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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

HoC_1shot50

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Dimethyl sulfoxide ( DMSO ) , a well-known differentiation inducer in several myeloid cells , also induces a reversible G(1) arrest in many cell lines . We recently showed that DMSO induces a G(1) phase arrest in Chinese hamster ovary ( CHO ) cells , by restoring contact inhibition and preventing high density-dependent apoptosis . CHO cells are frequently used in cell biology and mutagenesis studies due to their good growth capacity and ease of manipulation but are very difficult to synchronize by serum starvation since they detach from monolayers when they reach confluence . In this study we investigated the possibility of using DMSO to reversibly synchronize CHO cells in the G(1) phase of the cell cycle and analysed whether toxic effects follow the arrest using growth curve , sister chromatid exchange and micronuclei assays . We carried out a kinetic analysis of the arrest by DMSO and re-entry into the cell cycle after drug release by cytofluorimetric analysis of DNA content and bromodeoxyuridine incorporation . We show that CHO cells are efficiently and reversibly arrested in G(1) by DMSO in concentrations ranging between 1 and 2% . In our experiments , >90% of cells grown for 96 h in presence of the drug were arrested in G(1) and synchronously re-entered S phase approximately 8-12 h after release . Furthermore , expression levels of p27 were down-regulated during G(1) progression and cyclin D3 and E expression patterns were similar to those observed after serum starvation . No detectable cytotoxicity or genetic damage were induced in G(1) released cells as revealed by the tests employed . Our results show that DMSO is a very powerful inducer of G(1) synchronization in CHO cells without detectable cytotoxic or genetic effects in cell populations released from G(1) arrest . DMSO synchronization represents a model system in which to analyse protein activities regulating G(1) progression and investigate the response of G(1) cells to mutagen treatments . OUTPUT:

sustaining proliferative signaling;evading growth suppressors;genomic instability and mutation

HoC_1shot51

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment ( as well as their accumulation in human adipose tissue ) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity . A variety of musk fragrances were tested using the E-screen assay . A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks ( musk xylene , musk ketone ) , a major metabolite of musk xylene ( p-amino-musk xylene ) , and the polycyclic musk fragrance AHTN . This indicates that these substances do , in fact , demonstrate estrogenic activity . Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated . It must be noted , however , that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol . The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances , a group of substances that have not yet been well characterized in respect to their toxicological properties , has also been shown to be weakly estrogenically active in vitro . E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK , the macrocyclic musk fragrances ethylene brassylate , ethylene dodecandioate , and cyclopentadecanolide , are not estrogenically active . OUTPUT:

sustaining proliferative signaling

HoC_1shot52

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Mutations in the Nf2 tumor suppressor gene lead to tumor formation in humans and mice and cellular overproliferation phenotypes in Drosophila . The Nf2 encoded protein , merlin , shares close sequence similarity in its amino terminus to members of the band 4.1 family of membrane-cytoskeletal linkers . Similarities between merlin and this family suggest a role for merlin in regulating cytoskeletal function . However , the mechanism of the tumor suppressing activity of merlin is not yet understood . Mutational analysis of Nf2 in flies has led to the identification of a dominant-negative allele , which harbors mutations in the amino terminus of the protein . Here , we report that expression of a murine analog of this amino-terminal mutant of Nf2 leads to complete transformation of NIH3T3 fibroblasts in culture . Cells that express this Nf2 mutant allele display disruptions of the actin cytoskeleton , lack of contact inhibition of growth , and anchorage-independent growth . Finally , fibroblasts that express this mutant Nf2 allele form tumors when injected into nude mice . OUTPUT:

genomic instability and mutation;evading growth suppressors

HoC_1shot53

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: p107 Links to cyclin A/CDK2 ( cyclin-dependent kinase 2 ) and cyclin E/CDK2 that are important cell cycle regulators . However , p107 expression remains unclear in almost all kinds of human solid tumours . To clarify the expression of p107 in colorectal tumours , 22 normal mucosae , 9 hyperplastic polyps , 60 adenomas , 198 primary carcinomas , 21 lymph-nodal metastases , and 10 hepatic metastases were immunohistochemically stained for p107 , cyclin A , cyclin E , CDK2 and Ki67 . Results were measured using labelling indices ( LIs). p107 LIs surpassed the highest value in normal tissues in six of nine hyperplastic polyps , 54 of 60 adenomas , 144 of 198 primary cancers , 13 of 21 nodal foci and three of 10 hepatic foci. p107 LIs also apparently rose from normal through hyperplasia and adenoma to early carcinoma . However , they declined in liver-metastatic foci , and in primary cancers showing large size , mucinous type , venous invasion , lymphatic invasion , poorly differentiated type , deep invasion , lymph-nodal metastasis , hepatic metastasis or advanced stage . Low p107 LIs were also linked to a poor survival , particularly in stage-III patients . As the p107 LI gradually rose , the CDK2 ( in primary cancers only ) , cyclin A , cyclin E and Ki67 LIs were elevated concurrently-in both adenomas and primary cancers . Thus , in colorectal tumours , p107 expression rises abnormally and gradually during carcinogenesis and then falls during invasion , and thereby probably perturbs the cell-cycle control and promotes carcinogenesis and invasion . Clinically , reduced p107 may indicate a poorer prognosis . OUTPUT:

activating invasion and metastasis

HoC_1shot54

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 , initially observed during subculturing of normal diploid fibroblasts , can also be induced by chronic exposure to cellular stress , such as UV light , oxidative stress , or DNA damaging agents . Here we demonstrate that stable expression of an activated form of MKK6 ( MKK6EE ) , a direct activator of the stress-induced p38(HOG) mitogen-activated protein kinase pathway , is sufficient for inducing features of senescence including a flattened , vacuolated , and irregular morphology , staining for acidic beta-galactosidase , and accumulation of age-associated pigments . Consistent with the senescent phenotype , p38(HOG) activation induces a G(1) cell cycle arrest , which is permanent and irreversible after 4 days . MKK6EE also induces biochemical features of senescence in a p38-dependent manner , including enhanced expression of p21(CIP) , a cyclin-dependent kinase inhibitor . Microarray analysis of MKK6EE cells showed a pattern of gene expression noted previously in Werner Syndrome and senescent fibroblasts . These results define p38(HOG) as an intracellular pathway that activates a senescence checkpoint in tumor cells and may play a role in Ras- or stress-induced senescence . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot55

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Malignant mesothelioma ( MM ) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested . Three different primary cultures ( MMGe-1 , MES MM 98 , and MES 1 ) and one immortalized cell line ( MSTO 211 H ) of human MM were studied in order to evaluate the HER-2/neu expression . Three out of four cell lines showed a different level of c-erbB-2 expression , the highest being detected on the MSTO 211 H cell line ( fibroblastic phenotype ) , whereas MMGe-1 resulted negative . The effect of the anti-HER-2/neu antibody ( Trastuzumab ) alone , and in combination with cisplatin ( CDDP ) at different doses ( ranging from 0.1 to 100 microg/ml ) , was studied on all the c-erB-2 positive cell lines . Trastuzumab was able to inhibit cell proliferation in a time-dependent manner , with growth inhibition also obtained at low concentrations ( 0.1-1 microg/ml ) . Combined treatment with Trastuzumab ( 10 microg/ml ) and CDDP ( 1 microg/ml ) showed synergism . Our results were encouraging , and suggest a rationale for further investigations in a clinical setting . OUTPUT:

sustaining proliferative signaling

HoC_1shot56

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands ( PD-L ) and is suggested to play a role in the maintenance of self-tolerance . In the present study , we examined possible roles of the PD-1/PD-L system in tumor immunity . Transgenic expression of PD-L1 , one of the PD-L , in P815 tumor cells rendered them less susceptible to the specific T cell antigen receptor-mediated lysis by cytotoxic T cells in vitro , and markedly enhanced their tumorigenesis and invasiveness in vivo in the syngeneic hosts as compared with the parental tumor cells that lacked endogenous PD-L . Both effects could be reversed by anti-PD-L1 Ab . Survey of murine tumor lines revealed that all of the myeloma cell lines examined naturally expressed PD-L1 . Growth of the myeloma cells in normal syngeneic mice was inhibited significantly albeit transiently by the administration of anti-PD-L1 Ab in vivo and was suppressed completely in the syngeneic PD-1-deficient mice . These results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 and PD-L may provide a promising strategy for specific tumor immunotherapy . OUTPUT:

avoiding immune destruction

HoC_1shot57

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 metastatic spread of malignant neoplasms is associated with active migration of cancer cells . The migration of neoplastic cells during the metastatic process may be affected by various extracellular factors , including chemoattractants , haptotactic signals , electric fields , substrate anisotropy , and cell-to-cell contacts . We examined the effect of homotypic collisions and heterotypic interactions with normal human skin fibroblasts on the motile activity of Walker carcinosarcoma cells . It was found that Walker carcinosarcoma cells moving in a dense population neither show contact inhibition of movement when colliding with one another nor increase their motile activity as a result of contact stimulation of motility . On the other hand , when plated onto the surface of aligned fibroblasts , Walker carcinosarcoma cells migrated mainly along the long axes of underlying fibroblasts as a result of contact guidance . The directional character of movement ( but not the speed of migration ) of Walker carcinosarcoma cells on the surface of aligned fibroblasts was completely effaced by RGD-containing synthetic peptide at a concentration of 1 mg/ml but not by 5 microM verapamil ( selective voltage-gated calcium channel inhibitor ) or 10 microM gadolinium chloride ( non-specific blocker of mechanosensitive ion channels ) . The suppression of directional character of migration of tumour cells by RGD-containing peptide was associated with the decrease in the amount of fibronectin macromolecules attached to fibroblasts . This suggests that alignment and anisotropic distribution of fibronectin macromolecules may be responsible for contact guidance of tumour cells moving on the surface of fibroblasts . OUTPUT:

evading growth suppressors

HoC_1shot58

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 G protein-coupled human gastrin-releasing peptide receptor ( hGRP-R ) is frequently found aberrantly expressed in human cancers of the colon , stomach , and lung , and its ligand-specific activation has been implicated in cell proliferation and differentiation . Here , we demonstrated hGRP-R activation stimulated sustained cyclic AMP response element binding protein ( CREB ) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway . In contrast , intracellular calcium , ERK1/2 , protein kinase A , and PI3 kinase were not involved . This novel signaling mechanism might be of importance for regulation of CREB-dependent gene expression in human cancer expressing functional hGRP-R . OUTPUT:

sustaining proliferative signaling

HoC_1shot59

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 rat colonic adenocarcinoma was implanted subcutaneously ( s.c. ) in nude mice . After 7 days , the animals were divided into different groups . Two groups received subcutaneous injections twice daily with 3 or 6 micro g/kg body weight octreotide , galanin and serotonin . Three groups were respectively treated with 20 , 30 , and 40 micro g/kg body weight of the previously mentioned bioactive substances . Control group received only saline solution in the same fashion as treated animals . The treatment lasted for 5 days . The tumour volume and weight , the relative density of blood vessels , of tumour necrotic tissue , of apoptotic nuclei and of proliferating nuclei were measured . Apoptosis was detected by in situ labelling of nuclear DNA fragmentation according to TUNEL method , and proliferation by immunocytochemistry . Morphometry was done with the classical stereological point-counting method . Food consumption , animal weight , faeces weight and its water content were measured for 3 days before and after treatment . Triple therapy with 3 and 6 micro g/kg body weight had no effect on any of the parameters measured , except in reducing the relative volume density of tumour blood vessels . Treatment with 20 , 30 and 40 micro g/kg body weight of the previously mentioned bioactive substances reduced the tumour volume , the relative volume density of blood vessels and increased the relative volume density of necrotic tissue and of apoptotic nuclei ( in the 20 micro g group ) . However , there was no difference between treated mice and controls regarding the relative volume density of proliferating nuclei . There was no statistical difference between treated animals regarding food consumption , body weight , faeces weight and its water content before and during treatment . The present study confirms that triple therapy with octreotide , galanin and serotonin causes regression of a rat colon carcinoma . It further showed that optimum treatment dose is 20 micro g/kg body weight of each bioactive substance . Moreover , this therapy regime does not show apparent side effects in the experiments carried out on mice . OUTPUT:

resisting cell death;inducing angiogenesis

HoC_1shot60

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Exposure to ultraviolet B ( UVB ) radiation ( 280-320 nm ) is the primary etiologic factor associated with the development of basal cell carcinoma ( BCC ) . The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise eliminate them . Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation . Humans , like mouse strains , display variations in dermal mast cell prevalence . In a study of Danish and South Australian BCC patients and control subjects , one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant . This skin site was investigated to avoid any changes in mast cell prevalence caused by sun exposure . Two sections ( 4 microm ) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells . Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total dermal area ( expressed as mast cells per square millimeter ) . This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations . We hypothesize that mast cells function in humans , as in mouse strains , by initiating immunosuppression following UV irradiation and , thereby , allowing a permissive environment for the development of BCC . Thus , a high dermal mast cell prevalence as demonstrable in buttock skin is a significant predisposing factor for development of BCC in humans . OUTPUT:

avoiding immune destruction

HoC_1shot61

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE Overexpression of epidermal growth factor receptor ( EGFR ) in glioblastoma multiforme ( GBM ) secondary to EGFR gene amplification is associated with a more aggressive tumor phenotype and a worse clinical outcome . The purpose of this study was to analyze whether blocking this receptor with the anti-EGFR chimeric monoclonal antibody C225 would decrease proliferation and increase apoptosis in GBM cells . METHODS EGFR expression and amplification were analyzed for seven human GBM cell lines . These lines were then exposed to different concentrations of C225 for 48 hours , 72 hours , and 7 days , after which time cytotoxicity , apoptosis , and vascular endothelial growth factor expression were assessed in vitro . Two EGFR-amplified human GBM were implanted in the flanks of nude mice , and the animals received C225 twice per week intraperitoneally for 5 weeks . Tumor volumes and survival times were compared with those of sham-treated mice . RESULTS EGFR gene amplification was demonstrated in three of the primary GBM lines . C225 treatment produced significant cytotoxicity in all three EGFR-amplified GBM lines , but not in unamplified lines . Flow cytometry demonstrated increased apoptosis in C225-treated , EGFR-amplified GBM lines , but not in unamplified lines . There was a decrease in vascular endothelial growth factor expression in all GBM lines with exposure to C225 . Tumor-bearing mice treated with C225 experienced significant inhibition of tumor growth as well as a 200% increase in median survival . CONCLUSION Blocking EGFR in GBM cells that overexpress this receptor significantly changes tumor cell biology by promoting apoptosis while decreasing proliferation and vascular endothelial growth factor expression . This approach holds great promise for the treatment of patients with GBMs . OUTPUT:

sustaining proliferative signaling;resisting cell death;inducing angiogenesis

HoC_1shot62

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Glycolysis is known to be the primary energy source in most cancer cells . We investigated here the effect of clotrimazole ( 1-(alpha-2-chlorotrityl)imidazole ) , the antifungal azole derivative , which was recently recognized as calmodulin antagonist , on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate , the two stimulatory signal molecules of glycolysis , and on ATP content and cell viability in LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells . We found that clotrimazole induced a significant , dose- and time-dependent reduction in the levels of glucose 1,6-bisphosphate , fructose 1,6-bisphosphate , ATP , and cell viability . These findings suggest that clotrimazole causes a reduction in glycolysis and ATP levels , which eventually leads to cell destruction after 3 h of treatment . Since cell proliferation was also reported to be inhibited by calmodulin antagonists , this substance is most promising agent in treatment of cancer by inhibiting both cell proliferation and the glycolytic supply of ATP required for cancer cell growth . OUTPUT:

cellular energetics

HoC_1shot63

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 immune system of vertebrates is able to detect bacterial DNA based on the presence of unmethylated CpG motifs . We examined the therapeutic potential of oligodeoxynucleotides with CpG motifs ( CpG ODN ) in a colon carcinoma model in BALB/c mice . Tumors were induced by s.c. injection of syngeneic C26 cells or Renca kidney cancer cells as a control . Injection of CpG ODN alone or in combination with irradiated tumor cells did not protect mice against subsequent tumor challenge . In contrast , weekly injections of CpG ODN into the margin of already established tumors resulted in regression of tumors and complete cure of mice . The injection site was critical , since injection of CpG ODN at distant sites was not effective . Mice with two bilateral C26 tumors rejected both tumors upon peritumoral injection of one tumor , indicating the development of a systemic immune response . The tumor specificity of the immune response was demonstrated in mice bearing a C26 tumor and a Renca tumor at the same time . Mice that rejected a tumor upon peritumoral CpG treatment remained tumor free and were protected against rechallenge with the same tumor cells , but not with the other tumor , demonstrating long term memory . Tumor-specific CD8 T cells as well as innate effector cells contributed to the antitumor activity of treatment . In conclusion , peritumoral CpG ODN monotherapy elicits a strong CD8 T cell response and innate effector mechanisms that seem to act in concert to overcome unresponsiveness of the immune system toward a growing tumor . OUTPUT:

avoiding immune destruction

HoC_1shot64

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 still difficult to decide on the treatment modalities for advanced esophageal carcinoma when the prognostic factors of T4 esophageal cancer are not fully understood . In this article , we report that among 71 patients with T4 thoracic esophageal cancer , 49 underwent esophagectomy , 9 had curative resection ( R0 group ) , and 40 had palliative resection ( R1/2 group ) . A total of 22 patients had palliative treatments : bypass in 5 ( bypass group ) , gastrostomy or jejunostomy in 6 ( stoma group ) , and radiochemotherapy alone in 11 ( nonoperation group ) . Clinicopathologic characteristics were retrospectively investigated . Treatment-related deaths occurred in 7 ( 10% ) : none in R0 , 3 ( 8% ) in R1/2 , 3 ( 60% ) in bypass , and 1 ( 17% ) in stoma group . Swallowing was improved in 50 ( 70% ) patients : 9 ( 100% ) in R0 , 30 ( 75% ) in R1/2 , 1 ( 20% ) in bypass , 3 ( 50% ) in stoma , and 7 ( 64% ) in the nonoperation group . One- , two- , and three-year overall survival rates were 56% , 22% , and 22% in the R0 group and 35% , 19% and 6% in the R1/2 group , respectively ( p = 0.19 ) . In the bypass , stoma , and nonoperation groups , none survived 1.6 years . The factors influencing the survival rate of the 49 patients undergoing esophagectomy were grade of lymph node metastasis , amount of perioperative blood transfusion , lymph vessel , and blood vessel invasion . Among these , independent prognostic factors for survival were amount of blood transfusion ( -6 units vs. -7 units , p <0.0001 ) and grade of lymph node metastasis [ none- or peritumoral [ lymph nodes adjacent to the main tumor or at a nearby location ( <3 cm ) from the tumor ] metastasis vs. more distant metastasis [ lymph nodes at a distant location ( &gt ; 3 cm) ] , p = 0.016 ] . Bypass and stoma operation neither prolonged the survival nor improved the difficulty of swallowing compared with radiochemotherapy alone . Esophagectomy can achieve the best improvement of swallowing and the longest survival with an acceptable mortality rate . Esophageal carcinoma patients with T4 disease and distinct metastasis in the lymph nodes at a distant location ( >3 cm ) from the primary tumor may not benefit from an esophageal resection . OUTPUT:

activating invasion and metastasis

HoC_1shot65

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 key issue in the development of the central nervous system ( CNS ) is understanding the molecular mechanisms regulating cell number . The present study examines the role of CD81 ( previously known as TAPA , the target of the antiproliferative antibody ) in the control of brain size and glial cell number . CD81 is a member of the tetraspanin family of proteins . This group of small membrane proteins is associated with the regulation of cell migration and mitotic activity . Glial cells express CD81 , and antibodies directed against this protein suppress the mitotic activity of cultured cells . In this study , we examine the effects of the CD81 -/- mutation on the CNS of mature mice . These mice have extremely large brains , as much as 30% larger than the brains of wild-type ( +/+ ) littermates . The increase in brain weight is accompanied by an increase in the number astrocytes and microglia , whereas the number of neurons and oligodendrocytes in the CD81 -/- animals appears to be normal . When the CD81 -/- mutation is placed on different genetic backgrounds , there is a remarkable range in the penetrance of the null allele phenotype , demonstrating that the mutation can be affected by modifier loci . This work provides support for the role of CD81 in the regulation of astrocyte and microglial number , perhaps by regulating cell proliferation by a contact inhibition-dependent mechanism . OUTPUT:

genomic instability and mutation;evading growth suppressors

HoC_1shot66

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 ( PRC17 ) . When overexpressed in 3T3 mouse fibroblast cells , PRC17 induced growth in low serum , loss of contact inhibition , and tumor formation in nude mice . The PRC17 gene product contains a GTPase-activating protein ( GAP ) catalytic core motif found in various Rab/Ypt GAPs , including RN-Tre . Similar to RN-Tre , we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis . Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities , suggesting that GAP activity is essential for its oncogenic function . Whereas PRC17 is amplified in 15% of prostate cancers , it is highly overexpressed in approximately one-half of metastatic prostate tumors . The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers . OUTPUT:

evading growth suppressors;genomic instability and mutation;activating invasion and metastasis

HoC_1shot67

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Hormone-independent tumor growth and metastasis are associated with increased mortality in human prostate cancer . In this study , we evaluate a potential role for ligand-mediated activation of HER2 receptor tyrosine kinase in androgen-independent prostate cancers . HER2 , HER3 , and epidermal growth factor receptor were detected in the androgen-independent cell line 22Rv1 . Heregulin stimulation results in receptor phosphorylation and cell proliferation that is inhibited by increasing concentrations of anti-HER2 recombinant humanized monoclonal antibody ( rhuMAb ) 2C4 . Furthermore , inhibition of tumor growth was observed in xenografts derived from 22Rv1 cells when treated with rhuMAb 2C4 in a dose-dependent manner . These studies provide a framework , both in vitro and in vivo , to examine the molecular mechanisms of ligand-driven HER2 activation in androgen-independent tumorigenesis . OUTPUT:

sustaining proliferative signaling

HoC_1shot68

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer . We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature . In the present study , we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases . We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998 , and analyzed the corresponding primary colorectal cancers clinicopathologically . Microscopic bile duct invasion was found in 89 of 217 cases ( 40.6% ) and , of these cases , 23 ( 10.6% ) had macroscopic intrabiliary extension . Histological sections of the corresponding primary colorectal cancer were available in eight ( group A ) of these 23 cases . These were compared with 20 cases , selected randomly , of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases . These patients underwent hepatectomy during the same period as group A and were used as a control ( group B ) . The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B ( P &lt ; 0.01 ) , while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups . These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases . Careful histological evaluation is important even for metastatic tumors . OUTPUT:

activating invasion and metastasis

HoC_1shot69

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease ( GVHD ) . However , optimal dosage is still under debate . Thirty-one consecutive children , mainly with haematological malignancies , were transplanted in a single institution with such donors , selected by HLA-A -B compatibility by serology and DRB1* by DNA typing . Antithymocyte globulin ( Thymoglobuline ; Sangstat ) was infused at days -3 , -2 , -1 . Total dosage varied : 16 patients received a median of 7.5 mg/kg ( 2.5 to 10.5 : low-dose group ) , and 15 a median of 15.5 mg/kg ( 14.4 to 19.4 : high-dose group ) . Post-transplant GVHD prophylaxis consisted of cyclosporine , short-course methotrexate and steroids . CD3(+) , CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group . Median time to reach 100 CD4(+) cells was 8 months vs 4 months ( P = 0.03 ) . Median time to normal CD19(+) cells was 16 months vs 8 months ( P = 0.01 ) . CD16(+)CD56(+) and CD8(+) cell reconstitution was similar . Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections ( P = 0.009 ) . Although obtained from a limited number of patients , our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution . OUTPUT:

avoiding immune destruction

HoC_1shot70

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Human fibroblasts undergo cellular senescence after a finite number of divisions , in response to the erosion of telomeres . In addition to being terminally arrested in the cell cycle , senescent fibroblasts express genes that are normally induced upon wounding , including genes that remodel the extracellular matrix . We have identified the novel zinc finger protein APA-1 , whose expression increased in senescent human fibroblasts independent of telomere shortening . Extended passage , telomerase-immortalized fibroblasts had increased levels of APA-1 as well as the cyclin-dependent kinase inhibitor p16 . In fibroblasts , APA-1 was modified by the ubiquitin-like protein SUMO-1 , which increased APA-1 half-life , possibly by blocking ubiquitin-mediated degradation . Overexpression of APA-1 did not cause cell cycle arrest ; but , it induced transcription of the extracellular matrix-remodeling genes MMP1 and PAI2 , which are associated with fibroblast senescence . MMP1 and PAI2 transcript levels also increased in telomerase-immortalized fibroblasts that had high levels of APA-1 , demonstrating that the matrix-remodeling phenotype of senescent fibroblasts was not induced by telomere attrition alone . APA-1 was able to transactivate and bind to the MMP1 promoter , suggesting that APA-1 is a transcription factor that regulates expression of matrix-remodeling genes during fibroblast senescence . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot71

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 activity , a cardinal requirement for immortalization , is a crucial step in the development of cancer and has been studied in many kinds of malignant tumours for clinical diagnostic and/or prognostic utilities . Using a PCR-based TRAP assay , we investigated telomerase activity in 8 adenomatous polyps , 9 dysplastic polyps , and in 36 paired cancer-normal mucosa specimens , one liver and one spleen metastasis from patients resected for sporadic colorectal cancer . Telomerase was absent or very low in normal mucosa and in adenomatous polyps . Dysplastic polyps and adenocarcinoma samples showed telomerase activity , with higher levels in cancer tissues compared to dysplastic lesions . A high telomerase activity was shown to be associated with late-staged cancers and metastasis , providing arguments supporting the role of telomerase not only in the development but also in the progression of colorectal carcinoma . Moreover , telomerase evaluation may help to confirm the malignant transformation in polypoid colorectal lesions with different levels of dysplastic alterations . OUTPUT:

activating invasion and metastasis

HoC_1shot72

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 search for potential biomarkers used to monitor the process of immortalization , we investigated the relative level of telomerase activity and other immortal phenotypes in the SHEE esophageal epithelial cell line . This human fetal esophageal epithelial cell line , induced by human papilloma virus ( HPV ) 18 E6E7 , was continually propagated over 100 passages . Fourteenth passage cells ( SHEE14 ) were cultured in a flask with a serum-free medium and continually cultured to the 30th passage ( SHEE30 ) . Cells of SHEE14 , SHEE20 and SHEE30 were examined according to cell morphology , cell cycle , apoptosis , contact-inhibition growth , anchorage- dependency , dose-dependency to epithelial growth factors ( EGF ) , telomerase activity and tumorigenicity . The SHEE14 cells exhibited good differentiation with contact-inhibition and anchorage-dependent growth . The SHEE20 cells exhibited increase of senescent and apoptotic cells , and difficulty in propagation . The SHEE30 cells exhibited a higher proliferative index and some undifferentiated cells , with weakened contact-inhibition and anchorage-dependent growth . The telomerase was activated in cells of SHEE30 , but not in SHEE14 and SHEE20 cells . The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30 . Three groups of cells displayed lack of tumor formation in nude mice . Compared with SHEE14 and SHEE20 , SHEE30 cells were of immortalized status with immortal phenotype , which consisted of telomerase activity , increase of cell proliferation , weakened contact-inhibition and anchorage-dependent growth , dose dependency to EGF and lack of tumor formation . From passage 14 to 30th passage , SHEE cells went through cellular senescence , apoptosis and immortalization . With a view toward diagnostic and biological aspects , telomerase activity is a crucial step and a cardinal requirement for immortalization . The telomerase activity and other immortal phenotypes are potential markers for monitoring the process of immortalization . OUTPUT:

evading growth suppressors;enabling replicative immortality;resisting cell death

HoC_1shot73

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Nur77 is an orphan receptor . Although Nur77 affects cell proliferation and apoptosis through its capability of binding to a variety of response elements and regulating their transactivation activities , the intrinsic function of Nur77 is not yet fully understood ; in particular , its regulation of apoptosis and proliferation has been characterized as cell type-dependent and agent context-dependent . In this study , Nur77 can be seen to regulate apoptosis via its expression and translocation , rather than its transactivation activity in gastric cancer cells . Nur77 was constitutively expressed in BGC-823 cells . The tetradecanoylphorbol-1,3-acetate ( TPA ) treatment not only resulted in up-regulation of the Nur77 mRNA level , but also led to translocation of Nur77 protein from the nucleus to the mitochondria , and caused the release of cytochrome c . This TPA-induced translocation of Nur77 was in association with the initiation of apoptosis in gastric cancer cells . Although all-trans retinoic acid ( ATRA ) could not induce apoptosis in BGC-823 cells due to failure of stimulating Nur77 translocation , expression of Nur77 in the nucleus was required for cell growth inhibition by ATRA . Transfection of antisense Nur77 receptor into BGC-823 cells resulted in resistance of cell growth against ATRA inhibition , and the cells were still arrested in the S phase . Furthermore , the action of Nur77 in TPA-induced apoptosis was mediated through a protein kinase C signaling pathway , while mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways were responsible for the regulation of Nur77 mRNA expression . Taken together , the data revealed the dual functioning mechanisms of Nur77 in gastric cancer cells in response to TPA and ATRA . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot74

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Intracystic papillary carcinoma ( IPC ) of the breast is a rare form of noninvasive breast cancer . An appreciation of associated pathology with IPC may be critical in surgical decision-making . METHODS The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed . Three patient groups were identified according to the pathologic features of the primary tumor : IPC alone , IPC with associated ductal carcinoma in situ ( DCIS ) , and IPC with associated invasion with or without DCIS . Types of treatment and outcomes were compared between groups . RESULTS Forty patients were treated for IPC during the study period . Fourteen had pure IPC , 13 had IPC with DCIS , and 13 had IPC with invasion . The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery ( mastectomy or segmental mastectomy ) performed and whether radiation therapy was administered . The disease-specific survival rate was 100% . CONCLUSIONS When IPC is identified , it is frequently associated with DCIS and or invasion . Standard therapy should be based on associated pathology . The role of radiation therapy in pure IPC remains to be determined . OUTPUT:

activating invasion and metastasis

HoC_1shot75

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Retinoic acid ( RA ) and its derivatives inhibit the proliferation of normal human mammary epithelial cells ( HMEC ) and some breast carcinoma lines by mechanisms which are not fully understood . To identify genes that mediate RA-induced cell growth arrest , an HMEC cDNA library was synthesized and subtractive screening was performed . We identified the interleukin-1beta ( IL-1beta ) gene as an RA induced gene in HMEC . Northern blot analyses showed that the IL-1beta gene was up-regulated as early as 2 h after RA treatment . Results from the treatment of HMEC with cycloheximide and actinomycin D indicated that the regulation of the IL-1beta gene by RA occurred at the transcriptional level and that the IL-1beta gene is a direct , downstream target gene of RA . To evaluate the effects of IL-1beta on cell proliferation , the proliferation of HMEC was measured in the presence of RA or IL-1beta , or both . Either RA or IL-1beta could significantly inhibit the proliferation of HMEC . However , the addition of soluble IL-1 receptor antagonist ( sIL-1ra ) to the cell culture medium did not block RA-induced HMEC growth inhibition , whereas sIL-1ra did block the growth inhibition of HMEC by IL-1beta . IL-1beta expression was not observed in the three carcinoma cell lines , MCF-7 , MDA-MB-231 , and MDA-MB-468 , as compared to the HMEC . Growth curves of the breast carcinoma cell lines showed strong inhibitory effects of RA and IL-1beta on the growth of the estrogen receptor ( ER ) positive MCF-7 cell line , but only a small effect on the ER negative MDA-MB-231 cells . The expression of the IL-1beta gene was also transcriptionally activated by RA in normal epithelial cells of prostate and oral cavity . Our results suggest that : ( a ) the IL-1beta gene is a primary target of RA receptors in HMEC ; ( b ) the enhanced expression of the IL-1beta gene does not mediate the RA-induced growth arrest of HMEC ; and ( c ) the expression of the IL-1beta gene is low or absent in all three human breast carcinoma cell lines examined , but the defect in the IL-1beta signaling pathway may be different in ER positive versus ER negative carcinoma cells . OUTPUT:

sustaining proliferative signaling

HoC_1shot76

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Genetic immunotherapy with tumor antigen gene-modified dendritic cells ( DC ) generates robust immunity , although antitumor protection is not complete in all models . Previous experience in a model in which C57BL/6 mice immunized with DC transduced with adenoviral vectors expressing MART-1 demonstrated a 20-40% complete protection to a tumor challenge with B16 melanoma cells . Tumors that did develop in immunized mice had slower growth kinetics compared to tumors implanted in na�ve mice . In the present study , we wished to determine if the supraphysiological production of the Th1-skewing cytokine interleukin-12 ( IL-12 ) could enhance immune activation and antitumor protection in this model . In a series of experiments immunizing mice with DC cotransduced with MART-1 and IL-12 , antitumor protection and antigen-specific splenocyte cytotoxicity and interferon gamma production inversely correlated with the amount of IL-12 produced by DC . This adverse effect of IL-12 could not be explained by a direct cytotoxic effect of natural killer cells directed towards DC , nor the production of nitric oxide leading to down-regulation of the immune response - the two mechanisms previously recognized to explain immune-suppressive effects of IL-12-based vaccine therapy . In conclusion , in this animal model , IL-12 production by gene-modified DC leads to a cytokine-induced dose-dependent inhibition of antigen-specific antitumor protection . OUTPUT:

avoiding immune destruction

HoC_1shot77

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) is the most potent tumor promoter ever tested in rodents . Although it is known that most of TCDD actions are mediated by binding to the aryl hydrocarbon receptor ( AhR ) , the mechanisms leading to tumor promotion still remain to be elucidated . Loss of contact inhibition is one characteristic hallmark in tumorigenesis . In rat liver epithelial WB-F344 cells , TCDD induces a release from contact inhibition , which is manifested by a twofold increase in cell number when TCDD ( 1 nM for 48 h ) is added to confluent cells in the presence of serum , but not when given to exponentially growing or subconfluent , serum-deprived WB-F344 cells . Loss of G1 arrest was also shown by flow cytometric analysis . We demonstrate that TCDD treatment significantly increases cyclin D2 and cyclin A protein levels and show by immunofluorescence that these proteins accumulate in the nucleus . Although TCDD treatment leads to a strong increase in cyclin D2/cdk4 and cyclin A/cdk2 complex formation , we could only detect an elevation of cyclin A/cdk2 activity . In accordance with a lack of elevated cdk4 activity , no decrease in the amount of hypophosphorylated retinoblastoma protein could be shown after TCDD treatment . The importance of increased cyclin A/cdk2 activity for TCDD-dependent release from contact inhibition was shown by the fact that the cdk2/cdc2-specific inhibitor olomoucine ( 25 microM ) abolished TCDD response . These data indicate cyclin A-dependent loss of G1 arrest after TCDD treatment mainly downstream of the retinoblastoma protein . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot78

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Retinoblastoma ( Rb ) is the most common intraocular tumor of childhood . In this study we examined primary Rb specimens and Rb cell lines for the expression of immunoglobulin superfamily ( IgSF ) antigens : MHC class I and II ( MHC-I and MHC-II ) , neural cell adhesion molecule ( NCAM ) , intercellular adhesion molecule-1 ( ICAM-1 ) , and Thy-1 , which play an important role in immune system and tumor cell interactions . MHC-I and-II , ICAM-1 ( CD54 ) , NCAM ( CD56 ) , and Thy-1 ( CDw90 ) immunoreactivity was studied in eight primary Rb biopsy specimens using immunohistochemistry , three using immunoelectron microscopy , and six Rb cell lines using flow cytometry ( FCM ) . Parenchymal and vascular-associated cells , phenotypically similar to retinal microglia , strongly expressed MHC-II immunoreactivity and were distributed throughout primary Rb specimens . However , MHC-II expression on Rb cell lines was similar to nonspecific control levels . Tumor cells in primary Rb specimens displayed high NCAM , moderate Thy-1 , and low MHC-I and ICAM-1 immunolabeling . Tumor vasculature expressed low to moderate MHC-I and ICAM-1 immunoreactivity and moderate Thy-1 immunoreactivity . NCAM was not detected on the vasculature of primary Rb specimens . Rb cell lines displayed variable expression of Thy-1 , ICAM-1 , and MHC-I . NCAM was highly expressed on five of six Rb cell lines . The high levels of constitutive NCAM immunoreactivity on Rb tumor cells confirm the neuroectodermal origins of this tumor . Additionally , the variable expression of Thy-1 may suggest separate neural lineages or differences in the maturational status ofsome Rb tumors . The presence of a population of infiltrating MHC-II-positive cells in primary Rb tumors has implications for immunomodulation of Rb growth . OUTPUT:

avoiding immune destruction

HoC_1shot79

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than nonstressed ones . Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells ( BCR-ABL(+) ) express HSP60 and HSP72 on their surface . To explore how the immune system distinguishes stressed from nonstressed apoptotic tumor cells , we analyzed the responses of dendritic cells to these 2 types of apoptotic cells . We found that nonstressed and heat-stressed apoptotic 12B1-D1 cells were taken up by dendritic cells in a comparable fashion . However , when stressed apoptotic 12B1-D1 cells were coincubated with immature dendritic cells for 24 hours , this resulted in greater up-regulation of costimulatory molecules ( CD40 , CD80 , and CD86 ) on the surface of dendritic cells . Moreover , stressed apoptotic 12B1-D1 cells were more effective in stimulating dendritic cells to secrete interleukin-12 ( IL-12 ) and in enhancing their immunostimulatory functions in mixed leukocyte reactions . Furthermore , we demonstrated that immunization of mice with stressed apoptotic 12B1-D1 cells induced the secretion of T helper-1 ( T(H)1 ) profile of cytokines by spleen cells . Splenocytes from mice immunized with stressed apoptotic cells , but not nonstressed ones , were capable of lysing 12B1-D1 and the parental 12B1 line , but not a B-cell leukemia line , A20 . Our data indicate that stressed apoptotic tumor cells are capable of providing the necessary danger signals , likely through increased surface expression of heat shock proteins ( HSPs ) , resulting in activation/maturation of dendritic cells and , ultimately , the generation of potent antitumor T-cell responses . OUTPUT:

avoiding immune destruction;resisting cell death

HoC_1shot80

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Hormone replacement therapy , which is a common menopausal treatment , is contraindicated in women with breast cancers due to concerns regarding the potential for breast cell proliferation . As such , there is a need for alternative methods for treating menopausal symptoms . To determine the influence of one such alternative , black cohosh ( Cimicifuga racemosa [ CR] ) , on estrogen-dependent mammary cancers , we conducted an in vitro investigation of the effect of an isopropanolic CR-extract on the proliferation of estrogen receptor-positive breast cancer cells . The experiments were performed using the human breast adenocarcinoma ( MCF-7 ) cell test system , an established in vitro model for estrogen-dependent tumors . The influence of CR-extract on the proliferation of the MCF-7 cells was determined by measuring the incorporation of radioactively labeled thymidine . Under estrogen-deprived conditions , the CR-extract ( 10(-3)-10(-5) dilutions ) significantly inhibited MCF-7 cell proliferation . Additionally , application of the CR-extract inhibited estrogen-induced proliferation of MCF-7 cells . Moreover , the proliferation-inhibiting effect of tamoxifen was enhanced by the CR-extract . Such data that suggest a non-estrogenic , or estrogen-antagonistic effect of CR on human breast cancer cells lead to the conclusion that CR treatment may be a safe , natural remedy for menopausal symptoms in breast cancer . OUTPUT:

sustaining proliferative signaling

HoC_1shot81

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION AND AIMS The survival of pancreatic cancer patients with portal vein resection is extremely poor due to the high incidence of liver metastasis . The occurrence of liver metastasis is decreased by locoregional arterial infusion after pancreatic surgery . Chemosensitivity tests can provide the basis for individualized chemotherapy in each patient and predict the clinical response . Therefore , the current study was designed to clarify whether locoregional chemotherapy based on the results of chemosensitivity tests has the clinical effects of preventing liver metastasis and improving survival for patients with portal vein resection . METHODOLOGY The resected specimens from 40 of 47 patients with resection of pancreatic cancer were assessed for chemosensitivity to various anticancer drugs . Fourteen patients underwent portal vein resection due to direct invasion , and nine of these patients received intra-arterial adjuvant chemotherapy on the basis of the results of MTT assay to prevent liver metastasis . The remaining five patients received no chemotherapy . RESULTS None of the patients who received intra-arterial chemotherapy had liver metastasis , and this group of patients had improved survival . The mean survival of patients with intra-arterial chemotherapy was significantly longer than that of patients without chemotherapy ( 25.6 months with chemotherapy versus 9.4 months without chemotherapy ) . CONCLUSION A pilot study of postoperative intra-arterial chemotherapy showed the reduction of liver metastasis and improvement of survival among pancreatic cancer patients with portal vein resection . OUTPUT:

activating invasion and metastasis

HoC_1shot82

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Tumor cells are elusive targets for immunotherapy due to their heterogeneity and genetic instability . Here we describe a novel , oral DNA vaccine that targets stable , proliferating endothelial cells in the tumor vasculature rather than tumor cells . Targeting occurs through upregulated vascular-endothelial growth factor receptor 2 ( FLK-1 ) of proliferating endothelial cells in the tumor vasculature . This vaccine effectively protected mice from lethal challenges with melanoma , colon carcinoma and lung carcinoma cells and reduced growth of established metastases in a therapeutic setting . CTL-mediated killing of endothelial cells indicated breaking of peripheral immune tolerance against this self antigen , resulting in markedly reduced dissemination of spontaneous and experimental pulmonary metastases . Angiogenesis in the tumor vasculature was suppressed without impairment of fertility , neuromuscular performance or hematopoiesis , albeit with a slight delay in wound healing . Our strategy circumvents problems in targeting of genetically unstable tumor cells . This approach may provide a new strategy for the rational design of cancer therapies . OUTPUT:

activating invasion and metastasis;avoiding immune destruction;inducing angiogenesis

HoC_1shot83

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 INK4a/ARF tumor suppressor locus is implicated in the senescence-like growth arrest provoked by oncogenic Ras in primary cells . INK4a and ARF are distinct proteins encoded by transcripts in which a shared exon is decoded in alternative reading frames . Here we analyze dermal fibroblasts ( designated Q34 ) from an individual carrying independent missense mutations in each copy of the common exon . Both mutations alter the amino acid sequence of INK4a and functionally impair the protein , although they do so to different degrees . Only one of the mutations affects the sequence of ARF , causing an apparently innocuous change near its carboxy terminus . Unlike normal human fibroblasts , Q34 cells are not permanently arrested by Ras or its downstream effectors Ets1 and Ets2 . Moreover , ectopic Ras enables the cells to grow as anchorage-independent colonies , and in relatively young Q34 cells anchorage independence can be achieved without addition of telomerase or perturbation of the p53 pathway . Whereas ARF plays the principal role in Ras-induced arrest of mouse fibroblasts , our data imply that INK4a assumes this role in human fibroblasts . OUTPUT:

genomic instability and mutation

HoC_1shot84

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Using standard culture conditions , primary human mammary epithelial cells ( HMECs ) undergo a premature , transient growth arrest termed M0 ( mortality stage 0 ) after 10-15 population doublings in vitro . It has been reported that emergence from this growth arrest by the abrogation of p16(INK4a) , a cyclin-dependent kinase inhibitor , and expression of the catalytic component of human telomerase ( hTERT ) are necessary for HMEC immortalization . Here we show that primary HMECs , grown on feeder layers , do not undergo this growth arrest and can be immortalized without abrogating p16 . These findings support the concept that the so-called M0 stage represents a cell culture stress-induced growth arrest and that hTERT is sufficient to immortalize HMECs when cultured under adequate conditions . OUTPUT:

enabling replicative immortality

HoC_1shot85

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Optimal lymphocyte activation requires the simultaneous engagement of stimulatory and costimulatory receptors . Stimulatory immunoreceptors are usually composed of a ligand-binding transmembrane protein and noncovalently associated signal-transducing subunits . Here , we report that alternative splicing leads to two distinct NKG2D polypeptides that associate differentially with the DAP10 and KARAP ( also known as DAP12 ) signaling subunits . We found that differential expression of these isoforms and of signaling proteins determined whether NKG2D functioned as a costimulatory receptor in the adaptive immune system ( CD8+ T cells ) or as both a primary recognition structure and a costimulatory receptor in the innate immune system ( natural killer cells and macrophages ) . This strategy suggests a rationale for the multisubunit structure of stimulatory immunoreceptors . OUTPUT:

avoiding immune destruction

HoC_1shot86

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Osteosarcoma is an aggressive primary bone cancer characterized by expression of platelet-derived growth factor ( PDGF ) and its cognate receptor . Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms . It has been reported previously that STI571 has specific activity in inhibiting select tyrosine kinase receptors , including PDGF and c-Kit . Osteosarcomas express low levels of c-Kit but abundant levels of PDGF receptor ( PDGFR ) . EXPERIMENTAL DESIGN To investigate the potential of STI571 as therapy for osteosarcoma , we studied its effects on PDGF-mediated cell growth in vitro and in an in vivo mouse model . RESULTS PDGF acted as a potent mitogen in a dose-dependent manner in two osteosarcoma cell lines . STI571 ( 1.0 micro M ) inhibited both PDGFR-alpha and PDGFR-beta phosphorylation and the downstream phosphorylation targets extracellular signal-regulated kinase and Akt . STI571 also inhibited PDGF-mediated growth and induced apoptosis in vitro as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining . To study the effect of STI571 alone or in combination with Taxol in an in vivo model , an osteosarcoma cell line ( KRIB ) was transplanted into the tibia of athymic nude mice . Mice were treated with STI571 ( 50 mg/kg p.o. q M-F ) , Taxol ( 8 mg/kg i.p. weekly ) , or STI571 plus Taxol for 6 weeks . There was no significant difference in tumor size between treatment and control mice . Aberrant signaling pathways downstream of the PDGFR in the v-Ki-ras oncogene-transformed KRIB cell line may in part explain this finding . CONCLUSIONS Our data demonstrate that STI571 inhibits PDGF-mediated growth and leads to apoptosis of osteosarcoma cells in vitro by selective inhibition of the PDGFR tyrosine kinase . The effectiveness of STI571 in our studies suggests targeting of PDGFRs as a novel treatment for osteosarcoma . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot87

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Onconase ( Onc ) is an amphibian ribonuclease of the pancreatic RNase family that is cytostatic and cytotoxic to several tumor lines . It also shows anti-tumor activity in mouse tumor models and is currently in phase III clinical trials . In animal tests and clinical trials Onc shows lesser toxicity and fewer side effects compared to most chemotherapeutic drugs . Intriguingly , repeated infusions of this protein do not cause apparent immunological reactions in patients . The aim of the present study was to investigate sensitivity to Onc of human lymphocytes during their mitogenic stimulation in response to the polyvalent mitogen phytohemagglutinin ( PHA ) , and in mixed allogeneic lymphocyte cultures . Unexpectedly , we observed that frequency of cells undergoing activation-induced apoptosis was markedly increased in all cultures containing Onc . Apoptosis was measured by flow cytometry using markers that detect activation of caspases , the in situ presence of DNA strand breaks , and loss of fragmented DNA ( 'sub-G1 ' cell subpopulation ) . The enhancement of frequency of activation-induced apoptosis ( up to 244% ) was observed at 4.2-83 nM Onc concentration , which is at least an order magnitude lower than its minimal concentration reported to affect proliferation or induce apoptosis of leukemic and solid tumor cell lines . The cell cycle progression of lymphocytes that responded to PHA mitogenically was not affected at 8.3 or 83 nM Onc concentration . Because activation-induced apoptosis is the key mechanism regulating several in vivo immunological functions including induction of tolerance , the observed effects of Onc may explain the apparent lack of immune reactions to this protein in treated patients . The propensity of Onc to potentiate the activation-induced apoptosis suggests that this drug may have clinical utility as immunomodulating agent , e.g. , to suppress transplant rejection or treat autoimmune diseases . OUTPUT:

resisting cell death;avoiding immune destruction

HoC_1shot88

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 studied whether feeding pregnant female rats different high fat diets affects structural zones in the spleen and lymph nodes , involved in production of T and B cells , as well as cell kinetics and apoptosis in some offspring with mammary glands tumors . Rat mothers were fed either a 7% or 15% corn-oil or a 7% or 15% olive-oil diet . At four weeks of age , female offspring ( n=10-15 per group ) were transferred to 7% corn oil diet . Five-week old offspring were exposed twice to the carcinogen , dimethylbenz(a)antracene ( 10 mg/rat/week ) . Three months later , tumors were counted and sized , and samples from the spleen , axillary lymph nodes and tumors collected for immunohistochemical analyses . Feeding the mothers with both the 7% and 15% olive-oil diets significantly increased the number of tumor-free rats in offspring . Tumors were characterized with active mitosis , intensive lymphoid infiltration inside a knot and high rates of apoptosis , particularly in tumors obtained from rats whose mothers were fed the 15% olive-oil diet . In the spleen , the 15% olive-oil diet significantly increased the areas of the follicles and germinal centers but only in tumor-free rats . In tumor-bearing rats , areas of germinal centers increased compared to the 7% olive-oil diet . The 15% olive-oil diet increased all areas of the lymph nodes in tumor-free rats , while in tumor-bearing rats , this diet increased the areas of the cortex and mantle layer . We conclude that exposure to various diets in utero and during lactation affects the immune system . In addition , the promotion of apoptosis may play a key role in the mechanisms involved in the transplacental effects on mammary tumor development as seen using a 15% olive-oil diet , similar to the high fat diets of Mediterranean countries . OUTPUT:

resisting cell death;avoiding immune destruction

HoC_1shot89

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Annexin II is secreted into the extracellular environment , where , via interactions with specific proteases and extracellular matrix proteins , it participates in plasminogen activation , cell adhesion , and tumor metastasis and invasion . However , mechanisms regulating annexin II transport across the cellular membrane are unknown . In this study , we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 ( IGF-1 ) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin ( NIH-3T3(IR) ) or IGF-1 receptor ( NIH-3T3(IGF-1R) ) . Stimulation of insulin and IGF-1 receptors by insulin caused a temporary dissociation of annexin II from these receptors , which was accompanied by an increased amount of extracellular annexin II detected in the media of PC12 , NIH-3T3(IR) , and NIH-3T3(IGF-1R) cells but not in that of untransfected NIH-3T3 cells . Activation of a different growth factor receptor , the platelet-derived growth factor receptor , did not produce such results . Tyrphostin AG1024 , a tyrosine kinase inhibitor of insulin and IGF-1 receptor , was shown to inhibit annexin II secretion along with reduced receptor phosphorylation . Inhibitors of a few downstream signaling enzymes including phosphatidylinositol 3-kinase , pp60c-Src , and protein kinase C had no effect on insulin-induced annexin II secretion , suggesting a possible direct link between receptor activation and annexin II secretion . Immunocytochemistry revealed that insulin also induced transport of the membrane-bound form of annexin II to the outside layer of the cell membrane and appeared to promote cell aggregation . These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion . OUTPUT:

sustaining proliferative signaling

HoC_1shot90

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma . Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism . A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin ( AFB1-albumin adducts ) . A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan , were employed in this study . Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay , hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay , as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction . The detection rate of AFB1-albumin adducts was significantly higher in males ( 42.5% ) than in females ( 21.6% ) ( multivariate-adjusted odds ratio=2.6 , 95% confidence interval=1.4-5.0 ) . The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers ( 42.8% ) than in non-carriers ( 36.6% ) ( multivariate-adjusted odds ratio=1.4 , 95% confidence interval=1.0-2.1 ) . In addition , the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1 . In conclusion , this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population . This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection . OUTPUT:

genomic instability and mutation

HoC_1shot91

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 large number of human cancers display alterations in the Ink4a/cyclin D/Cdk4 genetic pathway , suggesting that activation of Cdk4 plays an important role in oncogenesis . Here we report that Cdk4-null mouse embryonic fibroblasts are resistant to transformation in response to Ras activation with dominant-negative ( DN ) p53 expression or in the Ink4a/Arf-null background , judged by foci formation , anchorage-independent growth , and tumorigenesis in athymic mice . Cdk4-null fibroblasts proliferate at normal rates during early passages . Whereas Cdk4(+/+)Ink4a/Arf(-/-) cells are immortal in culture , Cdk4(-/-)Ink4a/Arf(-/-) cells undergo senescence during continuous culture , as do wild-type cells . Activated Ras also induces premature senescence in Cdk4(-/-)Ink4a/Arf(-/-) cells and Cdk4(-/-) cells with DNp53 expression . Thus , Cdk4 deficiency causes senescence in a unique Arf/p53-independent manner , which accounts for the loss of transformation potential . Cdk4-null cells express high levels of p21(Cip1/Waf1) with increased protein stability . Suppression of p21(Cip1/Waf1) by small interfering RNA ( siRNA ) , as well as expression of HPV-E7 oncoprotein , restores immortalization and Ras-mediated transformation in Cdk4(-/-)Ink4a/Arf(-/-) cells and Cdk4(-/-) cells with DNp53 expression . Therefore , Cdk4 is essential for immortalization , and suppression of Cdk4 could be a prospective strategy to recruit cells with inactive Arf/p53 pathway to senescence . OUTPUT:

enabling replicative immortality

HoC_1shot92

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Alterations of the epidermal growth factor receptor ( EGFR ) gene are common in some forms of cancer and the most frequent is a deletion of exons 2-7 . We have previously shown that this mutant receptor , called DeltaEGFR , confers enhanced tumorigenicity to glioblastoma cells through elevated proliferation and reduced apoptotic rates of the tumor cells in vivo . To understand the molecular mechanisms that underlie DeltaEGFR-enhanced proliferation , we examined the gene products that control cell cycle progression . We found that levels of the cyclin-dependent kinase ( CDK ) inhibitor , p27 , were lower in U87MG.DeltaEGFR tumors than in parental U87MG or control U87MG.DK tumors . Consequently , CDK2-cyclin A activity was also elevated , concomitant with the RB protein hyperphosphorylation . In addition , activated phosphatidylinositol 3-kinase ( PI3-K ) and phosphorylated Akt levels were also elevated in the U87MG.DeltaEGFR tumors . U87MG.DeltaEGFR cells failed to arrest in G(1) in response to serum starvation in vitro and while maintaining high levels of PI3-K activity and hyperphosphorylated RB . Treatment of U87MG.DeltaEGFR cells with LY294002 , a PI3-K inhibitor , caused reduced levels of phosphorylated Akt and concomitantly up-regulated levels of p27 . Expression of a kinase dead dominant-negative Akt mutant in the U87MG.DeltaEGFR cells similarly resulted in up-regulation of p27 and down-regulation of tumorigenicity in vivo . These results suggest that the constitutively active DeltaEGFR can enhance cell proliferation in part by down-regulation of p27 through activation of the PI3-K/Akt pathway . This pathway may represent another therapeutic target for treatment of those aggressive glioblastomas expressing DeltaEGFR . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot93

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Whole body hyperthermia ( WBH ) has been used as an adjunct to radio-/chemotherapy in patients with various malignant diseases . Although clear evidence is still missing , it has been hypothesized that an activation of the immune system might contribute to the therapeutic effect of WBH . To examine whether a treatment with 60-minute 41.8 degrees C WBH as an adjunct to chemotherapy ( WBH-CT ) induces an activation of T cells , blood samples were collected at numerous time points before and up to 48 h post-treatment . The aim of this study was to examine the effect of WBH-CT on the expression of a broad range of activation markers on peripheral blood lymphocytes ( PBL ) , on serum cytokines and intracellular cytokine levels in T cells , and the capacity of these cells to proliferate . Immediately after 41.8 degrees C WBH-CT treatment , a drastic increase in peripheral natural killer ( NK ) cells ( P<0.05 ) and CD56+ cytotoxic T lymphocytes ( CTL ; P<0.01 ) in the patients ' peripheral blood was observed . At 5 h post-treatment , the percentages of both effector cell types had returned to baseline levels . This transient phenomenon was accompanied by a short period of reduced T cell activity , indicated by diminished serum levels of soluble interleukin-2 receptors ( sIL-2R ) at 3 h post-WBH-CT ( P<0.05 ) and decreased lymphocytic proliferation at the same point in time . This first phase was followed by a marked but short-lived increase in the patients ' serum levels of interleukin-6 ( IL-6 ; P<0.01 ) during the first 5 h following treatment , with a subsequent decrease to baseline levels at 24 h and significantly increased serum levels of tumor necrosis factor-alpha ( TNF-alpha ) at 0 h ( P<0.01 ) , 3 h ( P<0.05 ) , 5 h ( P<0.05 ) and 24 h ( P<0.01 ) post-WBH-CT . The third phase of the immunological consequences of WBH-CT consisted of an increase in the percentage of peripheral cytotoxic T lymphocytes ( CTL ) expressing CD56 , reaching a maximum at 48 h post-WBH ( P<0.01 ) . Furthermore , the percentage of CD4+ T cells expressing the T cell activation marker CD69 increased nearly two-fold over time , reaching its maximum at 48 h ( P<0.05 ) . As an additional marker for T cell activation , serum levels of sIL-2R increased markedly ( P<0.01 ) , reaching maximum levels at the same point in time . Elevated intracellular concentrations of interferon-gamma ( IFN-gamma ) and/or TNF-alpha in CD8+ T cells were found in 4 out of 5 patients at 24 h post-WBH-CT . Since similar changes were not observed in patients receiving chemotherapy alone , this is the first study to provide evidence for prolonged WBH-CT-induced activation of human T cells . OUTPUT:

avoiding immune destruction

HoC_1shot94

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 To investigate the progressive transformation of immortal cells of human fetal esophageal epithelium induced by human papillomavirus , and to examine biological criteria of sequential passage of cells , including cellular phenotype , proliferative rate , telomerase , chromosome and tumorigenicity . METHODS The SHEE cell series consisted of immortalized embryonic esophageal epithelium which was in malignant transformation when cultivated over sixty passages without co-carcinogens . Cells of the 10th , 31st , 60th and 85th passages were present in progressive development after being transfected with HPV . Cells were cultivated in a culture flask and 24-hole cultural plates . Progressive changes of morphology , cell growth , contact-inhibition , and anchorage-dependent growth characteristics were examined by phase contrast microscopy . The cell proliferation rate was assayed by flow cytometry . The modal number of chromosomes was analyzed . HPV18E(6)E(7) was detected by Western blot methods and activities of telomerase were analyzed by TRAP . Tumorigenicity of cells was detected with soft agar plates cultivated and with tumor formation in SCID mice . RESULTS In morphological examination the 10th passage cells were in good differentiation , the 60th and 85th passages cells were in relatively poor differentiation , and the 31st passage cells had two distinct differentiations . The characteristics of the 85th and 60th passage cells were weakened at contact-inhibition and anchorage-dependent growth . Karyotypes of four stages of cells belonged to hyperdiploid or hypotriploid , and bimodal distribution of chromosomes appeared in the 31st and 60th passage cells . All of these characteristics combined with a increasing trend . The activities of telomerase were expressed in the latter three passages . Four fourths of SCID mice in the 85th passage cells and one fourth of SCID mice in the 60th passage cells developed tumors , but the cells in the 10th and 31st passage displayed no tumor formation . CONCLUSION In continual cultivation of fetal esophageal epithelial cells with transduction of HPV18E(6)E(7) , cells from the 10th to the 85th passage were changed gradually from preimmortal , immortal , precancerous to malignantly transformed stages . All of these changes were in a dynamic progressive process . The establishment of a continuous line of esophageal epithelium may provide a in vitro model of carcinogenesis induced by HPV . OUTPUT:

evading growth suppressors;enabling replicative immortality

HoC_1shot95

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 report the formation , detection , quantitation and structural characterization of products resulting from the adduction of deoxynucleosides ( deoxyadenosine , deoxyguanosine , deoxycytidine and 5-methyldeoxycytidine ) to the catechol estrogens ( CE ) of estrone , estradiol-17beta and estradiol-17 alpha . The crude products are obtained in a one-pot synthesis through oxidation of catechols to quinones and subsequent Michael-type reaction with the deoxynucleosides in acidic medium . In all experiments , adducts are detected by electrospray ionization mass spectrometry analysis after HPLC separation ( LC/ESI/MS(n) ) . The two pyrimidines deoxycytidine and 5-methyldeoxycytidine yield only CE adducts to deoxynucleosides , which correspond to stable adducts on DNA . For purines , the results depend on the CE ( 2,3- or 3,4-catechols ) used , the function and configuration on carbon 17 ( ketone for estrone , alcohol for alpha and beta isomers of estradiol ) , and on the purine itself ( deoxyadenosine or deoxyguanosine ) . Both stable adducts and deglycosylated adducts are formed , and therefore formation of stable adducts on DNA as well as the loss of purines from the DNA strands could be possible . MS(2) and MS(3) experiments prove to be relevant for further structural determinations , enabling in some cases the elucidation of the regiochemistry of adduction on the A and B rings of the steroid moiety . OUTPUT:

genomic instability and mutation

HoC_1shot96

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Triggering tumor necrosis factor receptor-1 ( TNFR1 ) induces apoptosis in various cell lines . In contrast , stimulation of TNFR1 in L929sA leads to necrosis . Inhibition of HSP90 , a chaperone for many kinases , by geldanamycin or radicicol shifted the response of L929sA cells to TNF from necrosis to apoptosis . This shift was blocked by CrmA but not by BCL-2 overexpression , suggesting that it occurred through activation of procaspase-8 . Geldanamycin pretreatment led to a proteasome-dependent decrease in the levels of several TNFR1-interacting proteins including the kinases receptor-interacting protein , inhibitor of kappa B kinase-alpha , inhibitor of kappa B kinase-beta , and to a lesser extent the adaptors NF-kappaB essential modulator and tumor necrosis factor receptor-associated factor 2 . As a consequence , NF-kappa B , p38MAPK , and JNK activation were abolished . No significant decrease in the levels of mitogen-activated protein kinases , adaptor proteins TNFR-associated death domain and Fas-associated death domain , or caspase-3 , -8 , and -9 could be detected . These results suggest that HSP90 client proteins play a crucial role in necrotic signaling . We conclude that inhibition of HSP90 may alter the composition of the TNFR1 complex , favoring the caspase-8-dependent apoptotic pathway . In the absence of geldanamycin , certain HSP90 client proteins may be preferentially recruited to the TNFR1 complex , promoting necrosis . Thus , the availability of proteins such as receptor-interacting protein , Fas-associated death domain , and caspase-8 can determine whether TNFR1 activation will lead to apoptosis or to necrosis . OUTPUT:

resisting cell death

HoC_1shot97

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Genomic instability has long been recognized as the main feature of neoplasia and a factor modulating individual cancer susceptibility . There are attempts to find effective assays of both individual DNA repair capacity and genetic instability , and their relation to the cancer risk . Genetic predisposition plays an important role in the etiology and development of head and neck squamous cell carcinoma ( HNSCC ) . The aim of our study was to search for a correlation between chromosomal instability and DNA repair capacity in HNSCC patients and healthy controls . The chromosomal instability was measured by the number of bleomycin ( BLM)-induced chromosomal aberrations and diepoxybutane ( DEB)-induced sister chromatid exchanges . The DNA repair capacity was assessed using the DEB-induced adaptive response ( AR ) . The HNSCC patients in our study showed a significant increase in chromosomal instability after a preterminal exposure of their lymphocytes to either BLM for the last 5 h or DEB for the last 24 h of incubation . However , the AR was higher in HNSCC patients than in the control group , suggesting an increase in the DNA repair capacity in the cancer patients as compared to the control . There is no correlation between the DNA repair capacity estimated on the basis of preterminal exposures to BLM and DEB and the DNA repair capacity estimated on the basis of the adaptive response to DEB . The preterminal exposure and the adaptive response test may activate different DNA repair mechanisms . OUTPUT:

genomic instability and mutation

HoC_1shot98

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Deregulation of D-type cyclin-dependent kinases ( CDK4 and 6 ) is widely observed in various human cancers , illustrating their importance in cell cycle control . Like other cyclin-dependent kinases ( CDKs ) , assembly with cyclins is the most critical step for activation of CDK4/6 . As previously reported elsewhere , we observed that the level of cyclinD1-CDK4 complex and its associated kinase activity were significantly low in asynchronously proliferating mouse embryo fibroblasts lacking both p21(Cip1) and p27(Kip1) ( p21/p27-null MEFs ) . These evidences imply that p21(Cip1) and p27(Kip1) CDK inhibitors are ' essential activators ' of cyclin D-kinases . We , however , discovered here that both the assembly and activation of cyclin D1-CDK4 complex occur when quiescent p21/p27-null MEFs were stimulated to re-enter the cell cycle . This mitogen-induced cyclin D1-kinase activity was blocked by overexpression of p16(INK4a) and resulted in the inhibition of S phase entry in p21/p27-null MEFs . Furthermore , ectopic expression of p34(SEI-1) , a mitogen-induced CDK4 binding protein , increased the levels of active cyclinD1-CDK4 complex in asynchronously proliferating p21/p27-null MEFs . Together , our results suggest that there are several independent ways to stimulate the assembly of cyclin D1-CDK4 kinases . Although p21(Cip1) and p27(Kip1) play a role in this process , our results demonstrate that additional mechanisms must occur in G0 to S phase transition . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot99

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Rho GTPases are signaling molecules known to control cell motility . Several recent studies have suggested a role for Rho proteins in mediating tumor metastasis independent of their affects on cell proliferation . As Rho proteins require post-translational modification with a geranlygeranyl moiety for full activity , we tested the affect of blocking geranylation on localization , downstream signaling , and stimulation of invasion . Expression of a constitutively active Rho construct in A375 melanoma cells dramatically stimulated invasion through Matrigel membranes ; however , a constitutively active RhoA mutated so that it cannot be geranylated , failed to stimulate invasion . Moreover , expression of epitope or GFP tagged modifications of this nongeranylatable constitutively active Rho demonstrated that geranylation is necessary for correct cellular localization of Rho . Geranylation was also found to be necessary for full downstream activation of serum response factor mediated transcription . Pharmacologic inhibition of Rho geranylation produced similar inhibition of Rho localization , signaling , and invasion . Our results suggest that inhibition of Rho geranylation may be an attractive pharmacologic target for inhibiting melanoma metastasis . OUTPUT:

activating invasion and metastasis