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clinicalnlplab

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HoC_1shot_test

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HoC_1shot200

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence , apoptosis , aging and aging-associated pathologies . Telomere shortening and genomic instability have also been associated with replicative senescence , aging and cancer . Here we show that mitochondrial dysfunction leads to telomere attrition , telomere loss , and chromosome fusion and breakage , accompanied by apoptosis . An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria , suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability . Further , nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria . This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging-associated pathologies . OUTPUT:

resisting cell death;genomic instability and mutation;tumor promoting inflammation

HoC_1shot201

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 present a new cell line , EJ established from an invasive endometrioid adenocarcinoma of the uterine corpus in a 56-year-old patient . The cells show rapid growth in culture with a doubling time of 16 h and high migration activity . Monolayer-cultured cells were polygonal in shape showing a tendency to pile up without contact inhibition . Subcutaneous transplantation of the EJ cells into nude mice formed solid tumors that were histologically diagnosed as adenocarcinoma , whereas no metastasis was observed . Cultured EJ cells produced tissue polypeptide antigen ( IPA ) . Genetic and molecular analyses revealed high telomerase activity but not estrogen receptor alpha expression . Using the DNA sequencing technique , we have screened EJ cells for p53 mutation in exon 5 to 8 but no mutation of p53 was observed . This cell line appears to represent the development of a more malignant clone with divergent receptor function and growth behavior , and provides us with an interesting new tool for the study of tumorigenesis in the human endometrium . OUTPUT:

activating invasion and metastasis;evading growth suppressors;sustaining proliferative signaling;genomic instability and mutation

HoC_1shot202

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 studied the mutagenic specificity of abasic sites using the yeast oligonucleotides transformation assay . We introduced oligonucleotide containing a natural abasic site and a tetrahydrofuran abasic site into Rev1 mutants , rev1AA , which contains mutations of Asp467 and Glu468 residues of Rev1p to Ala in order to inactivate dCMP transferase activity , and rev1 delta , which lacks its whole coding sequence . The transformation efficiencies of rev1AA with abasic-containing oligonucleotides were lower than those of B7528 , a strain proficient in REV1 gene , but much higher than rev1 delta mutant . Sequence analysis opposite the lesions showed that the mutation spectra were different among these three strains . OUTPUT:

genomic instability and mutation

HoC_1shot203

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Vascular endothelial growth factor A ( VEGF-A ) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis . SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase . We have developed a reproducible murine model for neuroblastoma , a childhood cancer , based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells . We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels , that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume &gt ; 1.4 ml , and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals . Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity . SU5416 treatment also suppressed tumor angiogenesis , despite an increase in plasma VEGF-A levels per ml tumor volume during therapy . Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma . OUTPUT:

inducing angiogenesis

HoC_1shot204

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Epidermal growth factor ( EGF ) and transforming growth factor alpha ( TGF alpha ) content was measured in normal ovaries and benign ovarian tumours . Epidermal growth factor was present in 12.7% of normal ovaries , with a range 0.030-0.533 ng/mg DNA , and in 31.8% of benign ovarian tumours , with a range 0.1335-2.080 ng/ml DNA . TGF alpha was present in 84.5% of normal ovaries , with a range of values from 0.037-18.2 ng/mg DNA , and in 84.1% of benign ovarian tumours , with a range of 0.083-195 ng/mg DNA . The TGF alpha content in post menopausal benign ovarian tumours was significantly higher ( P &lt ; 0.0001 ) than TGF alpha in the pre-menopausal normal ovarian group . The frequency of detection and levels of TGF alpha measured were significantly higher than those of EGF in the normal ovary group ( P &lt ; 0.001 ) and also in the benign ovarian group ( P &lt ; 0.005 ) . We conclude that TGF alpha is the predominant growth factor present in normal ovaries and benign ovarian tumours . OUTPUT:

sustaining proliferative signaling

HoC_1shot205

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 effects of high and low dietary fat ( 20% vs. 0.5% corn oil ) , and of the prostaglandin synthetase inhibitor indomethacin ( 0.005% w/w ) , on tumour incidence , tumour growth , hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene ( DMBA)-induced rat breast cancer . The high dietary-fat group showed a significantly higher tumour incidence , larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group . Indomethacin reduced tumour incidence significantly , but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups . No significant difference was noted in the hormone-receptor status of the tumours . Growth factors ( TGF-alpha and IGF-II ) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group , but indomethacin rather reduced the growth-factor expression . It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation , while indomethacin has dual effects : a stimulating effect on tumour proliferation , but an inhibiting effect on tumour incidence . It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation . OUTPUT:

sustaining proliferative signaling

HoC_1shot206

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Previous studies have shown that the E7 gene of human papillomavirus ( HPV ) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells ( HFE ) and that the efficiency was increased in cooperation with the respective E6 gene , whereas the HPV6 E6 or E7 gene was not active in HFE . To detect weak immortalizing activities of the HPV6 genes , cells were infected with recombinant retroviruses containing HPV genes , alone and in homologous and heterologous combinations . The HPV6 genes , alone or together ( HPV6 E6 plus HPV6 E7 ) , were not able to immortalize cells . However the HPV6 E6 gene , in concert with HPV16 E7 , increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone . Interestingly , 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized , whereas neither gene alone was sufficient . Thus , the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16 . Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture , resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer . Additionally , combinations of genes that immortalized HFE cells ( HPV16 E6 plus HPV16 E7 , HPV16 E6 plus HPV6 E7 , and HPV6 E6 plus HPV16 E7 ) also stimulated proliferation . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot207

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 oncogenic potential of a human papillomavirus type 16 ( HPV16 ) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes . The HPV16 variant was able to extend the lifespan of , but failed to immortalize , human keratinocytes . It could however cooperate with an activated ras oncogene to transform primary rodent cells . Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein . DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional , but a deletion in the viral E2 open reading frame was detected . This truncated E2 only weakly stimulated transcription of the viral regulatory region . Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency . These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer . OUTPUT:

enabling replicative immortality

HoC_1shot208

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 " high-risk " human papillomavirus types 16 ( HPV-16 ) and 18 ( HPV-18 ) have been etiologically implicated in the majority of human cervical carcinomas . In these cancers , the viral DNAs are often integrated into the host genome so that expression of the E1 and the E2 genes is lost , suggesting that disruption of these regulatory genes plays an important role in carcinogenic progression . Previous studies defining the viral genes affecting HPV-16 transformation functions have used the " prototype " viral genome , which was cloned from a human cervical carcinoma and later discovered to harbor a mutation in the E1 gene . In this study , we have corrected this mutation and have evaluated the effect of mutations of either the E1 or the E2 gene on the efficiency of HPV-16 immortalization of human keratinocytes . Mutation of either the E1 gene or the E2 gene in the background of a " wild-type " HPV-16 genome markedly increased immortalization capacity . Mutations were also generated in the E2-binding sites located upstream of the P97 promoter , which directs synthesis of the viral E6 and E7 transforming genes . E2 negatively regulates the P97 promoter through binding at adjacent sites . Surprisingly , the mutation of these sites only partially relieved the negative effect of E2 on viral immortalization , implicating additional mechanisms in the E2 repression of viral immortalization functions . Our results provide genetic evidence that the E1 and E2 gene products each can repress HPV-16 immortalization and support the hypothesis that a selective growth advantage is provided by integration of the viral genome in a manner that causes the loss of expression of either E1 or E2 . OUTPUT:

enabling replicative immortality;genomic instability and mutation

HoC_1shot209

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Human papillomavirus type 16 ( HPV16 ) E6 and E7 are selectively retained and expressed in HPV16-associated human genital tumors . E6 is active in several cell culture assays , including transformation of NIH 3T3 cells , trans activation of the adenovirus E2 promoter , and cooperation with E7 to immortalize normal human keratinocytes . Biochemically , the HPV16 E6 protein has been shown to bind to tumor suppressor protein p53 in vitro and induce its degradation in a rabbit reticulocyte lysate . To examine the relationship between the various biological activities of E6 and inactivation of p53 , we tested the abilities of dominant negative mutants of p53 to substitute functionally for E6 in the three cell culture assays . While wild-type p53 inhibited keratinocyte proliferation , both mouse and human mutant p53s , in conjunction with E7 , increased proliferation of the keratinocytes , resulting in generation of immortalized lines . However , in contrast to E6 , mutant p53 was unable to induce transformation or trans activate the adenovirus E2 promoter in NIH 3T3 cells . These results suggest that inactivation of wild-type p53 is necessary for HPV-induced immortalization of human keratinocytes and that different or additional activities are required for E6-dependent transformation and trans activation of NIH 3T3 cells . OUTPUT:

enabling replicative immortality

HoC_1shot210

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 order to determine the in vivo immune response in glioblastoma , monoclonal and polyclonal antibodies specific for inflammatory leukocytes and immunoregulatory products were utilized to stain tissue from four surgical specimens . The more activated the inflammatory cells , the more activated the tumors appeared to be . In the tumor with the largest infiltration ( Case 3 ) , inflammatory cells were stained for interferon-gamma , interleukin-2 , interleukin-1 beta , lymphotoxin , tumor necrosis factor-alpha , and transforming growth factor-beta . The tumor cells also expressed interleukin-1 beta , interleukin-6 , transforming growth factor-beta , tumor necrosis factor-alpha , and prostaglandin E. In contrast , in the tumor with the least inflammatory response ( Case 1 ) , the tumor cells did not express any cytokines . Expression of cytokines by glioma cells was modest in the two cases with modest inflammatory responses . Cellular inflammation , primarily consisting of T cells and macrophages with few or no B cells or natural killer cells , was two- to 15-fold greater outside the tumor than within . In contrast to leukocytes outside the tumor , which were activated and expressing class II major histocompatibility antigens , leukocytes within the tumor parenchyma or at the tumor's edge were negative for these antigens . In the four specimens studied here , the tumor cells themselves were also negative for class II major histocompatibility antigens . These findings , although preliminary , suggest that inflammatory cells within gliomas are inactivated and that glioma cells may increase the expression of immunosuppressive cytokines in response to an increased lymphocyte infiltrate . This observation , if corroborated by more extensive studies , may help to explain the failure of immune treatments in glioblastoma multiforme . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot211

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: NIH-3T3 cells are non-tumorigenic when injected into athymic mice . If these cells are mixed with an extract of basement-membrane proteins ( matrigel ) and injected s.c. , they form locally invasive and highly vascularized tumors . Cells cultured from the NIH-3T3-matrigel-induced tumors showed a transformed phenotype and lacked contact inhibition . When cultured in a gel of matrigel , they proliferated and formed branched and invasive colonies . In contrast , the parental NIH-3T3 cells cultured on matrigel remained as cell aggregates and were not invasive . I.V. injections of the tumor-derived NIH-3T3 cells produced many colonies on the surface of the lungs , whereas the parental NIH-3T3 cells were not metastatic . Zymographic analysis of the conditioned media obtained from both the tumor-derived and parental NIH-3T3 cells demonstrated higher amounts of the 72-kDa gelatinase ( type-IV collagenase ) enzyme in the tumor-derived cells . Also , tumor-derived NIH-3T3 cells , but not parental NIH-3T3 cells , secreted the 92-kDa type-IV collagenase . These studies suggest that the interaction of pre-malignant NIH-3T3 cells with extracellular matrix components may contribute to the process of tumor progression . OUTPUT:

activating invasion and metastasis;inducing angiogenesis;evading growth suppressors

HoC_1shot212

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Elevated serum levels of vasoactive intestinal peptide ( VIP ) are associated with some cases of neuroblastoma and correlate with a favorable prognosis . VIP has previously been shown in our laboratory to cause the in vitro growth inhibition and morphological differentiation of the human neuroblastoma cell line , LA-N-5 . It is now shown that LA-N-5 cells express immunoreactive VIP and bear specific VIP receptors . Antagonism of endogenous VIP , either by competitive inhibition or receptor blockade , increased cell proliferation , suggesting that VIP is operative in normal growth regulation . Intracellular and extracellular levels of VIP were also shown to increase significantly during the retinoic acid-induced differentiation of these cells . Furthermore , a concomitant marked increase in VIP receptor expression was demonstrated with cellular differentiation . These receptors remain functional as evidenced by a matching increase in the level of detectable cAMP generated in response to exogenous VIP . It is concluded that VIP is a normal autoregulator of neuroblastoma cell growth and differentiation , and that retinoic acid-mediated differentiation may be , in part , due to endogenous VIP . OUTPUT:

sustaining proliferative signaling

HoC_1shot213

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Retrovirally induced immunosuppression may elevate the incidence of chemically induced cancers . A proposed hypothesis to explain this relationship is the increased free radical activity observed during retroviral infection and carcinogen activation . We previously found that vitamin E retarded growth of esophageal tumors accompanied by reductions of free radical products . This study investigated the contribution that retroviral immunosuppression has on esophageal cancer induced by the carcinogen N-nitrosomethylbenzylamine ( NMBzA ) , and the response that increased levels of dietary vitamin E has on this induced carcinogenesis . Female C57BL/6 mice received NMBzA or vehicle ( corn oil ) i.p. weekly for 3 weeks . Then some of the mice were infected with LP-BM5 murine retrovirus and fed diets containing 30 IU vitamin E or 172 IU vitamin E/kg of diet . As an assessment of free radical activity , exhaled ethane was measured prior to killing the animals at 26 weeks . Esophagi from the various mice groups were assessed for size and frequency of tumors . Livers homogenates were analyzed for vitamins A and E , lipid fluorescence , conjugated dienes and malondialdehyde . Hepatic levels of vitamin A and E were decreased ( P &lt ; 0.05 ) and indices of lipid peroxidation were greater ( P &lt ; 0.05 ) in NMBzA-treated mice relative to controls . Lipid peroxidation and serum transaminases ( ALT and AST ) were greatest in mice given NMBzA and infected with the retroviruses . Incidence of esophageal tumors were also greatest in the NMBzA-treated , immunocompromised animals . Mice fed vitamin E-supplemented diets showed increased ( P &lt ; 0.05 ) hepatic concentrations of vitamin E and vitamin A , decreased activities of serum transaminases , decreased indices of lipid peroxidation , and decreased size and frequency of esophageal tumors in both the immunocompromised and non-immunocompromised mice . These results suggest that vitamin E plays an antioxidant function that retards the incidence of esophageal cancers in immunocompromised and non-immunocompromised animals . OUTPUT:

avoiding immune destruction

HoC_1shot214

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The immune status of spleen and the effect of surgical treatment in advanced gastric cancer ( AGC ) patients were evaluated by means of testing NK cell activity , T-lymphocyte subsets and circulating immune complex ( CIC ) . The results showed ( 1 ) the significant impairment of NK cell activity and T-lymphocyte subsets , were decreased in CD3+ , CD4+ cells and increased in CD6+ cells resulting in CD4+/CD8+ cell ratio decrease in peripheral blood lymphocytes ( PBL ) , splenic venous blood lymphocytes ( SVL ) and spleen cells ( SC ) of AGC , as compared with PBL of normal population ; ( 2 ) NK cell activity or CD4+/CD8+ cell ratio of SVL and SC were significantly lower than those of PBL in AGC patients , mainly caused by marked decrease of CD4+ cells in SC ; ( 3 ) NK cell activity , CD4+ cells and CD4+/CD8+ cell ratio were significantly elevated in most of AGC cases receiving either radical gastrectomy ( R2+ ) or extensive radical gastrectomy ( R3 ) . A striking declination in CD8+ cells were found only after R3 operation ; ( 4 ) after a short period ( 10-14 days ) or a long period ( 2-4 years ) of radical gastrectomy , NK cell activity and T-lymphocyte subsets showed no significant differences between R2+ and R3 operation . As a rule , AGC would weaken immune function of patients , and along with the development of the tumor , the immunosuppression in the spleen would be generated gradually . For these reasons , a complete tumor resection would be necessary to improve the immunocompetence , and the combined splenectomy might be advisable if indicated . OUTPUT:

avoiding immune destruction

HoC_1shot215

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Although chemotherapy offers promise of increased survival for children with medulloblastoma and glioblastoma multiforme , drug resistance occurs frequently , resulting in tumor progression and death . Resistance to nitrosoureas and methylating agents , which damage DNA , can be mediated by a DNA repair protein , O6-alkylguanine-DNA alkyltransferase ( AGAT ) . Depletion of this protein with alkylguanines or methylating agents , however , restores tumor cell sensitivity to the cytotoxicity of chloroethylnitrosoureas ( e.g. , carmustine [ BCNU] ) . PURPOSE This study was designed to determine whether resistance to the activity of nitrosourea ( the drug BCNU ) in BCNU-resistant human medulloblastoma ( D341 Med ) and human glioblastoma multiforme ( D-456 MG ) can be reversed by the methylating agent streptozocin and the O6-substituted guanines O6-methylguanine and O6-benzylguanine . METHODS Xenografts were grown subcutaneously in athymic BALB/c mice . BCNU was administered as a single intraperitoneal injection at doses of 100 mg/m2 , 75 mg/m2 , or 38 mg/m2--i.e. , 1.0 , 0.75 , or 0.38 , respectively , of the dose lethal to 10% of treated animals ( LD10 ) . Mice were treated intraperitoneally with a single dose of O6-benzylguanine or O6-methylguanine ( 240 mg/m2 ) or with streptozocin ( 600 mg/m2 ) daily for 4 days . Response was assessed by tumor growth delay and tumor regression . AGAT activity in the xenografts was measured at 1 and 6 hours after pretreatment , at the time tumors were excised . RESULTS Pretreatment with O6-benzylguanine , O6-methylguanine , or streptozocin reduced AGAT activity to 4% , 25% , and 95% of control values , respectively , in D341 Med and 0% , 0% , and 25% of control values , respectively , in D-456 MG 1 hour after injection . After 6 hours , levels changed to 7% , 61% , and 116% of control values in D341 Med and 0% , 79% , and 21% of control values in D-456 MG , respectively . Both D341 Med and D-456 MG xenografts were completely resistant to BCNU at its LD10 . Pretreatment with O6-benzylguanine increased BCNU sensitivity in both types of xenograft . In contrast , treatment with BCNU plus O6-methylguanine or streptozocin did not produce growth delays substantially different from those produced by BCNU alone , reflecting the more efficient depletion of AGAT by O6-benzylguanine . Following therapy with BCNU plus O6-benzylguanine at 0.38 LD10 , tumor regressions were seen in eight of 10 D341 Med and in all 10 D-456 MG xenografts . CONCLUSION We recommend comprehensive clinical toxicologic evaluation of combination therapy with O6-benzylguanine plus BCNU , which would allow subsequent design of phase I clinical trials . OUTPUT:

genomic instability and mutation

HoC_1shot216

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Semi-conservative replication of double-stranded DNA in eukaryotic cells is an asymmetric process involving leading and lagging strand synthesis and different DNA polymerases . We report a study to analyze the effect of these asymmetries when the replication machinery encounters alkylation-induced DNA adducts . The model system is an EBV-derived shuttle vector which replicates in synchrony with the host human cells and carries as marker gene the bacterial gpt gene . A preferential distribution of N-methyl-N-nitrosourea ( MNU)-induced mutations in the non transcribed DNA strand of the shuttle vector pF1-EBV was previously reported . The hypermutated strand was the leading strand . To test whether the different fidelity of DNA polymerases synthesizing the leading and the lagging strands might contribute to MNU-induced mutation distribution the mutagenesis study was repeated on the shuttle vector pTF-EBV which contains the gpt gene in the inverted orientation . We show that the base substitution error rates on an alkylated substrate are similar for the replication of the leading and lagging strands . Moreover , we present evidence that the fidelity of replication opposite O6-methylguanine adducts of both the leading and lagging strands is not affected by the 3 ' flanking base . The preferential targeting of mutations after replication of alkylated DNA is mainly driven by the base at the 5 ' side of the G residues . OUTPUT:

genomic instability and mutation

HoC_1shot217

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The involvement of signal transduction systems in the initial attachment of two murine B16 melanoma clones of differing metastatic potential to extracellular matrix components was examined to learn more of the early events in cell-matrix interaction . Clones of high and low metastatic capacity attached similarly in the absence of any stimulators , exhibiting a two phase time course of attachment with 100% attachment by 60 min . A slight difference in attachment characteristics between the clones was seen in response to phorbol ester stimulation , which significantly inhibited attachment of the low metastatic clone but which had no effect on the highly metastatic clone . Total protein kinase C activity and distribution was similar for both clones . Attachment of both clones was severely reduced , however , if intracellular calcium was elevated or intracellular calmodulin inhibited . This study suggests that signal transduction mechanisms are involved in melanoma cell attachment to matrix proteins and offers an approach to pharmacological manipulation of these cell-matrix interactions which may be relevant to reducing metastatic spread . OUTPUT:

activating invasion and metastasis

HoC_1shot218

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Normal human lung fibroblast diploid cells , WI-38 , become senescent after a definite number of divisions . VA-13 is a line of immortalized cells established by transformation of WI-38 cells by SV40 virus . To determine whether SV40 large T ( SV40-T ) antigen is essential for this immortalization of WI-38 cells we introduced an antisense gene for T antigen into VA-13 . Two morphologically different types of antisense transformant ( VA-AS5-8 and VA-AS37-8 ) were obtained . In both antisense transformants the expression of T antigen was reduced by more than 70% as compared to that in the parent cells . The morphology of the antisense transformants indicated a partial conversion to the senescent phenotype of WI-38 . The relative number of cells in the S phase of the antisense transformants was decreased as compared to that in cultures of VA-13 and about 50% of cells were at G1/0 . The doubling time of the transformants was prolonged to close to the doubling time of WI-38 . The level of expression of retinoblastoma protein ( pRB ) complexed with SV40-T antigen of the antisense transformants was significantly decreased although the level of total pRB was much higher than that in VA-13 . The pRB was present exclusively in the underphosphorylated form . Thus , the decreased level of formation of the complex between SV40-T and pRB or the underphosphorylation of pRB may explain the suppression of growth of antisense transformants . Together , these results show that an antisense gene for SV40-T antigen can efficiently block the cell proliferation and the cell immortalization of VA-13 cells . OUTPUT:

enabling replicative immortality;sustaining proliferative signaling

HoC_1shot219

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: c-myc , c-erbB-2 , and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas . The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues . Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors , while the level of expression in normal breast tissue was much less than that in breast cancer . Membrane staining of the c-erbB-2 protein was demonstrated in 29% ( 4 of 14 ) of noninvasive ductal carcinomas and in 45% ( 19 of 42 ) of invasive breast carcinomas . None of the 11 normal breast tissue samples was positive . The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue , 4.57 +/- 1.36% for noninvasive ductal carcinoma , and 12.76 +/- 2.18% for invasive breast cancer . In 42 invasive breast carcinomas , the expression of c-myc , c-erbB-2 , and Ki-67 proliferation marker were compared with lymph node status , estrogen receptor status , progesterone receptor status , and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status . We concluded that they might be additional prognostic factors for breast carcinoma . OUTPUT:

sustaining proliferative signaling

HoC_1shot220

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 modifying effects of an immunosuppressive agent , 6-mercaptopurine ( 6-MP ) , on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride ( CCl4 ) or furfural were studied in male F344 rats . Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression , and significantly enhanced the induction of gamma-glutamyltranspeptidase ( GGT)-positive foci and nodules in the CCl4 but not furfural case . Glutathione S-transferase P ( GST-P)-positive preneoplastic lesions were not affected . Moreover , phenobarbital ( PB ) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model , no promotion influence being exerted after treatment with the non-carcinogenic furfural . This study , therefore , suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural . OUTPUT:

avoiding immune destruction

HoC_1shot221

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Amplification of the HER-2 ( c-erbB-2 ) gene and overexpression of the p185HER-2 gene product is found in approximately one-third of primary human breast and ovarian cancers and is associated with a poor clinical outcome of early relapse and death . The HER-2 gene encodes a cell-surface growth factor receptor with intrinsic tyrosine kinase activity . Wild-type human HER-2 has been shown to act as a potent oncogene when over-expressed in mouse fibroblasts . Recent data suggest that the mechanism by which HER-2 mediates transformation requires the interaction of the epidermal growth factor ( EGF ) receptor . To test whether overexpression of normal human HER-2 can transform cells independently of the EGF receptor , we have introduced multiple copies of HER-2 into the EGF receptor-negative cell line , NR6 , and have performed assays for both transformation and tumorigenicity . Engineered NR6 cells that overexpress the HER-2 gene product display a highly transformed and tumorigenic phenotype as compared with control cells . Additionally , a monoclonal antibody to the extracellular domain of the HER-2 receptor is able to inhibit the proliferation of the overexpressing cells in vitro as well as tumor growth in vivo . This study provides clear evidence that HER-2-mediated transformation can be achieved independently of the EGF receptor . OUTPUT:

sustaining proliferative signaling

HoC_1shot222

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: One of the immunosuppressive effects of both ultraviolet ( UV ) light and chemical carcinogens is to deplete Langerhans cells ( LC ) from the epidermis , suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis . Retinoids such as all-trans-retinoic acid ( RA ) are natural or synthetic derivatives of vitamin A ; RA binds to nuclear receptors in the skin , effecting transcription of a wide range of genes . Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate ( TPA ) from depleting the density of LC in murine epidermis . In contrast , topical RA did not itself alter the normal LC density . RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer . Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells ( Thy-1+ dEC ) . However , the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation . The reasons for this are unclear , however , it is possible that RA does not inhibit some other immunosuppressive effect of UV light . Temarotene , a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis . Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis . OUTPUT:

avoiding immune destruction

HoC_1shot223

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Results generated by the immunohistochemical staining with PC10 , a new monoclonal antibody recognizing PCNA ( a nuclear protein associated with cell proliferation ) in formalin-fixed and paraffin-embedded tissue were compared with those of Ki-67 labeling and DNA flow cytometry in 47 consecutive non-small cell lung cancer ( NSCLC ) . PCNA reactivity was observed in all samples and confined to the nuclei of cancer cells . Its frequency ranged from 0 to 80% ( 37.7 +/- 23.6 ) and larger sized , early-staged and DNA aneuploid tumors expressed a significant higher number of PCNA-reactive cells . The PCNA and Ki-67 labeling rates were closely correlated ( r = 0.383 , P = 0.009 ) . By flow cytometry , we observed a good correlation among PCNA labeling and S-phase fraction ( r = 0.422 , P = .0093 ) and G1 phase ( r = 0.303 , P = .051 ) of the cell cycle . Results indicate that PCNA labeling with PC10 is a simple method for assessing the proliferative activity in formalin-fixed , paraffin-embedded tissue of NSCLC and correlates well with Ki-67 labeling and S-phase fraction of the cell cycle . OUTPUT:

sustaining proliferative signaling

HoC_1shot224

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: HER-2/neu gene expression , DNA ploidy and proliferation index were studied in 250 cases of breast cancer . Expression of HER-2/neu was determined by using an antibody to the HER-2/neu receptor . Ki-67 antibody was used to determine the proliferation index of the breast cancers , and the Feulgen method was used to assess DNA amounts in the tumor cells . Histochemical staining was quantitated by image analysis . Of the cancers studied , 72 were positive for overexpression of HER-2/neu protein ; of these , 62 ( 86% ) possessed near-tetraploid DNA content , and 47 ( 65% ) had more than one G0G1 stem line ( polyploid ) of DNA distribution . Cells from the cases negative for HER/2-neu overexpression contained DNA amounts that ranged from diploid to varying degrees of aneuploid . A significant difference in the amounts of cellular proliferation in HER-2/neu overexpressing cancers was found between those that expressed the HER-2/neu receptor on their membranes and those that exhibited mainly cytoplasmic receptors . OUTPUT:

sustaining proliferative signaling

HoC_1shot225

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Reactive oxygen species ( ROS ) produced by phagocytic cells induce oxidative stress during chronic inflammation . ROS play a role in the pathogenesis of a broad range of diseases including autoimmune , cardiac and neoplastic abnormalities . We found that sera of patients with a variety of inflammatory dermatoses contain elevated levels of antibodies ( Ab ) binding to an oxidized DNA base derivative , 5-hydroxymethyl-2'deoxyuridine ( HMdU ) coupled to bovine serum albumin , as determined by the enzyme-linked immunosorbent assay . Patients with immune complex diseases and a history of neoplasm elaborated the highest titers of anti-HMdU Ab . Titers from sera of psoriatic subjects were lower than from the aforementioned groups but were still significantly elevated ( p &lt ; 0.001 ) above those of healthy controls . Treatment of inflammatory dermatoses with systemic antiinflammatory and cytotoxic drugs significantly lowered the titers [ p &lt ; 0.005 ( immune complex ) or p &lt ; 0.001 ( psoriasis and neoplastic ) diseases ] , suggesting that this assay may be of value in monitoring the response to therapy in these diseases . OUTPUT:

tumor promoting inflammation

HoC_1shot226

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 panel of primary human cells and virus-transformed derivatives were tested for events that coincide with immortalization . In all primary and precrisis cells , two proteins of 92 and 150 kDa that shared an epitope with p53 were found ; in most of their immortalized derivatives , however , they were absent . Expression of these proteins may be involved in senescence . OUTPUT:

enabling replicative immortality

HoC_1shot227

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Lipoprotein lipase ( LPL ) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins . LPL is a member of a family of hydrolytic enzymes that include hepatic lipase and pancreatic lipase . Based on primary sequence homology of LPL to pancreatic lipase , Ser-132 , Asp-156 , and His-241 have been proposed to be part of a domain required for normal enzymic activity . We have analyzed the role of these potential catalytic residues by site-directed mutagenesis and expression of the mutant LPL in human embryonic kidney-293 cells . Substitution of Ser-132 , Asp-156 , and His-241 by several different residues resulted in the expression of an enzyme that lacked both triolein and tributyrin esterase activities . Mutation of other conserved residues , including Ser-97 , Ser-307 , Asp-78 , Asp-371 , Asp-440 , His-93 , and His-439 resulted in the expression of active enzymes . Despite their effect on LPL activity , substitutions of Ser-132 , Asp-156 , and His-241 did not change either the heparin affinity or lipid binding properties of the mutant LPL . In summary , mutation of Ser-132 , Asp-156 , and His-241 specifically abolishes total hydrolytic activity without disrupting other important functional domains of LPL . These combined results strongly support the conclusion that Ser-132 , Asp-156 , and His-241 form the catalytic triad of LPL and are essential for LPL hydrolytic activity . OUTPUT:

genomic instability and mutation

HoC_1shot228

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Human diploid fibroblasts have a limited life span in vitro , and spontaneous immortalization is an extremely rare event . We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization . Comparison of a preimmortal transformant ( SVtsA/HF-A ) with its uncloned and cloned immortalized derivatives ( AR5 and HAL ) has failed to reveal any major alteration involving the simian virus 40 genome . Karyotypic analysis , however , demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21 . The karyotypic analysis was corroborated by DNA analyses . Southern analysis demonstrated that only one copy of three proto-oncogene loci ( ros1 , c-myb , and mas1 ) on 6q was retained in immortal cells . Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 ( D6S87 ) showed loss of heterozygosity . In addition , elevated expression of c-myb ( 6q22-23 ) was observed . We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization , consistent with the presence of a growth suppressor gene . OUTPUT:

enabling replicative immortality

HoC_1shot229

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 new cell line , CB109 , has been established from a human glioblastoma multiforme . The cytoskeleton was positive for glial fibrillary acidic protein , vimentin and fibronectin . Hyaluronan ( HA ) and the HA-binding protein hyaluronectin ( HN ) were expressed in the cell cytoplasm and in the extracellular matrix of spheroids and plated cells . Hyaluronidase did not prevent spheroid formation suggesting that HA was not involved in the cell-cell adhesion . HA precoating prevented cell adherence to the plates and favoured spheroid formation . HA was secreted in relatively large amounts into the culture medium . High performance liquid chromatography demonstrated that HA was in the high molecular weight form . The rate of HN secretion by cells was very low . Basic fibroblast growth factor significantly increased the proliferation in vitro and tumour growth after grafting into nude mice . The epidermal growth factor receptor was not expressed on cultivated CB109 cells . Cytogenetic analysis showed polysomy 7 , structural rearrangement of chromosome 10 short arm and a translocation 13q13-q14 without detectable alteration of the RB gene . OUTPUT:

sustaining proliferative signaling

HoC_1shot230

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize ; they have been called metastasizing mixed tumor ( MZMT ) of salivary glands . We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT . At the time of discovery of metastatic disease , the patients , six women and five men , ranged in age from 20 to 83 years . Primary sites of involvement included the parotid gland ( eight cases ) , submandibular gland ( two cases ) , and the nasal septum ( one case ) . With one exception , all the patients had at least a single recurrences of their primary mixed tumor , but two or more recurrences were the norm before development of metastatic foci . The metastases were discovered from six to 52 years following the occurrence of the primary tumor . Metastatic deposits were identified in bone , lung , regional lymph nodes , skin , kidney , retroperitoneum , oral cavity , pharynx , calvarium , and central nervous system . The metastases either occurred simultaneously with an episode of recurrent mixed tumor ( n = 5 ) or from 5 to 29 years after a recurrence ( n = 6 ) . The treatment of the primary , recurrent , and metastatic neoplasms was surgical excision . Follow-up , ranging from 8 months to 16 years following the diagnosis of MZMT , revealed seven patients to be alive without disease ( 64% ) and two dead of causes unrelated to metastatic disease ( 18% ) . Two patients ( 18% ) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors . Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases . Aneuploid DNA cell content was identified in two of the cases . DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors . Retrospective analysis of histologic parameters ( mitotic rate , cellular pleomorphism , infiltrative growth , vascular or lymphatic invasion ) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms . OUTPUT:

activating invasion and metastasis;genomic instability and mutation

HoC_1shot231

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Despite an increasing incidence of human breast cancer , its etiology remains unknown . Since some environmental chemicals are stored in human breast fat and are rodent mammary carcinogens , determining the genotoxic potential of environmental agents in this key target tissue is important . An assay was developed for detecting genotoxic activity , as unscheduled DNA synthesis ( UDS ) , induced by chemicals and UV radiation in early passage cultures of normal human mammary epithelial cells ( HMEC ) derived from 5 different women . In order to measure UDS in culture , reduction in the percentage of cells in S-phase was accomplished either by depriving the cells of epidermal growth factor and bovine pituitary extract or by contact inhibition of growth . Cultures were incubated with test chemicals for 24 h in the presence of [ 3H]-thymidine . UDS was quantitated autoradiographically as net grains per nucleus ( nuclear grains minus cytoplasmic background , population average ) with &gt ; or = 6 net nuclear grains considered in repair for any individual cell . A positive response was observed with UV radiation , benzo(a)-pyrene , aflatoxin B1 , ethylmethanesulfonate , 1,6-dinitropyrene , 2-acetylaminofluorene , and tobacco smoke condensate but not 7,12-dimethylbenz(a)anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin . These results demonstrate that HMEC from all 5 women examined have the ability to metabolize a variety of environmental chemicals to DNA-reactive forms . Furthermore , some chemicals known either to cause mammary cancer in rodents or to be contaminants in human breast tissue are genotoxic in HMEC . A positive response in passage 9 cultures was observed only with direct acting agents , suggesting that HMEC may lose their metabolic capabilities in longer-term cultures . The HMEC UDS assay may be used to address the role of environmental agents in human breast cancer by determining whether chemicals are DNA reactive or metabolized to DNA reactive species in this critical target tissue . OUTPUT:

genomic instability and mutation

HoC_1shot232

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: DNA single-strand breaks and associated growth inhibition induced by the thymidylate synthase inhibitor N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazoline-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid ( ICI D1694 ) were quantitated using the human ileocecal adenocarcinoma cell line , HCT-8 . The effects of different concentrations and schedules of [ 6R,S]-5-formyltetrahydrofolate ( [ 6RS]LV ) and 2'-deoxy-thymidine ( dThd ) on drug growth inhibition and DNA damage were also evaluated . The drug concentrations for 50% inhibition of cell growth in culture following 2-h and 72-h exposures were 0.073 and 0.003 microM , respectively . After a 2-h drug exposure , the occurrence of DNA single-strand breaks ( SSBs ) was time dependent . It was detectable at 8 h and reached a maximum at about 24 h , 34 +/- 3 ( SD ) and 305 +/- 34 rad equivalents with 0.1 microM ( 50% inhibition concentration ) and 1.0 microM ( 90% inhibition concentration ) ICI D1694 , respectively . A significant level of DNA SSBs ( 101 +/- 13 rad equivalents ) was still detectable at 72 h after the 2-h treatment with 1 microM ICI D1694 . No significant level of DNA SSBs was detected when cells were exposed simultaneously to ICI D1694 and 20 microM [ 6RS]LV . Complete rescue of drug-induced DNA SSBs could be achieved when cells were exposed to 10 microM dThd starting no later than 4 h after drug treatment . The growth inhibition of ICI D1694 was abrogated by [ 6RS]LV in a concentration-dependent manner . Complete protection was achieved when cells were exposed simultaneously to 1 microM ICI D1694 and 5 microMs [ 6RS]LV or to 3 microMs dThd immediately after drug treatment . The results demonstrate that : ( a ) the growth inhibition of ICI D1694 is a function of time and schedule ; ( b ) the growth inhibition is accompanied by extensive DNA single-strand breaks and slow repair ; ( c ) at 1 microM ICI D1694 , 3 microMs dThd and 5 microMs [ 6RS]LV can completely rescue cells from drug effects when dThd is added up to 4 h following drug treatment or when [ 6RS]LV is given in combination with the drug ; ( d ) interference of [ 6RS]LV with ICI D1694 action may be occurring at the level of drug uptake and at intracellular targets , while dThd interferes with the drug action at intracellular targets . OUTPUT:

genomic instability and mutation

HoC_1shot233

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Numerous studies have reported a correlation between production of 72-kDa ( MMP-2 ) and 92-kDa ( MMP-9 ) type-IV collagenases/gelatinases and the metastatic potential of cancer cells . An abrogating effect of tissue inhibitors of metalloproteinases ( TIMP-1 and TIMP-2 ) on metastases has also been noted . In this report we have used sensitive enzyme-linked immunoassays to measure MMP-2 , MMP-9 , TIMP-1 and TIMP-2 levels in eight human lung-cancer cell lines which were characterized for biological behavior in nude mice . We demonstrated that the Calu-6 and A549 cell lines with the highest metastatic , invasive and tumorigenic potential secreted the highest levels of MMP-2 . MMP-9 and TIMP-1 secretions were comparatively low in all cell lines . TIMP-2 secretion , which exceeded MMP-2 secretion for all cell lines , did not correlate with metastatic potential . To further explore these correlations , the metastatic Calu-6 cell line was transfected with a K-rev-1 cDNA expression construct . The K-rev revertant cell lines demonstrated a more differentiated phenotype and were less tumorigenic , invasive and metastatic in nude mice . Nonetheless , the Calu-6 revertant cell lines secreted higher levels of MMP-2 than the parent cell line . In conclusion , invasion and metastasis by lung-cancer cells requires not only enhanced MMP production , but also other less well-understood tumorigenic characteristics . The multiplicity of factors required by cancer cells for dissemination helps to explain the minute fraction of cancer cells from a primary tumor that ever develop into a metastasis . OUTPUT:

activating invasion and metastasis

HoC_1shot234

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol . MCF-7 cells were treated with growth factors in the presence and absence of oestradiol . Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF-alpha ) and basic fibroblast growth factor ( bFGF ) . Platelet derived growth factor ( PDGF ) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol . In the absence of oestradiol , there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive . In the presence of oestradiol , the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist . Overall , bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin . The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression . OUTPUT:

sustaining proliferative signaling

HoC_1shot235

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Previous reports showed that treatment with non-steroidal anti-inflammatory agents ( NSAIA ) can alter the growth profile of a variety of tumours . In this study , the effect of NSAIA treatment on the growth of the primary tumour and the appearance of spontaneous pulmonary metastases , was investigated . A mammary adenocarcinoma of non-detected immunogenicity , C7HI , was grafted subcutaneously in the lateral flank of Balb/c mice . Oral treatment with approximately 1 mg kg-1 day-1 piroxicam delayed both tumour growth and the growth of pulmonary metastases . Survival of mice bearing the primary tumour was significantly lengthened by anti-inflammatory treatment . Similarly , in separate experiments , after surgical removal of the primary tumour by day 34 after grafting , the group of mice treated orally with piroxicam also exhibited a higher survival rate than the control group . Upon surgical removal of the primary tumour 34 days after grafting , piroxicam treatment significantly decreased both the number and size of pulmonary metastases . The results of this study lends support to the hypothesis that inhibition or modulation of inflammation may delay tumour organisation and growth . It is suggested that piroxicam treatment may be an appropriate adjunct therapy to delay the appearance of pulmonary metastases and to increase life-expectancy in a host whose primary tumour has to be surgically removed . OUTPUT:

activating invasion and metastasis;tumor promoting inflammation

HoC_1shot236

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 quercetin , a flavonoid found in many plants , on the proliferation of human leukemic T-cells was analyzed . Quercetin reversibly blocked the cell cycle at a point 3-6 h before the start of DNA synthesis . Expression of the growth-related genes histone H4 , cyclin A and B , and p34cdc2 was suppressed in cells blocked with quercetin . Comparison of the quercetin arrest points with those of the cell cycle inhibitors aphidicolin and mimosine revealed a temporal order of arrest points in G1 of quercetin , mimosine , and aphidicolin . Mimosine and aphidicolin did not inhibit the expression of cyclin A or p34cdc2 , whereas all three reagents inhibited expression of cyclin B. Low concentrations of the protein inhibitor cycloheximide inhibited release of the quercetin but not the mimosine or aphidicolin block . A [ 35S]methionine-labeled M(r) 60,000 protein disappeared in quercetin-treated cells and was rapidly synthesized after removal of quercetin , suggesting the possibility that the M(r) 60,000 protein induces DNA synthesis after the cell is released from a quercetin block . These results suggest the usefulness of quercetin in studies of the regulation of late G1 phase . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot237

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Previous studies have demonstrated that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ( NNK ) induced liver tumors in F344 rats but not in Syrian golden hamsters . The aim of this study was to determine whether there was a correlation between the persistence of O6-methylguanine ( O6-mGua ) adducts and the rate of recovery of O6-methylguanine-DNA methyltransferase ( O6-mGuaT ) after depletion in the liver and susceptibility to NNK in F344 rat and Syrian golden hamster injected s.c. with NNK ( 80 mg/kg ) . The levels of both 7-methylguanine and O6-mGua reached a maximum 24 h after NNK treatment . O6-mGua in NNK-treated rat liver was undetectable after 48 h . In the rat , the depletion of O6-mGuaT activity occurred within 4 h following NNK treatment . A subsequent rapid recovery of enzyme activity was observed 36 h after NNK exposure . In contrast , high levels of O6-mGua persisted in hamster liver DNA and no O6-mGuaT activity was detected up to 336 h after NNK injection . Thus , the persistence of O6-mGua in hamster liver is most likely related to a lack of recovery of the O6-mGuaT . These results suggested that factors other than O6-mGua may be determining NNK-induced hepatocarcinogenesis in rats . An aldehyde generated by alpha-hydroxylation of NNK , 4-oxo-4-(3-pyridyl)butanal , inhibited O6-mGuaT activity in rat hepatocytes , suggesting that this aldehyde contributes to the carcinogenicity of NNK by inhibiting this repair enzyme . OUTPUT:

genomic instability and mutation

HoC_1shot238

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The aim of this study was to address whether there is a fundamental difference in regulation of histone gene expression in cells that have become quiescent but retain the ability to proliferate , compared with those cells that have differentiated . We compared multiple levels of regulation of histone gene expression during 3T3-L1 pre-adipocyte differentiation . Confluent cells induced to differentiate by treatment with insulin , dexamethasone , and isobutylmethylxanthine initially exhibited an increased proliferative response compared with cells given serum alone . This initial differentiation response was associated with a twofold increase in both histone gene transcription and cellular histone mRNA levels , as well as with enhanced sequence-specific binding of nuclear factors to the proximal cell-cycle-regulatory element of the H4 histone promoter . Transforming growth factor beta 1 , an inhibitor of 3T3-L1 differentiation , increased both the percentage of proliferating cells and the cellular levels of histone mRNA when given in addition to serum stimulation , but no enhancement of these parameters was observed upon addition of TGF beta 1 to the differentiation treatment . Interestingly , although TGF beta 1 enhanced binding of nuclear factors to the proximal cell cycle regulatory element of the histone promoter , these protein/DNA interactions were not associated with an increase in histone transcription . Our results are consistent with the down-regulation of histone gene expression at confluency being controlled primarily at the post-transcriptional level , in contrast to an increased involvement of transcriptional down-regulation at the onset of differentiation . OUTPUT:

sustaining proliferative signaling

HoC_1shot239

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Apoptosis , programmed cell death , was previously shown to be induced by the mAb anti-APO-1 ( IgG3 , kappa ) by binding to the APO-1 cell surface Ag , a new member of the nerve growth factor/TNF receptor superfamily . To investigate the role of the Ig H chain Fc regions we compared induction of apoptosis by the original mAb IgG3 anti-APO-1 with anti-APO-1 F(ab')2 fragments and different anti-APO-1 isotypes ( IgG1 , IgG2b , IgG2a , and IgA ) isolated by sequential sublining . We found that IgG3 was the most active isotype ; IgG1 , IgG2a , and IgA showed intermediate activity , and IgG2b and F(ab')2 were inactive . Cytotoxic activity of the inactive or less active antibody preparations was fully reconstituted by protein A , anti-mouse Ig , or anti-mouse Ig F(ab')2 , respectively . Thus , APO-1-mediated induction of apoptosis was dependent on efficient cross-linking of APO-1 cell surface Ag , indirectly augmented by anti-APO-1 Fc-Fc self-aggregation . Because of their different in vitro activity we selected IgG3- , IgG2b- , and IgA anti-APO-1 to test their antitumor activity against solid human B lymphoblastoid tumors in SCID mice . The isotypes showed a different serum half-life ( IgG3 : 9.2-10.4 days , IgG2b : 1.9-2.6 days , and IgA : 14.1-29.2 h ) and a different initial tumor localization 4 h after i.p. injection ( IgG3 around the blood vessels , IgG2b homogeneously , and IgA heterogeneously distributed in the tumor ) . All antibody preparations induced tumor regression by induction of apoptosis , even IgG2b anti-APO-1 inactive in vitro without cross-linking . The activity of IgA anti-APO-1 , which did not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity indicates that apoptosis may be used as the main if not the only mechanism of induction of tumor regression in vivo . As with in vitro , IgG3 anti-APO-1 was the most effective isotype also in vivo . This result suggests that cross-linking of APO-1 on the tumor cell surface may also be required for tumor regression by apoptosis in vivo . Taken together , our data show that selective targeting of apoptosis to tumors may be an efficient antitumor mechanism . OUTPUT:

resisting cell death

HoC_1shot240

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: At present , isoniazid ( INH ) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer , although it is not clear whether or not this reduces the antitumor efficacy of BCG . In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs . INH was given on the 3 days around each BCG instillation . We found that the administration of INH severely impaired the immunological effects of BCG . The induction of mononuclear cell infiltration in the bladder wall was reduced . Enlargement of the regional lymph nodes ( weight and number of cells ) , and increase of MHC Class II expression on the lymph node cells , normally observed after intravesical BCG administration , were inhibited by INH . Systemic immunity , measured by the DTH reaction in the skin to PPD , was also diminished due to the combined treatment of BCG with INH . When INH was administered during the last 4 of 6 BCG instillations , the immune response to BCG was still impaired . A five-fold increase of the dose of BCG did not overcome the effect of INH . INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced . Although INH concentrations in the urine were high at the onset of the instillation , in vitro experiments indicated that the effect of INH may not be caused by killing of the BCG organisms shortly after application in the bladder . In conclusion , our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG . As this response may be important for the antitumor effect of BCG , urologists should be cautious with the prophylactic use of INH . The influence on the antitumor efficacy is now investigated in man . OUTPUT:

avoiding immune destruction

HoC_1shot241

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Histopathological features of the lymph node involvement were studied in 104 patients with thoracic esophageal cancer who underwent subtotal esophagectomy combined with extended radical lymph adenectomy in cervicothoracoabdominal region . Metastatic involvement was found in a total number of 503 lymph nodes from 73 patients by histologic examination . The mean of long and short diameter was found to be less than 5mm in 125 ( 24.9% ) of these 503 nodes . The involved area on the section was less than one third in 149 nodes ( 29.6% ) , and was significantly smaller in mediastinal lymph nodes than those in cervical or abdominal ones . Sixty-seven ( 13.3% ) of 503 nodes were partially invaded by micrometastasis of 1mm or less in diameter . Micrometastasis also more frequently occurred in mediastinal nodes with a statistically significant difference . Extranodal proliferation ( ENP ) of cancer cells was found in 106 nodes ( 21.1% ) , and extranodal lymphatic and/or blood vessel invasion ( ENly , v ) was also recognized in 60 nodes ( 11.9% ) . Micrometastasis and ENP with or without ENly , v were found in 24 ( 32.9% ) and 29 ( 39.7% ) of 73 patients with positive lymph node metastasis , respectively . Postoperative survival rate in patients with micrometastasis and/or ENP with or without ENly , v was inferior to that in patients with neither of them . OUTPUT:

activating invasion and metastasis

HoC_1shot242

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 cytotoxic activity of cyclosporin A ( CsA ) and the three non-immuno-suppressive CsA analogues B3-243 , WO-039 and B3-665 were studied in tumor cell lines representing both classical and atypical forms of multidrug resistance ( MDR ) : T-ALL GM3639 L100 cells selected for vincristine ( vcr ) resistance and displaying characteristics of classical MDR , including P-glycoprotein ( pgp ) expression and increased drug efflux which can be inhibited by pgp blockers ( e.g. verapamil ) , and U-1285/ADR , a small cell lung cancer ( SCLC ) cell line selected for doxorubicin resistance which lacks pgp , is insensitive to pgp-blockers and shows cross resistance to cis-platinum . At 1 micrograms/ml CsA was the most active agent in reversing Vcr resistance in L100 cells followed by B3-243 and WO-039 , with no effect of B3-665 . Parental LO cells were only marginally sensitized to Vcr by these agents . No reversing effect of any cyclosporin was observed in the U-1285/ADR or its parental cell line . Compared to LO cells , L100 cells showed a marked hypersensitivity to CsA &gt ; B3-243 &gt ; WO-039 with B3-665 being inactive . No collateral sensitivity was observed for cyclosporins in U-1285/ADR cells . Although of different magnitude , the pattern of cytotoxic activity for the different cyclosporins alone closely parallelled that of L100 cells for U-1285 , U1285/ADR and LO cells . The results indicate that not only the collateral sensitivity in classical MDR but also the cytotoxic actions of cyclosporins per se on tumor cells alone are independent of immunosuppressive activity . The results also suggest a structure-activity relationship for cyclosporin-induced cytotoxicity similar to , but independent of , MDR reversing activity . OUTPUT:

avoiding immune destruction

HoC_1shot243

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 transforming growth factor-beta 1 ( TGF-beta 1 ) and interleukin-1 beta ( IL-1 beta ) on LDL receptor in Hep G2 cells was investigated . A greater than two-fold stimulation of the binding and internalisation of [ 125I]-labelled LDL at 37 degrees C was observed after an 18-h incubation of the cells with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml compared with control cells . Scatchard analysis of the binding of [ 125I]-labelled LDL at 4 degrees C after an 18-h incubation of the cells with 1170 units/ml IL-1 beta and 5 ng/ml TGF-beta 1 showed that they were both acting primarily by increasing LDL receptor number . The increase in LDL receptor activity could not be attributed to an increase in cell proliferation as TGF-beta 1 at concentrations from 0.05 ng/ml to 50 ng/ml had no significant effect on either cell number or [ 3H]thymidine incorporation into DNA whilst IL-1 beta inhibited DNA synthesis by more than 80% at a concentration of 11,700 units/ml but had significant effect on cell number . Cholesterol biosynthesis from [ 14C]acetate , in contrast to the stimulation of LDL receptor activity , was inhibited by approximately two-fold by incubation with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml . OUTPUT:

sustaining proliferative signaling

HoC_1shot244

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Using monolayer cultures of clonally isolated C3 and T5 rat prostate cancer cells , we determined that acidic ( aFGF ) and basic ( bFGF ) fibroblast growth factors profoundly enhanced T5 cell thymidine incorporation with half-maximum stimulation at 0.53 and 0.35 ng/ml , respectively . In contrast , aFGF or bFGF enhancement of C3 cell thymidine incorporation was about 5% of that of T5 cells , and effects were principally mitogen concentration independent . Saturation analyses and cross-linking studies established that both C3 and T5 cells contained high-affinity FGF receptors of 120 and 145 kilodaltons and that receptor content and Kd of C3 and T5 cells were comparable. aFGF or bFGF stimulation of T5 cell thymidine incorporation profoundly decreased as cell plating density was reduced from 1.5 x 10(5) to 1.0 x 10(4) cells/well . The modest response of C3 cells to either aFGF or bFGF also decreased as cell plating density was reduced . Because heparin preserves FGF biological activity and enhances bFGF binding to high-affinity FGF receptors , we examined the effect of heparin on FGF stimulation of C3 cell thymidine incorporation . We found that changes in cell plating density and/or medium heparin concentration had variable , inconsistent effects . These were C3 cell plating density associated and included inhibition or modest enhancement of FGF effects . Binding analyses established that high-affinity bFGF binding of C3 and T5 cells immediately prior to assessing FGF-stimulated thymidine incorporation was comparable and independent of cell plating density , implying that C3 cell FGF insensitivity was not attributable to differences in C3 and T5 cell FGF receptor content at the time of mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS ) OUTPUT:

sustaining proliferative signaling

HoC_1shot245

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium . The effects on cell proliferation , glycolysis , and glutaminolysis were investigated . Of all adenosine derivatives tested , AMP was the most efficient inhibitor of cell proliferation . In AMP-treated cells , DNA synthesis decreased , whereas RNA and protein syntheses rose normally with time . In terms of carbohydrate metabolism , lactate production from glucose was drastically reduced ; therefore , most of lactate produced must have been derived from glutamine . Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed . In contrast , actual glycolytic flux rates declined , whereas key glycolytic enzyme activities increased . Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells . Based on the lowered NAD level in the AMP-treated cells , lactate dehydrogenase , but not malate dehydrogenase , was impaired ; thereby the whole of glycolysis was inhibited . In compensation , glutamine catabolism was increased . NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels . A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented . OUTPUT:

cellular energetics

HoC_1shot246

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Gamma-radiation , tetrandrine , bistratene A , and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human BM13674 cell line 8 h after treatment . Apoptosis induced in BM13674 cells by these diverse agents was markedly inhibited by 1 microM okadaic acid , a tumour promoter that inhibits protein phosphatases 1 and 2A . This compound also inhibited the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation . The inhibition of apoptosis was confirmed using fluorescence microscopy and DNA gel electrophoresis . Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations . Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells . The present data provides further support that posttranslational modification of proteins , in particular , phosphorylation/dephosphorylation status , plays an important role in inhibition/activation of programmed cell death in different human cells after exposure to several cytotoxic agents . OUTPUT:

resisting cell death

HoC_1shot247

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Intracellular pH ( pHi ) plays a critical role in the entry of cells into the DNA-synthesis phase of the cell cycle . Alterations in pHi may contribute to abnormal proliferative responses such as those seen in tumorigenic cells . We observed that alkaline stress leads to genomic transformation of Madin-Darby canine kidney ( MDCK ) cells . Transformed cells ( F cells ) form " foci " in culture , lack contact inhibition , and are able to migrate , typical characteristics of dedifferentiated tumorigenic cells . F cells exhibit spontaneous biorhythmicity . Rhythmic transmembrane Ca2+ flux activates plasma membrane K+ channels and Na+/H+ exchange . This leads to periodic changes of membrane voltage and pHi at about one cycle per minute . We conclude that endogenous oscillatory activity could be a trigger mechanism for DNA synthesis , proliferation , and abnormal growth of renal epithelial cells in culture . OUTPUT:

evading growth suppressors

HoC_1shot248

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

activating invasion and metastasis

HoC_1shot249

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Photodynamic therapy ( PDT ) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue . We therefore investigated interstitial tumour illumination as a means of selective PDT . A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats . Photofrin was administered ( 5 mg kg-1 i.v. ) 2 days before laser illumination . Tumours with a mean ( +/- s.e. ) diameter of 5.7 +/- 0.1 mm ( n = 106 , 20 days after implantation ) were illuminated with 625 nm light , at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100 , 200 , 400 , 800 or 1600 J cm-1 . Control groups received either laser illumination only , Photofrin only or diffuser insertion only . Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas . Long-term effects were studied on day 36 . To determine the biochemistry of liver damage and function , serum ASAT and ALAT levels were measured on day 1 and 2 , and antipyrine clearance on day 1 . Tumour and surrounding liver necrosis increased with light dose delivered ( P &lt ; 0.001 ) . Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals . No deterioration in liver function was found . The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage . OUTPUT:

resisting cell death

HoC_1shot250

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Fifty-six previously untreated stage-I ( according to Rai ) chronic lymphocytic leukemia ( CLL ) patients were examined for their clinical data , immunological characteristics , and hormonal values . Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin ( PHA ) , concanavalin A ( ConA ) , pisum sativatum agglutinin ( PSA ) , wheat germ agglutinin ( WGA ) , recombinant interleukin 2 ( IL 2 ) , and dextran sulfate ( DxS ) ; also by decreased immunoglobulin levels ( IgG , IgA , IgE ) and increased beta 2-microglobulin ( beta 2-M ) values . Simultaneously , dysregulation of the hypothalamic-pituitary-adrenal axis , immune system integration , imbalance of sex hormones , and changes in thyroid hormones were observed in the same group of patients . Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy . OUTPUT:

avoiding immune destruction

HoC_1shot251

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 wanted to investigate the effects of gamma radiation on DNA single-strand breaks ( SSB ) and glutathione ( GSH ) levels in mononuclear blood cells ( MNC ) of radiotherapy technicians . DNA SSB in MNC of radiotherapy technicians who use ( 60)Co-gamma source in their works were detected by alkaline filter elution and compared to control subjects . In addition , GSH levels were measured using the enzymatic method in MNC . Blood samples were collected from radiotherapy technicians on Monday and Friday . DNA SSB levels were found to be significantly higher in smoking controls compared to non-smoking controls . Significant increases of 36% and 49% in DNA SSB were detected from Monday to Friday for non-smoking and smoking radiotherapy technicians , respectively . GSH levels were found to be decreased significantly from Monday to Friday . Gamma-radiation resulted in increased DNA SSB levels of MNC in radiotherapy technicians throughout the working week and these breaks have been observed to be repaired at the weekend . Smoking habit caused an additional increase in the SSBs observed in radiotherapy technicians . OUTPUT:

genomic instability and mutation

HoC_1shot252

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 growth-inhibitory effects of ketoconazole , an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes , were tested in human colon and breast cancer cell lines . In the serum independent HT29-S-B6 colon cell clone , ketoconazole reduced cell proliferation and [ 3H]thymidine incorporation in a dose-dependent fashion , with a 50% inhibitory concentration of approximately 2.5 microM . Flow cytometry showed an accumulation of cells in the G0-G1 phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase . Ketoconazole also inhibited [ 3H]thymidine incorporation in the hormone-independent breast cancer cells MDA-MB-231 and Evsa-T , with respective 50% inhibitory concentration of approximately 13 and 2 microM . The mechanism of action of ketoconazole is unknown . However , another lipoxygenase inhibitor , BW755C , inhibited only weakly [ 3H]-thymidine incorporation and accumulated the cells in S and G2 . Conversely , clotrimazole and SKF525A , inhibitors of cytochrome P-450 enzymes , had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole , other azole derivatives which do not inhibit cytochrome P-450 enzymes , had no effect . The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole . OUTPUT:

sustaining proliferative signaling

HoC_1shot253

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type ( epithelial ) and R-type ( round ) . Pure cultures of each type were obtained by subcloning , and both have maintained their characteristic phenotypes for at least 1 year ( 40 passages ) . E-type cells are the major ( &gt ; 98% ) type in the parental SW480 cell line . They form flat epithelial-like colonies . In contrast , R-type cells , which constitute a minor fraction ( &lt ; 2% ) of the parental cell line , have a rounded shape and grow in clusters of piled-up cells . Compared to E-type cells or the parental SW480 cells , isolated R-type cells display decreased doubling time , loss of contact inhibition , less adhesiveness to culture plates , higher anchorage-independent growth in soft agar , and a much more aneuploid karyotype . When injected s.c. into nude mice , R-type cells produce much larger tumors within the same period of time than E-type cells , and the tumors are less differentiated than those produced by the E-type cells . Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant , and the results suggest that this is due to one or a few genetic changes . Taken together , these findings suggest that the R-type cells represent a more malignant variant of the E-type cells . They may be useful , therefore , for studying mechanisms involved in tumor progression . OUTPUT:

evading growth suppressors

HoC_1shot254

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Many reports have emphasized the role of gastrin as a growth factor for normal gastrointestinal mucosa and gastrointestinal cancers . Recent studies have pointed out that this peptide acts also as a growth factor for the pancreatic cancer cell line AR42J . This effect is mediated by gastrin [ cholecystokinin ( CCK)-B ] receptors . In the present study , we investigated gastrin ( CCK-B ) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6 , comparing it to normal rat pancreas , and we also characterized CCK receptor subtypes in this tumor . The results showed that there is extensive gastrin binding to the DSL-6 pancreatic carcinoma . No evidence of specific gastrin binding to normal pancreas was found . Analysis of the ability of gastrin-17-I to inhibit 125I-gastrin-I binding demonstrated that gastrin bound to a single class of receptors with a Kd of 0.21 +/- 0.04 nM and a binding capacity of 184 +/- 29 fmol/mg protein. 125I-Gastrin-I binding was inhibited by the specific CCK-B receptor antagonist L365,260 approximately 40 times more effectively than by the specific CCK-A receptor antagonist L364,718 . Analysis of the ability of cholecystokinin octapeptide ( CCK-8 ) to inhibit 125I-Bolton-Hunter-CCK-8 binding revealed two CCK binding sites , i.e. , a high affinity site and a low affinity site . The observed binding affinities of CCK-8 were then introduced into the computer analysis of the dose-inhibition curve of the ability of gastrin-17-I to inhibit binding of 125I-Bolton-Hunter-CCK-8 , which was significantly better fit by a three-site model than by a two-site model . The three sites meet the criteria for CCK-B , high affinity CCK-A , and low affinity CCK-A receptors . The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites . This study demonstrated that DSL-6 pancreatic carcinoma expresses three subtypes of CCK receptors . Gastrin ( CCK-B ) receptors , which were not detected in normal rat pancreas , constitute about one third of the total high affinity CCK receptors . We suggest that novel expression of gastrin ( CCK-B ) receptors may be generated by gene mutation or amplification during carcinogenesis and may play an important role in promoting tumor growth . OUTPUT:

sustaining proliferative signaling

HoC_1shot255

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Hepatocyte growth factor ( HGF ) , a mesenchymal-derived factor which regulates growth , motility , and morphogenesis of epithelial and endothelial cells , functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney . We have now obtained evidence that transforming growth factor-beta 1 ( TGF-beta 1 ) and glucocorticoids are negative regulators for HGF gene expression . When TGF-beta 1 or dexamethasone was added to cultures of MRC-5 human embryonic lung fibroblasts and HL-60 human promyelocytic leukemic cells , the amount of HGF secreted into the culture medium was inhibited to 30-40% of that of control cultures by 10 ng/ml TGF-beta 1 and to 40-50% by 10(-6) M dexamethasone . The inhibitory effect of TGF-beta 1 and dexamethasone on HGF synthesis in MRC-5 cells was additive , thereby suggesting that TGF-beta 1 and dexamethasone exert effects through distinct mechanisms . Hydrocortisone also inhibited HGF synthesis with the same potency as dexamethasone ; however , testosterone , estriol , and beta-estradiol had no effect . The rate of HGF synthesis in MRC-5 cells , as measured by pulse labeling with [ 35S]methionine and subsequent immunoprecipitation , was suppressed to 30-40% of the control with 10 ng/ml TGF-beta 1 , and to 30-45% by 10(-6) M dexamethasone . HGF mRNA levels in MRC-5 cells and HL-60 cells were dose-dependently suppressed by TGF-beta 1 and dexamethasone ; 10 ng/ml TGF-beta 1 suppressed HGF mRNA levels to 32% and 35% of control culture , respectively , in MRC-5 cells and HL-60 cells , and 10(-6) M dexamethasone suppressed to 43% and 38% , respectively . Thus , TGF-beta 1 and glucocorticoids seem to inhibit HGF synthesis by suppressing the expression of the HGF gene . We propose that a negative regulation of HGF gene expression by TGF-beta 1 or glucocorticoids may be involved in physiological or pathological processes during tissue regeneration . OUTPUT:

sustaining proliferative signaling

HoC_1shot256

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Peptide 11 , CDPGYIGSR-NH2 , is a segment of laminin which blocks tumor cell invasion . A high affinity laminin receptor in tumor cells is thought to be blocked by the carboxyl-terminal YIGSR , and conformational energy calculations suggest that the glycine in YIGSR allows an important conformational bend . We replaced the YIGSR glycine residue in peptide 11 with either D-alanine or L-alanine to allow or disfavor the proposed glycine bend . We found the Gly7-->D-Ala7 analog to be equal to peptide 11 in inhibiting tumor cell invasion of basement membrane matrix . The Gly7-->L-Ala7 analog was much less capable of invasion inhibition . Two-dimensional 1H-1H NMR was used to study the solution conformations of the peptide 11 analogs . NOESY experiments revealed close NH-NH contacts in peptide 11 and the D-Ala7 analog , but not in the L-Ala7 analog . Molecular dynamics generated low energy structures with excellent NOE agreement for peptide 11 and its analogs . Both peptide 11 and the D-Ala7 analog , but not the less active L-Ala7 analog , were predicted to have similar bends around Gly7 or D-Ala7 . These results suggest that a bend in the YIGSR region of peptide 11 may be important for the binding of laminin to its metastasis-associated receptor . OUTPUT:

activating invasion and metastasis

HoC_1shot257

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Many breast cancers are estrogen independent , and even in patients who initially respond to estrogen suppression therapy , the regression is often temporary . We have recently shown that antagonists of bombesin and gastrin-releasing peptide , including RC-3095 , inhibit the growth of pancreatic , colonic , and prostatic cancers in experimental animals . This effect was associated with a substantial decrease in epidermal growth factor ( EGF ) receptor levels in pancreatic and colon cancers . OUTPUT:

sustaining proliferative signaling

HoC_1shot258

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 effects of angiostatin(AS) gene mediated by liposome on human pancreatic cancer cell line SW1990 . METHODS Angiostatin gene was cloned into the eukaryotic expression vector pRC/CMV . The recombinant of pRC/CMV-AS was introduced into the pancreatic cancer cell line , SW1990 . The mechanism of anti-tumor was studied and tested . RESULTS The eukaryotic expression vector pRC/CMV-AS was identified by the restriction digest. pRC/CMV-AS was stably integrated into the target cells and expressed by Western blot and drug-sensitivity tests , and inhibited the vascular endothelial cells proliferation in vitro . In addition , the effects of the angiostatin vector on reducing the volume of tumors implanted in nude mouse models were also noted . CONCLUSION This study demonstrated that the recombinant pRC/CMV-AS mediated by liposome may play a potential role in the treatment of pancreatic cancer in the future . OUTPUT:

inducing angiogenesis

HoC_1shot259

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Cytokines are known to play an important role in host defense by regulating the function , growth , and differentiation of the cells of the immune system . We hypothesize that , in the tumor microenvironment , tumor cells and resident tissue cells ( e.g. , fibroblasts ) also produce cytokines that may regulate the local immune response to tumors . Initially , homogenates of eight head and neck squamous cell carcinomas ( HNSCC ) were assayed for the presence of interleukin-1 ( IL-1 ) , interleukin-4 ( IL-4 ) , interleukin-6 ( IL-6 ) , and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) to establish the presence of these cytokines in the tumors in vivo . We detected IL-1 in all tumor homogenates and IL-4 , IL-6 , and GM-CSF in some homogenates . To assess the ability of HNSCC to produce these cytokines , supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines . No IL-1 was detected , although baseline levels of IL-4 , IL-6 , and GM-CSF were present . However , the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 ( p &lt ; 0.01 ) , IL-6 ( p &lt ; 0.001 ) , and GM-CSF ( p &lt ; 0.02 ) . These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells . Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells . OUTPUT:

avoiding immune destruction;tumor promoting inflammation

HoC_1shot260

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Capillary endothelial cells can be induced to form capillary-like structures in vitro by plating on fibronectin-coated dishes ( Ingber , D. E. , and Folkman , J . ( 1989 ) J. Cell Biol. 109 , 317-330 ) , thereby mimicking angiogenesis . To assess the role of glycoproteins bearing asparagine-linked oligosaccharides in this process , we tested the effect of oligosaccharide processing inhibitors on the formation of capillary tubes . Deoxymannojirimycin , a compound that prevents synthesis of hybrid and complex-type oligosaccharides , inhibited the formation of capillary tubes . In contrast , swainsonine , an inhibitor that blocks synthesis of complex- but not hybrid-type oligosaccharides , did not inhibit tube formation . Lectin affinity chromatography of 2-[3H] mannose-labeled glycopeptides from endothelial cells induced to form tubes did not reveal a striking difference in the spectrum of oligosaccharides compared to uninduced cells . Since endothelial cells formed tubes normally in the presence of swainsonine , we analyzed glycopeptides from swainsonine-treated induced and uninduced cells . Cells induced to form tubes were enriched in monosialylated hybrid-type oligosaccharides sensitive to alpha-fucosidase , beta-galactosidase , and beta-N-acetylhexosaminidase , suggestive of sialyl Lewis-X determinants . We used an enzyme-linked immunoassay to measure sialyl Lewis-X epitopes on capillary endothelial cells and found that both induced and uninduced cells expressed sialyl Lewis-X epitopes . Deoxymannojirimycin and , to a lesser extent , swainsonine reduced the level of sialyl Lewis-X epitopes in cells induced to form capillary tubes , but neither compound affected the level of epitopes in cell monolayers . We conclude that synthesis of at least hybrid-type oligosaccharides is required for capillary tube formation in vitro and that an increase in monosialylated , fucosylated glycans on asparagine-linked oligosaccharides occurs during this process . OUTPUT:

inducing angiogenesis

HoC_1shot261

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 UT-7 cell line was established from a patient with a megakaryoblastic leukemia ( Komatsu et al , Cancer Res 51 : 341 , 1991 ) . Its proliferation is strictly dependent on the presence of hematopoietic growth factors including erythropoietin ( Epo ) , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , and interleukin-3 ( IL-3 ) . We investigated the differentiation capacities of this cell line under the action of several growth factors , using immunomarkers , flow cytometry , and ultrastructural techniques . In the presence of GM-CSF and IL-3 , eosinophil and basophil promyelocytes were detected , as well as a few cells with erythroid and megakaryocytic ( MK ) differentiation features . In contrast , Epo induced a marked erythroid differentiation with an increase of glycophorin A expression , accompanied by a few hemoglobinized cells . Differentiation induced by the growth factors took 24 to 48 hours to begin , and increased with cell passages to a plateau at 2 weeks of culture . However , this was not only due to a cell selection because the differential effects of Epo and GM-CSF were observed from a single cell clone and the phenotype could be reversed by opposite growth factors , even after a long period of culture . We subsequently investigated the phenotype of UT-7 in the presence of combinations of Epo , IL-3 , and GM-CSF , and showed that GM-CSF and IL-3 act predominantly over Epo . This effect was mediated by a rapid downmodulation of Epo receptors by GM-CSF at messenger RNA and binding sites levels , without a change in receptor affinities . On the other hand , Epo had no effect on number and affinity of GM-CSF receptors . This study shows that UT-7 is a growth factor-dependent pluripotent cell line in which commitment may be directed by a hierarchical action of growth factors through an early and rapid transmodulation of growth factor receptors . OUTPUT:

sustaining proliferative signaling

HoC_1shot262

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Chromatographic , peptide mapping and mass spectrometric analysis were used to examine hemoglobin ( Hb ) from heavy drinkers and abstainers for alcohol consumption-related modifications . Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different ( p &lt ; 0.05 ) amounts of " fast " hemoglobin . The presence of higher amounts of " fast " Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications . To further examine Hb for modifications , tryptic peptides of the " fast " hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry ( PDMS). [ 14C]acetaldehyde ( AcH)-Hb was synthesized in vivo for use as a standard . Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [ 14C]acetaldehyde-Hb . The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides ; the two pairs of peptides co-migrated on HPLC . A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb . The modified peptides were found in five of six heavy drinker samples . This is the first description of site-specific AcH-Hb adducts occurring in vivo . The routine detection of such adducts has potential for characterizing usual alcohol intake . OUTPUT:

genomic instability and mutation

HoC_1shot263

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 tumor growth-dependent elevation in the hepatic levels of Zn and metallothionein ( MT ) , without a change in the level of Cu , was found in mice and rats bearing solid tumors in the inguinal region . The levels of Zn and MT thus elevated gave a significant correlation ( r = 0.95 ) between them . Nevertheless , when tumor-bearing mice and rats were fed a Zn-deficient diet , the hepatic levels of Zn and MT did not increase . In mice in which inflammation was induced at the same region , on the other hand , hepatic levels of Zn and MT increased transiently after the injection of turpentine or carrageenan even when they were fed the Zn-deficient diet . These results suggest that the elevation of MT and Zn levels can be a helpful marker for detecting malignancy . OUTPUT:

tumor promoting inflammation

HoC_1shot264

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 induction of apoptosis by glucocorticoids in isolated thymocytes has been studied extensively . However , it is not known whether or not the same changes occur after in vivo glucocorticoid treatment . In order to investigate this , we have studied the changes occurring in thymocytes isolated from rats , from 2-24 hr after a dose of dexamethasone ( 1 mg/kg ) , which caused 50% thymic atrophy . Thymocytes were separated into four fractions by isopycnic Percoll gradients . A loss of cells occurred within 2-8 hr , primarily in only one of the two major fractions of normal thymocytes . This loss of normal thymocytes coincided with the appearance of small dense cells with characteristic features of apoptosis including condensed chromatin , increased DNA fragmentation , internucleosomal DNA cleavage and a " hypodiploid " peak on flow cytometric analysis . Striking differences occurred in the cellular composition of the different Percoll fractions with time . Initially ( up to 4 hr ) , the pattern of changes occurring in vivo resembled those found in vitro . However , at later times , the complex fate of apoptotic cells in vivo , such as phagocytosis , are not observed in the in vitro studies . OUTPUT:

resisting cell death

HoC_1shot265

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Cell kinetics and activity of ornithine decarboxylase ( ODC ) were studied during the process of 1-hydroxyanthraquinone ( 1-HA)-induced intestinal carcinogenesis in rats . Starting at 6 weeks of age , a total of 37 male ACI/N rats were divided into two groups and treated as follows : group I ( 18 rats ) received diet containing 1% 1-HA for 12 months ; group II ( 19 rats ) was given the basal diet alone . Sub-groups of 5-7 rats were sequentially killed at 4 , 8 and 12 months for evaluation of the length , cell numbers and 5-bromo-2'-deoxyuridine ( BrDU ) labeling indices of large bowel crypts together with ODC activity . All kinetic and ODC data indicated increased DNA synthesis and proliferation at all time points . Morphological observation of the intestines also revealed melanosis , crypt abscesses and erosion , becoming more pronounced with length of exposure to the anthraquinone . The data thus suggest that cell proliferation in the crypts of the cecum or colon is important for 1-HA-induced intestinal carcinogenesis . OUTPUT:

sustaining proliferative signaling

HoC_1shot266

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 use of substrates containing well defined adducts at precise sites , is required to perform a careful analysis of the toxic and mutagenic potential of a lesion . As a first step in this direction the octamer 5'-d(CCGGCGGT) , containing the sequence of the codons 12 d(GGC) and 13 d(GGT) of the human H-ras gene , was reacted with the antitumoral drug cis-diamminedichloroplatinum(II) . The platinated products have been purified by HPLC . A first set of experiments , including enzymatic digestions with nuclease P1 followed by alkaline phosphatase and acid-catalysed hydrolysis , allowed us to determine which bases were engaged in the cis-DDP lesions . Our results indicate that only guanine residues were chelated with cisplatin to yield bifunctional adducts . Furthermore , by performing enzymatic digestions with phosphodiesterases , we have located the adducts with respect to the 5 ' end of the octamer . Among the purified and characterized platinated oligonucleotides , three present a particular interest , since we have shown here that the cis-d(GpG) adduct is precisely situated either at the d(GGC) or at the d(GGT) or at both sites of their sequence . OUTPUT:

genomic instability and mutation

HoC_1shot267

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 exploited properties of photosensitizers to study an aspect of the packing of chromatin in the cell nucleus . The fluorescent photosensitizers mesotetra(3-hydroxyphenyl) porphyrin and Photofrin II were both localized in the nuclear membrane and other membrane structures , but could not be found inside the nuclei . Light exposure of cells at 1 degrees C in the presence of the sensitizers induced DNA double-strand breaks . The length distributions of DNA fragments were determined by pulsed field gel electrophoresis . Because DNA damage is produced mainly via singlet oxygen diffusing less than 0.1 microns from the sensitizer , DNA double-strand breaks were supposedly produced within this distance of the nuclear membrane . Consistent with this , with prolonged illumination and with increasing concentrations of sensitizer the distribution of DNA fragment lengths reached a plateau level . In contrast , with the hydrophilic , intranuclear sensitizer meso-tetra(4-sulphonatophenyl)porphyrin , no such plateau level was found . The plateau distributions of DNA fragment lengths of different cell types had the same general shape with average fragment lengths ranging from 174 to 194 kilobasepairs . Particular genes , c-myc , fos and p53 , were found on broad distributions of photocleaved fragment lengths . The results indicate that on each side of the genes the locus of the chromatin fibre situated close to the nuclear membrane , varied randomly . OUTPUT:

genomic instability and mutation

HoC_1shot268

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process , methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M . All transformants examined revealed an alteration in DNA methylation in some of the genes , although these changes were variable among them . A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes , whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes . Resultant data indicate that the alteration of DNA methylation is closely related to transformation process , yet how this involvement occurs is complex and remains unclear . OUTPUT:

evading growth suppressors

HoC_1shot269

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 compared gadolinium diethylenetriaminepentaacetic acid ( Gd-DTPA ) enhanced T1-weighted images ( T1-Gd ) with the histopathological findings in 13 patients with bone or soft tissue sarcomas . Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients . The necrotic or cystic areas in the tumor were not enhanced , rendering them distinctly . The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients . Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced . Thus , the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd . Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot270

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 extended our studies on the relationship between cisplatin/carboplatin-induced DNA damage in readily accessible tissue(s) and clinical response to therapy . Such an approach may assist in the study of cancer drug resistance and in establishing parameters for assessing human populations for sensitivity to DNA damaging agents in the environment . Platinum-DNA adduct levels were measured by atomic absorbance spectrometry . DNA repair capacity was assessed in human T-lymphocytes by the ability to repair cisplatin lesions in cellular DNA or in transfected plasmid DNA . In a " blinded " study of 21 patients receiving combination cisplatin/carboplatin drug therapy , there was a direct relationship between DNA damage in leukocytes and disease response ( summary two-sided p = 0.00011 ) . The cohort of patients had 15 different tumor types , suggesting that blood tissue and tumor tissue of an individual may process platinum-DNA damage similarly regardless of the tissue of origin of the tumor . In leukocytes in vivo , persistence and accumulation were prominent features of the cisplatin-DNA adduct profile . Functional DNA repair capacity has been studied in eight human leukocyte cell lines in vitro ( three , T-cells ; three , B-cells ; one , monocytic ; one , promyelocytic ) , using a host cell reactivation assay with cisplatin-damaged pRSVcat . In the three T cell lines studied , host cell reactivation efficiency was directly related to the cells ' abilities to repair cisplatin-damaged cellular DNA ( correlation coefficient = 0.993).(ABSTRACT TRUNCATED AT 250 WORDS ) OUTPUT:

genomic instability and mutation

HoC_1shot271

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: PRL induces quiescent Nb2 rat T-lymphoma cells to undergo mitogenesis . Upon PRL stimulation , the transcription factor interferon regulatory factor-1 ( IRF-1 ) is induced as a novel T-cell activation gene in Nb2 cells . Surprisingly , IRF-1 is expressed twice during a single PRL-induced growth cycle : first during the early G1 phase , in an immediate transient peak from 15 min to 2 h , and second during the G1/S phase transition , in a broader peak beginning at 8 h . The unusual biphasic expression of IRF-1 mRNA is accompanied both times by de novo IRF-1 protein synthesis . However , the rate of IRF-1 protein turnover appears to be different in G1 and S phases . IRF-1 protein expressed in G1 exhibits a half-life of about 25 min , whereas in the S phase , the half-life is about 60 min . By washing out PRL at various times during G1 , we found a direct correlation among the length of PRL exposure , the second peak of IRF-1 mRNA expression , and DNA synthesis . Our data suggest that PRL and one putative nuclear mediator , IRF-1 , may be important in two distinct phases of the cell cycle : first in cell cycle activation , and then in S phase progression . OUTPUT:

sustaining proliferative signaling

HoC_1shot272

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Psoralen photoreaction with DNA produces interstrand crosslinks , which require the activity of excision and recombinational pathways for repair . Yeast replicating plasmids , carrying the HIS3 , TRP1 , and URA3 genes , were photoreacted with psoralen in vitro and transfected into Saccharomyces cerevisiae cells . Repair was assayed as the relative transformation efficiency . A recombination-deficient rad52 strain was the least efficient in the repair of psoralen-damaged plasmids ; excision repair-deficient rad1 and rad3 strains had repair efficiencies intermediate between those of rad52 and RAD cells . The level of repair also depended on the conditions of transformant selection ; repair was more efficient in medium lacking tryptophan than in medium from which either histidine or uracil was omitted . The plasmid repair differential between these selective media was greatest in rad1 cells , and depended on RAD52 . Plasmid-chromosome recombination was stimulated by psoralen damage , and required RAD52 function . Chromosome to plasmid gene conversion was seen most frequently at the HIS3 locus . In RAD and rad3 cells , the majority of the conversions were associated with plasmid integration , while in rad1 cells most were non-crossover events . Plasmid to chromosome gene conversion was observed most frequently at the TRP1 locus , and was accompanied by plasmid loss . OUTPUT:

genomic instability and mutation

HoC_1shot273

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 investigate a potential mechanism of invasion and metastasis of oral cancers , and the possibility of the adhesion molecules being markers for evaluating the prognosis of oral cancers . METHODS Randomly selecting achieved paraffin blocks , including 60 cases of squamous cell carcinoma(SCC) , 30 cases of verrucous carcinoma(VC) of oral mucosa and 30 cases of basal cell carcinoma ( BCC ) of epidermis . All cases were followed up . Using immunohistochemistry method ( Envision ) to detect the expression of E-cadherin antibody and observe under light microscope . RESULTS The studies demonstrated that 38.2% of SCC had recurrence and/or metastases after operation . However , only 0.0% and 0.04% , in VC and BCC , respectively , had recurrence and/or metastases . There was significant difference on prognoses between SCC and VC or BCC . The immunostaining showed significant difference of E-cad expression between SCC and VC ( P<0.01 ) , SCC and BCC ( P<0.05 ) . The former was weaker than VC and BCC . However , no difference was showed in E-cad expression between VC and BCC ( P>0.05 ) . CONCLUSION E-cad plays an important role in maintaining the phenotype of epithelial cell of SCC and normal oral mucosa . The degree of expression of E-cad was correlated with the ability of invasion and/or metastasis of SCC , VC and BCC . It indicates that E-cad may be as a helpful marker to evaluate the prognosis of oral cancers . OUTPUT:

activating invasion and metastasis

HoC_1shot274

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 our study we investigated the level of apoptosis in PBMCs and the serological level of sFas ( CD95/APO-1 ) in 22 patients with malignant melanoma ( 12 patients with unique cutaneous primary tumour and 10 patients with unique brain metastasis ) . The first determination was performed before tumour excision and the second at 6-7 months after excision . Results in patients with primary tumour in the first determination : 6 patients with over normal values in PBMCs apoptosis and 5 patients with increased values of sFas . In the second determination : apoptosis was increased in 5 patients and sFas level was increased in 4 cases . In patients with metastases in the first determination apoptosis of PBMC was increased in 7 cases and sFas in 5 cases . In the second determination apoptosis was increased in 4 cases and sFas was increased in 4 cases . Our results show that half of the investigated patients presented elevated values of PBMCs apoptosis and Fas receptor both before and 6-7 months after tumour excision . Apoptosis values for PBMCs and sFas values were with 1/4 higher than normals . There was no difference in clinical evolution of the patients with normal or increased values for studied parameters . Clinical evolution was performed for 1 year . The presence of increased values for PBMCs and sFas after tumour excision , primary or metastasis is surprising and hard to explain . It is possible that tumoral evolution induces a disregulation at PBMCs level or other cells level that persists unexpectedly , after tumour excision or apoptotic processes , in a certain level to be independent and anterior to tumour development . OUTPUT:

resisting cell death;activating invasion and metastasis

HoC_1shot275

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Contrary to the paradigm that cancer incidence increases indefinitely with age , significant data now suggest cancer incidence may markedly reduce beyond age 80 years for humans and beyond 800 days for mice , and is not inevitable . We show that increasing cellular senescence with age is a possible cause of this reduction , since senescent cells are removed from the pool of cells that retain proliferative ability necessary for cancer . We further show that animal interventions appearing to alter senescence , p53 mutation and melatonin dosing , support the prediction that increasing senescence rate reduces cancer while reducing lifespan , and vice versa . Studies of environmental agents associated with increased cancer might be re-examined to find if there is an association with longevity increases , which may markedly alter our view of such agents . We also show that if an agent functions by slowing both senescence and carcinogenesis , longevity is increased while reducing cancer . Dietary restriction is the only known intervention that accomplishes this , but there may be others . OUTPUT:

enabling replicative immortality;genomic instability and mutation

HoC_1shot276

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Epidermal growth factor ( EGF ) receptor is inversely related to expression of estrogen receptor ( ER ) and progesterone receptor in primary breast tumors and is a negative predictor for response to endocrine therapy . To investigate a possible causal role of EGF receptor expression in breast cancer progression to hormone independence , we have created an experimental cell system . Epidermal growth factor receptor complementary DNA was introduced in estrogen-dependent ZR-75-1 breast cancer cells , and the resulting ZR/HERc cells exhibited a mitogenic response to epidermal growth factor , thus bypassing estrogen dependence . This EGF-induced proliferation could not be inhibited by antiestrogens . In addition , we noted changes in cell morphology and keratin expression of EGF-stimulated ZR/HERc cells , suggestive of an altered differentiation state . Furthermore , intolerance of functional ER and EGF receptor signal transduction pathways in ZR/HERc cells was observed during simultaneous activation , which possibly explains the inverse relationship of ER and EGF receptor expression in primary tumors . In contrast to the parental cells , ZR/HERc cells rapidly progressed to a stable ER-negative phenotype when cultured in the presence of the antiestrogen hydroxy-tamoxifen . These results suggest a possible role for EGF receptor in progression of breast cancer to hormone independence . OUTPUT:

sustaining proliferative signaling

HoC_1shot277

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 mice fed a diet supplemented with red clover isoflavones the prostatic epithelium displays a significant increase in the production of estrogen receptor beta and the adhesion protein E-cadherin but a decrease in transforming growth factor beta1 . These proteins are estrogenically-induced markers of proliferation , maintenance of histological architecture , preservation of cell phenotype and reduction of the potential for neoplastic and metastatic transformation . This study suggests that red clover isoflavones represent a non-toxic dietary treatment for prostatic hyperplasia and a reduction in the potential for neoplastic transformation . OUTPUT:

sustaining proliferative signaling

HoC_1shot278

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Limited options for the treatment of prostate cancer have spurred the search for new therapies . One innovative approach is the use of targeted alpha therapy ( TAT ) to inhibit cancer growth , using an alpha particle emitting radioisotope such as ( 213)Bi . Because of its short range and high linear energy transfer ( LET ) , alpha-particles may be particularly effective in the treatment of cancer , especially in inhibiting the development of metastatic tumors from micro-metastases . Prostate-specific membrane antigen ( PSMA ) is expressed in prostate cancer cells and the neovasculature of a wide variety of malignant neoplasms including lung , colon , breast and others , but not in normal vascular endothelium . The expression is further increased in higher-grade cancers , metastatic disease and hormone-refractory prostate cancer ( PCA ) . J591 is one of several monoclonal antibodies ( mabs ) to the extracellular domain of PSMA . Chelation of J591 mab with ( 213)Bi forms the alpha-radioimmunoconjugate ( AIC ) . The objective of this preclinical study was to design an injectable AIC to treat human prostate tumors growing subcutaneously in mice . The anti-proliferative effects of AIC against prostate cancer were tested in vitro using the MTS assay and in vivo with the nude mice model . Apoptosis was documented using terminal deoxynucleotidyl transferase [ TdT]-mediated deoxyuridinetriphosphate [ dUTP ] nick end-labeling ( TUNEL ) assay , while proliferative index was assessed using the Ki-67 marker . We show that a very high density of PSMA is expressed in an androgen-dependent human PCA cell line ( LNCaP-LN3 ) and in tumor xenografts from nude mice . We also demonstrate that the AIC extensively inhibits the growth of LN3 cells in vitro in a concentration-dependent fashion , causing the cells to undergo apoptosis . Our in vivo studies showed that a local AIC injection of 50 microCi at 2 days post-cell inoculation gave complete inhibition of tumor growth , whereas results for a non-specific AIC were similar to those for untreated mice . Further , after 1 and 3 weeks post-tumor appearance , a single ( 100 microCi/100 microl ) intra-lesional injection of AIC can inhibit the growth of LN3 tumor xenografts ( volume<100 mm(3) ) in nude mice . Tumors treated with AIC decreased in volume from a mean 46+/-14 mm(3) in the first week or 71+/-15 mm(3) in the third week to non-palpable , while in control mice treated with a non-specific AIC using the same dose , tumor volume increased from 42 to 590 mm(3) . There were no observed side effects of the treatment . Because of its in vitro cytotoxicity and these anti-proliferative properties in vivo , the ( 213)Bi-J591 conjugate has considerable potential as a new therapeutic agent for the treatment of prostate cancer . OUTPUT:

resisting cell death

HoC_1shot279

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 it has been demonstrated that discrete origins of DNA replication exist in eukaryotic cellular chromosomes , the detailed organization of a eukaryotic cellular origin remains to be determined . Linker substitution mutations were constructed across the entire Saccharomyces cerevisiae chromosomal origin , ARS1 . Functional studies of these mutants revealed one essential element ( A ) , which includes a match to the ARS consensus sequence , and three additional elements ( B1 , B2 , and B3 ) , which collectively are also essential for origin function . These four elements arranged exactly as in ARS1 , but surrounded by completely unrelated sequence , functioned as an efficient origin . Element B3 is the binding site for the transcription factor-origin binding protein ABF1 . Other transcription factor binding sites substitute for the B3 element and a trans-acting transcriptional activation domain is required . The multipartite nature of a chromosomal replication origin and the role of transcriptional activators in its function present a striking similarity to the organization of eukaryotic promoters . OUTPUT:

genomic instability and mutation

HoC_1shot280

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Glutathione S-transferase ( GST ) class Mu activity was determined in 145 unrelated hospital patients in Berlin by measuring their conjugation activity towards the specific substrate trans-stilbene oxide ( TSO ) with two substrate concentrations ( 50 and 250 microM ) in homogenates prepared from lymphocytes . Eighty individuals ( 55.2% ) had an activity lower than 10 pmol/min/10(6) lymphocytes and were classified as GST class Mu deficient . In 142 of 145 cases , phenotype was confirmed by the results of a genotyping procedure using the polymerase chain reaction technique . Two fragments of 273 and about 650 bp including one and two introns , respectively , could always be amplified from genomic DNA in individuals with high GST class Mu activity and could not be amplified in persons with impaired glutathione-TSO conjugation activity . This indicates that persons with low activity carry a large deletion mutation within the GST class Mu gene . The enzymatically determined antimode between low and high activity determined as 10 pmol/min/1 million lymphocytes in the assay with 50 microM TSO could be clearly confirmed by genotyping . OUTPUT:

genomic instability and mutation

HoC_1shot281

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Ovarian surface epithelial cells undergo several rounds of division to repair the wound created by follicular rupture at the time of ovulation . This cyclical requirement for cell division , when not interrupted by the long anovulatory rest periods that occur during pregnancy and lactation , may contribute to the development of ovarian cancer . PURPOSE AND METHODS To test this hypothesis , we isolated rat ovarian surface epithelial cells from 10 adult female Fisher rats , initiated two mixed-population and seven clonal cell lines , and repeatedly subcultured these cells in vitro for more than 20 passages . We then tested them for the acquisition of the following four features associated with transformation : 1 ) the loss of contact inhibition , 2 ) the capacity for substrate-independent growth , 3 ) the ability to form tumors when injected subcutaneously and/or intraperitoneally into athymic mice , and 4 ) cytogenetic abnormalities . RESULTS Loss of contact inhibition was observed in all nine late-passage cell lines . Six of the nine late-passage , but none of the early-passage , cell lines tested exhibited a capacity for substrate-independent growth that was augmented in a dose-dependent manner by epidermal growth factor . Two late-passage cell lines ( clone 2 and mixed-population 2 ) generated tumors in athymic BALB/c mice within 3 weeks following subcutaneous injection of 5 x 10(6) cells , whereas similar numbers of early-passage cells from the same cell lines failed to generate palpable tumors . Late-passage clone 7 cells were tumorigenic when 5 x 10(7) cells were injected intraperitoneally . Two of the cell lines analyzed exhibited alterations involving losses of part or all of one member of the chromosome 5 pair . Clone 2 possessed an interstitial deletion , del(5)(q21.3q24) , consistent with the loss of an uncloned putative tumor suppressor gene at 5q22q23 previously reported to reside near the loci for the interferon alpha , interferon beta , and c-jun genes . Early-passage clone 7 cells exhibited chromosome 5 monosomy , while late-passage cells contained one normal chromosome 5 and a derivative ( 5q12q ) . Southern analysis of the three cell lines revealed no consistent loss of loci for the interferon and c-jun genes , although early-passage clone 7 cells had one half the gene copy number for the interferon beta and c-jun genes and both early- and late-passage clone 7 cells lacked DNA sequences hybridizing with the probe for interferon alpha . CONCLUSION This pattern of passage-dependent spontaneous transformation of rat ovarian surface epithelial cells in vitro supports the hypothesis that repetitious ovulation contributes to the etiology of human ovarian cancer . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot282

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 hypothesis that rodent cells can be immortalized by the direct induction of a single mutation-like event was tested by initiating cultures of benzo(a)pyrene treated Syrian hamster embryo cells with low inocula and expanding these few cells maximally until senescence prevented further culturing or immortalization took place . According to the mutation hypothesis immortalization is hardly to be expected under these conditions . However , immortalization was frequently observed . Therefore the induction of immortalization appears indirect . The progeny of benzo(a)pyrene treated cells immortalized with a rate of 3.9 x 10(-8)/cell/generation , which is 64 times higher than the spontaneous rate . The results are in line with the probabilistic theory developed in 1980 by both Fernandez et al . ( Proc . Natl . Acad . Sci . USA , 77 : 7272-7276 , 1980 ) and Kennedy et al . ( Proc . Natl . Acad . Sci . USA , 77 : 7262-7266 , 1980 ) , which states that treatment of cells with a carcinogen can result in a so-called activated state of the treated cells which is transmitted to the progeny and which results in an enhanced rate of transforming events . OUTPUT:

enabling replicative immortality

HoC_1shot283

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 protein toxins ricin , abrin , Shiga toxin , and diphtheria toxin were found to induce lysis of several cell lines in a manner characteristic for programmed cell death or apoptosis . The toxins induced DNA degradation , and light and electron microscopical studies revealed that lysis was preceded by reorganization of intracellular vacuoles , cell blebbing , and chromatin condensation both in Vero and in MDCK cells . Cell lysis was efficiently inhibited by cycloheximide and 3-methyladenine ( 3MA ) , a specific inhibitor of autophagy . Cycloheximide , which like 3MA inhibits autophagy , protected even when added at a time when the protein synthesis had been blocked by ricin , suggesting that the effect of cycloheximide on cell lysis is independent of its ability to inhibit protein synthesis . Also theophylline and dibutyryl-cGMP had some protective effect , whereas a number of compounds reported to protect against apoptosis in other systems were without protective effects . The data suggest that autophagy is important for the toxin-induced cell lysis . OUTPUT:

resisting cell death

HoC_1shot284

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype . The expressions of two tumor suppressor genes , the retinoblastoma ( Rb ) gene and the p53 gene , were investigated during senescence , crisis , and cell line establishment . In temperature-sensitive ( ts)-v-erb B erythroblasts and ts-v-src fibroblasts ( as well as in v-myc macrophages ) , loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization . In contrast , expression of the Rb gene was unchanged at all stages of immortalization . Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts , even in lines that were immortal and lacked p53 . The results demonstrate that the process of immortalization is distinct from cell transformation , probably requiring different mutational events . OUTPUT:

enabling replicative immortality;genomic instability and mutation

HoC_1shot285

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Findings of increased numbers of epidermal growth factor receptors ( EGF-R ) and increased expression of transforming growth factor alpha ( TGF-alpha ) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF-alpha in an autocrine manner . In the studies presented here , we have examined this hypothesis using two human renal carcinoma cell lines , SKRC-4 and SKRC-29 . We demonstrated that both SKRC-4 and SKRC-29 cells were growth stimulated by greater than 35% when cultured in the presence of TGF-alpha or EGF and were inhibited by 29% to 46% if cultured in the presence of anti-EGF-R monoclonal antibody 225 . Treatment of cells with TGF-alpha enhanced the levels of expression of EGF-R mRNA and TGF-alpha mRNA . In addition , incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF-alpha species in the culture medium . Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF-alpha and that this regulatory pathway can be interrupted using antibody to its receptor , EGF-R . OUTPUT:

sustaining proliferative signaling

HoC_1shot286

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: The immune system has an important role in tumor appearance and spreading . One of the most efficient subpopulations of cytotoxic cells in the destruction of tumors are NK cells . NK cells are activated and increase their cytotoxic potential and modulate their cytokine production after treatment with IFNgamma , IL-12 , TNFalpha and IL-2 . The investigation of the activity of NK cells was performed on peripheral blood lymphocytes ( PBL ) of 16 healthy controls and of 40 patients with metastatic breast carcinoma . Modulation of NK cells was performed with IL-2 , IL-7 , IL-12 , TNFalpha , monoclonal antibodies ( mAb ) for TNFalpha and TNFalpha receptors type I and II , as well as with sera of healthy controls and patients with breast cancer in different clinical stages . Modulating effect of the applied factors after in vitro treatment of PBL was evaluated by the cytotoxic assay using 51chromium . Our results indicate that IL-2 significantly increased the activity of NK cells of controls and breast cancer patients . The sera of patients with advanced breast cancer significantly reduced NK cell activity . IL-7 , IL-12 and mAb for TNFalpha do not significantly change the activity of NK cells . The presence of anti-TNFalpha mAb did not change the inhibitory effect of the sera of breast cancer patients with advanced disease on the activity of NK cells of controls and patients with breast cancer . Blocking of TNFalpha Rcs with mAbs decrease the reactivity of NK cells for IL-2 . The treatment of breast cancer patients with advanced clinical stage of breast cancer with IL-2 , as an additional therapy , could be advantageous , as NK cells after this treatment increase their cytotoxic activity against tumor cells and can improve therapeutical results . OUTPUT:

avoiding immune destruction

HoC_1shot287

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Considerable debate centers on the optimal treatment for vulvar melanoma , as well as those clinicopathological factors influencing prognosis . We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990 . Primary tumors were assessed according to Chung ( 47 patients ) and Breslow ( 65 patients ) microstaging systems . Fifty-nine patients ( 76% ) underwent radical vulvectomy , ten patients ( 13% ) had a partial vulvectomy , and nine patients ( 12% ) had a wide local excision . Fifty-six also underwent inguinal node dissection . Median follow-up was 193 months . Median survival was 63 months . Ten-year survival by Chung level was as follows : I 100% ; II , 81% ; III , 87% ; IV , 11% ; V , 33% . Ten-year survival by tumor thickness was as follows : 0.75 mm , 48% ; 0.75-1.5 mm , 68% ; 1.51-3.0 mm , 44% ; greater than 3.0 mm , 22% . Increased depth of invasion was associated with increased incidence of inguinal node metastasis . Cox regression analysis demonstrated prognostic significance for tumor thickness ( P less than 0.001 ) , inguinal node metastasis ( P less than 0.001 ) , and older age at diagnosis ( P less than 0.001 ) . Radical vulvectomy did not seem to improve survival over less radical procedures . Based on this experience , we recommend radical local excision for patients with malignant melanoma of the vulva . Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection . OUTPUT:

activating invasion and metastasis

HoC_1shot288

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Many human cellular and tissue compartments are supersaturated with respect to calcium oxyanion salts . In order to prevent the formation of injurious crystals efficient anti-crystallization protective mechanisms must be necessary . We suggest that depletion of such systems , particularly in ageing organisms and under conditions of oxidative stress , plays an important role in degenerative and inflammatory diseases , including cancer . OUTPUT:

tumor promoting inflammation

HoC_1shot289

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Tricyclic antidepressants , such as amitriptyline ( Elavil ) , and the nontricyclic agent , fluoxetine ( Prozac ) , bind to growth-regulatory intracellular histamine receptors , associated with anti-estrogen binding sites in microsomes and nuclei . The prototype anti-estrogen binding site/intracellular histamine receptor ligand , N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl , inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo . Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl , we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression ( equivalent human dose range , approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine ) . All experiments were performed blinded . In studies of growth stimulation of transplantable syngeneic tumors , groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells , followed 24 h later by daily i.p. injections of saline , amitriptyline , or fluoxetine . Tumor latency ( fibrosarcoma ) , aggregate tumor weight ( s.c. injected melanoma ) , or time to death from pulmonary metastasis ( i.v. injected melanoma ) was determined ; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo . In a mammary carcinogenesis model , the effects of chronic saline , amitriptyline , or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene ( DMBA ) were compared . Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5 , as compared to none of 20 saline controls ( P less than 0.002 ) . Similarly , 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline ( P less than 0.001 ) . For both models , tumor latency decreased 30-40% and , in the DMBA model , tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls . Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro . While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells , a significant ( P less than 0.01 ) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS ) OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot290

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Twelve postmenopausal women ( 54-93 years ) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery . Seven premenopausal patients ( 32-50 years ) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma . Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis , hormone receptor determination and analysis of proliferation fraction . Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy . Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells . A decreased proliferation fraction was observed in two tumors responding to tamoxifen . Eight patients , all with estrogen receptor positive tumors , had stable disease . Progressive disease was observed in two patients with less than 25% receptor positive cells . In these tumors the percentage of proliferating cells remained high during therapy . Objective response was recorded for six patients treated with chemotherapy . The clinical response was reflected in a decreased proliferation fraction . No correlation was observed between response and percentage of proliferating cells in the untreated tumor . The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas . OUTPUT:

sustaining proliferative signaling

HoC_1shot291

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Because PRL has growth factor activities in several tissues , we have asked whether it also has autocrine growth factor activity in pituitary GH3 cells . GH3 cells were grown at increasing densities in the presence or absence of antirat PRL ( polyclonal and monoclonal ) or nonspecific antibodies . Cell proliferation increased with increasing cell density , as did the concentration of PRL in the medium . Antirat PRL , but not control antibody , markedly inhibited but did not eliminate cell proliferation , and this effect was diminished with increasing PRL concentration in the medium . PRL receptors were demonstrated on 40-50% of the cells by indirect immunofluorescence using a specific antirat PRL receptor monoclonal antibody . Cell surface PRL was colocalized to the same 40-50% of the cells and copatched or cocapped along with the receptors . Absence or presence of PRL receptors did not correlate with stage of the cell cycle , as judged by ethidium bromide dual labeling . Cell surface PRL was found to be on PRL-containing cells . These data have fulfilled four criteria necessary for establishment of a substance as a secreted autocrine growth factor : 1 ) the factor must be secreted ; 2 ) in log growth phase , increased cell proliferation should occur at increased cell densities ; 3 ) the cells must display a receptor for the factor ; and 4 ) there must be a growth response to the factor . Thus we have established that PRL is an autocrine growth factor for at least 40-50% of the GH3 cell population . This , to our knowledge , is the first example of autocrine growth factor activity of a major hormone normotopically expressed . OUTPUT:

sustaining proliferative signaling

HoC_1shot292

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 study focuses on the effects of combined oral contraceptives ( COCs ) on the onset of cervical dysplasia among Zimbabwean women . Women who had used COCs for at least 2 years and were in continued use were compared to non-users of COCs ( control group ) . It was difficult to establish the average period of contraceptive use because in most instances there was no proper documentation on the exact dates as to when the subjects started using COCs . The number of subjects with each condition was noted from each of the following age groups ; <20 years , 20-29years , 30-39years , 40-49years and >50years . It was found that the percentage of the control group with benign conditions was higher than that of COC users in all age groups . Significant differences at 95 percent confidence level were noted for the 20-29 years age group ( z= -2.21 ) and 40-49 years age group ( z= -2.53).The number of subjects in the <20 years and >50 years age groups were too small for z-score computation . No significant differences were noted for mild to moderate cervical inflammation in all age groups . There was a higher percentage of COC users with severe cervical inflammation compared to the control group in all age groups . Significant differences were noted in the 30-39 years age group ( z=3.45 ) and 40-49 years age group ( z= 1.98 ) . A higher percentage of CIN I was noted among pooled COC users compared to the control group ( z= 2.00 ) although no significant differences were obtained within different age groups . In conclusion , severe cervical inflammation and CIN I are more frequent among Zimbabwean women who use COCs as compared to non-users of COCs . Frequencies of advanced CIN are low among women who undergo routine cytological screening because this enables early detection and subsequent treatment . OUTPUT:

tumor promoting inflammation

HoC_1shot293

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 constructed plasmids pS3G-1 and pSG4 that contain single acetylaminofluorene adducts within contiguous runs of three ( 5'-CCCG1G2G3-3' ) and four ( 5'-CG1GGG4T-3' ) guanine residues , respectively . In Escherichia coli , the frequency of induced -1 frameshift mutations was strongly dependent on the position of modification : pS3G-G3 was approximately 100-fold and 10-fold more mutagenic than pS3G-G1 and pS3G-G2 , respectively ; pSG4-G4 was approximately 600-fold more mutagenic than pSG4-G1 . Mutagenesis was SOS-dependent and was markedly reduced in bacteria that were proficient in nucleotide excision repair as compared to a repair-deficient uvrA6 mutant . DNA sequencing showed that -1 frameshift events in pS3G-1 consisted of either targeted mutations ( greater than 90% of induced mutations ) within the guanine sequence or semitargeted mutations ( greater than 10% ) in the 5 ' flanking repetitive cytosine sequence . Semitargeted events , which were observed when acetylaminofluorene modification was at G1 and G2 , show that a lesion can reduce the fidelity of replication at positions 5 ' to its location on the template strand . No semitargeted frameshifts were observed in plasmid pSG4 , which lacks a repetitive sequence 5 ' to the adduct . Our results are consistent with a model for frameshift mutagenesis in which the acetylaminofluorene adduct ( i ) allows accurate incorporation of cytosine opposite the bulky lesion during DNA synthesis and ( ii ) impedes elongation of primer/template termini formed opposite the adduct or 5 ' to the adduct on the template strand , providing increased opportunity for the formation of slipped frameshift intermediates . OUTPUT:

genomic instability and mutation

HoC_1shot294

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Novel photosensitizers Hypocrellin A ( HA ) and Hypocrellin B ( HB ) , lipid soluble perylquinone derivatives of the genus Hypericum have a strong photodynamic effect on tumors and viruses . However , the mechanisms of tumor cell death induced by HA and HB are still unclear . In this study , we attempt to elucidate the photodynamic effects of HA and HB compounds in poorly differentiated ( CNE2 ) and moderately differentiated ( TW0-1 ) human nasopharyngeal carcinoma ( NPC ) cells as well as human mucosal colon ( CCL-220.1 ) and bladder ( SD ) cells . Using these cell lines we investigated few hall marks of apoptotic commitments in a drug and light dose dependent manner . Tumor cells photoactivated with HA and HB showed cell size shrinkage and an increase in the sub-diploid DNA content . A loss of membrane phospholipid asymmetry associated with apoptosis was induced by all tumor cell lines as evidenced by the externalization of phosphatidylserine . Western blot analysis of poly ( ADP-ribose ) polymerase , a caspases substrate , showed the classical cleavage pattern ( 116 to 85kDa ) associated with apoptosis in HA and HB-treated cell lysates . In addition , PARP cleavage was blocked by using tetrapepdide caspases inhibitors such as DEVD or z-VAD . These results demonstrate that tumor cell death induced by HB and HA is mediated by caspase proteases . This study also identifies both colon and bladder cells were more sensitive cell lines than NPC ( CNE2 and TWO-1 ) cell lines . OUTPUT:

resisting cell death

HoC_1shot295

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 cytotoxic activity , the induction of apoptosis , and the interstrand cross-linking efficiency in the A2780cisR ovarian tumor cell line , after replacement of the two NH3 nonleaving groups in trans-[PtCl2(NH3)2] ( trans-DDP ) by dimethylamine and isopropylamine . The data show that trans-[PtCl2(NH(CH)2)(NHCH(CH3)2)] is able to circumvent resistance to cis-[PtCl2(NH3)2] ( cis-DDP , cisplatin ) in A2780cisR cells . In fact , trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] shows a cytotoxic potency higher than that of cis-DDP and trans-DDP , with the mean IC50 values being 11 , 58 , and 300 microM , respectively . In addition , at equitoxic doses ( concentrations of the platinum drugs equal to their IC50 values ) and after 24 hours of drug treatment , the level of induction of apoptosis by trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] is twice that produced by cis-DDP . Under the same experimental conditions , trans-DDP does not induce significant levels of apoptosis in A2780cisR cells . After 24 hours of incubation of A2780cisR cells at concentrations equal to the IC0o value of the platinum drugs , the level of DNA interstrand cross-links ( ICLs ) induced by trans-[PtCI2(NH(CH)2)(NHCH(CH3)] is two and three times higher , respectively , than those induced by cis-DDP and trans-DDP . We also found that trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] formed DNA ICLs between guanine and complementary cytosine . We propose that , in A2780cisR cells , the induction of apoptosis by trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] is related to its greater ability ( relative to cis-DDP and trans-DDP ) to form DNA ICLs . OUTPUT:

resisting cell death;genomic instability and mutation

HoC_1shot296

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time . The apoptotic cancer cell contracted , became rounder and divorced from adjacent cells ; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane ; the endoplasmic reticulums ( ER ) expanded and fused with the cellular membrane ; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma . Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediatedin situ nick end labeling ( TUNEL ) . It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample . The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency ( ULF ) pulsed gradient magnetic field ; the nuclei DNA contents decreased , indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells . It was suggested that magnetic field could inhibit the metabolism of cancer cell , lower its malignancy , and restrain its rapid and heteromorphic growth . Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour , it could be used as a new method to treat cancer . OUTPUT:

resisting cell death

HoC_1shot297

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Partial DNA fragments of Botrytis cinerea field isolates encoding the putative osmosensor histidine kinase gene ( BcOS1 ) were cloned by polymerase chain reaction amplification and the predicted amino acid sequences were compared between dicarboximide-sensitive and resistant field isolates . The predicted BcOS1p is highly homologous to osmosensor histidine kinase OS1p from Neurospora crassa including the N-terminal six tandem repeats of approximately 90 amino acids . Four dicarboximide-resistant isolates of B. cinerea ( Bc-19 , Bc-45 , Bc-682 , and Bc-RKR ) contained a single base pair mutation in their BcOS1 gene that resulted in an amino acid substitution in the predicted protein . In these resistant isolates , codon 86 of the second repeat , which encodes an isoleucine residue in sensitive strains , was converted to a codon for serine . The mutation of Botrytis field resistant isolates was located on the second unit of tandem amino acid repeats of BcOS1p , whereas the point mutations of the fifth repeat of OS1p confer resistance to both dicarboximides and phenylpyrroles and also osmotic sensitivity in Neurospora crassa . These results suggest that an amino acid substitution within the second repeat of BcOS1p is responsible for phenotypes of field resistant isolates ( resistant to dicarboximides but sensitive to phenylpyrroles , and normal osmotic sensitivity ) in B. cinerea . OUTPUT:

genomic instability and mutation

HoC_1shot298

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: An aqueous extract of Kefir , fermented milk originally produced in the Caucasus mountains , suppressed morphological changes of human melanoma HMV-1 and SK-MEL cells and human normal fibroblastTIG-1 cells caused by UVC-irradiation , suggesting that UV damage can be suppressed by the Kefir extract . The addition of the Kefir extract after UVC-irradiation of HVM-1 cells resulted in a remarkable decrease in intracellular reactive oxygen species ( ROS ) which had been increased by UVC irradiation . The Kefir extract also stimulated unscheduled DNA synthesis and suppressed UVC-induced apoptosis of HMV-1 cells . A colony formation assay revealed that the Kefir extract rescued HMV-1 cells from cell death caused by UVC irradiation . The Kefir extract , as well as methyl methanethiosulfonate which is known to enhance the nucleotide excision repair ( NER ) activity , exhibited strong thymine dimer repair-enhancing activity . Epigalocatechin exhibited a weak NER activity but vitamins A , C , and E and catechin showed no NER activity . The thymine dimer repair-enhancing factors in the Kefir extract were heat-stable and assumed to be molecules with a molecular weight of less than 5000 . The treatment of HMV-1 cells with the Kefir extract during or before UVC- irradiation also prevented the generation of ROS and thymine dimmer , and suppressed the apoptosis of HMV-1 cells , suggesting that application of Kefir can prevent UV damage . OUTPUT:

tumor promoting inflammation;genomic instability and mutation;resisting cell death

HoC_1shot299

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Biomaterials such as polyetherurethans ( PEUs ) are the scaffolding , which is indispensable for the development of the bio-artificial organs . However , PEUs can induce tumors in subcutaneous implantation sites in rat . We have shown that the different inhibitory potential of gap junctional intercellular communication ( GJIC ) on the surface of the biomaterials , including PEUs , is a key step in determining the tumorigenic potential . Here we show that suppression of a gap junctional protein connexin 43 ( Cx43 ) plays an important role in in vivo tumorigenesis induced by PEUs for the first time and that Cx43 transfection may be an effective strategy for preventing tumorigenesis induced by biomaterials . Rat tumor cell line U41 is derived from tumors in the subcutaneous implantation of PEU films . The GJIC and the expression of Cx43 were suppressed in U41 . The restoration of normal phenotype , such as reduction of growth rate , recovery of contact inhibition and loss of colony formation ability in soft agar , was achieved by Cx43 transfection . These results strongly suggest that suppression of Cx43 expression plays an important role in the development of rat malignant fibrous histiocytoma ( MFHC ) caused by PEUs and that Cx43 transfection is effective for prevention of tumorigenesis induced by PEUs . OUTPUT:

evading growth suppressors