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clinicalnlplab

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HoC_1shot_test

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HoC_1shot0

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Ghrelin was identified in the stomach as an endogenous ligand specific for the growth hormone secretagogue receptor ( GHS-R ) . GHS-R is found in various tissues , but its function is unknown . Here we show that GHS-R is found in hepatoma cells . Exposure of these cells to ghrelin caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1 ( IRS-1 ) , association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1 , mitogen-activated protein kinase activity , and cell proliferation . Unlike insulin , ghrelin inhibited Akt kinase activity as well as up-regulated gluconeogenesis . These findings raise the possibility that ghrelin modulates insulin activities in humans . OUTPUT:

sustaining proliferative signaling

HoC_1shot1

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 The epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ZD1839 ( Iressa ; AstraZeneca Pharmaceuticals , Alderley Park , United Kingdom ) is under development as an anticancer agent . We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin , an EGFR-dependent tissue , in cancer patients participating in ZD1839 phase I clinical trials . PATIENTS AND METHODS We studied 104 pre- and/or on-ZD1839 therapy ( approximately at day 28 of therapy ) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839 . We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated ( phosphorylated ) EGFR . Effects on receptor signaling ( activated mitogen-activated protein kinase [ MAPK] ) , proliferation , p27(KIP1) , and maturation were also assessed . RESULTS Histopathologically , the stratum corneum of the epidermis was thinner during therapy ( P <.001 ) . In hair follicles , prominent keratin plugs and microorganisms were found in dilated infundibula . ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells ( P <.001 ) . In addition , ZD1839 inhibited MAPK activation ( P <.001 ) and reduced keratinocyte proliferation index ( P <.001 ) . Concomitantly , ZD1839 increased the expression of p27(KIP1) ( P <.001 ) and maturation markers ( P <.001 ) and increased apoptosis ( P <.001 ) . These effects were observed at all dose levels , before reaching dose-limiting toxicities . CONCLUSION ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo . These effects were profound at doses well below the one producing unacceptable toxicity , a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials . OUTPUT:

sustaining proliferative signaling;evading growth suppressors;resisting cell death

HoC_1shot2

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Adoptive transfer of immunity against hepatitis B surface antigen ( HBsAg ) was previously shown to facilitate suppression of experimental human hepatocellular carcinoma ( HCC ) expressing HBsAg in athymic mice . We have shown that oral tolerance induces antigen-specific immune suppression of HBsAg by feeding hepatitis B virus ( HBV ) antigens . In the present study we evaluated the effect of oral tolerance induction toward HBV or HCC antigens on the growth of experimental HCC-expressing HBsAg in mice . Tolerance induction was induced in mice by 5 oral feedings of 1 microg HBV antigens or HCC-extracted proteins ( 50 microg protein ) before vaccination with recombinant HBsAg . Splenocytes ( 2 x 10(6) ) from these mice were transferred to sublethally irradiated athymic BALB/c mice previously transplanted subcutaneously with 10(7) human hepatoma Hep3B cells . Adoptive transfer of splenocytes immunized toward HBsAg prevented tumor growth . At 4 weeks after splenocyte transplantation , tumor volume and serum alpha-fetoprotein ( AFP ) levels in athymic mice transplanted with splenocytes immunized to HBsAg were undetectable as compared with 1,048 +/- 738 mm(3) and 2,500 +/- 1,431 ng/ml in recipients of na�ve splenocytes ( p &lt ; 0.0001 ) . Mice receiving splenocytes tolerized toward Hep3B cells , as manifested by reduced serum HBs antibody levels , reduced HBV-specific stimulation index and reduced HBV-specific-IFN gamma spot-forming cells , had early tumor growth evident by elevated AFP serum levels , weight loss and mortality , which were suppressed at 6 weeks . Mice transplanted with splenocytes tolerized toward HBV antigens did not have direct evidence of tumor growth . Induction of oral tolerance toward HCC-extracted proteins enabled transient tumor growth in this model . This effect was mediated through downregulation of the anti-HBV immune response . OUTPUT:

avoiding immune destruction

HoC_1shot3

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 secretion of immunosuppressive factors like transforming growth factor-beta ( TGF-beta ) by tumor cells has been recognized as one of the mechanisms involved in tumor immunological escape . This study aimed to examine whether dendritic cell ( DC ) immunization could reverse TGF-beta-induced immunosuppression by simulating the in vivo interaction among infused DCs , host T cells , and tumor-secreted TGF-beta in an in vitro study . We found that both immature and mature DCs were relatively resistant to TGF-beta . The addition of TGF-beta to naive human CD4+ T cells , which are required by genetically modified DC to elicit antitumor immunity , resulted in their hyporesponsiveness to DC stimulation in a dose-dependent manner . When activated by allogeneic DCs in the presence of TGF-beta , CD4+ T cells displayed a reduced capacity to proliferate . More importantly , activated CD4+ T cells induced by DC stimulation were very sensitive to TGF-beta , and this susceptibility was enhanced by their previous exposure to TGF-beta . The underlying mechanism was linked to TGF-beta-induced apoptosis of activated T cells . However , the presence of stimulation from DC or antibodies to CD3 plus CD28 could partly reverse the immunosuppressive effect of TGF-beta on activated CD4+ T cells . Taken together , our results indicate that the efficacy of DC immunization may be impaired by tumor-derived TGF-beta . OUTPUT:

sustaining proliferative signaling;avoiding immune destruction;resisting cell death

HoC_1shot4

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: To characterize the impact of increased production of TGF-beta in a xenograft model of human breast cancer , TGF-beta-responsive MDA-231 cells were genetically modified by stable transfection so as to increase their production of active TGF-beta1 . Compared with control cells , cells that produced increased amounts of TGF-beta proliferated in vitro more slowly . In vivo , however , tumors derived from these cells exhibited increased proliferation and grew at an accelerated pace . To evaluate the role of autocrine TGF-beta signaling , cells were also transfected with a dominant-negative truncated type II TGF-beta receptor ( TbetaRII ) . Disruption of autocrine TGF-beta signaling in the TGF-beta-overexpressing cells reduced their in vivo growth rate . Co-inoculation of Matrigel with the TGF-beta-overexpressing cells expressing the truncated TbetaRII compensated for their diminished in vivo growth capacity , compared with the TGF-beta-overexpressing cells with an intact autocrine loop . Tissue invasion by the tumor was a distinctive feature of the TGF-beta-overexpressing cells , whether or not the autocrine loop was intact . Furthermore , tumors derived from TGF-beta-overexpressing cells , irrespective of the status of the autocrine TGF-beta-signaling pathway , had a higher incidence of lung metastasis . Consistent with the suggestion that TGF-beta's enhancement of invasion and metastasis is paracrine-based , we observed no significant differences among the cell clones in an in vitro invasion assay . Thus , in this experimental model system in vitro assays of cell proliferation and invasion do not accurately reflect in vivo observations , perhaps due to autocrine and paracrine effects of TGF-beta that influence the important in vivo-based phenomena of tumor growth , invasion , and metastasis . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot5

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL-Rs in these cells . Here , we show that PRL , though it failed to activate mouse peritoneal resident macrophages ( RMs ) , acted as a second signal and activated mouse peritoneal inflammatory macrophages ( EMs ) to a tumoricidal state . The cytotoxicity of mouse tumor-associated macrophages ( TAMs ) isolated at day 1 of tumor ( Ehrlich ascites carcinoma , EAC ) growth was enhanced by PRL . However , with progression of tumor growth , TAMs became nonresponsive to the hormone . PRL-induced killing of P815 target cells by EMs and TAMs was independent of TNF but correlated with the hormone-induced augmentation of NO2(-) and O2(-) release in these macrophages . Administration of PRL in vivo inhibited EAC growth and augmented NO2(-) release by TAMs . PRL synergized with the TH1 cytokine IFN-gamma , a known activator of macrophages , in inducing tumor killing and release of NO2(-) from EMs and TAMs . The hormone might activate macrophages at least partially , through the release of IFN-gamma as anti-IFN-gamma blocked IFN-gamma- as well as PRL-induced cytotoxicity in EMs . The TH2 cytokine IL-4 suppressed PRL-induced activation of macrophages . PRL induced release of IL-12 from EMs also , which suggested that the hormone might drive the TH1 response through IL-12 . Our observations further suggest that PRL alone and in synergy with IFN-gamma , released through induction of IL-12 , may generate tumoricidal macrophages and thus regulate the antitumor immune response of tumor hosts . OUTPUT:

tumor promoting inflammation

HoC_1shot6

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Primary fibroblasts respond to activated H-RAS(V12) by undergoing premature arrest , which resembles replicative senescence . This irreversible ' fail-safe mechanism ' requires p19(ARF) , p53 and the Retinoblastoma ( Rb ) family : upon their disruption , RAS(V12)-expressing cells fail to undergo senescence and continue to proliferate . Similarly , co-expression of oncogenes such as c-MYC or E1A rescues RAS(V12)-induced senescence . To identify novel genes that allow escape from RAS(V12)-induced senescence , we designed an unbiased , retroviral complementary DNA library screen . We report on the identification of DRIL1 , the human orthologue of the mouse Bright and Drosophila dead ringer transcriptional regulators . DRIL1 renders primary murine fibroblasts unresponsive to RAS(V12)-induced anti-proliferative signalling by p19(ARF)/p53/p21(CIP1) , as well as by p16(INK4a) . In this way , DRIL1 not only rescues RAS(V12)-induced senescence but also causes these fibroblasts to become highly oncogenic . Furthermore , DRIL1 immortalizes mouse fibroblasts , in the presence of high levels of p16(INK4a) . Immortalization by DRIL1 , whose product binds the pRB-controlled transcription factor E2F1 ( ref. 8 ) , is correlated with induction of E2F1 activity . Correspondingly , DRIL1 induces the E2F1 target Cyclin E1 , overexpression of which is sufficient to trigger escape from senescence . Thus , DRIL1 disrupts cellular protection against RAS(V12)-induced proliferation downstream of the p19(ARF)/p53 pathway . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot7

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Oncostatin M ( OSM ) , an interleukin-6 type cytokine , acts via the gp130 signaling receptor to inhibit proliferation and induce differentiation of breast cancer cells . EGF , a mitogen for breast cells , signals via EGFR/ErbB tyrosine kinase receptors which are implicated in breast cancer pathogenesis . Here we show paradoxically that EGF enhanced the OSM-induced inhibition of proliferation and induction of cellular differentiation in both estrogen receptor positive and negative breast cancer cells . This functional synergism was also seen with heregulin but not SCF , PDGF or IGF-1 , indicating that it was specific to EGF-related growth factors . Immunoprecipitation experiments revealed that gp130 was constitutively associated with ErbB-2 and ErbB-3 . There was a similar association between the OSMRbeta and ErbB-2 . Furthermore , EGF unexpectedly induced tyrosine phosphorylation of gp130 . We show that OSM induced phosphorylation of STAT3 . Both OSM and EGF activated the p42/44 MAP kinases , but while the MEK inhibitor , PD98059 , ablated the OSM-induced inhibition , it only partially ablated the inhibitory effects of OSM plus EGF . Thus , we have demonstrated that the receptors and signalling pathways of two apparently unrelated growth factors were intimately linked , resulting in an unexpected biological effect . This provides a new mechanism for generating signalling diversity and has potential clinical implications in breast cancer . OUTPUT:

sustaining proliferative signaling

HoC_1shot8

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: p53 is a tumor suppressor gene that is mutated in many human malignancies , including gastric cancer . It remains unclear why patients with germ-line p53 mutations ( i.e. , Li-Fraumeni syndrome ) are not at increased risk for gastric adenocarcinoma , despite the fact that they show a high rate of many other tumors . Furthermore , the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections ( such as Helicobacter spp. ) has not been investigated . To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer , p53(+/-) and wild-type ( WT ) C57BL/6 mice were infected with H. felis . The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection . The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation , parietal and chief cell loss , mucus metaplasia , and helicobacter colonization . Nonparametric statistical analysis was performed to determine the effects of p53(+/-) , infection status , and postinoculation ( p.i. ) time on inflammation , preneoplastic changes , invasive lesions , and helicobacter colonization. mRNA expression for gammaIFN , interleukin ( IL)-1 , IL-10 , and IL-4 was quantified by PCR . Sera were also evaluated for H. felis antibody by ELISA . Antral inflammation increased significantly with time in infected mice . There was a significant , protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele ( P &lt ; 0.05 ) . Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i. ; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice . None of these lesions were observed in 33 p53(+/-) mice , infected or not , at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response . In sera from WT mice , IgG2a , considered a proinflammatory Th1 response , continued to rise throughout the 15-month study ( P &lt ; 0.004 ) . In contrast , IgG2a levels of the p53(+/-) mice were 50-60% lower than those of the WT mice at each time point ( P range , <0.012 to 0.002 ) and did not progress in magnitude between 12 and 15 months of chronic H. felis infection ( P = 0.167). mRNA levels for gammaIFN and IL-1 were significantly up-regulated in WT mice infected with H. felis ( P &lt ; 0.05 ) but were slightly elevated or were at background levels in p53(+/-) mice . IL-10 and IL-4 mRNA expression was not significantly different from control samples . Our results support the hypothesis that germ-line deletion of one p53 allele results in a down-regulated Th1 response to gastric helicobacter infection , possibly because of T-cell senescence , which may indirectly protect against the development of gastric cancer and other epithelial-derived neoplasms associated with chronic inflammation . OUTPUT:

tumor promoting inflammation;activating invasion and metastasis;enabling replicative immortality

HoC_1shot9

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype , a critical feature in tumorigenesis . The inactivation of multiple pathways that positively regulate senescence are required for immortalization . To identify these pathways in an unbiased manner , we performed DNA microarray analyses to assess the expression of 20,000 genes in human prostate epithelial cells ( HPECs ) passaged to senescence . These gene expression patterns were then compared with those of HPECs immortalized with the human Papillomavirus 16 E7 oncoprotein . Senescent cells display gene expression patterns that reflect their nonproliferative , differentiated phenotype and express secretory proteases and extracellular matrix components . A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes : the chemokine BRAK , DOC1 , and a member of the insulin-like growth factor axis , IGFBP-3 . Expression of these genes is found to be uniformly lost in human prostate cancer cell lines and xenografts , and previously , their inactivation was documented in tumor samples . Thus , these genes may function in novel pathways that regulate senescence and are inactivated during immortalization . These changes may be critical not only in allowing cells to bypass senescence in vitro but in the progression of prostate cancer in vivo . OUTPUT:

enabling replicative immortality

HoC_1shot10

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 and amplification of cyclin D1 were investigated by immunohistochemistry and differential polymerase chain reaction ( dPCR ) in 440 formalin-fixed primary breast carcinoma tissues . Overexpression of cyclin D1 was detected in 60% ( 263/440 ) and amplification of cyclin D1 was noted in 27% ( 119/440 ) of the primary breast carcinomas . Molecular analysis demonstrated that cyclin D1 was amplified in 30% ( 7/23 ) of the comedo DCIS , 22% ( 9/41 ) of the comedo DCIS and 32% ( 13/41 ) of the adjacent invasive ductal carcinomas , 30% ( 82/270 ) of the invasive ductal carcinomas , 27% ( 9/33 ) of the invasive lobular carcinomas , 19% ( 4/21 ) of the colloid carcinomas and 13% ( 2/15 ) of the medullary carcinomas . Cyclin D1 was amplified in 11% ( 2/19 ) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions . Our observation showed that cyclin D1 was strongly positive in 61% ( 14/23 ) of the comedo subtype , 61% ( 11/18 ) of the non-comedo subtype , 59% ( 24/41 ) of the comedo DCIS and 63% ( 26/41 ) of the adjacent invasive ductal carcinomas , 53% ( 10/19 ) of the non-comedo DCIS and 58% ( 11/19 ) of the adjacent invasive lesions , 58% ( 157/270 ) of the invasive ductal carcinomas , 73% ( 24/33 ) of the invasive lobular carcinomas , 52% ( 11/21 ) of the colloid carcinomas and 27% ( 4/15 ) of the medullary carcinomas . A significant association was observed between in situ components and adjacent invasive lesions for cyclin D1 expression ( p<0.05 ) and amplification ( p<0.05 ) . A significant relationship was noted between amplification of cyclin D1 and lymph node metastases ( p<0.05 ) but not with histological grade ( p>0.05 ) , estrogen receptor status ( p>0.05 ) and proliferation index ( Ki-67 and PCNA ) ( p>0.05 ) . However , overexpression of cyclin D1 was statistically associated with well differentiated tumors ( p<0.05 ) and estrogen receptor positivity ( p<0.05 ) . No relationship was seen with nodal status ( p>0.05 ) and proliferation index ( Ki-67 and PCNA ) ( p>0.05 ) . These observations suggest that tumors positive for cyclin D1 protein may have features of good prognosis but amplification of cyclin D1 gene could be an indicator of tumors with poor prognostic features . Although majority of the Malaysian patients belong to younger age group ( <50 years old ) , amplification and expression of cyclin D1 was not statistically associated with patient age ( p>0.05 ) . These observations indicate that amplification and up-regulation of cyclin D1 may be independent of patient age . Moreover , overexpression and amplification of cyclin D1 in preinvasive , preinvasive and adjacent invasive lesions , and invasive carcinomas suggest that the gene may play an important role in early and late stages of breast carcinogenesis . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot11

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Interferon-gamma ( IFN-gamma ) has pleiotropic activities other than its antivirus action , including cell growth inhibition , natural killer ( NK ) cell and cytotoxic T lymphocyte ( CTL ) activation , and angiogenesis inhibitory activity , and these activities are supposed to be involved in its antitumour activity . However , it has not been completely elucidated which activity is mainly involved in the tumour suppression in vivo . In this study , we analysed inhibitory mechanisms of endogenous IFN-gamma against B16 melanoma experimental metastasis . After intravenous injection of tumour cells , tumour deposits in the lungs and liver were increased and life span was shorter in IFN-gamma(-/-) mice , indicating important roles for IFN-gamma in antitumour mechanisms . Interestingly , tumour deposits were not increased in IFN-gamma receptor ( R)(-/- ) mice . Furthermore , only low levels of cell-mediated immunity against the tumour and activation of NK cells were observed , indicating that antimetastatic effects of IFN-gamma is not mediated by host cells . The survival period of B16 melanoma-bearing IFN-gamma R(-/-) mice was , however , shorter than wild-type mice . These observations suggest that IFN-gamma prevents B16 melanoma experimental metastasis by directly inhibiting the cell growth , although antitumour host functions may also be involved in a later phase . OUTPUT:

activating invasion and metastasis

HoC_1shot12

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: P53 activity plays a key role in mammalian cells when they undergo replicative senescence at their Hayflick limit . To determine whether p63 proteins , members of the family of p53-related genes , are also involved in this process , we examined their expression in serially passaged rat embryo fibroblasts . Upon senescence , two truncated DeltaNp63 proteins decreased in abundance whereas two TAp63 isoforms accumulated. 2-D gel analysis showed that the DeltaNp63 proteins underwent post-translational modifications in both proliferating and senescent cells . Direct binding of DeltaNp63 proteins to a p53 consensus motif was greater in proliferating cells than senescent cells . In contrast p63alpha isoforms bound to DNA in a p53 dependent manner and this was higher in senescent cells than proliferating cells . An interaction of p63alpha proteins with SV40 large tumour antigen was also detected and ectopic expression of DeltaNp63alpha can extend the lifespan of rat embryo fibroblasts . Taken together the results indicate that p63 proteins may play a role in replicative senescence either by competition for p53 DNA binding sites or by direct interaction with p53 protein bound to DNA . OUTPUT:

enabling replicative immortality

HoC_1shot13

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Mesotheliomas are malignant tumors of the pleural and peritoneal membranes which are often associated with asbestos exposure and with Simian virus 40 ( SV40 ) infection . Telomerase activity is repressed in somatic cells and tissues but is activated in immortal and malignant cells . We evaluated telomerase activity in seven primary malignant mesothelioma biopsies and matched lung specimens and 20 mesothelioma cell lines and eight corresponding primary tumor cultures . All the tumor biopsies , and nearly all primary cell mesothelioma cultures and cell lines were telomerase positive . The findings in cell lines paralleled those observed in primary cultures in cases where paired samples were available . Next , we found that SV40 , a DNA tumor virus present in approximately 50% of mesothelioma biopsies in the USA , induced telomerase activity in primary human mesothelial cells , but not in primary fibroblasts . Telomerase activity became detectable as early as 72 h following wild-type ( strain 776 ) SV40 infection , and a clear DNA ladder was detectable 1 week after infection . The amount of telomerase activity increased during passage in cell culture and appeared to parallel increases in the cellular amounts of the SV40 large T-antigen . Thus , SV40 infection leads to telomerase activity before the infected mesothelial cells become transformed and immortalized . SV40 infection of human fibroblasts did not cause detectable telomerase activity . We also determined that the SV40 small t-antigen ( tag ) plays an important role in inducing telomerase activity because this activity was undetectable or minimal in mesothelial cells infected and/or transformed by SV40 tag mutants . Asbestos alone did not induce telomerase activity , and asbestos did not influence telomerase activity in mesothelial cells infected with SV40 . Induction of telomerase activity by SV40 may be related to the very high rate of mesothelial cell immortalization that is characteristically associated with SV40 infection of mesothelial cells . OUTPUT:

enabling replicative immortality

HoC_1shot14

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Treatment of cells with the anti-cancer drug camptothecin ( CPT ) induces topoisomerase I ( Top1)-mediated DNA damage , which in turn affects cell proliferation and survival . In this report , we demonstrate that treatment of the wild-type HCT116 ( wt HCT116 ) human colon cancer cell line and the isogenic p53(-/-) HCT116 and p21(-/-) HCT116 cell lines with a high concentration ( 250 nm ) of CPT resulted in apoptosis , indicating that apoptosis occurred by a p53- and p21-independent mechanism . In contrast , treatment with a low concentration ( 20 nm ) of CPT induced cell cycle arrest and senescence of the wt HCT116 cells , but apoptosis of the p53(-/-) HCT116 and p21(-/-) HCT116 cells . Further investigations indicated that p53-dependent expression of p21 blocked apoptosis of wt HCT116 cells treated with 20 nm , but not 250 nm CPT . Interestingly , blocking of the apoptotic pathway , by Z-VAD-FMK , in p21(-/-) HCT116 cells following treatment with 20 nm CPT did not permit the cells to develop properties of senescence . These observations demonstrated that p21 was required for senescence development of HCT116 cells following treatment with low concentrations of CPT . OUTPUT:

resisting cell death;enabling replicative immortality;sustaining proliferative signaling

HoC_1shot15

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: AIMS Tumour cell growth results from a disturbance in the balance between the rate of proliferation and cell death . In this study , proteins involved in the regulation of cell cycle arrest and apoptosis were studied as possible factors responsible for uncontrolled cell growth in colorectal cancer . METHODS The expression of proteins involved in these processes was investigated in 48 metastases from patients with colorectal cancer and compared with eight normal colon mucosa samples and 14 primary tumours . Both primary tumours and metastases were obtained from eight patients . The expression of thymidylate synthase ( TS ) , p53 , retinoblastoma protein ( Rb ) , Fas receptor , Fas ligand , bcl-2 , mcl-1 , bax , and bcl-x was measured using immunohistochemistry . Proliferation was determined by Ki67 staining , whereas apoptosis was assessed by M30 immunostaining , which recognises cleaved cytokeratin 18 . RESULTS In the limited number of cases in which paired comparisons were possible , the expression of TS and Ki67 was significantly higher in metastases than in the matched primary tumour samples ( p = 0.014 and 0.016 , respectively ) , whereas Rb expression was lower in metastases than in primary tumours ( p = 0.024 ) . Fas receptor expression was high in normal mucosa but absent in primary tumours and metastases , whereas the opposite was seen for p53 . The expression of bax , mcl-1 , and bcl-x in normal mucosa was more apical than that seen in malignant cells , where a more diffuse expression pattern was seen ( p &lt ; 0.04 ) . Apoptosis was more abundant in primary tumours than in metastases . CONCLUSIONS These results demonstrate that proliferation and apoptosis are disturbed during colorectal cancer progression , and this is accompanied by loss of Rb and Fas expression , the accumulation of p53 and TS , and changes in the expression patterns of bax , mcl-1 , and bcl-xl . OUTPUT:

activating invasion and metastasis;sustaining proliferative signaling;resisting cell death

HoC_1shot16

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 well known that cell-mediated immunity is suppressed in patients with neoplastic diseases . We have reported that soluble receptors for interleukin-2 ( sIL-2R ) and tumor necrosis factor ( sTNF-R1 ) are elevated in the serum of patients with advanced colorectal cancer . The presence of these soluble receptors and immunosuppressive cytokines , including interleukin-10 ( IL-10 ) , might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum ( cisplatin ) has been reported to immunomodulate , especially when used in low dose in combination with 5-Fluorouracil ( 5-FU ) . In this study , cisplatin and UFT , a form of uracil and tegafur which is a prodrug of 5-FU , were administered with immunomodulator Polysaccharide K ( PSK ) to ten patients with colorectal cancer , who showed distant metastasis in the liver or lung , and the serum levels of sIL-2R and sTNF-R1 and the production of gamma-interferon ( gamma-INF ) and interleukin-10 by peripheral blood mononuclear cells were measured . The serum concentrations of sIL-2R and the production of IL-10 were reduced ( p &lt ; 0.05 ) after 2 months of treatment . Thus , this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer . OUTPUT:

activating invasion and metastasis;avoiding immune destruction

HoC_1shot17

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor , and this is typically seen as a failure of treatment . We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53 . We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo . Our results suggest that p53 and p21 play a central role in the onset of senescence , whereas p16(INK4a) function may be involved in maintaining senescence . Thus , like apoptosis , senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome . OUTPUT:

enabling replicative immortality;genomic instability and mutation;resisting cell death

HoC_1shot18

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Senescence limits the proliferative capacity of primary cells in culture . We describe here a genetic screen to identify genes that allow bypass of this checkpoint . Using retroviral cDNA expression libraries , we identify BCL6 as a potent inhibitor of senescence . BCL6 is frequently activated in non-Hodgkin's lymphoma , but its mechanism of action has remained unclear . BCL6 efficiently immortalizes primary mouse embryonic fibroblasts and cooperates with RAS in oncogenic transformation . BCL6 overrides the senescence response downstream of p53 through a process that requires induction of cyclin D1 expression , as cyclin D1 knockout fibroblasts are specifically resistant to BCL6 immortalization . We show that BCL6 expression also dramatically extends the replicative lifespan of primary human B cells in culture and induces cyclin D1 expression , indicating that BCL6 has a similar activity in lymphoid cells . Our results suggest that BCL6 contributes to oncogenesis by rendering cells unresponsive to antiproliferative signals from the p19(ARF)-p53 pathway . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot19

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Proliferator-activated receptor gamma ( PPARgamma ) is a nuclear receptor , which mainly associates with adipogenesis , but also appears to facilitate cell differentiation or apoptosis in certain malignant cells . This apoptosis induction by PPARgamma is increased by co-stimulation with tumor necrosis factor ( TNF)-alpha-related apoptosis-inducing ligand ( TRAIL ) , a member of the TNF family . In this study , we investigated the effect of PPARgamma on Fas-mediated apoptosis in hepatocellular carcinoma ( HCC ) cell lines . PPARgamma was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-Delta-12,14-prostaglandin J2 ( 15d- PGJ2 ) , a PPARgamma ligand , inhibited cellular proliferation in HepG2 , SK-Hep1 or HLE cells , unlike pioglitazone , another PPARgamma ligand , which did not have a significant influence on proliferation of these cells . However , 15d-PGJ2 facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone . These results suggest that PPARgamma can augment TNF-family-induced apoptosis . OUTPUT:

resisting cell death

HoC_1shot20

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 events have been associated with senile plaques , one of the pathological hallmarks of Alzheimer's disease ( AD ) . It is believed that aggregated beta-amyloid ( betaA ) proteins , which form the core of these plaques , may be responsible for triggering the inflammatory reaction . In the present study , the ability of aluminum ( Al ) to initiate similar inflammatory events was investigated in a human glioblastoma cell line . A 6-day exposure to either lipopolysaccharide ( LPS ) or aluminum sulfate caused a significant increase in the rate of proliferation of the glioblastoma cells . Both treatments also caused activation of the immune-responsive transcription factor NF-kappaB although there were time-related differences . The levels of secreted cytokines , interleukin-6 ( IL-6 ) and tumor necrosis factor alpha ( TNF-alpha ) were both increased by the LPS treatment although exposure to Al decreased the secretion of the former while elevating the levels of the latter . These events may be due to the activation of glial cells and subsequent stress response to either Al complexes or LPS . Although exposure to either stress factor caused a stimulation of inflammatory markers , there were time-dependent differences in the response . This may reflect the ability of the cells to discern different stress factors and thus orchestrate an innate immune response profile distinct to each immunogen . OUTPUT:

tumor promoting inflammation

HoC_1shot21

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Telomerase is a ribonucleoprotein enzyme that functions to maintain telomeres , the terminal DNA that protects chromosomal integrity , regulating cellular replicative life span . Telomerase is not expressed in most normal human somatic cells but is active in stabilizing telomeres of certain self-renewing cell populations and most malignant cells , making the enzyme an appealing target for anticancer therapy . We describe here a novel cross-species approach to telomerase inhibition . Ectopic expression of the human telomerase catalytic reverse transcriptase component in murine cells inhibited endogenous murine telomerase activity . Using this approach , telomerase inhibition in immortal murine fibroblasts resulted in critical telomere shortening , leading to slowed proliferation , abnormal morphology , altered cell cycle , and telomere dysfunction with cytogenetic instability , followed by apoptotic cell death . Subpopulations of two telomerase-inhibited clones escaped widespread apoptosis , showing proliferative recovery in culture despite persistently inhibited telomerase activity with progressive telomere shortening and dysfunction . This study , by targeting immortal murine cells for telomerase inhibition , demonstrates the importance of telomerase to murine cell immortalization and telomere maintenance . Moreover , the murine model used here should prove useful in further evaluating telomerase inhibition as an anticancer therapy . OUTPUT:

enabling replicative immortality;resisting cell death

HoC_1shot22

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 rare immunohistochemical study using 28 surgical sections of human chondrosarcoma revealed that 67.9% of tumour cells had weak ( 10-40% ) or strong ( >40% ) positive immunoreaction for peroxisome proliferator-activated receptor-gamma . The expression of peroxisome proliferator-activated receptor-gamma mRNA and protein in human chondrosarcoma cell line OUMS-27 was also determined by reverse transcription-polymerase chain reaction and immunocytochemistry , respectively . Furthermore , the effects of peroxisome proliferator-activated receptor-gamma ligands on cell proliferation and survival were investigated in OUMS-27 cells . Pioglitazone , a selective ligand for peroxisome proliferator-activated receptor-gamma , and 15-deoxy-Delta(12,14)-prostaglandin J(2) ( 15d-PGJ(2) ) , a putative endogenous ligand for peroxisome proliferator-activated receptor-gamma , inhibited the proliferation of OUMS-27 cells in a dose-dependent manner . The mechanism of cytotoxic effects of 15d-PGJ(2) was via apoptosis as shown by DNA fragmentation using TUNEL stain and DNA ladder formation , and by ultrastructural analysis using transmission electron microscopy . Flow-cytometric analysis using annexin-V-fluorescein and propidium iodide detected the early change of apoptosis , as well as necrosis of OUMS-27 cells at 4 h after co-incubation with 15d-PGJ(2) . These results suggest that peroxisome proliferator-activated receptor-gamma may play a significant role in the pathogenesis of chondrosarcoma , and peroxisome proliferator-activated receptor-gamma ligands , especially 15d-PGJ(2) , may be of therapeutic value in the treatment of human chondrosarcoma . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot23

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Notch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages . In addition , truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and , when introduced into mouse bone marrow stem cells , cause T-cell neoplasms . However , functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking . Here we show that Notch1 is highly expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large cell lymphoma . We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro . We further provide evidence that in Hodgkin and anaplastic large cell lymphoma , Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells . Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions , and it seems likely that these interactions contribute to lymphomagenesis in vivo . Thus , our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot24

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: UVB from solar radiation is both an initiating and promoting agent for skin cancer . We have found that primary human keratinocytes undergo an apoptotic response to UVB . To determine whether these responses are altered during the course of immortalization , we examined markers of apoptosis in primary human foreskin keratinocytes ( HFK ) transduced with either a retroviral vector expressing the E6 and E7 genes of HPV-16 or with empty vector alone ( LXSN-HFK ) . Whereas LXSN-HFK as well as early passage keratinocytes expressing HPV-16 E6 and E7 ( p7 E6/7-HFK ) were both moderately responsive to UVB irradiation , late passage-immortalized keratinocytes ( p27 E6/7-HFK ) were exquisitely sensitive to UVB-induced apoptosis . After exposure to UVB , enhanced annexin V-positivity and internucleosomal DNA fragmentation were observed in p27 E6/7-HFK compared with either LXSN- or p7 E6/7-HFK . Caspase-3 fluorometric activity assays as well as immunoblot analysis with antibodies to caspase-3 and poly(ADP-ribose) polymerase revealed elevated caspase-3 activity and processing at lower UVB doses in p27 E6/7-HFK compared with LXSN- or p7 E6/7-HFK . In addition , the caspase inhibitor DEVD-CHO reduced the apoptotic response and increased survival of all three HFK types . Immunoblot analysis revealed that caspase-8 was activated in all three cell types , but caspase-9 was only activated in p27 E6/7-HFK . Cell cycle analysis further showed that only p27 E6/7-HFK exhibit G(2)/M accumulation that is enhanced by UVB treatment . This accumulation was associated with a rapid down-regulation of Bcl-2 in these cells . The immortalization process subsequent to the expression of HPV E6 and E7 may therefore determine UVB sensitivity by switching the mode of apoptosis from a caspase-8 to a Bcl-2-caspase-9-mediated pathway of apoptosis . OUTPUT:

resisting cell death;enabling replicative immortality

HoC_1shot25

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 histological malignancy and the second leading cause of cancer deaths among North American men . There has been considerable interest in the chemopreventative properties of selenium . In this study , we assessed whether selenium inhibits cell growth and associated cell cycle regulatory proteins . Human PCA cells ( LNCaP , PC3 , PC3-AR2 , and PC3-M ) were incubated with and without selenium ( Seleno-DL-methionine , 150 microM ) for 24 , 48 , and 72 h . Cells were fixed and stained with propidium iodide for flow cytometry analysis . In parallel experiments , total protein was extracted , immunoprecipitated with cyclin E antibody , and analyzed by Western blot for the expression of cell cycle markers . Treatment with selenium caused G1 arrest and an 80% reduction in the S phase of LNCaP with no effect on PC3 . However , PC3 cells transfected with the androgen receptor ( PC3-AR2 ) exhibited a G2/M arrest and a marked reduction ( 57% ) in the S phase during cell cycle progression . In the analysis of cell cycle regulatory molecules , selenium-treated cells demonstrated a significant induction of cyclin-dependent kinase inhibitors Cip1/p21 and Kip1/p27 . These data suggest that selenium possesses strong antiproliferative properties in regard to human PCA . This effect appears to be dependent on the presence of a functioning androgen receptor . This provides a theoretical basis for Phase III studies of selenium in PCA prevention . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot26

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Interactions of CD70 , a tumor necrosis factor-related cell surface ligand and its receptor , CD27 , are thought to play an important role for T- , B- , and natural killer-cell activation . However , ligation of CD27 can also induce apoptosis . Human glioblastoma is paradigmatic for cancer-associated immunosuppression . We identified CD70 as a radioinducible gene in U87 MG glioma cells . A screening of a panel of human glioma cell lines revealed that 11 of 12 cell lines expressed CD70 mRNA and protein . Two human neuroblastoma cell lines did not express CD70 . CD70 mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53-independent manner . No alteration in CD70 expression was observed after glioma cell exposure to cytotoxic drugs such as lomustine . CD70 protein was also detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic astrocytomas in vivo . CD27 expression was not detected in any glioma cell line , and there was no evidence for autocrine or backward signaling of the CD70 system in human glioma cells . Unexpectedly , CD70 expressed on glioma cells did not increase the immunogenicity of glioma cells in vitro . In contrast , CD70-positive glioma cells induced apoptosis in peripheral blood mononuclear cells ( PBMCs ) in a CD70-dependent manner . Neutralization of CD70 expressed on glioma cells prevented apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures of glioma cells and PBMCs . The effects of CD70-expressing glioma cells on PBMCs were mimicked by agonistic CD27 antibodies . Conversely , the shedding of CD27 by PBMCs was identified as a possible escape mechanism from glioma cell-induced CD70-dependent apoptosis . Thus , induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas . OUTPUT:

resisting cell death;avoiding immune destruction

HoC_1shot27

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 t(10;11)(p12;q23) chromosomal translocation in human acute myeloid leukemia results in the fusion of the MLL and AF10 genes . The latter codes for a novel leucine zipper protein , one of many MLL fusion partners of unknown function . In this report , we demonstrate that retroviral-mediated transduction of an MLL-AF10 complementary DNA into primary murine myeloid progenitors enhanced their clonogenic potential in serial replating assays and led to their efficient immortalization at a primitive stage of myeloid differentiation . Furthermore , MLL-AF10-transduced cells rapidly induced acute myeloid leukemia in syngeneic or severe combined immunodeficiency recipient mice . Structure/function analysis showed that a highly conserved 82-amino acid portion of AF10 , comprising 2 adjacent alpha-helical domains , was sufficient for immortalizing activity when fused to MLL . Neither helical domain alone mediated immortalization , and deletion of the 29-amino acid leucine zipper within this region completely abrogated transforming activity . Similarly , the minimal oncogenic domain of AF10 exhibited transcriptional activation properties when fused to the MLL or GAL4 DNA-binding domains , while neither helical domain alone did . However , transcriptional activation per se was not sufficient because a second activation domain of AF10 was neither required nor competent for transformation . The requirement for alpha-helical transcriptional effector domains is similar to the oncogenic contributions of unrelated MLL partners ENL and ELL , suggesting a general mechanism of myeloid leukemogenesis by a subset of MLL fusion proteins , possibly through specific recruitment of the transcriptional machinery . OUTPUT:

enabling replicative immortality

HoC_1shot28

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 retinoic acid receptor beta2 ( RARbeta2 ) protein is a putative tumor suppressor that inhibits proliferation and can induce apoptosis when introduced into breast , cervical , lung , and pancreatic cancer cell lines . To determine if RARbeta2 suppresses proliferation of mammary-derived cancer cells in vivo , we transduced MDA-MB-435 breast cancer cells with the LXSN retroviral vector containing RARbeta2 and implanted LXSN vector- or RARbeta2-transduced cells into the mammary fat pads of nude and severe combined immune deficiency ( SCID ) mice . We analyzed the xenografts for several tumor parameters , including tumor size , inflammation , vascularity , mitoses , tumor recurrence at the primary site following resection , and metastases . We found that 19 of 52 mice inoculated with vector-transduced cells developed metastases in multiple organs while only one of 55 mice receiving RARbeta2-transduced cells displayed evidence of metastases ( p &lt ; 0.000001 , combined experiments , two-tailed Fisher's exact test ) . Moreover , RARbeta2-tumor cell recipient mice had a lower incidence of post-resection tumor recurrence ( 8/55 vs. 25/52 , p = 0.0004 ) , 34% less necrosis ( in three of four experiments , p = 0.001 ) , and 39% fewer mitoses in tumor tissue ( p &lt ; 0.000001 ) . Our findings suggest that RARbeta2 may play a role in inhibiting the metastatic cascade in a mouse mammary gland xenograft tumor model and is a potential candidate for therapeutic intervention in human breast cancer . OUTPUT:

activating invasion and metastasis

HoC_1shot29

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity . Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms . Here , we show that SIRT1 , the human Sir2 homolog , is recruited to the promyelocytic leukemia protein ( PML ) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras ( Ha-rasV12 ) . SIRT1 binds and deacetylates p53 , a component of PML nuclear bodies , and it can repress p53-mediated transactivation . Moreover , we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation . When overexpressed in primary mouse embryo fibroblasts ( MEFs ) , SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence . Taken together , our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence . OUTPUT:

enabling replicative immortality

HoC_1shot30

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 The goal of this study was to characterize the AFP receptor , its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402 . METHODS Cell proliferation enhanced by AFP was detected by MTT assay , 3H-thymidine incorporation and S-stage percentage of cell cycle analysis . With radioactive labeled 125I-AFP for receptor binding assay ; cAMP accumulation , protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium ( Ca2+i ) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope . The expression of oncogenes N- ras , p 53 , and p21( ras ) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively . RESULTS It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay , ( 3)H-thymidine incorporation and S-phase percentage up to 2-fold . Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9 x10(-8)mol . ( -1)L respectively . Pretreatment of cells with AFP resulted in a significant increase ( 625% ) in cAMP accumulation . The activity of protein kinase A activity were increased up to 37.5 , 122.6 , 73.7 and 61.2% at treatment time point 2 , 6 , 12 and 24 hours . The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204% at 4 min . The results also showed that AFP(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells . In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control . CONCLUSION These results demonstrate that AFP is a potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells . Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium to regulate the expression of oncogenes . OUTPUT:

sustaining proliferative signaling

HoC_1shot31

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Astrocytoma arises in the central nervous system as a tumor of great lethality , in part because of the invasive potential of the neoplastic cells that are able to release extracellular matrix-degrading enzymes . Furin convertase activates several precursor matrix metalloproteases involved in the breakdown of the extracellular matrix . In the present study inhibition of furin was achieved by gene transfer of alpha(1)-antitrypsin Portland ( PDX ) cDNA . EXPERIMENTAL DESIGN This furin inhibitor was transfected into two tumorigenic astrocytoma cell lines . The inhibitory effect was evaluated using in vivo tumorigenicity , invasion , and proliferation assays , as well as by investigating impairment of furin substrate processing . RESULTS Expression of PDX prevented the s.c. growth of the transfected cells . Invasion assays demonstrated that PDX-transfected cells exhibited a reduced invasive ability in vitro and in vivo . Furthermore , s.c. growth of PDX transfectant xenotransplants showed a significant reduction in size that coincided with a significant decrease of the in vitro doubling time and of the in vivo cell proliferation ability . Additional studies showed that the furin substrates insulin-like growth factor IR , transforming growth factor beta and membrane type 1-matrix metalloprotease were not activated in PDX-expressing astrocytoma cells . CONCLUSIONS PDX expression in astrocytoma cells demonstrated a direct mechanistic link between furin inhibition , and decreased astrocytoma proliferation and invasive ability . Because furin inhibition inhibits both invasiveness and cell growth in astrocytoma , furin should be considered a promising target for glioblastoma therapy . OUTPUT:

activating invasion and metastasis

HoC_1shot32

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Elevated insulin-like growth factor binding protein-related protein 1 ( IGFBP-rP1 ) mRNA in senescent human mammary epithelial cells suggested that the IGFBP-3 gene product may inhibit cell proliferation . To test this hypothesis , we used a retroviral vector to express IGFBP-rP1 cDNA in the IGFBP-rP1-deficient MCF-7 breast cancer cell line . Compared with control vector-transduced cells , cumulative cell numbers for IGFBP-rP1-transduced polyclonal or clonal cell cultures were reduced by 39 and 74% , respectively , after 1 week . Medium conditioned by IGFBP-rP1-producing cultures reduced cumulative cell numbers in parental MCF-7 cultures by 20% compared with medium from cultures of a control vector-transduced cell line . Nuclear fragmentation analysis and cell proliferation assays completed in the presence of the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone excluded apoptosis as the responsible mechanism . The percentage of cells containing senescence-associated beta-galactosidase activity was doubled compared with control cell cultures . Flow cytometry analysis indicated that twice as many noncycling cells were present in the IGFBP-rP1-transduced MCF-7 cell cultures compared with controls . These findings indicate that IGFBP-rP1 is an inhibitor of MCF-7 breast cancer cell proliferation and may act via a cellular senescence-like mechanism . OUTPUT:

resisting cell death;enabling replicative immortality;sustaining proliferative signaling

HoC_1shot33

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 modelled multiple stages of malignant transformation of human endothelial cells ( ECs ) by overexpressing the catalytic subunit of human telomerase ( hTERT ) , together with SV40 T antigen ( SV40T ) and oncogenic N-ras . Transfection with hTERT alone , led to the immortalization of two out of three cultures of bone marrow-derived ECs ( BMECs ) . One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation . BMECs transfected with hTERT alone were functionally and phenotypically normal . BMECs transfected with SV40T ( BMSVTs ) had an extended lifespan , but eventually succumbed to crisis . BMSVTs exhibited a partially transformed phenotype , demonstrating growth factor independence , altered antigen expression and forming tiny , infrequent colonies in vitro . Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures . BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo . BMECs co-expressing SV40T , hTERT and N-ras exhibited an overtly transformed phenotype ; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo . These investigations demonstrate transformation of human ECs to an overtly malignant phenotype . This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias , as well as for testing drugs designed to curtail aberrant EC growth . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling;inducing angiogenesis

HoC_1shot34

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 association between acute myeloid leukaemia ( AML ) and the aberrant expression of Hoxa9 is evidenced by ( 1 ) proviral activation of Hoxa9 and Meis1 in BXH-2 murine AML , ( 2 ) formation of the chimeric Nup98-HoxA9 transactivator protein as a consequence of the t(7;11) translocation in human AML , and ( 3 ) the strong expression of HoxA9 and Meis1 in human AML . In mouse models , enforced retroviral expression of Hoxa9 alone in marrow is not sufficient to cause rapid AML , while co-expression of Meis1 and Hoxa9 induces rapid AML . In contrast , retroviral expression of Nup98-HoxA9 is sufficient to cause rapid AML in the absence of enforced Meis1 expression . Previously , we demonstrated that Hoxa9 could block the differentiation of murine marrow progenitors cultured in granulocyte-macrophage colony-simulating factor ( GM-CSF ) . These progenitors lacked Meis1 expression , could not proliferate in stem cell factor ( SCF ) , but could differentiate into neutrophils when switched into granulocyte colony-simulating factor ( G-CSF ) . Ectopic expression of Meis1 in these Hoxa9 cells suppressed their G-CSF-induced differentiation , permitted proliferation in SCF , and therein offered a potential explanation of cooperative function . Because Meis1 binds N-terminal Hoxa9 sequences that are replaced by Nup98 , we hypothesized that Nup98-HoxA9 might consolidate the biochemical functions of both Hoxa9 and Meis1 on target gene promoters and might evoke their same lymphokine-responsive profile in immortalized progenitors . Here we report that Nup98-HoxA9 , indeed mimicks Hoxa9 plus Meis1 coexpression - it immortalizes myeloid progenitors , prevents differentiation in response to GM-CSF , IL-3 , G-CSF , and permits proliferation in SCF . Unexpectedly , however , Nup98-Hoxa9 also enforced strong transcription of the cellular Hoxa9 , Hoxa7 and Meis1 genes at levels similar to those found in mouse AML's generated by proviral activation of Hoxa9 and Meis1 . Using Hoxa9(-/-) marrow , we demonstrate that expression of Hoxa9 is not required for myeloid immortalization by Nup98-HoxA9 . Rapid leukaemogenesis by Nup98-HoxA9 may therefore result from both the intrinsic functions of Nup98-HoxA9 , as well as of those of coexpressed HOX and MEIS1 genes . OUTPUT:

enabling replicative immortality

HoC_1shot35

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 : Previously , we have observed that highly unsaturated dietary ( n-3 ) fatty acids inhibit cell proliferation in conjunction with stimulation of insulin-like growth factor-binding protein ( IGFBP)-6 secretion in Caco-2 cells , a human colon carcinoma cell line . METHODS : To test the converse hypothesis that inhibition of endogenous IGFBP-6 secretion stimulates Caco-2 cell proliferation , cells were transfected with the antisense IGFBP-6 expression construct or pcDNA3 vector only , and single colonies resistant to G418 sulfate were isolated . RESULTS : Our initial studies indicated that three antisense clones grew faster and produced less IGFBP-6 than two pcDNA3 clones , so antisense IGFBP-6 #5 and pcDNA3 #8 were selected for further detailed analysis . Both the control and antisense clones grew in serum-free medium reaching a plateau density at day eight . However , the antisense clone grew at a rate faster than that of the control and reached a final density that was 31 +/- 3% higher than the control . Northern blot , ligand blot and immunoblot analyses revealed that accumulation of IGFBP-6 mRNA and concentrations of IGFBP-6 peptide produced by the antisense clone were decreased by 80-90% compared to the control . The doubling times of the antisense and control clones were 21.9 +/- 0.4 and 24.8 +/- 0.3 h ( P &lt ; 0.05 ) , respectively . Exogenous IGF-I and IGF-II ( 0.2-200 nmol/L ) stimulated proliferation of both the control and antisense clones in a dose-dependent manner , but the relative potency and efficacy of IGF-II was higher in the antisense clone compared to the control . These results indicate that suppression of IGFBP-6 secretion correlates with an increase in the basal rate of Caco-2 cell growth . CONCLUSIONS : Our findings are consistent with the hypothesis that IGFBP-6 inhibits cell growth by binding to endogenously produced IGF-II , thereby preventing IGF-II from interacting with the IGF-I receptor to stimulate cellular proliferation by an autocrine mechanism . OUTPUT:

sustaining proliferative signaling

HoC_1shot36

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Direct experimental evidence implicates telomere erosion as a primary cause of cellular senescence . Using a well characterized model system for breast cancer , we define here the molecular and cellular consequences of adriamycin treatment in breast tumor cells . Cells acutely exposed to adriamycin exhibited an increase in p53 activity , a decline in telomerase activity , and a dramatic increase in beta-galactosidase , a marker of senescence . Inactivation of wild-type p53 resulted in a transition of the cellular response to adriamycin treatment from replicative senescence to delayed apoptosis , demonstrating that p53 plays an integral role in the fate of breast tumor cells treated with DNA-damaging agents . Stable introduction of hTERT , the catalytic protein component of telomerase , into MCF-7 cells caused an increase in telomerase activity and telomere length . Treatment of MCF-7-hTERT cells with adriamycin produced an identical senescence response as controls without signs of telomere shortening , indicating that the senescence after treatment is telomere length-independent . However , we found that exposure to adriamycin resulted in an overrepresentation of cytogenetic changes involving telomeres , showing an altered telomere state induced by adriamycin is probably a causal factor leading to the senescence phenotype . To our knowledge , these data are the first to demonstrate that the mechanism of adriamycin-induced senescence is dependent on both functional p53 and telomere dysfunction rather than overall shortening . OUTPUT:

enabling replicative immortality;genomic instability and mutation;resisting cell death

HoC_1shot37

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 thyroid hormone ( triiodothyronine , T(3) ) and breast cancer is unclear . We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor ( TR alpha 1 ) , of its ligand T(3) , and of its retroviral , mutated counterpart , the v-erbA oncogene , on the proliferation capacity of nontumorigenic mammary epithelial cells ( EpH4 ) . We found that EpH4 cells expressing ectopically TR ( EpH4 + TR alpha 1 ) or v-erbA ( EpH4 + v-erbA ) proliferated faster than parental EpH4 cells that contained low levels of endogenous TR . T(3) inhibited DNA synthesis and proliferation in EpH4 + TR alpha 1 cells but not EpH4 or EpH4 + v-erbA cells . The study of cell-cycle genes showed that T(3) decreased cyclin D1 RNA and protein levels in EpH4 + TR alpha 1 cells . In addition , T(3) downregulated the expression of T1 , a gene that is overexpressed in human breast adenocarcinomas and is induced by mitogens , serum , and several oncogenes and cytokines . Inhibition of the T1 gene by T(3) required both de novo mRNA and protein synthesis . Furthermore , T(3) abolished the induction of T1 by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and inhibited the activity of an activation protein 1-dependent promoter ( -73-Col-CAT ) in EpH4 + TR alpha 1 cells , suggesting that interference with activation protein 1 transcription factor plays a part in the inhibition of the T1 gene . Our results showed that T(3) reduced the proliferation of mammary epithelial cells and inhibited the expression of cyclin D1 and T1 genes . OUTPUT:

sustaining proliferative signaling

HoC_1shot38

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Urokinase plasminogen activator receptor ( uPAR ) activates alpha5beta1 integrin and ERK signaling , inducing in vivo proliferation of HEp3 human carcinoma . Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin ( FN ) induced growth pathway . Its activation is ligand-independent and does not require high EGFR , but does require high uPAR expression . Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated . Domain 1 of uPAR is crucial for EGFR activation , and FAK links integrin and EGFR signaling . Inhibition of EGFR kinase blocks uPAR induced signal to ERK , implicating EGFR as an important effector of the pathway . Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo . These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling , providing cancer cells with proliferative advantage . OUTPUT:

sustaining proliferative signaling

HoC_1shot39

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 recently developed surface-shielded transferrin-polyethylenimine ( Tf-PEI)/DNA delivery systems that target reporter gene expression to distant tumors after systemic application . In the present study , we used surface-shielded Tf-PEI/DNA complexes for delivering the gene for a highly potent cytokine , tumor necrosis factor-alpha ( TNFalpha ) . TNFalpha is known for its ability to induce hemorrhagic tumor necrosis and tumor regression . However , the therapeutic application of TNFalpha is hampered by its high systemic toxicity dictating the need to target TNFalpha activity to the tumor . Systemic application of surface-shielded Tf-PEI complexes with the TNFalpha gene resulted in preferential expression of TNFalpha in the tumor without detectable TNFalpha serum levels , in contrast to the application of nontargeted complexes . Tumor-targeted TNFalpha gene delivery induced pronounced hemorrhagic tumor necrosis and inhibition of tumor growth in three murine tumor models of different tissue origins , Neuro2a neuroblastoma , MethA fibrosarcoma , and M-3 melanoma , with complete tumor regressions observed in the MethA model . No systemic TNF-related toxicity was observed due to the localization of the TNFalpha activity to the tumor . Targeted gene therapy may be an attractive strategy applicable to highly active , yet toxic , molecules such as TNFalpha . OUTPUT:

resisting cell death

HoC_1shot40

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease ( LPD ) secondary to organ/bone marrow transplant-related immunosuppression ( 30 : 11 liver , 10 heart/lung , 8 kidney and 1 bone marrow ) , other drug-induced immunosuppression ( 2 ) , congenital immunodeficiency ( 8 ) or human immunodeficiency virus ( HIV)-related immune dysfunction ( 2 ) . Ages ranged from 10 months to 17 years and there were 15 girls . Pathology was centrally reviewed and showed polymorphic features in 5 cases , monomorphic in 23 , mixed pattern in 5 patients and 9 other types . Using the Revised European-American Classification of Lymphoid Neoplasms , 5 were B lymphoblastoid , 24 were high-grade B and 14 were other subtypes . Using the Pittsburgh classification , 9 were lymphadenopathic , 10 were systemic , 25 were lymphomatous and , with the Murphy grouping for non-Hodgkin's lymphoma ( NHL ) , 10 were localized and 32 non-localized . Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive . Thirty-five patients were evaluable for clonality ; 24 were monoclonal and 11 were polyclonal . Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24 , which was sustained in 11 . Nineteen patients received chemotherapy , 14/18 evaluable responded , which was sustained in 8 cases . Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died . In the largest group of patients , solid organ transplants , no significant clinical or biological characteristics that predicted outcome were identified . In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective . OUTPUT:

avoiding immune destruction

HoC_1shot41

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 have indicated that females may be at greater risk of smoking associated lung cancer compared with males . Several lines of biochemical evidence support these observations . A possible role of circulating steroid hormones in the etiology of lung cancer has been hypothesized . In the present paper , we have studied the expression of the estrogen receptors ( ER)-alpha and ER beta in histologically normal human lung tissue and lung tumor cell lines . Relative ER mRNA levels were measured by reverse transcriptase-PCR and normalized to the level of expression of the glyceraldehyde 3-phosphate dehydrogenase gene ( GAPDH ) . In lung tissue , an ER alpha transcript was found at various levels in 38 out of 46 cases ( 83% ) . ER beta was expressed in all cases . The ERs were expressed at similar levels in females and males , and the levels of ER alpha and ER beta mRNA were significantly related ( P<0.0001 ) . Compared with the lung tissue , ER expression levels were lower in 16 human lung tumor cell lines and two immortalized human bronchial epithelial cell lines . Five of the tumor cell lines ( 31% ) expressed detectable levels of ER alpha and both of the immortalized cell lines showed a weak ER alpha expression level . All cell lines expressed the ER beta . The lung cell lines BEAS-2B and DB354 showed significantly reduced cell proliferation in response to tamoxifen and a minor increased growth in response to 17 beta-estradiol . In conclusion , ER genes are abundantly expressed in both histologically normal human lung and lung tumor cell lines . This indicates a possible role of ERs in lung carcinogenesis . OUTPUT:

sustaining proliferative signaling

HoC_1shot42

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 beneficial effect of yoghurt consumption on health and on the improvement of the mucosal immune system is well established , as is the diet-associated risk of colon cancer . In an experimental model in BALB/c mice we demonstrated that yoghurt added to the diet for 10 consecutive days , with the procedure repeated each 10 days for 6 months , inhibited the development of a colorectal carcinoma induced by 1,2 dimethylhydrazine ( DMH ) . The immunoregulatory mechanisms involved in the inhibition of tumour growth by yoghurt were also examined in these studies . We determined B lymphocytes IgA(+) and IgG(+) , as well as CD4(+) and CD8(+) T cells in the large intestine . We measured cellular apoptosis and the cytokines TNF-alpha , IFN-gamma and IL-10 . An increase in the number of IgA(+) ( P<0.01 ) was observed , but not in IgG(+) ( P<0.01 ) , or in the CD4(+) population ( P<0.01 ) in the mice treated with DMH and yoghurt . While in the group with the carcinogen there was an enhancement in the IgG(+) B cells ( P<0.01 ) and CD8(+) T cells ( P<0.01 ) . Yoghurt increased the number of apoptotic cells and induced IFN-gamma and TNF-alpha cytokine release , their production being regulated by an increase in IL-10 ( P<0.001 ) . We demonstrated that yoghurt may exert antitumour activity by a decrease in the inflammatory immune response mediated by IgA(+) increase , apoptosis induction and IL-10 release . OUTPUT:

tumor promoting inflammation;resisting cell death

HoC_1shot43

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Ovarian steroids are one of the strongest risk factors for breast cancer . Sex hormone-binding globulin ( SHBG ) binds and transports sex steroids in the blood , regulating their bioavailable fraction and access to target cells . It can also inhibit the estradiol-induced proliferation of breast cancer cells through its membrane receptor . Three coding-region polymorphisms , which lead to an amino acid change , have been reported . We studied the influence of these three polymorphisms on breast cancer risk in three different populations : Polish familial breast cancer cases , 27% of them carrying a BRCA1/BRCA2 mutation , Nordic familial and sporadic breast cancer cases . The reported G to A polymorphism in exon 1 was not found in the 423 analyzed samples . Instead , we found a C to T transition causing an arg to cys amino acid change within the same codon in one Polish breast cancer patient and her daughter . Both of them were heterozygotes for the exon 8 G to A polymorphism as well . They were diagnosed for bilateral breast cancer and carried a BRCA1 mutation ( 5382insC ) . Analysis of the tumor samples showed that they had lost the wild-type allele both at exons 1 and 8 of the SHBG gene . Analysis of the other Polish samples showed no correlation of the exon 8 polymorphism to breast cancer , bilateral breast cancer , BRCA1/BRCA2 mutations or age at diagnosis . No association of the exon 8 polymorphism with breast cancer in the Nordic familial or sporadic cases was found . The C to T polymorphism located in exon 4 was rare in all the studied populations ( overall allele frequency 0.011 ) . However , in each of the study populations there was a trend for a lower variant allele frequency in cancer cases than in controls . Variant allele frequency in all the breast cancer cases was significantly lower than in all the controls ( chi(2) = 5.27 , P-value 0.02 ; odds ratio = 0.23 , 95% confidence interval 0.05-0.84 ) . OUTPUT:

genomic instability and mutation

HoC_1shot44

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Current antibody-based immunotherapeutic approaches under evaluation for breast carcinoma are limited in target scope . For example , administration of the human epidermal growth factor receptor ( EGFR ) antibody , alone or in combination with a chemotherapeutic drug , is thought to primarily inhibit tumor cell proliferation . The aim of this study was to assess the effects of a combined blockade designed to inhibit tumor growth by inhibition of proliferation rate and the proinflammatory effects of interleukin ( IL ) 8 . EXPERIMENTAL DESIGN A human breast carcinoma cell line that produces high levels of IL-8 was injected s.c. into severe combined immunodeficient mice . IL-8 has been reported to augment the progression of some human tumors ; thus , we used a human IL-8 antibody , ABXIL8 , in combination with anti-EGFR , ABXEGFR , to inhibit the metastasis of MDA231 tumors . RESULTS Whereas anti-IL-8 alone had no appreciable antimetastatic effect , the combination of ABXIL8 significantly enhanced the antitumor effects of ABXEGFR , resulting in greater survival of SCID tumor-bearing mice . This effect on survival was correlated with decreased metastatic spread and decreased tumor size in mice receiving both antibodies . Intriguingly , in vitro studies indicate that this antibody combination markedly inhibited matrix metalloproteinase activity associated with MDA-231 cells to a greater degree than either antibody alone . CONCLUSION Combined administration of these two human antibodies using growth factor blockade in conjunction with chemokine blockade may thus provide a more effective approach for treatment of metastatic human breast carcinoma . OUTPUT:

activating invasion and metastasis

HoC_1shot45

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 HOX11 gene encodes a homeodomain transcription factor that is essential for spleen development during embryogenesis . HOX11 is also leukaemogenic , both through its clinical association with childhood T-cell acute lymphoblastic leukaemia , and its ability to immortalize other haematopoietic cell lineages experimentally . To examine the pathological role of HOX11 in tumorigenesis , we constitutively expressed HOX11 cDNA in J2E murine erythroleukaemic cells , which are capable of terminal differentiation . Enforced HOX11 expression was found to induce a profound alteration in J2E cellular morphology and differentiation status . Our analyses revealed that HOX11 produced clones with a preponderance of less differentiated cells that were highly adherent to plastic . Morphologically , the cells overexpressing HOX11 were larger and had decreased globin levels , as well as a reduction in haemoglobin synthesis in response to erythropoietin ( EPO ) . Immunocytochemical analysis confirmed the immature erythroid phenotype imposed by HOX11 , with clones transfected with HOX11 demonstrating expression of the c-Kit stem cell marker , while retaining EPO receptor expression . Taken together , these results show that HOX11 alters erythroid differentiation , favouring a less mature progenitor-like stage . This supports the notion that disrupted haematopoietic cell differentiation is responsible for pre-leukaemic immortalization by the HOX11 oncoprotein . OUTPUT:

enabling replicative immortality

HoC_1shot46

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene ( DMBA)-induced rat mammary tumors , by simultaneously investigating the expression of estrogen receptor-alpha ( ERalpha ) , estrogen receptor-beta ( ERbeta ) , progesterone receptor ( PR ) , apoptosis , neu , and markers of cell proliferation , such as proliferating cell nuclear antigen ( PCNA ) by immunohistochemistry . The percentage of ERalpha positive tumors was 65.8% in masses from control animals , and significantly dropped to 36.8% in tumors from soy treated rats ( P=0.010 ) . The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals ( P=0.066 ) . Moreover , the percentage of cases which were both ERalpha and ERbeta positive was significantly lower ( 17.6% ) in soy treated than in control animals ( 51.3% ) ( P=0.006 ) . The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats ( P=0.0006 ) . There were no statistically significant differences in the percentage of tumors positively stained for neu , apoptosis , or PCNA , in control vs. soy treated rats . However , when analyzing the reciprocal correlation among the different biochemical parameters we showed that , in treated animals , the majority of ERalpha positive tumors ( 91.7% ) were also PCNA positive ( P=0.036 ) . The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors ( 25 vs. 5% ) ( P=0.0031 ) . Moreover , an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive ( P=0.011 ) . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot47

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 vast majority of breast cancers are carcinomas that arise from mammary epithelial cells ( MECs ) . One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence . However , the precise genetic changes that are responsible for this event in MECs is largely unknown . Here , we report that Bmi-1 , originally identified as a c-Myc cooperating oncoprotein , can bypass senescence , extend the replicative life span , and immortalize MECs . Furthermore , Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines . Overexpression of Bmi-1 in MECs led to activation of human telomerase reverse transcriptase ( hTERT ) transcription and induction of telomerase activity . Telomerase induction by Bmi-1 was an early event in the extension of the replicative life span and immortalization . Bmi-1 was not overexpressed in hTERT-immortalized MECs , suggesting that Bmi-1 functions upstream of hTERT . Although , c-Myc has been reported to induce telomerase in MECs , Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT promoter . Deletion analysis of the Bmi-1 protein suggested that the RING finger , as well as a conserved helix-turn-helix-turn domain , were required for its ability to induce telomerase and immortalize MECs . These data suggest that Bmi-1 regulates telomerase expression in MECs and plays a role in the development of human breast cancer . OUTPUT:

enabling replicative immortality

HoC_1shot48

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Immunosuppression has been related to the incidence of tumor apparition , including endocrine tumors . The intrasplenic ovarian tumor ( luteoma ) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and , from the immunological perspective , is located in a critical organ involved in immune response . To establish if immunosuppression could alter the development of this experimental tumor , the effects of cyclosporin A ( CsA ) and dexamethasone ( Dex ) were evaluated . After surgery , tumor-bearing and sham animals were kept without treatment for 4 weeks ; thereafter , they were distributed into CsA ( 25 mg/kg ) , Dex ( 0.1 mg/kg ) , or vehicle ( 75:25 castor oil:ethanol ) groups and were injected on alternate days for 50 days . Body weight was evaluated weekly . Animals were sacrificed after a jugular vein blood sample was obtained . Thymi were weighed . Tumors were measured and placed in formaline for histological studies . Serum luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) , prolactin ( PRL ) , and estradiol were measured by radioimmunoassay . Hematological parameters were determined . CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals ( P &lt ; 0.01 ) . Dex significantly impaired weight increase in both groups of animals . CsA induced a significant weight loss in sham animals , not observed in tumor-bearing animals . Dex induced thymus weight loss in both groups , whereas CsA induced thymus weight loss only in sham animals . Only Dex induced a decrease in lymphocyte number in both groups . CsA induced an increase in monocyte number only in sham animals . Treatments did not alter LH , FSH , or estradiol , whereas PRL was increased by CsA only in sham rats . Neither Dex nor CsA induced any significant variations in tumor volume , nor did they alter tumor histology . In addition , no visible metastases or alterations in other organs were observed . We conclude that , though immunological parameters were altered by the treatments , immunosuppressor drugs did not condition tumor development . In addition , tumors secrete one or more factor/s that counteract CsA effect . OUTPUT:

activating invasion and metastasis;avoiding immune destruction

HoC_1shot49

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 knowledge of alterations in regulation of autophagy during tumorigenesis may also help our understanding of its normal control . We established an experimental system and reported recently that autophagic capacity , measured as the cell's capability of increasing segregation ( formation of autophagosomes ) and subsequent degradation of cytoplasmic quanta were highly increased in premalignant nodule cells 6 months after initiation by azaserine in the rat pancreas in vivo . In the present study , we followed changes of these autophagic functions throughout the tumour progression . We carried out electron-microscopic morphometrical analysis of the expansion of autophagic vacuole compartment and subcompartments induced by vinblastine ( an in vivo segregation enhancer ) , as well as their regression upon segregation-inhibitor cycloheximide post-treatment . Premalignant tumour samples were taken at month 5 , month 8 ( nodules ) , month 10 and month 15 ( adenomas ) after initiation . In all these stages , a highly increased and varying autophagic capacity was found compared with the host tissue . The basal ( non-stimulated ) autophagic compartment was measurable only at month 5 and month 15 , and its regression upon cycloheximide was consistent with increased basal autophagic activity . Compared with the host tissue , autophagic capacity profoundly decreased in the differentiated and anaplastic adenocarcinomas at month 20 , when , surprisingly , cycloheximide was unable to inhibit segregation . Our conclusion is that down-regulation of the cycloheximide sensitive segregation and a partly compensatory up-regulation of an alternative pathway of segregation might occur along with malignant transformation . OUTPUT:

resisting cell death