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hippocrates

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HoC_1shot_train

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[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: INTRODUCTION Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with estrogen receptor ( ER)-positive breast cancer . However , there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner . METHODS In this study we assessed gene expression changes at multiple time points ( days 1 , 2 , 4 , 7 , 14 ) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis , proliferation and angiogenesis within 2 days of therapy . RESULTS Hierarchical clustering identified six time-related gene expression patterns , which separated into three groups : two with early/transient responses , two with continuous/late responses and two with variable response patterns . The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation ( e.g . BUB1B , CCNA2 , CDKN3 , MKI67 , UBE2C ) , whereas the continuous/late changed genes represented the more classical estrogen response genes ( e.g . TFF1 , TFF3 , IGFBP5 ) . Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer . The profiles of genes that were most differentially expressed on days 2 , 4 and 7 following treatment were able to predict prognosis , whereas those most changed on days 1 and 14 were not , in four tamoxifen treated datasets representing a total of 404 patients . CONCLUSIONS Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner . Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The Salvador/Warts/Hippo ( Hippo ) signaling pathway defines a novel signaling cascade regulating cell contact inhibition , organ size control , cell growth , proliferation , apoptosis and cancer development in mammals . The upstream regulation of this pathway has been less well defined than the core kinase cassette . KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP , but functional consequences of these biochemical changes have not been previously addressed . We show that in MCF10A cells , loss of KIBRA expression displays epithelial-to-mesenchymal transition ( EMT ) features , which are concomitant with decreased LATS and YAP phosphorylation , but not MST1/2 . In addition , ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA , Willin and Merlin differentially regulate genes controlled by YAP . Finally , reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype , an aggressive sub-group with EMT features and a poor prognosis .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: AIMS To screen the genes and possible signal transduction pathways with which nucleostemin ( NS ) interacts and explore the mechanism of NS in prostate cancer . METHODS NS-specific short-hairpin RNA expression plasmid was used to downregulate the NS level in PC-3 cells and the changes of cell cycle were studied . After that , oligonucleotide DNA microarray was used to screen the genome changes in PC-3 cells and quantitative real-time PCR was used to further confirm the differentially expressed genes . RESULTS Detection of cell cycle showed a decrease of S stage and an increase of G1 stage after downregulation of NS. 219 differentially expressed genes were found and these genes were involved in cell cycle , cell proliferation , signal transduction , cell apoptosis and cell differentiation , and so on . Genes related to cell cycle were discussed emphatically . INK4 family genes ( P15 , P16 , P18 ) were upregulated while cyclin D1 HDAC1 were downregulated . These genes were tightly related to CDK4/6-cyclin D and pRb-E2F1 complexes . CONCLUSION NS is an important G1/S checkpoint regulator and it could regulate cell cycles via a p53-independent pathway in prostate cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Acrolein ( Acr ) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust . It can also be produced endogenously by oxidation of polyunsaturated fatty acids . The Acr-derived 1,N(2)-propanodeoxyguanosine ( Acr-dG ) adducts in DNA are mutagenic lesions that are potentially involved in human cancers . In this study , monoclonal antibodies were raised against Acr-dG adducts and characterized using ELISA . They showed strong reactivity and specificity toward Acr-dG , weaker reactivity toward crotonaldehyde- and trans-4-hydroxy-2-nonenal-derived 1,N(2)-propanodeoxyguanosines , and weak or no reactivity toward 1,N(6)-ethenodeoxyadenosine and 8-oxo-deoxyguanosine . Using these antibodies , we developed assays to detect Acr-dG in vivo : first , a simple and quick FACS-based assay for detecting these adducts directly in cells ; second , a highly sensitive direct ELISA assay for measuring Acr-dG in cells and tissues using only 1 μg of DNA without DNA digestion and sample enrichment ; and third , a competitive ELISA for better quantitative measurement of Acr-dG levels in DNA samples . The assays were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA , and the results were confirmed by LC-MS/MS-MRM . An immunohistochemical assay was also developed to detect and visualize Acr-dG in HT29 cells as well as in human oral cells . These antibody-based methods provide useful tools for the studies of Acr-dG as a cancer biomarker and of the molecular mechanisms by which cells respond to Acr-dG as a ubiquitous DNA lesion .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Urokinase-type plasminogen activator ( u-PA ) plays an important role in tumor growth and metastasis . The aim of this work was to study the u-PA production , in vitro and in vivo , in a transplantable murine mammary adenocarcinoma ( M3 ) , moderately metastatic to lung , and in a related tumor variant ( MM3 ) , highly metastatic to the same organ , during tumor development . At different times post-transplantation , tumors were employed to prepare either primary cell cultures or homogenates . PA activity from conditioned media ( CM ) , cell lysates ( CLs ) and tumor homogenates ( THs ) was quantitated by means of a fibrinolytic assay . Immunoneutralization and zymographic assays were performed to identify the PA present in both tumors . PA activity in CM , CLs and THs , that was undetectable at early stages , increased significantly along the growth of M3 adenocarcinoma . Secreted PA activity in MM3 CM was measurable at early stages and consistently increased up to 37 days post-transplantation , but a marked fall of activity was found at 48 days . PA activity in MM3 THs exhibited the same enhancement and late fall found in vitro . A positive correlation was observed between tumor size and THs PA values in both tumors . The PA present in cell cultures and THs was identified as of the u-PA type . These results support the hypothesis that high u-PA levels are important for tumor invasion and that the stage of tumor development is a critical factor in their PA activity .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Radix of Asiasarum heterotropoides var. mandshuricum F. Maekawa ( A. radix ) has been prescribed for treating pain , allergies and inflammatory disorders in traditional oriental medicine . However , only limited information on the anticancer effects of A. radix is currently available . The aim of this study was to determine the anticancer effect of the ethanol extract of A. radix ( EEAR ) on HCT-116 human colon cancer cells and to investigate its underlying mechanisms of action . EEAR significantly induced G2/M cell cycle arrest and apoptosis in HCT-116 cells . EEAR-induced apoptosis was observed in parallel with activation of caspases and an increased ratio of Bax ( pro-apoptotic)/Bcl2 ( anti-apoptotic ) . Western blot analyses revealed that EEAR elevated the expression of p53 and p21(Waf/Cip1) and decreased the expression of the regulator proteins of G2/M phase progression , such as cdc2 and cyclin B. The upregulation of p53 by EEAR was due to the increased levels of p53 mRNA without a similar increase in proteasome-mediated p53 degradation . EEAR-induced apoptosis in HCT-116 cells was dependent on p53 expression , as determined by siRNA-mediated p53 knockdown . Taken together , these results suggest that EEAR inhibits the growth of the HCT-116 cells through induction of G2/M cell cycle arrest and apoptosis , which are mediated by p53 expression .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The epidermal growth factor receptor ( EGFR ) is a member of the HER family receptors and its activation induced by its natural ligand EGF results in colon cancer growth and progression . Panitumumab ( pmAb ) is a fully human IgG2 anti-EGFR antibody that blocks the EGFR actions . In the present study , we evaluated the effects of pmAb on the EGF-mediated cellular responses in a panel of colon cancer cells ( HCT-8 , HT-29 , DLD-1 and HCT-116 ) . HCT-1116 and DLD-1 cells showed no significant EGF-dependent cell proliferation ; HT-29 and HCT-8 exhibited an EGF-dependent proliferation , with HCT-8 cells to be the most responsive with significant EGFR phosphorylation upon treatment with EGF . The effects of pmAb were then evaluated in the most EGF-responsive cells , HCT-8 . In that respect , pmAb impedes the signaling cascade mediated by EGFR intracellular phosphorylation and activity of focal adhesion kinase ( FAK ) as well as the EGF-induced invasive and migratory potential of colon cancer cells . At the level of matrix effectors implicated in colon cancer progression we report that pmAb is a potent inhibitor of constitute and EGF-mediated gene expression of certain matrix effectors , such as membrane-type 1 metalloproteinase ( MT1-MMP ) , extracellular metalloproteinases inducer ( EMMPRIN ) , urokinase plasminogen activator ( uPA ) and syndecan-4 . The obtained data demonstrated that pmAb is a specific blocker of EGF-mediated EGFR activation , resulting in a significant inhibition of colon cancer cell proliferation in early stages of growth , migration and invasiveness as well as of matrix effector implicated in cancer progression .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Placental Growth Factor ( PGF ) is a key molecule in angiogenesis . Several studies have revealed an important role of PGF primarily in pathological conditions ( e.g. : ischaemia , tumour formation , cardiovascular diseases and inflammatory processes ) suggesting its use as a potential therapeutic agent . However , to date , no information is available regarding the genetics of PGF variability . Furthermore , even though the effect of environmental factors ( e.g. : cigarette smoking ) on angiogenesis has been explored , no data on the influence of these factors on PGF levels have been reported so far . Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors : a study sample from two isolated villages in the Cilento region , South Italy ( N=871 ) and a replication sample from the general Danish population ( N=1,812 ) . A significant difference in PGF mean levels was found between the two cohorts . However , in both samples , we observed a strong correlation of PGF levels with ageing and sex , men displaying PGF levels significantly higher than women . Interestingly , smoking was also found to influence the trait in the two populations , although differently . We have then focused on genetic risk factors . The association between five single nucleotide polymorphisms ( SNPs ) located in the PGF gene and the plasma levels of the protein was investigated . Two polymorphisms ( rs11850328 and rs2268614 ) were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample . These results , for the first time , support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Trabecular meshwork ( TM ) cells have widely been used as an invitro model for glaucoma research . However , primary TM cells suffer the disadvantages of limited cell numbers and slow rates of proliferation . We discovered a spontaneously transformed bovine TM ( BTM ) cell line , BTM-28T . This cell line proliferated rapidly in low-glucose culture medium but also demonstrated contact inhibition in high-glucose culture medium . BTM-28T cells expressed key TM cell markers including α-smooth muscle actin ( α-SMA ) , laminin and collagen IV ( col IV ) . Also , 100nM dexamethasone ( DEX ) enhanced the formation of cross-linked actin networks ( CLANs ) in confluent BTM-28T cell cultures . Transforming growth factor beta 2 ( TGFβ2 ) induced the expression of fibronectin ( FN ) , plasminogen activator inhibitor-1 ( PAI-1 ) , and connective tissue growth factor ( CTGF ) in our cell cultures . This cell line will be helpful to better understand the aqueous humor outflow pathway as related to the pathophysiology of glaucoma .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The submandibular gland-derived tumor cell line SCA-9 is considered a useful tool to study the signaling pathways involved in proliferation , and their regulation , triggered by different stimuli . It is proposed that the non neuronal cholinergic system : acethylcholine , the enzymes that synthesize and degrade it , and the nicotinic and muscarinic receptors , play a key role in tumorigenesis . Here , we investigate the role of muscarinic receptors in SCA-9 cell proliferation , and the modulation of cholinergic signaling pathways exerted by the nuclear transcription factor κB ( NF-κB ) . The activation of cholinergic receptors by carbachol ( 10⁻⁹M ) increased cell proliferation ( P<0.001 ) . This was prevented by preincubating cells with the muscarinic antagonist atropine but not by mecamylamine , a nicotinic receptor blocker . Phospholipase C ( PLC)/nitric oxide synthase ( NOS)/arginase pathway is involved in this effect , since carbachol stimulated nitric oxide production , increased NOS2 and NOS3 expressions , urea production , and arginase II expression ( P<0.001 ) . Also , phospholipase A₂ ( PLA₂)/cyclooxygenase ( COX ) pathway is up-regulated in carbachol-induced SCA-9 cell proliferation , because prostaglandin E₂ liberation ( P<0.001 ) is increased and COX-1 expression is turned up ( P<0.001 ) . Interactions between PLC/NOS/arginases and PLA₂/COX pathways via its metabolites were detected . SCA-9 cells exhibit a constitutive activation of NF-κB , which regulates carbachol-induced NOS2 and 3 , arginase II and COX-1 expressions . In addition , protein kinase C is involved in the up-regulation of NOS2 and arginase II enzymes induced by carbachol via NF-κB . In conclusion , the activation of cholinergic receptors in SCA-9 tumor cells promotes proliferation via muscarinic effector enzymes , and reveals the participation of NF-κB at this step of tumorigenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The cellular mechanisms of anti-androgen-induced tumor regression have not been investigated in great detail . We have compared the induction of cell death in the androgen-dependent , non-invasive LNCaP prostate cancer cell line by Casodex and TNF-alpha . Both agents induce a dose and time-dependent decrease in cell viability in vitro . However , Casodex does not induce classical DNA fragmentation to oligonucleosomes typically induced by TNF-alpha , but rather induces cleavage to form intermediate 60 kb DNA fragments . RT-PCR based analysis demonstrates that in LNCaP cells Casodex coordinately alters the expression of steady-state level of mRNAs of several matrix metalloproteases and their cognate inhibitors ( most notably MMP2 and TIMP1 ) . Zymography and reverse zymography confirm that the ratio of metalloprotease(s) to inhibitor(s) is altered in favor of activation of the proteases . In a small percentage of the treated LNCaP cells , the activation of the extracellular matrix ( ECM)-proteases by Casodex also induces an invasive phenotype . The acquisition of an invasive phenotype is not seen when LNCaP cells are treated with TNF-alpha , and is not seen when the LNCaP cells are treated with both compounds simultaneously , suggesting that the phenomenon may be specific to particular classes of compounds . These observations have significant implications in the treatment of prostate cancer , since the appearance of a more aggressive phenotype following treatment is clearly undesirable .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PURPOSE Pyruvate kinase isoenzyme M2 ( PKM2 ) is a key enzyme in aerobic glycolysis ; inhibition of PKM2 leads to the tumor growth inhibition . In this study , the effects of combined treatment with cisplatin ( DDP ) and a plasmid that expresses a short hairpin RNA ( shRNA ) targeting PKM2 on the growth of human A549 xenograft lung cancer model were investigated . METHODS The expression of PKM2 in A549 cells was determined by immunofluorescence . PKM2 expression levels were evaluated by Western blot analysis . In a human A549 lung cancer xenograft model , the effects of treatment with shRNA , with or without cisplatin , on tumor volume were determined . Apoptosis and cell proliferation status were examined to determine the mechanisms of tumor growth inhibition . RESULTS Expression of shRNA targeting PKM2 resulted in inhibition of PKM2 expression in A549 cells . In the lung cancer xenograft model , average tumor volume in the group treated with both cisplatin and shRNA was statistically lower than those of other groups ( P &lt ; 0.05 ) . The levels of apoptotic cells were significantly higher in samples from animals in the combined treatment group than those from untreated animals ( P &lt ; 0.05 ) . The cell proliferation rate , as determined by counting cells labeled with an anti-phospho-histone H3 , a marker for mitosis , was lower in samples from animals treated with both cisplatin and shRNA than in samples from other groups ( P &lt ; 0.05 ) . CONCLUSIONS Use of RNA interfering ( RNAi ) targeting PKM2 significantly inhibited tumor growth when combined with cisplatin in a human A549 lung cancer xenograft model . The enhanced antitumor activity of the combined treatment compared to treatment with shRNA alone may result in part from increased induction of apoptosis and augmented inhibition of cancer cell proliferation .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Widespread changes in gene expression drive tumorigenesis , yet our knowledge of how aberrant epigenomic and transcriptome profiles arise in cancer cells is poorly understood . Here , we demonstrate that metabolic transformation plays an important role . Butyrate is the primary energy source of normal colonocytes and is metabolized to acetyl-CoA , which was shown to be important not only for energetics but also for HAT activity . Due to the Warburg effect , cancerous colonocytes rely on glucose as their primary energy source , so butyrate accumulated and functioned as an HDAC inhibitor . Although both mechanisms increased histone acetylation , different target genes were upregulated . Consequently , butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring , whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect . These findings link a common metabolite to epigenetic mechanisms that are differentially utilized by normal and cancerous cells because of their inherent metabolic differences .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Chromosomal DNA must be in single-strand form for important transactions such as replication , transcription , and recombination to occur . The single-strand DNA ( ssDNA ) is more prone to damage than double-strand DNA ( dsDNA ) , due to greater exposure of chemically reactive moieties in the nitrogenous bases . Thus , there can be agents that damage regions of ssDNA in vivo while being inert toward dsDNA . To assess the potential hazard posed by such agents , we devised an ssDNA-specific mutagenesis reporter system in budding yeast . The reporter strains bear the cdc13-1 temperature-sensitive mutation , such that shifting to 37°C results in telomere uncapping and ensuing 5 ' to 3 ' enzymatic resection . This exposes the reporter region , containing three closely-spaced reporter genes , as a long 3 ' ssDNA overhang . We validated the ability of the system to detect mutagenic damage within ssDNA by expressing a modified human single-strand specific cytosine deaminase , APOBEC3G . APOBEC3G induced a high density of substitutions at cytosines in the ssDNA overhang strand , resulting in frequent , simultaneous inactivation of two reporter genes . We then examined the mutagenicity of sulfites , a class of reactive sulfur oxides to which humans are exposed frequently via respiration and food intake . Sulfites , at a concentration similar to that found in some foods , induced a high density of mutations , almost always as substitutions at cytosines in the ssDNA overhang strand , resulting in simultaneous inactivation of at least two reporter genes . Furthermore , sulfites formed a long-lived adducted 2'-deoxyuracil intermediate in DNA that was resistant to excision by uracil-DNA N-glycosylase . This intermediate was bypassed by error-prone translesion DNA synthesis , frequently involving Pol ζ , during repair synthesis . Our results suggest that sulfite-induced lesions in DNA can be particularly deleterious , since cells might not possess the means to repair or bypass such lesions accurately .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: To examine the association of cell cycle regulatory gene inactivation with human cell immortalization , we determined the expression status of INK4a , Rb , and WAF1/ CIP1 , in eleven in vitro immortalized human cell lines , including fibroblasts and keratinocytes . Two human papillomavirus type 16 E6 expressing cell lines with telomerase activity , including a fibroblast cell line and a keratinocyte cell line , expressed no detectable p16(INK4a) . These cell lines had a hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1) . All of seven fibroblast cell lines immortalized either spontaneously or by ( 60)Co , X-rays , 4-nitroquinoline 1-oxide or aflatoxin B(1) , maintaining their telomeres by the ALT ( alternative lengthening of telomeres ) pathway , displayed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . Levels of p21(WAF1/CIP1) expression varied among the cell lines . Two fibroblast cell lines that became immortalized following infection with a retrovirus vector encoding human telomerase catalytic subunit ( hTERT ) cDNA were also accompanied by inactivation of p16(INK4a) and pRb pathways . Acquisition of telomerase activity alone was not sufficient for immortalization of these cell lines . Taken together , all the cell lines including fibroblasts and keratinocytes , with either telomerase activity or the ALT pathway for telomere maintenance showed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . These demonstrate the association of inactivation of both p16(INK4a) and pRb with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Polymorphisms in DNA repair genes are associated with ability to remove DNA lesions , and therefore may contribute to an individual's susceptibility to different types of cancer . Base excision repair ( BER ) , and nucleotide excision repair ( NER ) are the main DNA repair pathways . The present study was conducted to determine the frequency distribution of single nucleotide polymorphisms ( SNPs ) selected for genes in these two pathways i.e . OGG1 Exon 7 ( C1245G ) , XPC Intron 9 ( PAT ) , and Exon 15 ( A33512C ) in a North Indian population in comparison with global populations . METHODS Genotyping was achieved by PCR-based analysis in 224 normal healthy , unrelated individuals of similar ethnicity . RESULTS Allelic frequencies in wild type of OGG1 Exon 7 C>G were 73% ( C ) ; XPC PAT D>I 75% ( D ) ; and XPC Exon 15 A>C 60.71.9% A. On the other hand , the variant allele frequency were 27% ( G ) in OGG1 Exon 7 C>G ; 25% ( I ) in XPC PAT ; and 28.1% ( C ) in XPC Exon 15 A>C . Major differences from other ethnic populations were observed . CONCLUSIONS Our results suggest that frequency distribution in these DNA repair genes exhibited a distinctive pattern in our population which could be attributed to ethnic variation . This could assist in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: MicroRNAs ( miRNAs ) are small noncoding RNAs , 19-24 nucleotides in length , that regulate gene expression and are expressed aberrantly in most types of cancer . MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers . It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs . Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism , by binding as ligands to receptors of the Toll-like receptor ( TLR ) family , murine TLR7 and human TLR8 , in immune cells , triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis . Thus , by acting as paracrine agonists of TLRs , secreted miRNAs are key regulators of the tumor microenvironment . This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread , thus representing a possible target for cancer treatment .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Geraniol ( GOH ) , a naturally occurring monoterpene , has been shown to have antiproliferative , cell cycle arrest and apoptosis-inducing effects , and represents a promising cancer chemopreventive agent . In the present study , we investigated the chemopreventive potential of GOH ( 50 and 100 mg kg(-1) body weight ) against 7,12-dimethylbenz[a]anthracene ( DMBA)/12-O-tetradecanoylphorbol 13-acetate ( TPA)-mediated skin tumorigenesis in Swiss albino mice . The topical treatment of GOH , 30 min prior to TPA ( 2 µg per 200 µl of acetone ) treatment significantly inhibited TPA-induced skin edema , hyperplasia , COX-2 induction and oxidative stress response . The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [ (3) H ] thymidine incorporation by 53% ( P < 0.001 ) and 41% ( P < 0.001 ) , respectively . We found that GOH treatment significantly inhibited the tumor incidence and number of tumors ( P < 0.001 ) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice . Furthermore , we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor . Consistently , GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions . Thus , it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Cholangiocarcinoma , a type of malignant tumor , originates from epithelial cells of the bile duct . Perineural invasion is common path for cholangiocarcinoma metastasis , and it is highly correlated with postoperative recurrence and poor prognosis . It has been reported that muscarinic acetylcholine receptor M3 ( mAChR M3 ) is widely expressed in digestive tract cancer , and may play an important role in the proliferation , differentiation , transformation and carcinogenesis of tumors . This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma . METHODS Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas ( 40 cases ) and normal bile duct tissues ( 9 ) , as well as to investigate nerve infiltration . The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation . The experimental data were analyzed by the Chi-square test . RESULTS The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated ( 69% , 9/13 ) than in well- and moderately-differentiated cholangiocarcinomas ( 30% , 8/27 ) ( X2=5.631 , P<0.05 ) . The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma ( 50% , 14/28 ) was higher than that in cholangiocarcinomas from the middle and lower common bile duct ( 25% , 3/12 ) ( X2=2.148 , P<0.05 ) . Cholangiocarcinomas with distant metastasis had a strongly-positive expression rate ( 75% , 9/12 ) , which was much higher than those without distant metastasis ( 29% , 8/28 ) ( X2=7.410 , P<0.01 ) . The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group . CONCLUSIONS The expression of mAChR M3 is influenced by the extent of differentiation , distant metastasis and the site of cholangiocarcinoma . It also plays a key role in the proliferation and metastasis of cholangiocarcinoma .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Sonodynamic therapy ( SDT ) has shown great potential in target cancer therapy , but it induced cell death modes hasn't been fully investigated . This study was to examine autophagic and apoptotic responses to protoporphyrin IX ( PpIX ) mediated SDT in murine leukemia L1210 cells . After SDT , the occurrence of autophagy was identified by morphological observation and biochemical analysis . Meanwhile , the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death . The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies , which indicated that impairment of autophagy enhanced the anti-tumor effect of SDT through induction of apoptosis and necrosis , while caspase inhibition didn't affect autophagic vacuoles formation or protect SDT induced cytotoxicity . The findings supported that autophagic vacuoles formed upstream and independently from caspase-dependent cell death . Additionally , the possible mechanism of SDT-induced autophagy was evaluated by measurement of ROS ( reactive oxygen species ) formation . Result suggested ROS play important role in initiating autophagy , possibly through the sono-damaged mitochondria being enclosed by autophagic vacuoles . All together , these data indicate that autophagy may be cytoprotective in our experimental system , and point to an important insight into how autophagy inhibitors , in combination with SDT may contribute a regimen for cancer therapy .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We investigated the effects of valproic acid ( VPA ) , a histone deacetylase inhibitor , in combination with hydralazine , a DNA methylation inhibitor , on the expression of cell-surface Fas and MHC-class I-related chain molecules A and B ( MICA and B ) , the ligands of NKG2D which is an activating receptor of NK cells , and on production of their soluble forms in HOS , U-2 OS and SaOS-2 human osteosarcoma cell lines . We also examined the susceptibility of these cells to Fas- and NK cell-mediated cell death . VPA did not increase the expression of Fas on the surface of osteosarcoma cells , while hydralazine did , and the combination of VPA with hydralazine increased the expression of cell-surface Fas . In contrast , the combination of VPA with hydralazine did not increase the production of soluble Fas by osteosarcoma cells . Both VPA and hydralazine increased the expression of cell-surface MICA and B in osteosarcoma cells , and their combination induced a greater increase in their expression . VPA inhibited the production of both soluble MICA and MICB by osteosarcoma cells while hydralazine produced no effect . Both VPA and hydralazine enhanced the susceptibility of osteosarcoma cells to Fas- and NK cell-mediated cell death and the combination of VPA with hydralazine further enhanced the effects . The present results suggest that combined administration of VPA and hydrazine is valuable for enhancing the therapeutic effects of immunotherapy for osteosarcomas .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid ( EPA ) are able to suppress cell proliferation and inhibit tumor growth . The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated ( Atm)-deficient mice , a genetic cancer model that is associated with increased levels of oxidative stress . We analyzed toxicity , proliferation , cell-cycle progression , and apoptosis of EPA in vitro and latency to tumorigenesis in vivo . Because of the impact of reactive oxygen species ( ROS ) on the tumor incidence in ataxia telangiectasia ( AT ) , we further analyzed the effect of EPA on the generation of ROS and oxidative DNA damage ( ODD ) . EPA effectively inhibited proliferation , altered cell-cycle progression , and induced apoptosis of tumor cells ( AT-4 ) . EPA showed no effect on the latency to tumorigenesis in Atm-deficient mice . EPA treatment was accompanied by a significant increase of ROS and ODD . Our results demonstrate the antiproliferative effect of EPA on tumor cells by alteration of cell-cycle progression and induction of apoptosis in vitro . On the other hand , EPA treatment of Atm-deficient mice led to the formation of ROS and accumulation of ODD that might have abrogated the anticarcinogenic effect caused by EPA .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We report a case of recurrent gastric cancer successfully treated by a combination of CPT-11 and CDDP as the third- line chemotherapy . A 78-year-old man with advanced gastric cancer underwent a curative distal gastrectomy . Three years later , the tumor marker level began to rise and computed tomography ( CT ) revealed lymph node metastasis invading the pancreas resulting in pancreatic duct dilatation . S-1 treatment was initiated but was discontinued because of a systemic exanthem . Paclitaxel was administrated as secondary chemotherapy . But , after 2 courses , a further increase in the tumor marker level and portal vein invasion were observed . Combination therapy of CPT-11 and CDDP was administered as the third-line chemotherapy . After 3 courses , the tumor marker level normalized , tumor size decreased , and the invasion was eliminated . Third-line chemotherapy against recurrent gastric cancer should be considered if patient performance status ( PS ) is maintained .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

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

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The DNA damage response ( DDR ) cascade and ROS ( reactive oxygen species ) signaling are both involved in the induction of cell death after DNA damage , but a mechanistic link between these two pathways has not been clearly elucidated . This study demonstrates that ROS induction after treatment of cells with neocarzinostatin ( NCS ) , an ionizing radiation mimetic , is at least partly mediated by increasing histone H2AX . Increased levels of ROS and cell death induced by H2AX overexpression alone or DNA damage leading to H2AX accumulation are reduced by treating cells with the antioxidant N-Acetyl-L-Cysteine ( NAC ) , the NADP(H) oxidase ( Nox ) inhibitor DPI , expression of Rac1N17 , and knockdown of Nox1 , but not Nox4 , indicating that induction of ROS by H2AX is mediated through Nox1 and Rac1 GTPase . H2AX increases Nox1 activity partly by reducing the interaction between a Nox1 activator NOXA1 and its inhibitor 14-3-3zeta . These results point to a novel role of histone H2AX that regulates Nox1-mediated ROS generation after DNA damage .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: It is well established that aberrant production of inflammatory mediators has been associated with most the toxic manifestations and the genesis of different chronic diseases including cancer . The basic aim of the present study is to investigate the effects of soy isoflavones ( SIF ) on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced cutaneous inflammatory responses and to explore the underlying molecular mechanisms . We have studied the protective effects of SIF against TPA induced oxidative stress , pro-inflammatory cytokines level , activation of NF-κB , expression of COX-2 and ki-67 in mouse skin . Animals were divided into five groups I-V ( n=6 ) . Groups II , III and IV received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day , for 2 days . Animals of the groups III and IV were pre-treated with SIF 1.0 μg ( D1 ) and 2.0 μg ( D2 ) topically 30 min prior to each TPA administration , while groups I and V were given acetone ( 0.2 ml ) and SIF ( D2 ) , respectively . We have found that SIF pretreatment significantly inhibited TPA induced oxidative stress , proinflammatory cytokines production and activation of NF-κB . SIF also inhibited the expression of COX-2 and ki-67 . Histological findings further supported the protective effects of SIF against TPA-induced cutaneous damage . Thus , our results suggest that inhibitory effect of SIF on TPA-induced cutaneous inflammation includes inhibition of proinflammatory cytokines , attenuation of oxidative stress , activation of NF-κB and expression of COX-2 .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PURPOSE Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration ( AMD ) enables sensitive use of antiangiogenic drugs and reduces adverse side effects . So far , no in vivo imaging methods are available to specifically label active angiogenesis . Here , we report such a technique using fluorophore-labeled cationic liposomes ( CL ) detected with a standard clinical in vivo scanning laser ophthalmoscope ( SLO ) . METHODS C57Bl/6 mice underwent laser coagulations at day 0 ( d0 ) to induce choroidal neovascularization ( CNV ) . Liposomes labeled with Oregon green , rhodamine ( Rh ) , or indocyanine green ( ICG ) were injected into the tail vein at various time points after laser coagulation , and their fluorescence was observed in vivo 60 min later using an SLO , or afterwards in choroidal flatmounts or cryosections . RESULTS SLO detected accumulated fluorescence only in active CNV lesions with insignificant background noise . The best signal was obtained with CL-ICG . Choroidal flatmounts and cryosections of the eye confirmed the location of retained CL in CNV lesions . Neutral liposomes , in contrast , showed no accumulation . CONCLUSIONS These results establish fluorophore-labeled CL as high affinity markers to selectively stain active CNV . This novel , non-invasive SLO imaging technique could improve risk assessment and indication for current intraocular antiangiogenic drugs in neovascular eye diseases , as well as monitor therapeutic outcomes . Labeling of angiogenic vessels using CL can be of interest not only for functional imaging in ophthalmology but also for other conditions where localization of active angiogenesis is desirable .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer . We examined peripheral blood lymphocyte ( PBL ) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma ( mRCC ) who received combined treatment with IL-2 , interferon-?-2a and dendritic cell vaccine . We examined gene expression , cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry ( FCM ) . Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors ( HD ) . PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways , which was also reflected in lymphocyte subset distribution . Overall , PBL gene expression post-treatment ( POST ) was not significantly different than pre-treatment ( PRE ) . Nevertheless , treatment related changes in gene expression ( post-treatment minus pre-treatment ) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding ( R ) patients compared to non-responding ( NR ) patients . In addition , we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients . While exploratory in nature , this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy . This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Cytokeratin ( CK ) 19-positive hepatocellular carcinoma ( HCC ) has been reported to have a poor prognosis . The mechanism of the development of CK19-positive HCC remains to be studied . To clarify this , in vitro experiments were performed using human HCC cell lines ( PLC-5 , HepG2 ) , and the phenotypic changes after stimulation with several growth factors were examined using quantitative reverse transcriptase PCR , western blotting , and immunofluorescence staining . In vivo experiments using human HCC specimens obtained from a total of 78 patients and clinicopathological analysis were also performed . Among the growth factors tested , epidermal growth factor ( EGF ) had prominent effects on inducing CK19 expression in PLC-5 and HepG2 , which was accompanied by the reduced expression of α-fetoprotein in PLC-5 . The induction of CK19 expression after EGF stimulation was accompanied by the phosphorylation of c-Jun-N-terminal kinase ( JNK)/stress-activated protein kinase , which was blocked by the addition of JNK inhibitors . EGF also increased proliferative abilities and invasive properties of the HCC cell lines . In vivo , 9 ( 12% ) of 78 HCC cases showed positive immunohistochemical staining of CK19 . The extent of positive immunohistochemical signals of EGF , EGF receptor ( EGFR ) , and JNK expression was significantly intense in CK-19-positive HCC than those of CK19-negative HCC . Clinicopathological analysis showed that CK19-positive HCC had a high incidence of portal vein invasion , extrahepatic metastasis and an early relapse , which was associated with the worsened 2-year disease free survival . These results indicate that the activation of the EGF-EGFR signaling pathway is associated with the development of CK19-positive HCC , and the EGF-induced increase in growth abilities of HCC may account for the poor prognosis of the patients .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Certain components of apples have been shown to prevent cancer growth and impede cancer progression . We hypothesized that extracted apple polysaccharides ( APs ) might , therefore , have anticancer effects , through a mechanism involving the induction of apoptosis in cancer cells , partly via the NF-κB pathway . Two human colorectal cancer ( CRC ) cell lines , HT-29 and SW620 , were exposed to different concentrations of APs ( 0.01 , 0.1 or 1 mg/ml ) . Cell apoptosis was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay by flow cytometry and incorporation of 5'-bromodeoxyuridine ( BrdU ) into DNA to identify the proliferating cell fraction , using fluorescence microscopy in vitro . The protein levels of NF-κB/p65 , I-κBα , pI-κBα , Bax , Bcl-xl and Bcl-2 were evaluated by western blotting . The target sites of APs on CRC cells were assessed by flow cytometry . At concentrations of 0.1 and 1 mg/ml , APs showed apoptosis-inducing effects , increased expressions of Bax , nuclear p65 and cytoplasmic pI-κBα , and decreased expressions of Bcl-2 , Bcl-xl and cytoplasmic I-κBα . APs induced apoptosis by slightly activating the NF-κB pathway ; the AP target site could be the Toll-like receptor 4 on the cell membrane . These results demonstrate the potential of APs as agents for clinical prevention and treatment of CRC .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The orphan receptor TR3 is an important regulator of cell proliferation and apoptosis . However , whether TR3 is involved in regulating the stem-like properties of cancer cells remains unknown . The present study shows that TR3 expression is increased in gastric tumorsphere cells and is positively correlated with cancer stem cell ( CSC ) characteristics . Knocking down TR3 leads to the suppression of its stem-like properties in both gastric cancer cells and tumorsphere cells . This process involves the decreased expression of the stemness-related genes Oct-4 and Nanog and the invasion-related gene MMP-9 . We further identify Nanog as a new target for the transcription factor TR3 . Together , these data demonstrate for the first time that TR3 is essential for the maintenance of stem-like properties in human gastric cancer cells and implicate TR3 as a new therapeutic target for gastric cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Vanadium pentoxide , commercially the most important compound of vanadium , presents a potential occupational hazard during the cleaning of oil-fired boilers and furnaces , the handling of catalysts , and during the refining , processing , or burning of vanadium-rich mineral ores or fossil fuels . Vanadium pentoxide was nominated for study by the National Cancer Institute as a representative of the metals class study . Male and female F344/N rats and B6C3F1 mice were exposed to vanadium pentoxide ( 99% pure ) by inhalation for 16 days , 14 weeks , or 2 years . Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood. 16-DAY STUDY IN RATS : Groups of five male and five female rats were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 2 , 4 , 8 , 16 , or 32 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 16 days . Three males in the 32 mg/m(3) group died before the end of the study . Mean body weights of males and females exposed to 8 mg/m(3) or greater were less than those of the chamber controls . Clinical findings included rapid respiration and hypoactivity in rats exposed to 16 or 32 mg/m(3) . Relative lung weights of 4 mg/m(3) or greater males and 2 mg/m(3) or greater females were significantly greater than those of the chamber controls . Lavage fluid analysis indicated an inflammatory response in the lung that was either directly mediated by vanadium pentoxide or was secondary to lung damage induced by vanadium pentoxide exposure. 16-DAY STUDY IN MICE : Groups of five male and five female mice were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 2 , 4 , 8 , 16 , or 32 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 16 days . All males exposed to 32 mg/m(3) and one 8 mg/m(3) male died or were killed moribund before the end of the study . Mean body weights of 16 mg/m(3) males and 8 mg/m(3) or greater females were significantly less than those of the chamber controls , and the 32 mg/m(3) females lost weight during the study . Absolute and relative lung weights of 4 mg/m(3) or greater males and all exposed groups of females and liver weights of 16 mg/m(3) males were significantly greater than those of the chamber controls . The mediastinal lymph nodes were enlarged in 4 , 8 , and 16 mg/m(3) males and females , and lymphoid hyperplasia was confirmed histologically . Lavage fluid analysis indicated an inflammatory response in the lung that was either directly mediated by vanadium pentoxide or was secondary to lung damage induced by vanadium pentoxide exposure. 3-MONTH STUDY IN RATS : Groups of 10 male and 10 female rats were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 1 , 2 , 4 , 8 , or 16 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 3 months . Seven males and three females exposed to 16 mg/m(3) died during the study . Mean body weights were significantly less in males exposed to 4 mg/m(3) or greater and in females exposed to 16 mg/m(3) . Abnormal breathing , thinness , lethargy , abnormal posture , and ruffled fur were observed in rats exposed to 16 mg/m(3) . Hematology results indicated that exposure of rats to vanadium pentoxide induced a microcytic erythrocytosis in males and females . Absolute and relative lung weights were significantly greater for 4 mg/m(3) or greater males and females than for the chamber controls as were the relative lung weights of 2 mg/m(3) males . The estrous cycle of females exposed to 8 mg/m(3) was significantly longer than that of the chamber control group , and the number of cycling females in the 16 mg/m(3) group was reduced . The incidences of several nonneoplastic lesions of the lung and nose were significantly increased in males and females exposed to 2 mg/m(3) or greater . Data from pulmonary function analyses indicated that a restrictive lung disease was present in male and female rats exposed to 4 mg/m(3) or greater , while an obstructive lung disease was present only in the 16 mg/m(3) groups. 3-MONTH STUDY IN MICE : Groups of 10 male and 10 female mice were exposed to par\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Immortalization ( senescence bypass ) is a critical rate-limiting step in the malignant transformation of mammalian somatic cells . Human cells must breach at least two distinct senescence barriers to permit unfettered clonal evolution during cancer development : ( 1 ) stress- or oncogene-induced premature senescence ( SIPS/OIS ) , mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive pathways , and ( 2 ) replicative senescence triggered by telomere shortening . In contrast , because their telomerase is constitutively active , cells from small rodents possess only the SIPS/OIS barrier , and are therefore useful for studying SIPS/OIS bypass in isolation . Dermal fibroblasts from the Syrian hamster ( SHD cells ) are exceptionally resistant to spontaneous SIPS bypass , but it can be readily induced following exposure to a wide range of chemical and physical carcinogens . Here we show that a spectrum of carcinogen-specific mutational and epigenetic alterations involving the INK4A ( p16 ) , p53 and INK4B ( p15 ) genes are associated with induced SIPS bypass . With ionizing radiation , immortalization is invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2 locus . In comparison , SHD cells immortalized by the powerful polycyclic hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the DNA-binding domain of p53 coupled with INK4 alterations such as loss of expression of p15 . Epimutational silencing of p16 is the primary event associated with immortalization by nickel , a human non-genotoxic carcinogen . As SIPS/OIS bypass is a prerequisite for the immortalization of normal diploid human epithelial cells , our results with the SHD model will provide a basis for delineating combinations of key molecular changes underpinning this important event in human carcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Insulin-like growth factor ( IGF)-I receptor ( IGF-IR ) signaling is required for carcinogenicity and progression of several cancers but the function of this pathway and its utility as a therapeutic target have not been studied comprehensively in biliary tract carcinomas ( BTC ) . We investigated the immunohistochemical expression of elements of the IGF axis , matrilysin , overexpression of p53 and the methylation status of the IGFBP-3 promoter in 80 surgically resected BTC . We also assessed the effect of IGF-IR blockade on signal transduction , proliferation and survival in three BTC cell lines using a new tyrosine kinase inhibitor , BMS-536924 , and dominant negative IGF-IR ( IGF-IR/dn ) . The effects of IGF-IR blockade was also studied in nude mouse xenograft models . IGF-I was expressed in 60% and IGF-II in 50% of tumors . High expression was associated with tumor size . IGF-IR was expressed in 69% of the cases and was associated with advanced stage and matrilysin expression . Hypermethylation of the IGFBP-3 promoter was detected in 41% of BTC and was inversely correlated with p53 expression . BMS-536924 blocked autophosphorylation of IGF-IR and both Akt and ERK activation by both IGF-I and insulin . BMS-536924 suppressed proliferation and tumorigenicity in vitro in a dose-dependent fashion . This inhibitor upregulated chemotherapy-induced apoptosis in a dose-dependent fashion . Moreover , IGF-IR blockade was effective against tumors in mice . IGF-IR might identify a subset of BTC with a particularly aggressive phenotype and is a candidate therapeutic target in this disease . BMS-536924 might have significant therapeutic utility .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PURPOSE : Prostate cancer ( PCa ) development is often associated with deletion or silencing of tumor suppressor PTEN , a negative regulator of the PI3K-Akt pathway , leading to resistance to various therapies . Therefore , the PI3K/Akt pathway plays a central role in various cellular processes leading to malignant phenotype , and , consequently is an attractive target . However , the efficacy of AKT inhibitors is limited by resistance mechanisms that result in minimal tumor cell death . Methods:Effects of Akt inhibitor AZD5363 were investigated on cell proliferation , apoptosis , Akt pathway and survival mechanisms . We then examined the impacts of inhibition of autophagy combined with AZD5363 on cell proliferation and apoptosis . Furthermore , the anti-cancer activity of combination treatment of the lysosomotropic inhibitor of autophagy ( chloroquine ) with Akt inhibitor AZD5363 was evaluated in PC-3 prostate cancer xenografts . RESULTS : we show that AZD5363 affected Akt downstream pathway by reducing p-mTOR , p-P70S6K and p-S6K . While AZD5363 monotherapy induced G2 growth arrest and autophagy , it failed to induce significant apoptosis in PC-3 and DU145 PCa cells . Blocking autophagy using pharmacological inhibitors or genetic inhibitors enhanced cell death induced by AZD5363 in these PCa cells . Importantly , the combination of AZD5363 with chloroquine significantly reduced tumor volume by 84.9% compared with the control group and by 77.5% compared with either drug alone in PC3 xenografts . CONCLUSIONS : These data demonstrate that Akt inhibitor AZD5363 , synergizes with the lysosomotropic inhibitor of autophagy , chloroquine , to induce apoptosis and delay tumor progression in PCa models that are resistant to monotherapy AZD5363 , providing a new therapeutic approach potentially translatable to patients .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors . Agro-industrial wastes , such as cotton and curaua fibers , are used to prepare nanofibers for use in thermoplastic films , where they are combined with polymeric matrices , and in biomedical applications such as tissue engineering , amongst other applications . The development of products containing nanofibers offers a promising alternative for the use of agricultural products , adding value to the chains of production . However , the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated . This has resulted in the creation of the new area of nanotoxicology , which addresses the toxicological aspects of these materials . PURPOSE AND METHODS Contributing to these developments , the present work involved a genotoxicological study of different nanofibers , employing chromosomal aberration and comet assays , as well as cytogenetic and molecular analyses , to obtain preliminary information concerning nanofiber safety . The methodology consisted of exposure of Allium cepa roots , and animal cell cultures ( lymphocytes and fibroblasts ) , to different types of nanofibers . Negative controls , without nanofibers present in the medium , were used for comparison . RESULTS The nanofibers induced different responses according to the cell type used . In plant cells , the most genotoxic nanofibers were those derived from green , white , and brown cotton , and curaua , while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua . An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed . CONCLUSION This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental impacts .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo . In this study , we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo . The human pancreatic cancer cell line Hs-776T ( HS-W ) produces slow-growing tumors in SCID mice . Cells of a variant form ( HS-R ) of Hs-776T produced faster-growing tumors compared to HS-W . Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) . Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2 , but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R . Cell proliferation was similar in both tumor types in vivo , whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells ( EC ) . Subsequently , VEGF was over-expressed in Hs-776T cells ( HS-VF ) , resulting in rapidly growing tumors and lowering tumor and EC apoptosis . Collectively , our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND As a highly conserved system , the activation of the Notch pathway has been implicated in the tumorigenesis of various hematologic diseases , including leukemias , lymphomas , and multiple myeloma . The Notch3 receptor is frequently expressed in T-cell acute lymphoblastic leukemia ( T-ALL ) . METHODS To explore its possibility as a therapeutic target for T-ALL , we investigated the effect of Notch3 silencing on Jurkat and SupT1 cells using a novel tumor-specific short hairpin RNA ( shRNA ) driven by survivin promoters . RESULTS We found that downregulated expression of Notch3 correlated with significant apoptosis and inhibition of proliferation . CONCLUSION These facts suggest that downregulating expression of Notch3 could attenuate the Notch signaling activity in T-ALL . All these results indicate that inhibition of Notch3 expression can result in potent antitumor activity in T-ALL .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: While human embryonic stem cells ( hESCs ) and human embryonal carcinoma cells ( hECCs ) have been studied extensively at the levels of the genome , transcriptome , proteome and epigenome our knowledge of their corresponding metabolomes is limited . Here , we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry ( GC-MS ) . Whilst some metabolites are common to both cell types , representing the self-renewal and house-keeping signatures , others were either higher ( e.g. , octadecenoic acid , glycerol-3-phosphate , 4-hydroxyproline ) or lower ( e.g. , glutamic acid , mannitol , malic acid , GABA ) in hESCs ( H9 ) compared to hECCs ( NTERA2 ) , these represent cell type specific signatures . Further , our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O(2) while oxidative phosphorylation ( OXPHOS ) is impaired or even shut down . RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1 , UQCRB and COX , increase in TCA cycle activity and decreased lactate metabolism . These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Human esophageal adenocarcinoma ( EAC ) develops in a sequence from gastroesophageal reflux disease ( GERD ) , columnar-lined esophagus ( CLE ) , dysplasia , and eventually to EAC . We established a rat surgical EAC model with esophagogastroduodenal anastomosis ( EGDA ) to mimic the staged process of esophageal adenocarcinogenesis . Profiling of the AA metabolites with mass spectrometry showed that prostaglandin E2 ( PGE2 ) , leukotriene B4 ( LTB4 ) , 15-hydroeicosatetraenoic acid ( HETE ) , 12-HETE , 8-HETE and 5-HETE all increased at the esophagoduodenal junction after EGDA as compared with the proximal esophagus , with PGE2 as the major metabolite . Consistent with this profile , cyclooxygenase 2 ( Cox2 ) was overexpressed in the basal cell layer of esophageal squamous epithelium , CLE cells and EAC tumor cells of the EGDA rats , as compared with the normal esophageal epithelium . Sulindac ( a Cox inhibitor ) , nordihydroguaiaretic acid ( NDGA , a lipoxygenase inhibitor ) and alpha-difluoromethylornithine ( DFMO , an ornithine decarboxylase inhibitor ) were tested for their possible inhibitory actions against the formation of EAC in the rat EGDA model . In a short-term study ( for 4 weeks after surgery ) , dietary administration of both sulindac ( 300 and 600 p.p.m. ) and NDGA ( 100 p.p.m. ) effectively reduced the EGDA-induced inflammation . In a long-term chemoprevention study ( for 40 weeks after surgery ) , 300 p.p.m. sulindac , alone or in combination with 100 p.p.m . NDGA or 0.5% DFMO , decreased the tumor incidence from 57.7 to 26.9% , or 16.7 or 20% , respectively ( P &lt ; 0.05 ) . NDGA alone ( 100 and 200 p.p.m. ) slightly decreased the tumor incidence to 52.4 and 37% , respectively , although the difference was not statistically significant . DFMO alone did not show significant effects on tumor incidence . Inhibition of tumor formation by sulindac was correlated with lowered levels of PGE2 . In conclusion , sulindac exerted its chemopreventive effect against the formation of EAC in the rat EGDA model possibly through its inhibition of Cox .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Glioblastoma multiforme is the most aggressive primary brain tumor in adults . Overexpression of the EGF receptor ( EGFR ) is recognized as a widespread oncogenic signature in glioblastoma multiforme , but the complexity of its contributions is not fully understood , nor the most effective ways to leverage anti-EGFR therapy in this setting . Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria ( OXPHOS ) , a phenomenon termed the Warburg effect , which is a general feature of oncogenesis . In this study , we report that hypoxia drives expression of the pyruvate dehydrogenase kinase ( PDK1 ) and EGFR along with the hypoxia-inducing factor ( HIF)-1α in human glioblastoma multiforme cells . PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation , initiating a feed-forward loop that can sustain malignant progression . RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1α expression , shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation . In clinical specimens of glioblastoma multiforme , we found that immunohistochemical expression of PDK1 , EGFR , and HIF-1α were elevated in glioblastoma multiforme specimens when compared with normal brain tissues . Collectively , our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Nitric oxide ( NO)-releasing non-steroidal anti-inflammatory drugs ( NO-NSAIDs ) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs , possess anti-proliferative , pro-apoptotic and anti-cancer activities . Here , we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice . Topical application of NO-sulindac reduced tumor incidence , number ( p<0.05 ) and volume ( p<0.005 ) as compared to UVB ( alone)-irradiated vehicle-treated mice . An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio . The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced . However , proliferation was identified as the major target of NO-sulindac in this study . A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed . The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway . UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2 , p38 and JNK1/2 . In this regard , NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2 , the direct NFκB transcription target proteins . NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial-mesenchymal transition . A marked decrease in the expression of mesenchymal markers such as Fibronectin , N-cadherin , SNAI , Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors . Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;tumor promoting inflammation;activating invasion and metastasis" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Melittin ( 1 ) is a major polypeptide in honey bee venom that has been used traditionally against chronic inflammation and cancer . However , its molecular mechanism has not been determined . In this study , the antitumor effect of 1 was compared with that of NS398 , a cyclooxygenase-2 ( COX-2 ) inhibitor , in vivo and in vitro . Subcutaneous injection of 1 at 0.5 and 5 mg/kg suppressed significantly vascular endothelial growth factor ( VEGF)-A-transfected highly metastatic Lewis lung cancer ( VEGF-A-hm LLC ) tumor growth by 25% and 57% , respectively . Also , 1 inhibited significantly the number of vessels around VEGF-A-hm LLC cells . The results were superior to those obtained in the mice treated with NS398 . Compound 1 dose-dependently inhibited proliferation and tube formation in human umbilical vein endothelial cells ( VEGF-A-HUVECs ) , without affecting cell viability in native HUVECs . In addition , 1 decreased the expression of VEGF receptor-2 ( VEGFR-2 ) , COX-2 , and prostaglandin E(2) ( PGE(2) ) in VEGF-A-transfected HUVECs . These effects were accompanied by a reduction of the phosphorylation of extracellular signal-regulated kinase 1/2 and c-jun N-terminal kinase , whereas it increased the phosphorylation of p38 mitogen-activated protein kinase ( MAPK ) . SB203580 abolished the downregulation of COX-2 and VEGFR-2 and the inhibition of cell proliferation by 1 . The antitumor activity of 1 may be associated with antiangiogenic actions via inhibiting VEGFR-2 and inflammatory mediators involved in the MAPK signaling pathway .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE To investigate the relationship between lymphangiogenesis and lymphatic metastasis in cervical squamous carcinoma . METHODS Eighty cases of invasive cervical squamous cancer were selected as objects of our study . Double immunohistochemical staining with antibodies against lymphatic vessel endothelial hyaluronan receptor 1 and Ki-67 was used to label the lymphatic vessels and mark the proliferative lymphatic vessels in cervical squamous cancer . The peritumoral lymphatic vessel density and intratumoral lymphatic vessel density was assessed . The lymphatic vessels proliferation index was evaluated by calculating Ki-67 proliferation index ( PI ) to reflect the lymphangiogenesis of cervical squamous cancer . Then the correlation between lymphangiogenesis and clinicopathologic features of cervical squamous cancer was analyzed . RESULTS The LVD of cervical cancer ( 15.23 � 3.6 ) was clearly higher than that of the adjacent normal cervical subepithelial tissues ( 9.9 � 2.5 , P &lt ; 0.001 ) . The peritumoral lymphatic vessel density of cervical cancer ( 18.75 � 4.3 ) was significantly higher than the intratumoral lymphatic vessel density of cervical cancer ( 11.71 � 4.9 , P &lt ; 0.001 ) . Lymphatic PI ( LPI ) of cervical cancer ( 0.258 � 0.07 ) was higher than that of the adjacent normal cervical subepithelial tissues ( 0.068 � 0.08 , P &lt ; 0.001 ) . The peritumoral lymphatic vessel PI of cervical cancer ( 0.324 � 0.06 ) was notably higher than the intratumoral lymphatic vessel PI of cervical cancer ( 0.232 � 0.06 , P &lt ; 0.001 ) . Peritumoral lymphatic vessel density and peritumoral lymphatic vessel were clearly associated with the lymph node metastasis ( P = 0.001 and P = 0.002 , respectively ) and lymphovascular space invasion ( P = 0.024 and P = 0.01 , respectively ) . CONCLUSIONS The high density of peritumoral lymphatic vessels is a potential predictor of more aggressive phenotype of cervical squamous cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Within the family of protein kinase C ( PKC ) molecules , the novel isoform PRKCE ( PKCɛ ) acts as a bona fide oncogene in in vitro and in vivo models of tumorigenesis . Previous studies have reported expression of PKCɛ in breast , prostate and lung tumors above that of normal adjacent tissue . Data from the cancer genome atlas suggest increased copy number of PRKCE in triple negative breast cancer ( TNBC ) . We find that overexpression of PKCɛ in a non-tumorigenic breast epithelial cell line is sufficient to overcome contact inhibition and results in the formation of cellular foci . Correspondingly , inhibition of PKCɛ in a TNBC cell model results in growth defects in two-dimensional ( 2D ) and three-dimensional ( 3D ) culture conditions and orthotopic xenografts . Using stable isotope labeling of amino acids in a cell culture phosphoproteomic approach , we find that CTNND1/p120ctn phosphorylation at serine 268 ( P-S268 ) occurs in a strictly PKCɛ-dependent manner , and that loss of PKCɛ signaling in TNBC cells leads to reversal of mesenchymal morphology and signaling . In a model of Ras activation , inhibition of PKCɛ is sufficient to block mesenchymal cell morphology . Finally , treatment with a PKCɛ ATP mimetic inhibitor , PF-5263555 , recapitulates genetic loss of function experiments impairing p120ctn phosphorylation as well as compromising TNBC cell growth in vitro and in vivo . We demonstrate PKCɛ as a tractable therapeutic target for TNBC , where p120ctn phosphorylation may serve as a readout for monitoring patient response.Oncogene advance online publication , 1 April 2013 ; doi:10.1038/onc.2013.91 .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Angiogenesis plays an important role in the progression of colorectal cancer ( CRC ) . Studies have indicated vascular endothelial growth factor ( VEGF ) is the predominant angiogenic factor . Cyclin D1 ( CCND1 ) induces production of VEGF and is required for migration of blood vessels . Our aim was to determine the roles of CCND1 and VEGF overexpression in CRC patients . METHODS We analyzed clinicopathological features , VEGF and CCND1 expressions by immunohistochemical ( IHC ) staining in 100 stage I-III CRC patients ( 44 were postoperative relapsed ; 56 were postoperative non-relapsed ) to determine the correlation between clinicopathologic features and co-existence of CCND1 and VEGF . Furthermore , the clinical outcomes of co-existence of CCND1 and VEGF were investigated . RESULTS Multivariate analysis showed vascular invasion ( P = 0.019 ) , VEGF overexpression ( P = 0.033 ) , and high postoperative serum carcinoembryonic antigen ( CEA ) levels ( P = 0.022 ) were independent predictors of postoperative relapse . Co-existence of CCND1 and VEGF overexpression had significantly poorer disease-free survival rates ( P  = 0.004 ) and overall survival rates ( P = 0.001 ) than other phenotypes . CONCLUSIONS Co-existence of CCND1 and VEGF overexpression would potentially assist in TNM staging systems to predict the prognosis of these patients who would benefit from intensive follow-up and therapeutic programs .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The SR/CR mouse phenotype , first described in 1999 in BALB/c and later bred into C57BL/6 mice , is resistant to cancer formation following high doses of cancer cells administered intraperitoneally . The tumor cell targeting and destruction mechanisms have not been identified . By fluorescence-activated cell sorting analysis , the immune response of SR/CR mice after intraperitoneal injection of cancer cells was investigated and compared with parent strain mice . A massive influx of leukocytes into the peritoneal cavity was found . A large fraction of these leukocytes were polymorphonuclear granulocytes , macrophages and natural killer cells . A relative decrease in influx of B-cells compared with controls was demonstrated . Increased proportions of leukocytes belonging to the innate immune system were also demonstrated in splenocytes of SR/CR mice . Cytospins of peritoneal fluid from SR/CR mice after cancer cell injection showed formations of immune cells morphologically resembling polymorphonuclear granulocytes and macrophages adjoining the cancer cells . The results point to the potential involvement of innate immune cells in cancer immunology . Our data support migration of polymorphonuclear granulocytes , macrophages and NK cells into the peritoneum of the SR/CR mouse in response to intraperitoneal injection of S180 cancer cells . The cell composition of spleens of SR/CR mice reflected the differential regulation of the innate immune cells in peritoneal exudates . Both peritoneal exudates and the spleens of SR/CR mice contained decreased proportions of B-cells compared with BALB/c and C57BL/6 mice . We reproduce important aspects of previous published data and further extend them by showing differentially regulated populations of splenocytes including B-lymphocytes in SR/CR mice compared with parent strain controls . Importantly , this differentially regulated immune response of SR/CR mice could not be found in response to challenge with the lymphoma cell line EL-4 .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Cell migration plays important roles in natural processes involving embryonic development , inflammation , wound healing , cancer metastasis and angiogenesis . Cell migration on various biomaterials is also believed to improve the rate of wound healing and implant therapies in the tissue-engineering field . This study measured the distance traversed , or mileage , of mouse fibroblasts on a silk fibroin surface . Fibroblasts on the fibroin surface moved with better progress during 24 h than cells on collagen or fibronectin surfaces . Results obtained by quantitative real-time reverse transcription-polymerase chain reaction ( qRT-PCR ) revealed that fibroblasts on the fibroin surface expressed transforming growth factor β-induced protein ( TGFBI ) , which is an extracellular matrix ( ECM ) protein , stronger than on other surfaces in the early cell-culture stages . These results demonstrate that the fibroin surface shows higher potential to enhance cell migration and the production of ECM than a collagen or fibronectin surface .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Hypoxia has long been linked to the Warburg effect , yet the underlying mechanism remains largely unclear . It is also not known if lncRNAs are involved in the contribution of hypoxia to the Warburg effect . Here we show that lincRNA-p21 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis . Hypoxia/HIF-1α-induced lincRNA-p21 is able to bind HIF-1α and VHL and thus disrupts the VHL-HIF-1α interaction . This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation . These data indicate the existence of a positive feedback loop between HIF-1α and lincRNA-p21 that promotes glycolysis under hypoxia . The ability of lincRNA-p21 to promote tumor growth is validated in mouse xenograft models . Together , these findings suggest that lincRNA-p21 is an important player in the regulation of the Warburg effect and also implicate lincRNA-p21 as a valuable therapeutic target for cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Barrett's esophagus ( BE ) is caused by gastroesophageal reflux with consecutive mucosal inflammation , predisposing patients to the development of esophageal adenocarcinoma ( EAC ) . We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography , a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function . RESULTS Biopsies were taken during endoscopy from BE , EAC , and normal control tissue , and proteomic microscopy was performed on 32 different epitopes . When the significance level was set to p &lt ; 0.0005 and the search depth to five antibody combinations , controls and BE can be differentiated by 63 , controls and EAC by 3222 , and BE from EAC by 1521 distinct protein combinations.For example , the number of activated apoptotic naïve and memory T cells was significantly increased only in BE , whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC . In contrast , the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC . Confirming different pathways in BE and EAC , the number of T lymphocytes with p53 expression and downregulation of bcl2 expression ( CD3+p53+Bcl2-NfkB- ) was significantly increased in EAC compared to BE and controls . Interestingly , the number of precursor T cells ( CD7+ ) was significantly elevated only in EAC . These cells lack Bax and caspase-8 , suggesting impaired apoptosis in the early stages of T cell differentiation . CONCLUSION Proteomic analysis showed for the first time that proteins , which are critically involved in the mucosal immune system of the esophagus , are distinctly expressed in BE and EAC , whereas others are comparably altered in both diseases , suggesting that many pathogenic events might be shared by both diseases . Topological proteomic analysis , therefore , helps us to understand the different pathogenic events in the underlying disease pathways .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Bladder cancer is one of the most common tumors of the genitourinary tract ; however , the molecular events underlying growth and invasion of the tumor remain unclear . Here , role of the CXCR7 receptor in bladder cancer was further explored . CXCR7 protein expression was examined using high-density tissue microarrays . Expression of CXCR7 showed strong epithelial staining that correlated with bladder cancer progression . In vitro and in vivo studies in bladder cancer cell lines suggested that alterations in CXCR7 expression were associated with the activities of proliferation , apoptosis , migration , invasion , angiogenesis and tumor growth . Moreover , CXCR7 expression was able to regulate expression of the proangiogenic factors IL-8 or VEGF , which may involve in the regulation of tumor angiogenesis . Finally , we found that signaling by the CXCR7 in bladder cancer cells activates AKT , ERK and STAT3 pathways . The AKT and ERK pathways may reciprocally regulate , which are responsible for in vitro and in vivo epithelial to mesenchymal transition ( EMT ) process of bladder cancer . Simultaneously targeting the two pathways by using U0126 and LY294002 inhibitors or using CCX733 , a selective CXCR7 antagonist drastically reduced CXCR7-induced EMT process . Taken together , our data show for the first time that CXCR7 plays a role in the development of bladder cancer . Targeting CXCR7 or its downstream-activated AKT and ERK pathways may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for bladder cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death;sustaining proliferative signaling" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression . Using genome-wide chromatin-binding profiles , we describe binding of p53 also to regions located distantly from any known p53 target gene . Interestingly , many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions . We demonstrate that these p53-bound enhancer regions ( p53BERs ) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation . Furthermore , p53BERs produce , ina p53-dependent manner , enhancer RNAs ( eRNAs ) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest . Thus , our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site . Moreover , eRNA production from p53BERs is required for efficient p53 transcription enhancement .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: In the present study we examined the effects of menadione , a redox cycling agent , on structural changes of human osteosarcoma line 143B cells . It has been previously reported that menadione can cause necrotic or apoptotic cell death in a concentration- depending manner . In our experimental model , cells were treated with 100 microM menadione for 24 hours . Using electron microscopy technique cells carrying three kinds of morphological changes were detected : necrotic cells , apoptotic cells and those demonstrating a co-existence of apoptotic and necrotic features in one single cell .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Integrin αvβ3 plays a role in insulin-like growth factor 1 ( IGF1 ) signaling ( integrin-IGF1 receptor ( IGF1R ) cross-talk ) in non-transformed cells in anchorage-dependent conditions . We reported previously that IGF1 directly binds to αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation in these conditions . The integrin-binding defective IGF1 mutant ( R36E/R37E ) is defective in inducing ternary complex formation and IGF signaling , whereas it still binds to IGF1R . We studied if IGF1 can induce signaling in anchorage-independent conditions in transformed Chinese hamster ovary cells that express αvβ3 ( β3-CHO ) cells . Here we describe that IGF1 signals were more clearly detectable in anchorage-independent conditions ( polyHEMA-coated plates ) than in anchorage-dependent conditions . This suggests that IGF signaling is masked by signals from cell-matrix interaction in anchorage-dependent conditions . IGF signaling required αvβ3 expression , and R36E/R37E was defective in inducing signals in polyHEMA-coated plates . These results suggest that αvβ3-IGF1 interaction , not αvβ3-extracellular matrix interaction , is essential for IGF signaling . Inhibitors of IGF1R , Src , AKT , and ERK1/2 did not suppress αvβ3-IGF-IGF1R ternary complex formation , suggesting that activation of these kinases are not required for ternary complex formation . Also , mutations of the β3 cytoplasmic tail ( Y747F and Y759F ) that block β3 tyrosine phosphorylation did not affect IGF1R phosphorylation or AKT activation . We propose a model in which IGF1 binding to IGF1R induces recruitment of integrin αvβ3 to the IGF-IGF1R complex and then β3 and IGF1R are phosphorylated . It is likely that αvβ3 should be together with the IGF1-IGF1R complex for triggering IGF signaling .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The induction of apoptosis by glucocorticoids in isolated thymocytes has been studied extensively . However , it is not known whether or not the same changes occur after in vivo glucocorticoid treatment . In order to investigate this , we have studied the changes occurring in thymocytes isolated from rats , from 2-24 hr after a dose of dexamethasone ( 1 mg/kg ) , which caused 50% thymic atrophy . Thymocytes were separated into four fractions by isopycnic Percoll gradients . A loss of cells occurred within 2-8 hr , primarily in only one of the two major fractions of normal thymocytes . This loss of normal thymocytes coincided with the appearance of small dense cells with characteristic features of apoptosis including condensed chromatin , increased DNA fragmentation , internucleosomal DNA cleavage and a \" hypodiploid \" peak on flow cytometric analysis . Striking differences occurred in the cellular composition of the different Percoll fractions with time . Initially ( up to 4 hr ) , the pattern of changes occurring in vivo resembled those found in vitro . However , at later times , the complex fate of apoptotic cells in vivo , such as phagocytosis , are not observed in the in vitro studies .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: NK1 is a tachykinin receptor highly relevant to tumorigenesis and metastasis development in breast cancer and other carcinomas . Despite the substantial efforts done to develop potent NK1 receptor antagonists , none of these antagonists had shown good antitumor activity in clinical trials . Now , we have tested the effect of inhibition of the neuropeptide Substance P ( SP ) , a NK1 ligand , as a potential therapeutic approach in cancer . We found that the inhibition of SP with antibodies strongly inhibit cell growth and induce apoptosis in breast , colon , and prostate cancer cell lines . These effects were accompained by a decrease in the mitogen-activated kinase singaling pathway . Interestingly , in some cell lines SP abrogation decreased the steady state of Her2 and EGFR , suggesting that SP-mediated signaling is important for the basal activity of these ErbB receptors . In consequence , we observed a blockade of the cell cycle progression and the inhibition of several cell cycle-related proteins including mTOR . SP inhibition also induced cell death in cell lines resistant to Lapatinib and Trastuzumab that have increased levels of active Her2 , suggesting that this therapeutic approach could be also effective for those cancers resistant to current anti-ErbB therapies . Thus , we propose a new therapeutic strategy for those cancers that express NK1 receptor and/or other tachykinin receptors , based in the immuno-blockade of the neuropeptide SP .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Osteosarcoma is a high-grade malignant bone tumor that manifests ingravescent clinical behavior . The intrinsic events that confer malignant properties on osteosarcoma cells have remained unclear , however . We previously established two lines of mouse osteosarcoma cells : AX cells , which are able to form tumors in syngeneic mice , and AXT cells , which were derived from such tumors and acquired an increased tumorigenic capacity during tumor development . We have now identified Igf2 mRNA-binding protein3 ( Imp3 ) as a key molecule responsible for this increased tumorigenicity of AXT cells in vivo . Imp3 is consistently up-regulated in tumors formed by AX cells , and its expression in these cells was found to confer malignant properties such as anchorage-independent growth , loss of contact inhibition , and escape from anoikis in vitro . The expression level of Imp3 also appeared directly related to tumorigenic ability in vivo which is the critical determination for tumor-initiating cells . The effect of Imp3 on tumorigenicity of osteosarcoma cells did not appear to be mediated through Igf2-dependent mechanism . Our results implicate Imp3 as a key regulator of stem-like tumorigenic characteristics in osteosarcoma cells and as a potential therapeutic target for this malignancy .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Recent surveys indicate that Pi intake has increased steadily as Pi-containing foods have increased . Our previous study demonstrated that high dietary Pi strongly stimulated lung tumorigeneis . In order to answer the issue whether low Pi may be chemopreventive , we examined the effects of low Pi on lung cancer . Eighteen 5-wk-old male K-ras(LA1) lung cancer model mice were randomly allocated to 2 groups . One group was fed a normal diet ( 0.5% Pi ) and other group was fed low Pi ( 0.1% Pi ) diet for 4 wk . Lung cancer development was evaluated by histopathological examination , Western blot , kinase assay , and immunohistochemistry . Low Pi increased the expression of sodium-dependent phosphate co-transporter 2b , and activated Akt signal with decreased PTEN expression in the lungs of K-ras(LA1) mice . Low Pi increased the Akt/mTOR-mediated protein translation through upregulating the phosphorylation of p70S6K and 4E-BP1 . In addition , low Pi stimulated cell cycling as evidenced by altered cell cycle regulators such as cyclin D1 and D3 . Finally , low Pi increased lung tumorigenesis in K-ras(LA1) mice compared to the normal diet group . Our results clearly demonstrated that low Pi also promoted lung tumorigenesis , thus suggesting that an appropriate intake of dietary Pi may be critical for lung cancer prevention as well as treatment .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Centrosome overduplication or amplification has been observed in many human cancers and in premalignant tissue , but the mechanisms leading to such centrosome aberrations are not fully understood . We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human fibroblasts , especially in a polyploid subpopulation . This study examines localization of p53 protein at centrosomes in mitotic cells , which is often observed in association with DNA damage response , to investigate a possible association between p53 localization and numerical centrosome aberrations induced by cellular senescence . Cultures at later passages or the 4th day after exposure to H(2)O(2) showed increased frequencies of mitotic cells with supernumerary centrosomes , especially in a polyploid subpopulation . Immunohistochemical analysis frequently showed p53-positive foci in mitotic cells , and some were localized at centrosomes . The number of p53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence . Supernumerary centrosomes showed higher frequencies of p53 localization compared to normally duplicated centrosomes . Centrosome-associated p53 protein was phosphorylated at Ser15 . These data suggest a possible association between localization of p53 protein and numerical centrosome aberrations in replicatively or prematurely senescent cells .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: It is well known that ErbB2 , a receptor tyrosine kinase , localizes to the plasma membrane . Here we describe a novel observation that ErbB2 also localizes in mitochondria of cancer cells and patient samples . We found that ErbB2 translocates into mitochondria through association with mtHSP70 . Additionally , mitochondrial ErbB2 ( mtErbB2 ) negatively regulates mitochondrial respiratory functions . Oxygen consumption and activities of complexes of the mitochondrial electron transport chain were decreased in mtErbB2-overexpressing cells . Mitochondrial membrane potential and cellular ATP levels were also decreased . In contrast , mtErbB2 enhanced cellular glycolysis . The translocation of ErbB2 and its impact on mitochondrial function are kinase dependent . Interestingly , cancer cells with higher levels of mtErbB2 were more resistant to the ErbB2-targeting antibody trastuzumab . Our study provides a novel perspective on the metabolic regulatory function of ErbB2 and reveals that mtErbB2 has an important role in the regulation of cellular metabolism and cancer cell resistance to therapeutics .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: UNLABELLED Oxygen free radicals and their reactive derivatives participate in formation of chronic inflammation states , which facilitate development of gastrointestinal tract tumors . Oxidative stress is one of the main causes of damage to cell membranes in result of exacerbated lipid peroxidation process . End products of lipid peroxidation ( aldehydes , organic peroxides ) react with important biological macromolecules such as DNA and proteins , cause changes in cell membrane structure and properties leading to loss of its integrity . Intensification of the lipid peroxidation process is a factor which may also lead to a malfunction in the antioxidant barrier , which further weakens the defense of cells against oxygen free radicals and promotes the onset and development of cancer . The aim of the study was the determination of lipid peroxidation level in gastrointestinal tract tumors ( stomach , liver , colon , and colorectal cancer to liver metastases ) . MATERIAL AND METHODS Materials for studies were obtained from 150 patients with gastrointestinal tract tumors : 10 with stomach cancer , 30 with malignant and benign liver cancers , 60 with primary colorectal cancer , and 50 with metachronous colorectal cancer liver metastases . We also investigated 25 patients with liver cirrhosis , which was treated as a pre-cancerous condition . In total , 175 patients were examined . Tumor specimens , and normal adjacent tissues ( 6-7 cm from the edge of the tumor ) , which served as control tissue in studies , were collected from patients ( with their consent ) during surgery . Additionally , liver specimens were collected from patients with liver cirrhosis . Lipid peroxidation level was determined spectrophotometrically as a concentration of final lipid peroxidation products , which in reaction with tiobarbituric acid ( TBA ) form colour complex ( thiobarbituric acid-reactive substances - TBARS ) . RESULTS The study showed the highest concentration of TBARS in benign , and the lowest in malignant liver tumors . Other types of gastrointestinal tumors studied , were characterized by similar levels of lipid peroxidation . TBARS concentration in these tumors was approximately 2-fold higher than in malignant liver tumors and much lower than in benign tumors . In all cancers of the digestive tract with the exception of malignant liver tumors increased level of TBARS was found , comparing with control tissue . The concentration of TBARS in cirrhotic liver was lower than in control . The level of lipid peroxidation in liver cirrhosis and malignant liver tumors was similar . There were no significant differences in TBARS concentration in the tumors of particular sections of the intestine and normal colon . The highest concentration of TBARS was found in G1 grade of colorectal cancer . In subsequent grades of cells differentiation ( G2 and G3 ) its concentration was lower . The highest level of lipid peroxidation , expressed as the concentration of TBARS was found in the I stage of colorectal cancer clinical advancement . The significantly lowest concentration of TBARS was shown for stage II ( UICC ) . CONCLUSIONS The level of lipid peroxidation in cancerous cells of gastrointestinal tract indicates increased oxidative stress . The changes of lipid peroxidation level--a marker of oxidative stress in gastrointestinal tumors appear to be closely associated with their development stages ( liver cirrhosis/malignant liver cancer ; colorectal cancer/colorectal cancer liver metastases ) and are likely to create such conditions , in which cancerous cells may proliferate , undergo gradual dedifferentiation and malignancy , and generate metastases .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns ( DAMPs ) . However , how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions , in the absence of pathogen associated molecular patterns ( PAMPs ) , remains poorly understood . Here , we examined antigen-specific CD8(+) T-cell responses to primary sterile necrotic tumor cells both in vitro and in vivo . We found that primary necrotic cells alone fail to generate CD8(+) T cell-dependent immune responses toward cell-associated antigens . We show that necrotic cells trigger CD8(+) T-cell immunity only in the presence of PAMPs or analogs , such as p(dI-dC) and/or unmethylated CpG DNA . The electroporation of tumor cells with these PAMPs prior to necrosis induction triggered antigen-specific CD8(+) T-cell responses through a TLR9/MyD88-dependent pathway . In addition , we found that necrotic cells contain factors that can block the cross-priming of CD8(+) T cells even under non-sterile conditions and can serve as a possible mechanism of immunosuppression . These results suggest that antigen-specific CD8(+) T-cell responses to primary necrotic tumor cells can be induced in the presence of PAMPs and thus have a substantial impact on the development of antitumor vaccination strategies .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: An aqueous extract of Kefir , fermented milk originally produced in the Caucasus mountains , suppressed morphological changes of human melanoma HMV-1 and SK-MEL cells and human normal fibroblastTIG-1 cells caused by UVC-irradiation , suggesting that UV damage can be suppressed by the Kefir extract . The addition of the Kefir extract after UVC-irradiation of HVM-1 cells resulted in a remarkable decrease in intracellular reactive oxygen species ( ROS ) which had been increased by UVC irradiation . The Kefir extract also stimulated unscheduled DNA synthesis and suppressed UVC-induced apoptosis of HMV-1 cells . A colony formation assay revealed that the Kefir extract rescued HMV-1 cells from cell death caused by UVC irradiation . The Kefir extract , as well as methyl methanethiosulfonate which is known to enhance the nucleotide excision repair ( NER ) activity , exhibited strong thymine dimer repair-enhancing activity . Epigalocatechin exhibited a weak NER activity but vitamins A , C , and E and catechin showed no NER activity . The thymine dimer repair-enhancing factors in the Kefir extract were heat-stable and assumed to be molecules with a molecular weight of less than 5000 . The treatment of HMV-1 cells with the Kefir extract during or before UVC- irradiation also prevented the generation of ROS and thymine dimmer , and suppressed the apoptosis of HMV-1 cells , suggesting that application of Kefir can prevent UV damage .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation;resisting cell death" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Partial or whole-brain irradiation is often required to treat both primary and metastatic brain cancer . Radiation-induced normal tissue injury , including progressive cognitive impairment , however , can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year in the United States . Although the exact mechanisms underlying radiation-induced late effects remain unclear , oxidative stress and inflammation are thought to play a critical role . Microglia are key mediators of neuroinflammation . Peroxisomal proliferator-activated receptor ( PPAR ) δ has been shown to be a potent regulator of anti-inflammatory responses . Thus , we hypothesized that PPARδ activation would modulate the radiation-induced inflammatory response in microglia . Incubating BV-2 murine microglial cells with the PPARδ agonist L-165041 prevented the radiation-induced increase in : ( i ) intracellular reactive oxygen species generation , ( ii ) Cox-2 and MCP-1 expression , and ( iii ) IL-1β and TNF-α message levels . This occurred , in part , through PPARδ-mediated modulation of stress-activated kinases and proinflammatory transcription factors . PPARδ inhibited NF-κB via transrepression by physically interacting with the p65 subunit and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular reactive oxygen species generation . These data support the hypothesis that PPARδ activation can modulate radiation-induced oxidative stress and inflammatory responses in microglia .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Previous studies have shown that the E7 gene of human papillomavirus ( HPV ) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells ( HFE ) and that the efficiency was increased in cooperation with the respective E6 gene , whereas the HPV6 E6 or E7 gene was not active in HFE . To detect weak immortalizing activities of the HPV6 genes , cells were infected with recombinant retroviruses containing HPV genes , alone and in homologous and heterologous combinations . The HPV6 genes , alone or together ( HPV6 E6 plus HPV6 E7 ) , were not able to immortalize cells . However the HPV6 E6 gene , in concert with HPV16 E7 , increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone . Interestingly , 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized , whereas neither gene alone was sufficient . Thus , the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16 . Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture , resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer . Additionally , combinations of genes that immortalized HFE cells ( HPV16 E6 plus HPV16 E7 , HPV16 E6 plus HPV6 E7 , and HPV6 E6 plus HPV16 E7 ) also stimulated proliferation .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Ionizing radiation is a potent inducer of DNA damage because it causes single- and double-strand breaks , alkali-labile sites , base damage , and crosslinks . The interest in ionizing radiation is due to its environmental and clinical implications . Single-strand breaks , which are the initial damage induced by a genotoxic agent , can be used as a biomarker of exposure , whereas the more biologically relevant double-strand breaks can be analyzed to quantify the extent of damage . In the present study the effects of 137CS gamma-radiation at doses of 1 , 5 , and 10 Gray on DNA and subsequent repair by C3H10T1/2 cells ( mouse embryo fibroblasts ) were investigated . Two versions of the comet assay , a sensitive method for evaluating DNA damage , were implemented : the alkaline one to detect single-strand breaks , and the neutral one to identify double-strand breaks . The results show a good linear relation between DNA damage and radiation dose , for both single-strand and double-strand breaks . A statistically significant difference with respect to controls was found at the lowest dose of 1 Gy . Heterogeneity in DNA damage within the cell population was observed as a function of radiation dose . Repair kinetics showed that most of the damage was repaired within 2 h after irradiation , and that the highest rejoining rate occurred with the highest dose ( 10 Gy ) . Single-strand breaks were completely repaired 24 h after irradiation , whereas residual double-strand breaks were still present . This finding needs further investigation .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Fifty-six previously untreated stage-I ( according to Rai ) chronic lymphocytic leukemia ( CLL ) patients were examined for their clinical data , immunological characteristics , and hormonal values . Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin ( PHA ) , concanavalin A ( ConA ) , pisum sativatum agglutinin ( PSA ) , wheat germ agglutinin ( WGA ) , recombinant interleukin 2 ( IL 2 ) , and dextran sulfate ( DxS ) ; also by decreased immunoglobulin levels ( IgG , IgA , IgE ) and increased beta 2-microglobulin ( beta 2-M ) values . Simultaneously , dysregulation of the hypothalamic-pituitary-adrenal axis , immune system integration , imbalance of sex hormones , and changes in thyroid hormones were observed in the same group of patients . Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: It is known that sperm samples from recurrent pregnancy loss ( RPL ) couples have an increase in their sperm DNA fragmentation ( SDF ) , but no studies have been performed in order to identify differences between single stranded SDF ( ssSDF ) and double stranded SDF ( dsSDF ) in these patients . This could be relevant because the type of DNA damage could have different effects . Semen samples were classified attending their clinical status : 25 fertile donors and 20 RPL patients with at least two unexplained first trimester miscarriages . SDF was analysed using alkaline and neutral Comet assay , SCD test and pulsed-field gel electrophoresis ( PFGE ) , and ROC analysis including data from 105 more infertile patients ( n = 150 ) was performed to establish predictive threshold values . SDF for alkaline and neutral Comet , and the SCD test was analysed in these categories of individuals . Data revealed the presence of two subgroups within fertile donors . The values obtained were 21.10±9.13 , 23.35±10.45 and 12.31±4.31 , respectively , for fertile donors with low values for both ssSDF and dsSDF ; 27.86±12.64 , 80.69±12.67 and 12.43±5.22 , for fertile donors with low ssSDF and high dsSDF ; and 33.61±15.50 , 84.64±11.28 and 19.28±6.05 , for unexplained RPL patients , also showing a low ssSDF and high dsSDF profile . This latter profile was seen in 85% of unexplained RPL and 33% of fertile donors , suggesting that it may be associated to a male risk factor for undergoing RPL . ROC analysis regarding recurrent miscarriage set the cut-off value at 77.50% of dsDNA SDF . PFGE for low ssSDF and high dsSDF profile samples and positive controls treated with DNase , to induce dsDNA breaks , showed a more intense band of about 48 kb , which fits the toroid model of DNA compaction in sperm , pointing out that some nuclease activity may be affecting their sperm DNA in RPL patients . This work identifies a very specific SDF profile related to the paternal risk of having RPL .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type ( epithelial ) and R-type ( round ) . Pure cultures of each type were obtained by subcloning , and both have maintained their characteristic phenotypes for at least 1 year ( 40 passages ) . E-type cells are the major ( &gt ; 98% ) type in the parental SW480 cell line . They form flat epithelial-like colonies . In contrast , R-type cells , which constitute a minor fraction ( &lt ; 2% ) of the parental cell line , have a rounded shape and grow in clusters of piled-up cells . Compared to E-type cells or the parental SW480 cells , isolated R-type cells display decreased doubling time , loss of contact inhibition , less adhesiveness to culture plates , higher anchorage-independent growth in soft agar , and a much more aneuploid karyotype . When injected s.c. into nude mice , R-type cells produce much larger tumors within the same period of time than E-type cells , and the tumors are less differentiated than those produced by the E-type cells . Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant , and the results suggest that this is due to one or a few genetic changes . Taken together , these findings suggest that the R-type cells represent a more malignant variant of the E-type cells . They may be useful , therefore , for studying mechanisms involved in tumor progression .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Cancer cells convert glucose preferentially to lactate even in the presence of oxygen ( aerobic glycolysis-Warburg effect ) . New concepts in cancer treatment aim at inhibition of aerobic glycolysis . Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation . Therefore , the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells . We investigated the effects of ( R)-(+)-α-lipoic acid ( LPA ) and dichloroacetate ( DCA ) , possible activators of pyruvate dehydrogenase , on suppression of aerobic glycolysis and induction of cell death . The neuroblastoma cell lines Kelly , SK-N-SH , Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations ( 0.1-30 mM ) of LPA and DCA . The effects of both compounds on cell viability/proliferation ( WST-1 assay ) , [ 18F]-FDG uptake , lactate production and induction of apoptosis ( flow cytometric detection of caspase-3 ) were evaluated . Furthermore , NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA ( i.p , 18.5 mg/kg ) starting at day 7 p.i. . Tumor development was measured with a sliding calliper and monitored via [ 18F]-FDG-PET . Residual tumors after therapy were examined histopathologically . These data suggests that LPA can reduce ( 1 ) cell viability/proliferation , ( 2 ) uptake of [ 18F]-FDG and ( 3 ) lactate production and increase apoptosis in all investigated cell lines . In contrast , DCA was almost ineffective . In the mouse xenograft model with s.c . SkBr3 cells , daily treatment with LPA retarded tumor progression . Therefore , LPA seems to be a promising compound for cancer treatment .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Mitochondrial uncoupling protein 2 ( UCP2 ) can moderate oxidative stress by favoring the influx of protons into the mitochondrial matrix , thus reducing electron leakage from respiratory chain and mitochondrial superoxide production . Here , we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly increases reactive oxygen species ( ROS ) production inhibiting pancreatic adenocarcinoma cell growth . We also show that UCP2 inhibition triggers ROS-dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase ( GAPDH ) , formation of autophagosomes , and the expression of the autophagy marker LC3-II . Consistently , UCP2 over-expression significantly reduces basal autophagy confirming the anti-autophagic role of UCP2 . Furthermore , we demonstrate that autophagy induced by UCP2 inhibition determines a ROS-dependent cell death , as indicated by the apoptosis decrease in the presence of the autophagy inhibitors chloroquine ( CQ ) or 3-methyladenine ( 3-MA ) , or the radical scavenger NAC . Intriguingly , the autophagy induced by genipin is able to potentiate the autophagic cell death triggered by gemcitabine , the standard chemotherapeutic drug for pancreatic adenocarcinoma , supporting the development of an anti-cancer therapy based on UCP2 inhibition associated to standard chemotherapy . Our results demonstrate for the first time that UCP2 plays a role in autophagy regulation bringing new insights into mitochondrial uncoupling protein field .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The recent approval of a prostate cancer vaccine has renewed hope for anticancer immunotherapies . However , the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies . Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy , but they often are used at high doses in the clinic to prune tumor vessels and paradoxically may compromise various therapies . Here , we demonstrate that targeting tumor vasculature with lower vascular-normalizing doses , but not high antivascular/antiangiogenic doses , of an anti-VEGF receptor 2 ( VEGFR2 ) antibody results in a more homogeneous distribution of functional tumor vessels . Furthermore , lower doses are superior to the high doses in polarizing tumor-associated macrophages from an immune inhibitory M2-like phenotype toward an immune stimulatory M1-like phenotype and in facilitating CD4(+) and CD8(+) T-cell tumor infiltration . Based on this mechanism , scheduling lower-dose anti-VEGFR2 therapy with T-cell activation induced by a whole cancer cell vaccine therapy enhanced anticancer efficacy in a CD8(+) T-cell-dependent manner in both immune-tolerant and immunogenic murine breast cancer models . These findings indicate that vascular-normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies . Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients , our study suggests a strategy to use antiangiogenic agents in breast cancer more effectively with active immunotherapy and potentially other anticancer therapies .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;avoiding immune destruction" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE To sort and identify side population ( SP ) cancer stem cells ( CSC ) in human prostate cancer ( PCa ) cell lines . METHODS Stem-like cells were isolated from five PCa cell lines Du145 , IA8 , LNCaP , TSU-Pr and PC-3 using FACS based on CD133+ CD44+ immunophenotype and SP in Hoechst staining . The in vitro growth pattern and tumorigenicity of SP stem cells were verified by soft agar colony-formation trial . LNCaP/SP cells were selected for further identification of stem cell properties using immunostaining , proliferation and invasion assay . Eventually , tumorigenicity and metastasis ability of LNCaP/SP were confirmed by xenograft experiments . RESULTS The percentages of CSCs of the CD133 CD44 + immunophenotype were extremely low in the five PCa cell lines . On the contrary , the percentages of the isolated SP cells were significantly higher in Du145 ( [ 0.15 +/- 0.02]% ) , IA8 ( [ 0.60 +/- 0.07 ]% ) , LNCaP ( [ 0.8 +/- 0.1]% ) and TSU-PrL ( [ 2.0 +/- 0.4]% ) , but none was detected in PC-3 . Besides , IA8/SP , LNCaP/SP and TSU-PrL/SP cells showed a significantly greater colony-forming efficiency than non-side population ( NSP ) cells ( P &lt ; 0.05 ) . Compared with LNCaP/NSP cells , LNCaP/SP cells exhibited high expressions of integrin alpha2 , Nanog , CD44 , OCT4 and ABCG2 , remarkably enhanced invasive and proliferative potentials in vitro , and markedly increased tumorigenicity and metastasis ( P &lt ; 0.01 ) . CONCLUSION SP sorting is more suitable than CD133+ CD44+ selection for enriching CSCs from PCa cell lines , and LNCaP/ SP represents a typical CSC population .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Tumor cells trigger angiogenesis through overexpression of various angiogenic factors including vascular endothelial growth factor ( VEGF ) and angiopoietin 1 ( Ang1 ) . Therefore , inhibition of the expression of both VEGF and Ang1 , the initial step of tumor angiogenesis , is a promising strategy for cancer chemoprevention and therapy . Grape seed proanthocyanidins ( GSPs ) are widely consumed dietary supplements that have antitumor activity . Due to their polymeric structure , GSPs are poorly absorbed along the gastrointestinal tract and can reach the colon at high concentrations , allowing these chemicals to act as chemopreventive agents for colon cancer . In the present study , we found that GSPs inhibited colon tumor-induced angiogenesis and , thus , the growth of colon tumor xenografts on the chick chorioallantoic membranes . The mechanisms of their action were related to inhibiting the expression of both VEGF and Ang1 through scavenging reactive oxygen species . Previous studies have demonstrated that the chemopreventive effects of GSPs on colon cancer are associated with their growth inhibitory and apoptosis-inducing effects . Our results demonstrate another mechanism by which GSPs inhibit colon tumor growth , which will be helpful for developing GSPs as a pharmacologically safe angiopreventive agent against colorectal cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The ALKBH family of proteins are highly expressed in various types of human cancer where they are involved in tumor growth and progression . However , multiple isoforms of ALKBH exist and the effect of individual isoforms on the development of urinary bladder cancer is unknown , particularly the molecular mechanisms involved in the progression from a noninvasive to invasive phenotype . We examined the role and function of ALKBH2 in human bladder cancer development in vitro and provide the first report that suppression of ALKBH2 in a human urothelial carcinoma cell line , KU7 , reduced the expression of the transmembrane mucin protein , MUC1 , and induced G1 cell cycle arrest . Moreover , reduction of ALKBH2 suppressed epithelial to mesenchymal transition ( EMT ) via increasing E-cadherin and decreasing vimentin expression . Transfection of MUC1 siRNA inhibited cell proliferation and EMT to the same extent as ALKBH2 gene silencing in vitro . ALKBH2 knockdown significantly suppressed MUC1 expression and tumor volume of bladder cancers in vivo as assessed in an orthotopic mouse model using ALKBH2 shRNA transfected KU7 cells . Immunohistochemical examination showed high expression levels of ALKBH2 in human urothelial carcinoma samples , especially in high-grade , superficially and deeply invasive carcinomas ( pT(1) and >pT(2) ) , and in carcinoma in situ but not in normal urothelium . This study demonstrates that ALKBH2 is an upstream molecule of the oncoprotein , MUC1 , and regulates cell cycle and EMT , resulting in progression of urothelial carcinomas .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The expression of \" growth arrest and DNA damage inducible genes 45 and 153 \" is related to apoptotic induction of cells . GADD45 is an effector gene of the tumor suppressor p53 , and GADD153 is associated with cellular function of cancer prevention . Curcumin , isolated from the plant Curcuma longa ( LINN ) , has been investigated as a promising cancer preventive in food because curcumin , a phenolic and coloring compound , is widely ingested in the Indian subcontinent . However , the exact mechanisms of action of curcumin have not yet been clearly elucidated . Based on our successful results with green tea catechins as cancer preventive , we studied the relationship between the expression of GADD45 and 153 and apoptotic induction in human lung cancer cell line PC-9 . In our study curcumin increased the expression of GADD45 and 153 in a p53-independent manner . Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the cell-cycle followed by strong induction of apoptosis . Treatment with GADD45 and 153 small interfering RNAs ( siRNAs ) inhibited the apoptotic induction in PC-9 cells by curcumin . Moreover , curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27 , while it inhibited the expression of numerous genes , including Bcl-2 , cyclin D1 , CDK2 , CDK4 and CDK6 . All the results with PC-9 cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime mechanism in the anticancer activity of curcumin .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Diallyl disulfide ( DADS ) is a major organo-sulfur compound derived from garlic ( Allium sativum ) , which inhibits the proliferation of various types of cancer cells . In this study we investigated the effect of DADS on the induction of apoptosis , as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells . Treatment of B16F-10 cells with nontoxic concentrations of DADS resulted in the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner . Cell-cycle analysis revealed that the occurrence of the sub-G1 peak was significantly elevated in DADS-treated cells . DADS treatment also down-reguated Bcl-2 expression and up-regulated p53 , caspase-9 , and caspase-3 expression in B16F-10 melanoma cells . The study also reveals that DADS inhibited the activation and nuclear translocation of p65 , p50 , and c-Rel subunits of nuclear factor ( NF)-B and other transcription factors , such as c-fos , activated transcription factor-2 , and cyclic adenosine monophosphate response element-binding protein , in B16F-10 melanoma cells The pro-inflammatory cytokine production and gene expression of tumor necrosis factor ( TNF)-α , interleukin ( IL)-1β , IL-6 , and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) were down-regulated in DADS-treated cells compared with control B16F-10 metastatic melanoma cells . DADS induces caspase-dependent apoptosis through a mitochondria-mediated intrinsic pathway in B16F-10 melanoma cells by activating p53 and caspase-3 gene expression and suppressing pro-inflammatory cytokines and NF-B-mediated Bcl-2 activation .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The anti-tumor antibiotic salinomycin ( Sal ) was recently identified as a selective inhibitor of breast cancer stem cells ; however , the effect of Sal on hepatocellular carcinoma ( HCC ) is not clear . This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC . HCC cell lines ( HepG2 , SMMC-7721 , and BEL-7402 ) were treated with Sal . Cell doubling time was determinated by drawing growth curve , cell viability was evaluated using the Cell Counting Kit 8 . The fraction of CD133(+) cell subpopulations was assessed by flow cytometry . We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+)cell subpopulations in HCC cells . Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases . Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining . Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio . Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays . Compared to control , β-catenin expression is significantly down-regulated upon Sal addition . The Ca(2+) concentration in HCC cells was examined by flow cytometry and higher Ca(2+) concentrations were observed in Sal treatment groups . The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls . Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo . Finally , the role of Sal on in vivo Wnt/β-catenin signaling was evaluated by Western blot and immunohistochemistry . This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/β-catenin signaling via increased intracellular Ca(2+) levels .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;resisting cell death" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels . It is a complex process , involving both pro- and anti-angiogenic factors , and plays a significant role in physiological and pathophysiological processes such as embryonic development , atherosclerosis , post-ischemic vascularization of the myocardium , tumor growth and metastasis , rheumatoid arthritis etc . This is the first report of zinc oxide ( ZnO ) nanoflowers that show significant pro-angiogenic properties ( formation of new capillaries from pre-existing blood vessels ) , observed by in vitro and in vivo angiogenesis assays . The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation . Additionally , it helps to promote endothelial cell ( EA.hy926 cells ) migration in wound healing assays . Formation of reactive oxygen species ( ROS ) , especially hydrogen peroxide ( H(2)O(2))-a redox signaling molecule , might be the plausible mechanism for nanoflower-based angiogenesis . Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases , where angiogenesis plays a significant role .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE The signalling molecule protein kinase B ( Akt ) modulates many cellular processes . Phosphatidylinositol 3-kinase ( PI3K)/Akt signalling pathways play important roles in tumour angiogenesis . The aim of this study was to determine the role of phosphorylated Akt ( pAkt ) in angiogenesis and its correlation with vascular endothelial growth factor ( VEGF)-A in gastric adenocarcinoma . METHODS Tumour tissue and matched healthy gastric mucosa were obtained from patients undergoing surgical resection of gastric adenocarcinoma . Akt and pAkt were detected via Western blotting . VEGF-A , pAkt and CD34 were examined by immunohistochemistry . RESULTS Akt and pAkt protein levels were significantly higher in gastric cancer tissue than in normal tissue ( n = 48 patients ) . Positive VEGF-A immunostaining was significantly associated with pAkt immunostaining . Microvessel density was correlated with both VEGF-A and pAkt positivity . CONCLUSIONS Phosphorylated Akt and VEGF-A are involved in angiogenesis of gastric adenocarcinoma , and Akt activation may contribute to angiogenesis via VEGF-A upregulation . The PI3K/Akt/VEGF signalling pathway may be involved in gastric adeno carcinoma .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Thyroid hormone ( T(3) ) mediates cellular growth , development , and differentiation by binding to the nuclear thyroid hormone receptor ( TR ) . Recent studies suggest that long-term hypothyroidism is associated with human hepatocellular carcinoma ( HCC ) independent from other major HCC risk factors . Dickkopf ( DKK ) 4 , a secreted protein , antagonizes the Wnt signal pathway . In this study , we demonstrate that T(3) may play a suppressor role by inducing DKK4 expression in HCC cells at both the messenger RNA ( mRNA ) and protein levels . DKK4 was down-regulated in 67.5% of HCC cancerous tissues . The decrease in DKK4 levels was accompanied by a concomitant decrease in TR protein levels in the matched cancerous tissues in 31% of tissues compared by immunoblotting with the adjacent noncancerous tissues . Further , TR and DKK4 expression levels were positively correlated in both normal and cancerous specimens by tissue array analysis . In function assays , stable DKK4 transfected into J7 or HepG2 cells decreased cell invasion in vitro . Conversely , knocking down DKK4 restores cell invasiveness . DKK4-expressing J7 clones showed increased degradation of β-catenin , but down-regulation of CD44 , cyclin D1 , and c-Jun . To investigate the effect of DKK4 and TR on tumor growth in vivo , we established a xenograft of J7 cells in nude mice . J7-DKK4 and J7-TRα1 overexpressing mice , which displayed growth arrest , lower lung colony formation index , and smaller tumor size than in control mice , supporting an inhibitory role of DKK4 in tumor progression . CONCLUSION : Taken together , these data suggest that the TR/DKK4/Wnt/β-catenin cascade influences the proliferation and migration of hepatoma cells during the metastasis process and support a tumor suppressor role of the TR .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Brain-metastatic breast cancer ( BMBC ) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown . Recent work has demonstrated that deregulation of epidermal growth factor receptor ( EGFR ) may correlate with BMBC progression . However , the exact contribution that EGFR makes to BMBC remains unclear . METHODS The role of EGFR in BMBC was explored by serial analyses in a brain-trophic clone of human MDA-MB-231 breast carcinoma cells ( 231-BR cells ) . EGFR expression was inhibited by stable short-hairpin RNA transfection or by the kinase inhibitor erlotinib , and it was activated by heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) . Cell growth and invasion activities also were analyzed in vitro and in vivo . RESULTS EGFR inhibition or activation strongly affected 231-BR cell migration/invasion activities as assessed by an adhesion assay , a wound-healing assay , a Boyden chamber invasion assay , and cytoskeleton staining . Also , EGFR inhibition significantly decreased brain metastases of 231-BR cells in vivo . Surprisingly , changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay , an anchorage-independent growth assay , and cell cycle analysis . Immunoblot analysis suggested that EGFR drives cells ' invasiveness capability mainly through phosphoinositide 3-kinase/protein kinase B and phospholipase C γ downstream pathways . In addition , EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen-activated protein kinase pathway . CONCLUSIONS The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231-BR cells , providing new evidence of the potential value of EGFR inhibition in treating BMBC .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: A 39-year-old male without contributory medical history had sustained progressive double vision , ptosis , and trigeminal pain for 2 weeks . Physical examination revealed total ophthalmoplegia and visual field defect with normal blood examination and chest radiography . Cranial computed tomography revealed a hyperdense mass in the left frontotemporal fossae with bony erosion . Magnetic resonance imaging confirmed a broad-based , intensely enhanced extraaxial tumor of 4x4x4 cm diameter with dural tail sign . Cerebral angiography demonstrated insignificant blood supply both from the internal carotid and middle meningeal arteries . Nearly total tumor resection was achieved via orbitofrontotemporal craniotomy . Intraoperative findings revealed the extraaxial tumor with broad attachment to the dura mater and invasion to the optic and oculomotor nerves . Histological examination revealed hypercellular tumor with significant cell atypism , mitotic activity , and focal necrosis . Immunohistochemical staining was positive for AE1/3 and c-kit , but negative for glial fibrillary acidic protein . Systemic examination performed postoperatively revealed a thymic tumor without additional remote lesions . The final diagnosis was metastatic brain tumor from thymic carcinoma . Rapid progression of neurological impairment inconsistent with a benign extraaxial tumor needs prompt surgical intervention .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: An epithelial cell line , referred to as A163 , was established from breast carcinoma derived from a patient with a strong family history of breast cancer but no known breast cancer susceptibility mutation . A163 was propagated in a serum-free culture medium including the epidermal growth factor . Immunophenotypic characterization demonstrated a mixed luminal and basal-like phenotype . When epidermal growth factor was excluded from the culture medium , A163 entered a quiescent period followed by a period of increased cell proliferation in a subpopulation of the cells . The epidermal growth factor-independent subpopulation retained the basal-like phenotype of the parental cell line . Karyotype and fluorescent in situ hybridization analysis showed an amplification of epidermal growth factor receptor on 7q in A163-S1 only , resulting in high expression of total and phosphorylated epidermal growth factor receptor . The A163-S1 sub-line piles up in culture , indicating a loss of contact inhibition . When grown on transwell filters , A163 shows basal expression of P63 and cytokeratin 14 , whereas A163-S1 expresses P63 ubiquitously , and has lost the basal specific expression of cytokeratin 14 , indicating a loss of polarity . Furthermore , when cultured in reconstituted basement membrane matrix , A163 form polarized normal like acini . In contrast , A163-S1 form large disorganized structures with lack of polarity . These cell lines may prove useful to understand molecular changes in breast cancer progression , in particular basal-like breast cancer subtype with bad prognosis and no current treatment options .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors" } ]