated paraganglioma within the parathyroid is rare , and should be separated from parathyroid adenoma , hyperplasia or metastatic disease to assure appropriate management . OUTPUT:

activating invasion and metastasis;resisting cell death

HoC_1shot395

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Stannous chloride ( SnCl(2) ) and UVA induce DNA lesions through ROS . The aim of this work was to study the toxicity induced by UVA preillumination , followed by SnCl(2) treatment . E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents . The survival assays showed ( i ) The nfo mutant was the most sensitive to SnCl(2) ; ( ii ) lethal synergistic effect was observed after UVA pre-illumination , plus SnCl(2) incubation , the nfo mutant being the most sensitive ; ( iii ) wild type and nfo mutants , transformed with pBW21 plasmid ( nfo(+) ) had their survival increased following treatments . The alkaline agarose gel electrophoresis assays pointed that ( i ) UVA induced DNA breaks and fpg mutant was the most sensitive ; ( ii ) SnCl(2)-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics ; ( iii ) UVA + SnCl(2) promoted an increase in DNA breaks than SnCl(2) and , again , nfo mutant displayed the slowest repair kinetics . In summary , Nfo protects E. coli cells against damage induced by SnCl(2) and UVA + SnCl(2) . OUTPUT:

genomic instability and mutation

HoC_1shot396

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Tamoxifen , a selective oestrogen receptor modulator ( SERM ) , and brivanib alaninate , a vascular endothelial growth factor receptor 2 ( VEGFR-2 ) inhibitor , are two target specific agents that result in a substantial decrease in tumour growth when given alone . Tamoxifen activates SERM stimulated breast and endometrial tumour growth . Tamoxifen and brivanib alaninate have side-effects that can affect therapeutic outcomes . The primary goal of the current study was to evaluate the therapeutic effects of lower doses of both agents when given in combination to mice with SERM sensitive , oestrogen stimulated tumour xenografts ( MCF-7 E2 tumours ) . Experiments were conducted to evaluate the response of SERM stimulated breast ( MCF-7 Tam , MCF-7 Ral ) and endometrial tumours ( EnCa 101 ) to demonstrate the activity of brivanib alaninate in SERM resistant models . EXPERIMENTAL DESIGN In the current study , tumour xenografts were minced and bi-transplanted into the mammary fat pads of athymic , ovariectomised mice . Preliminary experiments were conducted to determine an effective oral dose of tamoxifen and brivanib alaninate that had minimal effect on tumour growth . Doses of 125 microg of tamoxifen and 0.05 mg/g of brivanib alaninate were evaluated . An experiment was designed to evaluate the effect of the two agents together when started at the time of tumour implantation . An additional experiment was done in which tumours were already established and then treated , to obtain enough tumour tissue for molecular analysis . RESULTS Brivanib alaninate was effective at inhibiting tumour growth in SERM sensitive ( MCF-7 E2 ) and SERM stimulated ( EnCa 101 , MCF-7 Ral , MCF-7 Tam ) models . The effect of the low dose drug combination as an anti-tumour strategy for SERM sensitive ( MCF-7 E2 ) in early treatment was as effective as higher doses of either drug used alone . In established tumours , the combination is successful at decreasing tumour growth , while neither agent alone is effective . Molecular analysis revealed a decreased phosphorylation of VEGFR-2 in tumours that were treated with brivanib alaninate and an increase in VEGFA transcription to compensate for the blockade of VEGFR-2 by increasing the transcription of VEGFA . Tamoxifen increases the phosphorylation of VEGFR-2 and this effect is abrogated by brivanib alaninate . There was also increased necrosis in tumours treated with brivanib alaninate . CONCLUSION Historically , tamoxifen has a role in blocking angiogenesis as well as the blockade of the ER . Tamoxifen and a low dose of an angiogenesis inhibitor , brivanib alaninate , can potentially be combined not only to maximise therapeutic efficacy but also to retard SERM resistant tumour growth . OUTPUT:

resisting cell death;inducing angiogenesis;sustaining proliferative signaling

HoC_1shot397

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Exposure to benzo[a]pyrene ( BaP ) can induce inflammatory skin diseases and skin cancer , which are both associated to oxidative stress . BaP is known to bind with high specificity to the aryl hydrocarbon receptor ( AhR ) , modifying the expression of CYP1A1 , involved both in cancer and inflammation . While the current knowledge is based on murine skin and cell culture data , in this study human healthy skin has been treated with 5muM BaP in conditions simulating occupational and environmental exposure . AhR and CYP1A1 expression was evaluated by Western blotting , which revealed their presence even in control untreated skin ; both enzyme and receptor increased more than twofold after exposure to BaP . AhR expression level was lower than CYP1A1 in basal conditions and following induction . Oxidative stress was evaluated in terms of MTT reduction , protein peroxidation and reactive oxygen species ( ROS ) formation . A significant increase in ROS and carbonyl compound production , as well as reduced tissue viability have been determined by BaP . The results of this experiment indicate that BaP , an AhR agonist , can significantly increase receptor and CYP1A1 expression and induce oxidative stress in human skin , confirming the involvement of this pathway in the pathogenesis of tissue damage due to polycyclic aromatic hydrocarbons . OUTPUT:

tumor promoting inflammation

HoC_1shot398

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Cantharidin is an active constituent of mylabris , a traditional Chinese medicine . It is a potent and selective inhibitor of protein phosphatase 2A ( PP2A ) that plays an important role in control of cell cycle , apoptosis , and cell-fate determination . Owing to its antitumor activity , cantharidin has been frequently used in clinical practice . In the present study , we investigated the therapeutic potential of cantharidin in pancreatic cancer . Cantharidin efficiently inhibited the growth of pancreatic cancer cells , but presented a much lighter toxicity effect against normal pancreatic duct cells . It caused G2/M cell-cycle arrest that was accompanied by the down-regulation of cyclin-dependent kinase 1 ( CDK1 ) and up-regulation of p21 expression . It induced apoptosis and elevated the expressions of pro-apoptotic factors tumor necrosis factor-alpha ( TNF-alpha ) , TNF-related apoptosis inducing receptor 1 ( TRAILR1 ) , TRAILR2 , Bad , Bak , and Bid , and decreased the expression of anti-apoptotic Bcl-2 . Activation of caspase-8 and caspase-9 suggested that both extrinsic and intrinsic pathways are involved in the induction of apoptosis . Interestingly , unlike previous studies on other cancer cells , we found that the inhibitory role of cantharidin is independent of oxidative stress in pancreatic cancer cells . Mitogen-activated protein kinases ( MAPKs ) , including ERK , JNK , and p38 , were activated after treatment with cantharidin . Inhibition of JNK , but not ERK or p38 , alleviated the cytotoxity effect of cantharidin , suggesting cantharidin exerted its anticancer effect through the JNK-dependent way . Hence , in addition to being an attractive candidate compound with therapeutic potential , cantharidin also highlighted the possibility of using PP2A as a therapeutic target for pancreatic cancer treatment . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot399

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: 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 . OUTPUT:

sustaining proliferative signaling;inducing angiogenesis