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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: Caveolin-1 ( -/- ) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts . Here , we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 ( -/- ) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers . More specifically , the transcriptional profiles of Cav-1 ( -/- ) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node ( LN ) metastasis . This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein ( by immuno-histochemical staining in the fibroblast compartment ) is significantly associated with increased LN-metastasis . We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress , DNA damage/repair , inflammation , hypoxia , and aerobic glycolysis , consistent with the \" Reverse Warburg Effect \" . Finally , the tumor stroma of \" metastasis-prone \" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease . This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress . These processes may include oxidative stress , NO over-production ( peroxynitrite formation ) , inflammation , hypoxia , and mitochondrial dysfunction , which are thought to occur in Alzheimer?s disease pathology . Thus , a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress , aerobic glycolysis , and inflammation , driving the \" Reverse Warburg Effect \" in the tumor micro-environment and cancer cell metastasis .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;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: BACKGROUND Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response . In the present study , we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma . METHODS Ninety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined . All patients underwent radical thoracic surgery of primary tumor ( lobectomy or pneumonectomy ) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry . Follow-up was available for all patients ; mean duration of follow-up was 27.50 ± 14.07 months ( range 0.2-57 months , median 24 months ) . RESULTS Sixty-three patients ( 65.2% ) died during the follow-up period . The mean survival time was 32.2 ± 1.9 months ( 95% confidence interval [ CI ] : 28.5-35.8 months ; median 30.0 months ) ; 1- , 2- and 3-year survival rates were 86.5% ± 3.5% , 57.3% ± 5.1% , and 37.1% ± 5.4% , respectively . Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression ( 35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression , P = 0.009 ; hazard ratio [ HR ] 1.95 , 95% CI : 1.15-3.30 ) . Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival ( HR 2.15 , 95% CI : 1.22-3.79 , P = 0.026 ) . A combined p53/γ-H2AX analysis was performed , and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes . CONCLUSION Our study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer . Further studies are needed to confirm our results .\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: OBJECTIVE To study the effect of Zilongjin ( ZLJ , a composite Chinese drug ) on proliferation and apoptosis of human breast carcinoma cell line MCF-7 . METHODS MCF-7 cells were randomly divided into four groups depending on the culture solution used , the control group , cultured with 1640 medium not contained ZLJ ; and the three ZJL groups cultured with medium contained low ( 1.5 mg/mL ) , moderate ( 3 mg/mL ) and high ( 6 mg/mL ) dosage of ZLJ crude drug respectively . The changes of cell proliferation were assessed by cell growth curve assay and methyl thiazolyl tetrazolium ( MTT ) assay . And the cell apoptosis was analyzed by flow cytometry , Hoechst 33342 staining and DNA ladder assay . RESULTS Compared with that in the normal control , the counts of cells in the three ZLJ groups were decreased significantly ( P<0.05 ) at such time point as 24 , 48 , 72 , 96 , 120 , and 144 h . Furthermore , apart from the comparison of the growth inhibition rate between the low and moderate dosage group at 24 and 72 h which were found to be no significant difference ( P>0.05 ) , the comparison f that among the three ZLJ groups appeared to be significant difference ( P<0.05 ) . The inhibitory effect of ZLJ on cell proliferation of MCF-7 was time- and dose-dependent ; it could retard cells in G0/G1 cell phase ; apoptosis of MCF-7 cell was induced by moderate and high dosage of ZLJ with revealing of apoptotic body and DNA ladder formation . CONCLUSION ZLJ shows cell proliferation inhibitory and apoptosis inducing effects on human breast cancer cell line MCF-7 , and thus to realize its anti-tumor action .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The effect of quercetin , a flavonoid found in many plants , on the proliferation of human leukemic T-cells was analyzed . Quercetin reversibly blocked the cell cycle at a point 3-6 h before the start of DNA synthesis . Expression of the growth-related genes histone H4 , cyclin A and B , and p34cdc2 was suppressed in cells blocked with quercetin . Comparison of the quercetin arrest points with those of the cell cycle inhibitors aphidicolin and mimosine revealed a temporal order of arrest points in G1 of quercetin , mimosine , and aphidicolin . Mimosine and aphidicolin did not inhibit the expression of cyclin A or p34cdc2 , whereas all three reagents inhibited expression of cyclin B. Low concentrations of the protein inhibitor cycloheximide inhibited release of the quercetin but not the mimosine or aphidicolin block . A [ 35S]methionine-labeled M(r) 60,000 protein disappeared in quercetin-treated cells and was rapidly synthesized after removal of quercetin , suggesting the possibility that the M(r) 60,000 protein induces DNA synthesis after the cell is released from a quercetin block . These results suggest the usefulness of quercetin in studies of the regulation of late G1 phase .\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: We have modelled multiple stages of malignant transformation of human endothelial cells ( ECs ) by overexpressing the catalytic subunit of human telomerase ( hTERT ) , together with SV40 T antigen ( SV40T ) and oncogenic N-ras . Transfection with hTERT alone , led to the immortalization of two out of three cultures of bone marrow-derived ECs ( BMECs ) . One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation . BMECs transfected with hTERT alone were functionally and phenotypically normal . BMECs transfected with SV40T ( BMSVTs ) had an extended lifespan , but eventually succumbed to crisis . BMSVTs exhibited a partially transformed phenotype , demonstrating growth factor independence , altered antigen expression and forming tiny , infrequent colonies in vitro . Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures . BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo . BMECs co-expressing SV40T , hTERT and N-ras exhibited an overtly transformed phenotype ; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo . These investigations demonstrate transformation of human ECs to an overtly malignant phenotype . This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias , as well as for testing drugs designed to curtail aberrant EC growth .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The ability of p53 to alter , at the transcriptional level , the gene expression of downstream targets is critical for its role as a tumor suppressor . Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators , histone acetyltransferases , and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction . We demonstrate here , however , that the promoter regions for the p53 target genes , p21 , 14-3-3sigma , and KARP-1 , exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell . In contrast , p53 response elements , which resided outside the immediate promoter regions , existed within DNase I-resistant chromatin domains . Thus , p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element . As such , these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression .\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: Neuroblastoma ( NB ) , a common pediatric neoplasm , consists of two main cell populations : neuroblastic/ganglionic cells and Schwann cells . NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors . Recent studies suggest that Schwann cells influence NB tumor growth via secreted factors that induce differentiation , suppress proliferation , and inhibit angiogenesis . Two angiogenesis inhibitors , pigment epithelium-derived factor and tissue inhibitor of metalloproteinase-2 , have been detected in Schwann cell secretions . Here , we isolated another Schwann cell-derived secreted inhibitor of angiogenesis , a 43-kDa protein identified as SPARC ( secreted protein acidic and rich in cysteine ) , an extracellular matrix protein . We found SPARC to be critical for the antiangiogenic phenotype of cultured Schwann cells . We also show that purified SPARC potently inhibits angiogenesis and significantly impairs NB tumor growth in vivo . SPARC may be an effective candidate for the treatment of children with clinically aggressive , Schwannian stroma-poor NB tumors .\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: This study intended to investigate the expression of the ZEB1 and E-cadherin proteins in lung squamous cell carcinoma ( LSCC ) tissues and to examine the clinicopathological correlation between protein levels and LSCC . RT-PCR and Western blot were used to examine the expression of ZEB1 and E-cadherin mRNAs and proteins in LSCC tissues as well as in adjacent normal tissues , and then analyze the relationship between the clinicopathological characteristics and the expression changes of ZEB1 and E-cadherin mRNAs in LSCC . In addition , RNAi was used to knockdown the expression of the ZEB1 gene in Human HCC827 cells ; subsequently , changes in the invasive ability of the resultant cells were studied . The positive rates of ZEB1 and E-cadherin mRNAs in LSCC tissues were 69.2 and 38.5% , respectively . They differed significantly from the corresponding positive rates in the adjacent normal lung tissues ( 15.4 and 80.8% , p<0.05 ) . There was a negative correlation between the protein levels of ZEB1 and E-cadherin in LSCC tissues ( r=-0.714 , p<0.001 ) ; in addition , it was found that ZEB1 protein expression in LSCC tissues was significantly higher than that in the neighboring normal lung tissues ( p<0.05 ) , and its expression was also significantly higher in patients with lymph node metastases and distant metastases compared to those patients without metastatic disease ( p<0.05 ) . On the contrary , E-cadherin expression was significantly lower in LSCC tissues than that in the neighboring normal tissue ( p<0.05 ) . It was lower in patients with lymph node metastasis and distant metastasis compared to patients without metastatic disease ( p<0.05 ) . However , the expression of ZEB1 and E-cadherin was independent of gender , age , tumor size , or tumor differentiation level ( p>0.05 ) . Transfection of ZEB1 siRNA into HCC827 cells significantly reduced the ZEB1 protein level ( p<0.01 ) and significantly elevated E-cadherin levels ( p<0.01 ) . Moreover , significantly less ZEB1 siRNA-transfected cells migrated through Transwell chambers in the LSCC tissue than that in the control groups ( untransfected or transfected with control siRNA , p<0.01 ) . The expression of the ZEB1 gene in LSCC tissues is downregulated with the expression of E-cadherin . On the other hand , the expression of siRNA against ZEB1 promotes E-cadherin expression and suppresses the invasive ability conferred by E-cadherin . In conclusion , our data suggested that overexpression of the ZEB1 gene is possibly associated with the occurrence , development , invasion of LSCC .\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: OBJECTIVES Oxidative stress and pro-inflammatory mediators have been implicated in breast carcinogenesis . We attempted to evaluate the markers of oxidative stress , antioxidant mechanism and the inflammatory pathway in patients with breast cancer . METHODS This study was carried out in departments of Biochemistry and Surgery , Maulana Azad Medical College and associated Hospitals , New Delhi , India . A total of 60 cases of carcinoma of the breast and 60 healthy controls were included in the study . The parameters that were assayed include markers of oxidative stress-conjugated dienes , thiobarbitone reactive substances ( TBARS ) , antioxidants-superoxide dismutase ( SOD ) , catalase ( CAT ) , glutathione peroxidase ( GPx ) , glutathione ( GSH ) and markers of inflammation-interleukin-6(IL-6) and ferritin . RESULTS There was a significant decline in the antioxidant levels and a significant rise in oxidant levels in patients with carcinoma of the breast , compared to controls . The inflammatory markers-IL-6 and ferritin-were also significantly higher in patients with breast cancer . A significantly positive correlation was observed between the IL-6 levels and conjugated dienes with the stage of breast carcinoma ; whilst a significantly negative correlation was observed between the levels of conjugated dienes and superoxide dismutase and superoxide dismutase levels with the disease staging . CONCLUSIONS This study underlines the interplay between inflammatory pathways and oxidative stress in the pathogenesis of breast cancer . MINI ABSTRACT : An intense research is underway to identify the possible risk factors and the molecular mechanisms involved in pathogenesis of breast cancer . Inflammation and oxidative stress are two such etiologies investigated in our study .\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 have studied the mutagenic specificity of abasic sites using the yeast oligonucleotides transformation assay . We introduced oligonucleotide containing a natural abasic site and a tetrahydrofuran abasic site into Rev1 mutants , rev1AA , which contains mutations of Asp467 and Glu468 residues of Rev1p to Ala in order to inactivate dCMP transferase activity , and rev1 delta , which lacks its whole coding sequence . The transformation efficiencies of rev1AA with abasic-containing oligonucleotides were lower than those of B7528 , a strain proficient in REV1 gene , but much higher than rev1 delta mutant . Sequence analysis opposite the lesions showed that the mutation spectra were different among these three strains .\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 Cisplatin chemotherapy often causes acute kidney injury in cancer patients . The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation , activation of p53 tumour suppressor protein and tubular apoptosis . Luteolin , a flavone found in medicinal herbs and plants , has been reported to exhibit anti-inflammatory , antioxidant and anticarcinogenic activities . The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism . METHODS C57BL/6 mice were treated with cisplatin ( 20 mg/kg ) with or without treatment with luteolin ( 50 mg/kg for 3 days ) . Renal function , histological changes , degree of oxidative stress and tubular apoptosis were examined . The effects of luteolin on cisplatin-induced expression of renal p53 , PUMA-α and Bcl-2 family proteins were evaluated . RESULTS Treatment of mice with cisplatin resulted in renal damage , showing an increase in blood urea nitrogen and creatinine levels , tubular damage , oxidative stress and apoptosis . Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction , reducing tubular cell damage , oxidative stress and apoptosis . Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation , PUMA-α , Bax and caspase-3 activity that were significantly decreased by treatment with luteolin . CONCLUSION These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney .\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: Reactive oxygen species ( ROS ) produced by phagocytic cells induce oxidative stress during chronic inflammation . ROS play a role in the pathogenesis of a broad range of diseases including autoimmune , cardiac and neoplastic abnormalities . We found that sera of patients with a variety of inflammatory dermatoses contain elevated levels of antibodies ( Ab ) binding to an oxidized DNA base derivative , 5-hydroxymethyl-2'deoxyuridine ( HMdU ) coupled to bovine serum albumin , as determined by the enzyme-linked immunosorbent assay . Patients with immune complex diseases and a history of neoplasm elaborated the highest titers of anti-HMdU Ab . Titers from sera of psoriatic subjects were lower than from the aforementioned groups but were still significantly elevated ( p &lt ; 0.001 ) above those of healthy controls . Treatment of inflammatory dermatoses with systemic antiinflammatory and cytotoxic drugs significantly lowered the titers [ p &lt ; 0.005 ( immune complex ) or p &lt ; 0.001 ( psoriasis and neoplastic ) diseases ] , suggesting that this assay may be of value in monitoring the response to therapy in these diseases .\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: Interactions of CD70 , a tumor necrosis factor-related cell surface ligand and its receptor , CD27 , are thought to play an important role for T- , B- , and natural killer-cell activation . However , ligation of CD27 can also induce apoptosis . Human glioblastoma is paradigmatic for cancer-associated immunosuppression . We identified CD70 as a radioinducible gene in U87 MG glioma cells . A screening of a panel of human glioma cell lines revealed that 11 of 12 cell lines expressed CD70 mRNA and protein . Two human neuroblastoma cell lines did not express CD70 . CD70 mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53-independent manner . No alteration in CD70 expression was observed after glioma cell exposure to cytotoxic drugs such as lomustine . CD70 protein was also detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic astrocytomas in vivo . CD27 expression was not detected in any glioma cell line , and there was no evidence for autocrine or backward signaling of the CD70 system in human glioma cells . Unexpectedly , CD70 expressed on glioma cells did not increase the immunogenicity of glioma cells in vitro . In contrast , CD70-positive glioma cells induced apoptosis in peripheral blood mononuclear cells ( PBMCs ) in a CD70-dependent manner . Neutralization of CD70 expressed on glioma cells prevented apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures of glioma cells and PBMCs . The effects of CD70-expressing glioma cells on PBMCs were mimicked by agonistic CD27 antibodies . Conversely , the shedding of CD27 by PBMCs was identified as a possible escape mechanism from glioma cell-induced CD70-dependent apoptosis . Thus , induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Certain hexavalent chromium ( Cr(VI) ) compounds are well established occupational respiratory tract carcinogens . However , despite extensive studies , the cellular and molecular mechanisms underlying Cr(VI)-induced lung cancer remain poorly understood . In fact , the models used were often suboptimal and yielded conflicting results that were heavily dependent upon the system and experimental conditions employed . Here , we investigated the effects of chronic subcytotoxic and mildly cytotoxic ( 0.1-2 microM ) Cr(VI) exposures on cultures of human bronchial epithelial cells , the main targets of Cr(VI) carcinogenicity . Our studies with the nontumorigenic BEAS-2B cell line suggest that relatively short exposures ( h ) to sublethal Cr(VI) doses ( 0.1-1 microM ) may render these cells less sensitive to contact inhibition . We have also observed a reduced sensitivity to Cr(VI)-induced apoptosis shortly after the beginning of exposure to a mildly cytotoxic Cr(VI) dose ( 2 microM ) . Further studies are needed to determine whether these two phenotypes are involved in the Cr(VI)-induced carcinogenic process . Additionally , evidence gathered in this study strongly points to a Cr(VI) interference with cell adhesion to the substratum and with cell-cell interactions . Finally , by chronically exposing BEAS-2B cells to mildly cytotoxic Cr(VI) doses ( 1 and 2 microM ) , we were able to induce changes in cell morphology and pattern of growth characteristic of an early phase of pre-malignant progression .\n OUTPUT:\n " }, { "from": "agent", "value": "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: BACKGROUND The isothiocyanate sulforaphane ( SFN ) possesses interesting anticancer activities . However , recent studies reported that SFN promotes the formation of reactive oxygen species ( ROS ) as well as DNA breakage . METHODOLOGY/PRINCIPAL FINDINGS We investigated whether SFN is able to damage RNA , whose loss of integrity was demonstrated in different chronic diseases . Considering the ability of SFN to protect from genotoxicity , we also examined whether SFN is able to protect from RNA damage induced by different chemicals ( doxorubicin , spermine , S-nitroso-N-acetylpenicillamine , H(2)O(2) ) . We observed that SFN was devoid of either RNA damaging and RNA protective activity in human leukemic cells . It was able to potentiate the RNA damage by doxorubicin and spermine . In the first case , the effect was attributable to its ability of modulating the bioreductive activation of doxorubicin . For spermine , the effects were mainly due to its modulation of ROS levels produced by spermine metabolism . As to the cytotoxic relevance of the RNA damage , we found that the treatment of cells with a mixture of spermine or doxorubicin plus SFN increased their proapoptotic potential . Thus it is conceivable that the presence of RNA damage might concur to the overall toxic response induced by a chemical agent in targeted cells . CONCLUSIONS/SIGNIFICANCE Since RNA is emerging as a potential target for anticancer drugs , its ability to enhance spermine- and doxorubicin-induced RNA damage and cytotoxicity could represent an additional mechanism for the potentiating effects of SFN associated with anticancer drugs .\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: The glutathione peroxidases , a family of selenocysteine-containing redox enzymes , play pivotal roles in balancing the signaling , immunomodulatory , and deleterious effects of reactive oxygen species ( ROS ) . The glutathione peroxidase GPX3 is the only extracellular member of this family , suggesting it may defend cells against ROS in the extracellular environment . Notably , GPX3 hypermethylation and underexpression occur commonly in prostate , gastric , cervical , thyroid , and colon cancers . We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis , a process characterized by oxidative stress and inflammation , comparing Gpx3(-/-) mice in an established two-stage model of inflammatory colon carcinogenesis . Gpx3-deficient mice exhibited an increased tumor number , though not size , along with a higher degree of dysplasia . In addition , they exhibited increased inflammation with redistribution toward protumorigenic M2 macrophage subsets , increased proliferation , hyperactive WNT signaling , and increased DNA damage . To determine the impact of acute gene loss in an established colon cancer line , we silenced GPX3 in human Caco2 cells , resulting in increased ROS production , DNA damage and apoptosis in response to oxidative stress , combined with decreased contact-independent growth . Taken together , our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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: Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer . Here , we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger ( SDGE ) are potent inhibitors of proliferation of endometrial cancer cells . SDGE , isolated from six different batches of ginger rhizomes , consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50) of 1.25 �g/ml . SDGE also enhanced the anti-proliferative effect of radiation and cisplatin . Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3 . GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE , with the isomers neral and geranial constituting 30-40% . Citral , a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50) 10 �M ( 2.3 �g/ml ) . Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells . SDGE was more effective in inducing cancer cell death than citral , suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death . SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential . Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE . This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax . Inhibitor of p53 , pifithrin-α , attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg) SKOV-3 cells . Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer .\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: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity that mainly targets vascular endothelial growth factor receptors , and recently , it has been shown to be an active agent for the treatment of malignant pheochromocytomas . Previously , we demonstrated that sunitinib directly inhibited mTORC1 signaling in rat pheochromocytoma PC12 cells . Although autophagy is a highly regulated cellular process , its relevance to cancer seems to be complicated . It is of note that inhibition of mTORC1 is a prerequisite for autophagy induction . Indeed , direct mTORC1 inhibition initiates ULK1/2 autophosphorylation and subsequent Atg13 and FIP200 phosphorylation , inducing autophagy . Here , we demonstrated that sunitinib significantly increased the levels of LC3-II , concomitant with a decrease of p62 in PC12 cells . Following sunitinib treatment , immunofluorescent imaging revealed a marked increased punctate LC3-II distribution . Furthermore , Atg13 knockdown significantly reduced its protein level , which in turn abolished sunitinib-induced autophagy . Moreover , inhibition of autophagy by siRNAs targeting Atg13 or by pharmacological inhibition with ammonium chloride , enhanced both sunitinib-induced apoptosis and anti-proliferation . Thus , sunitinib-induced autophagy is dependent on the suppression of mTORC1 signaling and the formation of ULK1/2-Atg13-FIP200 complexes . Inhibition of autophagy may be a promising therapeutic option for improving the anti-tumor effect of sunitinib .\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 tumor suppressor p27(Kip1) is an inhibitor of cyclin/cyclin-dependent kinase ( CDK ) complexes and plays a crucial role in cell cycle regulation . Nevertheless , p27 function in the tumorigenesis of the uterine cervix has been poorly defined . Some phenomenon hints that HPV E7 protein can enhance p27 expression , which is contradictory to HPV E7's property of increasing cell proliferation rate . So , in the present study , we have examined the effect of E7 on p27 expression . Though the levels of p27 are increased after HPV E7 expression , most of the p27 protein localized in the cytoplasm and have no function on cell cycle arrest and contact inhibition . The cell migration rate is elevated when p27 is high expression and located in cytoplasm . The results indicated that E7-p27 interaction not only abolished the p27's cell cycle inhibitory function by sequestering it to the cytoplasm , but also endow the cell with invasive property which is the feature of malignant cells .\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: Nucling is a stress-inducible protein associated with apoptosomes . The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis . We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well . Here we show that hepatocellular carcinoma ( HCC ) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout ( KO ) mice than wild-type ( WT ) mice . Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males . In the background of Nucling-KO mice , we observed the up-regulation of TNFalpha , spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver . In addition , we observed a decrease in the number of Kupffer cells ( KCs ) in the KO mice . KCs are important for the hepatic immune system , acting as phagocytes or antigen-presenting cells ( APCs ) . We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha . These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver . We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Colorectal cancer represents one of the most challenging diseases . Increasing evidence indicates that aberrant expression of microRNAs ( miRNAs ) is related to pathogenesis of colorectal cancer . Cancer cells reprogram metabolic pathways to sustain higher proliferation rates . Whether mechanisms underlying the role of miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms through which miRNAs alter cancer metabolism are as yet unknown . Herein , we show that miR-124 , miR-137 and miR-340 are associated with poor prognosis of colorectal cancer . Expression of these miRNAs inhibits the growth of colorectal cancer cells . PKM ( pyruvate kinase isozyme ) alternative splicing proteins ( PTB1/hnRNAPA1/hnRNAPA2 ) , which control the inclusion of exon 9 ( PKM1 ) or exon 10 ( PKM2 ) , are targeted by miR-124 , miR-137 and miR-340 . Consequently , miR-124 , miR-137 and miR-340 switch PKM gene expression from PKM2 to PKM1 . High ratios of PKM1/PKM2 inhibit the glycolysis rate , but elevate the glucose flux into oxidative phosphorylation . These results demonstrate that miRNAs ( miR-124 , miR-137 and miR-340 ) impair colorectal cancer growth by counteracting the Warburg effect due to regulating alternative splicing of the PKM gene .\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: Apoptosis , programmed cell death , was previously shown to be induced by the mAb anti-APO-1 ( IgG3 , kappa ) by binding to the APO-1 cell surface Ag , a new member of the nerve growth factor/TNF receptor superfamily . To investigate the role of the Ig H chain Fc regions we compared induction of apoptosis by the original mAb IgG3 anti-APO-1 with anti-APO-1 F(ab')2 fragments and different anti-APO-1 isotypes ( IgG1 , IgG2b , IgG2a , and IgA ) isolated by sequential sublining . We found that IgG3 was the most active isotype ; IgG1 , IgG2a , and IgA showed intermediate activity , and IgG2b and F(ab')2 were inactive . Cytotoxic activity of the inactive or less active antibody preparations was fully reconstituted by protein A , anti-mouse Ig , or anti-mouse Ig F(ab')2 , respectively . Thus , APO-1-mediated induction of apoptosis was dependent on efficient cross-linking of APO-1 cell surface Ag , indirectly augmented by anti-APO-1 Fc-Fc self-aggregation . Because of their different in vitro activity we selected IgG3- , IgG2b- , and IgA anti-APO-1 to test their antitumor activity against solid human B lymphoblastoid tumors in SCID mice . The isotypes showed a different serum half-life ( IgG3 : 9.2-10.4 days , IgG2b : 1.9-2.6 days , and IgA : 14.1-29.2 h ) and a different initial tumor localization 4 h after i.p. injection ( IgG3 around the blood vessels , IgG2b homogeneously , and IgA heterogeneously distributed in the tumor ) . All antibody preparations induced tumor regression by induction of apoptosis , even IgG2b anti-APO-1 inactive in vitro without cross-linking . The activity of IgA anti-APO-1 , which did not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity indicates that apoptosis may be used as the main if not the only mechanism of induction of tumor regression in vivo . As with in vitro , IgG3 anti-APO-1 was the most effective isotype also in vivo . This result suggests that cross-linking of APO-1 on the tumor cell surface may also be required for tumor regression by apoptosis in vivo . Taken together , our data show that selective targeting of apoptosis to tumors may be an efficient antitumor mechanism .\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 epithelial-mesenchymal transition ( EMT ) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis . Besides their therapeutic effects , accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells ; however , the mechanism(s) still remains unclear . Here , we investigated the role of β-catenin signaling in doxorubicin ( Dox)-induced EMT in human gastric cancer cell line BGC-823 . We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells . We also found that β-catenin signaling was activated upon Dox treatment . Inhibition of β-catenin by indomethacin ( Indo ) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability . Our results showed that β-catenin signaling was critical to Dox-induced EMT . Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Prostate cancer ( PCA ) is the most common histological malignancy and the second leading cause of cancer deaths among North American men . There has been considerable interest in the chemopreventative properties of selenium . In this study , we assessed whether selenium inhibits cell growth and associated cell cycle regulatory proteins . Human PCA cells ( LNCaP , PC3 , PC3-AR2 , and PC3-M ) were incubated with and without selenium ( Seleno-DL-methionine , 150 microM ) for 24 , 48 , and 72 h . Cells were fixed and stained with propidium iodide for flow cytometry analysis . In parallel experiments , total protein was extracted , immunoprecipitated with cyclin E antibody , and analyzed by Western blot for the expression of cell cycle markers . Treatment with selenium caused G1 arrest and an 80% reduction in the S phase of LNCaP with no effect on PC3 . However , PC3 cells transfected with the androgen receptor ( PC3-AR2 ) exhibited a G2/M arrest and a marked reduction ( 57% ) in the S phase during cell cycle progression . In the analysis of cell cycle regulatory molecules , selenium-treated cells demonstrated a significant induction of cyclin-dependent kinase inhibitors Cip1/p21 and Kip1/p27 . These data suggest that selenium possesses strong antiproliferative properties in regard to human PCA . This effect appears to be dependent on the presence of a functioning androgen receptor . This provides a theoretical basis for Phase III studies of selenium in PCA prevention .\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: It was proved that nuclear factor-kappa B play an important role in the activation of immune cell , anti-virus , various stress reaction , and regulation of apoptosis , etc . The objective of this study was to investigate the effect of NF-kappa B signal-transduction pathway on apoptosis of hepatic carcinoma cell line-7721 induced by TNF-alpha .\n OUTPUT:\n " }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Retinoic acid ( RA ) and its derivatives inhibit the proliferation of normal human mammary epithelial cells ( HMEC ) and some breast carcinoma lines by mechanisms which are not fully understood . To identify genes that mediate RA-induced cell growth arrest , an HMEC cDNA library was synthesized and subtractive screening was performed . We identified the interleukin-1beta ( IL-1beta ) gene as an RA induced gene in HMEC . Northern blot analyses showed that the IL-1beta gene was up-regulated as early as 2 h after RA treatment . Results from the treatment of HMEC with cycloheximide and actinomycin D indicated that the regulation of the IL-1beta gene by RA occurred at the transcriptional level and that the IL-1beta gene is a direct , downstream target gene of RA . To evaluate the effects of IL-1beta on cell proliferation , the proliferation of HMEC was measured in the presence of RA or IL-1beta , or both . Either RA or IL-1beta could significantly inhibit the proliferation of HMEC . However , the addition of soluble IL-1 receptor antagonist ( sIL-1ra ) to the cell culture medium did not block RA-induced HMEC growth inhibition , whereas sIL-1ra did block the growth inhibition of HMEC by IL-1beta . IL-1beta expression was not observed in the three carcinoma cell lines , MCF-7 , MDA-MB-231 , and MDA-MB-468 , as compared to the HMEC . Growth curves of the breast carcinoma cell lines showed strong inhibitory effects of RA and IL-1beta on the growth of the estrogen receptor ( ER ) positive MCF-7 cell line , but only a small effect on the ER negative MDA-MB-231 cells . The expression of the IL-1beta gene was also transcriptionally activated by RA in normal epithelial cells of prostate and oral cavity . Our results suggest that : ( a ) the IL-1beta gene is a primary target of RA receptors in HMEC ; ( b ) the enhanced expression of the IL-1beta gene does not mediate the RA-induced growth arrest of HMEC ; and ( c ) the expression of the IL-1beta gene is low or absent in all three human breast carcinoma cell lines examined , but the defect in the IL-1beta signaling pathway may be different in ER positive versus ER negative carcinoma cells .\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: Hepatocellular carcinoma ( HCC ) is the most prevalent liver tumor and a deadly disease with limited therapeutic options . Dysregulation of cell signaling pathways is a common denominator in tumorigenesis , including hepatocarcinogenesis . The epidermal growth factor receptor ( EGFR ) signaling system is commonly activated in HCC , and is currently being evaluated as a therapeutic target in combination therapies . We and others have identified a central role for the EGFR ligand amphiregulin ( AR ) in the proliferation , survival and drug resistance of HCC cells . AR expression is frequently up-regulated in HCC tissues and cells through mechanisms not completely known . Here we identify the β-catenin signaling pathway as a novel mechanism leading to transcriptional activation of the AR gene in human HCC cells . Activation of β-catenin signaling , or expression of the T41A β-catenin active mutant , led to the induction of AR expression involving three specific β-catenin-Tcf responsive elements in its proximal promoter . We demonstrate that HCC cells expressing the T41A β-catenin active mutant show enhanced proliferation that is dependent in part on AR expression and EGFR signaling . We also demonstrate here a novel cross-talk of the EGFR system with fibroblast growth factor 19 ( FGF19 ) . FGF19 is a recently identified driver gene in hepatocarcinogenesis and an activator of β-catenin signaling in HCC and colon cancer cells . We show that FGF19 induced AR gene expression through the β-catenin pathway in human HCC cells . Importantly , AR up-regulation and EGFR signaling participated in the induction of cyclin D1 and cell proliferation elicited by FGF19 . Finally , we demonstrate a positive correlation between FGF19 and AR expression in human HCC tissues , therefore supporting in clinical samples our experimental observations . These findings identify the AR/EGFR system as a key mediator of FGF19 responses in HCC cells involving β-catenin signaling , and suggest that combined targeting of FGF19 and AR/EGFR may enhance therapeutic efficacy .\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: Gastrointestinal stromal tumor ( GIST ) is a prototype of mutant KIT oncogene-driven tumor . Prolonged tyrosine kinase inhibitor ( TKI ) treatment may result in a resistant phenotype through acquired secondary KIT mutation . Heat shock protein 90 ( HSP90AA1 ) is a chaperone protein responsible for protein maturation and stability , and KIT is a known client protein of HSP90AA1 . Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway . In this study , we demonstrated that NVP-AUY922 ( AUY922 ) , a new class of HSP90AA1 inhibitor , is effective in inhibiting the growth of GIST cells expressing mutant KIT protein , the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells . The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines . Surprisingly , AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway . The blockade of autophagy alone led to the accumulation of the KIT protein , highlighting the role of autophagy in endogenous KIT turnover . The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B- , acridine orange- or SQSTM1-labeled autophagosome , and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity . Therefore , the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs , but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation .\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: We have previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer . We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature . In the present study , we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases . We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998 , and analyzed the corresponding primary colorectal cancers clinicopathologically . Microscopic bile duct invasion was found in 89 of 217 cases ( 40.6% ) and , of these cases , 23 ( 10.6% ) had macroscopic intrabiliary extension . Histological sections of the corresponding primary colorectal cancer were available in eight ( group A ) of these 23 cases . These were compared with 20 cases , selected randomly , of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases . These patients underwent hepatectomy during the same period as group A and were used as a control ( group B ) . The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B ( P &lt ; 0.01 ) , while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups . These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases . Careful histological evaluation is important even for metastatic tumors .\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: OBJECTIVES Toxicity caused by pharmacological and chemical substances , including carbon tetrachloride ( CCl(4) ) , is a major pathological factor for liver injury . Therefore , strategies to prevent toxicity are needed for maintaining a healthy liver . This study was designed to determine whether recombinant bovine pancreatic trypsin inhibitor ( rBPTI ) , a non-specific serine protease inhibitor , prevents CCl(4)-induced liver injury in mice . METHODS Mice were treated with CCl(4) in the presence or absence of co-treatment with rBPTI . Liver sections were prepared for histopathological assessment . Liver function was evaluated by detecting serum levels of alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) and liver index . Liver oxidative stress and inflammation were examined by detecting the liver malondialdehyde level and glutathione and superoxide dismutase activity , and serum tumour necrosis factor-alpha level , respectively . KEY FINDINGS CCl(4) induced hepatocyte necrosis , inflammatory cell infiltration and fatty degeneration , which were ameliorated by co-treatment with rBPTI in a concentration-dependent manner . Furthermore , rBPTI prevented CCl(4)-induced disruption of liver function . Importantly , rBPTI reduced CCl(4)-induced liver oxidative stress response and pro-inflammatory cytokine production . CONCLUSIONS These results indicated that rBPTI exerted a protective effect on CCl(4)-induced liver injury in mice . Thus , rBPTI may have potential application for prevention of liver injury induced by metabolism of drugs and toxic substances .\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: Cantharidin is an active constituent of mylabris , a traditional Chinese medicine . It is a potent and selective inhibitor of protein phosphatase 2A ( PP2A ) that plays an important role in control of cell cycle , apoptosis , and cell-fate determination . Owing to its antitumor activity , cantharidin has been frequently used in clinical practice . In the present study , we investigated the therapeutic potential of cantharidin in pancreatic cancer . Cantharidin efficiently inhibited the growth of pancreatic cancer cells , but presented a much lighter toxicity effect against normal pancreatic duct cells . It caused G2/M cell-cycle arrest that was accompanied by the down-regulation of cyclin-dependent kinase 1 ( CDK1 ) and up-regulation of p21 expression . It induced apoptosis and elevated the expressions of pro-apoptotic factors tumor necrosis factor-alpha ( TNF-alpha ) , TNF-related apoptosis inducing receptor 1 ( TRAILR1 ) , TRAILR2 , Bad , Bak , and Bid , and decreased the expression of anti-apoptotic Bcl-2 . Activation of caspase-8 and caspase-9 suggested that both extrinsic and intrinsic pathways are involved in the induction of apoptosis . Interestingly , unlike previous studies on other cancer cells , we found that the inhibitory role of cantharidin is independent of oxidative stress in pancreatic cancer cells . Mitogen-activated protein kinases ( MAPKs ) , including ERK , JNK , and p38 , were activated after treatment with cantharidin . Inhibition of JNK , but not ERK or p38 , alleviated the cytotoxity effect of cantharidin , suggesting cantharidin exerted its anticancer effect through the JNK-dependent way . Hence , in addition to being an attractive candidate compound with therapeutic potential , cantharidin also highlighted the possibility of using PP2A as a therapeutic target for pancreatic cancer treatment .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The effects of high and low dietary fat ( 20% vs. 0.5% corn oil ) , and of the prostaglandin synthetase inhibitor indomethacin ( 0.005% w/w ) , on tumour incidence , tumour growth , hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene ( DMBA)-induced rat breast cancer . The high dietary-fat group showed a significantly higher tumour incidence , larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group . Indomethacin reduced tumour incidence significantly , but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups . No significant difference was noted in the hormone-receptor status of the tumours . Growth factors ( TGF-alpha and IGF-II ) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group , but indomethacin rather reduced the growth-factor expression . It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation , while indomethacin has dual effects : a stimulating effect on tumour proliferation , but an inhibiting effect on tumour incidence . It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation .\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: Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor , and this is typically seen as a failure of treatment . We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53 . We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo . Our results suggest that p53 and p21 play a central role in the onset of senescence , whereas p16(INK4a) function may be involved in maintaining senescence . Thus , like apoptosis , senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;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: MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium . The effects on cell proliferation , glycolysis , and glutaminolysis were investigated . Of all adenosine derivatives tested , AMP was the most efficient inhibitor of cell proliferation . In AMP-treated cells , DNA synthesis decreased , whereas RNA and protein syntheses rose normally with time . In terms of carbohydrate metabolism , lactate production from glucose was drastically reduced ; therefore , most of lactate produced must have been derived from glutamine . Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed . In contrast , actual glycolytic flux rates declined , whereas key glycolytic enzyme activities increased . Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells . Based on the lowered NAD level in the AMP-treated cells , lactate dehydrogenase , but not malate dehydrogenase , was impaired ; thereby the whole of glycolysis was inhibited . In compensation , glutamine catabolism was increased . NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels . A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented .\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: Splenic haemangiosarcomas ( HSAs ) from 122 dogs were characterized and classified according to their patterns of growth , survival time post splenectomy , metastases and chemotherapy . The most common pattern of growth was a mixture of cavernous , capillary and solid tumour tissue . Survival time post splenectomy was independent of the growth pattern ; however , it was influenced by chemotherapy and metastases . Immunohistochemical assessment of the expression of angiogenic factors ( fetal liver kinase-1 , angiopoietin-2 , angiopoietin receptor-2 and vascular endothelial growth factor A ) and conventional endothelial markers ( CD31 , factor VIII-related antigen ) revealed variable expression , particularly in undifferentiated HSAs . Therefore , a combination of endothelial markers should be used to confirm the endothelial origin of splenic tumours .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: Considerable debate centers on the optimal treatment for vulvar melanoma , as well as those clinicopathological factors influencing prognosis . We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990 . Primary tumors were assessed according to Chung ( 47 patients ) and Breslow ( 65 patients ) microstaging systems . Fifty-nine patients ( 76% ) underwent radical vulvectomy , ten patients ( 13% ) had a partial vulvectomy , and nine patients ( 12% ) had a wide local excision . Fifty-six also underwent inguinal node dissection . Median follow-up was 193 months . Median survival was 63 months . Ten-year survival by Chung level was as follows : I 100% ; II , 81% ; III , 87% ; IV , 11% ; V , 33% . Ten-year survival by tumor thickness was as follows : 0.75 mm , 48% ; 0.75-1.5 mm , 68% ; 1.51-3.0 mm , 44% ; greater than 3.0 mm , 22% . Increased depth of invasion was associated with increased incidence of inguinal node metastasis . Cox regression analysis demonstrated prognostic significance for tumor thickness ( P less than 0.001 ) , inguinal node metastasis ( P less than 0.001 ) , and older age at diagnosis ( P less than 0.001 ) . Radical vulvectomy did not seem to improve survival over less radical procedures . Based on this experience , we recommend radical local excision for patients with malignant melanoma of the vulva . Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection .\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: Unlike the growth factor dependence of normal cells , cancer cells can maintain growth factor-independent glycolysis and survival through expression of oncogenic kinases , such as BCR-Abl . Although targeted kinase inhibition can promote cancer cell death , therapeutic resistance develops frequently , and further mechanistic understanding is needed . Cell metabolism may be central to this cell death pathway , as we have shown that growth factor deprivation leads to decreased glycolysis that promotes apoptosis via p53 activation and induction of the proapoptotic protein Puma . Here , we extend these findings to show that elevated glucose metabolism , characteristic of cancer cells , can suppress protein kinase Cδ ( PKCδ)-dependent p53 activation to maintain cell survival after growth factor withdrawal . In contrast , DNA damage-induced p53 activation was PKCδ independent and was not metabolically sensitive . Both stresses required p53 Ser(18) phosphorylation for maximal activity but led to unique patterns of p53 target gene expression , showing distinct activation and response pathways for p53 that were differentially regulated by metabolism . Consistent with oncogenic kinases acting to replace growth factors , treatment of BCR-Abl-expressing cells with the kinase inhibitor imatinib led to reduced metabolism and p53- and Puma-dependent cell death . Accordingly , maintenance of glucose uptake inhibited p53 activation and promoted imatinib resistance . Furthermore , inhibition of glycolysis enhanced imatinib sensitivity in BCR-Abl-expressing cells with wild-type p53 but had little effect on p53-null cells . These data show that distinct pathways regulate p53 after DNA damage and metabolic stress and that inhibiting glucose metabolism may enhance the efficacy of and overcome resistance to targeted molecular cancer therapies .\n OUTPUT:\n " }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The CD4+CD25+ regulatory T cell ( Treg ) is a special kind of T cell subset . Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases , transplantation tolerance and cancer . Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance . The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma ( HCC ) . A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods . Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status . The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ( 18.8% � 1.26% ) was found to be significantly higher than that in normal mice ( 9.99% � 1.90% ) ( P<0.01 ) . Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice , while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed . Anti-tumour immunity was suppressed , and this might be associated with the increase of Tregs . Our observations suggest that the CD4+CD25+Treg/ CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer .\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: Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress , inflammation , and aberrant nucleotide biosynthesis . Human inosine triphosphate pyrophosphatase ( ITPA ) hydrolyzes triphosphates of noncanonical purine bases ( i.e. , ITP , dITP , XTP , dXTP , or their mimic : 6-hydroxyaminopurine ( HAP ) deoxynucleoside triphosphate ) and thus regulates nucleotide pools and protects cells from DNA damage . We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA . A human polymorphic allele of the ITPA , 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP . The polymorphism has been associated with adverse reaction to purine base-analog drugs . The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant . The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs .\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 Androgens and the androgen receptor ( AR ) play important roles in the development of male urogenital organs . We previously found that mice with total AR knockout ( ARKO ) and epithelial ARKO failed to develop normal prostate with loss of differentiation . We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate . However , AR roles of stromal fibroblasts in prostate development remain unclear . METHODS To further probe the stromal fibroblast AR roles in prostate development , we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts ( FSP-ARKO ) . We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development . RESULTS The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation , increased apoptosis , and decreased collagen composition . Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors . To further confirm these in vivo findings , we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells , as well as decrease of some stromal growth factors . CONCLUSIONS Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate , but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: We show that sufficient concentrations of gold nanoparticles produced by an original synthesis method in EMT-6 and CT-26 cancer cells make it possible to detect the presence , necrosis and proliferation of such cells after inoculation in live mice . We first demonstrated that the nanoparticles do not interfere with the proliferation process . Then , we observed significant differences in the tumor evolution and the angiogenesis process after shallow and deep inoculation . A direct comparison with pathology optical images illustrates the effectiveness of this approach .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;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: Chromatographic , peptide mapping and mass spectrometric analysis were used to examine hemoglobin ( Hb ) from heavy drinkers and abstainers for alcohol consumption-related modifications . Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different ( p &lt ; 0.05 ) amounts of \" fast \" hemoglobin . The presence of higher amounts of \" fast \" Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications . To further examine Hb for modifications , tryptic peptides of the \" fast \" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry ( PDMS). [ 14C]acetaldehyde ( AcH)-Hb was synthesized in vivo for use as a standard . Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [ 14C]acetaldehyde-Hb . The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides ; the two pairs of peptides co-migrated on HPLC . A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb . The modified peptides were found in five of six heavy drinker samples . This is the first description of site-specific AcH-Hb adducts occurring in vivo . The routine detection of such adducts has potential for characterizing usual alcohol intake .\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: Regulation of adaptive immunity by innate immune cells is widely accepted . Conversely , adaptive immune cells can also regulate cells of the innate immune system . Here , we report for the first time the essential role of B cells in regulating macrophage ( Mφ ) phenotype . In vitro B cell/Mφ co-culture experiments together with experiments in transgenic mice models for B-cell deficiency or overexpression showed B1 cells to polarize Mφ to a distinct phenotype . This was characterized by downregulated TNF-α , IL-1β and CCL3 , but upregulated IL-10 upon LPS stimulation ; constitutive expression of M2 Mφ markers ( e.g . Ym1 , Fizz1 ) and overexpression of TRIF-dependent cytokines ( IFN-β , CCL5 ) . Mechanistically , this phenotype was linked to a defective NF-κB activation , but a functional TRIF/STAT1 pathway . B1-cell-derived IL-10 was found to be instrumental in the polarization of these Mφ . Finally , in vivo relevance of B1-cell-induced Mφ polarization was confirmed using the B16 melanoma tumor model where adoptive transfer of B1 cells induced an M2 polarization of tumor-associated Mφ . Collectively , our results define a new mechanism of Mφ polarization wherein B1 cells play a key role in driving Mφ to a unique , but M2-biased phenotype . Future studies along these lines may lead to targeting of B1 cells to regulate Mφ response in inflammation and cancer .\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: BRIT1 protein ( also known as MCPH1 ) contains 3 BRCT domains which are conserved in BRCA1 , BRCA2 , and other important molecules involved in DNA damage signaling , DNA repair , and tumor suppression . BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients . Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways . To investigate its physiological role and dissect the underlying mechanisms , we generated BRIT1(-/-) mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability . Both BRIT1(-/-) mice and mouse embryonic fibroblasts ( MEFs ) were hypersensitive to gamma-irradiation . BRIT1(-/-) MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation . Notably , BRIT1(-/-) mice were infertile and meiotic homologous recombination was impaired . BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis , and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis . In mutant spermatocytes , DNA double-strand breaks ( DSBs ) were formed , but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired . In addition , we found that BRIT1 could bind to RAD51/BRCA2 complexes and that , in the absence of BRIT1 , recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered , indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site . Collectively , our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages , and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice .\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: A tumor growth-dependent elevation in the hepatic levels of Zn and metallothionein ( MT ) , without a change in the level of Cu , was found in mice and rats bearing solid tumors in the inguinal region . The levels of Zn and MT thus elevated gave a significant correlation ( r = 0.95 ) between them . Nevertheless , when tumor-bearing mice and rats were fed a Zn-deficient diet , the hepatic levels of Zn and MT did not increase . In mice in which inflammation was induced at the same region , on the other hand , hepatic levels of Zn and MT increased transiently after the injection of turpentine or carrageenan even when they were fed the Zn-deficient diet . These results suggest that the elevation of MT and Zn levels can be a helpful marker for detecting malignancy .\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: BACKGROUND Angiogenesis is an essential process in cancer growth maintenance , and metastasis . Angiopoietin-2 promotes tumor angiogenesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization . Enhanced expression of angiopoietin-2 has been reported in lung cancer tissue . Survivin is one of the inhibitors of apoptosis protein that has been shown to play a key role in cancer progression , and in tumor angiogenesis . Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation . AIM To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance . PATIENTS AND METHODS Patients with lung cancer as NSCLC ( n=70 ) and healthy volunteers ( n=10 ) were enrolled . Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay ( ELIZA ) . RESULTS Median serum angiopoietin-2 levels with lung cancer ( 2730pg/mL ) ranged from 1171 to 6541pg/mL was higher than the median of the control group ( 1795pg/mL ) ranged from 1076 to 2730/mL , p<0.001 . Median serum survivin levels were also higher in patients with lung cancer ( 53.0pg/mL ) ranged from 39.3 to 96.3pg/mL than the median of the control group ( 48.8pg/mL ) ranged from 38.0 to 74.6pg/mL , but did not reach statistical significance p=0.206 . In all patients with lung cancer , serum angiopoietin-2 was not significantly correlated with survivin ( r=0.073 , p=0.657 ) . Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types , stage progression , and metastasis among the patients with NSCLC . CONCLUSIONS Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique .\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: Angiogenesis , the formation of new blood vessels from pre-existing vascular beds , is essential for tumor growth , invasion , and metastasis . Luteolin is a common dietary flavonoid found in fruits and vegetables . We studied the antiangiogenic activity of luteolin using in vitro , ex vivo , and in vivo models . In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation , migration , invasion and tube formation of endothelial cells , which are key events in the process of angiogenesis . Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay ( CAM ) and matrigel plug assay . Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9 . Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 in HUVECs . Proinflammatory cytokines such as IL-1β , IL-6 , IL-8 , and TNF-α level were significantly reduced by the treatment of luteolin in PC-3 cells . Luteolin ( 10 mg/kg/d ) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model , indicating that luteolin inhibited tumorigenesis by targeting angiogenesis . CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin . Moreover , luteolin reduced cell viability and induced apoptosis in prostate cancer cells , which were correlated with the downregulation of AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 expressions . Taken together , our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis .\n OUTPUT:\n " }, { "from": "agent", "value": "inducing angiogenesis;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: To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma ( RCC ) patients , we compared autologous and allogeneic CD8(+) T cell responses against RCC line from RCC patients and their HLA-matched donors , using mixed lymphocyte/tumor cell cultures ( MLTCs ) . In addition , we analyzed the expression of molecules associated with cell cycle regulation . Autologous MLTC responder CD8(+) T cells showed cytotoxic activity against RCC cell lines ; however the analysis of the distribution of CD8(+) T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy . In RCC patients , a decreased proliferative response to tumor , associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle , was observed . These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8(+) effector cells . If validated , this may define a therapeutic target in the setting of patients with RCC .\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: INTRODUCTION Necrosis at the tumor center is a common feature of aggressive breast cancers and has been associated with poor prognosis . It is commonly identified by means of invasive histopathology , which often correlates with morbidity and potential tumor cell dissemination , and limits the reconstruction of the whole necrotic domain . In this study we hypothesized that non covalent association to serum albumin ( SA ) and covalent binding to ligands for tumor-abundant cell receptors should synergistically drive selective accumulation and prolonged retention of imaging and therapeutic agents in breast tumor necrotic domains enabling in vivo identification , imaging and possibly treatment of such tumors . METHODS Cyclo-Arg-Gly-Asp-D-Phe-Lys ( c(RGDfK) ) were conjugated to bacteriochlorophyll-derivatives ( Bchl-Ds ) , previously developed as photodynamic agents , fluorescent probes and metal chelators in our lab . The c(RGDfK) component drives ligation to alphaVbeta3 integrin receptors over-expressed by tumor cells and neo-vessels , and the Bchl-D component associates to SA in a non-covalent manner . STL-6014 , a c(RGDfK)-Bchl-D representative , was i.v. injected to CD-1 , nude female mice bearing necrotic and non-necrotic human MDA-MB-231-RFP breast cancer tumors . The fluorescence signals of the Bchl-Ds and RFP were monitored over days after treatment , by quantitative whole body imaging and excised tumor/tissue samples derived thereof . Complementary experiments included competitive inhibition of STL-6014 uptake by free c(RGDfK) , comparative pharmacokinetics of nonconjugated c(RGDfK) Bchl-D ( STL-7012 ) and of two human serum albumin ( HSA ) conjugates : HSA-STL-7012 and HSA-STL-6014 . RESULTS STL-6014 and STL-7012 formed complexes with HSA ( HSA/STL-6014 , HSA/STL-7012 ) . STL-6014 , HSA-STL-7012 and HSA-STL-6014 , selectively accumulated at similar rates , in tumor viable regions over the first 8 h post administration . They then migrated into the necrotic tumor domain and presented tumor half lifetimes ( T1/2 ) in the range of days where T1/2 for HSA-STL-6014 &gt ; STL-6014 &gt ; HSA-STL-7012 . No accumulation of STL-7012 was observed . Pre-injection of c(RGDfK) excess , prevented the uptake of STL-6014 in the small , but not in the large tumors . CONCLUSIONS Non-covalent association to SA and covalent binding to c(RGDfK) , synergistically enable the accumulation and prolonged retention of Bchl-Ds in the necrotic regions of tumors . These findings provide novel guidelines and strategy for imaging and treatment of necrotic tumors .\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: Although regulatory T cells ( T(regs) ) are known to suppress self-reactive autoimmune responses , their role during T cell responses to nonself antigens is not well understood . We show that T(regs) play a critical role during the priming of immune responses in mice . T(reg) depletion induced the activation and expansion of a population of low-avidity CD8(+) T cells because of overproduction of CCL-3/4/5 chemokines , which stabilized the interactions between antigen-presenting dendritic cells and low-avidity T cells . In the absence of T(regs) , the avidity of the primary immune response was impaired , which resulted in reduced memory to Listeria monocytogenes . These results suggest that T(regs) are important regulators of the homeostasis of CD8(+) T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory .\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: OBJECTIVE To study the effects of genistein on the proliferation , apoptosis induction and expression of related gene proteins of human colon cancer cells in vitro and in vivo , and its mechanisms of action . METHODS MTT colorimetric assay was used to detect the effects of genistein on the proliferation of human colon adenocarcinoma SW480 cells . Light and transmission electron microscopy were used to study the histological and ultrastructural changes . Flow cytometry was used to determine the effects of genistein on cell cycle and apoptosis . Flow cytometry and immunohistochemistry were used to determine the effects of genistein on apoptosis induction and expression of related gene proteins of colon cancer cells . RESULTS The MTT colorimetric assay showed that genistein inhibited the proliferation of SW480 cells in a dose-dependent and time-dependent manner , and the highest inhibition rate was 60.2% after 80 microg/ml genistein treatment for 72 h . The light microscopy revealed that many genistein-treated cancer cells were shrunken , disrupted , or showing cytoplasmic vacuolization . The electron microscopic examination showed cell shrinkage , nuclear fragmentation and pronounced chromatin condensation , sometimes formed crescent chromatin condensation attached to the nuclear membrane . The results of flow cytometry showed that : after SW480 cells were treated with 0 , 20 , 40 , 80 microg/ml genistein for 48 h , the FI values of PCNA were 1.49 +/- 0.02 , 1.28 +/- 0.04 , 1.14 +/- 0.03 , and 0.93 +/- 0.08 ; the FI values of VEGF were 1.75 +/- 0.02 , 1.34 +/- 0.06 , 1.32 +/- 0.04 , and 1.23 +/- 0.04 ; the fluorescence index ( FI ) values of p21 were 1.26 +/- 0.05 , 1.36 +/- 0.06 , 1.61 +/- 0.03 , and 1.73 +/- 0.03 , respectively . There were statistically significant differences between the control group and each treatment group ( P &lt ; 0.05 or P &lt ; 0.01 ) . The scores of immunohistochemical staining of PCNA and VEGF proteins were decreased , while p21 increased . There were statistically significant differences between the control group and each treatment group ( P &lt ; 0.05 or P &lt ; 0.01 ) . CONCLUSION Genistein can inhibit the growth of colon cancer cells via apoptosis induction and cell cycle arrest at G(2)/M phase . The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA , and up-regulation of the expression of p21 .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;evading growth suppressors;sustaining proliferative signaling;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: Identification of the proteins that are associated with estrogen receptor ( ER ) status is a first step towards better understanding of the hormone-dependent nature of breast carcinogenesis . Although a number of gene expression analyses have been conducted , protein complement has not been systematically investigated to date . Because proteins are primary targets of therapeutic drugs , in this study , we have attempted to identify proteomic signatures that demarcate ER-positive and -negative breast cancers . Using highly enriched breast tumor cells , replicate analyses from 3 ERα+ and 3 ERα- human breast tumors resulted in the identification of 2,995 unique proteins with ≥2 peptides . Among these , a number of receptor tyrosine kinases and intracellular kinases that are abundantly expressed in ERα+ and ERα- breast cancer tissues were identified . Further , label-free quantitative proteome analysis revealed that 236 proteins were differentially expressed in ERα+ and ERα- breast tumors . Among these , 141 proteins were selectively up-regulated in ERα+ , and 95 proteins were selectively up-regulated in ERα- breast tumors . Comparison of differentially expressed proteins with a breast cancer database revealed 98 among these have been previously reported to be involved in breast cancer . By Gene Ontology molecular function , dehydrogenase , reductase , cytoskeletal proteins , extracellular matrix , hydrolase , and lyase categories were significantly enriched in ERα+ , whereas selected calcium-binding protein , membrane traffic protein , and cytoskeletal protein were enriched in ERα- breast tumors . Biological process and pathway analysis revealed that up-regulated proteins of ERα+ were overrepresented by proteins involved in amino acid metabolism , proteasome , and fatty acid metabolism , while up-regulated proteins of ERα- were overrepresented by proteins involved in glycolysis pathway . The presence and relative abundance of 4 selected differentially abundant proteins ( liprin-α1 , fascin , DAP5 , and β-arrestin-1 ) were quantified and validated by immunohistochemistry . In conclusion , unlike in vitro cell culture models , the in vivo signaling proteins and pathways that we have identified directly from human breast cancer tissues may serve as relevant therapeutic targets for the pharmacological intervention of breast 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: Protein tyrosine kinase 6 ( PTK6 ) is a non-receptor tyrosine kinase expressed in epithelial cancers . Disruption of Ptk6 decreases azoxymethane-induced colon tumorigenesis in mice by preventing signal transducer and activator of transcription 3 activation . Relocalization of PTK6 in prostate cancers contributes to increased growth . Although not expressed in normal breast or ovary , PTK6 promotes anchorage-independent survival of breast and ovarian tumor cells . We identified several potential PTK6 substrates in the human SW620 colon cancer cell line using mass spectrometry , including FAK ( focal adhesion kinase ) . We show that FAK is a direct substrate of PTK6 in vitro and in vivo . Expression of membrane-targeted active PTK6 ( Palm-PTK6-YF ) induces constitutive activation of FAK and cell morphology changes , which are independent of SRC family kinases in Src-/- , Yes-/- , Fyn-/- ( SYF ) mouse embryonic fibroblasts ( MEFs ) . Palm-PTK6-YF expressing SYF cells are transformed and overcome contact inhibition , form colonies in transformation assays , proliferate in suspension and form tumors in a xenograft model . Expression of FAK and Palm-PTK6-YF in Fak-/- MEFs synergistically activates AKT and protects cells against anoikis . However , expression of Palm-PTK6-YF in Akt1/2-/- MEFs fails to protect cells from anoikis , indicating AKT is critical in PTK6 and FAK-mediated survival signaling . In a conditional Pten knockout murine prostate cancer model , we identify prostate epithelial cells with enhanced activation of endogenous PTK6 and FAK at the plasma membrane . Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis , which can be rescued by exogenous expression of FAK . Our data reveal important roles for a PTK6-FAK-AKT signaling axis in promoting anchorage-independent cell survival .\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: Ataxia telangiectasia mutated ( ATM ) kinase is a central player in cellular response to DNA damage . Phosphorylation of the histone H2AX by ATM is required for the accumulation of repair proteins at the sites of double-strand breaks . Recently , it was reported that the histone acetyltransferase Tat interactive protein-60 ( IPP60 ) is required to acetylate ATM prior to its activation . The RuvB-like proteins TIP48 and TIP49 are known to be necessary for the assembly and functional activity of the TIP60 acetyltransferase complex . In the present communication , we investigated the requirements of IIP48 and IIP49 for ATM activation by monitoring the cell cycle distribution and H2AX phosphorylation after irradiation of IIP48- and IIP49-depleted cells . We found that neither the cell cycle norgammay-H2AX were affected in IIP48- and IIP49-silenced cells , suggesting that the IIP60 chromatin modification complex is not engaged in DNA damage signaling upstream of ATM .\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: Gamma-radiation , tetrandrine , bistratene A , and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human BM13674 cell line 8 h after treatment . Apoptosis induced in BM13674 cells by these diverse agents was markedly inhibited by 1 microM okadaic acid , a tumour promoter that inhibits protein phosphatases 1 and 2A . This compound also inhibited the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation . The inhibition of apoptosis was confirmed using fluorescence microscopy and DNA gel electrophoresis . Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations . Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells . The present data provides further support that posttranslational modification of proteins , in particular , phosphorylation/dephosphorylation status , plays an important role in inhibition/activation of programmed cell death in different human cells after exposure to several cytotoxic agents .\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: IL-16 is a ligand and chemotactic factor for CD4+ T cells . IL-16 inhibits the CD3 mediated lymphocyte activation and proliferation . The effects of IL-16 on the target cells are dependent on the cell type , the presence of co-activators etc . To understand the regulation function and mechanism of IL-16 on target cells , we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro . We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose ( 10(-9)M ) , but inhibited the growth of the cells at higher concentration ( 10(-5)M ) . Results showed that 10(-5) M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells . The treatment blocked the expression of FasL , but up-regulated the c-myc and Bid expression in the cells . Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells , respectively . The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner . The growth-inhibiting effects of rIL-16 might be Fas/FasL independent , but , associated with the activation of PKC , up-regulated expression of c-Myc and Bid , and the participation of the ERK signal pathway in Jurkat cells .\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 aim of the present study was to evaluate immunomodulator ginsan , a polysaccharide extracted from Panax ginseng , on carbon tetrachloride ( CCl(4))-induced liver injury . BALB/c mice were injected i.p. with ginsan 24 h prior to CCl(4) administration . Serum liver enzyme levels , histology , expression of antioxidant enzymes , and several cytokines/chemokines were subsequently evaluated . Ginsan treatment markedly suppressed the serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels , and hepatic histological necrosis increased by CCl(4) treatment . Ginsan inhibited CCl(4) induced lipid peroxidation through the cytochrome P450 2E1 ( CYP2E1 ) downregulation . The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents , such as superoxide dismutase ( SOD ) , catalase , and glutathione peroxidase ( GPX ) as well as restoration of the hepatic glutathione ( GSH ) concentration . The marked increase of proinflammatory cytokines ( IL-1beta , IFN-gamma ) and chemokines ( MCP-1 , MIP-2beta , KC ) in CCl(4) treated mice was additionally attenuated by ginsan , thereby preventing leukocyte infiltration and local inflammation . Our results suggest that ginsan effectively prevent liver injury , mainly through downregulation of oxidative stress and inflammatory response .\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: Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells ( the Warburg Effect ) . Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems , and the molecular mechanisms underlying the shifts remain unknown . With proteomics , we observed increased glycolysis in disused human diaphragm muscle . In disused muscle , lung cancer , and H(2)O(2)-treated myotubes , we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase ( PFKm , >2 fold , P<0.05 ) and accumulation of lactate ( >150% , P<0.05 ) . Using microRNA profiling , we identify miR-320a as a regulator of PFKm expression . Reduced miR-320a levels ( to ∼50% of control , P<0.05 ) are associated with the increased PFKm in each of these diverse systems . Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions . Further , miR-320a appears to regulate oxidative stress-induced PFKm expression , and reduced miR-320a allows greater induction of glycolysis in response to H(2)O(2) treatment . We show that this microRNA-mediated regulation occurs through PFKm's 3 ' untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a . These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature .\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: Metastatic breast tumors undergo epithelial-to-mesenchymal transition ( EMT ) , which renders them resistant to therapies targeted to the primary cancers . The mechanistic link between mtDNA ( mitochondrial DNA ) reduction , often seen in breast cancer patients , and EMT is unknown . We demonstrate that reducing mtDNA content in human mammary epithelial cells ( hMECs ) activates Calcineurin ( Cn)-dependent mitochondrial retrograde signaling pathway , which induces EMT-like reprogramming to fibroblastic morphology , loss of cell polarity , contact inhibition and acquired migratory and invasive phenotype . Notably , mtDNA reduction generates breast cancer stem cells . In addition to retrograde signaling markers , there is an induction of mesenchymal genes but loss of epithelial markers in these cells . The changes are reversed by either restoring the mtDNA content or knockdown of CnAα mRNA , indicating the causal role of retrograde signaling in EMT . Our results point to a new therapeutic strategy for metastatic breast cancers targeted to the mitochondrial retrograde signaling pathway for abrogating EMT and attenuating cancer stem cells , which evade conventional therapies . We report a novel regulatory mechanism by which low mtDNA content generates EMT and cancer stem cells in hMECs.Oncogene advance online publication , 4 November 2013 ; doi:10.1038/onc.2013.467 .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;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: There are many growth factors influencing the expansion of multiple myeloma ( MM ) . Angiogenesis is a process that may enhance MM growth , in various manners . Among them , insulin-like growth factor-1 ( IGF-1 ) is a major factor , acting in many levels . The aim of the study was to measure serum levels of IGF-1 in newly diagnosed MM patients and to correlate them with clinical stage of the disease and with markers of angiogenesis , such as vascular endothelial growth factor ( VEGF ) , hepatocyte growth factor ( HGF ) , and interleukin-6 and 15 ( IL-6 and IL-15 ) . Serum levels of the above factors were measured , by ELISA , in 57 newly diagnosed MM patients and in 20 healthy controls . There was no difference in serum levels of IGF-1 in MM patients and in controls , contrary to angiogenic factors , which were higher in MM patients ( p &lt ; 0.001 ) . Similarly , IGF-1 did not correlate with clinical stage of the disease nor the other angiogenic factors , which also correlated with each other ( p &lt ; 0.001 ) . Serum IGF-1 concentrations are not influenced in MM patients . Therefore , although it is a proliferation cytokine , it cannot be used as marker of disease activity .\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: Properly regulated keratinocyte cell death is fundamentally important to maintain structural integrity and homeostatic function of epidermis . Moreover , from an oncological perspective , therapeutic approaches selectively targeting apoptosis of malignant cell types while sparing normal keratinocytes in surrounding skin is desirable . Apo2Ligand/tumor necrosis factor-related apoptosis-inducing ligand ( Apo2L/TRAIL ) has been observed to preferentially induce cytopathic effects on transformed/malignant cell types compared with their non-neoplastic counterparts . In this report , two different biologically active preparations of Apo2L/TRAIL , a non-tagged version , NT-Apo2L/TRAIL , and a leucine zipper fusion protein , LZ-Apo2L/TRAIL , were examined for their ability to trigger apoptosis in normal human keratinocytes , and in an immortalized cell line ( HaCaT cells ) . Differences between these preparations were observed , including : NT-Apo2L/TRAIL induced less keratinocyte apoptosis compared with LZ-Apo2L/TRAIL ; NT-Apo2L/TRAIL also induced less apoptosis of HaCaT cells compared with LZ-Apo2L/TRAIL ; LZ-Apo2L/TRAIL but not NT-Apo2L/TRAIL induced cytotoxic effects when keratinocytes became growth arrested due to undergoing spontaneous replicative senescence--a biological state previously observed to be resistant to UV-light-induced apoptosis . Similarities between preparations included : an enhanced ability for both Apo2L/TRAIL preparations to kill a greater relative percentage of HaCaT cells compared with keratinocytes ; enhanced cytotoxicity towards keratinocytes that had their NF-B activity inhibited ; a dependence of both Apo2L/TRAIL preparations on FADD and caspase activation ; triggering of the same caspase cascades including caspase 8 and 3 ; and an ability to induce apoptosis even when HaCaT cells and keratinocytes were transduced to overexpress either Bcl-2 or Bcl-x(L) ( survival factors that reduce susceptibility to UV-light-induced apoptosis ) . These results indicate that while both preparations of Apo2L/TRAIL possess biological activity , there are important differences as regards their ability to induce apoptosis in normal and immortalized keratinocytes . Moreover , the death receptor pathway triggered by LZ-Apo2L/TRAIL can overcome the apoptotic resistance normally observed in response to UV-light mediated by Bcl-2/Bcl-x(L) , as well as by the state of cellular senescence . Unraveling the molecular basis for these differential biological effects may reveal a new strategic role for these death receptor/ligands linked to apoptosis in maintaining the dynamic balance of keratinocyte proliferation , differentiation , and cell death necessary to achieve a homeostatic thickness and function of normal skin . In addition , it may be possible to utilize these Apo2L/TRAIL preparations for the treatment of various sun-induced skin cancers as they can differentially trigger apoptosis of transformed keratinocytes , or keratinocytes with abnormal NF-kappaB signaling , while sparing adjacent normal keratinocytes .\n OUTPUT:\n " }, { "from": "agent", "value": "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: INTRODUCTION AND AIMS The survival of pancreatic cancer patients with portal vein resection is extremely poor due to the high incidence of liver metastasis . The occurrence of liver metastasis is decreased by locoregional arterial infusion after pancreatic surgery . Chemosensitivity tests can provide the basis for individualized chemotherapy in each patient and predict the clinical response . Therefore , the current study was designed to clarify whether locoregional chemotherapy based on the results of chemosensitivity tests has the clinical effects of preventing liver metastasis and improving survival for patients with portal vein resection . METHODOLOGY The resected specimens from 40 of 47 patients with resection of pancreatic cancer were assessed for chemosensitivity to various anticancer drugs . Fourteen patients underwent portal vein resection due to direct invasion , and nine of these patients received intra-arterial adjuvant chemotherapy on the basis of the results of MTT assay to prevent liver metastasis . The remaining five patients received no chemotherapy . RESULTS None of the patients who received intra-arterial chemotherapy had liver metastasis , and this group of patients had improved survival . The mean survival of patients with intra-arterial chemotherapy was significantly longer than that of patients without chemotherapy ( 25.6 months with chemotherapy versus 9.4 months without chemotherapy ) . CONCLUSION A pilot study of postoperative intra-arterial chemotherapy showed the reduction of liver metastasis and improvement of survival among pancreatic cancer patients with portal vein resection .\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: Given the important role of CXCR4 in cancer metastasis , microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion . Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior . CXCR4 is upregulated in several cancer cells under hypoxic conditions , suggesting a relationship between tumor hypoxia and CXCR4 . However , the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood . KATO III gastric cancer cells were exposed to hypoxia or normoxia . CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry . Wound healing , migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12 , a major CXCR4 ligand . CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATOIII cells following exposure to hypoxia . This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses ( migration and invasion ) to CXCL12 treatment in vitro . The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA . Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner , and that upregulation of CXCR4 plays a role in cancer cell migration and invasion . Thus , disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The goal of this study was to determine the prevalence of sequence variants in the class I beta-tubulin ( clone m40 ) gene and their occurrence in human tumors and cancer cell lines . DNA was isolated from 93 control individuals representing a wide variety of ethnicities , 49 paclitaxel-naive specimens ( 16 ovarian cancers , 17 non-small cell lung cancers , and 16 ovarian cancer cell lines ) , and 30 paclitaxel-resistant specimens ( 9 ovarian cancers , 9 ovarian cancer cell lines , and 12 ovarian cancer xenografts in nude mice ) . Denaturing high-performance liquid chromatography and direct sequence analysis detected two silent polymorphisms in exon 4 , Leu217Leu ( CTG/CTA ) and Gly400Gly ( GGC/GGT ) , with minor allele frequencies of 17 and 0.5% , respectively . Five nucleotide substitutions and one single-base deletion were detected in introns 1 , 2 , and 3 and in the 3 ' untranslated region . Analysis of 49 paclitaxel-naive and 30 paclitaxel-resistant specimens revealed no additional polymorphisms in the coding region . In addition , no amino acid replacements were found in chimpanzee , gorilla , and orangutan in comparison to human . Our data demonstrate a very high degree of sequence conservation in class I beta-tubulin , suggesting that all residues are important in tubulin structure and function . Individual variation in response to treatment with paclitaxel is not likely to be caused by genetic variations in the beta-tubulin drug target . Moreover , acquired mutations in class I beta-tubulin are unlikely to be a clinically relevant cause of drug resistance .\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: Elevated aerobic glycolysis in cancer cells ( the Warburg effect ) may be attributed to respiration injury or mitochondrial dysfunction , but the underlying mechanisms and therapeutic significance remain elusive . Here we report that induction of mitochondrial respiratory defect by tetracycline-controlled expression of a dominant negative form of DNA polymerase γ causes a metabolic shift from oxidative phosphorylation to glycolysis and increases ROS generation . We show that upregulation of NOX is critical to support the elevated glycolysis by providing additional NAD+ . The upregulation of NOX is also consistently observed in cancer cells with compromised mitochondria due to the activation of oncogenic Ras or loss of p53 , and in primary pancreatic cancer tissues . Suppression of NOX by chemical inhibition or genetic knockdown of gene expression selectively impacts cancer cells with mitochondrial dysfunction , leading to a decrease in cellular glycolysis , a loss of cell viability , and inhibition of cancer growth in vivo . Our study reveals a previously unrecognized function of NOX in cancer metabolism and suggests that NOX is a potential novel target for cancer treatment .\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: Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc . We investigate the effect of zinc deficiency on DNA damage , expression of DNA-repair enzymes , and downstream signaling events in a cell-culture model . Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress . Low intracellular zinc increased DNA single-strand breaks ( comet assay ) . Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease ( APE ) . Repletion with zinc restored cell growth and reversed DNA damage . APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression . The ability of the transcription factors p53 , nuclear factor kappaB , and activator protein 1 ( AP1 ) to bind to consensus DNA sequences was decreased markedly with zinc deficiency , as assayed by electrophoretic mobility-shift assays . Thus , low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression , but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc .\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: PRL induces quiescent Nb2 rat T-lymphoma cells to undergo mitogenesis . Upon PRL stimulation , the transcription factor interferon regulatory factor-1 ( IRF-1 ) is induced as a novel T-cell activation gene in Nb2 cells . Surprisingly , IRF-1 is expressed twice during a single PRL-induced growth cycle : first during the early G1 phase , in an immediate transient peak from 15 min to 2 h , and second during the G1/S phase transition , in a broader peak beginning at 8 h . The unusual biphasic expression of IRF-1 mRNA is accompanied both times by de novo IRF-1 protein synthesis . However , the rate of IRF-1 protein turnover appears to be different in G1 and S phases . IRF-1 protein expressed in G1 exhibits a half-life of about 25 min , whereas in the S phase , the half-life is about 60 min . By washing out PRL at various times during G1 , we found a direct correlation among the length of PRL exposure , the second peak of IRF-1 mRNA expression , and DNA synthesis . Our data suggest that PRL and one putative nuclear mediator , IRF-1 , may be important in two distinct phases of the cell cycle : first in cell cycle activation , and then in S phase progression .\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: Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis . The possibility was tested that interleukin-8 ( IL-8 ) , which is a cytokine that is chemotactic for lymphocytes and neutrophils , is also angiogenic . Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells . Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha . An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity . These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis , tumor growth , and wound repair .\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: Androgen deprivation is currently a standard-of-care , first-line therapy for prostate cancer in the United States . Although this regimen effectively regresses androgen-dependent disease , relapse often occurs in an androgen-independent manner and is associated with poor prognosis . Such castration-resistant prostate cancer represents a major clinical challenge , and the mechanisms underlying castration resistance are not fully understood . Epithelial-mesenchymal transition ( EMT ) is a key developmental process and has also been implicated in cancer metastasis and therapeutic resistance in recent years . However , the factors contributing to EMT in human cancers remain unclear . Here , we show that both normal mouse prostate tissue and human LuCaP35 prostate tumor explants display an EMT as well as increased stem cell-like features following androgen deprivation . Importantly , we observed similar changes in mesenchymal features in prostate tumors from patients treated with androgen-deprivation therapy . In addition , we have delineated a feedback loop involving the androgen receptor and the Zeb1 transcription factor that seems to mediate this transition . In summary , we show for the first time that androgen deprivation induces EMT in both normal prostate and prostate cancer , revealing a potentially important consequence of a standard-of-care treatment for prostate cancer . This finding could have significant implications for second-line treatment strategies in this clinical setting .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Death receptors ( DR ) of the TNF family function as anti-tumor immune effector molecules . Tumor cells , however , often exhibit DR-signaling resistance . Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack . The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis . METHODOLOGY/PRINCIPAL FINDINGS The ability of radiation to modulate the expression of multiple death receptors ( Fas/CD95 , TRAILR1/DR4 , TRAILR2/DR5 , TNF-R1 and LTβR ) was examined in colorectal tumor cells . The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays . The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined . We found that radiation increased surface expression of Fas , DR4 and DR5 but not LTβR or TNF-R1 in these cells . Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation . Sub-lethal tumor cell irradiation alone exhibited minimal cell death , but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis , but not LTβR-induced death . Furthermore , radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation . Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L) and c-FLIP protein expression , this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types . CONCLUSIONS/SIGNIFICANCE Irradiation of tumor cells can overcome Fas and TRAIL resistance that is long lasting . Overall , results of these investigations suggest that non-lethal doses of radiation can be used to make human tumors more amenable to attack by anti-tumor effector molecules and cells .\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 insulin-like growth factor ( IGF ) pathway represents one of the most studied molecular regulatory networks in oncology . Clinical trials investigating the therapeutic value of anti-IGF1 receptor ( IGF1R ) therapies in cancer , including prostate cancer , are ongoing . However , the multiple functions of the IGF network in the prostate are not entirely known . To elucidate the effects of IGF and insulin ( INS ) on prostate cells , we stimulated prostate cancer ( PC3 , DU145 , LNCaP , DUCaP ) and noncancerous prostate cells ( EP156T , RWPE-1 ) and observed differing responses : whereas cancer cells responded to IGF and INS exposure by way of enhanced cell proliferation and glucose consumption , basal to luminal differentiation was induced in noncancerous cells . The same diverse responses were observed when the growth factor receptors IGF1R or INSR were overexpressed . Down-regulation of IGF1R or INSR isoform A ( INSRA ) also inhibited only proliferation of cancer cells . The proliferative response induced by the INSR in cancer cells was mediated solely by the INSRA . Moreover we observed that the receptors of the IGF network mutually influence their expression and exert redundant functions , thus underscoring the functional molecular network formed by IGF , INS , IGF1R , and INSR . Collectively we found that both IGF1R and INSRA have oncogenic effects in prostate cancer , but the IGF network also has important physiological functions in the noncancerous prostate . These data provide new insights into the biology of the IGF network in the prostate , thereby facilitating the design and interpretation of clinical studies investigating IGF1R targeting agents .\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: BACKGROUND Special AT-rich binding protein-1 ( SATB1 ) reprograms chromatin organization and transcription profiles to promote tumour growth and metastasis . AIMS This study aimed to confirm the effects of SATB1 on the growth and metastasis of liver cancer and its specific regulation mechanism . METHODS SATB1 expression was evaluated in human hepatoma tissue , adjacent noncancerous tissue and seven kinds of liver cancer cell lines . Cell cycle , cell proliferation , apoptosis and epithelial-mesenchymal transition ( EMT ) was investigated after enhanced or silenced expression of SATB1 . The regulatory action of SATB1 on the expression of genes that are known to regulate cell cycle progression , apoptosis and EMT and the specific apoptotic pathway on which it acts were further analysed . Nude mice that received subcutaneous implantation were used to study the effects of SATB1 on tumour growth in vivo . RESULTS Our data show that the high expression of SATB1 was observed in the human hepatocellular carcinoma tissue ( 26/45 ) and liver cancer cell lines with high metastatic potential . SATB1 upregulated CDK4 and downregulated p16 ( INK ) ( 4A ) to promote cell cycle progression and cell proliferation and prevented apoptosis by inhibiting the FADD-caspase-8-caspase-3 death receptor-mediated apoptosis pathway . SATB1 also induced EMT concomitant with increased expression of Snail1 , Slug , Twist and vimentin and decreased expression of E-cadherin , tight junction protein ZO-1 and desmoplakin . SATB1 promoted the growth of tumour in vivo . CONCLUSION These data suggest that the SATB1 gene may play an important role in the development and progression of liver cancer by regulation of genes related to cell cycle progression , apoptosis and EMT .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: BACKGROUND Glioblastoma is the most common and most aggressive form of malignant glioma and is very difficult to treat . Controlling tumour cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients . Since constitutive activation of nuclear factor-κB ( NF-κB ) is necessary for tumour progression , NF-κB may be an important pharmacological target for this disease . Our study aimed to evaluate the antitumour effects of parthenolide , a NF-κB inhibitor , in two human glioblastoma cell lines ( U87MG and U373 ) and in glioblastoma xenografts . Furthermore , we aimed to investigate the molecular mechanisms underlying these effects . METHODS The anti-invasive and anti-angiogenic effects of parthenolide were analysed using in vitro invasion and angiogenesis assays . Parthenolide-induced growth inhibition of glioblastoma cells in vitro was determined using the MTT ( methyl thiazolyl tetrazolium ) assay . In addition , the effect of parthenolide on orthotropic implantation in vivo was evaluated using an intracerebral human glioblastoma xenograft model . RESULTS We found that parthenolide suppresses proliferation , invasion , and tumour- induced angiogenesis of glioblastoma cells . Molecular studies demonstrated that parthenolide suppresses gene and protein expression of angiogenic factors . Furthermore , parthenolide reduced Akt phosphorylation and activated mitochondrial signalling , suggesting that the antitumour function of parthenolide may be mediated not only by the inhibition of NF-κB but also by the inhibition of Akt signalling and the activation of apoptotic proteins . Parthenolide suppressed neovascularity and tumour growth in glioblastoma xenografts . CONCLUSION The present study identified parthenolide as a new therapeutic agent for glioblastomas .\n OUTPUT:\n " }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Background and Objective . The cell cycle is regulated by proteins at different checkpoints , and dysregulation of this cycle plays a role in carcinogenesis . Matrix metalloproteinases ( MMPs ) are enzymes that degrade collagen and promote tumour infiltration . The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder ( UCB ) . Patients and Methods . This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder . Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs . Results . Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence . Also , normal p16 expression was related to a lower risk of tumour progression . MMP2 , p21 , cyclin D1 , and pRb showed no significant results that could estimate progression or recurrence . Conclusions . Normal p16 expression is associated with a lower risk of tumour progression , but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB .\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: Cellular senescence , initially observed during subculturing of normal diploid fibroblasts , can also be induced by chronic exposure to cellular stress , such as UV light , oxidative stress , or DNA damaging agents . Here we demonstrate that stable expression of an activated form of MKK6 ( MKK6EE ) , a direct activator of the stress-induced p38(HOG) mitogen-activated protein kinase pathway , is sufficient for inducing features of senescence including a flattened , vacuolated , and irregular morphology , staining for acidic beta-galactosidase , and accumulation of age-associated pigments . Consistent with the senescent phenotype , p38(HOG) activation induces a G(1) cell cycle arrest , which is permanent and irreversible after 4 days . MKK6EE also induces biochemical features of senescence in a p38-dependent manner , including enhanced expression of p21(CIP) , a cyclin-dependent kinase inhibitor . Microarray analysis of MKK6EE cells showed a pattern of gene expression noted previously in Werner Syndrome and senescent fibroblasts . These results define p38(HOG) as an intracellular pathway that activates a senescence checkpoint in tumor cells and may play a role in Ras- or stress-induced senescence .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: PURPOSE We did this retrospective study to explore the association between epidermal growth factor receptor ( EGFR ) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer ( NSCLC ) . MATERIALS AND METHODS We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007 . The start of tyrosine kinase inhibitor therapy was treated as a censoring event . Corresponding surgical specimens of primary tumors were used to test for EGFR mutations . RESULTS Thirty patients presented with local recurrence and distant recurrence was identified in 56 . Thirty-four of the 86 patients ( 40% ) harbored EGFR mutations . Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence ( 48% versus 23% ; P = 0.024 ) . On multivariate analysis , distant recurrence was associated with a high frequency of EGFR mutations ( OR , 3.3 ; P = 0.028 ) . Survival analysis showed poor survival of patients with mutated EGFR ( HR , 2.3 ; P = 0.017 ) or with non-adenocarcinoma histology ( HR , 3.3 ; P = 0.001 ) . CONCLUSION The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients . In addition , our data indicate unfavorable disease process of EGFR mutated tumors . Further studies need to be conducted to validate these findings .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;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: AIM The study was designed to explore the effects of antisense human telomerase RNA ( ahTR ) on the malignant phenotype of gastric carcinoma cell line SGC-7901 , and its potential role in gene therapy for tumors . METHODS An ahTR eukaryotic expression vector , including the sequence of template region of telomere repeats , was constructed by recombinant technology of molecules and then transfected into gastric carcinoma cell line SGC-7901 by liposome DOTAP . Subsequently , the expression of hTR RNA and ahTR RNA by reverse transcription-polymerase chain reaction , telomerase activity by telomeric repeat amplification protocol-ELISA ( TRAP-ELISA ) , telomere length by Southern blotting , cell morphology under light microscope , cellular proliferation capacity by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay , cell-cycle distribution by flow cytometry , efficiency of clone formation in soft agar , and tumorigenecity in nude mice were examined and evaluated in ahTR-transfected cells , control plasmid pCI-neo transfected cells and their parental cells . RESULTS An ahTR eukaryotic expression vector was constructed and successfully transfected into SGC-7901 cells . The telomerase activity in ahTR-transfected SGC-7901 cells decreased from 100% to approximately 25% , and telomere length in the cells shortened to 3.35 from 4.08 Kb at 60 population doublings . Compared with the parental cells and pCI-neo transfected cells , ahTR-transfected cells displayed some morphological changes , such as decreased atypia , and recovery of contact inhibition and density inhibition under light microscope . Furthermore , ahTR-transfected cells displayed decreased invasive capacity in Borden's chamber invasive model , increased G0/G1 phase rate and apoptotic rate . Surprisingly , ahTR-transfected SGC-7901 cells lost their capacity for clone formation in soft agar and tumorigencity in nude mice . CONCLUSION Antisense-hTR transfection can inhibit the growth of SGC-7901 cells and partially reverse the malignant phenotypes . This study provides an exciting approach for cancer therapy by inhibiting telomerase activity using an antisense gene .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors;activating invasion and metastasis;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 t(10;11)(p12;q23) chromosomal translocation in human acute myeloid leukemia results in the fusion of the MLL and AF10 genes . The latter codes for a novel leucine zipper protein , one of many MLL fusion partners of unknown function . In this report , we demonstrate that retroviral-mediated transduction of an MLL-AF10 complementary DNA into primary murine myeloid progenitors enhanced their clonogenic potential in serial replating assays and led to their efficient immortalization at a primitive stage of myeloid differentiation . Furthermore , MLL-AF10-transduced cells rapidly induced acute myeloid leukemia in syngeneic or severe combined immunodeficiency recipient mice . Structure/function analysis showed that a highly conserved 82-amino acid portion of AF10 , comprising 2 adjacent alpha-helical domains , was sufficient for immortalizing activity when fused to MLL . Neither helical domain alone mediated immortalization , and deletion of the 29-amino acid leucine zipper within this region completely abrogated transforming activity . Similarly , the minimal oncogenic domain of AF10 exhibited transcriptional activation properties when fused to the MLL or GAL4 DNA-binding domains , while neither helical domain alone did . However , transcriptional activation per se was not sufficient because a second activation domain of AF10 was neither required nor competent for transformation . The requirement for alpha-helical transcriptional effector domains is similar to the oncogenic contributions of unrelated MLL partners ENL and ELL , suggesting a general mechanism of myeloid leukemogenesis by a subset of MLL fusion proteins , possibly through specific recruitment of the transcriptional machinery .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Using monolayer cultures of clonally isolated C3 and T5 rat prostate cancer cells , we determined that acidic ( aFGF ) and basic ( bFGF ) fibroblast growth factors profoundly enhanced T5 cell thymidine incorporation with half-maximum stimulation at 0.53 and 0.35 ng/ml , respectively . In contrast , aFGF or bFGF enhancement of C3 cell thymidine incorporation was about 5% of that of T5 cells , and effects were principally mitogen concentration independent . Saturation analyses and cross-linking studies established that both C3 and T5 cells contained high-affinity FGF receptors of 120 and 145 kilodaltons and that receptor content and Kd of C3 and T5 cells were comparable. aFGF or bFGF stimulation of T5 cell thymidine incorporation profoundly decreased as cell plating density was reduced from 1.5 x 10(5) to 1.0 x 10(4) cells/well . The modest response of C3 cells to either aFGF or bFGF also decreased as cell plating density was reduced . Because heparin preserves FGF biological activity and enhances bFGF binding to high-affinity FGF receptors , we examined the effect of heparin on FGF stimulation of C3 cell thymidine incorporation . We found that changes in cell plating density and/or medium heparin concentration had variable , inconsistent effects . These were C3 cell plating density associated and included inhibition or modest enhancement of FGF effects . Binding analyses established that high-affinity bFGF binding of C3 and T5 cells immediately prior to assessing FGF-stimulated thymidine incorporation was comparable and independent of cell plating density , implying that C3 cell FGF insensitivity was not attributable to differences in C3 and T5 cell FGF receptor content at the time of mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS )\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: Various endocrine disrupting chemicals ( EDCs ) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation . Among EDCs , bisphenolA ( BPA ) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [ methoxychlor ( MXC) ] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors ( ERs ) , causing human health problems such as abnormal reproduction and carcinogenesis . In this study , we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells . MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line ; these cells are , therefore , a useful invitro model for detecting estrogenic activity in response to EDCs . We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay . We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH . To determine whether BPA and MXC stimulate cancer cell growth though ER signaling , we co-treated the cells with agonists ( propyl pyrazoletriol , PPT ; and diarylpropionitrile , DPN ) or an antagonist ( ICI 182,780 ) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs . These studies confirmed the carcinogenicity of EDCs invitro . As a result , BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes , especially ones affecting the G1/S transition via ERα signaling . These collective results confirm the carcinogenicity of these EDCs invitro . Further studies are required to determine whether EDCs promote carcinogenesis invivo .\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: Hypoxia–reoxygenation ( HR ) is a primary driver of angiogenesis in both atherogenesis and tumorigenesis . The main target of hypoxia-driven proangiogenic signaling is adherens junctions responsible for contact inhibition of endothelial cells . We analyzed the effects of hypoxia ( 8–12 hours ) followed by a brief period of reoxygenation ( 2 hours ) ( HR ) on angiogenesis and integrity of adherens junction in cultured human umbilical vein endothelial cells as well as the effects of aspirin on modulation of human umbilical vein endothelial cells ' response to HR . Cells exposed to HR displayed considerable enhancement of tube formation ( angiogenesis ) on matrigel . Immunocytostaining of near-confluent cells revealed that HR caused disruption of adherens junctions and internalization of their components VE-cadherin , p120 catenin , and b-catenin . Additionally , HR resulted in the appearance of binucleated cells , and VE-cadherin in colocalization with b-catenin was found to be positioned between the separating nuclei . Presence of aspirin ( acetylsalicylic acid , 1 mM ) resulted in preservation of adherens junctions on the cellular membrane and prevented angiogenesis as well as mitosis . HR caused upregulation LOX-1 , the p47(phox) subunit of NADPH , while reducing transcription of endothelial nitric oxide synthase . Aspirin had no effect on endothelial nitric oxide synthase and canceled the transcriptional activation of the LOX-1 and p47(phox) subunit of NADPH oxidase . Based on these data , we hypothesize that aspirin preserves the integrity of adherens junctions and thus blunts angiogenic response to HR through downregulation of LOX-1 and the LOX-1-mediated p47(phox) component of NADPH oxidase transcription , thus preventing NADPH oxidase assembly and function .\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: Tea ( Camellia sinensis ) is one of the most popular beverages , consumed worldwide . The health promoting properties of tea have been attributed to its antioxidative polyphenolic constituents and their oxidative products . The aim of the present study was to evaluate the chemopreventive efficacy of a black tea infusion on azoxymethane induced colonic preneoplastic lesions , the aberrant crypt foci in Sprague-Dawley rats . Rats were injected with azoxymethane ( 15mg/kg.b.w. ) and received oral administration of 1% and 2% ( w/v ) tea infusions from the 1(st)day of carcinogen application . The treatment was continued for 12 weeks . The colons were then assessed for aberrant crypt foci and compared with the untreated carcinogen control group . In situ cell proliferation and in situ apoptosis were also estimated using Brdu incorporation and the TUNEL method , respectively . Aberrant crypt foci were reduced significantly ( by 44% in the 1% tea-treated and by about 40% in 2% tea-treated group ) . Significant decrease in proliferation and increase in apoptosis suggest a possible interplay between the two processes resulting in inhibition of colon carcinogenesis by black tea .\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: When the cell cycle is arrested , even though growth-promoting pathways such as mTOR are still active , then cells senesce . For example , induction of either p21 or p16 arrests the cell cycle without inhibiting mTOR , which , in turn , converts p21/p16-induced arrest into senescence ( geroconversion ) . Here we show that geroconversion is accompanied by dramatic accumulation of cyclin D1 followed by cyclin E and replicative stress . When p21 was switched off , senescent cells ( despite their loss of proliferative potential ) progressed through S phase , and levels of cyclins D1 and E dropped . Most cells entered mitosis and then died , either during mitotic arrest or after mitotic slippage , or underwent endoreduplication . Next , we investigated whether inhibition of mTOR would prevent accumulation of cyclins and loss of mitotic competence in p21-arrested cells . Both nutlin-3 , which inhibits mTOR in these cells , and rapamycin suppressed geroconversion during p21-induced arrest , decelerated accumulation of cyclins D1 and E and decreased replicative stress . When p21 was switched off , cells successfully progressed through both S phase and mitosis . Also , senescent mouse embryonic fibroblasts ( MEFs ) overexpressed cyclin D1 . After release from cell cycle arrest , senescent MEFs entered S phase but could not undergo mitosis and did not proliferate . We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence .\n OUTPUT:\n " }, { "from": "agent", "value": "sustaining proliferative signaling;enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Colorectal cancer ( CRC ) is one of the leading causes of cancer deaths in Western countries . A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease . MicroRNAs ( miRNAs ) are aberrantly expressed in cancers and appear to have both diagnostic and prognostic significance . In this study , we identified novel miRNAs associated with recurrence of CRC , and their possible mechanism of action . TaqMan� Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosas and 46 microsatellite stable CRC tumors . Four miRNAs ( miR-362-3p , miR-570 , miR-148a* and miR-944 ) were expressed at a higher level in tumors from patients with no recurrence ( p &lt ; 0.015 ) , compared to tumors from patients with recurrence . A significant association with increased disease free survival was confirmed for miR-362-3p in a second independent cohort of 43 CRC patients , using single TaqMan� microRNA assays . In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability , and proliferation mainly due to cell cycle arrest . E2F1 , USF2 and PTPN1 were identified as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p . Subsequently , these genes were confirmed as direct targets by Luciferase reporter assays . Their knockdown in vitro phenocopied the effects of miR-362-3p over-expression . We conclude that miR-362-3p may be a novel prognostic marker in CRC , and hypothesize that the positive effects of augmented miR-362-3p expression may in part be mediated through the targets E2F1 , USF2 and PTPN1. � 2012 Wiley Periodicals , Inc .\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: INTRODUCTION During selective segregation of DNA , a cell asymmetrically divides and retains its template DNA . Asymmetric division yields daughter cells whose genome reflects that of the parents ' , simultaneously protecting the parental cell from genetic errors that may occur during DNA replication . We hypothesized that long-lived epithelial cells are present in immortal , premalignant cell populations , undergo asymmetric division , retain their template DNA strands , and cycle both during allometric growth and during pregnancy . METHODS The glands of 3-week old immune competent Balb/C female mice were utilized intact or cleared of host epithelium and implanted with ductal-limited , lobule-limited , or alveolar-ductal progenitor cells derived from COMMA-D1 pre-malignant epithelial cells. 5-bromo-2-deoxyuridine ( 5-BrdU ) was administered to identify those cells which retain their template DNA . Nulliparous mice were then either injected with [ (3)H]-thymidine ( (3)H-TdR ) to distinguish 5-BrdU-label retaining cells that enter the cell cycle and euthanized , or mated , injected with ( 3)H-TdR , and euthanized at various days post-coitus . Sections were stained for estrogen receptor-α(ER-α) or progesterone receptor ( PR ) via immunohistochemistry . Cells labelled with both 5-BrdU and ( 3)H-TdR were indicative of label-retaining epithelial cells ( LREC ) . RESULTS Cells that retained a 5-BrdU label and cells labelled with [ (3)H]-thymidine were found in all mice and were typically detected along the branching epithelium of mature mouse mammary glands . Cells containing double-labelled nuclei ( LREC ) were found in the intact mammary gland of both pregnant and nulliparous mice , and in mammary glands implanted with pre-malignant cells . Double-labelled cells ( (3)H-TdR/5-BrdU ) represent a small portion of cells in the mammary gland that cycle and retain their template DNA ( 5-BrdU ) . Some label-retaining cells were also ER-α or PR positive . LRECs distributed their second label ( (3)H-TdR ) to daughter cells ; and this effect persisted during pregnancy . LRECs , and small focal hyperplasia , were found in all immortalized premalignant mammary implant groups . CONCLUSIONS The results indicate that a subpopulation of long-lived , label-retaining epithelial cells ( LRECs ) is present in immortal premalignant cell populations . These LRECs persist during pregnancy , retain their original DNA , and a small percentage express ER-α and PR . We speculate that LRECs in premalignant hyperplasia represent the long-lived ( memory ) cells that maintain these populations indefinitely .\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: Signal transducers and activators of transcription 3 ( Stat3 ) is activated by cytokines and growth factors in lung cancers and regulates expression of genes implicated in cell growth , survival , and transformation . Previously , we found that mice with a deletion of the G protein-coupled receptor , family C , group 5 , member a ( Gprc5a ) gene develop lung tumors , indicating that Gprc5a is a tumor suppressor . Herein , we show that epithelial cells from Gprc5a knockout mouse lung ( Gprc5a(-/-) cells ) survive better in vitro in medium deprived of exogenous growth factors and form more colonies in semisolid medium than their counterparts from wild-type mice ( Gprc5a(+/+) cells ) . Stat3 tyrosine 705 phosphorylation and expression of several Stat3-regulated antiapoptotic genes were higher in Gprc5a(-/-) than in Gprc5a(+/+) cells . Both cell types secreted leukemia inhibitory factor ( Lif ) ; however , whereas Stat3 activation was persistent in Gprc5a(-/-) cells , it was transient in Gprc5a(+/+) cells . Lung adenocarcinoma cells isolated from Gprc5a(-/-) mice also exhibited autocrine Lif-mediated Stat3 activation . The level of Socs3 , the endogenous Stat3 inhibitory protein , was higher in Gprc5a(+/+) than in Gprc5a(-/-) cells , and expression of the tumor suppressor stabilized Socs3 . Inhibition of Stat3 signaling in Gprc5a(-/-) normal and cancer cells by the Janus-activated kinase 2 inhibitor AG490 or by a dominant negative Stat3(Y705F) increased starvation-induced apoptosis and inhibited colony formation . These results show that persistent Stat3 activation is important for the survival and transformation of Gprc5a(-/-) lung cells and suggest that the tumor suppressive effects of Gprc5a are mediated , at least in part , by inhibition of Stat3 signaling through Socs3 stabilization .\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: Genomic instability drives tumorigenesis , but how it is initiated in sporadic neoplasias is unknown . In early preneoplasias , alterations at chromosome fragile sites arise due to DNA replication stress . A frequent , perhaps earliest , genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus , leading to loss of Fhit protein expression . Because common chromosome fragile sites are exquisitely sensitive to replication stress , it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products . Here , we show in normal , transformed , and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks . Using DNA combing , we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse . The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels ; notably , restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells . Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest , allowing continued cell proliferation and ongoing chromosomal instability . This finding was in accord with in vivo studies , as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci . Furthermore , cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications , including amplification of the Mdm2 gene , suggesting that Fhit loss-induced genome instability facilitates transformation . We propose that loss of Fhit expression in precancerous lesions is the first step in the initiation of genomic instability , linking alterations at common fragile sites to the origin of genome instability .\n OUTPUT:\n " }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling;enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: OBJECTIVE To construct the eukaryotic expression vector for Max interacting protein 1 ( Mxi1 ) . METHODS The full length cDNA of Mxi1 gene obtained from fetal lymphocyte and KG1 cells were inserted into plasmid pDs-red2-N1 respectively to generate pDs-red2-N1/Mri1 ( wild/mutation type ) . Then the recombinant vector was transfected into Cos-7 cells via liposome. 48 hours post transfection , mRNA of Mri1 gene was detected by RT-PCR and Mxi1 protein expression was detected by flow cytometry and fluorescence microscope in the Cos-7 cells . RESULTS The eukaryotic expression vector of Mxi1 was constructed and transfected into eukaryotic cells successfully . The expression of red fluorescence protein in the transfected Cos-7 cells was observed under fluorescence microscope which implied the expression of Mxi1 . The transfect efficiency of both wild and mutation type were in a high level in 3 days after transfected , which lasted to 6 d . RT-PCR amplified the total RNA extracted from the transfected Cos-7 cells could find increased mRNA level of Mxi1 gene . CONCLUSION We successfully constructed the eukaryote expression vector for Mri1 gene ; Cos-7 cells transfected with the vector via liposome could express Mxi1 protein . These could be useful for the further study of the Myc gene modulation .\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: Tumour cells primarily utilize aerobic glycolysis for energy production , a phenomenon known as the Warburg effect . Its mechanism is not well understood . The tumour suppressor gene p53 is frequently mutated in tumours . Many tumour-associated mutant p53 ( mutp53 ) proteins not only lose tumour suppressive function but also gain new oncogenic functions that are independent of wild-type p53 , defined as mutp53 gain of function ( GOF ) . Here we show that tumour-associated mutp53 stimulates the Warburg effect in cultured cells and mutp53 knockin mice as a new mutp53 GOF . Mutp53 stimulates the Warburg effect through promoting GLUT1 translocation to the plasma membrane , which is mediated by activated RhoA and its downstream effector ROCK . Inhibition of RhoA/ROCK/GLUT1 signalling largely abolishes mutp53 GOF in stimulating the Warburg effect . Furthermore , inhibition of glycolysis in tumour cells greatly compromises mutp53 GOF in promoting tumorigenesis . Thus , our results reveal a new mutp53 GOF and a mechanism for controlling the Warburg effect .\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: A panel of primary human cells and virus-transformed derivatives were tested for events that coincide with immortalization . In all primary and precrisis cells , two proteins of 92 and 150 kDa that shared an epitope with p53 were found ; in most of their immortalized derivatives , however , they were absent . Expression of these proteins may be involved in senescence .\n OUTPUT:\n " }, { "from": "agent", "value": "enabling replicative immortality" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: Radiation-induced carcinogenesis is a major concern both for astronauts on long-term space missions and for cancer patients being treated with therapeutic radiation . Exposure to radiation induces oxidative stress and chronic inflammation , which are critical initiators and promoters of carcinogenesis . Many studies have demonstrated that non-steroidal anti-inflammatory drugs and antioxidants can reduce the risk of radiation-induced cancer . In this study , we found that a synthetic triterpenoid , CDDO-Me ( bardoxolone methyl ) , was able to protect human colon epithelial cells ( HCECs ) against radiation-induced transformation . HCECs that were immortalized by ectopic expression of hTERT and cdk4 and exhibit trisomy for chromosome 7 ( a non-random chromosome change that occurs in 37% of premalignant colon adenomas ) can be transformed experimentally with one combined exposure to 2 Gy of protons at 1 GeV/nucleon followed 24 h later by 50 cGy of ( 56)Fe ions at 1 GeV/nucleon . Transformed cells showed an increase in proliferation rate and in both anchorage-dependent and independent colony formation ability . A spectrum of chromosome aberrations was observed in transformed cells , with 40% showing loss of 17p ( e.g. loss of one copy of p53 ) . Pretreatment of cells with pharmacological doses of CDDO-Me , which has been shown to induce antioxidative as well as anti-inflammatory responses , prevented the heavy-ion-induced increase in proliferation rate and anchorage-dependent and independent colony formation efficiencies . Taken together , these results demonstrate that experimentally immortalized human colon epithelial cells with a non-random chromosome 7 trisomy are valuable premalignant cellular reagents that can be used to study radiation-induced colorectal carcinogenesis . The utility of premalignant HCECs to test novel compounds such as CDDO-Me that can be used to protect against radiation-induced neoplastic transformation is also demonstrated .\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: Lung cancer is primarily caused by exposure to tobacco smoke . Tobacco smoke contains numerous carcinogens , including polycyclic aromatic hydrocarbons ( PAH ) . The most common PAH studied is benzo[a]pyrene ( B[a]P ) . B[a]P is metabolically activated through multiple routes , one of which is catalyzed by aldo-keto reductase ( AKR ) to B[a]P-7,8-dione ( BPQ ) . BPQ undergoes a futile redox cycle in the presence of NADPH to generate reactive oxygen species ( ROS ) . ROS , in turn , damages DNA . Studies with a yeast p53 mutagenesis system found that the generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because of similarities between the patterns ( types of mutations ) and spectra ( location of mutations ) and those seen in lung cancer . The patterns were dominated by G to T transversions , and the spectra in the experimental system have mutations at lung cancer hotspots . To address repair mechanisms that are responsible for BPQ induced damage we observed the effect of mutating two DNA repair genes OGG1 and APE1 ( APN1 in yeast ) and tested them in a yeast reporter system for p53 mutagenesis . There was an increase in both the mutant frequency and the number of G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1 yeast . Knocking out APN2 increased mutagenesis in the apn1 cells . In addition , we did not find a strand bias on p53 treated with BPQ in ogg1 yeast . These studies suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ , Apn1 and Apn2 have redundant functions and that the stand bias seen in lung cancer may not be due to impaired repair of oxidative lesions .\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 used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 ( PRC17 ) . When overexpressed in 3T3 mouse fibroblast cells , PRC17 induced growth in low serum , loss of contact inhibition , and tumor formation in nude mice . The PRC17 gene product contains a GTPase-activating protein ( GAP ) catalytic core motif found in various Rab/Ypt GAPs , including RN-Tre . Similar to RN-Tre , we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis . Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities , suggesting that GAP activity is essential for its oncogenic function . Whereas PRC17 is amplified in 15% of prostate cancers , it is highly overexpressed in approximately one-half of metastatic prostate tumors . The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers .\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 xeroderma pigmentosum group C ( XPC ) protein specifically involved in genome-wide damage recognition for nucleotide excision repair ( NER ) was purified as a tight complex with HR23B , one of the two mammalian homologs of RAD23 in budding yeast . This XPC-HR23B complex exhibits strong binding affinity for single-stranded DNA , as well as preferential binding to various types of damaged DNA . To examine the structure-function relationship of XPC , a series of truncated mutant proteins were generated and assayed for various binding activities . The two domains participating in binding to HR23B and damaged DNA , respectively , were mapped within the carboxy-terminal half of XPC , which also contains an evolutionary conserved amino acid sequence homologous to the yeast RAD4 protein . We established that the carboxy-terminal 125 amino acids are dispensable for both HR23B and damaged DNA binding , while interactions with transcription factor IIH ( TFIIH ) are significantly impaired by truncation of this domain . Furthermore , deletion of the extreme carboxy-terminal domain totally abolished XPC activity in the cell-free NER reaction . These results suggest that following initial damage recognition , the carboxy terminus of XPC may be essential for the recruitment of TFIIH , and that most truncation mutations identified in XP-C patients result in non-functional proteins .\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: Protein kinase B ( AKT)/mammalian target of rapamycin ( mTOR ) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors , and has been shown to be important therapeutic targets for cancer . The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma ( HA ) . Twenty-five cases of human HA tissues were collected . The expression of AKT , mTOR and proliferating cell nuclear antigen ( PCNA ) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA . AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR ( rAd5-Am ) , used for infecting proliferating phase HA-derived endothelial cells ( HDEC ) . The expression of AKT , mTOR and PCNA was detected by Real-time PCR and Western blot assays . Cell proliferative activities were determined by MTT assay , and cell cycle distribution and apoptosis were analyzed by flow cytometry . As a consequence , the expression of AKT , mTOR and PCNA was significantly increased in proliferative phase HA , while that was decreased in involutive phase . Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities , and induced cell apoptosis and cycle arrest with the decreased expression of AKT , mTOR and PCNA in proliferative phase HDEC . In conclusion , the activity of AKT/mTOR pathway was increased in proliferative phase HA , while it was decreased in involutive phase . Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression , and induce apoptosis and cycle arrest in proliferative phase HDEC , suggesting that AKT/mTOR pathway might represent the important therapeutic targets for human HA .\n OUTPUT:\n " }, { "from": "agent", "value": "resisting cell death;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: UNLABELLED Activation of beta-catenin , the central effector of the canonical Wnt pathway and a recognized oncogene , has been implicated in hepatocellular carcinoma . We examined N-nitrosodiethylamine ( DEN)-induced tumorigenesis in hepatic beta-catenin conditional knockout mice ( beta-cat KO ) . Male beta-cat KO and age- and sex-matched littermate controls were given a single intraperitoneal DEN injection and followed for 6-12 months for hepatic tumors . Hepatic tumors were characterized for histology , proliferation , apoptosis , oxidative stress , and specific proteins by way of western blot , immunohistochemistry , and coprecipitation studies . For in vivo tumor intervention studies , specific inhibitors were administered intraperitoneally or through drinking water . Intriguingly , beta-cat KO mice showed a paradoxical increase in susceptibility to DEN-induced tumorigenesis . This accelerated tumorigenesis is due to increased injury and inflammation , unrestricted oxidative stress , fibrosis , and compensatory increase in hepatocyte proliferation secondary to platelet-derived growth factor receptor alpha ( PDGFRalpha)/phosphoinositide 3-kinase ( PIK3CA)/Akt activation and c-Myc overexpression . In vitro suppression of beta-catenin expression in hepatoma cells led to enhanced PDGFRalpha expression , which was abrogated in the presence of nuclear factor kappaB ( NF-kappaB ) inhibitor . Daily treatment of 6-month-old DEN-exposed beta-cat KO with PDGFRalpha inhibitor dramatically reduced tumor numbers and size . Inclusion of N-acetyl-L-cysteine , a known antioxidant and NF-kappaB inhibitor , in the drinking water led to complete abolition of tumorigenesis in DEN-exposed beta-cat KO . CONCLUSION Loss of beta-catenin impairs the liver's ability to counteract DEN-induced oxidative stress and enhances tumorigenesis through PDGFRalpha/PIK3CA/Akt signaling . Blockade of PDGFRalpha or oxidative stress dramatically affects beta-catenin-deficient tumorigenesis . Also , hepatoma cells use PDGFRalpha/PIK3CA signaling as an escape mechanism following beta-catenin suppression , and their sequential suppression profoundly impedes tumor proliferation .\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: SWAP-70 , a phosphatidylinositol trisphosphate ( PtdIns(3,4,5)P(3) ) binding protein , has been suggested to be involved in transformation of mouse embryo fibroblasts ( MEFs ) as well as membrane ruffling after growth factor stimulation of the cells . A mutant , SWAP-70-374 , was found to be able to bind to F-actin in vitro , whereas wild-type SWAP-70 failed to do so . This mutant was present at the plasma membrane without any stimulation while the wild-type protein was present only in the cytosol unless cells were stimulated with EGF . Expression of this mutant in MEFs resulted in morphologic transformation , fast growth , and loss of contact inhibition , suggesting that SWAP-70 with this mutation can transform the cells . ERK1/2 was activated in SWAP-70-374-transformed cells . Use of MEK inhibitors revealed that the ERK1/2 pathway does not affect the cell growth of MEFs but is responsible for loss of contact inhibition . To investigate the function of SWAP-70 further , drugs that can inhibit SWAP-70-dependent cell responses were screened . Among various drugs , sanguinarine was found to inhibit transformation of MEFs by SWAP-70-374 . This drug was able to inhibit SWAP-70-mediated membrane ruffling as well , suggesting that its effect was closely related to the SWAP-70 signaling pathway . These results suggest that SWAP-70-374 can activate some signaling pathways , including the ERK1/2 pathway , to transform MEFs .\n OUTPUT:\n " }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.\n OUTPUT: sustaining proliferative signaling;resisting cell death\n\n INPUT: The suppression of MAPK and oxidative stress could be an important anti-inflammatory mechanism . Fucoidan regulates MAPK activity in several cell lines . However , the mechanism for the anti-inflammatory and oxidative stress effect of low molecular weight fucoidan ( LMWF ) is poorly understood in RAW264.7 cells . The objective of this study was to examine the critical role of LMWF during LPS-induced inflammation in RAW264.7 cells . To determine the potential role of LMWF , we analysed pro-inflammatory cytokine , transcription factor , inflammation-related and oxidative stress related protein expression in vitro during LPS-induced inflammation in RAW264.7 cells . In this study , we demonstrated the anti-inflammatory effects of LMWF on LPS-induced inflammation in macrophages through the regulation of signalling pathways , including its effect on the attenuation of inflammatory cytokines , such as IL-1β , IL-1 and TNF-α , and the degradation of phosphorylated p38 MAPK , ERK1/2 and JNK . This study also demonstrates that LMWF might block NO as well as the expression of reactive oxygen species ( ROS ) , which subsequently inhibits the iNOS and COX-2 expression induced by LPS . Based on these findings , we suggest that LMWF might have great potential as an external pathogen prevention and intervention agent for inflammatory diseases .\n OUTPUT:\n " }, { "from": "agent", "value": "tumor promoting inflammation" } ]