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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: Periplocin is one of cardenolides isolated from cortex periplocae which is used for treatment of rheumatoid arthritis and reinforcement of bones and tendons in traditional medicine . Here , we investigated the anti-tumor activity of periplocin against lung cancer cells bothin vitro and in vivo , and explored its anti-cancer mechanism . Periplocin inhibited the growth of lung cancer cells and induced their apoptosis in time- and dose-dependent manners by cell cycle arrest in G0/G1 phase . Periplocin exhibited anti-tumor activity both in human ( A549 ) and mouse ( LL/2 ) lung cancer xenograft models . Immunohistochemical analysis revealed that intratumoral angiogenesis was significantly suppressed . Furthermore , anti-cancer activity mediated by periplocin was associated with decreased level of phosphorylated AKT and ERK both in vitro and in vivo , which were important for cell growth and survival . Moreover , periplocin induced apoptosis by downregulating Bcl-2 and upregulating Bax , leading to activation of caspase-3 and caspase-9 . These findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo , which could be attributed to the inhibition of proliferation and the induction of apoptosis signaling pathway , such as AKT and ERK . These observations provide further evidence on the anti-tumor effect of periplocin , and it may be of importance to further explore its potential role as a therapeutic agent for cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;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: OBJECTIVES The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters . METHODS The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically . Stereologic method was used for evaluation of the percentage of positively stained tumor cells . RESULTS Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 ( r = 0.74 , p &lt ; 0.001 ) . MCM-2 and Ki-67 expression was significantly associated with histologic grade ( p &lt ; 0.05 ) , and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status ( p &lt ; 0.05 ) . No significant association was observed between MCM-2 or Ki-67 expression and patient age , tumor size , lymph node status , clinical stage and menopausal status . CONCLUSION Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity ( Ki-67 labelling index ) . Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma ( Tab. 1 , Fig. 4 , Ref. 34 ) . Full Text ( Free , PDF ) www.bmj.sk .\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 growth-inhibitory effects of ketoconazole , an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes , were tested in human colon and breast cancer cell lines . In the serum independent HT29-S-B6 colon cell clone , ketoconazole reduced cell proliferation and [ 3H]thymidine incorporation in a dose-dependent fashion , with a 50% inhibitory concentration of approximately 2.5 microM . Flow cytometry showed an accumulation of cells in the G0-G1 phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase . Ketoconazole also inhibited [ 3H]thymidine incorporation in the hormone-independent breast cancer cells MDA-MB-231 and Evsa-T , with respective 50% inhibitory concentration of approximately 13 and 2 microM . The mechanism of action of ketoconazole is unknown . However , another lipoxygenase inhibitor , BW755C , inhibited only weakly [ 3H]-thymidine incorporation and accumulated the cells in S and G2 . Conversely , clotrimazole and SKF525A , inhibitors of cytochrome P-450 enzymes , had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole , other azole derivatives which do not inhibit cytochrome P-450 enzymes , had no effect . The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole .\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: Whole body hyperthermia ( WBH ) has been used as an adjunct to radio-/chemotherapy in patients with various malignant diseases . Although clear evidence is still missing , it has been hypothesized that an activation of the immune system might contribute to the therapeutic effect of WBH . To examine whether a treatment with 60-minute 41.8 degrees C WBH as an adjunct to chemotherapy ( WBH-CT ) induces an activation of T cells , blood samples were collected at numerous time points before and up to 48 h post-treatment . The aim of this study was to examine the effect of WBH-CT on the expression of a broad range of activation markers on peripheral blood lymphocytes ( PBL ) , on serum cytokines and intracellular cytokine levels in T cells , and the capacity of these cells to proliferate . Immediately after 41.8 degrees C WBH-CT treatment , a drastic increase in peripheral natural killer ( NK ) cells ( P<0.05 ) and CD56+ cytotoxic T lymphocytes ( CTL ; P<0.01 ) in the patients ' peripheral blood was observed . At 5 h post-treatment , the percentages of both effector cell types had returned to baseline levels . This transient phenomenon was accompanied by a short period of reduced T cell activity , indicated by diminished serum levels of soluble interleukin-2 receptors ( sIL-2R ) at 3 h post-WBH-CT ( P<0.05 ) and decreased lymphocytic proliferation at the same point in time . This first phase was followed by a marked but short-lived increase in the patients ' serum levels of interleukin-6 ( IL-6 ; P<0.01 ) during the first 5 h following treatment , with a subsequent decrease to baseline levels at 24 h and significantly increased serum levels of tumor necrosis factor-alpha ( TNF-alpha ) at 0 h ( P<0.01 ) , 3 h ( P<0.05 ) , 5 h ( P<0.05 ) and 24 h ( P<0.01 ) post-WBH-CT . The third phase of the immunological consequences of WBH-CT consisted of an increase in the percentage of peripheral cytotoxic T lymphocytes ( CTL ) expressing CD56 , reaching a maximum at 48 h post-WBH ( P<0.01 ) . Furthermore , the percentage of CD4+ T cells expressing the T cell activation marker CD69 increased nearly two-fold over time , reaching its maximum at 48 h ( P<0.05 ) . As an additional marker for T cell activation , serum levels of sIL-2R increased markedly ( P<0.01 ) , reaching maximum levels at the same point in time . Elevated intracellular concentrations of interferon-gamma ( IFN-gamma ) and/or TNF-alpha in CD8+ T cells were found in 4 out of 5 patients at 24 h post-WBH-CT . Since similar changes were not observed in patients receiving chemotherapy alone , this is the first study to provide evidence for prolonged WBH-CT-induced activation of human T cells .\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: Tobacco-induced oxidative stress leads to chronic inflammation and is implicated in the development of many human epithelial cancers , including head and neck cancer . Cigarette smoke exposure was shown to induce the expression of the ΔNp63α and nitric oxide synthase ( NOS)-2 in head and neck squamous cell carcinoma cells and immortalized oral keratinocytes . The NOS2 promoter was found to contain various cognate sequences for several transcription factors including interferon regulatory factor ( IRF)-6 and p63 , which were shown in vivo binding to the NOS2 promoter in response to smoke exposure . Small interfering ( si)-RNAs against both ΔNp63α and IRF6 decreased the induction of NOS2 promoter-driven reporter luciferase activity and were shown to inhibit NOS2 activity . Furthermore , both mainstream ( MSE ) and sidestream ( SSE ) smoking extracts induced changes in expression of autophagic marker , LC3B , while siRNA against ΔNp63α , IRF6 and NOS2 modulated these autophagic changes . Overall , these data support the notion that ΔNp63α/IRF6 interplay regulates NOS2 transcription , thereby underlying the autophagic-related cancer cell response to tobacco exposure .\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: Cancer cells preferentially metabolize glucose through aerobic glycolysis . This phenomenon , known as the Warburg effect , is an anomalous characteristic of glucose metabolism in cancer cells . Chronic inflammation is a key promoting factor of tumourigenesis . It remains , however , largely unexplored whether and how pro-tumourigenic inflammation regulates glucose metabolism in cancer cells . Here , we show that pro-inflammatory cytokines promote glycolysis in breast cancer cells , and that the inflammation-induced miR-155 functions as an important mediator in this process . We further show that miR-155 acts to upregulate hexokinase 2 ( hk2 ) , through two distinct mechanisms . First , miR-155 promotes hk2 transcription by activation of signal transducer and activator of transcription 3 ( STAT3 ) , a transcriptional activator for hk2 . Second , via targeting C/EBPβ ( a transcriptional activator for mir-143 ) , miR-155 represses mir-143 , a negative regulator of hk2 , thus resulting in upregulation of hk2 expression at the post-transcriptional level . The miR-155-mediated hk2 upregulation also appears to operate in other types of cancer cells examined . We suggest that the miR-155/miR-143/HK2 axis may represent a common mechanism linking inflammation to the altered metabolism in cancer cells .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;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 modifying effects of an immunosuppressive agent , 6-mercaptopurine ( 6-MP ) , on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride ( CCl4 ) or furfural were studied in male F344 rats . Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression , and significantly enhanced the induction of gamma-glutamyltranspeptidase ( GGT)-positive foci and nodules in the CCl4 but not furfural case . Glutathione S-transferase P ( GST-P)-positive preneoplastic lesions were not affected . Moreover , phenobarbital ( PB ) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model , no promotion influence being exerted after treatment with the non-carcinogenic furfural . This study , therefore , suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural .\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: We report the formation , detection , quantitation and structural characterization of products resulting from the adduction of deoxynucleosides ( deoxyadenosine , deoxyguanosine , deoxycytidine and 5-methyldeoxycytidine ) to the catechol estrogens ( CE ) of estrone , estradiol-17beta and estradiol-17 alpha . The crude products are obtained in a one-pot synthesis through oxidation of catechols to quinones and subsequent Michael-type reaction with the deoxynucleosides in acidic medium . In all experiments , adducts are detected by electrospray ionization mass spectrometry analysis after HPLC separation ( LC/ESI/MS(n) ) . The two pyrimidines deoxycytidine and 5-methyldeoxycytidine yield only CE adducts to deoxynucleosides , which correspond to stable adducts on DNA . For purines , the results depend on the CE ( 2,3- or 3,4-catechols ) used , the function and configuration on carbon 17 ( ketone for estrone , alcohol for alpha and beta isomers of estradiol ) , and on the purine itself ( deoxyadenosine or deoxyguanosine ) . Both stable adducts and deglycosylated adducts are formed , and therefore formation of stable adducts on DNA as well as the loss of purines from the DNA strands could be possible . MS(2) and MS(3) experiments prove to be relevant for further structural determinations , enabling in some cases the elucidation of the regiochemistry of adduction on the A and B rings of the steroid moiety .\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: Ataxia-telangiectasia mutated ( ATM ) is a cellular damage sensor that coordinates the cell cycle with damage-response checkpoints and DNA repair to preserve genomic integrity . However , ATM also has been implicated in metabolic regulation , and ATM deficiency is associated with elevated reactive oxygen species ( ROS ) . ROS has a central role in many physiological and pathophysiological processes including inflammation and chronic diseases such as atherosclerosis and cancer , underscoring the importance of cellular pathways involved in redox homeostasis . We have identified a cytoplasmic function for ATM that participates in the cellular damage response to ROS . We show that in response to elevated ROS , ATM activates the TSC2 tumor suppressor via the LKB1/AMPK metabolic pathway in the cytoplasm to repress mTORC1 and induce autophagy . Importantly , elevated ROS and dysregulation of mTORC1 in ATM-deficient cells is inhibited by rapamycin , which also rescues lymphomagenesis in Atm-deficient mice . Our results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy , identifying an integration node for the cellular damage response with key pathways involved in metabolism , protein synthesis , and cell survival .\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: In cancer cells , the aberrant conversion of pyruvate into lactate instead of acetyl-CoA in the presence of oxygen is known as the Warburg effect . The consequences and mechanisms of this metabolic peculiarity are incompletely understood . Here we report that p53 status is a key determinant of the Warburg effect . Wild-type p53 expression decreased levels of pyruvate dehydrogenase kinase-2 ( Pdk2 ) and the product of its activity , the inactive form of the pyruvate dehydrogenase complex ( P-Pdc ) , both of which are key regulators of pyruvate metabolism . Decreased levels of Pdk2 and P-Pdc in turn promoted conversion of pyruvate into acetyl-CoA instead of lactate . Thus , wild-type p53 limited lactate production in cancer cells unless Pdk2 could be elevated . Together , our results established that wild-type p53 prevents manifestation of the Warburg effect by controlling Pdk2 . These findings elucidate a new mechanism by which p53 suppresses tumorigenesis acting at the level of cancer cell metabolism .\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: DNA polymerases beta ( pol beta ) and eta ( pol eta ) are the only two eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro . Frameshift errors are an important aspect of mutagenesis . We have compared the types of frameshifts that occur during translesion synthesis past cisplatin and oxaliplatin adducts in vitro by pol beta and pol eta on a template containing multiple runs of nucleotides flanking a single platinum-GG adduct . Translesion synthesis past platinum adducts by pol beta resulted in approximately 50% replication products containing single-base deletions . For both adducts the majority of -1 frameshifts occurred in a TTT sequence 3-5 bp upstream of the DNA lesion . For pol eta , all of the bypass products for both cisplatin and oxaliplatin adducts contained -1 frameshifts in the upstream TTT sequence and most of the products of replication on oxaliplatin-damaged templates had multiple replication errors , both frameshifts and misinsertions . In addition , on platinated templates both polymerases generated replication products 4-8 bp shorter than the full-length products . The majority of short cisplatin-induced products contained an internal deletion which included the adduct . In contrast , the majority of oxaliplatin-induced short products contained a 3 ' terminal deletion . The implications of these in vitro results for in vivo mutagenesis are discussed .\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 have exploited properties of photosensitizers to study an aspect of the packing of chromatin in the cell nucleus . The fluorescent photosensitizers mesotetra(3-hydroxyphenyl) porphyrin and Photofrin II were both localized in the nuclear membrane and other membrane structures , but could not be found inside the nuclei . Light exposure of cells at 1 degrees C in the presence of the sensitizers induced DNA double-strand breaks . The length distributions of DNA fragments were determined by pulsed field gel electrophoresis . Because DNA damage is produced mainly via singlet oxygen diffusing less than 0.1 microns from the sensitizer , DNA double-strand breaks were supposedly produced within this distance of the nuclear membrane . Consistent with this , with prolonged illumination and with increasing concentrations of sensitizer the distribution of DNA fragment lengths reached a plateau level . In contrast , with the hydrophilic , intranuclear sensitizer meso-tetra(4-sulphonatophenyl)porphyrin , no such plateau level was found . The plateau distributions of DNA fragment lengths of different cell types had the same general shape with average fragment lengths ranging from 174 to 194 kilobasepairs . Particular genes , c-myc , fos and p53 , were found on broad distributions of photocleaved fragment lengths . The results indicate that on each side of the genes the locus of the chromatin fibre situated close to the nuclear membrane , varied randomly .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The role of regulatory T cells ( T(regs) ) in human colon cancer ( CC ) remains controversial : high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study . In mouse models of cancer , T(regs) have been reported to suppress inflammation and protect the host , suppress T cells and protect the tumor , or even have direct cancer-promoting attributes . These different effects may result from the presence of different T(reg) subsets . We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive , but compromised anti-inflammatory , properties ; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt . T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis . Indeed , ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions , suppressed inflammation , improved polyp-specific immune surveillance , and severely attenuated polyposis . Ablation of interleukin-6 ( IL-6 ) , IL-23 , IL-17 , or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt . Surprisingly , loss of IL-17A had a dual effect : IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer . Thus , we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation , potency of immune surveillance , and severity of disease outcome .\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: Lung cancers express the cholinergic autocrine loop , which facilitates the progression of cancer cells . The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers ( SCLCs ) . In this study we intended to investigate the growth inhibitory effect of R2HBJJ , a novel muscarinic antagonist , on non-small cell lung cancer ( NSCLC ) cells and the possible mechanisms . The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs . R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea . R2HBJJ markedly suppressed the growth of NSCLC cells , such as H1299 , H460 and H157 . In H1299 cells , both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin . Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition . Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection , respectively . Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb . Therefore , the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells . R2HBJJ , as a novel mAChRs antagonist , can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth , which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC .\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: By intravenous ( but not oral ) application of ascorbate , millimolar serum concentrations can be reached , which are preferentially cytotoxic to cancer cells . Cytotoxicity is mediated by transition metal-dependent generation of H(2)O(2) in the interstitial space . In this study , the sensitivity of neuroblastoma cells ( Kelly , SK-N-SH ) to ascorbate and H(2)O(2) and their defense mechanisms against H(2)O(2) were investigated . Since aerobic glycolysis ( the Warburg effect ) is a feature of many tumour cells , their glucose consumption and lactate production were monitored . Furthermore , synthesis and release of ferritin by neuroblastoma cells were analysed in order to examine whether ferritin is possibly an iron source for H(2)O(2) generation . Ascorbate ( 0.6-5.0 mM ) and H(2)O(2) ( 25-100 muM ) were found to be similarly cytotoxic to Kelly and SK-N-SH cells . In each case , cytotoxicity increased if cell concentrations decreased , in accordance with low cell concentrations having lower capacities to detoxify H(2)O(2) . Kelly and SK-N-SH cells produced and released remarkable amounts of lactate and ferritin . We propose the selective cytotoxicity of high dose ascorbate to tumour cells to be due to the preferential generation of H(2)O(2) in the acidic and ferritin-rich tumour microenvironment , combined with reduced defense systems against H(2)O(2) as a consequence of aerobic glycolysis .\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: In the present study , post-treatment effects of dietary turmeric on markers related to apoptosis , cell proliferation , and inflammation in 7,12-dimethylbenz(a)anthracene ( DMBA)-induced hamster buccal pouch ( HBP ) tumors were investigated . Tumors were induced by applying 0.5% DMBA topically to the HBP three times per week for 12 weeks . After tumor development , half of the animals continued on the control diet and the other half were shifted to a 1% turmeric diet for 4 weeks . To rule out DMBA discontinuation as a cause of inhibition in tumor growth , DMBA treatment was continued during dietary exposure of turmeric in another set of animals until the end of the experiment . The turmeric diet inhibited tumor growth in animals with or without DMBA carcinogen treatment compared to the animals on the control diet . When compared to hamsters bearing tumors that remained on the control diet , the buccal pouches of hamsters bearing tumors receiving turmeric showed the following results : ( 1 ) decreased cell proliferation ( diminished PCNA , cyclin D1 , and Bcl-2 ) and PCNA labelling index , ( 2 ) enhanced apoptosis ( increased Bax , caspase-3 , caspase-9 , and cytochrome c , and decreased survivin ) and apoptotic index , ( 3 ) decreased inflammation ( decreased Cox-2 ) , and ( 4 ) decreased MAPK activation ( p-ERK and p-p38 ) . These data indicate that tumor growth decreased due to the modulation of cellular pathways associated with cell proliferation and apoptosis .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We have investigated the possibility that photoexcited titanium dioxide ( TiO2 ) could inhibit the growth of malignant cells . We studied the anti-glioma effects of nano-TiO2 excited with ultraviolet A ( UVA ) irradiation both in vitro and in vivo . Transmission electron microscopy demonstrated that glioma cells take up TiO2 by phagocytosis , and vital staining revealed that TiO2 alone has no effect on glioma cell proliferation . However , if TiO2 was combined with UVA irradiation the proliferation rate was decreased significantly compared to controls ( P<0.05 ) . RT-PCR suggested that TiO2 induction of glioma cell apoptosis is associated with changes in the expression of genes encoding Bcl-2 family members . We then investigated the in vivo antitumor effects of combined TiO2 plus UVA treatment of established glioma tumors . TiO2 plus UVA led to pronounced areas of necrosis , elevated indices of apoptosis , delayed tumor growth , and increased survival compared with the TiO2-alone control group ( P<0.001 ) . Log-rank survival analysis showed that median survival duration was prolonged ( P<0.001 ) . These findings suggest that nano-TiO2 based photodynamic therapy has potential in the treatment of glioma .\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: HER-2/neu gene expression , DNA ploidy and proliferation index were studied in 250 cases of breast cancer . Expression of HER-2/neu was determined by using an antibody to the HER-2/neu receptor . Ki-67 antibody was used to determine the proliferation index of the breast cancers , and the Feulgen method was used to assess DNA amounts in the tumor cells . Histochemical staining was quantitated by image analysis . Of the cancers studied , 72 were positive for overexpression of HER-2/neu protein ; of these , 62 ( 86% ) possessed near-tetraploid DNA content , and 47 ( 65% ) had more than one G0G1 stem line ( polyploid ) of DNA distribution . Cells from the cases negative for HER/2-neu overexpression contained DNA amounts that ranged from diploid to varying degrees of aneuploid . A significant difference in the amounts of cellular proliferation in HER-2/neu overexpressing cancers was found between those that expressed the HER-2/neu receptor on their membranes and those that exhibited mainly cytoplasmic receptors .\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 immune system of vertebrates is able to detect bacterial DNA based on the presence of unmethylated CpG motifs . We examined the therapeutic potential of oligodeoxynucleotides with CpG motifs ( CpG ODN ) in a colon carcinoma model in BALB/c mice . Tumors were induced by s.c. injection of syngeneic C26 cells or Renca kidney cancer cells as a control . Injection of CpG ODN alone or in combination with irradiated tumor cells did not protect mice against subsequent tumor challenge . In contrast , weekly injections of CpG ODN into the margin of already established tumors resulted in regression of tumors and complete cure of mice . The injection site was critical , since injection of CpG ODN at distant sites was not effective . Mice with two bilateral C26 tumors rejected both tumors upon peritumoral injection of one tumor , indicating the development of a systemic immune response . The tumor specificity of the immune response was demonstrated in mice bearing a C26 tumor and a Renca tumor at the same time . Mice that rejected a tumor upon peritumoral CpG treatment remained tumor free and were protected against rechallenge with the same tumor cells , but not with the other tumor , demonstrating long term memory . Tumor-specific CD8 T cells as well as innate effector cells contributed to the antitumor activity of treatment . In conclusion , peritumoral CpG ODN monotherapy elicits a strong CD8 T cell response and innate effector mechanisms that seem to act in concert to overcome unresponsiveness of the immune system toward a growing tumor .\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: Cellular senescence has emerged as a critical tumor suppressive mechanism in recent years , but relatively little is known about how senescence occurs . Here , we report that secreted Frizzled-related protein 1 ( SFRP1 ) , a secreted antagonist of Wnt signaling , is oversecreted upon cellular senescence caused by DNA damage or oxidative stress . SFRP1 is necessary for stress-induced senescence caused by these factors and is sufficient for the induction of senescence phenotypes . We present evidence suggesting that SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma ( Rb ) pathway and that cancer-associated SFRP1 mutants are defective for senescence induction .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;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: Contrary to the paradigm that cancer incidence increases indefinitely with age , significant data now suggest cancer incidence may markedly reduce beyond age 80 years for humans and beyond 800 days for mice , and is not inevitable . We show that increasing cellular senescence with age is a possible cause of this reduction , since senescent cells are removed from the pool of cells that retain proliferative ability necessary for cancer . We further show that animal interventions appearing to alter senescence , p53 mutation and melatonin dosing , support the prediction that increasing senescence rate reduces cancer while reducing lifespan , and vice versa . Studies of environmental agents associated with increased cancer might be re-examined to find if there is an association with longevity increases , which may markedly alter our view of such agents . We also show that if an agent functions by slowing both senescence and carcinogenesis , longevity is increased while reducing cancer . Dietary restriction is the only known intervention that accomplishes this , but there may be others .\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: Oral squamous cell carcinoma ( OSCC ) is the most common malignant tumor in the oral and maxillofacial region . The mechanism of carcinogenesis of OSCC is still unclear . Based on the previous cell line , HIOEC-B(a)P-96 ( HB96 ) , which we obtained by HPV16 E6/E7-immortalized human oral epithelial cells ( HIOEC ) and benzo(a)pyrene inducement , we prepared a new HB-second generation cancer cell line ( HB-2 ) by continuous passage . Its characteristics such as morphology , proliferation activity , karyotype , and tumorigenesis were studied . The HB-2 cells displayed uncontrolled cell division and lost contact inhibition leading to cell overlap . Cells were polygonal and unevenly shaped , with an increased nucleus versus plasma ratio . Increased proliferative activity was confirmed by MTT assays . The tumorigenicity was confirmed by tumor growth experiments in nude mice . Therefore , the HB-2 and HB96 cell lines are useful tools to study the mechanism of carcinogenesis of OSCC in vitro for future genomic and proteomic analyses .\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: OBJECTIVE To investigate a potential mechanism of invasion and metastasis of oral cancers , and the possibility of the adhesion molecules being markers for evaluating the prognosis of oral cancers . METHODS Randomly selecting achieved paraffin blocks , including 60 cases of squamous cell carcinoma(SCC) , 30 cases of verrucous carcinoma(VC) of oral mucosa and 30 cases of basal cell carcinoma ( BCC ) of epidermis . All cases were followed up . Using immunohistochemistry method ( Envision ) to detect the expression of E-cadherin antibody and observe under light microscope . RESULTS The studies demonstrated that 38.2% of SCC had recurrence and/or metastases after operation . However , only 0.0% and 0.04% , in VC and BCC , respectively , had recurrence and/or metastases . There was significant difference on prognoses between SCC and VC or BCC . The immunostaining showed significant difference of E-cad expression between SCC and VC ( P<0.01 ) , SCC and BCC ( P<0.05 ) . The former was weaker than VC and BCC . However , no difference was showed in E-cad expression between VC and BCC ( P>0.05 ) . CONCLUSION E-cad plays an important role in maintaining the phenotype of epithelial cell of SCC and normal oral mucosa . The degree of expression of E-cad was correlated with the ability of invasion and/or metastasis of SCC , VC and BCC . It indicates that E-cad may be as a helpful marker to evaluate the prognosis of oral cancers .\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: An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists . In order to obtain large quantities of cells and reproducibility , human endothelial cells with extended life spans were developed by retroviral transfection . The resulting cells grown in a serum-free medium containing endothelial cell growth supplement ( ECGS ) have a telomerase activity , extended life spans of at least 21 passages , and an endothelial cell phenotype ( diI-acetylated-LDL upake , factor VIII-related antigen , VEGFR-1 and R-2 , and tissue-type plasminogen activator ( tPA) ) that resembled that of unaltered primary endothelial cells . Exceptions were ( i ) a higher expression of tPA , and ( ii ) a non-significant growth response to FGF-2 or VEGF stimulation . Within three-dimensional fibrin gels , specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells . Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS , respectively . Both cell types produced FGF-2 and VEGF cytokines . Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines . These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds .\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: Tumors are infiltrated by macrophages , T and B-lymphocytes , which may favor tumor development by promoting angiogenesis , growth and invasion . The aim of this study was to investigate the clinical relevance of the relative amount of macrophages ( CD68⁺ ) , T-cells ( CD3⁺ and B-cells ( CD20⁺ ) at the invasive front of breast carcinomas , and the expression of matrix metalloproteases ( MMPs ) and their inhibitors ( TIMPs ) either at the invasive front or at the tumor center . We performed an immunohistochemical study counting CD3 , CD20 and CD68 positive cells at the invasive front , in 102 breast carcinomas . Also , tissue sections were stained with MMP-2 , -9 , -11 , -14 and TIMP-2 antibodies , and immunoreactivity location , percentage of reactive area and intensity were determined at the invasive front and at the tumor center . The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center ( p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio , respectively for MMP-11 and TIMP-2 ) . In addition , a high CD68/(CD3+CD20) ratio ( >0.05 ) was directly associated with a higher probability of shortened relapse-free survival . Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival ( RR : 2.54 , CI : ( 1.23-5.24 ) , p<0.01 ) . Therefore , CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker .\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: Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects , including anti-inflammatory , cardio-protective , and cancer-protective activities . It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders . Ulcerative colitis is an idiopathic , chronic inflammatory disease of the colon associated with a high colon cancer risk . Here , we used a dextran sulfate sodium ( DSS ) mouse model of colitis , which resembles human ulcerative colitis pathology . Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner . Resveratrol significantly improves inflammation score , downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria , and modulates CD3(+) T cells that express tumor necrosis factor-alpha and IFN-gamma . Markers of inflammation and inflammatory stress ( p53 and p53-phospho-Ser(15) ) are also downregulated by resveratrol . Because chronic colitis drives colon cancer risk , we carried out experiments to determine the chemopreventive properties of resveratrol . Tumor incidence is reduced from 80% in mice treated with azoxymethane ( AOM ) + DSS to 20% in mice treated with AOM + DSS + resveratrol ( 300 ppm ) . Tumor multiplicity also decreased with resveratrol treatment . AOM + DSS-treated mice had 2.4 +/- 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol , which had 0.2 +/- 0.13 tumors per animal . The current study indicates that resveratrol is a useful , nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis .\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: Numerous scientific studies have examined the relationship between coffee consumption and an array of medical conditions , including cancer , and yet the direct effect of commercially brewed coffee on cancer cells has not been evaluated . The purpose of this study was to evaluate the antiproliferation effect of 4 different regular and decaffeinated coffee brews and 3 of coffee's bioactive ingredients-caffeine , chlorogenic acids , and caffeic acid-on 2 human ovarian cancer cell lines alone and in combination with cisplatin ( CDDP ) . Antiproliferation IC(50) for Brand A regular and decaffeinated coffee on A2780 cells was 1:70.79 ± 5.66 and 1:55.68 ± 2.00 dilution ( vol/vol ) in tissue culture medium ( mean ± standard error of the mean ; N = 12 ) , respectively , and slightly lower on A2780CP70 cells . Three other brands showed lower antiproliferation activity . Antiproliferation IC(50) concentrations of chlorogenic acids and caffeic acid are many folds lower than caffeine . In combination with CDDP , both Brand A coffee brews , and the 3 bioactive compounds , showed additive antiproliferation effect on both cancer cell lines . Flow cytometry analysis showed that coffee treatment induced apoptosis of A2780 and A2780CP70 cells . To our knowledge , this is the first report showing the antiproliferation activity and the additive effect with CDDP of commercially prepared coffee brews on human cancer cell lines .\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 Ras-assocation domain family ( RASSF ) of tumor suppressor proteins until recently contained six proteins named RASSF1-6 . Recently , four novel family members , RASSF7-10 , have been identified by homology searches for RA-domain-containing proteins . These additional RASSF members are divergent and structurally distinct from RASSF1-6 , containing an N-terminal RA domain and lacking the Sav/RASSF/Hpo ( SARAH ) domain . Here , we show that RASSF8 is ubiquitously expressed throughout the murine embryo and in normal human adult tissues . Functionally , RNAi-mediated knockdown of RASSF8 in non-small-cell lung cancer ( NSCLC ) cell lines , increased anchorage-independent growth in soft agar and enhanced tumor growth in severe combined immunodeficiency ( SCID ) mice . Furthermore , EdU staining of RASSF8-depleted cells showed growth suppression in a manner dependent on contact inhibition . We show that endogenous RASSF8 is not only found in the nucleus , but is also membrane associated at sites of cell-cell adhesion , co-localizing with the adherens junction ( AJ ) component beta-catenin and binding to E-cadherin . Following RASSF8 depletion in two different lung cancer cell lines using alternative small interfering RNA ( siRNA ) sequences , we show that AJs are destabilized and E-cadherin is lost from the cell membrane . The AJ components beta-catenin and p65 are also lost from sites of cell-cell contact and are relocalized to the nucleus with a concomitant increase in beta-catenin-dependent and nuclear factor-kappaB ( NF-kappaB)-dependent signaling following RASSF8 depletion . RASSF8 may also be required to maintain actin -cytoskeletal organization since immunofluorescence analysis shows a striking disorganization of the actin- cytoskeleton following RASSF8 depletion . Accordingly , scratch wound healing studies show increased cellular migration in RASSF8-deficient cells . These results implicate RASSF8 as a tumor suppressor gene that is essential for maintaining AJs function in epithelial cells and have a role in epithelial cell migration .\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: Pyruvate kinase M2 ( PKM2 ) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms . Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 Ile429/Leu431 through the ERK2 docking groove and phosphorylates PKM2 at Ser37 , but does not phosphorylate PKM1 . Phosphorylated PKM2 Ser37 recruits PIN1 for cis-trans isomerization of PKM2 , which promotes PKM2 binding to importin α5 and translocating to the nucleus . Nuclear PKM2 acts as a coactivator of β-catenin to induce c-Myc expression , resulting in the upregulation of GLUT1 , LDHA and , in a positive feedback loop , PTB-dependent PKM2 expression . Replacement of wild-type PKM2 with a nuclear translocation-deficient mutant ( S37A ) blocks the EGFR-promoted Warburg effect and brain tumour development in mice . In addition , levels of PKM2 Ser37 phosphorylation correlate with EGFR and ERK1/2 activity in human glioblastoma specimens . Our findings highlight the importance of nuclear functions of PKM2 in the Warburg effect and tumorigenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The evidence that androgen blockade-resistant prostate cancer , termed castration resistant , remains androgen receptor ( AR ) dependent is compelling . AR is re-activated through multiple mechanisms including expression of constitutively active splice variants that lack hormone binding domains ( HBDs ) . This highlights need to develop therapies that target regions other than the HBD . Because the p160 coactivators interact most strongly with the amino-terminus of AR , we examined the consequences of disrupting this interaction . We identified two overlapping SRC-1 peptides that interact with AR , but not with progesterone receptor . These peptides reduce AR and AR variant AR-V7 dependent induction of an AR responsive reporter . Using mammalian two hybrid assays , we found that the peptides interrupt the AR/SRC-1 , AR/SRC-2 and AR N/C interactions , but not SRC-1/CARM-1 interactions . Consistent with the SRC-1 dependence of induced , but not repressed genes , in LNCaP cells , the peptides inhibited hormone dependent induction of endogenous target genes including PSA and TMPRSS2 , but did not block AR dependent repression of UGT2B17 or inhibit vitamin D receptor activity . Simultaneous detection of SRC-1 peptides and PSA by double immunofluorescence in transfected LNCaP cells clearly demonstrated a strong reduction in PSA levels in cells expressing the peptides . The peptides also inhibited the AR dependent expression of PSA in castration resistant C4-2 cells . Moreover they inhibited androgen dependent proliferation of LNCaP cells and proliferation of C4-2 cells in androgen depleted medium without affecting AR negative PC-3 cells . Thus , the p160 coactivator binding site is a novel potential therapeutic target to inhibit AR activity .\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: Landmark studies of the status of DNA damage checkpoints and associated repair functions in preneoplastic and neoplastic cells has focused attention on importance of these pathways in cancer development , and inhibitors of repair pathways are in clinical trials for treatment of triple negative breast cancer . Cancer heterogeneity suggests that specific cancer subtypes will have distinct mechanisms of DNA damage survival , dependent on biological context . In this study , status of DNA damage response ( DDR)-associated proteins was examined in breast cancer subtypes in association with clinical features ; 479 breast cancers were examined for expression of DDR proteins γH2AX , BRCA1 , pChk2 , and p53 , DNA damage-sensitive tumor suppressors Fhit and Wwox , and Wwox-interacting proteins Ap2α , Ap2γ , ErbB4 , and correlations among proteins , tumor subtypes , and clinical features were assessed . In a multivariable model , triple negative cancers showed significantly reduced Fhit and Wwox , increased p53 and Ap2γ protein expression , and were significantly more likely than other subtype tumors to exhibit aberrant expression of two or more DDR-associated proteins . Disease-free survival was associated with subtype , Fhit and membrane ErbB4 expression level and aberrant expression of multiple DDR-associated proteins . These results suggest that definition of specific DNA repair and checkpoint defects in subgroups of triple negative cancer might identify new treatment targets . Expression of Wwox and its interactor , ErbB4 , was highly significantly reduced in metastatic tissues vs. matched primary tissues , suggesting that Wwox signal pathway loss contributes to lymph node metastasis , perhaps by allowing survival of tumor cells that have detached from basement membranes , as proposed for the role of Wwox in ovarian cancer spread .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;genomic instability and mutation;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The effects of glucocorticoid ( GC ) on the proliferation of Dunn Osteosarcoma ( OS ) cells were examined under in vitro culture conditions . Dexamethasone ( Dex ) inhibited the proliferation of Dunn OS cells in a dose-dependent manner , while the addition of anti-GC , RU486 , to the culture medium in part recovered Dex-induced growth inhibition . The number of maximum binding sites ( Bmax ) and the dissociation constant ( Kd ) value of glucocorticoid receptor ( GR ) in Dunn OS cells were 19,560 sites/cell and 5.2 +/- 0.8 nM , respectively . RU486 competed with labeled Dex against GR at a concentration of 10(-6) M. Western blot analysis of [ 3H]Dex-mesylate-labeled cell homogenate and immunohistochemical staining against GR further confirmed the presence of GR . Dex treatment of Dunn OS cells resulted in apoptosis with the characteristic internucleosomal DNA cleavage shown by the DNA ladder pattern in agarose gel electrophoresis . These data demonstrate that GC inhibits the proliferation of Dunn OS cells via GR , for which one possible mechanism in vitro is induction of apoptosis .\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: OBJECTIVE This study describes a new method used in the clinical laboratory at Hospital Israelita Albert Einstein to detect mutations in exons 8 and 17 of the KIT gene in patients with acute myeloid leukemia . METHODS Genomic DNA extraction was performed on 54 samples of peripheral blood or bone marrow from patients with acute myeloid leukemia . The extracted DNA was amplified by polymerase chain reaction and sequenced , and the fragments were analyzed . RESULTS Within the analyzed samples , we detected four mutations in exon 8 , two mutations in exon 17 , and mutations or a double mutation in one sample . CONCLUSION The tests detecting mutations in exon 8 and 17 on the KIT gene were successfully standardized . The test is now included among the routine diagnostics employed for patients at Hospital Israelita Albert Einstein clinical laboratory .\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: Human carcinomas are defined by recurrent chromosomal aneuploidies , which result in a tissue-specific distribution of genomic imbalances . In order to develop models for these genome mutations and to determine their role in tumorigenesis , we generated 45 spontaneously transformed murine cell lines from normal epithelial cells derived from bladder , cervix , colon , kidney , lung , and mammary gland . Phenotypic changes , chromosomal aberrations , centrosome number , and telomerase activity were assayed in control uncultured cells and in three subsequent stages of transformation . Supernumerary centrosomes , binucleate cells , and tetraploidy were observed as early as 48 hr after explantation . In addition , telomerase activity increased throughout progression . Live-cell imaging revealed that failure of cytokinesis , not cell fusion , promoted genome duplication . Spectral karyotyping demonstrated that aneuploidy preceded immortalization , consisting predominantly of whole chromosome losses ( 4 , 9 , 12 , 13 , 16 , and Y ) and gains ( 1 , 10 , 15 , and 19 ) . After transformation , focal amplifications of the oncogenes Myc and Mdm2 were frequently detected . Fifty percent of the transformed lines resulted in tumors on injection into immunocompromised mice . The phenotypic and genomic alterations observed in spontaneously transformed murine epithelial cells recapitulated the aberration pattern observed during human carcinogenesis . The dominant aberration of these cell lines was the presence of specific chromosomal aneuploidies . We propose that our newly derived cancer models will be useful tools to dissect the sequential steps of genome mutations during malignant transformation , and also to identify cancer-specific genes , signaling pathways , and the role of chromosomal instability in this process .\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: Vaccination is , in theory , a safe and effective approach for controlling disseminated or metastatic cancer due to the specificity of the mammalian immune system , yet its success in the clinic has been hampered thus far by the problem of immune tolerance to tumor self-antigen . Here we describe a DNA vaccination strategy that is able to control cancer by overcoming immune tolerance to tumor self-antigen . We engineered a DNA construct encoding a dimeric form of a secreted single chain trimer of major histocompatibility complex class I heavy chain , β2-microglobulin , and peptide antigen linked to immunoglobulin G ( SCT-Ag/IgG ) . The chimeric protein was able to bind to antigen-specific CD8+ T cells with nearly 100% efficiency and strongly induce their activation and proliferation . In addition , the chimeric protein was able to coat professional antigen-presenting cells through the Fc receptor to activate antigen-specific CD8+ T cells . Furthermore , intradermal vaccination with DNA encoding SCT-Ag/IgG could generate significant numbers of cytotoxic effector T cells against tumor self-antigen and leads to successful therapeutic outcomes in a preclinical model of metastatic melanoma . Our data suggest that the DNA vaccine strategy described in the current study is able to break immune tolerance against endogenous antigen and result in potent therapeutic antitumor effects . Such strategy may be used in other antigenic systems for the control of infections and/or cancers .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;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: Epidemiological studies exploring the connection between hypertension and cancer incidence find a higher cancer mortality in hypertensive patients , particularly elevated in hypertension associated with a stimulation of the renin-angiotensin-aldosterone system . Primary aldosteronism , with plasma aldosterone levels between 0.5 and 1 nM ( 18-36 ng/dL ) and local aldosterone levels up to 500 nM ( 18,000 ng/dL ) , is now recognised as a more common cause for hypertension . We recently found angiotensin II to be genotoxic due to its induction of oxidative stress . Since aldosterone in higher concentrations also has oxidative effects , its potential genotoxic action in pig LLC-PK1 cells with properties of proximal tubules was analysed . DNA damage was evaluated by two test systems : the comet assay , and the micronucleus frequency test . The results showed that aldosterone concentrations starting from 10 nM ( 360 ng/dL ) caused a significant increase of DNA damage monitored with the comet assay in LLC-PK1 , while there was no change in cell vitality and proliferation . The micronucleus frequency test revealed that 10 nM aldosterone also leads to the formation of micronuclei . Furthermore , the formation of superoxide radicals in the cells by this aldosterone concentration could be detected with the superoxide-specific stain dihydroethidium . Further evidence for oxidative stress-induced DNA damage was its reversibility by the antioxidants tempol and catalase . Addition of the steroidal mineralocorticoid receptor antagonist spironolactone or the novel selective nonsteroidal antagonist ( R)-BR-4628 reduced the DNA damage and the amount of superoxide radicals indicating a receptor-dependent process .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Folate ( vitamin B9 ) is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate ( dTMP ) and s-adenosylmethionine ( AdoMet ) . The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance , but still unclear . We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis , which is prominent in prostate cells . We , therefore , hypothesized that prostate cells might be highly susceptible to genetic , epigenetic and phenotypic changes consequent to folate restriction . RESULTS We studied the consequences of long-term , mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate ( TRAMP ) model , recapitulating different stages of prostate cancer ; benign , transformed and metastatic . High-performance liquid chromatography analysis demonstrated that mild folate depletion ( 100 nM ) sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines . Random oligonucleotide-primed synthesis ( ROPS ) revealed a significant increase in uracil misincorporation and DNA single strand breaks , while spectral karyotype analysis ( SKY ) identified five novel chromosomal rearrangements in cells grown with mild folate depletion . Using global approaches , we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine , indicating a broad effect of folate depletion on epigenetic regulation . These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion . CONCLUSIONS This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with supraphysiological amounts of folate ( 2 microM ) routinely used in tissue culture . In addition , we elucidate for the first time the contribution of these aspects to consequent phenotype changes in epithelial cells . These results provide a strong rationale for studying the effects of folate manipulation on the prostate in vivo , where cells might be more sensitive to changes in folate status resulting from folate supplementation or antifolate therapeutic approaches .\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: Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors . Although the full process depends on innate and adaptive immunity , it remains unclear whether innate immunity alone is capable of immunoediting . To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity , we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type , RAG2(-/-) , and RAG2(-/-)x γc(-/-) mice . We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity . This activity required natural killer ( NK ) cells and interferon γ ( IFN-γ ) , which mediated the induction of M1 macrophages . M1 macrophages could be elicited by administration of CD40 agonists , thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice . Our results suggest that in the absence of adaptive immunity , NK cell production of IFN-γ induces M1 macrophages , which act as important effectors during cancer immunoediting .\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: We report that all-trans retinoic acid ( ATRA ) in combination with zoledronic acid has strong synergistic cytotoxic and apoptotic effects against human hormone- and drug-refractory prostate cancer cells , PC-3 and DU-145 , in a time- and dose-dependent manner . We further investigated the effect of the combination treatment on the apoptotic process by both oligoarray and protein array analysis in DU-145 cells , in which the drug combination shows much more strong synergistic effects , as compared to PC-3 cells . Moreover , we have also performed real time-PCR array analysis to validate oligoarray results . We demonstrated that the combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in human androgen-and drug refractory prostate cancer cells DU-145 , at either transcriptional or translational levels . While expression of proapoptotic genes such as tumor necrosis factor receptor superfamily ( TNFRSF ) , Bad , Bax , Fas , FADD are induced with the exposure of the combination , expression of antiapoptotic genes or proteins such as members of inhibitor apoptosis family ( IAPs ) , MCL-1 , LTBR , p53 and bcl-2 are reduced . Because this novel combination treatment has fewer side effects than is generally the case with conventional cytotoxic agents , this regimen may be a good option for treatment of elderly prostate cancer patients .\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: OBJECTIVE To observe the anti-tumor recurrent and metastatic efficacy of Ru'ai Shuhou Recipe ( RSR ) on HER2 positive breast cancer , to evaluate the effects of RSR on the expressions of matrix metalloproteinases ( MMPs ) and the tissue inhibitor of metalloproteinases ( TIMPs ) in the recurrence and metastasis of HER2 positive breast cancer , thus revealing its anti-tumor recurrent and metastatic mechanisms . METHODS Selected were 30-week-old HER2/neu transgenic spontaneous breast cancer mice FVB/neu . The primary tumor resection was carried out . After surgery they were randomly divided into the blank control group , the RSR group , the Herceptin group , and the combination group ( RSR + Herceptin group ) . The treatment lasted for 4 months . The inhibition rate of the recurrent tumor volume and the inhibition rate of the lung metastasis were evaluated . The expressions of matrix metalloproteinase-2 ( MMP-2 ) , matrix metalloproteinase-9 ( MMP-9 ) , tissue inhibitor of metalloproteinase ( TIMP-1 ) , and TIMP-2 in the recurrent tumor tissue were detected using Western blot . RESULTS By the end of the treatment the average recurrent tumor volume was 11.11 +/- 8.71 cm3 in the blank control group and 5.56 +/- 5.55 cm3 of the RSR group , showing statistical difference between the two groups ( P = 0.037 ) . The average lung metastatic nodule was 16 in the blank control group and 10 in the RSR group . The inhibition rate of lung metastasis was 37. 85% in the RSR group , but with no statistical significance . The expression level of activated MMP-2 in the RSR group was down-regulated when compared with the blank control group , the Herceptin group , and the combination group ( P &lt ; 0.05 ) . The expression of MMP-9 of the RSR group , the Herceptin group , and the combination group was significantly down-regulated when compared with the blank control group ( P &lt ; 0.05 ) . The expression of MMP-9 of the RSR group and the combination group was further down-regulated when compared with the Herceptin group ( P &lt ; 0.05 ) . The expressions of both TIMP-1 and TIMP-2 of the RSR group , the Herceptin group , and the combination group were all up-regulated when compared with the blank control group ( P &lt ; 0.05 ) . The increased expression of TIMP-1 was more significantly in the RSR group and the combination group when compared with the Herceptin group ( P &lt ; 0.05 ) . It was higher in the combination group than in the RSR group ( P &lt ; 0.05 ) . CONCLUSIONS RSR could inhibit the tumor recurrence of FVB/neu mice . It could reduce the degradation of extracellular matrix and increase the protective effects of extracellular matrix . It might achieve its anti-tumor effect through effecting the invasive and metastatic capabilities of breast tumor cells .\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: Treatment of cells with the anti-cancer drug camptothecin ( CPT ) induces topoisomerase I ( Top1)-mediated DNA damage , which in turn affects cell proliferation and survival . In this report , we demonstrate that treatment of the wild-type HCT116 ( wt HCT116 ) human colon cancer cell line and the isogenic p53(-/-) HCT116 and p21(-/-) HCT116 cell lines with a high concentration ( 250 nm ) of CPT resulted in apoptosis , indicating that apoptosis occurred by a p53- and p21-independent mechanism . In contrast , treatment with a low concentration ( 20 nm ) of CPT induced cell cycle arrest and senescence of the wt HCT116 cells , but apoptosis of the p53(-/-) HCT116 and p21(-/-) HCT116 cells . Further investigations indicated that p53-dependent expression of p21 blocked apoptosis of wt HCT116 cells treated with 20 nm , but not 250 nm CPT . Interestingly , blocking of the apoptotic pathway , by Z-VAD-FMK , in p21(-/-) HCT116 cells following treatment with 20 nm CPT did not permit the cells to develop properties of senescence . These observations demonstrated that p21 was required for senescence development of HCT116 cells following treatment with low concentrations of CPT .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Autophagy , or autophagocytosis , is a selective intracellular degradative process involving the cell's own lysosomal apparatus . An essential component in cell development , homeostasis , repair and resistance to stress , autophagy may result in either cell death or survival . The targeted region of the cell is sequestered within a membrane structure , the autophagosome , for regulation of the catabolic process . A key factor in both autophagosome formation and autophagosome maturation is a protein encoded by the ultraviolet irradiation resistance-associated gene ( UVRAG ) . Conversely , the serine/threonine-specific protein kinase B ( PKB , also known as Akt ) , which regulates survival in various cancers , inhibits autophagy through mTOR activation . We found that Akt1 may also directly inhibit autophagy by down-regulating UVRAG both in a 293T transient transfection system and breast cancer cells stably expressing Akt1 . The UVRAG with mutations at putative Akt1-phosphorylation sites were still inhibited by Akt1 , and dominant-negative Akt1 also inhibited UVRAG expression , suggesting that Akt1 down-regulates UVRAG by a kinase activity-independent mechanism . We showed that Akt1 overexpression in MDA-MB-231 breast cancer cells down-regulated UVRAG transcription . Cells over-expressing Akt1 were more resistant than control cells to ultraviolet light-induced autophagy and exhibited the associated reduction in cell viability . Levels of the autophagosome indicator protein LC3B-II and mRFP-GFP-LC3 were reduced in cells that over-expressing Akt1 . Inhibiting Akt1 by siRNA or reintroducing UVRAG gene rescued the level of LC3B-II in UV-irradiation . Altogether , these data suggest that Akt1 may inhibit autophagy by decreasing UVRAG expression , which also sensitizes cancer cells to UV irradiation .\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: Testicular Germ Cell Tumors ( TGCT ) and patient-derived cell lines are extremely sensitive to cisplatin and other interstrand cross-link ( ICL ) inducing agents . Nevertheless , a subset of TGCTs are either innately resistant or acquire resistance to cisplatin during treatment . Understanding the mechanisms underlying TGCT sensitivity/resistance to cisplatin as well as the identification of novel strategies to target cisplatin-resistant TGCTs have major clinical implications . Herein , we have examined the proficiency of five embryonal carcinoma ( EC ) cell lines to repair cisplatin-induced ICLs . Using γH2AX staining as a marker of double strand break formation , we found that EC cell lines were either incapable of or had a reduced ability to repair ICL-induced damage . The defect correlated with reduced Homologous Recombination ( HR ) repair , as demonstrated by the reduction of RAD51 foci formation and by direct evaluation of HR efficiency using a GFP-reporter substrate . HR-defective tumors cells are known to be sensitive to the treatment with poly(ADP-ribose) polymerase ( PARP ) inhibitor . In line with this observation , we found that EC cell lines were also sensitive to PARP inhibitor monotherapy . The magnitude of sensitivity correlated with HR-repair reduced proficiency and with the expression levels and activity of PARP1 protein . In addition , we found that PARP inhibition strongly enhanced the response of the most resistant EC cells to cisplatin , by reducing their ability to overcome the damage . These results point to a reduced proficiency of HR repair as a source of sensitivity of ECs to ICL-inducing agents and PARP inhibitor monotherapy , and suggest that pharmacological inhibition of PARP can be exploited to target the stem cell component of the TGCTs ( namely ECs ) and to enhance the sensitivity of cisplatin-resistant TGCTs to standard treatments .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The main objective of the present investigation was to study the urinary neopterin excretion in the context of the activation of the adaptive cellular immune system at the tumor site . For this purpose , we compared pre-treatment urinary neopterin levels measured in 92 ovarian cancer patients , with intratumoral levels of mRNA transcripts from factors either involved in the adaptive antitumor immune defense ( CD3 , IFN-γ , IRF-1 , IRF-2 , SOCS1 and iNOS ) or immune tolerance ( FoxP3 ) . This study did not reveal an association between urinary neopterin and one of these investigated \" on tumor site transcripts \" . From all the factors reflecting the magnitude of the local adaptive antitumor response , intratumoral IRF-1 expression above the edge of the 25th percentile was found to predict most reliably favorable progression-free ( median 34 months vs. 10 months ; p &lt ; 0.001 ) and overall ( median 52 months vs. 16 months ; p &lt ; 0.001 ) survival . In contrast , pre-treatment urinary neopterin excretion above 275 μmol/mol creatinine , which indicates an unspecific activation of the innate immune system , was associated with a very poor overall survival with a median of only 11 months when compared with a median overall survival of 40 months in patients with lower urinary neopterin excretion ( p = 0.021 ) . Interestingly , the considerable survival benefit in patients with high IRF-1-expressing cancers was completely abrogated as well for progression-free as for overall survival when urinary neopterin concentrations were found to be concomitantly elevated . These findings demonstrate that in ovarian carcinomas the unspecific \" cancer-related inflammation \" contributes to a significant subversion of the adaptive antitumor immune defense mounted at the tumor site .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The vascular endothelial growth factor ( VEGF ) receptor tyrosine kinase inhibitor sunitinib has been approved for first-line treatment of patients with metastatic renal cancer and is currently being trialled in other cancers . However , the effectiveness of this anti-angiogenic agent is limited by the presence of innate and acquired drug resistance . By screening a panel of candidate growth factors we identified fibroblast growth factor 2 ( FGF2 ) as a potent regulator of endothelial cell sensitivity to sunitinib . We show that FGF2 supports endothelial proliferation and de novo tubule formation in the presence of sunitinib and that FGF2 can suppress sunitinib-induced retraction of tubules . Importantly , these effects of FGF2 were ablated by PD173074 , a small molecule inhibitor of FGF receptor signalling . We also show that FGF2 can stimulate pro-angiogenic signalling pathways in endothelial cells despite the presence of sunitinib . Finally , analysis of clinical renal-cancer samples demonstrates that a large proportion of renal cancers strongly express FGF2 . We suggest that therapeutic strategies designed to simultaneously target both VEGF and FGF2 signalling may prove more efficacious than sunitinib in renal cancer patients whose tumours express FGF2 .\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: Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan , China . The potent apoptotic activities of bigelovin in human leukemia U937 cells were shown in our previous study . The present study investigated the anti-angiogenic and immunomodulatory effects of bigelovin using transgenic zebrafish Tg(fli1a:EGFP)y1 with fluorescent blood vessels and human peripheral blood mononuclear cells ( PBMCs ) , respectively . Furthermore , the inhibitory activities of bigelovin on the human endothelial cell adhesion molecules ( CAMs ) were also examined . Our results showed that the growth of subintestinal vessels of the bigelovin-treated zebrafish embryos was significantly inhibited and the gene expressions in angiogenesis signaling pathways ( e.g . Ang2 and Tie2 ) of the zebrafish were down-regulated after bigelovin treatment . Besides , the proliferation and Th1 cytokines productions ( e.g . IFN-γ , IL-2 and IL-12 ) were suppressed in bigelovin-treated PBMCs . On the other hand , bigelovin was shown to significantly inhibit the human monocyte adhesion to human endothelial cells and the gene expressions of inflammation-related CAMs ( e.g . ICAM-1 , VCAM-1 and E-selectin ) were significantly down-regulated in bigelovin-treated human endothelial cells . In summary , our data provide the first evidence that bigelovin possesses anti-angiogenic and immunomodulatory activities , suggesting bigelovin may exert multi-target functions against cancer in animal models .\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: In this study , laboratory experiments were carried out in order to come to a better understanding of the fate of polycyclic aromatic hydrocarbons ( PAHs ) in the marine environment and especially on their bioaccumulation , biotransformation and genotoxic effects in fish . Juveniles of turbot ( Scophthalmus maximus ) were exposed to PAHs through different routes via ( 1 ) a mixture of dissolved PAHs , ( 2 ) a PAH-polluted sediment and ( 3 ) an oil fuel elutriate . Fish were exposed 4 days followed by a 6-day depuration period . In each experiment , PAH concentrations in the seawater of the tanks were analysed regularly by gas chromatography coupled with mass spectrometry . Muscle and liver samples were also analysed for parent PAH levels and PAH bioconcentration factors were calculated . Biotransformation was evaluated by measuring the levels of PAH metabolites in fish bile . Genotoxicity was assessed by the alkaline comet assay . Regardless of exposure route , the parent PAH concentrations in the liver and muscle showed a peak level 1 day after the beginning of the exposure , followed by a decrease up to the background level towards the end of the experiment , except for the exposure to dissolved PAHs for which levels were relatively low throughout the study . As a consequence , no bioaccumulation was observed in fish tissues at the end of the experiment . In contrast , regardless of exposure routes , a rapid production of biliary metabolites was observed throughout the whole exposure experiment . This was especially true for 1-hydroxypyrene , the major metabolite of pyrene . After 6 days of recovery in clean water , a significant decrease in the total metabolite concentrations occurred in bile . Fish exposed through either route displayed a significant increase in DNA strand breaks after 4 days of exposure , and significant correlations were observed between the level of biliary PAH metabolites and the level of DNA lesions in fish erythrocytes . Overall results indicate that exposure to either a mixture of dissolved PAHs , a PAH-contaminated sediment or a dispersed oil fuel elutriate leads to biotransformation and increase in DNA damage in fish . The quantification of PAH metabolites in bile and DNA damage in erythrocytes appear to be suitable for environmental monitoring of marine pollution either in the case of accidental oil spills or sediment contamination .\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: Glutathione S-transferase ( GST ) class Mu activity was determined in 145 unrelated hospital patients in Berlin by measuring their conjugation activity towards the specific substrate trans-stilbene oxide ( TSO ) with two substrate concentrations ( 50 and 250 microM ) in homogenates prepared from lymphocytes . Eighty individuals ( 55.2% ) had an activity lower than 10 pmol/min/10(6) lymphocytes and were classified as GST class Mu deficient . In 142 of 145 cases , phenotype was confirmed by the results of a genotyping procedure using the polymerase chain reaction technique . Two fragments of 273 and about 650 bp including one and two introns , respectively , could always be amplified from genomic DNA in individuals with high GST class Mu activity and could not be amplified in persons with impaired glutathione-TSO conjugation activity . This indicates that persons with low activity carry a large deletion mutation within the GST class Mu gene . The enzymatically determined antimode between low and high activity determined as 10 pmol/min/1 million lymphocytes in the assay with 50 microM TSO could be clearly confirmed by genotyping .\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: In the present study , the question was addressed whether anthocyanins interfere with the topoisomerase I poison irinotecan in vivo . In vivo complexes of enzyme to DNA bioassay was used to detect irinotecan-induced stabilization of topoisomerase I/DNA complexes and single cell gel electrophoresis to determine DNA-strand-break induction in the colon of male Wistar rats . Furthermore , analysis of anthocyanin concentrations in rat plasma and rat colon was included in the testing , demonstrating that anthocyanins reach the colon and the concentrations do not differ between rats that only received anthocyanins and the anthocyanin/irinotecan group . Blackberry extract was found to significantly reduce irinotecan-mediated topoisomerase I/DNA cleavable complex formation . Overall , anthocyanins did not notably increase cleavable complex formation . However , a significant increase of DNA damage was shown after a single dose of irinotecan as well as the single compounds cyanidin ( cy ) and cyanidin-3-glucoside ( cy-3-g ) . Furthermore , a significant reduction of irinotecan-induced DNA-strand breaks after a pretreatment with cy , cy-3-g and blackberry extract was observed . Thus , the question arises whether anthocyanin-rich preparations might interfere with chemotherapy or whether , due to low systemic bioavailability , the preparations might provide protective potential in the gastrointestinal tract .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The Hippo signaling pathway inhibits cell growth and regulates organ size through a kinase cascade that leads to the phosphorylation and nuclear exclusion of the growth-promoting transcriptional coactivator Yes-associated protein ( YAP)/Yorkie . It mediates contact inhibition of cell growth downstream of cadherin adhesion molecules and other cell surface proteins . Contact inhibition is often antagonized by mitogenic growth factor signaling . We report an important mechanism for this antagonism , inhibition of Hippo pathway signaling by mitogenic growth factors . EGF treatment of immortalized mammary cells triggers the rapid translocation of YAP into the nucleus along with YAP dephosphorylation , both of which depend on Lats , the terminal kinase in the Hippo pathway . A small-molecule inhibitor screen of downstream effector pathways shows that EGF receptor inhibits the Hippo pathway through activation of PI3-kinase ( PI3K ) and phosphoinositide-dependent kinase ( PDK1 ) , but independent of AKT activity . The PI3K-PDK1 pathway also mediates YAP nuclear translocation downstream of lysophosphatidic acid and serum as a result of constitutive oncogenic activation of PI3K . PDK1 associates with the core Hippo pathway-kinase complex through the scaffold protein Salvador . The entire Hippo core complex dissociates in response to EGF signaling in a PI3K-PDK1-dependent manner , leading to inactivation of Lats , dephosphorylation of YAP , and YAP nuclear accumulation and transcriptional activation of its target gene , CTGF . These findings show that an important activity of mitogenic signaling pathways is to inactivate the growth-inhibitory Hippo pathway and provide a mechanism for antagonism between contact inhibition and growth factor action .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;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: DNA-protein cross-links ( DPCs ) are formed upon exposure to a variety of chemical and physical agents and pose a threat to genomic integrity . In particular , acrolein and related aldehydes produce DPCs , although the chemical linkages for such cross-links have not been identified . Here , we report that oligodeoxynucleotides containing 1,N(2)-deoxyguanosine adducts of acrolein , crotonaldehyde , and trans-4-hydroxynonenal can form cross-links with the tetrapeptide Lys-Trp-Lys-Lys . We concluded that complex formation is mediated by a Schiff base linkage because DNA-peptide complexes were covalently trapped following reduction with sodium cyanoborohydride , and pre-reduction of adducted DNAs inhibited complex formation . A previous NMR study demonstrated that duplex DNA catalyzes ring opening for the acrolein-derived gamma-hydroxy-1,N(2)-propanodeoxyguanosine adduct to yield an aldehydic function ( de los Santos , C. , Zaliznyak , T. , and Johnson , F . ( 2001 ) J. Biol . Chem. 276 , 9077-9082 ) . Consistent with this earlier observation , the adducts under investigation were more reactive in duplex DNA than in single-stranded DNA , and we concluded that the ring-open aldehydic moiety is the induced tautomer in duplex DNA for adducts exhibiting high relative reactivity . Adducted DNA cross-linked to Arg-Trp-Arg-Arg and Lys-Trp-Lys-Lys with comparable efficiency , and N(alpha)-acetylation of peptides dramatically inhibited trapping ; thus , the reactive nucleophile is located at the N-terminal alpha-amine of the peptide . These data suggest that Schiff base chemistry can mediate DPC formation in vivo following the formation of stable aldehyde-derived DNA adducts .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The mammalian COP9 signalosome ( CSN ) complex is involved in cell transformation , but its molecular mechanism remains undetermined . Here we show that disruption of the fifth component ( CSN5 ) prevented the formation of tumors by p53-null cells transformed with an active form of Ras in subcutaneously injected mice . Depletion of CSN5 suppressed cell proliferation , and induced premature senescence characterized by upregulation of senescence-associated-β-galactosidase activity and increased expression of CDK inhibitors . CSN5-depleted cells exhibited enhanced activation of the PI3 kinase-Akt pathway , and chemical inhibition of this pathway reduced the level of senescence . Thus , CSN5 is suggested to be a novel target in cancer therapy and for drugs against tumor cells harboring mutated p53 .\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: Energy deregulation and abnormalities of tumor cell metabolism are critical issues in understanding cancer . Hereditary leiomyomatosis renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme fumarate hydratase ( FH ) , and one known to be highly metastatic and unusually lethal . There is considerable utility in establishing preclinical cell and xenograft models for study of disorders of energy metabolism , as well as in development of new therapeutic approaches targeting of tricarboxylic acid ( TCA ) cycle enzyme-deficient human cancers . Here we describe a new immortalized cell line , UOK 262 , derived from a patient having aggressive HLRCC-associated recurring kidney cancer . We investigated gene expression , chromosome profiles , efflux bioenergetic analysis , mitochondrial ultrastructure , FH catabolic activity , invasiveness , and optimal glucose requirements for in vitro growth . UOK 262 cells have an isochromosome 1q recurring chromosome abnormality , i(1)(q10) , and exhibit compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC . The cells also display glucose-dependent growth , an elevated rate of lactate efflux , and overexpression of the glucose transporter GLUT1 and of lactate dehydrogenase A ( LDHA ) . Mutant FH protein was present primarily in edematous mitochondria , but with catalytic activity nearly undetectable . UOK 262 xenografts retain the characteristics of HLRCC histopathology . Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme-deficient form of kidney cancer . This tumor model is the embodiment of the Warburg effect . UOK 262 provides a unique in vitro and in vivo preclinical model for studying the bioenergetics of the Warburg effect in human cancer .\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: Compound C , a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase ( AMPK ) , has been reported to cause apoptotic cell death in myeloma , breast cancer cells and glioma cells . In this study , we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells . Compound C can induce upregulation , phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma ( BCC ) cells . The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species ( ROS ) generation and associated with activated ataxia-telangiectasia mutated ( ATM ) protein . Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines , we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy . The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression . Overall , our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;genomic instability and mutation;tumor promoting inflammation;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: Recent studies indicate that cyclooxygenase-2 ( COX-2 ) is overexpressed in pancreatic adenocarcinoma and may play a critical role in this rapidly progressing form of cancer . A human pancreatic adenocarcinoma cell line , Mia PaCa-2 , was incubated for 18 hours with 5 micromol/L of rofecoxib ( Vioxx ) , a selective COX-2 inhibitor . Total RNA was isolated and gene expression analyzed by DNA microarray chips . In a separate experiment , athymic mice were orthotopically injected with 7.5 x 10(5) Mia PaCa-2 cells through a minilaparotomy . After 1 month , laparotomy was repeated to measure tumor size , and mice were randomized to receive reformulated rodent chow containing either 12.5 mg/kg/day of rofecoxib or no drug for 21 days . Tumor growth was assessed by comparing volume before and after treatment . In vitro , rofecoxib decreased gene expression of cyclin D1/PRAD1 , a key component of cell cycle progression , while increasing expression of several cell cycle arrest genes , including p21/WAF1 , p33/ING , GADD34 , and GADD45 ( P &lt ; 0.05 ) . In vivo , tumor growth was significantly reduced in treated vs. control mice ( P &lt ; 0.05 ) . No systemic toxicity was observed in mice receiving rofecoxib . These data suggest that rofecoxib slows the growth of human pancreatic cancer through changes in gene expression that favor cell cycle arrest .\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: Previous reports showed that treatment with non-steroidal anti-inflammatory agents ( NSAIA ) can alter the growth profile of a variety of tumours . In this study , the effect of NSAIA treatment on the growth of the primary tumour and the appearance of spontaneous pulmonary metastases , was investigated . A mammary adenocarcinoma of non-detected immunogenicity , C7HI , was grafted subcutaneously in the lateral flank of Balb/c mice . Oral treatment with approximately 1 mg kg-1 day-1 piroxicam delayed both tumour growth and the growth of pulmonary metastases . Survival of mice bearing the primary tumour was significantly lengthened by anti-inflammatory treatment . Similarly , in separate experiments , after surgical removal of the primary tumour by day 34 after grafting , the group of mice treated orally with piroxicam also exhibited a higher survival rate than the control group . Upon surgical removal of the primary tumour 34 days after grafting , piroxicam treatment significantly decreased both the number and size of pulmonary metastases . The results of this study lends support to the hypothesis that inhibition or modulation of inflammation may delay tumour organisation and growth . It is suggested that piroxicam treatment may be an appropriate adjunct therapy to delay the appearance of pulmonary metastases and to increase life-expectancy in a host whose primary tumour has to be surgically removed .\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: Many different cellular pathways have evolved to protect the genome from the deleterious effects of DNA damage that result from exposure to chemical and physical agents . Among these is a process called transcription-coupled repair ( TCR ) that catalyzes the removal of DNA lesions from the transcribed strand of expressed genes , often resulting in a preferential bias of damage clearance from this strand relative to its non-transcribed counterpart . Lesions subject to this type of repair include cyclobutane pyrimidine dimers that are normally repaired by nucleotide excision repair ( NER ) and thymine glycols ( TGs ) that are removed primarily by base excision repair ( BER ) . While the mechanism underlying TCR is not completely clear , it is known that its facilitation requires proteins used by other repair pathways like NER . It is also believed that the signal for TCR is the stalled RNA polymerase that results when DNA damage prevents its translocation during transcription elongation . While there is a clear role for some NER proteins in TCR , the involvement of BER proteins is less clear . To explore this further , we studied the removal of 7-methylguanine ( 7MeG ) and 3-methyladenine ( 3MeA ) from the dihydrofolate reductase ( dhfr ) gene of murine cell lines that vary in their repair phenotypes. 7MeG and 3MeA constitute the two principal N-methylpurines formed in DNA following exposure to methylating agents . In mammalian cells , alkyladenine DNA alkyladenine glycosylase ( Aag ) is the major enzyme required for the repair of these lesions via BER , and their removal from the total genome is quite rapid . There is no observable TCR of these lesions in specific genes in DNA repair proficient cells ; however , it is possible that the rapid repair of these adducts by BER masks any TCR . The repair of 3MeA and 7MeG was examined in cells lacking Aag , NER , or both Aag and NER to determine if rapid overall repair masks TCR . The results show that both 3MeA and 7MeG are removed without strand bias from the dhfr gene of BER deficient ( Aag deficient ) and NER deficient murine cell lines . Furthermore , repair of 3MeA in this region is highly dependent on Aag , but repair of 7MeG is equally efficient in the repair proficient , BER deficient , and NER deficient cell lines . Strikingly , in the absence of both BER and NER , neither 7MeG nor 3MeA is repaired . These results demonstrate that NER , but not TCR , contributes to the repair of 7MeG , and to a lesser extent 3MeA .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The immune status of spleen and the effect of surgical treatment in advanced gastric cancer ( AGC ) patients were evaluated by means of testing NK cell activity , T-lymphocyte subsets and circulating immune complex ( CIC ) . The results showed ( 1 ) the significant impairment of NK cell activity and T-lymphocyte subsets , were decreased in CD3+ , CD4+ cells and increased in CD6+ cells resulting in CD4+/CD8+ cell ratio decrease in peripheral blood lymphocytes ( PBL ) , splenic venous blood lymphocytes ( SVL ) and spleen cells ( SC ) of AGC , as compared with PBL of normal population ; ( 2 ) NK cell activity or CD4+/CD8+ cell ratio of SVL and SC were significantly lower than those of PBL in AGC patients , mainly caused by marked decrease of CD4+ cells in SC ; ( 3 ) NK cell activity , CD4+ cells and CD4+/CD8+ cell ratio were significantly elevated in most of AGC cases receiving either radical gastrectomy ( R2+ ) or extensive radical gastrectomy ( R3 ) . A striking declination in CD8+ cells were found only after R3 operation ; ( 4 ) after a short period ( 10-14 days ) or a long period ( 2-4 years ) of radical gastrectomy , NK cell activity and T-lymphocyte subsets showed no significant differences between R2+ and R3 operation . As a rule , AGC would weaken immune function of patients , and along with the development of the tumor , the immunosuppression in the spleen would be generated gradually . For these reasons , a complete tumor resection would be necessary to improve the immunocompetence , and the combined splenectomy might be advisable if indicated .\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: Background:Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma ( HCC ) . The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance , but such correlation is unclear in sorafenib resistance of HCC.Methods:Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line ( Huh-7R ; derived from sorafenib-sensitive Huh-7 ) were used . The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin . Dichloroacetate ( DCA ) , a pyruvate dehydrogenase kinase ( PDK ) inhibitor , and siRNA of hexokinase 2 ( HK2 ) were used to target relevant pathways of cancer metabolism . Cell viability , mitochondrial membrane potential , and sub-G1 fraction were measured for in vitro efficacy . Reactive oxygen species ( ROS ) , adenosine triphosphate ( ATP ) and glucose uptake were also measured . A subcutaneous xenograft mouse model was used for in vivo efficacy.Results:The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity ( R(2)=0.9067 , among sorafenib-naive cell lines ; P=0.003 , compared between Huh-7 and Huh-7 R ) . DCA reduced lactate production and increased ROS and ATP , indicating activation of oxidative phosphorylation ( OXPHOS ) . DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis ( sub-G1 ( combination vs sorafenib ) : Hep3B , 65.4±8.4% vs 13±2.9% ; Huh-7 R , 25.3± 5.7% vs 4.3±1.5% ; each P<0.0001 ) , whereas siRNA of HK2 did not . Sorafenib ( 10 mg kg(-1) per day ) plus DCA ( 100 mg kg(-1) per day ) also resulted in superior tumour regression than sorafenib alone in mice ( tumour size : -87% vs -36% , P<0.001).Conclusion:The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity , and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.British Journal of Cancer advance online publication , 20 December 2012 ; doi:10.1038/bjc.2012.559 www.bjcancer.com .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;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: Hypoxia in the tumor microenvironment plays a central role in the evolution of immune escape mechanisms by tumor cells . In this study , we report the definition of miR-210 as a miRNA regulated by hypoxia in lung cancer and melanoma , documenting its involvement in blunting the susceptibility of tumor cells to lysis by antigen-specific cytotoxic T lymphocytes ( CTL). miR-210 was induced in hypoxic zones of human tumor tissues . Its attenuation in hypoxic cells significantly restored susceptibility to autologous CTL-mediated lysis , independent of tumor cell recognition and CTL reactivity . A comprehensive approach using transcriptome analysis , argonaute protein immunoprecipitation , and luciferase reporter assay revealed that the genes PTPN1 , HOXA1 , and TP53I11 were miR-210 target genes regulated in hypoxic cells . In support of their primary importance in mediating the immunosuppressive effects of miR-210 , coordinate silencing of PTPN1 , HOXA1 , and TP53I11 dramatically decreased tumor cell susceptibility to CTL-mediated lysis . Our findings show how miR-210 induction links hypoxia to immune escape from CTL-mediated lysis , by providing a mechanistic understanding of how this miRNA mediates immunosuppression in oxygen-deprived regions of tumors where cancer stem-like cells and metastatic cellular behaviors are known to evolve .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;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: Epidermal growth factor receptor ( EGFR ) gene amplification and overexpression are commonly present in glioblastoma , and confer advantages of growth , invasiveness and radio/chemotherapy-resistance for tumour cells . Here , we assessed the role of EGFR activation for downstream mitogenic signalling in the commonly used glioblastoma cell line U251 . Despite the high expression level , activation of EGFR under standard culture conditions was low . Intact EGFR function was verified by the rapid phosphorylation of EGFR and downstream mitogen-activated protein(MAP) kinase ERK1/2 upon addition of exogenous EGF to serum-starved cells . By contrast , addition of fetal bovine serum ( FBS ) activated downstream ERK1/2 via the MAP kinase kinase without phosphorylating EGFR . A phosphoreceptor tyrosine kinase array showed FBS-induced activation of insulin-like growth factor-1 receptor ( IGF-1R),and the IGF-1R inhibitor AG1024 inhibited FBS-induced phosphorylation of ERK1/2 , implying IGF-1R as the major driver of FBS-associated mitogenic signalling in the absence of exogenous EGF . These findings have important implications for in vitro drug testing in glioblastoma . Moreover , activation of ERK1/2 was also strongly influenced by growth state and cell density of U251 cultures . Re-seeding exponentially growing cultures at high cell density induced p27/CDKN1B expression and suppressed P-ERK1/2 indicating a certain regulation of proliferation by contact inhibition . Strikingly , highly activated ERK1/2 signalling and cell cycle progression occurred when cells were released from plateau phase regardless of high seeding density . This phenomenon might implicate a proliferation response in the early recurrence observed after clinical therapy in glioblastoma patients . However , whether it will recapitulate in vivo remains to be demonstrated .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;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: Metastasis , commonly to the lung , is the major cause of mortality from testicular cancer . The aim of the present study was to examine the effect of a novel nutrient mixture ( NM ) containing ascorbic acid , amino acids and green tea extract on the inhibition of melanoma growth and metastasis using a model of intratesticular inoculation of B16FO cells into nude mice . Male athymic mice ( n=12 ) , 10-12 weeks of age , were inoculated with 5�10(5) B16FO melanoma cells in 100 μl of PBS into the right testis , while the left testis was left untreated . Following inoculation , the mice were randomly divided into two groups . The control group ( n=6 ) was fed a regular mouse chow diet and the NM 1% group ( n=6 ) the same diet , but supplemented with 1% NM . Four weeks later the mice were sacrificed and the abdominal cavity was opened . Mice in the control group exhibited extensive metastasis in the peritoneal cavity and severely enlarged right testes and necrotic seminiferous tubules . By contrast , in the NM 1% fed group there was no evidence of peritoneal metastasis in 50% of the animals and mild metastasis in the remaining 50% . The right testes were enlarged and seminiferous tubules in the area of invasion showed evidence of degeneration . No metastasis to the liver , kidney or spleen were evident in either group . However , severe lung metastasis was observed in 2 of 6 mice in the control group and mild metastasis in 2 of 6 mice in the NM 1% group . In conclusion , these results confirm earlier studies and verify the anti-metastatic potential of NM .\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: Findings of increased numbers of epidermal growth factor receptors ( EGF-R ) and increased expression of transforming growth factor alpha ( TGF-alpha ) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF-alpha in an autocrine manner . In the studies presented here , we have examined this hypothesis using two human renal carcinoma cell lines , SKRC-4 and SKRC-29 . We demonstrated that both SKRC-4 and SKRC-29 cells were growth stimulated by greater than 35% when cultured in the presence of TGF-alpha or EGF and were inhibited by 29% to 46% if cultured in the presence of anti-EGF-R monoclonal antibody 225 . Treatment of cells with TGF-alpha enhanced the levels of expression of EGF-R mRNA and TGF-alpha mRNA . In addition , incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF-alpha species in the culture medium . Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF-alpha and that this regulatory pathway can be interrupted using antibody to its receptor , EGF-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: LewisY ( LeY ) antigen is an oligosaccharide that is highly expressed at the cell surface in various human cancers . Increased LeY expression activates epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2 ) and promotes cell proliferation in EGFR-overexpressing cells . However , the effect of downregulation of LeY expression on cell proliferation in HER2-overexpressing cells remains unknown . FUT1 encodes α1,2-fucosyltransferase , a key enzyme for LeY synthesis . We knocked down FUT1 by short interfering RNA ( siRNA ) in four HER2-overexpressing human cancer cell lines , including NCI-N87 , MKN7 , SKBr3 and BT474 . We investigated whether downregulation of LeY and alteration in the glycosylation status of these cells affect cell proliferation and HER2 activation . Knocking down FUT1 expression markedly inhibited proliferation of NCI-N87 , which highly expressed EGFR and was sensitive to EGFR deprivation . Furthermore , FUT1 siRNA downregulated the total amount of HER2 protein , phosphorylation of HER2 and EGFR , and phosphorylation of extracellular signal-regulated kinase ( ERK ) in this cell line . Moreover , the marked downregulation of phosphorylation of HER2 and ERK was observed following short-time EGF-stimulation . These effects were not observed in the other three cell lines . Our results suggest that knockdown of FUT1 downregulates HER2 signaling via EGFR downregulation . FUT1 may serve as a new molecular target for HER2-overexpressing human cancers with activated EGFR signaling .\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 cytotoxic activity of cyclosporin A ( CsA ) and the three non-immuno-suppressive CsA analogues B3-243 , WO-039 and B3-665 were studied in tumor cell lines representing both classical and atypical forms of multidrug resistance ( MDR ) : T-ALL GM3639 L100 cells selected for vincristine ( vcr ) resistance and displaying characteristics of classical MDR , including P-glycoprotein ( pgp ) expression and increased drug efflux which can be inhibited by pgp blockers ( e.g. verapamil ) , and U-1285/ADR , a small cell lung cancer ( SCLC ) cell line selected for doxorubicin resistance which lacks pgp , is insensitive to pgp-blockers and shows cross resistance to cis-platinum . At 1 micrograms/ml CsA was the most active agent in reversing Vcr resistance in L100 cells followed by B3-243 and WO-039 , with no effect of B3-665 . Parental LO cells were only marginally sensitized to Vcr by these agents . No reversing effect of any cyclosporin was observed in the U-1285/ADR or its parental cell line . Compared to LO cells , L100 cells showed a marked hypersensitivity to CsA &gt ; B3-243 &gt ; WO-039 with B3-665 being inactive . No collateral sensitivity was observed for cyclosporins in U-1285/ADR cells . Although of different magnitude , the pattern of cytotoxic activity for the different cyclosporins alone closely parallelled that of L100 cells for U-1285 , U1285/ADR and LO cells . The results indicate that not only the collateral sensitivity in classical MDR but also the cytotoxic actions of cyclosporins per se on tumor cells alone are independent of immunosuppressive activity . The results also suggest a structure-activity relationship for cyclosporin-induced cytotoxicity similar to , but independent of , MDR reversing activity .\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: PTEN , a phosphoinositide-3-phosphatase , serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism . Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation , especially reactive carbonyl species , which are commonly occurring by-products of arachidonic acid peroxidation . Using MCF7 and HEK-293 cells , we report that several reactive aldehydes and ketones , e.g. electrophilic α,β-enals ( acrolein , 4-hydroxy-2-nonenal ) and α,β-enones ( prostaglandin A(2) , Δ12-prostaglandin J(2) and 15-deoxy-Δ-12,14-prostaglandin J(2) ) covalently modify and inactivate cellular PTEN , with ensuing activation of PKB/Akt kinase ; phosphorylation of Akt substrates ; increased cell proliferation ; and increased nuclear β-catenin signaling . Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation , oxidative stress , or aging .\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: 4-Hydroxy-2-nonenal ( HNE ) , a major racemic product of lipid peroxidation , reacts with histidine to form a stable HNE-histidine Michael addition-type adduct possessing three chiral centers in the cyclic hemiacetal structure . In the present study , we characterized configurational isomers of a HNE-N(alpha)-acetylhistidine adduct by NMR spectroscopy and by molecular orbital calculations . In addition , we raised monoclonal antibodies against ( R)-HNE-histidine and ( S)-HNE-histidine adducts , characterized their specificities , and examined in vivo localizations of each adduct under oxidative stress . To facilitate structural characterization of the configurational isomers of an HNE-histidine adduct , we prepared the ( R)-HNE-histidine and ( S)-HNE-histidine adducts by incubating N(alpha)-acetylhistidine with each HNE enantiomer , both of which provided two peaks ( Ra and Rb from ( R)-HNE-histidine and Sa and Sb from ( S)-HNE-histidine adducts ) in reversed-phase high-performance liquid chromatography . The NMR analysis showed that each peak was a mixture of two diastereomers . In addition , the analysis of the nuclear Overhauser effect enabled the determination of configurations of the eight isomers . The relative amounts of these isomers in the NMR analysis correlated with the relative energies calculated by molecular orbital methods . On the other hand , using ( R)-HNE-modified and ( S)-HNE-modified keyhole limpet hemocyanins as the antigens , we raised the monoclonal antibodies , mAbR310 and mAbS412 , which enantioselectively recognized the ( R)-HNE-histidine and ( S)-HNE-histidine adducts , respectively . Among the mixtures ( Ra , Rb , Sa , and Sb ) of diastereomers , mAbR310 showed the highest immunoreactivity to Rb ( the mixture of 2R,4S,5R and 2S,4S,5R isomers ) , whereas mAbS412 preferentially recognized Sa ( the mixture of 2R,4S,5S and 2S,4S,5S isomers ) . The presence of ( R)-HNE and ( S)-HNE epitopes in vivo was immunohistochemically examined in the kidney of rats exposed to the renal carcinogen , ferric nitrilotriacetate , by which nuclear and cytosolic stainings with mAbR310 and mAbS412 , respectively , were detected .\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: Basal cell hyperplasia classically has been described as having bland cytologic features . During the past 2 years , we have seen 12 cases ( 11 in consultation ) with atypical features that were confused with adenocarcinoma of the prostate . Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma ; in the 12th case , nuclei were enlarged , hyperchromatic , and moderately pleomorphic . Immunohistochemistry with antibodies against high-molecular-weight cytokeratin ( 34 beta E12 ) was performed in nine of the cases , verifying their basal cell nature . Additional findings in these cases were necrotic intraluminal secretions ( two cases ) , immature squamous metaplasia ( two cases ) , peculiar hyaline cytoplasmic globules ( two cases ) , adenosis ( one case ) , markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen ( one case ) , and intraluminal blue mucin ( two cases ) . We analyzed nine cases of typical basal cell hyperplasia , all of which showed classic features of basal cell hyperplasia with benign cytology . Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation . Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate , prostatic intraepithelial neoplasia , and basaloid carcinoma ( adenoid cystic carcinoma ) of the prostate .\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: OBJECTIVE The aims of this study were to analyse the results and long term outcome in a prospective non randomised trial of 74 patients treated by laparoscopic colo-rectal resection for cancer , and to determine wether survival and recurrence are or are not compromised by an initial laparoscopic approach . PATIENTS AND METHODS Seventy-four patients with colo-rectal carcinoma were included in a prospective trial and treated by laparoscopic resection . All patients were reviewed at 1 , 3 , and 6 months interval . A median of 5 years follow up was available . Forty-eight patients ( 65% ) had more than 3 years of follow up . RESULTS Six conversions ( 8.1% ) were necessary : 2 for tumor invasion of adjacent organs , 2 for limited margin resection in lower rectal tumors , 1 for small bowel injury and 1 for obesity . After surgery , passing flatus occurred at 34.3 +/- 16.7 h and oral intake could be reinstaured at 42.6 +/- 22 h . Mean postoperative stay was 8.2 +/- 3.4 days . No death occurred . The overall morbidity was about 13.5% . The rate of late complications was 5.4% . Two port site metastasis ( 2.6% ) were seen in locally advanced carcinoma . Recurrence rate at 5 years was 0% for Dukes A , 20% for Dukes B , 39.2% for Dukes C. Survival rate at 5 years was 100% for Dukes A , 80% for Dukes B , and 60.7% for Dukes C. These results are similar to those of conventional open surgery . CONCLUSION Laparoscopic colorectal resection for cancer can be performed safely , with a low morbidity and rare late complications . Long term follow up ( 5 years ) assessment shows similar outcome compared with conventional surgery .\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: Cytokine-dependent cell lines have been used to analyze the cytokine-induced cellular signaling and the mechanism of oncogenesis . In the current study , we analyzed MOTN-1 and PLT-2 cell lines established from different stages of a T-cell large granular lymphocyte leukemia patient ( Daibata et al. 2004 ) . MOTN-1 is IL-2-dependent derived from the chronic phase , whereas IL-2-independent PLT-2 is from the aggressive and terminal stage . They shared considerable chromosome abnormalities and the pattern of T-cell receptor rearrangement , presuming that the cytokine independence of PLT-2 was due to the additive genetic abnormality . Besides IL-2 , IL-15 supported MOTN-1 cell growth , because these receptors share beta- and gamma-subunits . IL-2 activated ERK , AKT and STAT pathway of MOTN-1 . STAT3 pathway of PLT-2 was also activated by IL-2 , suggesting intact IL-2 induces signal transduction of PLT-2 . However , ERK1/2 but not AKT , was continuously activated in PLT-2 , consistent with the increased Ras-activity of PLT-2 . Sequence analysis revealed KRAS G12A mutation but not NRAS and HRAS mutation of PLT-2 but not MOTN-1 . Another signaling molecule affecting Ras-signaling pathway , SHP2 , which has been frequently mutated in juvenile myelomonocytic leukemia ( JMML ) , did not show mutation . Moreover , MEK inhibitor , PD98059 , as well as farnesylation inhibitor inhibited PLT-2 cell growth . Using NIH3T3 and MOTN-1 , ERK activation , increased cell proliferation and survival by KRAS G12A were shown , suggesting the important role of KRAS G12A in IL-2-independent growth of PLT-2 . Taken together , KRAS G12A is important for IL-2-independent growth of PLT-2 cells and suggests the possibility of involvement of KRAS mutation with disease progression .\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: PURPOSE The epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ZD1839 ( Iressa ; AstraZeneca Pharmaceuticals , Alderley Park , United Kingdom ) is under development as an anticancer agent . We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin , an EGFR-dependent tissue , in cancer patients participating in ZD1839 phase I clinical trials . PATIENTS AND METHODS We studied 104 pre- and/or on-ZD1839 therapy ( approximately at day 28 of therapy ) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839 . We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated ( phosphorylated ) EGFR . Effects on receptor signaling ( activated mitogen-activated protein kinase [ MAPK] ) , proliferation , p27(KIP1) , and maturation were also assessed . RESULTS Histopathologically , the stratum corneum of the epidermis was thinner during therapy ( P <.001 ) . In hair follicles , prominent keratin plugs and microorganisms were found in dilated infundibula . ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells ( P <.001 ) . In addition , ZD1839 inhibited MAPK activation ( P <.001 ) and reduced keratinocyte proliferation index ( P <.001 ) . Concomitantly , ZD1839 increased the expression of p27(KIP1) ( P <.001 ) and maturation markers ( P <.001 ) and increased apoptosis ( P <.001 ) . These effects were observed at all dose levels , before reaching dose-limiting toxicities . CONCLUSION ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo . These effects were profound at doses well below the one producing unacceptable toxicity , a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors;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: Immunosuppression has been related to the incidence of tumor apparition , including endocrine tumors . The intrasplenic ovarian tumor ( luteoma ) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and , from the immunological perspective , is located in a critical organ involved in immune response . To establish if immunosuppression could alter the development of this experimental tumor , the effects of cyclosporin A ( CsA ) and dexamethasone ( Dex ) were evaluated . After surgery , tumor-bearing and sham animals were kept without treatment for 4 weeks ; thereafter , they were distributed into CsA ( 25 mg/kg ) , Dex ( 0.1 mg/kg ) , or vehicle ( 75:25 castor oil:ethanol ) groups and were injected on alternate days for 50 days . Body weight was evaluated weekly . Animals were sacrificed after a jugular vein blood sample was obtained . Thymi were weighed . Tumors were measured and placed in formaline for histological studies . Serum luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) , prolactin ( PRL ) , and estradiol were measured by radioimmunoassay . Hematological parameters were determined . CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals ( P &lt ; 0.01 ) . Dex significantly impaired weight increase in both groups of animals . CsA induced a significant weight loss in sham animals , not observed in tumor-bearing animals . Dex induced thymus weight loss in both groups , whereas CsA induced thymus weight loss only in sham animals . Only Dex induced a decrease in lymphocyte number in both groups . CsA induced an increase in monocyte number only in sham animals . Treatments did not alter LH , FSH , or estradiol , whereas PRL was increased by CsA only in sham rats . Neither Dex nor CsA induced any significant variations in tumor volume , nor did they alter tumor histology . In addition , no visible metastases or alterations in other organs were observed . We conclude that , though immunological parameters were altered by the treatments , immunosuppressor drugs did not condition tumor development . In addition , tumors secrete one or more factor/s that counteract CsA effect .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PTEN loss of function enhances proliferation , but effects on cellular energy metabolism are less well characterized . We used an inducible PTEN expression vector in a PTEN-null glioma cell line to examine this issue . While proliferation of PTEN-positive cells was insensitive to increases in glucose concentration beyond 2.5mM , PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to approximately 10mM , coinciding with a shift to glycolysis and \" glucose addiction \" . This demonstrates that the impact of loss of function of PTEN is modified by glucose concentration , and may be relevant to epidemiologic results linking hyperglycemia to cancer risk and cancer mortality .\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: Bisphenol A ( BPA ) is one of the most prevalent chemicals in daily-use materials , therefore , human exposure to BPA is ubiquitous . We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 ( GPR30)-mediated epidermal growth factor receptor ( EGFR)-extracellular regulated kinase ( ERK)-c-Fos pathway . However , through the same pathway GPR30 expression has been shown to be induced by EGF , an EGFR ligand . Thus , we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells . By transient transfection with expression plasmids , 10(-9)M BPA significantly transactivates the Gpr30-5'-flanking region through activating the GPR30 , cGMP-dependent protein kinase ( PKG ) , estrogen receptor-α ( ER-α ) , and EFGR-ERK pathways . Furthermore , an activator protein-1 ( AP-1 ) site located within this region is found to be responsible for the transactivation of BPA . Expectedly , through the same pathways , BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30 , p-ERK1/2 , p-Ser118-ER-α and cell proliferation by BPA . Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos , ER-α , and PKG pathways , presumably boosting the cells proliferation via a regulatory loop . The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA .\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: A prominent feature of inflammatory diseases is endothelial dysfunction . Factors associated with endothelial dysfunction include proinflammatory cytokines , adhesion molecules , and matrix degrading enzymes . At the transcriptional level , they are regulated by the histone deacetylase sirtuin ( SIRT ) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB ( NF-κB ) . The role of SIRT6 , also a histone deacetylase , in regulating inflammation in endothelial cells is not known . The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells ( HUVECs ) in the presence of lipopolysaccharide ( LPS ) . LPS decreased expression of SIRT6 in HUVECs . Knockdown of SIRT6 increased the expression of proinflammatory cytokines ( IL-1β , IL-6 , IL-8 ) , COX-prostaglandin system , ECM remodelling enzymes ( MMP-2 , MMP-9 and PAI-1 ) , the adhesion molecule ICAM-1 , and proangiogenic growth factors VEGF and FGF-2 ; cell migration ; cell adhesion to leukocytes . Loss of SIRT6 increased the expression of NF-κB , whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity . Taken together , these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation , vascular remodelling , and angiogenesis . SIRT6 may be a potential pharmacological target for inflammatory vascular diseases .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: Polycylic aromatic hydrocarbons ( PAHs ) are ubiquitous contaminants in the marine environment . Their toxicity is mainly linked to the ability of marine species to biotransform them into reactive metabolites . PAHs are thus often detected at trace levels in animal tissues . For biomonitoring purposes , this findings have two main consequences , ( i ) the determination of the PAH tissue concentration is not suitable for the evaluation of individual exposure to PAHs ( ii ) it can explain sometimes the lack of correlations obtained with relevant markers of toxicity such as genotoxicity biomarkers . The aim of the present study was to better investigate the link between PAH exposure and genotoxicity in marine flatfish . During a laboratory experiment , juvenile soles were exposed for four weeks to a mixture of three PAHs , namely benzo[a]pyrene , fluoranthene and pyrene , followed by one week of depuration . Fish were exposed via the trophic route to a daily PAH concentration of 120 μg/g food . Fish were sampled at different time points . The bioavailability and the biotransformation of PAHs were assessed by the measurement of biliary metabolites using a sensitive UPLC MS/MS method . The 7-ethoxyresorufine-O-deethylase was also measured in liver subcellular fractions as a biomarker of phase I biotransformation activities . Genotoxicity was assessed in parallel by the measurement of DNA strand breaks in fish erythrocytes by the alkaline comet assay . During this study , the high amount of PAH metabolites produced in sole demonstrated the bioavailability of PAHs and their biotransformation by fish enzymes . A positive correlation was observed between the level of hydroxylated PAH metabolites and genotoxicity as measured by the alkaline comet assay .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues . This was done to mimic the clinical setting where in , normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation . The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretreatment with macerated extract of Nigella sativa seeds ( 100 mg/kg ) , using alkaline comet assay , and also estimating biochemical and blood parameters such as levels of antioxidant enzymes superoxide dismutase and catalase , thiobarbituric acid reactive substances and protein oxidation in organs such as spleen , liver , brain and intestine haemoglobin and total leucocyte count , respectively . The results showed that the macerated extract of Nigella sativa seeds protected the liver , spleen , brain and intestines both in normal as well as tumour bearing mice . This study concludes that macerated extract of Nigella sativa seeds has protective effects against radiation-induced damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties . Hence macerated extract of Nigella sativa seeds , could be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating unwanted side effects of radiation in normal tissues .\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: Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle , which then stops when confluence is reached again . Although the events involved in cell cycle entry have been widely documented , those managing cell cycle exit have remained so far ill defined . We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p , which acts as a mandatory signal triggering cell cycle arrest when confluence is reached . Blocking miR-483-3p accumulation strongly delays cell cycle exit , maintains cells into a proliferative state and retards their differentiation program . Using two models of cell cycle synchronization ( i.e. mechanical injury and serum addition ) , we show that an ectopic upregulation of miR-483-3p blocks cell cycle progression in early G1 phase . This arrest results from a direct targeting of the CDC25A phosphatase by miR-483-3p , which can be impeded using an anti-miRNA against miR-483-3p or a protector that blocks the complex formation between miR-483-3p and the 3'-untranslated region ( UTR ) of CDC25A transcript . We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which , in turn , abolishes CDK4/6 capacity to associate with D-type cyclins . This prevents CDK4/6 kinases ' activation , impairs downstream events such as cyclin E stimulation and sequesters cells in early G1 . We propose this new regulatory process of cyclin-CDK association as a general mechanism coupling miRNA-mediated CDC25A invalidation to CDK post-transcriptional modifications and cell cycle control .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND : Although quiescence ( reversible cell cycle arrest ) is a key part in the life history and fate of many mammalian cell types , the mechanisms of gene regulation in quiescent cells are poorly understood . We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts . RESULTS : Using microarrays , we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts . Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles , indicating common changes induced by distinct quiescence signals . By analyzing the gene expression patterns of microRNA target genes with quiescence , we discovered a strong regulatory function for miR-29 , which is downregulated with quiescence . Using microarrays and immunoblotting , we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence . In addition , overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence . We also found that let-7 and miR-125 were upregulated in quiescent cells . Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence , while the combination of both together slowed cell cycle re-entry even further . CONCLUSIONS : microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles , in particular , the induction of extracellular matrix proteins in quiescent fibroblasts .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Dendritic cells ( DCs ) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system . Ductal pancreatic adenocarcinoma ( PDAC ) , the most common pancreatic cancer , is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence . METHODS We examined the systemic influence ductal pancreatic adenocarcinoma ( PDAC ) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors , chronic pancreatitis , and age-matched controls . RESULTS All groups examined , including PDAC , had decreased levels of myeloid DCs ( MDC ) and plasmacytoid DCs ( PDC ) and enhanced apoptosis in these cells as compared to controls . We found elevated levels of PGE2 and CXCL8 in subjects with PDAC , and chronic pancreatitis . Levels of these inflammatory factors were in part restored in PDAC after tumor resection , whereas the levels of DCs were impaired in the majority of these patients approximately 12 weeks after tumor removal . Our results prove that solid pancreatic tumors , including PDAC , systemically affect blood DCs . The impairments do not seem to be tumor-specific , since similar results were obtained in subjects with chronic pancreatitis . Furthermore , we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival . CONCLUSIONS Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs . Furthermore , the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival .\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: Lipoprotein lipase ( LPL ) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins . LPL is a member of a family of hydrolytic enzymes that include hepatic lipase and pancreatic lipase . Based on primary sequence homology of LPL to pancreatic lipase , Ser-132 , Asp-156 , and His-241 have been proposed to be part of a domain required for normal enzymic activity . We have analyzed the role of these potential catalytic residues by site-directed mutagenesis and expression of the mutant LPL in human embryonic kidney-293 cells . Substitution of Ser-132 , Asp-156 , and His-241 by several different residues resulted in the expression of an enzyme that lacked both triolein and tributyrin esterase activities . Mutation of other conserved residues , including Ser-97 , Ser-307 , Asp-78 , Asp-371 , Asp-440 , His-93 , and His-439 resulted in the expression of active enzymes . Despite their effect on LPL activity , substitutions of Ser-132 , Asp-156 , and His-241 did not change either the heparin affinity or lipid binding properties of the mutant LPL . In summary , mutation of Ser-132 , Asp-156 , and His-241 specifically abolishes total hydrolytic activity without disrupting other important functional domains of LPL . These combined results strongly support the conclusion that Ser-132 , Asp-156 , and His-241 form the catalytic triad of LPL and are essential for LPL hydrolytic activity .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The \" high-risk \" human papillomavirus types 16 ( HPV-16 ) and 18 ( HPV-18 ) have been etiologically implicated in the majority of human cervical carcinomas . In these cancers , the viral DNAs are often integrated into the host genome so that expression of the E1 and the E2 genes is lost , suggesting that disruption of these regulatory genes plays an important role in carcinogenic progression . Previous studies defining the viral genes affecting HPV-16 transformation functions have used the \" prototype \" viral genome , which was cloned from a human cervical carcinoma and later discovered to harbor a mutation in the E1 gene . In this study , we have corrected this mutation and have evaluated the effect of mutations of either the E1 or the E2 gene on the efficiency of HPV-16 immortalization of human keratinocytes . Mutation of either the E1 gene or the E2 gene in the background of a \" wild-type \" HPV-16 genome markedly increased immortalization capacity . Mutations were also generated in the E2-binding sites located upstream of the P97 promoter , which directs synthesis of the viral E6 and E7 transforming genes . E2 negatively regulates the P97 promoter through binding at adjacent sites . Surprisingly , the mutation of these sites only partially relieved the negative effect of E2 on viral immortalization , implicating additional mechanisms in the E2 repression of viral immortalization functions . Our results provide genetic evidence that the E1 and E2 gene products each can repress HPV-16 immortalization and support the hypothesis that a selective growth advantage is provided by integration of the viral genome in a manner that causes the loss of expression of either E1 or E2 .\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: Circulating tumour cells ( CTCs ) shed into blood from primary cancers include putative precursors that initiate distal metastases . Although these cells are extraordinarily rare , they may identify cellular pathways contributing to the blood-borne dissemination of cancer . Here , we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing , identifying Wnt2 as a candidate gene enriched in CTCs . Expression of WNT2 in pancreatic cancer cells suppresses anoikis , enhances anchorage-independent sphere formation , and increases metastatic propensity in vivo . This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 ( also known as TAK1 ) kinase . In humans , formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes , and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases . Thus , molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of 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: The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects . Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk . All mice developed tumors by 13 wk of promotion . However , in mice pretreated with 30 microL eugenol , no tumors were detected until 8 wk ( following anti-initiation protocol ) and until 14 wk ( following antipromotion protocol ) of tumor promotion . PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively . The effect of eugenol was assessed on specific stages of carcinogenesis . Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA . However , pretreatment with eugenol led to overexpression of these genes , which probably helped stimulate apoptosis of the initiated cells . To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol , its effect was investigated on markers of tumor promotion and inflammation : ODC activity and iNOS and COX-2 expression , and on levels of proinflammatory cytokines ( IL-6 , TNF-alpha , and PGE(2) ) . Eugenol markedly inhibited all . Eugenol also inhibited the upstream signaling molecule : NF-kappaB , which regulates the expression of these genes . TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol . From these results , it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative , anti-inflammatory , and antioxidant activities .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;evading growth suppressors;genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Inflammation which is an indispensable participant in tumor progression is intricately linked with redox modulation . The pro-inflammatory cytokine Tumor Necrosis Factor ( TNFalpha ) elevates reactive oxygen species ( ROS ) in glioblastoma multiforme ( GBM ) . As both TNFalpha and oxidative stress independently play role in regulating cytoskeletal organization and cell survival pathways we investigated whether TNFalpha mediated oxidative stress regulates responses that offer survival advantages to glioblastoma cells . Treatment with TNFalpha elevated Akt phosphorylation in glioma cells . Increased in Akt phosphorylation was concurrent with the decrease in ROS scavenger SOD-1 levels . TNFalpha mediated increase in Akt phosphorylation was dependent on oxidative stress as Akt phosphorylation was abrogated in the presence of ROS inhibitor and elevated in cells transfected with SOD-1 siRNA . TNFalpha altered actin cytoskeletal organization and increased Cdc42 levels . This increase in Cdc42 was concomitant with its increased interaction with scaffold protein IQGAP-1 . Also , we report for the first time a ROS dependent interaction between pAkt and IQGAP-1 in TNFalpha treated cells . Importantly , Akt inhibition not only reversed TNFalpha mediated changes in actin cytoskeletal organization but also abrogated anchorage independent growth . Together , these results suggest that TNFalpha induced oxidative stress affects Akt activation to regulate actin organization and growth of glioma cells .\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: We identified REDD1 as a novel transcriptional target of p53 induced following DNA damage . During embryogenesis , REDD1 expression mirrors the tissue-specific pattern of the p53 family member p63 , and TP63 null embryos show virtually no expression of REDD1 , which is restored in mouse embryo fibroblasts following p63 expression . In differentiating primary keratinocytes , TP63 and REDD1 expression are coordinately downregulated , and ectopic expression of either gene inhibits in vitro differentiation . REDD1 appears to function in the regulation of reactive oxygen species ( ROS ) ; we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress , which are both increased following ectopic expression of either TP63 or REDD1 . Thus , REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation .\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: Semiconductor nanoparticles ( NPs ) became important and wide-used tool for cell imaging because of their unique remarkable properties . Nevertheless , all previous investigations in this area were done on proliferating cells . For the first time , this work demonstrates strong influence of cell active proliferation/contact inhibition of proliferation on uptake of NPs . In addition , we show that cell division plays key-role in penetration of silicon carbide based NPs ( SiC NPs ) inside the cell nucleus . This may very likely concern other types of NPs able to reach the cell nuclei . In particular , observed effect of cell division gives perspectives for future selective cancer treatment with NPs .\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 The epidermal growth factor receptor ( EGFR ) is a validated therapeutic target in non-small cell lung cancer ( NSCLC ) . However , current single agent receptor targeting does not achieve a maximal therapeutic effect , and some mutations confer resistance to current available agents . In the current study we have examined , in different NSCLC cell lines , the combined effect of RNA interference targeting the EGFR mRNA , and inactivation of EGFR signaling using different receptor tyrosine kinase inhibitors ( TKIs ) or a monoclonal antibody cetuximab . METHODS NSCLC cells ( cell lines HCC827 , H292 , H358 , H1650 , and H1975 ) were transfected with EGFR siRNA and/or treated with the TKIs gefitinib , erlotinib , and afatinib , and/or with the monoclonal antibody cetuximab . The reduction of EGFR mRNA expression was measured by real-time quantitative RT-PCR . The down-regulation of EGFR protein expression was measured by western blot , and the proliferation , viability , caspase3/7 activity , and apoptotic morphology were monitored by spectrophotometry , fluorimetry , and fluorescence microscopy . The combined effect of EGFR siRNA and different drugs was evaluated using a combination index . RESULTS EGFR-specific siRNA strongly inhibited EGFR protein expression almost equally in all cell lines and inhibited cell growth and induced cell apoptosis in all NSCLC cell lines studied , albeit with a different magnitude . The effects on growth obtained with siRNA was strikingly different from the effects obtained with TKIs . The effects of siRNA probably correlate with the overall oncogenic significance of the receptor , which is only partly inhibited by the TKIs . The cells which showed weak response to TKIs , such as the H1975 cell line containing the T790M resistance mutation , were found to be responsive to siRNA knockdown of EGFR , as were cell lines with downstream TKI resistance mutations . The cell line HCC827 , harboring an exon 19 deletion mutation , was more than 10-fold more sensitive to TKI proliferation inhibition and apoptosis induction than any of the other cell lines . Cetuximab alone had no relevant in vitro activity at concentrations obtainable in the clinic . The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines , independent of the EGFR mutation status ( wild-type or sensitizing mutation or resistant mutation ) . The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA . CONCLUSIONS EGFR knockdown by siRNA further decreases the cell growth of lung cancer cells that are treated with TKIs or cetuximab alone , confirming that single agent drug targeting does not achieve a maximal biological effect . The siRNA inhibits EGFR oncogenic activity that bypasses downstream \" resistance \" mutations such as KRAS and PTEN . The combined treatment of siRNA and EGFR inhibitory agents is additive . The combination of a potent , irreversible kinase inhibitor such as afatinib , with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers , including those with downstream resistance mutations .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: To search for potential biomarkers used to monitor the process of immortalization , we investigated the relative level of telomerase activity and other immortal phenotypes in the SHEE esophageal epithelial cell line . This human fetal esophageal epithelial cell line , induced by human papilloma virus ( HPV ) 18 E6E7 , was continually propagated over 100 passages . Fourteenth passage cells ( SHEE14 ) were cultured in a flask with a serum-free medium and continually cultured to the 30th passage ( SHEE30 ) . Cells of SHEE14 , SHEE20 and SHEE30 were examined according to cell morphology , cell cycle , apoptosis , contact-inhibition growth , anchorage- dependency , dose-dependency to epithelial growth factors ( EGF ) , telomerase activity and tumorigenicity . The SHEE14 cells exhibited good differentiation with contact-inhibition and anchorage-dependent growth . The SHEE20 cells exhibited increase of senescent and apoptotic cells , and difficulty in propagation . The SHEE30 cells exhibited a higher proliferative index and some undifferentiated cells , with weakened contact-inhibition and anchorage-dependent growth . The telomerase was activated in cells of SHEE30 , but not in SHEE14 and SHEE20 cells . The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30 . Three groups of cells displayed lack of tumor formation in nude mice . Compared with SHEE14 and SHEE20 , SHEE30 cells were of immortalized status with immortal phenotype , which consisted of telomerase activity , increase of cell proliferation , weakened contact-inhibition and anchorage-dependent growth , dose dependency to EGF and lack of tumor formation . From passage 14 to 30th passage , SHEE cells went through cellular senescence , apoptosis and immortalization . With a view toward diagnostic and biological aspects , telomerase activity is a crucial step and a cardinal requirement for immortalization . The telomerase activity and other immortal phenotypes are potential markers for monitoring the process of immortalization .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;enabling replicative immortality;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: Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO(2) and H(2)O ( oxidative phosphorylation ) even in the presence of oxygen ( Warburg effect ) . Dichloroacetate ( DCA ) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA ( tricarboxylic acid cycle ) by indirect activation of pyruvate dehydrogenase ( PDH ) . This can subsequently lead to an increased flow of oxygen in the respiratory chain , associated with enhanced generation of reactive oxygen species ( ROS ) which may cause apoptosis . In order to investigate if DCA may be suitable for neuroblastoma therapy , it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption . The data show , that DCA ( in the low millimolar range ) is able to reduce lactate production , but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality , proliferation and apoptosis of the three cell lines investigated . Therefore , DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma 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: Infection by Opisthorchis viverrini , a risk factor for cholangiocarcinoma ( CCA ) may act through chronic inflammation , oxidative stress and lipid peroxidation ( LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine ( epsilondA ) , and 3,N4-etheno-2'-deoxycytidine ( epsilondC ) , markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients . In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model , in O. viverrini-infected hamsters that had received N-nitrosodimethylamine ( NDMA , 12.5 ppm in dw ) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method , from 21 up to 180 days post-O. viverrini-infection . In inflamed areas of the liver , etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct . Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters , treated with or w/o NDMA when compared with untreated controls . Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters . Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development . Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase ( ALP ) activity , bile duct hyperplasia , dysplasia , precancerous lesions , and CCA appearance . Also elevated expression of alkyladenine DNA glycosylase ( AAG ) , which excises 1,N6-ethenoadenine ( epsilonA ) was linked to higher adduct formation , suggesting imbalanced repair . Our results implicate accumulation of inflammation-related , promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;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: Reciprocity of inflammation , oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression . Whereas the mechanism of hypoxia-driven angiogenesis is well understood , the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure . Here we show that the end products of lipid oxidation , ω-(2-carboxyethyl)pyrrole ( CEP ) and other related pyrroles , are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma . The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 ( TLR2 ) , but not TLR4 or scavenger receptors on endothelial cells , leading to an angiogenic response that is independent of vascular endothelial growth factor . CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling . Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis . Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration . Taken together , these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns , providing a key link connecting inflammation , oxidative stress , innate immunity and angiogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: SCOPE Glyceollins are a novel class of soybean phytoalexins with potential cancer-preventive and antiestrogenic effects . The angiogenic cascade during tumor development consists of the release of angiogenic factors and binding of angiogenic factors to receptors on endothelial cells to activate downstream signaling pathways . However , the potential medicinal value of glyceollins , especially in antiangiogenesis , remains unexplored . METHODS AND RESULTS Here , we investigated the antiangiogenic activity of glyceollins and their underlying mechanisms . Glyceollins inhibited vascular endothelial growth factor ( VEGF ) or basic fibroblast growth factor ( bFGF ) induced in vitro angiogenic activity . Glyceollins inhibited VEGF receptor-2 or FGF receptor-1 activity and their downstream signaling pathways such as extracellular regulated kinase 1/2 , c-Jun N-terminal kinase , as well as p38 mitogen-activated protein kinase and focal adhesion kinase induced by VEGF or bFGF . Glyceollins significantly suppressed VEGF receptor-2 kinase activity assayed by the ELISA . Glyceollins significantly attenuated in vivo and ex vivo microvessel development in a dose-dependent manner and tumor growth by suppressing microvessel density in Lewis lung carcinoma ( LLC ) mouse xenograft . CONCLUSION Thus , glyceollins , elicited ingredients of soy source , target the signaling pathways mediated by VEGF or bFGF , providing new perspectives into potential therapeutics for preventing and treating hypervascularized diseases including cancer .\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: BACKGROUND In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis , whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells . We show that this may result in cancer via mitotic failure , recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer , to a biophysical defect that may contribute to cancer initiation . MODEL Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance , disrupted microtubule dynamics , and finally , genomic instability , from which cancers can arise . Specifically , we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer . CONCLUSIONS A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell . Contrary to current understanding , this effect may precipitate cancer development , rather than follow from it , providing new insights into carcinogenesis , cancer treatment , and prevention .\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 Human Barrett's cancer cell lines have numerous , poorly-characterized genetic abnormalities and , consequently , those lines have limited utility as models for studying the early molecular events in carcinogenesis . Cell lines with well-defined genetic lesions that recapitulate various stages of neoplastic progression in Barrett's esophagus would be most useful for such studies . METHODOLOGY/PRINCIPAL FINDINGS To develop such model cell lines , we started with telomerase-immortalized , non-neoplastic Barrett's epithelial ( BAR-T ) cells , which are spontaneously deficient in p16 , and proceeded to knock down p53 using RNAi , to activate Ras by introducing oncogenic H-Ras(G12V) , or both . BAR-T cells infected with either p53 RNAi or oncogenic H-Ras(G12V) alone maintained cell-to-cell contact inhibition and did not exhibit anchorage-independent growth in soft agar . In contrast , the combination of p53 RNAi knockdown with expression of oncogenic H-Ras(G12V) transformed the p16-deficient BAR-T cells , as evidenced by their loss of contact inhibition , by their formation of colonies in soft agar , and by their generation of tumors in immunodeficient mice . CONCLUSIONS/SIGNIFICANCE Through these experiments , we have generated a number of transformed and non-transformed cell lines with well-characterized genetic abnormalities recapitulating various stages of carcinogenesis in Barrett's esophagus . These lines should be useful models for the study of carcinogenesis in Barrett's esophagus , and for testing the efficacy of chemopreventive and chemotherapeutic agents .\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: PURPOSE Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative ( gemtuzumab ozogamicin , GO ) are a novel therapy option for acute myeloid leukaemia ( AML ) . Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies , including drug efflux or other mechanisms decreasing apoptosis . Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks ( DSBs ) accompanied by decreased DNA repair . METHODS We labelled anti-CD33 antibodies with the alpha-emitter ( 211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the ( 211)At-labelled antibodies , GO or unlabelled antibodies as controls . We also measured caspase-3/7 activity , DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free ( 211)At . RESULTS The mean labelling ratio of ( 211)At-labelled antibodies was 1:1,090 +/- 364 ( range : 1:738-1:1,722 ) in comparison to 2-3:1 for GO . Tumour cell binding of ( 211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33 . ( 211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution ( 1:1,000 ) . No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after ( 211)At-anti-CD33 ( 1:1,090 ) versus GO ( 1:1 ) treatment . CONCLUSION Our results suggest that ( 211)At is a promising , highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody . Labelling techniques leading to higher chemical yield and specific activities must be developed to increase ( 211)At-anti-CD33 therapeutic effects .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: AIMS Tumour cell growth results from a disturbance in the balance between the rate of proliferation and cell death . In this study , proteins involved in the regulation of cell cycle arrest and apoptosis were studied as possible factors responsible for uncontrolled cell growth in colorectal cancer . METHODS The expression of proteins involved in these processes was investigated in 48 metastases from patients with colorectal cancer and compared with eight normal colon mucosa samples and 14 primary tumours . Both primary tumours and metastases were obtained from eight patients . The expression of thymidylate synthase ( TS ) , p53 , retinoblastoma protein ( Rb ) , Fas receptor , Fas ligand , bcl-2 , mcl-1 , bax , and bcl-x was measured using immunohistochemistry . Proliferation was determined by Ki67 staining , whereas apoptosis was assessed by M30 immunostaining , which recognises cleaved cytokeratin 18 . RESULTS In the limited number of cases in which paired comparisons were possible , the expression of TS and Ki67 was significantly higher in metastases than in the matched primary tumour samples ( p = 0.014 and 0.016 , respectively ) , whereas Rb expression was lower in metastases than in primary tumours ( p = 0.024 ) . Fas receptor expression was high in normal mucosa but absent in primary tumours and metastases , whereas the opposite was seen for p53 . The expression of bax , mcl-1 , and bcl-x in normal mucosa was more apical than that seen in malignant cells , where a more diffuse expression pattern was seen ( p &lt ; 0.04 ) . Apoptosis was more abundant in primary tumours than in metastases . CONCLUSIONS These results demonstrate that proliferation and apoptosis are disturbed during colorectal cancer progression , and this is accompanied by loss of Rb and Fas expression , the accumulation of p53 and TS , and changes in the expression patterns of bax , mcl-1 , and bcl-xl .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype . The expressions of two tumor suppressor genes , the retinoblastoma ( Rb ) gene and the p53 gene , were investigated during senescence , crisis , and cell line establishment . In temperature-sensitive ( ts)-v-erb B erythroblasts and ts-v-src fibroblasts ( as well as in v-myc macrophages ) , loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization . In contrast , expression of the Rb gene was unchanged at all stages of immortalization . Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts , even in lines that were immortal and lacked p53 . The results demonstrate that the process of immortalization is distinct from cell transformation , probably requiring different mutational events .\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: Retrovirally induced immunosuppression may elevate the incidence of chemically induced cancers . A proposed hypothesis to explain this relationship is the increased free radical activity observed during retroviral infection and carcinogen activation . We previously found that vitamin E retarded growth of esophageal tumors accompanied by reductions of free radical products . This study investigated the contribution that retroviral immunosuppression has on esophageal cancer induced by the carcinogen N-nitrosomethylbenzylamine ( NMBzA ) , and the response that increased levels of dietary vitamin E has on this induced carcinogenesis . Female C57BL/6 mice received NMBzA or vehicle ( corn oil ) i.p. weekly for 3 weeks . Then some of the mice were infected with LP-BM5 murine retrovirus and fed diets containing 30 IU vitamin E or 172 IU vitamin E/kg of diet . As an assessment of free radical activity , exhaled ethane was measured prior to killing the animals at 26 weeks . Esophagi from the various mice groups were assessed for size and frequency of tumors . Livers homogenates were analyzed for vitamins A and E , lipid fluorescence , conjugated dienes and malondialdehyde . Hepatic levels of vitamin A and E were decreased ( P &lt ; 0.05 ) and indices of lipid peroxidation were greater ( P &lt ; 0.05 ) in NMBzA-treated mice relative to controls . Lipid peroxidation and serum transaminases ( ALT and AST ) were greatest in mice given NMBzA and infected with the retroviruses . Incidence of esophageal tumors were also greatest in the NMBzA-treated , immunocompromised animals . Mice fed vitamin E-supplemented diets showed increased ( P &lt ; 0.05 ) hepatic concentrations of vitamin E and vitamin A , decreased activities of serum transaminases , decreased indices of lipid peroxidation , and decreased size and frequency of esophageal tumors in both the immunocompromised and non-immunocompromised mice . These results suggest that vitamin E plays an antioxidant function that retards the incidence of esophageal cancers in immunocompromised and non-immunocompromised animals .\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: BACKGROUND Adult human mesenchymal stem cells ( hMSC ) have been shown to home to sites of carcinoma and affect biological processes , including tumour growth and metastasis . Previous findings have been conflicting and a clear understanding of the effects of hMSCs on cancer remains to be established . Therefore , we set out to investigate the impact of hMSCs on the oestrogen receptor positive , hormone-dependent breast carcinoma cell line MCF-7 . RESULTS In this study , we show the effects of hMSCs on cancer cells are mediated through a secreted factor(s) which are enhanced by cancer cell-hMSC contact/communication . In addition to enhanced proliferation when in co-culture with hMSCs , MCF-7 cells were found to have increased migration potential in vitro . Inhibition of ER signalling by the pure anti-oestrogen ICI 182,780 decreased the effect of hMSCs on MCF-7 cell proliferation and migration supporting a role for ER signalling in the hMSC/MCF-7 cell interaction . Additionally , hMSCs have been shown to secrete a wide variety of growth factors and chemokines including stromal cell-derived factor-1 ( SDF-1 ) . This coupled with the knowledge that SDF-1 is an ER-mediated gene linked with hormone-independence and metastasis led to the investigation of the SDF-1/CXCR4 signalling axis in hMSC-MCF-7 cell interaction . Experiments revealed an increase in SDF-1 gene expression both in vivo and in vitro when MCF-7 cells were cultured with hMSCs . SDF-1 treatment of MCF-7 cells alone increased proliferation to just below that seen with hMSC co-culture . Additionally , blocking SDF-1 signalling using a CXCR4-specific inhibitor decreased hMSC induced proliferation and migration of MCF-7 . However , the combined treatment of ICI and AMD3100 reduced MCF-7 cell proliferation and migration below control levels , indicating targeting both the ER and CXCR4 pathways is effective in decreasing the hMSCs induction of MCF-7 cell proliferation and migration . CONCLUSIONS The sum of these data reveals the relationship between tumour microenvironment and tumour growth and progression . Better understanding of the mechanisms involved in this tumour stroma cell interaction may provide novel targets for the development of treatment strategies for oestrogen receptor positive , hormone-independent , and endocrine-resistant breast carcinoma .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling" } ]