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clinicalnlplab

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HoC_1shot_test

like 1

HoC_1shot400

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects , including anti-inflammatory , cardio-protective , and cancer-protective activities . It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders . Ulcerative colitis is an idiopathic , chronic inflammatory disease of the colon associated with a high colon cancer risk . Here , we used a dextran sulfate sodium ( DSS ) mouse model of colitis , which resembles human ulcerative colitis pathology . Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner . Resveratrol significantly improves inflammation score , downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria , and modulates CD3(+) T cells that express tumor necrosis factor-alpha and IFN-gamma . Markers of inflammation and inflammatory stress ( p53 and p53-phospho-Ser(15) ) are also downregulated by resveratrol . Because chronic colitis drives colon cancer risk , we carried out experiments to determine the chemopreventive properties of resveratrol . Tumor incidence is reduced from 80% in mice treated with azoxymethane ( AOM ) + DSS to 20% in mice treated with AOM + DSS + resveratrol ( 300 ppm ) . Tumor multiplicity also decreased with resveratrol treatment . AOM + DSS-treated mice had 2.4 +/- 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol , which had 0.2 +/- 0.13 tumors per animal . The current study indicates that resveratrol is a useful , nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis . OUTPUT:

tumor promoting inflammation

HoC_1shot401

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND The current staging system provides an anatomical classification of lung tumors ; its secondary purpose is to allow the prognostic stratification of patients into homogeneous groups after surgery . In this work , intratumoral perineural invasion , lymphatic and blood vessel invasion together with the necrosis content of the tumor exclusive of the non-small cell cancer staging system were studied . METHODS During a 4-year period , 152 patients operated for non-small cell lung cancer ( NSCLC ) at our hospital were analyzed . Mean age of patients was 55.7 +/- 10.1 years . RESULTS Overall 5-year survival was 42.2 % . Mediastinal lymph node involvement , tumor size , incomplete resection , pneumonectomy , presence of necrosis and perineural invasion were significant prognosticators ( P = 0.03 , 0.04 , 0.0001 , 0.046 , 0.0246 , &lt ; 0.0001 , respectively ) . Multivariate analysis revealed that N status , perineural invasion , and the presence of necrosis were independent prognostic factors ( P = 0.006 , P = 0.001 , P = 0.001 , respectively ) . Patients who had stage I tumor with necrosis and perineural invasion had a lower survival rate than those with stage IIIA tumor without these histopathological features ( P = 0.04 ) . The presence of these histopathological characteristics in stage IIIA patients was a sign of a poorer prognosis ( P = 0.0001 ) . CONCLUSIONS Perineural invasion and the presence of necrosis independently indicated a dismal prognosis and their prognostic power is comparable to those of the TNM classification . These factors could be candidates for better survival stratification and the indicators of the need for adjuvant therapy in early stage lung cancer patients . OUTPUT:

activating invasion and metastasis;resisting cell death

HoC_1shot402

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: It has been shown that injecting a suspension of IFN-γ-secreting tumor cells results in their rejection . This effect has been attributed to IFN-γ preventing tumor stroma formation but not to a direct effect on the cancer cells . However , it is not known , which influence IFN-γ has on tumors with an established stroma . To address this question , the plasmacytoma cell line J558L was transduced with a vector allowing doxycycline-inducible IFN-γ gene expression . After the injection of the tumor cells into mice , IFN-γ was induced at different time points . Tumors did not grow when inducing IFN-γ immediately after tumor cell inoculation , while approximately half of the tumors were rejected when IFN-γ was induced in early established tumors within 2 weeks . Induction of IFN-γ 2-3 weeks after tumor cell inoculation was less efficient ( 0-17% rejection ) . IFN-γ induction in established tumors led to a reduction of CD146(+) endothelial cells and massive necrosis . Together , we show that vascularized tumors can be rejected by local IFN-γ expression , but that rejection of established tumors was less efficient over time . This suggests that transplanted tumors became less susceptible to local IFN-γ treatment the better they are established . OUTPUT:

resisting cell death;inducing angiogenesis

HoC_1shot403

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Palmitoylation is required for the activities of several cancer-associated proteins , making the palmitoyl acyltransferase ( PAT ) enzymes that catalyze these reactions potential targets for anticancer therapeutics . In this study , we sought to identify and characterize a human PAT with activity toward N-terminally myristoylated and palmitoylated proteins . NIH/3t3 cells were stably transfected with vectors containing no insert , wild type human DHHC20 , or a serine-substituted DHHS20 mutant . Compared with control cells , cells overexpressing wild-type DHHC20 displayed an increase in palmitoylation activity toward a peptide that mimics the N-terminus of myristoylated and palmitoylated proteins , but had no change in activity toward a peptide that mimics the C-terminus of farnesylated and palmitoylated proteins . Cells expressing DHHS20 had no significant change in activity toward either peptide . Overexpression of DHHC20 also caused phenotypic changes consistent with cellular transformation , including colony formation in soft agar , decreased contact inhibition of growth , and increased proliferation under low-serum conditions . Quantitative polymerase chain reaction analyses of human tissues demonstrated that DHHC20 is expressed in a tissue-specific manner , and is overexpressed in several types of human tumors , including ovarian , breast and prostate . Overall , these results demonstrate that DHHC20 is a human N-terminal-myristoyl-directed PAT involved in cellular transformation , that may play a role in cancer . OUTPUT:

evading growth suppressors

HoC_1shot404

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

resisting cell death

HoC_1shot405

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

evading growth suppressors;resisting cell death

HoC_1shot406

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

evading growth suppressors;sustaining proliferative signaling

HoC_1shot407

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: This research aims to give a new insight to the relationship between host local immune response and the biological behaviour of the tumor by evaluating of intratumoral natural killer ( NK ) cells and tumor necrosis factor-alpha ( TNFalpha ) expressions in oral squamous cell carcinomas . New paraffin sections of the deepest parts of the 46 cases of oral squamous cell carcinomas were immunohistochemically treated by CD57 , selected as NK cell indicator , and TNFalpha monoclonal antibodies . The tumors were graded according to histopathologic grading scores of invasive margins and categorized into 2 groups as " good " and " poor " prognostic groups . Fifteen cases , from which could be obtained full clinical data , were clinically staged and because of the scarcity of the cases in each group were divided , again , two groups as group 1 : stage I+stage II and group 2 : stage III+stage IV . The expression levels of CD57 and TNFalpha were evaluated according to histopathologic grading groups and clinical staging groups . The results showed that the density of CD57+cells ( NK cells ) was statistically lower in tumors graded as poor prognostic group compared to the cases in good prognostic group . On the contrary , expression level of TNFalpha was statistically higher in poor prognostic group . These findings suggested that increased secretion of TNFalpha in the tumors , which show high invasive potential , may be one of the facilitating factors for tumor invasion and be responsible from suppression of NK cells . Withdrawal of NK cells in the high invasive tumor areas also reminds the necessity of certain shared genetic rearrangements in tumor cells for getting protected from NK cell attacks and moving ahead within the extracellular matrix . OUTPUT:

activating invasion and metastasis

HoC_1shot408

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We report that all-trans retinoic acid ( ATRA ) in combination with zoledronic acid has strong synergistic cytotoxic and apoptotic effects against human hormone- and drug-refractory prostate cancer cells , PC-3 and DU-145 , in a time- and dose-dependent manner . We further investigated the effect of the combination treatment on the apoptotic process by both oligoarray and protein array analysis in DU-145 cells , in which the drug combination shows much more strong synergistic effects , as compared to PC-3 cells . Moreover , we have also performed real time-PCR array analysis to validate oligoarray results . We demonstrated that the combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in human androgen-and drug refractory prostate cancer cells DU-145 , at either transcriptional or translational levels . While expression of proapoptotic genes such as tumor necrosis factor receptor superfamily ( TNFRSF ) , Bad , Bax , Fas , FADD are induced with the exposure of the combination , expression of antiapoptotic genes or proteins such as members of inhibitor apoptosis family ( IAPs ) , MCL-1 , LTBR , p53 and bcl-2 are reduced . Because this novel combination treatment has fewer side effects than is generally the case with conventional cytotoxic agents , this regimen may be a good option for treatment of elderly prostate cancer patients . OUTPUT:

resisting cell death

HoC_1shot409

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The transcription factor NF-kappaB is constitutively active in pancreatic adenocarcinoma . Here we explore the contribution of NF-kappaB to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role . Block of NF-kappaB signalling by non-destructible IkappaBalpha rendered cells resistant to TGF-beta-induced epithelial-mesenchymal transition ( EMT ) . In contrast , NF-kappaB activation by TNF-alpha or expression of constitutively active IKK2 induced an EMT-phenotype with up-regulation of vimentin and ZEB1 , and down-regulation of E-cadherin . EMT could also be induced in cells with defective TGF-beta signalling . Functional assays demonstrated reduced or strongly enhanced migration and invasion upon NF-kappaB inhibition or activation , respectively . OUTPUT:

activating invasion and metastasis

HoC_1shot410

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Dendritic cells ( DCs ) are key regulators of innate and acquired immunity . The maturation of DCs is directed by signal transduction events downstream of toll-like receptors ( TLRs ) and other pattern recognition receptors . Here , we demonstrate that , in mouse DCs , TLR agonists stimulate a profound metabolic transition to aerobic glycolysis , similar to the Warburg metabolism displayed by cancer cells . This metabolic switch depends on the phosphatidyl inositol 3'-kinase/Akt pathway , is antagonized by the adenosine monophosphate ( AMP)-activated protein kinase ( AMPK ) , and is required for DC maturation . The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10 . Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses . OUTPUT:

cellular energetics;tumor promoting inflammation

HoC_1shot411

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We have investigated the possibility that photoexcited titanium dioxide ( TiO2 ) could inhibit the growth of malignant cells . We studied the anti-glioma effects of nano-TiO2 excited with ultraviolet A ( UVA ) irradiation both in vitro and in vivo . Transmission electron microscopy demonstrated that glioma cells take up TiO2 by phagocytosis , and vital staining revealed that TiO2 alone has no effect on glioma cell proliferation . However , if TiO2 was combined with UVA irradiation the proliferation rate was decreased significantly compared to controls ( P<0.05 ) . RT-PCR suggested that TiO2 induction of glioma cell apoptosis is associated with changes in the expression of genes encoding Bcl-2 family members . We then investigated the in vivo antitumor effects of combined TiO2 plus UVA treatment of established glioma tumors . TiO2 plus UVA led to pronounced areas of necrosis , elevated indices of apoptosis , delayed tumor growth , and increased survival compared with the TiO2-alone control group ( P<0.001 ) . Log-rank survival analysis showed that median survival duration was prolonged ( P<0.001 ) . These findings suggest that nano-TiO2 based photodynamic therapy has potential in the treatment of glioma . OUTPUT:

resisting cell death

HoC_1shot412

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

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot413

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Chronic inflammation , increased reactivity to self-antigens and incidences of cancer are hallmarks of aging . However , the underlying mechanisms are not well understood . Age-associated alterations in the DNA either due to oxidative damage , defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible . Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells . We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-alpha from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine . Investigations into the mechanisms revealed that DNA from aged subjects is not degraded , neither is it more damaged compared to DNA from young subjects . However , there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity . Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation , autoimmunity and cancer . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot414

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Tumor necrosis factor related apoptosis-inducing ligand ( TRAIL ) and agonistic anti-DR4/TRAIL-R1 and anti-DR5/TRAIL-R2 antibodies are currently under clinical investigation for treatment of different malignancies . TRAIL activates DR4 and DR5 and thereby triggers apoptotic and non-apoptotic signaling pathways , but possible different roles of DR4 or DR5 in these responses has poorly been addressed so far . In the present work , we analyzed cell viability , DISC formation as well as IL-8 and NF-kappaB activation side by side in responses to TRAIL and agonistic antibodies against DR4 ( mapatumumab ) and against DR5 ( lexatumumab ) in pancreatic ductal adenocarcinoma cells . We found that all three reagents are able to activate cell death and pro-inflammatory signaling . Death-inducing signaling complex ( DISC ) analysis revealed that mapatumumab and lexatumumab induce formation of homocomplexes of either DR4 or DR5 , whereas TRAIL additionally stimulated the formation of heterocomplexes of both receptors . Notably , blocking of receptors using DR4- and DR5-specific Fab fragments indicated that TRAIL exerted its function predominantly via DR4 . Interestingly , inhibition of PKC by Goe6983 enabled DR5 to trigger apoptotic signaling in response to TRAIL and also strongly enhanced lexatumumab-mediated cell death . Our results suggest the existence of mechanisms that silence DR5 for TRAIL- but not for agonistic-antibody treatment . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot415

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

genomic instability and mutation

HoC_1shot416

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Autotaxin ( ATX ) is an extracellular lysophospholipase D that generates lysophosphatidic acid ( LPA ) from lysophosphatidylcholine ( LPC ) . Both ATX and LPA have been shown to be involved in many cancers . However , the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma ( HCC ) remain elusive . RESULTS In this study , ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects . ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis . In addition , ATX expression was examined in normal human hepatocytes and liver cancer cell lines . Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did . Proinflammtory cytokine tumor necrosis factor alpha ( TNF-alpha ) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells , which led to a corresponding increase in lysophospholipase-D activity . Moreover , we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B ( NF-kappaB ) in basal and TNF-alpha induced ATX expression . Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion . CONCLUSIONS This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC . Our observation that links the TNF-alpha/NF-kappaB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis . OUTPUT:

tumor promoting inflammation;activating invasion and metastasis

HoC_1shot417

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Paclitaxel and pirarubicin exhibit cytotoxic and antitumor activities . However , little is known about the apoptosis-inducing effects of paclitaxel and pirarubicin on human osteosarcoma MG-63 cells . METHODS The effects of paclitaxel and pirarubicin on cell cycle arrest and apoptosis were studied in MG-63 cells using flow cytometry . PCNA , Bcl-2 , Bax , cyclin D1 and cyclin E expression was assessed by Western blotting . RESULTS Paclitaxel and pirarubicin caused G2/M and G0/G1 cell cycle arrest in MG-63 cells , respectively . Apoptosis of MG-63 cells mediated by paclitaxel was dependent on treatment duration . Interestingly , in cells treated with pirarubicin , apoptosis was related to treatment duration at concentrations of 10(2)-10(3) nM , whereas the effect of treatment duration was less marked at concentrations >10(4)-10(5) nM . Furthermore , paclitaxel and pirarubicin suppressed the expression of PCNA , cyclin D1 , cyclin E and Bcl-2 , and increased Bax expression . CONCLUSION These results suggest that the G2/M or G0/G1 cell cycle arrest and apoptosis induced by paclitaxel and pirarubicin are Bcl-2/Bax dependent , suggesting favorable effects of combination therapy with paclitaxel and pirarubicin in the treatment of osteosarcoma . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot418

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Epidemiologic studies have examined the association between fruit and vegetable ( F&V ) consumption and the risk of cancer . Several cancer-preventive mechanisms have been proposed , such as antioxidant properties and modulation of biotransformation enzyme activities ; both may be associated with reducing DNA damage and hence the mutation rate . We investigated , in a randomized , controlled , crossover feeding trial , the effect of 10 servings/day of botanically defined F&V for 2 wk on endogenous DNA damage ; resistance to gamma -irradiation damage ; and DNA repair capacity in lymphocytes , measured by the Comet assay . We also explored the association between the UGT1A1*28 polymorphism and serum bilirubin concentrations and DNA damage and repair measures . Healthy men ( n = 11 ) and women ( n = 17 ) , age 20 to 40 yr , provided blood samples at the end of each feeding period . Overall , F&V did not affect DNA damage and repair measures in lymphocytes . The number of UGT1A1*28 alleles was inversely associated with sensitivity to gamma -irradiation exposure and DNA repair capacity , but a biological mechanism to explain this association is unclear . A larger sample size is needed to investigate the association between bilirubin concentrations and endogenous DNA damage . With inconsistent findings in the literature , additional dietary intervention studies on the effect of F&V on DNA damage and repair are needed . OUTPUT:

genomic instability and mutation

HoC_1shot419

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE As we previously demonstrated , the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones , especially 6-iodo-5-hydroxy-eicosatrienoic acid ( delta-iodolactone ) . In this communication we compare the effect of iodide , molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines ( B-CPAP cells , FTC-133 cells and 8505C cells ) as well as on human breast cancer cells ( MCF 7 ) . METHODS Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium ( DMEM ) and MCF 7 cells in Rowswell Park Memorial Institute ( RPMI ) culture medium , both containing 10% ( v/v ) Fetal Calf Serum ( FCS ) , until they were confluent . Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM ( thyroid cancer cells ) or in RPMI medium ( MCF 7 cells ) both containing 5% FCS . Thereafter , different concentrations of iodide , iodine or delta-iodolactone were added for 24 h . Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells . Apoptosis was determined by a mitochondrial potential assay . RESULTS The growth rate of B-CPAP cells was unaffected by iodide , but was reduced by high concentreations of molecular iodine ( 100 and 500 microM ) . However , delta-iodolactone significantly reduced cell proliferation already with low concentrations ( 5 microM and 10 microM ) and further in a dose-dependent manner up to 82% . FTC-133 and 8505C cells were unaffected by iodide , iodine or delta-iodolactone . In contrast , in MCF 7 cells , molecular iodine ( 100 microM ) inhibited growth from 100% to 83% but delta-iodolactone ( 1 , 5 and 10 microM ) dose-dependently decreased growth rate from 100% to 82% and 62% , respectively . The inhibition of growth was through apoptosis , and not necrosis , as the amount of apoptotic cells corresponded to the growth inhibition . CONCLUSION delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells . OUTPUT:

resisting cell death

HoC_1shot420

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: NKX3.1 is a homeodomain protein that functions as a dosage sensitive prostate-specific transcription factor . Diminished NKX3.1 expression is associated with prostate epithelial cell proliferation in vitro and with increasing Gleason grade in patient samples . Mouse Nkx3.1 also functions as a negative regulator of prostate cell growth in prostate cancer models . Identifying biological and environmental factors that modulate NKX3.1 accumulation is therefore central to efforts aimed at elucidating prostate growth control mechanisms . To determine the effect of inflammation on Nxk3.1 accumulation , bacterial prostatitis was induced by intraurethral inoculation of a uropathogenic E. coli strain in mice . Nkx3.1 expression was profoundly reduced in infected prostate lobes and correlated with increased expression of a proliferation marker . Androgen receptor levels were also reduced in concert with Nkx3.1 , and a marked increase in the basal cell marker p63 was observed . Analyses of the inflammatory infiltrate revealed a classic acute inflammatory response that attained characteristics of a chronic state within fourteen days postinoculation . Comparison of the four prostate lobes revealed clear differences in the extent of inflammation . These data demonstrate that acute inflammation in response to a bacterial agent in the prostate is associated with a significant diminution in the level of a key regulator of prostate cell proliferation . These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth . OUTPUT:

sustaining proliferative signaling;tumor promoting inflammation

HoC_1shot421

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To clarify the relationship between the expression of pol beta and DNA damage /repair induced by Benzo(a)pyrene ( BaP ) . METHODS pol beta wild-type cells ( pol beta +/+ ) , pol beta null cells ( pol beta -/- ) and wild-type pol beta overexpressed cells ( pol beta oe ) which had the same genetic background were studied . Firstly , RT-PCR and Western blot targeting to pol beta were carried out to measure the expression of pol beta mRNA and protein in above three kinds of cells , then MTT test and single cell gel electrophoresis ( comet assay ) were used to compare cell viability and DNA damage/repair of the three kinds of cells when exposed to BaP . RESULTS There was pol beta deletion in pol beta -/- cells and the level of pol beta mRNA and protein in pol beta oe cells was twice higher than that in pol beta +/+ cells . BaP could induce DNA damage and reduce cell viability , when compared with pol beta +/+ cells , IC50 of pol beta -/- cells was remarkably lower , DNA was prone to damage and more difficult to be repaired , on the other hand , IC50 of pol beta oe cells was obviously higher and the damage effect on DNA was weaker and prone to be repaired . CONCLUSION Pol beta played an important role in the repair of DNA damage induced by BaP , deficiency of pol beta could decrease the DNA repair capability of cells , and overexpression of pol beta could help cells response to DNA damage and protect cells from death in a certain degree . OUTPUT:

genomic instability and mutation

HoC_1shot422

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The tumor suppressor LKB1 is inactivated in 90% of Peutz-Jeghers cancer syndrome , 30-40% of non-small cell lung carcinoma , and a variety of other cancers , indicating the loss of LKB1 activity is a critical step in oncogenesis . However , current understanding of LKB1 function is largely limited to the results from cancer cells , and how LKB1 inactivation initiates malignant transformation in normal cells remains unclear . Here we ablated endogenous expression of LKB1 in two normal cell lines : human embryonic kidney 293T cells ( HEK-293T cells ) and human umbilical vein endothelial cells ( HUVECs ) by LKB1-specific short hairpin RNAs . Downregulation of endogenous LKB1 lead to a facilitated G(1)/S transition , accompanied by a concomitant increase in Rb phosphorylation ( Ser(807/811) ) . Furthermore , reduced expression of p53 and p16 was observed in LKB1 ablated cells , while no differences were detected for cyclin D1 and cyclin E. These results jointly suggest that endogenous LKB1 knockdown accelerates cell cycle progression through G(1)/S checkpoint in HEK-293T cells and HUVECs , which is at least in part , mediated by decline of p53 and p16 pathways . Our findings provided a plausible mechanism by which loss of LKB1 expression in normal cells contributes to the formation of malignancies . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot423

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Although contact inhibition is a fundamental process for multicellular organisms , how proliferation is inhibited at high cellular densities remains poorly characterized . Here we show that 4E-BP1 , one major repressor of cap-dependent translation , plays a critical role in density-mediated cell cycle arrest. 4E-BP1 promoter is activated and 4E-BP1 protein amount increases as cells reach confluence . Conversely , a much less marked density-dependent inhibition of cell proliferation is observed upon 4E-BP1 silencing . We further show that at high density , progression through the G₁ phase of the cell cycle is faster and Cyclin D1 protein is induced in different cell types where 4E-BP1 has been either downregulated ( stable shRNA expression or transient siRNA transfection ) or removed ( knock-out ) . Thus 4E-BP1 appears as an important mediator of contact inhibition . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot424

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The development and progression of esophageal cancer is associated with multiple alterations in the genome , including loss of the tumor suppressor phosphatase and tensin homolog deleted from the chromosome 10 ( PTEN ) gene . The purpose of this study was to determine the effects of adenovirus-mediated MMAC/PTEN expression on the growth and survival of human esophageal cancer cells in vitro and in vivo . We found that compared to control cells , overexpression of PTEN significantly suppressed growth and induced apoptosis in esophageal cancer cell lines Eca-109 and TE-1 via downregulation of Bcl-2 expression and changes in cell-cycle progression . Adenovirus PTEN also inhibited the growth of subcutaneous tumor xenografts by significantly reducing tumor size in vivo . Thus our results confirm the proposed functional role of MMAC/PTEN as a regulator of esophageal cancer progression in vivo and in vitro . PTEN might be an important biological marker and potential therapeutic target in the treatment of human esophageal cancer . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot425

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To study the effect of anandamide ( AEA ) on necrosis in HepG2 cells and to explore the role of AEA in progression of liver cancer . METHODS Localization of the fatty acid hydrolytic enzyme ( FAAH ) , cannabinoid receptors 1(CB1) and cannabinoid receptors 2 ( CB2 ) proteins was detected in L02 and HepG2 cells using immunofluorescence . L02 and HepG2 cells were treated with different concentrations of AEA and methyl-beta-cyclodextrin , and the rates of cells necrosis were examined by PI stain . Meanwhile , the expression levels of FAAH , CB1 and CB2 receptor proteins , as well as P38 mitogen-activated protein kinase ( p-P38 MAPK ) and c-Jun-NH2-terminal kinase ( p-JNK ) proteins , were analyzed by Western blot . RESULTS The FAAH , CB1 and CB2 receptor proteins were observed both in cytoplasm and on membrane in L02 and HepG2 cells . The expression level of FAAH protein was higher in HepG2 than in L02 cells . The expression level of CB1 receptor protein was very low in both L02 and HepG2 cells . The expression level of CB2 receptor protein was high in both L02 and HepG2 cells . AEA treatment induced necrosis in HepG2 cells but not in L02 cells . Methyl-beta-cyclodextrin treatment prevented necrosis in HepG2 cells ( t = 3.702 ; 5.274 ; 3.503 , P less than 0.05 ) . The expression patterns of FAAH , CB1 and CB2 receptor protein in L02 and HepG2 cells were confirmed by western blot , which were consistent with the immunofluorescence results . AEA treatment increased the levels of p-P38MAPK and p-JNK proteins in a dose-dependent manner in HepG2 cells ( F = 11.908 ; 26.054 , P less than 0.05 ) and the increase can be partially by prevented by MCD ( t = 2.801 ; t = 12.829 , P less than 0.05 ) . CONCLUSION AEA treatment induces necrosis in HepG2 cells via CB1 and CB2 receptors and lipid rafts . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot426

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND Elevated levels of air pollution are associated with increased risk of lung cancer . Particulate matter ( PM ) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation , a lung cancer risk factor . Vanadium pentoxide ( V2O5 ) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans . In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage ( initiation-promotion ) model of pulmonary neoplasia in mice . RESULTS A/J , BALB/cJ ( BALB ) , and C57BL/6J ( B6 ) mice were treated either with the initiator 3-methylcholanthrene ( MCA ; 10 microg/g ; i.p. ) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment . Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid ( BALF ) , and chemokines , transcription factor activity , and MAPK signaling were quantified in lung homogenates . We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J ( 10.3 +/- 0.9 tumors/mouse ) and BALB ( 2.2 +/- 0.36 ) mice significantly above that observed with MCA/PBS or V2O5 alone ( P &lt ; 0.05 ) . No tumors were observed in the B6 mice in any of the experimental groups . Mice sensitive to tumor promotion by V2O5 were also found to be more susceptible to V2O5-induced pulmonary inflammation and hyperpermeability ( A/J>BALB>B6 ) . Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1 , higher NFkappaB and c-Fos binding activity , as well as sustained ERK1/2 activation in lung tissue . CONCLUSIONS In this study we demonstrate that V2O5 , an occupational and environmentally relevant metal oxide , functions as an in vivo lung tumor promoter among different inbred strains of mice . Further , we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation . These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways . OUTPUT:

tumor promoting inflammation

HoC_1shot427

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The mechanisms of formation of sister chromatid exchanges ( SCEs ) and chromosome aberrations following inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide were studied in Chinese hamster ovary cell lines deficient in different repair pathways . The results confirm earlier findings that ( a ) the ' spontaneous ' SCEs are formed due to the incorporated BrdU in the DNA , ( b ) ' spontaneous ' and induced SCEs originate from different mechanisms , and ( c ) SCEs and chromatid exchanges are formed by different pathways . OUTPUT:

genomic instability and mutation

HoC_1shot428

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Polycyclic aromatic hydrocarbons ( PAH ) such as dibenzo[a,l]pyrene ( DBP ) are wide-spread environmental pollutants most probably mutagenic and carcinogenic to humans . Detailed data on the cytogenetic effects of anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene ( DBPDE ) in mammalian cells are not available in the literature . The aim of this study is to elucidate the mechanisms involved in the induction of chromosomal aberrations and sister chromatid exchanges ( SCEs ) by DBPDE in mammalian cells . In order to achieve this a parental ( AA8 ) and different DNA repair-deficient Chinese hamster ovary cell lines such as UV4 , UV5 , UV61 ( nucleotide excision repair , NER ) , EM9 ( base excision repair , BER ) , irs1SF ( homologous recombination repair , HRR ) and V3-3 ( non-homologous end joining , NHEJ ) were used . The most sensitive cell lines for DBPDE-induced chromosome aberrations were EM9 and irs1SF , while EM9 and V3-3 cell lines were the most sensitive in terms of SCEs induction . It can be suggested that the BER pathway plays an important role in the repair of lesions induced by DBPDE , affecting both chromosomal aberrations and SCEs induction . Moreover , the HRR pathway seems to play a role in cellular resistance to DBPDE mainly in terms of chromosomal aberration induction while the NHEJ pathway takes part affecting only the induction of SCEs . OUTPUT:

genomic instability and mutation

HoC_1shot429

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Bulky DNA adducts are considered a potential biomarker of cancer risk . In this study , the association between various lifestyle , environmental , and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort . At enrollment , blood samples were collected and information on lifestyle , including dietary and smoking habits , obtained . Previously , bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort . Of these 500 individuals , data on 375 individuals were included in this study , excluding 125 cases , which developed lung cancer within the first 3 yr after blood sampling . Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined . Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses . Women tended to have higher adduct levels than men . Living in central Copenhagen and surface darkness of fried meat and fish were associated with quantitative higher adduct levels . No significant associations were found between dietary factors or smoking and DNA adduct levels . Further , the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels . Overall , our study showed only few associations between dietary , environmental , and genetic factors and levels of bulky DNA adducts measured in peripheral leukocytes in a general Danish population . OUTPUT:

genomic instability and mutation

HoC_1shot430

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND AND AIM The importance of glycolysis in cancer cells is well documented . The effects of inhibiting glycolysis using metabolic inhibitors iodoacetate ( IAA ) , an inhibitor of GAPDHase , and 3-bromopyruvate ( 3BP ) , an inhibitor of hexokinase-II , on survival and signaling of pancreatic cancer cells ( Panc-1 ) were investigated . MATERIALS AND METHODS Cellular survival was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay . Lactate dehydrogenase ( LDH ) assay was used to analyze the induced necrosis and protein levels were evaluated using Western blot analysis . RESULTS The results show that the inhibitors lowered cellular survival and increased cellular necrosis . Mitogenic signaling pathways were affected by 3BP but not by IAA . CONCLUSION We conclude that there may be a cross-talk between signaling pathways and glycolysis in regulating pancreatic cancer cell survival and signaling . Thus , a combination of agents that inhibit both energy production and cell signaling may provide a novel and effective approach to target pancreatic cancer effectively . OUTPUT:

resisting cell death;cellular energetics

HoC_1shot431

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma ( LGNPPA ) is extremely rare ; only four cases have been reported . Herein are presented the case reports of two Japanese male patients with thyroid-like LGNPPA . Macroscopically , these tumors were pedunculated polypoid masses on the roof of the nasopharynx . Microscopically , they were characterized by papillary and glandular epithelial proliferation . The papillae were complex and tightly packed with hyalinized fibrovascular cores and lined by columnar and pseudostratified cells with intervening spindle-shaped cells . Both cell types had round to oval vesicular nuclei with tiny nucleoli and mildly eosinophilic cytoplasm . Mitotic figures were not evident and necrosis was not observed . Psammoma bodies were seen focally in one of the patients . Transition from normal surface epithelium to tumor cells was identified in both cases . On immunohistochemistry the tumor cells were positive for cytokeratin ( CK)7 , CK19 , thyroid transcription factor-1 ( TTF-1 ) and vimentin . They were negative for CK5/6 , CK20 , thyroglobulin , S-100 protein and CD15 . In situ hybridization for EBV was negative . Nasopharyngeal tumors with similar morphological appearance should be examined for TTF-1 immunoreactivity , and patients should be clinically followed to determine the course of this unusual disease and the significance of TTF-1 expression . OUTPUT:

resisting cell death

HoC_1shot432

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We studied the effect of the immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene , with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor antigen ( TA ) . Slow progressor melanomas contained no activated T lymphocytes ( TL ) . In contrast , " aggressive " melanomas were infiltrated by activated TLs lacking effector molecules and expressing high levels of PD-1 , indicating an exhausted phenotype . Aggressive melanomas were also infiltrated by immature myeloid cells ( IMC ) . Infiltration was associated with local inflammation and systemic Th2/Th17-oriented chronic inflammation that seemed to impair further activation of TLs , as tumor-specific T cells adoptively transferred into mice bearing aggressive melanomas were poorly activated and failed to infiltrate the melanoma . This immunosuppression also led to the incapacity of these mice to reject inoculated TA-positive tumors , in contrast to slow-progressing melanoma-bearing mice , which were responsive . To test the role of adaptive immunity in tumor progression , we induced melanomas in immunodeficient RagKO compound mice . These mice developed aggressive but not slow-progressing melanomas at a higher frequency and with a shorter latency than immunocompetent mice . Immunodeficient mice also developed abnormal inflammation and infiltration of IMCs in a manner similar to immunocompetent mice , indicating that this phenotype was not dependent on adaptive immunity . Therefore , tumor-intrinsic factors distinguishing the two melanoma types control the initiation of inflammation , which was independent of adaptive immunity . The latter delayed development of aggressive melanomas but was overridden by inflammation . OUTPUT:

tumor promoting inflammation;avoiding immune destruction

HoC_1shot433

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Polycylic aromatic hydrocarbons ( PAHs ) are ubiquitous contaminants in the marine environment . Their toxicity is mainly linked to the ability of marine species to biotransform them into reactive metabolites . PAHs are thus often detected at trace levels in animal tissues . For biomonitoring purposes , this findings have two main consequences , ( i ) the determination of the PAH tissue concentration is not suitable for the evaluation of individual exposure to PAHs ( ii ) it can explain sometimes the lack of correlations obtained with relevant markers of toxicity such as genotoxicity biomarkers . The aim of the present study was to better investigate the link between PAH exposure and genotoxicity in marine flatfish . During a laboratory experiment , juvenile soles were exposed for four weeks to a mixture of three PAHs , namely benzo[a]pyrene , fluoranthene and pyrene , followed by one week of depuration . Fish were exposed via the trophic route to a daily PAH concentration of 120 μg/g food . Fish were sampled at different time points . The bioavailability and the biotransformation of PAHs were assessed by the measurement of biliary metabolites using a sensitive UPLC MS/MS method . The 7-ethoxyresorufine-O-deethylase was also measured in liver subcellular fractions as a biomarker of phase I biotransformation activities . Genotoxicity was assessed in parallel by the measurement of DNA strand breaks in fish erythrocytes by the alkaline comet assay . During this study , the high amount of PAH metabolites produced in sole demonstrated the bioavailability of PAHs and their biotransformation by fish enzymes . A positive correlation was observed between the level of hydroxylated PAH metabolites and genotoxicity as measured by the alkaline comet assay . OUTPUT:

genomic instability and mutation

HoC_1shot434

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Oxazaphosphorines are a class of DNA alkylating agents . The aim of the present study was to compare the possible influence of three new generation oxazaphosphorines , D-17272 ( mafosfamide cyclohexylamine salt ) , D-18864 ( 4-hydro-peroxy-cyclophosphamide ) , and D-19575 ( glufosfamide , beta-D-glucose-isophosphoramide mustard ) on DNA damage induction in the human histiocytic lymphoma U937 cells . The flow cytometry APO-BRDU assay , based on the TUNEL method , was used for the in situ detection of DNA strand breaks . After exposure of U937 cells to the oxazaphosphorines , the patterns of temporary changes in the frequency of TUNEL positive U937 cells , expressing DNA breakage , were determined . The effects of the oxazaphosphorines on U937 cells were dependent on the agent tested and its dose , and the time intervals after the drug application . The different potential of D-17272 , D-18864 and D-19575 to induce DNA strand breakage in the human histiocytic lymphoma U937 cells was shown . OUTPUT:

genomic instability and mutation

HoC_1shot435

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND/AIMS Adenocarcinoma of the gallbladder is a highly malignant neoplasm. p16 is a tumor suppressor gene protein , which is a cyclin-dependent kinase inhibitor that regulates the G1-S phase of the cell cycle . The purpose of the present study was to investigate the expression of p16 in gallbladder carcinoma and its precancerous conditions and to examine the relationship between p16 expression and clinicopathological parameters . METHODOLOGY Formalin-fixed , paraffin-embedded tissue sections from 20 cases of normal gallbladder , 20 cases of chronic cholecystitis , 20 cases of gallbladder adenoma , 20 cases of dysplasia , and 58 cases of adenocarcinoma were examined . The expression of p16 was evaluated by immunohistochemical analysis . RESULTS In normal gallbladder , no expression of p16 was found . In chronic cholecystitis , expression of p16 was not found . In gallbladder adenomas , expression of p16 was found in 20% ( 4/20 ) . In low grade dyspalsias , expression of p16 was not found . In high grade dysplasias , p16 expression was present in 45.0% ( 9/20 ) . In gallbladder adenocarcinomas , p16 expression was found in 27.6% ( 16/58 ) . Expression of p16 correlated significantly with histologic grade ( p &lt ; 0.05 ) . No correlation was found between p16 expression and age , gender , tumor size , gross type , location , vascular invasion , lymph node metastasis , and TNM stage , respectively . CONCLUSIONS P16 protein overexpression is an early and relatively common event in carcinogenesis of gallbladder carcinoma . Expression of p16 protein is absent in normal or chronic cholecystitis . Expression of p16 may be an ancillary diagnostic marker of gallbladder carcinoma and its precancerous conditions . OUTPUT:

evading growth suppressors

HoC_1shot436

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND/AIMS The use of chemotherapy in hepatocellular carcinoma is still controversial . The aim of this study was to investigate whether the combined use of epirubicin and progesterone has a synergistic effect on cell proliferation and apoptosis in HepG2 cells . METHODOLOGY Different concentrations of epirubicin ( 0.1 microg/ml , 0.25 microg/ml and 0.5microg/ml ) or progesterone ( 12.5 microM , 25 microM and 50 microM ) were added to HepG2 cells either alone or in combinations consisting of different concentrations of the two . Their effects on HepG2 cells were studied by ( 1 ) XTT assay for analysis of cell proliferation , ( 2 ) 3H-Thymidine incorporation for DNA synthesis , ( 3 ) annexin V-FITC/ propidium iodide ( PI ) flowcytometery for cell apoptosis , ( 4 ) flowcytometry for cell cycle distributions , and ( 5 ) reverse transcription-polymerase chain reaction for expression of cell cycle modulator , cyclin D1 . RESULTS 50 microM progesterone increased both the cytotoxic and apoptotic effects of 0.1 microg/ml epirubicin on HepG2 cells at 48 hr culture due to 50 microM progesterone accumulated cells in S phase of the cell cycle and subsequently reduced cyclin D1 expression . These effects on HepG2 cells induced by this combination were comparable to those induced by 0.5 microg/ml epirubicin alone . CONCLUSIONS In vitro , progesterone can increase the cytotoxicity and apoptosis induced by epirubicin on HepG2 cells . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot437

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Among several types of DNA lesions , the DNA double strand breaks ( DSBs ) are one of the most deleterious and harmful . Mammalian cells mount a coordinated response to DSBs with the aim of appropriately repair the DNA damage . Indeed , failure of the DNA damage response ( DDR ) can lead to the development of cancer-prone genetic diseases . The identification and development of drugs targeting proteins involved in the DDR is even more investigated , as it gives the possibility to specifically target cancer cells . Indeed , the administration of DNA repair inhibitors could be combined with chemo- and radiotherapy , thus improving the eradication of tumor cells . Here , we provide an overview about DSBs damage response , focusing on the role of the DSBs repair mechanisms , of chromatin modifications , and of the cancer susceptibility gene BRCA1 which plays a multifunctional role in controlling genome integrity . Moreover , the most investigated DSBs enzyme inhibitors tested as potential therapeutic agents for anti-cancer therapy are reported . OUTPUT:

genomic instability and mutation

HoC_1shot438

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters . METHODS The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically . Stereologic method was used for evaluation of the percentage of positively stained tumor cells . RESULTS Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 ( r = 0.74 , p &lt ; 0.001 ) . MCM-2 and Ki-67 expression was significantly associated with histologic grade ( p &lt ; 0.05 ) , and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status ( p &lt ; 0.05 ) . No significant association was observed between MCM-2 or Ki-67 expression and patient age , tumor size , lymph node status , clinical stage and menopausal status . CONCLUSION Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity ( Ki-67 labelling index ) . Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma ( Tab. 1 , Fig. 4 , Ref. 34 ) . Full Text ( Free , PDF ) www.bmj.sk . OUTPUT:

sustaining proliferative signaling

HoC_1shot439

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

sustaining proliferative signaling

HoC_1shot440

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

cellular energetics;genomic instability and mutation;tumor promoting inflammation

HoC_1shot441

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND CDC4/FBXW7 , encoding a ubiquitin ligase , maps to 4q32 and has been implicated as a tumor suppressor gene and therapeutic target in many tumor types . Mutations in colonic adenomas , and the frequent losses on 4q described in gastric cancer prompt speculation about the role of CDC4/FBXW7 in gastric carcinogenesis . METHODS We assessed the role of CDC4/FBXW7 in gastric cancer , through loss of heterozygosity ( LOH ) and multiplex ligation-dependent probe amplification ( MLPA ) on 47 flow-sorted gastric carcinomas including early-onset gastric cancers ( EOGC ) and xenografted conventional gastric carcinomas . Ploidy analysis was carried out on 39 EOGCs and immunohistochemistry of CDC4/FBXW7 and its substrates c-myc , c-jun , Notch and cyclin E was performed on 204 gastric carcinomas using tissue microarrays ( TMAs ) . Sequence analysis of CDC4/FBXW7 was carried out on gastric carcinoma cell lines and xenografts . RESULTS Loss of heterozygosity of CDC4/FBXW7 occurred in 32% of EOGCs , and correlated with loss of expression in 26% . Loss of expression was frequent in both EOGC and conventional gastric cancers . No CDC4/FBXW7 mutations were found and loss of CDC4/FBXW7 did not correlate with ploidy status . There was a significant correlation between loss of CDC4/FBXW7 expression and upregulation of c-myc . CONCLUSION Loss of CDC4/FBXW7 appears to play a role in both EOGC and conventional gastric carcinogenesis , and c-myc overexpression is likely to be an important oncogenic consequence of CDC4/FBXW7 loss . OUTPUT:

genomic instability and mutation

HoC_1shot442

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: XRCC4 , in association with DNA ligase IV , is thought to play a critical role in the ligation of two DNA ends in DNA double-strand break ( DSB ) repair through non-homologous end-joining ( NHEJ ) pathway . In the present study , we captured radiation-induced chromatin-recruitment of XRCC4 by biochemical fractionation using detergent Nonidet P-40 . A subpopulation of XRCC4 changed into a form that is resistant to the extraction with 0.5% Nonidet P-40-containing buffer after irradiation . This form of XRCC4 was liberated by micrococcal nuclease treatment , indicating that it had been tethered to chromatin DNA . This chromatin-recruitment of XRCC4 could be seen immediately ( &lt ; 0.1 hr ) after irradiation and remained up to 4 hr after 20 Gy irradiation . It was seen even after irradiation of small doses , i.e. , 2 Gy , but the residence of XRCC4 on chromatin was very transient after 2 Gy irradiation , returning to near normal level in 0.2-0.5 hr after irradiation . The chromatin-bound XRCC4 represented only approximately 1% of total XRCC4 molecules even after 20 Gy irradiation and the quantitative analysis using purified protein as the reference suggested that only a few XRCC4-DNA ligase IV complexes were recruited to each DNA end . We further show that the chromatin-recruitment of XRCC4 was not attenuated by wortmannin , an inhibitor of DNA-PK , or siRNA-mediated knockdown of the DNA-PK catalytic subunit ( DNA-PKcs ) , indicating that this process does not require DNA-PKcs . These results would provide us with useful experimental tools and important insights to understand the DNA repair process through NHEJ pathway . OUTPUT:

genomic instability and mutation

HoC_1shot443

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To study the clinicopathologic features , immunophenotype and ultrastructural features of sinonasal inflammatory myofibroblastic tumors ( IMT ) . METHODS The clinical and histologic features of 5 cases of sinonasal IMT were reviewed . Immunohistochemical study for vimentin , MSA , SMA , calponin , h-caldesmon , desmin , ALK , fibronectin , CK , S-100 and Ki-67 was carried out . Ultrastructural examination was also performed in two of the cases . RESULTS The patients age ranged from 28 to 62 years ( mean = 43 years ) . The male-to-female ratio was 2:3 . The clinical presentation included nasal obstruction , nasal discharge , nasal bleeding , facial pain , facial swelling , toothache and tear overflow . All of the 5 patients suffered from disease relapses ; and 4 of them had recurrences for more than 5 times . One patient had lymph node metastasis and 3 patients died of the disease . Histologically , the tumor cells were arranged in interlacing fascicles and sometimes haphazard in fashion . They were spindly in shape , cytoplasm eosinophilic with mild nuclear atypia and a low mitotic activity . The intervening stroma was myxoid in appearance accompanied by lymphocyte and plasma cell infiltration , abundant blood vessels and focal collagenized areas . In 3 of the recurrent cases , the tumor cells displayed increased nuclear atypia and mitotic activity ( average about 5 to 6 per 10 high-power fields ) , accompanied by patchy necrosis , less inflammatory cell infiltration and focal sarcomatous changes . Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin . SMA , MSA , calponin and fibronectin were variably expressed . Desmin was weakly positive in 1 case . The staining for h-caldesmon , ALK , S-100 and CK was negative . The Ki-67 proliferation index increased with tumor recurrences . Electron microscopy revealed abundant rough endoplasmic reticulum and dense body formation in the cytoplasm . There were an increased amount of collagen fibers in the stroma . CONCLUSIONS IMT rarely occurs in nasal cavity and paranasal sinuses . The tumor is prone to local invasion and recurrences , with subsequent progression to frank malignancy and distant metastasis , resulting in high mortality and poor prognosis . Complete surgical resection remains the main modality of treatment . OUTPUT:

activating invasion and metastasis;resisting cell death;tumor promoting inflammation;sustaining proliferative signaling

HoC_1shot444

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Recent research has shown that the Na(+)/K(+)-ATPase alpha1 subunit is a novel anti-cancer target , which plays pivotal roles in malignant cell ion transport , metabolism , migration and signal transduction . The purpose of the present study was to investigate the anti-cancer effects of ouabain and Na(+)/K(+)-ATPase alpha1 small interfering ribonucleic acid ( siRNA ) on HepG2 cell proliferation , apoptosis and cell cycle , and to explore the molecular mechanisms . The expression of Na(+)/K(+)-ATPase alpha1 subunit in human hepatocellular carcinoma ( HCC ) , normal liver tissues and human HCC line ( HepG2 , SMMC-7721 and Bel-7402 ) has been investigated . Using the ouabain and Na(+)/K(+)-ATPase alpha1 subunit siRNA , which target the Na(+)/K(+)-ATPase , we have evaluated the effects of inhibiting Na(+)/K(+)-ATPase alpha1 in human HepG2 cells with respect to cell proliferation , morphology , cell cycle , impact on intracellular Ca2++ , reactive oxygen species ( ROS ) concentration , and correlated gene expression level on messenger ribonucleic acid ( mRNA ) and protein . Our data showed that the expression Na(+)/K(+)-ATPase alpha1 subunit in HCC tissues is higher than that in normal liver tissues . Ouabain and Na(+)/K(+)-ATPase alpha1 siRNA could inhibit HepG2 cell proliferation . Ouabain could induce HepG2 cell apoptosis and generate S phase arrest , and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated , and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 ( CDK2)/proliferating cell nuclear antigen ( PCNA ) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A ( P21(CIP1) ) . We believe that targeting of the Na(+)/K(+)-ATPase alpha1 subunit in human HCC cells could provide new sight into the treatment of HCC . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot445

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Squamous cell carcinoma ( SCC ) is the most frequent cancer in organ transplant recipients ( OTRs ) . The immune system plays a major role in the fight against SCC , however , little is known about the local inflammatory response in SCC at all . We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs . RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis . SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4 , CD8 , TBET , GATA-3 , FOXP3 , RORC , IFN-gamma , IL-4 , TGF-beta , IL-10 , and IL-17A mRNA expression . Immunohistochemistry was carried out in SCC for CD3 , CD4 , CD8 , and FOXP3 expression . Considerable inflammation was seen in both patient groups . SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature . CD4(+) mRNA was diminished in immunosuppression . Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients . T-BET and IFN-gamma mRNA expression were decreased in the OTR group . Although Th17-weighted inflammation was unchanged , IL-17A mRNA level was markedly decreased with immunosuppression . Regulatory T cells , characterized by FOX-P3 and TGF-beta mRNA level , were decreased in OTRs . Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients . OUTPUT:

tumor promoting inflammation;avoiding immune destruction

HoC_1shot446

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Oral squamous cell carcinoma ( OSCC ) is the most common malignant tumor in the oral and maxillofacial region . The mechanism of carcinogenesis of OSCC is still unclear . Based on the previous cell line , HIOEC-B(a)P-96 ( HB96 ) , which we obtained by HPV16 E6/E7-immortalized human oral epithelial cells ( HIOEC ) and benzo(a)pyrene inducement , we prepared a new HB-second generation cancer cell line ( HB-2 ) by continuous passage . Its characteristics such as morphology , proliferation activity , karyotype , and tumorigenesis were studied . The HB-2 cells displayed uncontrolled cell division and lost contact inhibition leading to cell overlap . Cells were polygonal and unevenly shaped , with an increased nucleus versus plasma ratio . Increased proliferative activity was confirmed by MTT assays . The tumorigenicity was confirmed by tumor growth experiments in nude mice . Therefore , the HB-2 and HB96 cell lines are useful tools to study the mechanism of carcinogenesis of OSCC in vitro for future genomic and proteomic analyses . OUTPUT:

evading growth suppressors

HoC_1shot447

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

tumor promoting inflammation

HoC_1shot448

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The effect of polychlorinated biphenyls ( PCBs ) on Vero cell proliferation was investigated , with the attempts to assess the possible hormetic dose-response and to compare their structure-dependent toxicity . Both PCB congeners revealed low doses stimulation in our experiment . However , significant cytotoxicity was only observed in PCB 52 concentrations larger than 0.1 microg ml(-1) , while there was no significant inhibition in PCB 77-treated cells at concentrations selected . Furthermore , the time-dependent cytotoxic trends were different . The comparison between PCB 52 and PCB 77 indicated that the cytotoxic mechanisms involved in coplanar or non-coplanar PCB congener exposure were different , and this difference might be associated with individual genotoxicity and the release of contact inhibition , respectively . OUTPUT:

evading growth suppressors;genomic instability and mutation

HoC_1shot449

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Abstract The use of immunotherapeutics in melanoma has received much attention , and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation . Cytotoxic T lymphocyte-associated antigen 4 ( CTLA-4 ) serves as a negative regulator of immunity . Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses . Treatment with CTLA-4 blocking antibodies , however , is not without potential toxicities . Autoimmune side-effects , the most common being colitis-associated diarrhea , are frequently associated with clinical responses . In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities , we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor ( GVAX ; Cell Genesys , South San Francisco , CA , USA ) with periodic infusions of CTLA-4 blocking antibodies . This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients . Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells ( T(regs) ) . Effective anti-tumor immunity and serious autoimmunity can be disassociated . Further targeting of anti-tumor T(regs)in combinatorial therapy approaches may be a rich avenue of future investigation . OUTPUT:

avoiding immune destruction;resisting cell death

HoC_1shot450

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Pam3CSK4 , a synthetic TLR2 ligand , has been shown to expand CD4+ regulatory T cells ( Treg cells ) . Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy ( IT ) . This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population . PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times : before IT and 6 mo and 1 y after the maximum-tolerated dose . This study was performed without a placebo-controlled group . D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production . Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition . TUNEL revealed that CD8+CD25+ Treg cells , but not CD4+CD25+ Treg cells , directly induced CD4+CD45ROhi+ apoptosis . Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells ; therefore , it may be a good adjuvant for the treatment of mite allergies . OUTPUT:

evading growth suppressors;resisting cell death

HoC_1shot451

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

resisting cell death;tumor promoting inflammation

HoC_1shot452

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

resisting cell death

HoC_1shot453

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hepatocellular carcinoma ( HCC ) , one of the most frequent and deadliest cancers , has been increasing considerably in the United States . In the absence of a proven effective therapy for HCC , novel chemopreventive strategies are urgently needed to lower the current morbidity and mortality of HCC . Recently , we have reported that resveratrol , a compound present in grapes and red wine , significantly prevents diethylnitrosamine ( DENA)-induced liver tumorigenesis in rats , although the mechanism of action is not completely understood . In the present study , we have examined the underlying mechanisms of resveratrol chemoprevention of hepatocarcinogenesis by investigating the effects of resveratrol on oxidative damage and inflammatory markers during DENA-initiated rat liver carcinogenesis . There was a significant increase in hepatic lipid peroxidation and protein oxidation in carcinogen control animals compared with their normal counterparts at the end of the study ( 20 weeks ) . Elevated expressions of inducible nitric oxide synthase and 3-nitrotyrosine were noticed in the livers of the same animals . Dietary resveratrol ( 50-300 mg/kg ) administered throughout the study reversed all the aforementioned markers in a dose-responsive fashion in rats challenged with DENA . Resveratrol also elevated the protein and mRNA expression of hepatic nuclear factor E2-related factor 2 ( Nrf2 ) . Results of the present investigation provide evidence that attenuation of oxidative stress and suppression of inflammatory response mediated by Nrf2 could be implicated , at least in part , in the chemopreventive effects of this dietary agent against chemically induced hepatic tumorigenesis in rats . The outcome of this study may benefit the development of resveratrol in the prevention and intervention of human HCC . OUTPUT:

tumor promoting inflammation

HoC_1shot454

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: By intravenous ( but not oral ) application of ascorbate , millimolar serum concentrations can be reached , which are preferentially cytotoxic to cancer cells . Cytotoxicity is mediated by transition metal-dependent generation of H(2)O(2) in the interstitial space . In this study , the sensitivity of neuroblastoma cells ( Kelly , SK-N-SH ) to ascorbate and H(2)O(2) and their defense mechanisms against H(2)O(2) were investigated . Since aerobic glycolysis ( the Warburg effect ) is a feature of many tumour cells , their glucose consumption and lactate production were monitored . Furthermore , synthesis and release of ferritin by neuroblastoma cells were analysed in order to examine whether ferritin is possibly an iron source for H(2)O(2) generation . Ascorbate ( 0.6-5.0 mM ) and H(2)O(2) ( 25-100 muM ) were found to be similarly cytotoxic to Kelly and SK-N-SH cells . In each case , cytotoxicity increased if cell concentrations decreased , in accordance with low cell concentrations having lower capacities to detoxify H(2)O(2) . Kelly and SK-N-SH cells produced and released remarkable amounts of lactate and ferritin . We propose the selective cytotoxicity of high dose ascorbate to tumour cells to be due to the preferential generation of H(2)O(2) in the acidic and ferritin-rich tumour microenvironment , combined with reduced defense systems against H(2)O(2) as a consequence of aerobic glycolysis . OUTPUT:

cellular energetics

HoC_1shot455

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The Ras-assocation domain family ( RASSF ) of tumor suppressor proteins until recently contained six proteins named RASSF1-6 . Recently , four novel family members , RASSF7-10 , have been identified by homology searches for RA-domain-containing proteins . These additional RASSF members are divergent and structurally distinct from RASSF1-6 , containing an N-terminal RA domain and lacking the Sav/RASSF/Hpo ( SARAH ) domain . Here , we show that RASSF8 is ubiquitously expressed throughout the murine embryo and in normal human adult tissues . Functionally , RNAi-mediated knockdown of RASSF8 in non-small-cell lung cancer ( NSCLC ) cell lines , increased anchorage-independent growth in soft agar and enhanced tumor growth in severe combined immunodeficiency ( SCID ) mice . Furthermore , EdU staining of RASSF8-depleted cells showed growth suppression in a manner dependent on contact inhibition . We show that endogenous RASSF8 is not only found in the nucleus , but is also membrane associated at sites of cell-cell adhesion , co-localizing with the adherens junction ( AJ ) component beta-catenin and binding to E-cadherin . Following RASSF8 depletion in two different lung cancer cell lines using alternative small interfering RNA ( siRNA ) sequences , we show that AJs are destabilized and E-cadherin is lost from the cell membrane . The AJ components beta-catenin and p65 are also lost from sites of cell-cell contact and are relocalized to the nucleus with a concomitant increase in beta-catenin-dependent and nuclear factor-kappaB ( NF-kappaB)-dependent signaling following RASSF8 depletion . RASSF8 may also be required to maintain actin -cytoskeletal organization since immunofluorescence analysis shows a striking disorganization of the actin- cytoskeleton following RASSF8 depletion . Accordingly , scratch wound healing studies show increased cellular migration in RASSF8-deficient cells . These results implicate RASSF8 as a tumor suppressor gene that is essential for maintaining AJs function in epithelial cells and have a role in epithelial cell migration . OUTPUT:

evading growth suppressors

HoC_1shot456

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION A subpopulation of cancer cells , tumor-initiating cells , is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy . The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins , as well as a reduced propensity to undergo apoptosis or senescence . METHODS To test this hypothesis , we isolated CD24-/low/CD44+ tumor-initiating cells ( as mammospheres ) from MCF-7 breast cancer cells grown in adherent monolayer culture , and carried out a comprehensive comparison of cell death and DNA damage response pathways prior to and after exposure to ionizing radiation in mammospheres and monolayer MCF-7 cells . Single and double-strand break repair was measured by single-cell gel electrophoresis . The latter was also examined by phosphorylation of histone H2AX and formation of 53BP1 and Rad51 foci . Apoptosis was quantified by flow-cytometric analysis of annexin V-binding and senescence was analyzed on the basis of cellular beta-galactosidase activity . We employed the telomeric repeat amplification protocol to quantify telomerase activity . Expression of key DNA repair and cell cycle regulatory proteins was detected and quantified by western blot analysis . RESULTS Our data demonstrate that in comparison to the bulk population of MCF-7 cells ( predominantly CD24+/CD44+ ) , the MCF-7 mammosphere cells benefit from a multifaceted approach to cellular protection relative to that seen in monolayer cells , including a reduced level of reactive oxygen species , a more active DNA single-strand break repair ( SSBR ) pathway , possibly due to a higher level of expression of the key SSBR protein , human AP endonuclease 1 ( Ape1 ) , and a significantly reduced propensity to undergo senescence as a result of increased telomerase activity and a low level of p21 protein expression . No significant difference was seen in the rates of double-strand break repair ( DSBR ) between the two cell types , but DSBR in mammospheres appears to by-pass the need for H2AX phosphorylation . CONCLUSIONS Enhanced survival of MCF-7 tumor-initiating cells in response to ionizing radiation is primarily dependent on an inherent down-regulation of the senescence pathway . Since MCF-7 cells are representative of cancer cells that do not readily undergo apoptosis , consideration of senescence pathways may play a role in targeting stem cells from such tumors . OUTPUT:

enabling replicative immortality;evading growth suppressors;genomic instability and mutation;resisting cell death

HoC_1shot457

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Autophagy is activated in response to cellular stressors and mediates lysosomal degradation and recycling of cytoplasmic material and organelles as a temporary cell survival mechanism . Defective autophagy is implicated in human pathology , as disruption of protein and organelle homeostasis enables disease-promoting mechanisms such as toxic protein aggregation , oxidative stress , genomic damage , and inflammation . We previously showed that autophagy-defective immortalized mouse mammary epithelial cells are susceptible to metabolic stress , DNA damage , and genomic instability . We now report that autophagy deficiency is associated with endoplasmic reticulum ( ER ) and oxidative stress , and with deregulation of p62-mediated keratin homeostasis in mammary cells , allograft tumors , and mammary tissues from genetically engineered mice . In human breast tumors , high phospho(Ser73)-K8 levels are inversely correlated with Beclin 1 expression . Thus , autophagy preserves cellular fitness by limiting ER and oxidative stress , a function potentially important in autophagy-mediated suppression of mammary tumorigenesis . Furthermore , autophagy regulates keratin homeostasis in the mammary gland via a p62-dependent mechanism . High phospho(Ser73)-K8 expression may be a marker of autophagy functional status in breast tumors and , as such , could have therapeutic implications for breast cancer patients . OUTPUT:

resisting cell death

HoC_1shot458

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Hypoxia is one of the inevitable circumstances of various tumors . It controls various levels of regulation in tumor progression and results in tumor resistance to radiotherapy and chemotherapy . Here we investigated a synthetic TPZ derivative , N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide ( XQ2 ) , a novel compound that induced anti-cancer effects both in normoxia and in hypoxia , cell proliferation assay found that XQ2 exhibited a potent inhibitory effect on the tested cancer cell lines both in normoxia and in hypoxia . Flow cytometry and western blot studies indicated that XQ2 induces G2/M arrest and a caspase-dependent apoptosis in A549 cells . Additionally , intracellular reactive oxygen species ( ROS ) appear to play a key role in the anticancer effect of XQ2 in hypoxia . Taken together , our data suggest that XQ2 exerted anticancer action by suppressing the ROS level and triggering cell-cycle arrest and the caspase-dependent pathway , which is associated with apoptosis . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot459

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Magnetite iron nanoparticles have been widely used as contrast agents and in thermal therapy for cancer . However , their adverse effects on human health have not been fully investigated . In this study , iron oxide nanoparticles were prepared using inorganic iron chloride ( size : 5.3+/-3.6 nm in phosphate buffered saline , surface charge : 23.14 mV ) , and their inflammatory responses were investigated . When mice were treated with iron oxide nanoparticles ( 250 microg/kg , 500 microg/kg , and 1mg/kg ) by a single intratracheal instillation , the level of intracellular reduced glutathione ( GSH ) was decreased in the cells of bronchoalveolar lavage ( BAL ) fluid . The arrest of cell cycles in G1 phase was observed , but S-phase was significantly decreased . The concentrations of pro-inflammatory cytokines ( IL-1 , TNF-alpha , and IL-6 ) were dose-dependently increased at day 1 after instillation in the BAL fluid and in the blood . During the experimental period of 28 days , pro-inflammatory cytokines ( IL-1 , TNF-alpha , and IL-6 ) , Th0 cytokine ( IL-2 ) , Th1 type cytokine ( IL-12 ) , Th2 type cytokines ( IL-4 and IL-5 ) , TGF-beta , and IgE were also elevated . Expressions of many genes related with inflammation or tissue damage such as heat shock protein , matrix metalloproteinase , tissue inhibitors of metalloproteinases , and serum amyloid A were significantly induced . Formation of microgranuloma , which is one of the indicators for chronic inflammatory response , was observed in the alveolar space . In addition , distribution of B cell and CD8+ T cell in blood lymphocytes was increased at day 28 . Based on the result , iron oxide nanoparticles may subchronic induce inflammatory responses via oxidative stress in mice by a single intratracheal instillation . OUTPUT:

sustaining proliferative signaling;tumor promoting inflammation

HoC_1shot460

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Infection by Opisthorchis viverrini , a risk factor for cholangiocarcinoma ( CCA ) may act through chronic inflammation , oxidative stress and lipid peroxidation ( LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine ( epsilondA ) , and 3,N4-etheno-2'-deoxycytidine ( epsilondC ) , markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients . In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model , in O. viverrini-infected hamsters that had received N-nitrosodimethylamine ( NDMA , 12.5 ppm in dw ) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method , from 21 up to 180 days post-O. viverrini-infection . In inflamed areas of the liver , etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct . Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters , treated with or w/o NDMA when compared with untreated controls . Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters . Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development . Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase ( ALP ) activity , bile duct hyperplasia , dysplasia , precancerous lesions , and CCA appearance . Also elevated expression of alkyladenine DNA glycosylase ( AAG ) , which excises 1,N6-ethenoadenine ( epsilonA ) was linked to higher adduct formation , suggesting imbalanced repair . Our results implicate accumulation of inflammation-related , promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis . OUTPUT:

tumor promoting inflammation;genomic instability and mutation

HoC_1shot461

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors . When two cells touch , an adhesion link is created between them by means of transmembrane E-cadherin proteins . Simultaneously , their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links . Here , we propose a detailed quantitative model of the role of cytoplasmic beta-catenin and alpha-catenin proteins in this process , treated as a reaction-diffusion system . Upon cell-cell contact the concentration in alpha-catenin dimers increases , inhibiting actin branching and thereby reducing cellular motility and expansion pressure . This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin , beta-catenin , and alpha-catenin in the cellular phenotype and in tumorigenesis . In particular , we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene . Potential direct tests of our model are discussed . OUTPUT:

evading growth suppressors

HoC_1shot462

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Proliferation of non-transformed cells is regulated by cell-cell contacts , which are referred to as contact-inhibition . Vice versa , transformed cells are characterised by a loss of contact-inhibition . Despite its generally accepted importance for cell-cycle control , little is known about the intracellular signalling pathways involved in contact-inhibition . Unravelling the molecular mechanisms of contact-inhibition and its loss during tumourigenesis will be an important step towards the identification of novel target genes in tumour diagnosis and treatment . To better understand the underlying molecular mechanisms we identified the transcriptional programme of contact-inhibition in NIH3T3 fibroblast using high-density microarrays . Setting the cut off : >or=1.5-fold , P <or= 0.05 , 853 genes and 73 cDNA sequences were differentially expressed in confluent compared to exponentially growing cultures . Importing these data into GenMAPP software revealed a comprehensive list of cell-cycle regulatory genes mediating G0/G1 arrest , which was confirmed by RT-PCR and Western blot . In a narrow analysis ( cut off : >or=2-fold , P <or= 0.002 ) , we found 110 transcripts to be differentially expressed representing 107 genes and 3 cDNA sequences involved , for example , in proliferation , signal transduction , transcriptional regulation , cell adhesion and communication . Interestingly , the majority of genes was upregulated indicating that contact-inhibition is not a passive state , but actively induced . Furthermore , we confirmed differential expression of eight genes by semi-quantitative RT-PCR and identified the potential tumour suppressor transforming growth factor-beta ( TGF-beta)-1-induced clone 22 ( TSC-22 ; tgfb1i4 ) as a novel protein to be induced in contact-inhibited cells . OUTPUT:

evading growth suppressors

HoC_1shot463

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

evading growth suppressors;sustaining proliferative signaling

HoC_1shot464

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

tumor promoting inflammation

HoC_1shot465

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: AIMS AND BACKGROUND To investigate a six-drug combination in patients with nonmetastatic Ewing sarcoma , focusing on chemotherapy-induced necrosis and chemotherapy toxicity in adult and pediatric patients . METHODS AND STUDY DESIGN Alternating cycles of vincristine ( 1.5 mg/m2 ) , doxorubicin ( 80 mg/m2 ) and cyclophosfamide ( 1200 mg/m2 ) ( weeks 0 , 6 , 13 , 22 and 31 ) , ifosfamide ( 9 g/m2 ) , vincristine ( 1.5 mg/m2 ) , and actinomycin D ( 1.5 mg/m2 ) ( weeks 3 , 16 , 25 and 34 ) , and ifosfamide ( 9 g/m2 ) and etoposide ( 450 mg/m2 ) ( weeks 9 , 19 , 28 and 37 ) were administered . Primary chemotherapy-induced necrosis was graded : G3 ( complete necrosis ) , G2 ( microfoci of tumor cells ) and G1 ( macrofoci of tumor cells ) . RESULTS From 1996 to 1999 , 50 patients with Ewing sarcoma were enrolled . The median age was 23.5 years ( range , 4-56 ) . Chemotherapy-induced necrosis ( in 28 patients ) was G3 in 36% , G2 in 21% and G1 in 43% . At a median follow-up of 110 months ( range , 36-129 ) , 5-year overall survival and event-free survival were 72% and 66% , respectively . According to histologic response , 5-year event-free survival was 90% in G3 , 83% in G2 , and 42% in G1 ( P = 0.02 ) . In adult and pediatric ( <18 years ) patients , the incidence of G4 leukopenia was 62% and 74% , respectively , with febrile neutropenia in 13% and 21% , respectively . G4 thrombocytopenia occurred in 3% of cycles in adults and in 7% in pediatric patients . Platelet and red blood cell transfusions were required respectively in 1% and 11% of cycles in adults and in 6% and 24% of cycles in pediatric patients . CONCLUSIONS The six-drug combination can be administered safely in adult and pediatric populations . About 40% of patients have a poor chemotherapy-induced tumor necrosis , leading to poor probability of survival . New strategies are recommended to improve survival of poor responders to the six-drug combination . OUTPUT:

resisting cell death

HoC_1shot466

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

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot467

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Medicinal mushroom Ganoderma lucidum is one of the most esteemed natural products that have been used in the traditional Chinese medicine . In this article , we demonstrate that G. lucidum triterpene extract ( GLT ) suppresses proliferation of human colon cancer cells HT-29 and inhibits tumor growth in a xenograft model of colon cancer . These effects of GLT are associated with the cell cycle arrest at G0/G1 and the induction of the programmed cell death Type II-autophagy in colon cancer cells . Here , we show that GLT induces formation of autophagic vacuoles and upregulates expression of Beclin-1 ( 1.3-fold increase ) and LC-3 ( 7.3-fold increase ) proteins in colon cancer cells and in tumors in a xenograft model ( Beclin-1 , 3.9-fold increase ; LC-3 , 1.9-fold increase ) . Autophagy is mediated through the inhibition of p38 mitogen-activated protein kinase ( p38 MAPK ) because p38 MAPK inhibitor , SB202190 , induces autophagy and expression of Beclin-1 ( 1.2-fold increase ) and LC-3 ( 7.4-fold increase ) , and GLT suppresses phosphorylation of p38 MAPK ( approximately 60% inhibition ) in colon cancer cells . Taken together , our data demonstrate a novel mechanism responsible for the inhibition of colon cancer cells by G. lucidum and suggest GLT as natural product for the treatment of colon cancer . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot468

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone ( DHC ) , a novel synthetic flavonoid , and fisetin , a naturally occurring flavonol-in prostate cancer cells . In this study , we further examine the mechanisms of these compounds on survival and proliferation pathways . DHC and fisetin ( 1-50 microM ) caused a dose-dependent reduction in viability , a concomitant increase in apoptosis in PC3 cells at 72 h , and a decrease in clonogenic survival at 24 h treatment . DHC was considerably more potent than fisetin in these cytotoxicity assays . The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate ( LNCaP ) cells . Gene expression alterations in PC3 and LNCaP cells treated with 15 muM DHC and 25 microM fisetin for 6 to 24 h were determined by oligonucleotide array . Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category . In total , 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds . Other functional categories altered included chromosome organization , apoptosis , and stress response . These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro . OUTPUT:

enabling replicative immortality;evading growth suppressors;sustaining proliferative signaling

HoC_1shot469

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: In traditional biochemical experiments , the behavior of individual proteins is obscured by ensemble averaging . To better understand the behavior of proteins that bind to and/or translocate on DNA , we have developed instrumentation that uses optical trapping , microfluidic solution delivery , and fluorescent microscopy to visualize either individual proteins or assemblies of proteins acting on single molecules of DNA . The general experimental design involves attaching a single DNA molecule to a polystyrene microsphere that is then used as a microscopic handle to manipulate individual DNA molecules with a laser trap . Visualization is achieved by fluorescently labeling either the DNA or the protein of interest , followed by direct imaging using high-sensitivity fluorescence microscopy . We describe the sample preparation and instrumentation used to visualize the interaction of individual proteins with single molecules of DNA . As examples , we describe the application of these methods to the study of proteins involved in recombination-mediated DNA repair , a process essential for the maintenance of genomic integrity . OUTPUT:

genomic instability and mutation

HoC_1shot470

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

tumor promoting inflammation

HoC_1shot471

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

resisting cell death

HoC_1shot472

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To analyze the profiles of interleukin-2 ( IL-2 ) , IL-6 , IL-8 , IL-10 , tumor necrosis factor-alpha ( TNF-alpha ) , transforming growth factor-beta1 ( TGF-beta1 ) and interferon-gamma ( IFN-gamma ) in serum and the tumor microenvironment ( cyst fluid , ascites ) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status . We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors . DESIGN Prospective study . SETTING Tertiary referral hospital . POPULATION 51 women with epithelial ovarian cancer , 26 with benign ovarian tumors of epithelial origin and 21 healthy controls . METHODS The levels of cytokines were measured using ELISA sets . RESULTS We did not found differences in the levels of IFN-gamma , TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors . Women with advanced cancer had significantly higher serum IL-6 , IL-10 and TGF-beta1 levels than women with early stages or benign tumors . Moreover , women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10 , TGF-beta1 and IL-8 . The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors . The areas under curves constructed for the selected cutoff serum cytokines levels ( AUC-ROC ) showed good predictive values for IL-6 ( 0.87 ) , IL-10 ( 0.836 ) and IL-8 ( 0.797 ) . CONCLUSIONS Our results indicate on intensified inflammatory process in women with ovarian cancer ( accompanied by their immunosuppression ) . Preoperative analysis of serum IL-6 , IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot473

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES To evaluate and compare the incidence , TNM staging and the current strate- gy for the surgical treatment of renal cell carcinoma ( RCC ) in two European urologic institutions , situated in Varna , Bulgaria and in Bari , Italy . Both clinics have sound experience of RCC surgery , and modern laparoscopic equipment . A retrospective chart review of all patients with RCC diagnosed and treated in the last year was conducted at the two sites . MATERIALS AND METHODS In total , 88 patients ( 66 males and 22 females , mean age 58 years , range 24-81 years ) were enrolled in the study . Comparisons were made between some clinical and pathologic parameters with an established prognostic and therapeutic impact . The type of surgery perormed at both sites was analyzed as well . All these comparative studies were performed in relation to the 2008 EAU guidelines on the current management of RCC . Commercially available statistical software was used for the purpose . RESULTS The results showed no difference between the two sites regarding the RCC incidence and the patients ' age and gender . Significant differences ( p value &lt ; 0.0001 ) emerged in terms of : the median size of the tumors at surgery ( 8.5 cm in Varna , SD + 4.04 vs. 4.4 cm in Bari , SD _ 2.02 ) ; T-stage of the tumor ( Varna T T2-30% , T3-22% , T4-15% vs. Bari T1-64% , T2-12% , T3-24% , T4-0% ) ; N-positive disese ( 24% vs. 2% ) ; distant metastases ( 20% vs. 2% ) and presence of necrosis in the renal masses ( 37% vs. 19% ) . Thus , 85% of Varna patients underwent open radical nephrectomy , 11% nephron-sparing surgery and 4% explorative laparotomy , due to inoperability of the renal mass . Only 29% of Bari patients were treated by open radical nephrectomy , 12% underwent laparoscopic nephrectomy , 57% open partial nephrectomy and 2% laparoscopic partial tumor resection . Conclusions : These numbers demonstrate more advantageous tumour features at the Italian clinic in terms of organ-sparing surgical options ( open and laparoscopic ) , whereas in the Bulgarian clinic the tumour features pose certain limitations to the application of modern surgical techniques . This difference is due to early diagnosis of RCC in Italy , allowing treatment of smaller volume tumors . OUTPUT:

resisting cell death

HoC_1shot474

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The soluble hexavalent chromium Cr ( VI ) used in industrial welding is an environmental contaminant widely recognized to act as a carcinogen , mutagen and teratogen towards humans and animals . The carcinogenic potential of metals is a major issue in defining human health risk from exposure . In the present investigation , 93 welders and 60 control subjects with similar mean ages , smoking prevalences and alcohol consumption were enrolled for DNA damage analysis in blood leucocytes by Micronucleus assay ( MN ) and the Comet assay . DNA repair inhibition was also analyzed by assessing XPD gene polymorphism . Welders showed a significant increase in micronucleated cells compared to controls with respect to their smoking habits and alcohol consumption , age and years of exposure ( P<0.05 ) . Results indicated that the welders had a larger mean comet tail length than that of the controls ( P<0.05 ) . The current study suggested that chronic occupational exposure to Cr ( VI ) during welding could lead to increased levels of DNA damage and repair inhibition . OUTPUT:

genomic instability and mutation

HoC_1shot475

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE The study was undertaken to document and highlight the shortcomings of histopathology reporting of breast carcinoma in Pakistan so that improvements can be recommended and a standardized protocol devised . METHODS This was a descriptive cross sectional study and was conducted at Histopathology Department , Armed Forces Institute of Pathology , Rawalpindi from 1st January 2008 to 31st October 2008 . Fifty consecutive breast carcinoma reports received for review from different laboratories were analyzed for documentation of patients age , sex , type of procedure/specimen , specimen size , tumour size , invasive tumour type , invasive tumour grade , comment on excision margins , extent of lymph node involvement , insitu component , lymphovascular invasion , necrosis , skin involvement and tabular format . Frequencies and percentages were calculated for presence of these above mentioned variables in different reports , keeping in mind the possible information that could be obtained from a particular sample . RESULTS It was found that the variable least mentioned in the reports was in situ component commented upon in only 23.2% of reports . Necrosis was mentioned in 35% of reports . Tabular format was found in 36% of reports only . CONCLUSION Marked deficiencies are seen in histopathology reports for breast carcinoma due to the lack of any standardized reporting system . Separate checklist formats for trucut biopsies , lumpectomies and mastectomies should be introduced to ensure uniform reporting . OUTPUT:

resisting cell death

HoC_1shot476

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

avoiding immune destruction;resisting cell death

HoC_1shot477

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE To study the effect of necrostatin ( Nec-1 ) on apoptosis induced by aluminum ( Al ) , and approach the mechanism . METHODS Neural cell death model was made by 4 mmol/L Al treated neuroblastoma cells ( SH-SY5Y ) . Cell viabilities were detected at different concentrations of Al and/or Nec-1 . Hoechst 33342/PI double staining was used to observe apoptosis and ( or ) necrosis that were quantified by flow cytometry using Annexin V/PI double staining . Apoptotic pathway was tested by activities of Caspase-3 , Caspase-8 and Caspase-9 . In addition , the expression of NF-kappa B and Cyt-c was measured by immunocytochemistry . RESULTS Cell viabilities were significantly decreased with the increasing concentrations of Al ( P &lt ; 0.05 ) , which could be significantly upregulated by 60 micromol/L Nec-1 ( P &lt ; 0.05 ) and were correlated with the concentrations of Nec-1 ( P &lt ; 0.05 , P &lt ; 0.01 ) . Apoptosis and necrosis were observed under fluorescent microscope and quantified by flow cytometry , which suggested an increasing trend of apoptotic and necrotic rates ( P &lt ; 0.05 , P &lt ; 0.01 ) . Whereas , Nec-1 could not only decrease the necrotic rate but also apoptotic rate as well ( P &lt ; 0.05 , P &lt ; 0.01 ) . Data of Nec-1 on caspases activities showed that Nec-1 could not affect Caspase-9 activity ( P &gt ; 0.05 ) and Cty-c protein expression as well ( P &gt ; 0.05 ) . However , Nec-1 could reduce Caspase-8 activity significantly ( P &lt ; 0.05 , P &lt ; 0.01 ) and increase NF-kappa B protein expression ( P &lt ; 0.05 , P &lt ; 0.01 ) and finally decrease Caspase-3 activity ( P &lt ; 0.05 ) . CONCLUSION Nec-1 could reduce cell apoptosis induced by Al , through Caspase-8 pathway , and up-regulate the expression of NF-kappa B protein . OUTPUT:

resisting cell death

HoC_1shot478

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Bisphosphonates ( BPs ) are the current standard of care for bone lesions in patients with multiple myeloma ( MM ) but they are associated with a number of side effects such as osteonecrosis of the jaw . The exact mechanisms of osteonecrosis are not elucidated , and its physiopathology is based on several hypotheses such as a decrease in bone remodeling or an inhibitory effect on angiogenesis . The aim of our study was to investigate the mechanism involved in the pathogenesis of osteonecrosis . We examined the apoptosis of circulating endothelial progenitor cells in MM subjects before and after BP treatment and in osteonecrosis patients using a flow-cytometric analysis . Our data showed an increase in endothelial cell apoptosis in MM patients after BP administration and in osteonecrosis subjects . Our study seems in agreement with the hypothesis that BPs can inhibit angiogenesis interfering with endothelial cell proliferation and survival , leading to loss of blood vessels and avascular necrosis . OUTPUT:

inducing angiogenesis;resisting cell death

HoC_1shot479

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The biological activities of tocotrienols are receiving increasing attention . Herein , we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate ( TRAMP ) mouse model . Male TRAMP mice , 8 wk old , were fed 0.1% , 0.3% , or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old . Likewise , a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old . Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus . Furthermore , mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls . This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD ( Bcl(2) antagonist of cell death ) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27 . In contrast , the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups . Taken together , our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins , mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice . OUTPUT:

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot480

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

evading growth suppressors;sustaining proliferative signaling

HoC_1shot481

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: A novel compound 2-arylidene-4,7-dimethyl indan-1-one synthesized was screened for anticancer effect against the human breast adenocarcinoma cell line , MCF-7 . An IC50 value of &gt ; or = 80 microM , nontoxic to the normal breast cell line HBL-100 , showed complete inhibition of the MCF-7 cells . Analysis of mechanisms showed nuclear fragmentation and DNA laddering in gel electrophoresis . GSH and GR levels were found to be reduced after the compound treatment . Cell cycle analysis using fluorescent cytometry revealed G2/M phase arrest , which indicates the compound deserves consideration for further studies against cancer . OUTPUT:

resisting cell death;evading growth suppressors;sustaining proliferative signaling

HoC_1shot482

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

genomic instability and mutation;tumor promoting inflammation

HoC_1shot483

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION The homeobox-containing transcription factor muscle segment homeobox 2 ( Msx2 ) plays an important role in mammary gland development . However , the clinical implications of Msx2 expression in breast cancer are unclear . The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro . METHODS Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients . Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray ( TMA ) containing 281 invasive breast tumours . Finally , to assess the functional role of Msx2 in vitro , Msx2 was ectopically expressed in a highly invasive breast tumour cell line ( MDA-MB-231 ) and an immortalised breast cell line ( MCF10a ) , and these cell lines were examined for changes in growth rate , cell death and cell signalling . RESULTS Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis ( P = 0.011 ) . Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm . Cytoplasmic Msx2 expression was associated with low grade tumours ( P = 0.012 ) and Ki67 negativity ( P = 0.018 ) . Nuclear Msx2 correlated with low-grade tumours ( P = 0.015 ) , estrogen receptor positivity ( P = 0.038 ) , low Ki67 ( P = 0.005 ) and high cyclin D1 expression ( P = 0.037 ) . Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival ( P = 0.049 ) , recurrence-free survival ( P = 0.029 ) and overall survival ( P = 0.019 ) . Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis . Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase ( ERK ) and decreased levels of Survivin and the ' split ends ' ( SPEN ) protein family member RBM15 . CONCLUSIONS We conclude that increased Msx2 expression results in improved outcome for breast cancer patients , possibly by increasing the likelihood of tumour cell death by apoptosis . OUTPUT:

sustaining proliferative signaling;resisting cell death;evading growth suppressors

HoC_1shot484

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: This study aimed to investigate the mechanism by which the human lung cancer drug resistance-related gene BC006151 regulates chemosensitivity by down-regulating BC006151 expression via antisense gene transfer in H446/(C)DDP cells . A retroviral vector containing the antisense BC006151 sequence was constructed and transfected into H446/(C)DDP cells . Transfection of the empty vector served as a negative control . The two groups of transfected cells were treated with various chemotherapeutic agents , after which morphological changes in cell ultrastructure were compared by transmission electron microscopy , cell proliferation and chemosensitivity to particular chemotherapeutic agents were compared by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method , the effects of chemotherapy on cell cycle and apoptosis were compared by flow cytometry , and Bcl-2 was evaluated by immunohistochemistry and Western blot analysis . Results showed that apoptotic body-like structures were identified by transmission electron microscopy in the antisense gene-transfected cells . MTT founded that these cells exhibited a significantly lower level of proliferation than the control cells ( p<0.01 ) , together with a markedly increased sensitivity to various chemotherapeutic agents ( p<0.01 ) . Flow cytometry analysis revealed that a G1 phase arrest accounted for the reduction in proliferation in the antisense gene-transfected cells ; increased apoptosis was also detected ( p<0.01 ) . Both immunohistochemistry and western blot analysis confirmed that Bcl-2 expression was significantly down-regulated in the antisense gene-transfected cells compared to controls . In a word , down-regulation of BC006151 can significantly inhibit proliferation and increase apoptosis of H446/(C)DDP cells after chemotherapy , and this gene may play an important role in the development of multidrug resistance in lung cancer . OUTPUT:

resisting cell death;evading growth suppressors

HoC_1shot485

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

evading growth suppressors;resisting cell death;sustaining proliferative signaling

HoC_1shot486

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND The most deadly form of cancer is not lung or colon , breast or prostate ; it is any cancer that has become metastatic . Mortality due to metastatic melanoma , one of the most aggressive and deadly cancers , has increased steadily over the last several decades . Unfortunately , the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals . We sought to identify an effective and nontoxic agent against metastatic melanoma . METHODOLOGY/PRINCIPAL FINDINGS We chose to study Cloudman S-91 mouse melanoma cells ( sub-clone M3 , CCL53.1 ) because these cells are highly aggressive and metastatic , representing one of the deadliest types of cancer . Melanoma cells also had an experimental advantage because their morphology , which is easily monitored , relates to the physiology of metastatic cells and normal melanocytes . We chose to test methyl sulfone as a chemotherapeutic agent for two reasons . Because of its chemical structure , we speculated a potential anti-cancer activity by targeting microtubules . Equally important , methyl sulfone has a well-established safety profile in humans . Surprisingly , we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells , and the reemergence of phenotypes characteristic of healthy melanocytes . Briefly , over time methyl sulfone induced contact inhibition , loss of ability to migrate through an extracellular matrix , loss of anchorage-independent growth , proper wound healing followed by contact inhibition , irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes . CONCLUSIONS/SIGNIFICANCE Methyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma . Additionally , methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration , contact inhibition , wound healing and cellular senescence . OUTPUT:

enabling replicative immortality;evading growth suppressors;activating invasion and metastasis

HoC_1shot487

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION HER2 and estrogen receptor ( ER ) are important in breast cancer and are therapeutic targets of trastuzumab ( Herceptin ) and tamoxifen , respectively . Retinoids inhibit breast cancer growth , and modulate signaling by HER2 and ER . We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects . METHODS The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture , BT474 and SKBR3 . Assays of proliferation , apoptosis , differentiation , cell cycle distribution , and receptor signaling were performed . RESULTS In HER2-overexpressing/ER-positive BT474 cells , combining all-trans retinoic acid ( atRA ) with tamoxifen or trastuzumab synergistically inhibited cell growth , and altered cell differentiation and cell cycle . Only atRA/trastuzumab-containing combinations induced apoptosis . BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids ( atRA , 9-cis-retinoic acid , 13-cis-retinoic acid , or N-(4-hydroxyphenyl) retinamide ( fenretinide ) ( 4-HPR) ) combined with trastuzumab . In BT474 cells , none of the single agents except 4-HPR induced apoptosis , but again combinations of each retinoid with trastuzumab did induce apoptosis . In contrast , the single retinoid agents did cause apoptosis in SKBR3 cells ; this was only modestly enhanced by addition of trastuzumab . The retinoid drug combinations altered signaling by HER2 and ER . Retinoids were inactive in trastuzumab-resistant BT474 cells . CONCLUSIONS Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells . Treatment with such combinations may have benefit for breast cancer patients . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot488

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE The cytotoxic effect of the combination treatment of TNF-alpha and hyperthermia on L929 and TNF-alpha-resistant L929 ( rL929 ) cells was investigated . MATERIALS AND METHODS L929 cells were treated with TNF-alpha ( 5 ng/mL ) , heating at 43 degrees C or the combination of TNF-alpha and heating . The cells were harvested at different time within the 24-hour period . The viability and the type of cell death of the harvested cells were examined . RESULTS When L929 cells were treated with a combination of TNF-alpha and heating the cells died quickly and apoptosis increased to an overwhelming extent , especially in the group pre-treated with TNF-alpha for 1 h prior to heating . Although rL929 cells were resistant to TNF-alpha alone , the cells became sensitive to TNF-alpha treatment when combined with heating . Similar to the L929 cell , the cells also died rapidly and exhibited apoptosis to a higher extent . Using an Annexin-V-FITC kit and flow cytometer , we found that both necrosis and apoptosis occurred . Agarose gel electrophoresis of DNA extracted from treated cells showed that the DNA fragments were multiples of approximately 200 bp . Furthermore , by studying the kinetics of cell death and apoptosis , we found that the loss of cell membrane integrity preceded the DNA fragmentation in both L929 and rL929 cells . CONCLUSION The results suggested that hyperthermia may enhance the necrotic and apoptotic effects of TNF-alpha on some tumour cells and overcome the resistance of some tumour cells to TNF-alpha . OUTPUT:

resisting cell death

HoC_1shot489

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Chromosomal instability and the subsequent genetic mutations are considered to be critical factors in the development of the majority of solid tumors , but the mechanisms by which a stable diploid cell loses the ability to maintain genomic integrity are not well characterized . We have approached this critical issue through the use of high-throughput screens in untransformed diploid epithelial cells . In a screen of a cDNA library , we identified 13 kinases whose overexpression leads to increased ploidy . In a series of shRNA screens , we identified 16 kinases whose loss leads to increased ploidy . In both cDNA and shRNA screens , the majority of hits have not been linked previously to genomic stability . We further show that sustained loss of the shRNA screening hits leads to multipolar spindles and heterogeneous chromosome content , two characteristics of chromosomal instability . Loss of several of the kinases leads to loss of contact inhibition and to anchorage-independent growth , vital traits acquired during tumor development . We anticipate that this work will serve as a template for the comprehensive identification of pathways whose dysregulation can drive tumorigenesis through impaired karyotypic maintenance . OUTPUT:

genomic instability and mutation;evading growth suppressors

HoC_1shot490

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Taxol ( Paclitaxel ) is an important natural product for the treatment of solid tumors such as ovarian , breast , non-small-cell lung tumors , and some head and neck carcinomas . Different concentrations of taxol trigger distinct effects on cell death forms . In present study , cell counting kit ( CCK-8 ) assay , confocal fluorescence microscopy imaging , flow cytometry ( FCM ) and western blotting ( WB ) analysis were used to analyze the characteristics of cell death induced by low ( 35 nM ) and high ( 70 microM ) concentration of taxol respectively in human lung adenocarcinoma ( ASTC-a-1 ) cells . Our results showed that low concentration of taxol induced cell death dominantly in apoptotic fashion associated with nuclear fragmentation , protein synthesis , phosphatidylserine ( PS ) externalization , G2/M cell cycle arrest , Bax translocation into mitochondria and caspase-3 activation , whereas high concentration of this drug induced significant cytoplasm vacuolization , mitochondria swelling and paraptosis-like cell death form without protein synthesis that is necessary for paraptosis . Although the mechanism of high concentration of taxol-induced paraptosis-like cell death has not been clear , this finding might have a potential implication for cancer therapy , especially for apoptosis-resistant cancer . OUTPUT:

resisting cell death

HoC_1shot491

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

tumor promoting inflammation

HoC_1shot492

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types . Here we analysed polymorphisms in 5 genes involved in DNA repair ( XPD Asp312Asn and Lys751Gln , XRCC1 Arg399Gln , APE1 Asp148Glu , NBS1 Glu185Gln , and XPA G-4A ) and in a gene involved in regulation of the cell-cycle ( CCND1 A870G ) . We compared their frequencies in groups of colon , head and neck , and breast cancer patients , and 2 healthy control groups : ( 1 ) matched healthy Polish individuals and ( 2 ) a NCBI database control group . Highly significant differences in the distribution of genotypes of the APE1 , XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals . The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer ( OR = 1.9-2.3 and OR = 1.5-2.1 , respectively ) . Additionally , frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer . Importantly , no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients . The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses . OUTPUT:

evading growth suppressors;genomic instability and mutation

HoC_1shot493

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: BACKGROUND In this report , we explored the role of PKCalpha and PKCe as mediators of phorbol 12-myristate13-acetate ( PMA)-induced proliferation in pituitary tumor GH3B6 cells , and determined if the ERK1/2 and Akt pathways were activated . METHODS The GH3B6 cell proliferation was estimated by BrdU incorporation and the cell cycle progression by flow cytometric cell cycle analysis . We determined the expression of PKCalpha and PKCe in membrane and cytosolic fractions by western blotting . The subcellular redistribution of both PKC isozymes was analyzed by confocal microscopy . RESULTS Incubation with PMA for 15 min stimulated PKCalpha and PKCe activation , which was correlated with the phosphorylation of ERK1/2 but not Akt . The activation of both these PKC isozymes was closely associated with the stimulation of proliferation and the cell cycle progression induced by PMA in GH3B6 cells , an effect that was blocked by the inhibitors of PKCalpha ( Gö6976 ) and PKCe ( eV1-2 ) . In addition , the pretreatment with the inhibitor of ERK1/2 ( PD98059 ) prevented the mitogenic activity induced by treatment with PMA for 15 min . CONCLUSION We demonstrated that the activation of PKCalpha and PKCe by phorbol ester in tumor pituitary GH3B6 cells led to cell proliferation and cell cycle progression , effects that involved ERK1/2 activation . OUTPUT:

sustaining proliferative signaling

HoC_1shot494

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: In spite of numerous advances , the 5-year survival rate for head and neck squamous cell cancer has remained largely stagnant and few new anti-tumor drugs have been developed . PCH4 , a derivative of n-butylidenephthalide , has been investigated for its anti-tumor effects on oral squamous cell carcinoma ( OSCC ) . The aim of this study was to investigate the anti-tumor mechanism of a potential target gene , Nur77 , in OSCC cells , which can be induced by PCH4 treatment . Data show that PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and induced cell apoptosis in OSCC cells . When Nur77 translocation was blocked , the degree of tumor apoptosis caused by PCH4 was significantly inhibited ( p < 0.05 ) . Within the MAPK pathway , PCH4 only induced JNK phosphorylation . Furthermore , treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis ( p < 0.05 ) and decreased PCH4-induced Nur77 expression ( p < 0.05 ) . In a xenograft animal model , administration of PCH4 also showed anti-tumor effects . We have demonstrated that OSCC cells are sensitive to PCH4 and that Nur77 protein translocation from the nucleus to the cytoplasm might be associated with the induction of apoptosis by PCH4 . These results indicate that PCH4 may serve as a potential anti-tumor drug for OSCC therapy . OUTPUT:

resisting cell death

HoC_1shot495

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION Natural herbal compounds with novel actions different from existing breast cancer ( BCa ) treatment modalities are attractive for improving therapeutic efficacy and safety . We have recently shown that penta-1,2,3,4,6-O-galloyl-β-D-glucose ( PGG ) induced S-phase arrest in prostate cancer ( PCa ) cells through inhibiting DNA replicative synthesis and G(1) arrest , in addition to inducing cell death at higher levels of exposure . We and others have shown that PGG through intraperitoneal ( i.p. ) injection exerts a strong in vivo growth suppression of human PCa xenograft models in athymic nude mice . This study aims to test the hypothesis that the novel targeting actions of PGG are applicable to BCa cells , especially those lacking proven druggable targets . METHODS Mono-layer cell culture models of p53-wild type estrogen receptor ( ER)-dependent MCF-7 BCa cells and p53-mutant ER-/progesterone receptor ( PR)- and Her2-regular ( triple-negative ) MDA-MB-231 BCa were exposed to PGG for a comprehensive investigation of cellular consequences and molecular targets/mediators . To test the in vivo efficacy , female athymic mice inoculated with MDA-MB-231 xenograft were treated with 20mg PGG/kg body weight by daily gavage starting 4 days after cancer cell inoculation . RESULTS Exposure to PGG induced S-phase arrest in both cell lines as indicated by the lack of 5-bromo2'-deoxy-uridine ( BrdU ) incorporation into S-phase cells as well as G(1) arrest . Higher levels of PGG induced more caspase-mediated apoptosis in MCF-7 , in strong association with induction of P53 Ser(15) phosphorylation , than in MDA-MB-231 cells . The cell cycle arrests were achieved without an induction of cyclin dependent kinase ( CDK ) inhibitory proteins P21(Cip1) and P27(Kip1) . PGG treatment led to decreased cyclin D1 in both cell lines and over-expressing cyclin D1 attenuated G(1) arrest and hastened S arrest . In serum-starvation synchronized MCF-7 cells , down-regulation of cyclin D1 was associated with de-phosphorylation of retinoblastoma ( Rb ) protein by PGG shortly before G(1)-S transition . In vivo , oral administration of PGG led to a greater than 60% inhibition of MDA-MB231 xenograft growth without adverse effect on host body weight . CONCLUSIONS Our in vitro and in vivo data support PGG as a potential drug candidate for breast cancer with novel targeting actions , especially for a triple negative BCa xenograft model . OUTPUT:

evading growth suppressors;sustaining proliferative signaling;resisting cell death

HoC_1shot496

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Maintaining the integrity of the cell cycle is critical for ensuring that cells only undergo DNA replication and proliferation under controlled conditions in response to discrete stimuli . One mechanism by which the fidelity of this process is guaranteed is through the activation of cell cycle checkpoints . The mitotic spindle checkpoint , which is regulated by Aurora B kinase , ensures proper kinetochore attachment to chromosomes leading to equal distribution of chromosomes to daughter cells . We demonstrated that the mitogen-activated protein kinase ( MAPK ) cascade regulates mitotic progression and the spindle checkpoint . As demonstrated by immunofluorescence at kinetochores , depletion of Raf Kinase Inhibitory Protein ( RKIP ) , an inhibitor of Raf/MEK/ERK signaling , causes an increase in MAPK activity that inhibits Aurora B kinase activity . By monitoring mitotic index and transit time from nuclear envelope breakdown to anaphase , we demonstrated that RKIP depletion leads to a defective spindle checkpoint and genomic instability , particularly in response to drugs that disrupt microtubule function . OUTPUT:

sustaining proliferative signaling;genomic instability and mutation

HoC_1shot497

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Verbascum thapsus commonly known as ' mullein ' is part of a large family of Scrophulariaceae consisting of more than 360 species . From antiquity Verbascum thapsus has been used as a medicinal herb , it contains diverse polysaccharides , iroid glycosides , flavonoids , saponins , volatile oils and phenylentanoids . Inducible nitric oxide synthase ( iNOS ) represents one of the three isoforms that produce nitric oxide using L-arginine as a substrate in response to an increase in superoxide anion activated by NF-kB . It is implicated in different pathophysiological events and its expression increases greatly during an inflammatory process , due to oxidative stress and the activation of the enzymes of the antioxidant network such as SOD , CAT and GPx.In this study an inflammatory state was reproduced by treating THP-1 cells ( human myelomonocytic leukaemia ) with pro-inflammatory stimuli , such as LPS and IFN-gamma , obtaining an up-regulation both in the expression and in the activity of iNOS . The aim of the work was to investigate the antiinflammatory action of verbascoside using a concentration of 100 mum . The results show a significant decrease of the expression and activity of iNOS , extracellular O(2) ( - ) production , SOD , CAT and GPx activity when the cells were treated with verbascoside . Based on these results it is hypothesized that verbascoside has antiinflammatory properties since it reduces the production of superoxide radicals and consequently reduces the activity of iNOS . OUTPUT:

tumor promoting inflammation

HoC_1shot498

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Idarubicin is a synthetic anthracycline anticancer drug widely used in the treatment of some hematological malignancies . The studies in our laboratory have clearly demonstrated that idarubicin can undergo reductive bioactivation by NADPH-cytochrome P450 reductase to free radicals with resulting formation of DNA strand breaks , which can potentially contribute to its genotoxic effects [ Celik , H. , Arinç , E. , Bioreduction of idarubicin and formation of ROS responsible for DNA cleavage by NADPH-cytochrome P450 reductase and its potential role in the antitumor effect . J Pharm Pharm Sci , 11(4):68-82 , 2008 ] . In the current study , our aim was to investigate the possible protective effects of several phenolic antioxidants , quercetin , rutin , naringenin , resveratrol and trolox , against the DNA-damaging effect of idarubicin originating from its P450 reductase-catalyzed bioactivation . METHODS DNA damage was measured by detecting single-strand breaks in plasmid pBR322 DNA using a cell-free agarose gel method . RESULTS Our results indicated that , among the compounds tested , quercetin was the most potent antioxidant in preventing DNA damage . Quercetin significantly decreased the extent of DNA strand breaks in a dose-dependent manner ; 100 microM of quercetin almost completely inhibited the DNA strand breakage . Unlike quercetin , its glycosidated conjugate rutin , failed to provide any significant protection against idarubicin-induced DNA strand breaks except at the highest concentration tested ( 2 mM ) . The protective effects of other antioxidants were significantly less than that of quercetin even at high concentrations . Quercetin was found to be also an effective protector against DNA damage induced by mitomycin C. CONCLUSION We conclude that quercetin , one of the most abundant flavonoids in the human diet , is highly effective in reducing the DNA damage caused by the antitumor agents , idarubicin and mitomycin C , following bioactivation by P450 reductase . OUTPUT:

genomic instability and mutation

HoC_1shot499

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

resisting cell death;tumor promoting inflammation