Datasets:

clinicalnlplab

/

HoC_1shot_test

like 1

HoC_1shot100

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 immune function of microglia and macrophages in brain tumors , the expression of MHC class II and B7 costimulatory molecules in three rodent glioma models was examined . Microglia and macrophages , which accounted for 5-12% of total cells , expressed B7.1 and MHC class II molecules in the C6 and 9L tumors , but not RG2 gliomas . Interestingly , the expression of B7.1 and MHC class II molecules by microglia and macrophage was associated with an increase in the number of tumor-infiltrating lymphocytes in C6 and 9L tumors . B7.2 expression , which was present at low levels on microglia and macrophages in normal brain , did not significantly change in tumors . Interestingly , the expression of all three surface antigens increased after microglia were isolated from intracranial C6 tumors and cultured for a short period of time . We conclude that microglia immune activity may be suppressed in gliomas and directly correlates to the immunogenecity of experimental brain tumors . OUTPUT:

avoiding immune destruction

HoC_1shot101

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Comparative mutagenesis studies of N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene ( dG-AAF ) and N-(2'-deoxyguanosin-8-yl)-2-aminofluorene ( dG-AF ) adducts positioned in the Nar I restriction enzyme site were performed using Escherichia coli ( E. coli ) and simian kidney ( COS-7 ) cells . Oligodeoxynucleotides ( (5)(')TCCTCG(1)G(2)CG(3)CCTCTC ) containing a recognition sequence for the Nar I restriction enzyme were modified site-specifically with dG-AAF or dG-AF . Modified and unmodified oligomers inserted into single-stranded phagemid shuttle vectors were used to transform E. coli or to transfect COS-7 cells . Following replication in host cells , progeny plasmids were recovered and analyzed for mutations . In SOS-induced E. coli , dG-AAF primarily induced one- and two-base deletions . The mutational frequency varied , depending on the position modified in the Nar I site ; 91% two-base deletions were observed at G(3) , while 8.4% and 2.8% deletions were detected at G(2) and G(1) , respectively . In contrast , dG-AF at any position in the Nar I site failed to produce deletions , generating primarily G --&gt ; T transversions ( mutational frequency , 7.6-8.4% ) . In COS-7 cells , both dG-AAF and dG-AF primarily induced G --&gt ; T transversions . Mutation frequencies for dG-AAF were 9.4-24% , the highest values being at G(1) and G(3) . Mutation frequencies for dG-AF were 9.3-21% , the higher value at G(2) . We conclude from this study that the mutation potential of dG-AAF and dG-AF depends on the structure of the adduct , the sequence context of the lesion , and the host cell used for the experiment . OUTPUT:

genomic instability and mutation

HoC_1shot102

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 &amp ; OBJECTIVE Altered cell adhesion has a critical role in the development of epithelial cancers . E-cadherin act on the maintenance of cell-cell adhesion and its function was thought to be regulated by associated cytoplasmic proteins , such as alpha-catenin and beta-catenin . This study was designed to examine the expression of beta-catenin in gastric carcinoma and to determine the relationship between tumor characteristics and survival . METHODS Immunohistochemical staining of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was demonstrated in 43.2% and 44.6% of tumors respectively . Up to 63% of tumors stained abnormally for one or two components of the cadherin-catenin complex ( beta-catenin , E-cadherin ) . Abnormal beta-catenin and E-cadherin staining occurred more frequently in poor differentiated tumor than in good differentiated tumors ( P &lt ; 0.005 , respectively ) . There was a significant correlation between abnormal beta-catenin expression and depth of invasion(P &lt ; 0.025 ) . Moreover , abnormal beta-catenin expression was more frequent in tumors with positive lymph node metastasis ( 45/84 , 53.6% ) and distance metastasis(21/31 , 67.7% ) than in tumors without lymph node metastasis ( 19/64 , 29.7% ) ( P &lt ; 0.005 ) and distance metastasis ( 43/117 , 36.8% ) ( P &lt ; 0.005 ) . A survival advantage was noted in tumors retaining normal membranous expression of beta-catenin , independent of type , grade , or stage ( P &lt ; 0.005 ) . CONCLUSIONS Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma . The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker . OUTPUT:

activating invasion and metastasis

HoC_1shot103

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 an attempt to find a strategy to modulate the proliferation of vascular endothelial cells , we examined whether constitutive activation of proto-oncogen protein p21 ( Ras ) induced the reentry of confluent human umbilical vascular endothelial cells ( HUVECs ) into the S phase . When an adenovirus construct expressing a constitutively active Ras mutant ( Ad/RasG12V ) was infected into HUVECs , their morphology changed strikingly and they appeared to be transformed . However , Ad/RasG12V-infected HUVECs did not enter the S phase , as determined by assessing 3H-thymidine incorporation . In accordance with the above results , the expression of cyclin A both at the transcript and protein levels did not increase in Ad/RasG12V-infected HUVECs relative to that in control cells , although the expression of cyclin D1 was induced in Ad/RasG12V-infected cells . Interestingly , the expression of the cyclin-dependent kinase ( CDK ) inhibitor p21cip1 was remarkably increased while that of p27kip1 did not decrease in Ad/RasG12V-infected HUVECs . Furthermore , CDK2 activity was not induced in Ad/RasG12V-infected HUVECs . These results suggested that the constitutive activation of Ras promoted the reentry of confluent HUVECs in the G0 phase into the G1 phase , but not into the S phase . The results also indicated that the constitutive activation of Ras might have induced the persistent expression of p21cip1 and p27kip1 , and that this induction of p21cip1 and p27kip1 expression possibly caused the cell cycle arrest at the G1 phase . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot104

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: AIM The study was designed to explore the effects of antisense human telomerase RNA ( ahTR ) on the malignant phenotype of gastric carcinoma cell line SGC-7901 , and its potential role in gene therapy for tumors . METHODS An ahTR eukaryotic expression vector , including the sequence of template region of telomere repeats , was constructed by recombinant technology of molecules and then transfected into gastric carcinoma cell line SGC-7901 by liposome DOTAP . Subsequently , the expression of hTR RNA and ahTR RNA by reverse transcription-polymerase chain reaction , telomerase activity by telomeric repeat amplification protocol-ELISA ( TRAP-ELISA ) , telomere length by Southern blotting , cell morphology under light microscope , cellular proliferation capacity by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay , cell-cycle distribution by flow cytometry , efficiency of clone formation in soft agar , and tumorigenecity in nude mice were examined and evaluated in ahTR-transfected cells , control plasmid pCI-neo transfected cells and their parental cells . RESULTS An ahTR eukaryotic expression vector was constructed and successfully transfected into SGC-7901 cells . The telomerase activity in ahTR-transfected SGC-7901 cells decreased from 100% to approximately 25% , and telomere length in the cells shortened to 3.35 from 4.08 Kb at 60 population doublings . Compared with the parental cells and pCI-neo transfected cells , ahTR-transfected cells displayed some morphological changes , such as decreased atypia , and recovery of contact inhibition and density inhibition under light microscope . Furthermore , ahTR-transfected cells displayed decreased invasive capacity in Borden's chamber invasive model , increased G0/G1 phase rate and apoptotic rate . Surprisingly , ahTR-transfected SGC-7901 cells lost their capacity for clone formation in soft agar and tumorigencity in nude mice . CONCLUSION Antisense-hTR transfection can inhibit the growth of SGC-7901 cells and partially reverse the malignant phenotypes . This study provides an exciting approach for cancer therapy by inhibiting telomerase activity using an antisense gene . OUTPUT:

evading growth suppressors;activating invasion and metastasis;resisting cell death

HoC_1shot105

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 identified REDD1 as a novel transcriptional target of p53 induced following DNA damage . During embryogenesis , REDD1 expression mirrors the tissue-specific pattern of the p53 family member p63 , and TP63 null embryos show virtually no expression of REDD1 , which is restored in mouse embryo fibroblasts following p63 expression . In differentiating primary keratinocytes , TP63 and REDD1 expression are coordinately downregulated , and ectopic expression of either gene inhibits in vitro differentiation . REDD1 appears to function in the regulation of reactive oxygen species ( ROS ) ; we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress , which are both increased following ectopic expression of either TP63 or REDD1 . Thus , REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot106

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin ( TCDD ) . TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial , viral , and parasitic infections in exposed animals . Nearly 20 years after the Seveso , Italy , accident , we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones ( n = 62 ) and in the surrounding noncontaminated area ( n = 58 ) . Plasma IgG levels decreased with increasing TCDD plasma concentration ( r = -0.35 , p = 0.0002 ) . Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest ( &lt ; 3.5 ppt ) TCDD levels to 1,163 mg/dL in the group with the highest ( 20.1-89.9 ppt ) TCDD levels ( p = 0.002 ) . The association was significant ( p = 0.0004 ) after adjusting for age , sex , smoking , and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs . IgM , IgA , C3 , and C4 plasma concentrations did not exhibit any consistent association with TCDD levels . We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components . The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse . Methodologic issues , results , and possible sources of variation between studies are discussed . The possible long-term immunologic effects of TCDD exhibited by the participants of the present study , coupled with the increased incidence of lymphatic tumors in the area of the accident , warrant further investigation . OUTPUT:

avoiding immune destruction

HoC_1shot107

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: During mitotic exit , a small GTPase Tem1 needs to be activated . During most of the cell cycle , Tem1 activity is antagonized by a GTPase activating complex ( GAP ) composed of Bub2 and Bfa1 . Bfa1 protein has cell cycle regulated phosphorylation depending upon the Polo-like kinase Cdc5 . This phosphorylation dissociates Bfa1 from Tem1 and thus relieves the inhibition of Tem1 by the GAP complex . Bub2 and Bfa1 are also required to prevent mitotic exit when there is DNA damage , spindle damage or spindle misorientation at G(2)/M phase . While Cdc5 inhibits Bfa1/Bub2 , mutating the Cdc5 phosphorylation sites on Bfa1 does not have a strong activating effect on Bub2/Bfa1 , suggesting there must be additional regulation in this pathway . Here we report that Bub2 protein also has cell cycle regulated phosphorylation . This phosphorylation is partially dependent upon the Polo-like kinase Cdc5 and is consistent with negative regulation of the Bub2/Bfa1 GAP complex . Spindle damage or spindle misorientation prevents Bub2 phosphorylation . The spindle damage effect is dependent upon the spindle assembly checkpoint components Mad2 and Mps1 . Thus like Bfa1 , Bub2 protein is also controlled both during mitotic exit and in response to cell cycle checkpoints . Bub2 phosphorylation is likely to be controlled by a novel kinase . OUTPUT:

sustaining proliferative signaling;evading growth suppressors

HoC_1shot108

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Liquid chromatography coupled to tandem mass spectrometry has been used for the detection and the structural characterization of T-rich model oligonucleotides covalently modified by estradiol-2,3-quinone . After separation by gradient elution , adducts were analyzed by negative electrospray mass spectrometry , enabling to evidence and localize the modifications in the oligonucleotide sequence . Modifications by one molecule of estrogen were evidenced on purines ( A , G ) whereas no reaction was observed on pyrimidic bases ( T ) . Isomeric adducts were differentiated using tandem mass spectrometry , and energy resolved mass spectrometry allowed to underline differences in the behavior of the adducts towards collisional excitation into an ion trap device . OUTPUT:

genomic instability and mutation

HoC_1shot109

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Prostaglandin E(2) ( PGE(2) ) receptor subtype EP(2) , which is coupled to cAMP metabolism , is known to mediate proliferation of primary human keratinocytes in vitro . The effect of gain or loss of EP(2) receptors in immortalized human keratinocytes ( HaCat cells ) was examined . HaCat keratinocytes were transfected with sense or anti-sense constructs of the EP(2) receptor . Loss or gain of EP(2) expression was documented by immunoblot and associated changes in agonist-stimulated cAMP production . Loss or gain of EP(2) receptor expression correlated with alterations in plating efficiencies but with modest affects on growth . When cell lines were studied in an organ culture model , anti-sense clones were highly invasive compared with vector controls and sense transfectants . A marked increase in prostaglandin production is commonly seen in malignant lesions . Because prostaglandin receptors are known to undergo ligand-induced receptor down-regulation , we sought to determine whether EP(2) receptor down-regulation results in increased invasiveness . In vector controls , invasiveness was reproduced by ligand-dependent EP(2) receptor down-regulation as assessed by immunohistochemistry . In addition , loss of EP(2) receptor expression was associated with decreased paxillin expression , a critical component of focal adhesion assembly . Thus , down-regulation of EP(2) receptors represents a potential mechanism for neoplastic progression to an invasive phenotype . OUTPUT:

activating invasion and metastasis;sustaining proliferative signaling

HoC_1shot110

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 goal of this study was to determine the prevalence of sequence variants in the class I beta-tubulin ( clone m40 ) gene and their occurrence in human tumors and cancer cell lines . DNA was isolated from 93 control individuals representing a wide variety of ethnicities , 49 paclitaxel-naive specimens ( 16 ovarian cancers , 17 non-small cell lung cancers , and 16 ovarian cancer cell lines ) , and 30 paclitaxel-resistant specimens ( 9 ovarian cancers , 9 ovarian cancer cell lines , and 12 ovarian cancer xenografts in nude mice ) . Denaturing high-performance liquid chromatography and direct sequence analysis detected two silent polymorphisms in exon 4 , Leu217Leu ( CTG/CTA ) and Gly400Gly ( GGC/GGT ) , with minor allele frequencies of 17 and 0.5% , respectively . Five nucleotide substitutions and one single-base deletion were detected in introns 1 , 2 , and 3 and in the 3 ' untranslated region . Analysis of 49 paclitaxel-naive and 30 paclitaxel-resistant specimens revealed no additional polymorphisms in the coding region . In addition , no amino acid replacements were found in chimpanzee , gorilla , and orangutan in comparison to human . Our data demonstrate a very high degree of sequence conservation in class I beta-tubulin , suggesting that all residues are important in tubulin structure and function . Individual variation in response to treatment with paclitaxel is not likely to be caused by genetic variations in the beta-tubulin drug target . Moreover , acquired mutations in class I beta-tubulin are unlikely to be a clinically relevant cause of drug resistance . OUTPUT:

genomic instability and mutation

HoC_1shot111

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Our previous studies have shown that genistein inhibits the growth of PC3 prostate cancer cells and induces apoptosis by inhibiting nuclear factor kappaB ( NF-kappaB ) and Akt signaling pathways . To better understand the precise molecular mechanism(s) by which genistein exerts its effects on PC3 cells , we utilized cDNA microarray to interrogate 12,558 known genes to determine the gene expression profiles altered by genistein treatment . We found a total of 832 genes that showed a greater than twofold change after genistein treatment from two independent experiments with a high degree of concordance . Among these genes , 774 genes were down-regulated and 58 genes were up-regulated with genistein treatment . Cluster analysis showed nine different types of expression alternations . These genes were also subjected to cluster analysis according to their biological functions . We found that genistein regulated the expression of genes that are critically involved in the regulation of cell growth , cell cycle , apoptosis , cell signaling transduction , angiogenesis , tumor cell invasion and metastasis . Reverse transcription-polymerase chain reaction ( RT-PCR ) analysis was used to confirm the results of cDNA microarray , and the results of RT-PCR were consistent with the microarray data . We conclude that genistein affected the expression of a large number of genes that are related to the control of cell survival and physiologic behaviors . The gene expression profiles provide comprehensive molecular mechanism(s) by which genistein exerts its pleiotropic effects on cancer cells . Genistein-induced regulation of these genes may be further exploited for devising chemopreventive and/or therapeutic strategies for prostate cancer . OUTPUT:

activating invasion and metastasis;inducing angiogenesis;resisting cell death

HoC_1shot112

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 signal transducer and activator of transcription ( STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases ( Jak ) in response to interferon gamma(IFN-gamma) . The phosphorylated STAT1 translocates to the nucleus , where it turns on specific sets of IFN-gamma-inducible genes , such as the interferon regulatory factor ( IRF)-1 . We show here that gamma irradiation reduces the IFN-gamma mRNA expression . The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed . In contrast , the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample . Furthermore , we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes ' reaction ( MLR ) . These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals , thereby causing the immunosuppression of the Th1 response . OUTPUT:

avoiding immune destruction

HoC_1shot113

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Properly regulated keratinocyte cell death is fundamentally important to maintain structural integrity and homeostatic function of epidermis . Moreover , from an oncological perspective , therapeutic approaches selectively targeting apoptosis of malignant cell types while sparing normal keratinocytes in surrounding skin is desirable . Apo2Ligand/tumor necrosis factor-related apoptosis-inducing ligand ( Apo2L/TRAIL ) has been observed to preferentially induce cytopathic effects on transformed/malignant cell types compared with their non-neoplastic counterparts . In this report , two different biologically active preparations of Apo2L/TRAIL , a non-tagged version , NT-Apo2L/TRAIL , and a leucine zipper fusion protein , LZ-Apo2L/TRAIL , were examined for their ability to trigger apoptosis in normal human keratinocytes , and in an immortalized cell line ( HaCaT cells ) . Differences between these preparations were observed , including : NT-Apo2L/TRAIL induced less keratinocyte apoptosis compared with LZ-Apo2L/TRAIL ; NT-Apo2L/TRAIL also induced less apoptosis of HaCaT cells compared with LZ-Apo2L/TRAIL ; LZ-Apo2L/TRAIL but not NT-Apo2L/TRAIL induced cytotoxic effects when keratinocytes became growth arrested due to undergoing spontaneous replicative senescence--a biological state previously observed to be resistant to UV-light-induced apoptosis . Similarities between preparations included : an enhanced ability for both Apo2L/TRAIL preparations to kill a greater relative percentage of HaCaT cells compared with keratinocytes ; enhanced cytotoxicity towards keratinocytes that had their NF-B activity inhibited ; a dependence of both Apo2L/TRAIL preparations on FADD and caspase activation ; triggering of the same caspase cascades including caspase 8 and 3 ; and an ability to induce apoptosis even when HaCaT cells and keratinocytes were transduced to overexpress either Bcl-2 or Bcl-x(L) ( survival factors that reduce susceptibility to UV-light-induced apoptosis ) . These results indicate that while both preparations of Apo2L/TRAIL possess biological activity , there are important differences as regards their ability to induce apoptosis in normal and immortalized keratinocytes . Moreover , the death receptor pathway triggered by LZ-Apo2L/TRAIL can overcome the apoptotic resistance normally observed in response to UV-light mediated by Bcl-2/Bcl-x(L) , as well as by the state of cellular senescence . Unraveling the molecular basis for these differential biological effects may reveal a new strategic role for these death receptor/ligands linked to apoptosis in maintaining the dynamic balance of keratinocyte proliferation , differentiation , and cell death necessary to achieve a homeostatic thickness and function of normal skin . In addition , it may be possible to utilize these Apo2L/TRAIL preparations for the treatment of various sun-induced skin cancers as they can differentially trigger apoptosis of transformed keratinocytes , or keratinocytes with abnormal NF-kappaB signaling , while sparing adjacent normal keratinocytes . OUTPUT:

enabling replicative immortality;resisting cell death

HoC_1shot114

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: 4-Hydroxy-2-nonenal ( HNE ) , a major racemic product of lipid peroxidation , reacts with histidine to form a stable HNE-histidine Michael addition-type adduct possessing three chiral centers in the cyclic hemiacetal structure . In the present study , we characterized configurational isomers of a HNE-N(alpha)-acetylhistidine adduct by NMR spectroscopy and by molecular orbital calculations . In addition , we raised monoclonal antibodies against ( R)-HNE-histidine and ( S)-HNE-histidine adducts , characterized their specificities , and examined in vivo localizations of each adduct under oxidative stress . To facilitate structural characterization of the configurational isomers of an HNE-histidine adduct , we prepared the ( R)-HNE-histidine and ( S)-HNE-histidine adducts by incubating N(alpha)-acetylhistidine with each HNE enantiomer , both of which provided two peaks ( Ra and Rb from ( R)-HNE-histidine and Sa and Sb from ( S)-HNE-histidine adducts ) in reversed-phase high-performance liquid chromatography . The NMR analysis showed that each peak was a mixture of two diastereomers . In addition , the analysis of the nuclear Overhauser effect enabled the determination of configurations of the eight isomers . The relative amounts of these isomers in the NMR analysis correlated with the relative energies calculated by molecular orbital methods . On the other hand , using ( R)-HNE-modified and ( S)-HNE-modified keyhole limpet hemocyanins as the antigens , we raised the monoclonal antibodies , mAbR310 and mAbS412 , which enantioselectively recognized the ( R)-HNE-histidine and ( S)-HNE-histidine adducts , respectively . Among the mixtures ( Ra , Rb , Sa , and Sb ) of diastereomers , mAbR310 showed the highest immunoreactivity to Rb ( the mixture of 2R,4S,5R and 2S,4S,5R isomers ) , whereas mAbS412 preferentially recognized Sa ( the mixture of 2R,4S,5S and 2S,4S,5S isomers ) . The presence of ( R)-HNE and ( S)-HNE epitopes in vivo was immunohistochemically examined in the kidney of rats exposed to the renal carcinogen , ferric nitrilotriacetate , by which nuclear and cytosolic stainings with mAbR310 and mAbS412 , respectively , were detected . OUTPUT:

genomic instability and mutation

HoC_1shot115

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 ability of p53 to alter , at the transcriptional level , the gene expression of downstream targets is critical for its role as a tumor suppressor . Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators , histone acetyltransferases , and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction . We demonstrate here , however , that the promoter regions for the p53 target genes , p21 , 14-3-3sigma , and KARP-1 , exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell . In contrast , p53 response elements , which resided outside the immediate promoter regions , existed within DNase I-resistant chromatin domains . Thus , p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element . As such , these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression . OUTPUT:

genomic instability and mutation

HoC_1shot116

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 HT29 adenocarcinoma is a common model of epithelial cell differentiation and colorectal cancer and its death is an oft-analyzed response to TNF family receptor signaling . The death event itself remains poorly characterized and here we have examined the involvement of caspases using pan-caspase inhibitors. zVAD-fmk did not block death of HT29 cells in response to activation of the Fas , TRAIL , TNF , TWEAK and LTbeta receptors . The secondary induction of TNF or the other known bona fide death inducing ligands did not account for death following LTbeta receptor activation indicating that TNF family receptors can trigger a caspase-independent death pathway regardless of the presence of canonical death domains in the receptor . To provide a frame of reference , the phenotype of HT29 death was compared to four other TNF family receptor triggered death events ; Fas induced Jurkat cell apoptosis , TNF/zVAD induced L929 fibroblast necrosis , TNF induced death of WEHI 164 fibroblastoid cells and TNF/zVAD induced U937 death . The death of HT29 and U937 cells under these conditions is an intermediate form with both necrotic and apoptotic features . The efficient coupling of TNF receptors to a caspase-independent death event in an epithelial cell suggests an alternative approach to cancer therapy . OUTPUT:

resisting cell death

HoC_1shot117

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 cancer chemotherapeutic drugs designed to have cytotoxic actions on tumor cells have recently been shown to also have antiangiogenic activities . Endothelial cell migration and proliferation are key components of tumor angiogenesis , and agents that target the microtubule cytoskeleton can interfere with these processes . In this study , the effect on endothelial cell functions of the microtubule-stabilizing drugs Taxotere and Taxol were evaluated in three in vitro assays : a chemokinetic migration assay , an angiogenesis factor-mediated chemotactic migration assay , and a three-dimensional Matrigel tubule formation assay , using rat fat pad endothelial cells ( RFPECs ) and/or human umbilical vein endothelial cells ( HUVECs ) . Taxotere was active in all three assays at concentrations that were not cytotoxic and did not inhibit endothelial cell proliferation . In the RFPEC chemokinetic migration and in vitro tubule formation assays , the IC50 values were approximately 10(-9) M for both Taxotere and Taxol . HUVEC migration , however , was more sensitive to Taxotere , with an observed IC50 of 10(-12) M in a chemokinetic assay . In a Boyden chamber assay , HUVEC chemotaxis stimulated by either of two angiogenic factors , thymidine phosphorylase or vascular endothelial growth factor , was inhibited by Taxotere with an IC50 of 10(-11) M and was ablated at 10(-9) M. Taxotere was also up to 1000-fold more potent than Taxol in inhibiting either chemokinetic or chemotactic migration . When the microtubule cytoskeleton was visualized using immunofluorescence staining of alpha-tubulin , there were no gross morphological changes observed in HUVECs or RFPECs treated with Taxotere at concentrations that inhibited endothelial cell migration but not proliferation . The effects of Taxotere on migration were associated with a reduction in the reorientation of the cell's centrosome , at concentrations that did not affect gross microtubule morphology or proliferation . Reorientation of the centrosome , which acts as the microtubule organizing center , in the intended direction of movement is a critical early step in the stabilization of directed cell migration . These data indicate that endothelial cell migration correlates more closely with changes in microtubule plasticity than with microtubule gross structure . The antiangiogenic activity of Taxotere in vivo was assessed in a Matrigel plug assay . In this assay , the angiogenic response to fibroblast growth factor 2 was inhibited in vivo by Taxotere with an ID50 of 5.4 mg/kg when injected twice weekly over a 14-day period , and angiogenesis was completely blocked in mice that received 10 mg/kg Taxotere . The in vivo data further suggested that Taxotere had selectivity for endothelial cell migration and/or microvessel formation because infiltration of inflammatory cells into the Matrigel plug was much less sensitive to inhibition by Taxotere . In conclusion , Taxotere is a potent and potentially specific inhibitor of endothelial cell migration in vitro and angiogenesis in vitro and in vivo . OUTPUT:

inducing angiogenesis;tumor promoting inflammation

HoC_1shot118

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc . We investigate the effect of zinc deficiency on DNA damage , expression of DNA-repair enzymes , and downstream signaling events in a cell-culture model . Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress . Low intracellular zinc increased DNA single-strand breaks ( comet assay ) . Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease ( APE ) . Repletion with zinc restored cell growth and reversed DNA damage . APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression . The ability of the transcription factors p53 , nuclear factor kappaB , and activator protein 1 ( AP1 ) to bind to consensus DNA sequences was decreased markedly with zinc deficiency , as assayed by electrophoretic mobility-shift assays . Thus , low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression , but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc . OUTPUT:

tumor promoting inflammation;genomic instability and mutation

HoC_1shot119

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Ovarian hormones have a pivotal role in the control of proliferation in the mammary gland , and cumulative life-time exposure to ovarian hormones is known to be a determinant of breast cancer risk . We have shown previously that a p.o.-active , long-acting butyrate analogue , sodium phenylbutyrate ( PB ) , reduced proliferation in normal and malignant human breast cells in culture and reduced expression of ovarian hormone receptors , suggesting that PB had cellular effects consistent with decreasing breast cancer risk . The aim of this study was to determine the in vivo effects of PB in the normal mammary gland on epithelial cell proliferation , estrogen receptor alpha ( ER alpha ) expression , and cyclin D1 expression . BALB/c mice were treated with PB , delivered by mini-osmotic pumps , for 7 days . Moderate ( 250 mg/kg/day ) and high ( 500 mg/kg/day ) PB treatment resulted in a decrease in proliferation in mammary epithelial cells ( P &lt ; 0.001 ) , determined by bromodeoxyuridine incorporation . Analysis of ER alpha immunostaining revealed a significant reduction in moderate- and high-treatment groups ( P = 0.01 and P = 0.02 ) , and expression of cyclin D1 was virtually ablated ( P &lt ; 0.001 ) . Histone deacetylase inhibition is a known mechanism of butyrate action , and consistent with this , PB increased levels of acetylated histone H3 in the mammary gland . In summary , PB decreased proliferation in the mammary gland in vivo at clinically achievable doses . Decreased proliferation was accompanied by changes in the levels of ER alpha and cyclin D1 . These data show that PB modulates parameters thought to be involved in the carcinogenic process in the normal mammary gland , and compounds in this class may therefore be useful candidates for breast cancer chemoprevention . OUTPUT:

sustaining proliferative signaling

HoC_1shot120

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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/PURPOSE Although angiogenic factors may play an important role in the biology of neuroblastoma , which frequently spreads hematogenously , the mechanism remains unclear . The authors studied tumor progression and invasion from the perspective of angiogenesis and sought to understand the features of this type of tumor . METHODS Thirty-one specimens were resected from patients with neuroblastoma and the expression of vascular endothelial growth factor ( VEGF ) , and its receptor ( Flk-1 ) was examined using immunohistochemistry . The authors looked for correlations among the expressions of VEGF and its receptor with various clinicopathologic factors . In addition , they examined the expression and location of VEGF and Flk-1 mRNA in 10 primary neuroblastoma using in situ hybridization . RESULTS Both in situ hybridization and immunohistochemistry showed the presence of VEGF expression within the neuroblastoma cells . We found VEGF mRNA in neuroblastoma cells but not vascular endothelial cells according to in situ hybridization . Further , Flk-1 mRNA was present both in neuroblastoma cells and vascular endothelial cells . The level of VEGF expression was higher in unfavorable histology , using the criteria of Shimada , than in favorable histology . CONCLUSION The authors suggest that paracrine and autocrine systems are involved in the angiogenesis of neuroblastoma , and the expression of VEGF correlates with the prognosis in neuroblastoma . OUTPUT:

inducing angiogenesis

HoC_1shot121

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 investigated the effectiveness of continuous hyperthermic peritoneal perfusion ( CHPP ) for the peritoneal dissemination of gastric cancer . A total 124 patients with advanced gastric cancer were enrolled in this study . Prophylactic CHPP ( P-CHPP ) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination , and 79 patients without CHPP were a control group . Therapeutic CHPP ( T-CHPP ) was performed in 21 patients with peritoneal dissemination , and 52 patients without CHPP were a control group . There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP . Univariate analysis showed that location of tumor , tumor diameter , and lymph node metastasis influenced prognosis , but there was no prognostic factor in the Cox proportional regression hazard model . There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP . Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis , and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis . In the patients with CHPP , the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP . OUTPUT:

activating invasion and metastasis

HoC_1shot122

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Ionizing radiation is a potent inducer of DNA damage because it causes single- and double-strand breaks , alkali-labile sites , base damage , and crosslinks . The interest in ionizing radiation is due to its environmental and clinical implications . Single-strand breaks , which are the initial damage induced by a genotoxic agent , can be used as a biomarker of exposure , whereas the more biologically relevant double-strand breaks can be analyzed to quantify the extent of damage . In the present study the effects of 137CS gamma-radiation at doses of 1 , 5 , and 10 Gray on DNA and subsequent repair by C3H10T1/2 cells ( mouse embryo fibroblasts ) were investigated . Two versions of the comet assay , a sensitive method for evaluating DNA damage , were implemented : the alkaline one to detect single-strand breaks , and the neutral one to identify double-strand breaks . The results show a good linear relation between DNA damage and radiation dose , for both single-strand and double-strand breaks . A statistically significant difference with respect to controls was found at the lowest dose of 1 Gy . Heterogeneity in DNA damage within the cell population was observed as a function of radiation dose . Repair kinetics showed that most of the damage was repaired within 2 h after irradiation , and that the highest rejoining rate occurred with the highest dose ( 10 Gy ) . Single-strand breaks were completely repaired 24 h after irradiation , whereas residual double-strand breaks were still present . This finding needs further investigation . OUTPUT:

genomic instability and mutation

HoC_1shot123

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 peptides released during the fermentation of milk on the humoral immune system and on fibrosarcoma growth was studied . Lactobacillus helveticus was able to release peptidic compounds during milk fermentation due to its high proteolytic activity , as was shown by the degree of proteolysis and size-exclusion HPLC elution profiles . Three fractions of these compounds were separated and fed to mice during different periods ( 2 , 5 , and 7 d ) . The humoral immune response was assessed by following the number of IgA-secreting cells , and the antitumor activity was monitored by studying the regression of subcutaneously implanted fibrosarcomas . Feeding during 2 and 7 d with the medium-sized fraction ( Fraction II ) significantly increased the IgA-producing cells in the intestines , whereas feeding with the large compound fraction ( Fraction I ) during 5 d and the small compound fraction ( Fraction III ) during all three feeding periods provided similar increases . A double dose of Fraction II showed the highest IgA-producing cell count . The increase by Fraction III was shown to be caused by the presence of L-Tryptophan . Fraction II significantly decreased the size of fibrosarcoma when previously fed during 7 d , and feeding with Fraction I during 5 d decreased significantly its size after 35 d of growth . Although the mechanisms by which lactic acid bacteria enhance the immune system are not clear , this study clearly shows that bioactive compounds released in fermented milks contribute to the immunoenhancing and antitumor properties of these products . The release of bioactive peptides by lactic acid bacteria can have important implications on the modulation of the cellular immune response . OUTPUT:

avoiding immune destruction

HoC_1shot124

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Food-derived heterocyclic aromatic amines ( HCAs ) have proved to be carcinogenic in both rodents and nonhuman primates . Two different metabolic pathways are suggested for the metabolic activation of HCA . The hepatic pathway proceeds via a two-step process involving N-hydroxylation by cytochrome P4501A2 and subsequent O-acetylation by N-acetyltransferase-2 . An alternative pathway may be of particular interest in extrahepatic tissues and proceeds via one-electron oxidation catalyzed by prostaglandin H synthase ( PHS ) , rendering free-radical metabolites . In this study , we investigated the metabolic activation of two HCAs , 2-amino-3-methylimidazo[4,5-f]quinoline ( IQ ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , by two different enzyme systems in vitro , generating different primary and secondary reactive metabolites . Rat liver S9 mix and PHS were used as the activating system and represent the hepatic and extrahepatic pathways , respectively . Electron-spin resonance spectroscopy showed that both IQ and PhIP exerted inhibiting effects on PHS-mediated formation of hydroxyl radicals during the conversion of arachidonic acid to prostaglandins . Evidence for the formation of HCA free radicals was presented in an indirect way by the formation of glutathione-derived thiyl radicals , with purified PHS as the activating system . Activation by S9 mix did not result in the formation of detectable radical metabolites , showing that the two metabolic routes primarily led to the formation of different metabolites . In all electron-spin resonance experiments , IQ appeared to be more effective than PhIP . In contrasts , DNA adduct analysis by means of ( 32)P-postlabeling showed similar adduct patterns for S9 and PHS in single-stranded and double-stranded salmon testes DNA after incubation with PhIP , indicating the ultimate formation of a common reactive intermediate . For IQ , activation by PHS led to an additional adduct spot that was not present after S9 activation . Furthermore , activation of IQ resulted in higher adduct levels compared with PhIP for both activation pathways . Overall , adduct levels were higher in single-stranded DNA than double-stranded DNA . Our results showed that the hepatic and extrahepatic pathways resulted in different primary metabolites , while the ultimate formation of a similar reactive intermediate for PhIP , possibly an arylnitrenium ion , suggested that both pathways could play an important role in the onset of carcinogenesis . OUTPUT:

genomic instability and mutation

HoC_1shot125

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Cis-diamminedichloroplatinum ( II ) ( cisplatin ) is a well characterized antitumor drug used for the treatment of a variety of human cancers . The cytotoxicity of cisplatin is mainly mediated through the formation of DNA adducts , which are also believed to be responsible for the secondary malignancies produced by the drug . The aim of this study was to determine the in vivo mutagenic activity of cisplatin in the lacZ plasmid-based transgenic mouse model . The mutant frequency ( MF ) and the spectrum of mutations induced by cisplatin in the mouse liver were analyzed and compared to controls . The mean MF in the lacZ gene was increased 2-fold in mice treated with a single 6 mg/kg body weight dose of cisplatin and sacrificed after 17 and 28 days ( P = 0.001 and P &lt ; 0.0001 ) . Restriction analysis and sequencing of mutant DNA showed that cisplatin was able to induce both large deletions and point mutations . A specific profile of base substitution and frameshift mutations was identified in treated mice , consisting primarily of G:C-->A:T transitions at GpG and ApG sites , the preferential DNA binding sites of cisplatin , and single basepair deletions/insertions . The present results provide the first evidence that cisplatin has mutagenic activity in vivo and induces a characteristic pattern of mutations in the mouse liver . This mutagenicity may be responsible for its tumorigenic activity . OUTPUT:

genomic instability and mutation

HoC_1shot126

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Epidemiological data and animal models have provided evidence that nonsteroidal antiinflammatory drugs ( NSAIDs ) have an anticancer effect . However , the molecular mechanisms underlying these antineoplastic effects are not well understood . We described previously that expression levels of the chemokine receptor , CCR5 , and the beta2-integrin , Mac-1 , were down-regulated on primary monocytes after incubation in supernatants from human carcinoma cell lines , and that this down-regulation resulted in impaired monocyte function with respect to migration and adhesion . We now demonstrate that these impairments are also present in vivo . Monocytes from cancer patients displayed significantly reduced CCR5 levels and migration capacities in comparison to cells from healthy donors . Because migration is necessary for the antitumor activity of monocytes/macrophages , these deficits may contribute to the suppressed immune system seen in cancer patients . In a clinical study , we analyzed the effect of a selective COX-2 inhibitor , Rofecoxib , on the migration of monocytes derived from cancer patients . The results revealed significant improvement in migration equal to those levels seen in healthy donors . We conclude that in patients with cancer , the intake of Rofecoxib for 3 wk leads to significant restoration of monocyte function . These data may , at least in part , help explain the anticancer effects of NSAIDs . OUTPUT:

avoiding immune destruction

HoC_1shot127

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 colon carcinoma cell line CC531 is metastatic to liver after splenic injection in syngeneic rats . After repeated in vivo passages , a subline was selected that produced liver metastases at a considerably higher rate than the original cell line . These cells were characterized by increased intracellular glutathione , proliferation and ability to restore glutathione after exposure to oxidative stress , thus indicating an elevated resistance to oxidative stress . Furthermore , the increased metastatic ability was also accompanied by increased proliferation rate , adhesion to extracellular matrix proteins and endothelial cells , and secretion of a 60 kD matrix metalloproteinase . When cultured in vitro for a prolonged time ( more than 30 trypsinizations ) , the cells showed a reduced in vivo metastatic ability , reduced secretion of three metalloproteinases including the 60 kD proteinase , and reduced intracellular glutathione . These results indicate that metastatic ability can be influenced through several adaptive mechanisms , and that the cell's ability to resist oxidative stress and maintain intracellular glutathione are of central importance . OUTPUT:

activating invasion and metastasis;tumor promoting inflammation

HoC_1shot128

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Neuroblastoma ( NB ) , a common pediatric neoplasm , consists of two main cell populations : neuroblastic/ganglionic cells and Schwann cells . NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors . Recent studies suggest that Schwann cells influence NB tumor growth via secreted factors that induce differentiation , suppress proliferation , and inhibit angiogenesis . Two angiogenesis inhibitors , pigment epithelium-derived factor and tissue inhibitor of metalloproteinase-2 , have been detected in Schwann cell secretions . Here , we isolated another Schwann cell-derived secreted inhibitor of angiogenesis , a 43-kDa protein identified as SPARC ( secreted protein acidic and rich in cysteine ) , an extracellular matrix protein . We found SPARC to be critical for the antiangiogenic phenotype of cultured Schwann cells . We also show that purified SPARC potently inhibits angiogenesis and significantly impairs NB tumor growth in vivo . SPARC may be an effective candidate for the treatment of children with clinically aggressive , Schwannian stroma-poor NB tumors . OUTPUT:

inducing angiogenesis

HoC_1shot129

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 design and develop a novel , sensitive and versatile method for in vivo foot printing and studies of DNA damage , such as DNA adducts and strand breaks . METHODS Starting with mammalian genomic DNA , single-stranded products were made by repeated primer extension , these products were ligated to a double-stranded linker having a randomized 3 ' overhang , and used for PCR . DNA breaks in p53 gene produced by restriction endonuclease AfaI were detected by using this new method followed by Southern hybridization with DIG-labeled probe . RESULTS This randomized terminal linker-dependent PCR ( RDPCR ) method could generate band signals many-fold stronger than conventional ligation-mediated PCR ( LMPCR ) , and it was more rapid , convenient and accurate than the terminal transferase-dependent PCR ( TDPCR ) . CONCLUSION DNA strand breakage can be detected sensitively in the gene level by RDPCR . Any lesion that blocks primer extension should be detectable . OUTPUT:

genomic instability and mutation

HoC_1shot130

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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-protein cross-links ( DPCs ) are formed upon exposure to a variety of chemical and physical agents and pose a threat to genomic integrity . In particular , acrolein and related aldehydes produce DPCs , although the chemical linkages for such cross-links have not been identified . Here , we report that oligodeoxynucleotides containing 1,N(2)-deoxyguanosine adducts of acrolein , crotonaldehyde , and trans-4-hydroxynonenal can form cross-links with the tetrapeptide Lys-Trp-Lys-Lys . We concluded that complex formation is mediated by a Schiff base linkage because DNA-peptide complexes were covalently trapped following reduction with sodium cyanoborohydride , and pre-reduction of adducted DNAs inhibited complex formation . A previous NMR study demonstrated that duplex DNA catalyzes ring opening for the acrolein-derived gamma-hydroxy-1,N(2)-propanodeoxyguanosine adduct to yield an aldehydic function ( de los Santos , C. , Zaliznyak , T. , and Johnson , F . ( 2001 ) J. Biol . Chem. 276 , 9077-9082 ) . Consistent with this earlier observation , the adducts under investigation were more reactive in duplex DNA than in single-stranded DNA , and we concluded that the ring-open aldehydic moiety is the induced tautomer in duplex DNA for adducts exhibiting high relative reactivity . Adducted DNA cross-linked to Arg-Trp-Arg-Arg and Lys-Trp-Lys-Lys with comparable efficiency , and N(alpha)-acetylation of peptides dramatically inhibited trapping ; thus , the reactive nucleophile is located at the N-terminal alpha-amine of the peptide . These data suggest that Schiff base chemistry can mediate DPC formation in vivo following the formation of stable aldehyde-derived DNA adducts . OUTPUT:

genomic instability and mutation

HoC_1shot131

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Recent studies indicate that cyclooxygenase-2 ( COX-2 ) is overexpressed in pancreatic adenocarcinoma and may play a critical role in this rapidly progressing form of cancer . A human pancreatic adenocarcinoma cell line , Mia PaCa-2 , was incubated for 18 hours with 5 micromol/L of rofecoxib ( Vioxx ) , a selective COX-2 inhibitor . Total RNA was isolated and gene expression analyzed by DNA microarray chips . In a separate experiment , athymic mice were orthotopically injected with 7.5 x 10(5) Mia PaCa-2 cells through a minilaparotomy . After 1 month , laparotomy was repeated to measure tumor size , and mice were randomized to receive reformulated rodent chow containing either 12.5 mg/kg/day of rofecoxib or no drug for 21 days . Tumor growth was assessed by comparing volume before and after treatment . In vitro , rofecoxib decreased gene expression of cyclin D1/PRAD1 , a key component of cell cycle progression , while increasing expression of several cell cycle arrest genes , including p21/WAF1 , p33/ING , GADD34 , and GADD45 ( P &lt ; 0.05 ) . In vivo , tumor growth was significantly reduced in treated vs. control mice ( P &lt ; 0.05 ) . No systemic toxicity was observed in mice receiving rofecoxib . These data suggest that rofecoxib slows the growth of human pancreatic cancer through changes in gene expression that favor cell cycle arrest . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot132

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Several members of the phosphatidylinositol 3-kinase family play key roles in recognising and responding to damage in DNA , induced by a variety of chemicals and other agents . One of these , ATM , the product of the gene mutated in the human genetic disorder ataxia-telangiectasia ( A-T ) , recognises double strand breaks in DNA caused by ionizing radiation and radiomimetic chemicals . In order to study DNA damage recognition and the abnormalities of genome instability and cancer predisposition that occur in A-T patients , we generated a mouse model expressing a mutant form of Atm corresponding to a common human mutation . In this model , a 9 nucleotide in-frame deletion was introduced into the Atm gene and has been designated Atm-Delta SRI . These animals had a longer lifespan than Atm gene disrupted mice ( Atm(-/-) ) and they developed less thymic lymphomas . A characteristic of the lymphomas appearing in Atm-Delta SRI mice was an increased rate of apoptosis compared to the corresponding tumours in Atm(-/-) mice . Increased expression of FasL in these tumours may account for the higher levels of apoptosis . These results demonstrate that expression of mutant Atm in mice gives rise to phenotypic differences compared to Atm(-/-) mice and has implications for heterogeneity described in the human syndrome . OUTPUT:

genomic instability and mutation;resisting cell death

HoC_1shot133

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 esophageal adenocarcinoma ( EAC ) develops in a sequence from gastroesophageal reflux disease ( GERD ) , columnar-lined esophagus ( CLE ) , dysplasia , and eventually to EAC . We established a rat surgical EAC model with esophagogastroduodenal anastomosis ( EGDA ) to mimic the staged process of esophageal adenocarcinogenesis . Profiling of the AA metabolites with mass spectrometry showed that prostaglandin E2 ( PGE2 ) , leukotriene B4 ( LTB4 ) , 15-hydroeicosatetraenoic acid ( HETE ) , 12-HETE , 8-HETE and 5-HETE all increased at the esophagoduodenal junction after EGDA as compared with the proximal esophagus , with PGE2 as the major metabolite . Consistent with this profile , cyclooxygenase 2 ( Cox2 ) was overexpressed in the basal cell layer of esophageal squamous epithelium , CLE cells and EAC tumor cells of the EGDA rats , as compared with the normal esophageal epithelium . Sulindac ( a Cox inhibitor ) , nordihydroguaiaretic acid ( NDGA , a lipoxygenase inhibitor ) and alpha-difluoromethylornithine ( DFMO , an ornithine decarboxylase inhibitor ) were tested for their possible inhibitory actions against the formation of EAC in the rat EGDA model . In a short-term study ( for 4 weeks after surgery ) , dietary administration of both sulindac ( 300 and 600 p.p.m. ) and NDGA ( 100 p.p.m. ) effectively reduced the EGDA-induced inflammation . In a long-term chemoprevention study ( for 40 weeks after surgery ) , 300 p.p.m. sulindac , alone or in combination with 100 p.p.m . NDGA or 0.5% DFMO , decreased the tumor incidence from 57.7 to 26.9% , or 16.7 or 20% , respectively ( P &lt ; 0.05 ) . NDGA alone ( 100 and 200 p.p.m. ) slightly decreased the tumor incidence to 52.4 and 37% , respectively , although the difference was not statistically significant . DFMO alone did not show significant effects on tumor incidence . Inhibition of tumor formation by sulindac was correlated with lowered levels of PGE2 . In conclusion , sulindac exerted its chemopreventive effect against the formation of EAC in the rat EGDA model possibly through its inhibition of Cox . OUTPUT:

tumor promoting inflammation

HoC_1shot134

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 examine the association of cell cycle regulatory gene inactivation with human cell immortalization , we determined the expression status of INK4a , Rb , and WAF1/ CIP1 , in eleven in vitro immortalized human cell lines , including fibroblasts and keratinocytes . Two human papillomavirus type 16 E6 expressing cell lines with telomerase activity , including a fibroblast cell line and a keratinocyte cell line , expressed no detectable p16(INK4a) . These cell lines had a hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1) . All of seven fibroblast cell lines immortalized either spontaneously or by ( 60)Co , X-rays , 4-nitroquinoline 1-oxide or aflatoxin B(1) , maintaining their telomeres by the ALT ( alternative lengthening of telomeres ) pathway , displayed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . Levels of p21(WAF1/CIP1) expression varied among the cell lines . Two fibroblast cell lines that became immortalized following infection with a retrovirus vector encoding human telomerase catalytic subunit ( hTERT ) cDNA were also accompanied by inactivation of p16(INK4a) and pRb pathways . Acquisition of telomerase activity alone was not sufficient for immortalization of these cell lines . Taken together , all the cell lines including fibroblasts and keratinocytes , with either telomerase activity or the ALT pathway for telomere maintenance showed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . These demonstrate the association of inactivation of both p16(INK4a) and pRb with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells . OUTPUT:

enabling replicative immortality

HoC_1shot135

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: It was proved that nuclear factor-kappa B play an important role in the activation of immune cell , anti-virus , various stress reaction , and regulation of apoptosis , etc . The objective of this study was to investigate the effect of NF-kappa B signal-transduction pathway on apoptosis of hepatic carcinoma cell line-7721 induced by TNF-alpha . OUTPUT:

avoiding immune destruction;resisting cell death

HoC_1shot136

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 xeroderma pigmentosum group C ( XPC ) protein specifically involved in genome-wide damage recognition for nucleotide excision repair ( NER ) was purified as a tight complex with HR23B , one of the two mammalian homologs of RAD23 in budding yeast . This XPC-HR23B complex exhibits strong binding affinity for single-stranded DNA , as well as preferential binding to various types of damaged DNA . To examine the structure-function relationship of XPC , a series of truncated mutant proteins were generated and assayed for various binding activities . The two domains participating in binding to HR23B and damaged DNA , respectively , were mapped within the carboxy-terminal half of XPC , which also contains an evolutionary conserved amino acid sequence homologous to the yeast RAD4 protein . We established that the carboxy-terminal 125 amino acids are dispensable for both HR23B and damaged DNA binding , while interactions with transcription factor IIH ( TFIIH ) are significantly impaired by truncation of this domain . Furthermore , deletion of the extreme carboxy-terminal domain totally abolished XPC activity in the cell-free NER reaction . These results suggest that following initial damage recognition , the carboxy terminus of XPC may be essential for the recruitment of TFIIH , and that most truncation mutations identified in XP-C patients result in non-functional proteins . OUTPUT:

genomic instability and mutation

HoC_1shot137

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 different cellular pathways have evolved to protect the genome from the deleterious effects of DNA damage that result from exposure to chemical and physical agents . Among these is a process called transcription-coupled repair ( TCR ) that catalyzes the removal of DNA lesions from the transcribed strand of expressed genes , often resulting in a preferential bias of damage clearance from this strand relative to its non-transcribed counterpart . Lesions subject to this type of repair include cyclobutane pyrimidine dimers that are normally repaired by nucleotide excision repair ( NER ) and thymine glycols ( TGs ) that are removed primarily by base excision repair ( BER ) . While the mechanism underlying TCR is not completely clear , it is known that its facilitation requires proteins used by other repair pathways like NER . It is also believed that the signal for TCR is the stalled RNA polymerase that results when DNA damage prevents its translocation during transcription elongation . While there is a clear role for some NER proteins in TCR , the involvement of BER proteins is less clear . To explore this further , we studied the removal of 7-methylguanine ( 7MeG ) and 3-methyladenine ( 3MeA ) from the dihydrofolate reductase ( dhfr ) gene of murine cell lines that vary in their repair phenotypes. 7MeG and 3MeA constitute the two principal N-methylpurines formed in DNA following exposure to methylating agents . In mammalian cells , alkyladenine DNA alkyladenine glycosylase ( Aag ) is the major enzyme required for the repair of these lesions via BER , and their removal from the total genome is quite rapid . There is no observable TCR of these lesions in specific genes in DNA repair proficient cells ; however , it is possible that the rapid repair of these adducts by BER masks any TCR . The repair of 3MeA and 7MeG was examined in cells lacking Aag , NER , or both Aag and NER to determine if rapid overall repair masks TCR . The results show that both 3MeA and 7MeG are removed without strand bias from the dhfr gene of BER deficient ( Aag deficient ) and NER deficient murine cell lines . Furthermore , repair of 3MeA in this region is highly dependent on Aag , but repair of 7MeG is equally efficient in the repair proficient , BER deficient , and NER deficient cell lines . Strikingly , in the absence of both BER and NER , neither 7MeG nor 3MeA is repaired . These results demonstrate that NER , but not TCR , contributes to the repair of 7MeG , and to a lesser extent 3MeA . OUTPUT:

genomic instability and mutation

HoC_1shot138

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Saccharomyces cerevisiae , Mre11p , Rad50p , and Xrs2p function as a multiprotein complex that has a central role in several DNA repair mechanisms . Though Mre11p has both single-stranded and double-stranded 3'-5 ' exonuclease activity in vitro , null mutants of MRE11 , RAD50 , and XRS2 exhibit reduced 5'-3 ' resection of HO-induced double-strand breaks ( DSBs ) in vivo . In this study , we analyzed four mre11 mutants harboring changes in the N-terminus of Mre11p where the four phosphoesterase motifs specify the in vitro nuclease activities of Mre11p and its homologues . We find that the 5'-3 ' resection defects in vivo do not correlate with several mitotic phenotypes : non-homologous end-joining ( NHEJ ) , telomere length maintenance , and adaptation to the DNA damage-inducible G2/M checkpoint . Overexpression of the 5'-3 ' exonuclease Exo1p in a mre11Delta strain partially increased 5'-3 ' resection and partially suppressed both methyl methanesulfonate ( MMS ) hypersensitivity and adaptation phenotypes , but did not affect telomere length or NHEJ . Surprisingly , the co-expression of two alleles , mre11-58S and mre11-N113S , each of which confers MMS hypersensitivity and short telomeres , can fully complement the MMS sensitivity and shortened telomere length of mre11Delta cells . We propose that at least two separate activities associated with the N-terminus of Mre11p are required for its mitotic function . OUTPUT:

genomic instability and mutation;enabling replicative immortality

HoC_1shot139

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 explore the possibility of a new therapeutic strategy for leukemia by intervening in the DNA methylation to re-express p15 suppressor gene , methylation inhibitors , 5-Aza-2'-deoxycytidine ( 5-Aza-CdR ) and cell differentiation agent ( CDAII ) were used to treat myelogenous leukemia cell line KG1a in which p15 gene expression was suppressed due to DNA hypermethylation . The biological characteristics of KG1a cells untreated or treated with the agents were investigated and analyzed using morphology , methylation specific-PCR ( MSP ) , ( 3)H-labeled microassay technique , restriction endonuclease reaction , flow cytometry and immunofluorescence methods . The results indicated that both agents showed concentration-dependent and time-dependent inhibition of cell proliferation. 5-Aza-CdR and CDAII induced apoptosis and cell differentiation with G(2) and G(0)/G(1) arrest respectively . Furthermore , DNA methyltransferase activity and level of methylation in genomic DNA were decreased and p15 protein was re-expressed partially . It is concluded that it is possible to treat leukemia by intervening in the DNA methylation using methyltransferase inhibitors and it is worth to make a thorough study on mechanism of the new strategy . OUTPUT:

evading growth suppressors;resisting cell death

HoC_1shot140

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 purpose of this investigation was to study the variation of p73 gene expression in the apoptotic process of acute myeloid leukemia ( AML ) cell line U937 induced by methotrexate ( MTX ) . Morphological changes of apoptotic cells were observed with microscopy and Wright's + Giemsa staining . DNA ladder and cell cycle were examined by agarose gel electrophoresis and flow cytometry respectively . Using semi-quantitive reverse transcription-polymerase chain reaction ( RT-PCR ) , the expression of p73 mRNA was examined . Results showed that MTX could induce U937 cell apoptosis effectively . Condensed nuclei , fragmentation of chromosome and DNA ladder were seen after 6 hour following treatment of MTX 5 micro mol/L . Sub-G(1) peak and S + G(2)/M arrest were also determined by FCM , but the quantity of p73 expression was generally constant . In conclusion , U937 cell apoptosis induced by MTX did not change p73 mRNA level . OUTPUT:

resisting cell death

HoC_1shot141

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Free radical-induced cellular stress contributes to cancer during chronic inflammation . Here , we investigated mechanisms of p53 activation by the free radical , NO . NO from donor drugs induced both ataxia-telangiectasia mutated ( ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications , leading to an increase in p53 transcriptional targets and a G(2)M cell cycle checkpoint . Such modifications were also identified in cells cocultured with NO-releasing macrophages . In noncancerous colon tissues from patients with ulcerative colitis ( a cancer-prone chronic inflammatory disease ) , inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels . Immunostaining of HDM-2 and p21(WAF1) was consistent with transcriptionally active p53 . Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation . OUTPUT:

evading growth suppressors;genomic instability and mutation;tumor promoting inflammation

HoC_1shot142

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Adenoid cystic carcinoma ( ACC ) of the salivary glands is a highly infiltrative malignant tumour with a tendency for lung metastasis . Gene therapy could be a potentially effective therapy for ACC and its metastasis . The aims of the study were : To transduce interleukin-2 ( IL-2 ) gene into an ACC cell line with predisposition for lung metastasis ( ACC-M ) ; to compare the bioactivity of the gene-transduced cells and the parent cell line in vitro and in vivo . The IL-2 gene was transduced via a bicistronic retroviral vector into the ACC-M cells . The growth rate and DNA cell cycles of the parent ACC-M , the control viral vector AmGCEN , and the gene transduced AmIL-2 cell cultures were compared quantitatively and by flow cytometry , respectively . The tumourigenic ability of the three cell lines was verified by inoculation in athymic nude mice . The tumours developed were extracted and compared quantitatively and histologically . There was no difference in the growth rate and the DNA count between the ACC-M , AmGCEN , and AmIL-2 cell cultures . In the animal experiment , both the ACC-M and AmGCEN cells stimulated lung metastasis in all the mice , whereas there was no tumour found in the 1 x 10(6) AmIL-2 cells inoculation . On 3 x 10(6) AmIL-2 cells stimulation , three out of six mice developed tumours but the mass and volume of the tumours were smaller than the other two groups . Under light microscopy , the ACC-M tumours were mainly poorly differentiated with minimal cellular matrix , whereas the AmIL-2 tumours were well differentiated with ample matrix . The transduction of IL-2 gene can reduce the tumourigenicity of ACC-M cells and induces tumour cell differentiation in mice . The IL-2 gene can be a potential effective gene for the treatment of adenoid cystic carcinoma of salivary glands and its lung metastasis . OUTPUT:

activating invasion and metastasis

HoC_1shot143

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 mismatch repair ( MMR ) is the process by which incorrectly paired DNA nucleotides are recognized and repaired . A germline mutation in one of the genes involved in the process may be responsible for a dominantly inherited cancer syndrome , hereditary nonpolyposis colon cancer . Cancer progression in predisposed individuals results from the somatic inactivation of the normal copy of the MMR gene , leading to a mutator phenotype affecting preferentially repeat sequences ( microsatellite instability , MSI ) . Recently , we identified children with a constitutional deficiency of MMR activity attributable to a mutation in the h MLH1 gene . These children exhibited a constitutional genetic instability associated with clinical features of de novo neurofibromatosis type 1 ( NF1 ) and early onset of extracolonic cancer . Based on these observations , we hypothesized that somatic NF1 gene mutation was a frequent and possibly early event in MMR-deficient cells . To test this hypothesis , we screened for NF1 mutations in cancer cells . Genetic alterations were identified in five out of ten tumor cell lines with MSI , whereas five MMR-proficient tumor cell lines expressed a wild-type NF1 gene . Somatic NF1 mutations were also detected in two primary tumors exhibiting an MSI phenotype . Finally , a 35-bp deletion in the murine Nf1 coding region was identified in mlh1-/- mouse embryonic fibroblasts . These observations demonstrate that the NF1 gene is a mutational target of MMR deficiency and suggest that its inactivation is an important step of the malignant progression of MMR-deficient cells . OUTPUT:

genomic instability and mutation

HoC_1shot144

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: IL-16 is a ligand and chemotactic factor for CD4+ T cells . IL-16 inhibits the CD3 mediated lymphocyte activation and proliferation . The effects of IL-16 on the target cells are dependent on the cell type , the presence of co-activators etc . To understand the regulation function and mechanism of IL-16 on target cells , we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro . We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose ( 10(-9)M ) , but inhibited the growth of the cells at higher concentration ( 10(-5)M ) . Results showed that 10(-5) M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells . The treatment blocked the expression of FasL , but up-regulated the c-myc and Bid expression in the cells . Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells , respectively . The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner . The growth-inhibiting effects of rIL-16 might be Fas/FasL independent , but , associated with the activation of PKC , up-regulated expression of c-Myc and Bid , and the participation of the ERK signal pathway in Jurkat cells . OUTPUT:

resisting cell death

HoC_1shot145

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 triterpenoid fraction ( 100 and 200 mg/kg ) of the fruit bodies of Ganoderma lucidum inhibited primary solid-tumor growth in the spleen , liver metastasis and secondary metastatic tumor growth in the liver in intrasplenic Lewis lung carcinoma ( LLC)-implanted mice . In addition , the triterpenoid fraction ( 800 micrograms/mL ) inhibited angiogenesis induced by Matrigel ( a soluble basement membrane extract of the Engelbreth-Holm-Swam ( EHS ) tumor ) supplemented with vascular endothelial growth factor ( VEGF ) and heparin in an in vivo model . This suggested that the antitumor and antimetastatic activities of the triterpenoid fraction of G. lucidum might be due to the inhibition of tumor-induced angiogenesis . Next , we attempted to isolate the active substance(s) using the in vivo assay system of Matrigel-induced angiogenesis . The acidic fraction of the triterpenoid fraction inhibited the Matrigel-induced angiogenesis . Compound I was isolated from the acidic fraction as an active substance that inhibited the Martigel-induced angiogenesis . Compound I was identified as ganoderic acid F based on the data of IR , 1H- and 13C-NMR and MS analyses . OUTPUT:

activating invasion and metastasis;inducing angiogenesis

HoC_1shot146

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 experimental evidence that sulforaphane can exert chemopreventive effects , whether these effects are specific for neoplastic cells is not known . Following our previous demonstration that sulforaphane induces cell cycle arrest and apoptosis in human T lymphoblastoid Jurkat leukemia cells and increases p53 and bax protein expression , we tested sulforaphane on non-transformed phytohemagglutinin-stimulated human lymphocytes . Here , we demonstrate that sulforaphane arrested cell cycle progression in G , phase , through a decrease in the protein expression of cyclin D3 . Moreover , sulforaphane induced apoptosis ( and also necrosis ) , mediated by an increase in the expression of p53 . These findings suggest that sulforaphane is a growth modulator for T cells . Our in vitro evidence that sulforaphane is active and even cytotoxic in normal as well as transformed lymphocytes raises important questions regarding its suitability for cancer chemoprevention . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot147

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Glycol ethers are known reproductive and developmental toxins in laboratory animals , but little is known about their genotoxic effects in humans . In the current article , the authors tested the hypothesis that human in utero exposure to ethylene glycol monomethyl ether ( EGME ) is associated with the development of specific congenital anomalies and elevated levels of chromosome aberrations . The authors conducted a clinical and cytogenetic evaluation of 41 offspring of 28 females occupationally exposed to EGME for an average duration of 4.6 yr . Six offspring of 5 women who were occupationally exposed to EGME during pregnancy exhibited characteristic dysmorphic features that were not observed in 35 offspring of 23 women who worked in the same facility , but who were not pregnant at the time of exposure . Persistent cytogenetic damage was observed exclusively in all 6 in-utero-exposed offspring , but not in their 12 match non-in-utero-exposed controls . The study characterizes EGME as a human teratogen , as indicated by the prevalence of characteristic dysmorphic features and persistent cytogenetic damage in individuals exposed in utero to this chemical . OUTPUT:

genomic instability and mutation

HoC_1shot148

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 polymerases beta ( pol beta ) and eta ( pol eta ) are the only two eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro . Frameshift errors are an important aspect of mutagenesis . We have compared the types of frameshifts that occur during translesion synthesis past cisplatin and oxaliplatin adducts in vitro by pol beta and pol eta on a template containing multiple runs of nucleotides flanking a single platinum-GG adduct . Translesion synthesis past platinum adducts by pol beta resulted in approximately 50% replication products containing single-base deletions . For both adducts the majority of -1 frameshifts occurred in a TTT sequence 3-5 bp upstream of the DNA lesion . For pol eta , all of the bypass products for both cisplatin and oxaliplatin adducts contained -1 frameshifts in the upstream TTT sequence and most of the products of replication on oxaliplatin-damaged templates had multiple replication errors , both frameshifts and misinsertions . In addition , on platinated templates both polymerases generated replication products 4-8 bp shorter than the full-length products . The majority of short cisplatin-induced products contained an internal deletion which included the adduct . In contrast , the majority of oxaliplatin-induced short products contained a 3 ' terminal deletion . The implications of these in vitro results for in vivo mutagenesis are discussed . OUTPUT:

genomic instability and mutation

HoC_1shot149

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Mice defective in the mismatch repair ( MMR ) gene Msh2 manifest an enhanced predisposition to skin cancer associated with exposure to UVB radiation . This predisposition is further heightened if the mice are additionally defective for the nucleotide excision repair gene Xpc . To test the hypothesis that the predisposition of Msh2 mutant mice to skin cancer reflects a mutator phenotype associated with increased proliferation of skin cells following exposure to UV radiation , Msh2 mutant mice were exposed to the tumor promoter TPA . Such mice showed a robust proliferative response in the skin , but did not manifest evidence of dysplasia or neoplasia . We conclude that the predisposition of Msh2 mice to UVB radiation-induced skin cancer reflects an interaction between the processes of mismatch repair and some other excision repair mode , the exact nature of which remains to be established . OUTPUT:

genomic instability and mutation

HoC_1shot150

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Arsenic trioxide ( ATO ) is a novel agent to treat acute promyelocytic leukemia ( APL ) . ATO can degrade chimeric PML-RAR proteins and induce apoptosis in various cancer cells . However , its effects on primary hematopoietic CD34+ have not been examined . In this study , we compared the effects of ATO on HL60 leukemic cells and primary umbilical cord blood ( UCB ) CD34+ cells . HL60 cells and UCB CD34+ cells were cultured with different concentrations of ATO for up to three weeks and examined for changes of cell cycle . We found that ATO ( &lt ; or = 5 microM ) caused prolongation of G1/S and G2/M phase in a dose-dependent manner . The percentage of cells in G2/M increased significantly ( from 8.6 to 53.8% ) . High-dose ATO ( &gt ; or = 25 microM ) caused non-specific cell death in HL60 cells without any changes in cell cycle . In contrast to HL60 cells , UCB CD34+ cells were more resistant to high-dose ATO and most ATO-resistant CD34+ cells remained in G0/G1 phase . Primary cells that were resistant to ATO were rich in CD34+ cells . We further show that the ATO resistance was not related to the expression of P-glycoprotein ( MDR-1 ) . Our results suggest that the resistance to ATO in primitive UCB CD34+ cells is most likely related to its cell-cycle status . These results could be useful to design treatments for non-APL malignancies and to enrich hematopoietic stem cells in clinically applicable settings . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot151

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Vanadium pentoxide , commercially the most important compound of vanadium , presents a potential occupational hazard during the cleaning of oil-fired boilers and furnaces , the handling of catalysts , and during the refining , processing , or burning of vanadium-rich mineral ores or fossil fuels . Vanadium pentoxide was nominated for study by the National Cancer Institute as a representative of the metals class study . Male and female F344/N rats and B6C3F1 mice were exposed to vanadium pentoxide ( 99% pure ) by inhalation for 16 days , 14 weeks , or 2 years . Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood. 16-DAY STUDY IN RATS : Groups of five male and five female rats were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 2 , 4 , 8 , 16 , or 32 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 16 days . Three males in the 32 mg/m(3) group died before the end of the study . Mean body weights of males and females exposed to 8 mg/m(3) or greater were less than those of the chamber controls . Clinical findings included rapid respiration and hypoactivity in rats exposed to 16 or 32 mg/m(3) . Relative lung weights of 4 mg/m(3) or greater males and 2 mg/m(3) or greater females were significantly greater than those of the chamber controls . Lavage fluid analysis indicated an inflammatory response in the lung that was either directly mediated by vanadium pentoxide or was secondary to lung damage induced by vanadium pentoxide exposure. 16-DAY STUDY IN MICE : Groups of five male and five female mice were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 2 , 4 , 8 , 16 , or 32 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 16 days . All males exposed to 32 mg/m(3) and one 8 mg/m(3) male died or were killed moribund before the end of the study . Mean body weights of 16 mg/m(3) males and 8 mg/m(3) or greater females were significantly less than those of the chamber controls , and the 32 mg/m(3) females lost weight during the study . Absolute and relative lung weights of 4 mg/m(3) or greater males and all exposed groups of females and liver weights of 16 mg/m(3) males were significantly greater than those of the chamber controls . The mediastinal lymph nodes were enlarged in 4 , 8 , and 16 mg/m(3) males and females , and lymphoid hyperplasia was confirmed histologically . Lavage fluid analysis indicated an inflammatory response in the lung that was either directly mediated by vanadium pentoxide or was secondary to lung damage induced by vanadium pentoxide exposure. 3-MONTH STUDY IN RATS : Groups of 10 male and 10 female rats were exposed to particulate aerosols of vanadium pentoxide at concentrations of 0 , 1 , 2 , 4 , 8 , or 16 mg/m(3) by inhalation , 6 hours per day , 5 days per week for 3 months . Seven males and three females exposed to 16 mg/m(3) died during the study . Mean body weights were significantly less in males exposed to 4 mg/m(3) or greater and in females exposed to 16 mg/m(3) . Abnormal breathing , thinness , lethargy , abnormal posture , and ruffled fur were observed in rats exposed to 16 mg/m(3) . Hematology results indicated that exposure of rats to vanadium pentoxide induced a microcytic erythrocytosis in males and females . Absolute and relative lung weights were significantly greater for 4 mg/m(3) or greater males and females than for the chamber controls as were the relative lung weights of 2 mg/m(3) males . The estrous cycle of females exposed to 8 mg/m(3) was significantly longer than that of the chamber control group , and the number of cycling females in the 16 mg/m(3) group was reduced . The incidences of several nonneoplastic lesions of the lung and nose were significantly increased in males and females exposed to 2 mg/m(3) or greater . Data from pulmonary function analyses indicated that a restrictive lung disease was present in male and female rats exposed to 4 mg/m(3) or greater , while an obstructive lung disease was present only in the 16 mg/m(3) groups. 3-MONTH STUDY IN MICE : Groups of 10 male and 10 female mice were exposed to par OUTPUT:

tumor promoting inflammation

HoC_1shot152

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 efficent antitumor and antiviral cellular immune response requires optimal interferon-gamma ( IFN-gamma ) secretion and perforin expression in CD8(+) T cells . The aim of this study was to define whether CD4(+) and CD8(+) T cells from patients with undifferentiated carcinoma of nasopharyngeal type ( UCNT ) , a tumor regularly associated with the Epstein-Barr virus ( EBV ) , have abnormal phenotype profiles , cytokine production , perforin and CD3-zeta expressions . Our data showed that CD4 and CD8 subset distribution was not grossly altered in the peripheral blood of UCNT patients , while tumor biopsies contained an increased proportion of CD8(+) T cells . The analysis of the CD4(+) subset showed a defect in interleukin-2 ( IL-2 ) production and a moderate increase of IL-10 production , a situation consistent with a Th1/Th2 imbalance . We have also demonstrated that CD8(+) lymphocytes from UCNT patients had a marked impairment of IFN-gamma secretion and perforin expression . This impairment was not related to the presence of detectable EBV DNA in the plasma . In UCNT patients , the blockade of the perforin pathway and of IFN-gamma production may constitute important mechanisms for immune escape by the tumor and for impaired control of EBV replication . OUTPUT:

avoiding immune destruction

HoC_1shot153

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 Hepatocellular carcinoma ( HCC ) is a leading cause of death worldwide . Frequent cytogenetic abnormalities that occur in HCC suggest that tumor-modifying genes ( oncogenes or tumor suppressors ) may be driving selection for amplification or deletion of these particular genetic regions . In many cases , however , the gene(s) that drive the selection are unknown . Although techniques such as comparative genomic hybridization ( CGH ) have traditionally been used to identify cytogenetic aberrations , it might also be possible to identify them indirectly from gene-expression studies . A technique we have called comparative genomic microarray analysis ( CGMA ) predicts regions of cytogenetic change by searching for regional gene-expression biases . CGMA was applied to HCC gene-expression profiles to identify regions of frequent cytogenetic change and to identify genes whose expression is misregulated within these regions . RESULTS Using CGMA , 104 HCC gene-expression microarray profiles were analyzed . CGMA identified 13 regions of frequent cytogenetic change in the HCC samples . Ten of these regions have been detected in previous CGH studies ( +lq , -4q , +6p , -8p , +8q , -13q , -16q , -17p , +17q , +20q ) . CGMA identified three additional regions that have not been previously identified by CGH ( +5q , +12q , +19p ) . Genes located in regions of frequent cytogenetic change were examined for changed expression in the HCC samples . CONCLUSIONS Our results suggest that CGMA predictions using gene-expression microarray datasets are a practical alternative to CGH profiling . In addition , CGMA might be useful for identifying candidate genes within cytogenetically abnormal regions . OUTPUT:

genomic instability and mutation

HoC_1shot154

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE Although the adrenal gland is a common site of extrahepatic metastasis from hepatocellular carcinoma ( HCC ) , there are no definitive guidelines for the treatment of adrenal metastasis . This study examines the effectiveness of various treatments for this disease . METHODS We retrospectively analyzed 20 patients treated for adrenal metastasis of HCC by adrenalectomy ( n = 13 ) , transarterial chemoembolization ( TACE ) , or percutaneous ethanol injection therapy ( PEIT ) ( n = 7 ) . RESULTS There were no significant differences in cumulative survival rates between patients given adrenalectomy and those given TACE or PEIT , either after completing treatment for primary HCC or after the first treatment for adrenal metastasis . Six of seven patients with tumor thrombi in the inferior vena cava ( IVC ) from adrenal metastasis underwent adrenalectomy combined with intracaval thrombectomy , five of whom survived for more than 1 year after surgery , and two of whom are still alive without any recurrence more than 3 years after surgery . PEIT showed good results for small adrenal metastasis . CONCLUSION These findings suggest that therapeutic modalities should be chosen according to the clinical features of each individual , including the size of the metastatic tumor , whether there is invasion into the IVC , the function of the remaining liver , and the existence of intra- and/or nonadrenal extrahepatic lesions . Furthermore , intracaval tumor thrombectomy could be indicated for patients with IVC thrombus if they are suitable candidates for surgery . OUTPUT:

activating invasion and metastasis

HoC_1shot155

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Polo-like kinase 3 ( Plk3 , alternatively termed Prk ) is involved in the regulation of DNA damage checkpoint as well as in M-phase function . Plk3 physically interacts with p53 and phosphorylates this tumor suppressor protein on serine-20 , suggesting that the role of Plk3 in cell cycle progression is mediated , at least in part , through direct regulation of p53 . Here we show that Plk3 is rapidly activated by reactive oxygen species in normal diploid fibroblast cells ( WI-38 ) , correlating with a subsequent increase in p53 protein level . Plk3 physically interacts with Chk2 and the interaction is enhanced upon DNA damage . In addition , Chk2 immunoprecipitated from cell lysates of Daudi ( which expressed little Plk3 ) is capable of stimulating the kinase activity of purified recombinant Plk3 in vitro , and this stimulation is more pronounced when Plk3 is supplemented with Chk2 immunoprecipitated from Daudi after DNA damage . Furthermore , ectopic expression Chk2 activates cellular Plk3 . Together , our studies suggest Chk2 may mediate direct activation of Plk3 in response to genotoxic stresses . OUTPUT:

tumor promoting inflammation;genomic instability and mutation

HoC_1shot156

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists . In order to obtain large quantities of cells and reproducibility , human endothelial cells with extended life spans were developed by retroviral transfection . The resulting cells grown in a serum-free medium containing endothelial cell growth supplement ( ECGS ) have a telomerase activity , extended life spans of at least 21 passages , and an endothelial cell phenotype ( diI-acetylated-LDL upake , factor VIII-related antigen , VEGFR-1 and R-2 , and tissue-type plasminogen activator ( tPA) ) that resembled that of unaltered primary endothelial cells . Exceptions were ( i ) a higher expression of tPA , and ( ii ) a non-significant growth response to FGF-2 or VEGF stimulation . Within three-dimensional fibrin gels , specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells . Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS , respectively . Both cell types produced FGF-2 and VEGF cytokines . Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines . These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds . OUTPUT:

inducing angiogenesis

HoC_1shot157

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 glucocorticoid ( GC ) on the proliferation of Dunn Osteosarcoma ( OS ) cells were examined under in vitro culture conditions . Dexamethasone ( Dex ) inhibited the proliferation of Dunn OS cells in a dose-dependent manner , while the addition of anti-GC , RU486 , to the culture medium in part recovered Dex-induced growth inhibition . The number of maximum binding sites ( Bmax ) and the dissociation constant ( Kd ) value of glucocorticoid receptor ( GR ) in Dunn OS cells were 19,560 sites/cell and 5.2 +/- 0.8 nM , respectively . RU486 competed with labeled Dex against GR at a concentration of 10(-6) M. Western blot analysis of [ 3H]Dex-mesylate-labeled cell homogenate and immunohistochemical staining against GR further confirmed the presence of GR . Dex treatment of Dunn OS cells resulted in apoptosis with the characteristic internucleosomal DNA cleavage shown by the DNA ladder pattern in agarose gel electrophoresis . These data demonstrate that GC inhibits the proliferation of Dunn OS cells via GR , for which one possible mechanism in vitro is induction of apoptosis . OUTPUT:

sustaining proliferative signaling;resisting cell death

HoC_1shot158

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Steroid hormone receptors , including estrogen receptor-alpha ( ERalpha ) , are ligand-activated transcription factors , and hormone binding leads to depletion of receptor levels via preteasome-mediated degradation . NEDD8 ( neural precursor cell-expressed developmentally down-regulated ) is an ubiquitin-like protein essential for protein processing and cell cycle progression . We recently demonstrated that ubiquitin-activating enzyme ( Uba)3 , the catalytic subunit of the NEDD8-activating enzyme , inhibits ERalpha transcriptional activity . Here we report that Uba3-mediated inhibition of ERalpha transactivation function is due to increased receptor protein turnover . Coexpression of Uba3 with ERalpha increased receptor degradation by the 26S proteasome . Inhibition of NEDD8 activation and conjugation diminished polyubiquitination of ERalpha and blocked proteasome-mediated degradation of receptor protein . The antiestrogen ICI 182,780 is known to induce ER degradation . In human MCF7 breast cancer cells modified to contain a disrupted NEDD8 pathway , ICI 182,780 degradation of ERalpha was impaired , and the antiestrogen was ineffective at inhibiting cell proliferation . This study provides the first evidence linking nuclear receptor degradation with the NEDD8 pathway and the ubiquitin-proteasome system , suggesting that the two pathways can act together to modulate ERalpha turnover and cellular responses to estrogens . Based on our observation that an intact NEDD8 pathway is essential for the antiproliferation activity of the ICI 182,780 in ERalpha positive breast cancer cells , we propose that disruptions in the NEDD8 pathway provide a mechanism by which breast cancer cells acquire antiestrogen resistance while retaining expression of ERalpha . OUTPUT:

sustaining proliferative signaling

HoC_1shot159

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: PURPOSE The difference in radiosensitivity between two isogenic tumour cell lines was evaluated to determine whether factors such as sublethal and potentially damage repair , DNA double-strand break repair and fidelity of repair can be related to differences in radiosensitivity . MATERIALS AND METHODS The cell lines used were the ovarian carcinoma A2780s and a radiation-resistant derivative A2780cp . Radiation response was measured in terms of cell survival , recovery of sublethal ( SLD ) and potentially lethal damage ( PLD ) , induction of and recovery of DNA strand breaks , and fidelity of DNA repair using a cell-free plasmid assay . RESULTS While A2780cp was more resistant to radiation than A2780s , it showed less ability for recovery of SLD and PLD . DNA strand-break induction was the same for both cell lines , while only at very high doses did A2780cp show greater DNA strand-break recovery than A2780s . Fidelity of rejoining DNA was significantly higher in the A2780cp cell line . CONCLUSION The difference in radiosensitivity between these two cell lines was not related to recovery of PLD or SLD or to the induction of DNA damage . It appears that fidelity of DNA rejoining , which was significantly higher in the resistant cell line , may be related to the difference in radiosensitivity . OUTPUT:

genomic instability and mutation

HoC_1shot160

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: We studied the effect of oxidative stress induced by hyperoxia , hydrogen peroxide , or menadione on mouse leukemia P388 cells at early ( 4 days ) and late ( 7 days ) stages of tumor growth . Oxidative stress proved to inhibit cell division and to induce apoptosis . Seven-day leukemia cells feature lower proliferative potential and higher sensitivity to oxidative stress and platidiam . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot161

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 tea polyphenols and tea pigments on cell cycle of hepatic cancer cells were studied . HepG2 cells were incubated with 50 and 100 mg/L tea polyphenols and tea pigments for 48 h respectively . Flow cytometry , Western blot and RT-PCR analysis were used . Flow cytometry analysis showed that tea polyphenols and tea pigments induced G1 arrest . Western blot analysis showed tea polyphenols and tea pigments significantly inhibited the expression of cyclin D1 protein and induced higher expression of P21WAFI/CIPI protein . The result of RT-PCR analysis demonstrated that Cdk4 was significantly inhibited by tea polyphenols and tea pigments . It is concluded that the induction of cell cycle arrest may be an important mechanism of tea on cancer prevention . OUTPUT:

evading growth suppressors;sustaining proliferative signaling

HoC_1shot162

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 clinicopathological study of 41 cases of pituitary apoplexy in a series of 324 surgically treated pituitary adenomas is presented . In 23 patients , the predominant operative finding was hemorrhage with or without necrosis . However , there were 15 ( 37.7% ) cases where pale , necrotic tissue with no evidence of hemorrhage was found at surgery . Pale , necrotic material was particularly found when there was a long interval between the acute clinical event and surgery . It is concluded that the pale , necrotic debris represents one stage in the resorption process of blood after hemorrhagic necrosis of pituitary adenomas . This entity needs to be kept in mind especially since the material closely resemble the pultaceous material seen in craniopharyngiomas and epidermoid cysts . OUTPUT:

resisting cell death

HoC_1shot163

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Dietary antioxidants , such as the carotenoids , may protect DNA from oxidative damage . This has been proposed to explain the epidemiological association between higher consumption of fruits and vegetables , which are rich in antioxidants , and lower incidence of cancer . However , this remains to be demonstrated conclusively . The effects of carotenoid supplementation on 1 ) baseline DNA damage , 2 ) susceptibility of cellular DNA to oxidative attack , and 3 ) DNA repair were measured in the human lymphocyte cell line Molt-17 . Baseline DNA damage , susceptibility to oxidant attack ( 100 mumol/l H2O2 for 5 min at 4 degrees C ) , and disappearance of DNA single-strand breaks ( SSB ) after oxidative challenge were monitored by single-cell gel electrophoresis . DNA repair patch synthesis activity in cell extracts was determined using assays that measure nucleotide incorporation during repair of oxidative lesions in template DNA . Unlike single-cell gel electrophoresis , the parameters measured with these assays are not dependent on strand break religation . There was no evidence that beta-carotene , lutein , or beta-cryptoxanthin supplementation protected cellular DNA from oxidation under basal conditions or after oxidative challenge . However , only carotenoid-supplemented cells exhibited a significant decrease in numbers of SSB over a 2-h period after treatment with H2O2 . Carotenoid supplementation did not provoke any detectable change in repair patch synthesis activity . We conclude that supplementation with carotenoids at 8 mumol/l does not provide significant antioxidant protection for DNA in Molt-17 lymphocytes but may enhance recovery of cells from oxidative challenge , as measured by loss of SSB . We argue that these data are most consistent with carotenoids acting to enhance DNA strand break repair . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot164

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Angiogenesis is increased in hematologic malignancies , including non-Hodgkin lymphoma ( NHL ) . Elevated serum levels of two important angiogenic factors , vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) , are associated with a poor prognosis . Immunohistochemistry was used to evaluate 27 patients with NHL and bone marrow involvement ( 17 with low-grade B-cell NHL , including 7 with higher grade transformation ; 6 with intermediate-grade B-cell NHL ; and 4 with T-cell lymphoma ) . Among the 17 patients with low-grade B-cell NHL , results for 7 were positive for VEGF stain ( 41.2% ) , and results were negative for all other stains for VEGF receptors , bFGF , and bFGF receptors . In the 10 patients with intermediate-grade B-cell NHL and T-cell lymphoma , all VEGF staining was positive ( 100% ) , but bFGF staining was only weakly positive in 2 . Staining results for seven patients who had low-grade B-cell NHL with higher grade transformation showed that VEGF staining was positive in large lymphoid cells of 5 patients and in small lymphoid cells of one patient . Staining for the receptors VEGFR-1 and VEGFR-2 was positive in large lymphoid cells in four and two cases , respectively . Staining for bFGF was positive in two cases of large lymphoid cells . We concluded that VEGF , but not bFGF , was associated with higher tumor grading of NHL and high-grade transformation of low-grade lymphoma . OUTPUT:

inducing angiogenesis

HoC_1shot165

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 role of T cells in eradicating leukemic cells has been well demonstrated for chronic myeloid leukemia ( CML ) . Type 1 ( T1 ) T-cell cytokines play a major role in this antileukemic immune effect . Studies in cancer patients have demonstrated a decreased T1 cytokine production , measured by enzyme-linked immunosorbent assay ( ELISA ) , in cultures of peripheral blood mononuclear cells . This observation of malignancy-related suppressed T1 cytokines also occurs in untreated chronic-phase ( CP ) CML , raising the question of the influence of different CML treatment regimens on this immunosuppression . Intracellular flow cytometry ( ICF ) has facilitated the evaluation of cytokines on a single-cell level . This study analyzed T1 ( interferon-gamma ) cytokine production in purified peripheral blood T cells by ICF , comparing different therapy approaches for CML . Twenty-one newly diagnosed CP CML patients were compared with 24 patients treated with interferon-alpha ( IFN-alpha ) and to 30 allogeneic bone marrow transplant ( BMT ) recipients ( BCR-ABL negative by reverse-transcriptase polymerase chain reaction , and free of , or having only limited graft-versus-host disease at the time of study ) . Thirty-seven healthy controls were included . Our results showed a significantly decreased T-cell IFN-gamma synthesis in CP CML patients in relation to healthy controls ( P = 0.0007 ) . Treatment with IFN-alpha resulted in a shift from immunosuppression--documented for the group of untreated patients--to immunopotentiation , with an increase of T-cell IFN-gamma production ( P = 0.0266 ) . Notably , BMT enhanced IFN-gamma production of T cells to a level not only exceeding untreated patients ( P &lt ; 0.0001 ) but also healthy volunteers ( P &lt ; 0.0001 ) . The observation of T1 cytokine up-regulation with IFN-alpha therapy indicates that enhanced T-cell function may be achievable in patients with CML , even in the absence of an allo-response . OUTPUT:

avoiding immune destruction

HoC_1shot166

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Modulation of the balance between pro- and antiangiogenic factors holds great promise for the treatment of a broad spectrum of human disease ranging from ischemic heart disease to cancer . This requires both the identification of angiogenic regulators and their efficient delivery to target organs . Here , we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 ( termed PEX ) delivered by lentiviral vectors in different angiogenesis models . Transduction of human endothelial cells with PEX virus suppressed endothelial invasion and formation of capillary-like structures without affecting chemotaxis in vitro . Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes . PEX expression also inhibited tumor-induced angiogenesis and tumor growth in a nude mouse model . Thus , our study shows that lentiviral vectors can deliver sufficient quantities of antiangiogenic substances to achieve therapeutic effects in vivo . OUTPUT:

inducing angiogenesis

HoC_1shot167

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 anti-breast cancer drug tamoxifen has recently been shown to cause an increase in intracellular free-Ca(2+) concentrations ( [ Ca(2+)](i) ) in renal tubular cells , breast cells and bladder cells . Because tamoxifen is known to alter ovary function in human patients and in rats , the present study was aimed at exploring whether tamoxifen could alter Ca(2+) movement in Chinese hamster ovary ( CHO-K1 ) cells . Cytosolic free-Ca(2+) levels in populations of cells have been explored by using fura-2 as a fluorescent Ca(2+) indicator . Tamoxifen at concentrations above 1 micro M increased [ Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 8 micro M. The Ca(2+) signal was reduced by removing extracellular Ca(2+) , but was not affected by nifedipine , verapamil , diltiazem or ICI 182,780 ( an estrogen receptor antagonist ) . Pretreatment with 1 micro M thapsigargin ( an endoplasmic reticulum Ca(2+) pump inhibitor ) to deplete the endoplasmic reticulum Ca(2+) abolished 10 micro M tamoxifen-induced Ca(2+) release . Neither inhibition of phospholipase C with 2 micro M U73122 nor depletion of ryanodine-sensitive Ca(2+) stores with 50 micro M ryanodine affected tamoxifen-induced Ca(2+) release . Cell proliferation assays using ELISA revealed that overnight incubation with 5-10 micro M tamoxifen inhibited cell proliferation by 20% , and 20 micro M tamoxifen killed all cells . Together , the results suggest that , in CHO-K1 cells , tamoxifen induced a [ Ca(2+)](i) increase by causing store-Ca(2+) release from the endoplasmic reticulum in an phospholipase C-independent manner , and by inducing Ca(2+) influx . The action of tamoxifen appears to be dissociated from estrogen receptor activation . Longer incubation with tamoxifen ( >5 micro M ) was cytotoxic . OUTPUT:

sustaining proliferative signaling

HoC_1shot168

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 identification of molecular markers related to critical biological processes during carcinogenesis may aid in the evaluation of carcinogenic potentials of chemicals and chemical mixtures . Work from our laboratory demonstrated that a single treatment with N-methyl-N'-nitro-N-nitrosoguanidine ( MNNG ) enhanced spontaneous malignant transformation of the human keratinocyte cell line RHEK-1 . In contrast , chronic low-level exposure of cells to arsenic alone or in a mixture containing arsenic , cadmium , chromium , and lead inhibited malignant conversion . To identify changes in gene expression that influence these different outcomes , cDNA microarray technology was used . Analysis of multiple human arrays in MNNG-transformed RHEK-1 cells , designated OM3 , and those treated with arsenic or the arsenic-containing metal mixture showed unique patterns of gene expression . Genes that were overexpressed in OM3 included oncogenes , cell cycle regulators , and those involved in signal transduction , whereas genes for DNA repair enzymes and inhibitors of transformation and metastasis were suppressed . In arsenic-treated cells , multiple DNA repair proteins were overexpressed . Mixture-treated cells showed increased expression of a variety of genes including metallothioneins and integrin 4 . These cells showed decreased expression of oncogenes , DNA repair proteins , and genes involved in the mitogen-activated protein kinase pathway . For comparison we are currently analyzing gene expression changes in RHEK-1 cells transformed by other means . The goal of these studies is to identify common batteries of genes affected by chemical modulators of the carcinogenic process . Mechanistic studies may allow us to correlate alterations in their expression with sequential stages in the carcinogenic process and may aid in the risk assessment of other xenobiotics . OUTPUT:

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

HoC_1shot169

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Purpose of this work was to synthesize several cis-/trans- isomer pairs of the platinum(II) complexes , and study the extent and the mode of their antiproliferative activity on HeLa cells . Six platinum(II) isomer pairs have a general formula cis-/trans-[PtA2X2] , where A is ligand : ammonia ( NH3 ) , pyridine ( Py ) ; and X is ligand : chloride ion ( Cl- ) , bromide ion ( Br- ) , iodide ion ( I- ) , thiocyanato ion ( SCN- ) ; four compounds have different structural formulas , and these are cis-/trans-[Pt(NH2OH)2(NH3)2]Cl2 , and cis-/trans-Pt(Gly)2 , where Gly is bidentate glycinato ligand . Results of the MTT assay , showed that six cis- and one trans-platinum(II) complexes exhibited cytotoxicity ( IC50 ) ranging between 5 and 33 microM . Most of the cis-platinum(II) isomers caused significant alteration of cell cycle phases progression , and induced apoptosis in degree that varied among different compounds , as evaluated using flowcytometry and morphological study . Spectrophotometric analysis ( AAS ) indicated that there is no correlation between intracellular platinum(II) accumulation and cytotoxicity of tested complexes . OUTPUT:

resisting cell death;sustaining proliferative signaling

HoC_1shot170

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 deoxycholic acid ( DCA ) and ursodeoxycholic acid ( UDCA ) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP)-induced aberrant crypt foci ( ACF ) in the rat colon were examined . The effect of these bile acids on DNA adduct formation by PhIP in the colon was then analyzed , since the main action of PhIP is the formation of DNA adducts and subsequent gene mutations . For the ACF study , male F344 rats were administered PhIP-HCl ( 75 mg/kg , 10 doses ) by gavage , and a diet containing bile acid ( 0.4% DCA or UDCA ) was provided from 3 days before the first dose of PhIP for 8 weeks . The mean number of ACF per colon of DCA , UDCA and controls were 9.9 , 2.4 and 5.5 , respectively . The ACF number was significantly increased by DCA and decreased by UDCA ( P<0.001 ) . To examine the effect of bile acids on DNA adduct formation , male F344 rats were fed a diet supplemented with bile acids ( 0.1 or 0.4% of DCA and UDCA ) 7 days prior to the PhIP administration . All rats were administered a single dose of PhIP-HCl ( 50 mg/kg ) by gavage and sacrificed 48 hours later . DNA adduct levels of the 0.1% UDCA , 0.1% DCA and controls were 2.93 ( adducts/10(7) nucleotides ) , 2.65 and 1.10 , respectively . Those of 0.4% UDCA , 0.4% DCA and controls were 1.64 , 1.30 and 1.00 , respectively . The PhIP-DNA adduct level was significantly increased by administration of 0.1% UDCA , 0.1% DCA ( P<0.05 ) and 0.4% UDCA ( P<0.01 ) . The increasing effect of both DCA and UDCA on PhIP-induced DNA adduct formation was unexpected , and was not directly associated with ACF formation . OUTPUT:

genomic instability and mutation

HoC_1shot171

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Previously we have found deregulation of collagen metabolism in human pancreatitis and pancreatic cancer tissues . Insulin-like growth factor-I ( IGF-I ) is known to stimulate collagen biosynthesis through interaction with IGF-I receptor . IGF-I binding proteins ( BPs ) regulate the activity of IGF-I . We investigated whether serum and tissue IGF-I and IGF-BPs as well as tissue IGF-I receptor expression may reflect disturbances of collagen metabolism in patients with pancreatitis and pancreatic cancer . In pancreatitis tissue , a significant increase in IGF-I and IGFBP-3 content was accompanied by a distinct increase in IGF-I receptor expression , compared to control pancreas tissue . In contrast , serum from patients with pancreatitis did not show significant increases in IGF-I and IGFBP-3 levels , however , significant increases in IGFBP-1 level ( 2.5 fold ) . Moreover , a distinct decrease in radioactive IGF-binding to the BPs , compared to control serum , was found . Pancreatic cancer tissue and serum of patients with pancreatic cancer showed significant increases in IGF-I , IGFBP-3 and IGFBP-1 content , accompanied by dramatic increases in IGF-I tissue receptor expression , compared to controls . In serum of patients with pancreatic cancer distinct increases in radioactive IGF-binding to 46 kDa BP , compared to control serum , were observed . The data suggest that disturbances in tissue collagen metabolism during pancreatic diseases may result from deregulation of IGF-I homeostasis and that elevated serum levels of IGF-I , IGFBP-3 and IGFBP-1 may serve as markers of pancreatic cancer . OUTPUT:

sustaining proliferative signaling

HoC_1shot172

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 epidemiologic association between asbestos exposure and human malignant mesothelioma is well established . However , the molecular mechanisms linking asbestos exposure of humans and the subsequent mesothelioma formation is not well understood . The most frequent genetic changes found so far in human malignant mesothelioma ( HMM ) are deletions and point mutations in the tumor suppressor genes p16INK4a and NF2 . Whereas homozygous deletions appear to be the predominant mechanism leading to p16/CDKN2A inactivation , inactivating point mutations coupled with allelic loss mainly occur at the NF2 locus . In the present study , asbestos-treated human mesothelial cells ( HMC ) , SV40-transformed human mesothelial cells ( MeT-5A ) and a human mesothelioma cell line ( COLO ) were investigated for genetic changes of cell cycle genes ( cyclin D1 , p16INK4a , RB1 , CDK2 ) using multicolor fluorescence in situ hybridization ( mFISH ) in interphase cells . The results show that cyclin D1 is unaffected in all investigated cells . The p16INK4a gene locus was shown to be mutated in COLO cells but not in HMC . After labeling of CDK2 and RB1 , hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells . Our data indicate that disarrangement of the RB1 dependent pathway seems to be involved in mesothelioma formation . OUTPUT:

sustaining proliferative signaling

HoC_1shot173

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 cellular mechanisms of anti-androgen-induced tumor regression have not been investigated in great detail . We have compared the induction of cell death in the androgen-dependent , non-invasive LNCaP prostate cancer cell line by Casodex and TNF-alpha . Both agents induce a dose and time-dependent decrease in cell viability in vitro . However , Casodex does not induce classical DNA fragmentation to oligonucleosomes typically induced by TNF-alpha , but rather induces cleavage to form intermediate 60 kb DNA fragments . RT-PCR based analysis demonstrates that in LNCaP cells Casodex coordinately alters the expression of steady-state level of mRNAs of several matrix metalloproteases and their cognate inhibitors ( most notably MMP2 and TIMP1 ) . Zymography and reverse zymography confirm that the ratio of metalloprotease(s) to inhibitor(s) is altered in favor of activation of the proteases . In a small percentage of the treated LNCaP cells , the activation of the extracellular matrix ( ECM)-proteases by Casodex also induces an invasive phenotype . The acquisition of an invasive phenotype is not seen when LNCaP cells are treated with TNF-alpha , and is not seen when the LNCaP cells are treated with both compounds simultaneously , suggesting that the phenomenon may be specific to particular classes of compounds . These observations have significant implications in the treatment of prostate cancer , since the appearance of a more aggressive phenotype following treatment is clearly undesirable . OUTPUT:

resisting cell death;activating invasion and metastasis

HoC_1shot174

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 elucidate role of the three enzymes in hepatocarcinogenesis , hMTH1 , hOGG1 and hMYH , mRNA expression were examined by using RT/semi-quantitative real-time PCR and 8-O-HdG levels was studied by HPLC/ECD in HCC and non-tumorous liver tissue of 21 patients with hepatocellular carcinoma ( HCC ) . It was found that the 8-OHdG level in non-tumourous liver tissue was significantly higher than in HCC tissue ( P = 0.006 ) , and this was correlated with the degree of inflammation . The hMTH1 expression in HCC tissue was significantly higher than in non-tumorous liver tissue ( P = 0.014 ) . Inversely , The hMYH alpha expression was significantly increased ( P = 0.039 ) in non-tumorous liver tissue . No difference was seen in hOGG1 expression in non-tumorous liver and HCC tissue . A significant linear correlation between hMTH1 and hOGG1 expression was found both in HCC tissue ( r = 0.809 , P &lt ; 0.001 ) and in non-tumorous liver tissue ( r = 0.883 , P &lt ; 0.001 ) . Our findings suggested a reactive rather than pathogenic role of the DNA repair enzymes in the hepatocarcinogenesis . OUTPUT:

genomic instability and mutation;tumor promoting inflammation

HoC_1shot175

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVE The aims of this study were to analyse the results and long term outcome in a prospective non randomised trial of 74 patients treated by laparoscopic colo-rectal resection for cancer , and to determine wether survival and recurrence are or are not compromised by an initial laparoscopic approach . PATIENTS AND METHODS Seventy-four patients with colo-rectal carcinoma were included in a prospective trial and treated by laparoscopic resection . All patients were reviewed at 1 , 3 , and 6 months interval . A median of 5 years follow up was available . Forty-eight patients ( 65% ) had more than 3 years of follow up . RESULTS Six conversions ( 8.1% ) were necessary : 2 for tumor invasion of adjacent organs , 2 for limited margin resection in lower rectal tumors , 1 for small bowel injury and 1 for obesity . After surgery , passing flatus occurred at 34.3 +/- 16.7 h and oral intake could be reinstaured at 42.6 +/- 22 h . Mean postoperative stay was 8.2 +/- 3.4 days . No death occurred . The overall morbidity was about 13.5% . The rate of late complications was 5.4% . Two port site metastasis ( 2.6% ) were seen in locally advanced carcinoma . Recurrence rate at 5 years was 0% for Dukes A , 20% for Dukes B , 39.2% for Dukes C. Survival rate at 5 years was 100% for Dukes A , 80% for Dukes B , and 60.7% for Dukes C. These results are similar to those of conventional open surgery . CONCLUSION Laparoscopic colorectal resection for cancer can be performed safely , with a low morbidity and rare late complications . Long term follow up ( 5 years ) assessment shows similar outcome compared with conventional surgery . OUTPUT:

activating invasion and metastasis

HoC_1shot176

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Solar ultraviolet radiation is considered to be injurious rather than necessary for most organisms living on the earth . It is reported that the risk of skin cancer in humans increases by the depletion of the ozone layer . We have examined the genotoxicity of solar ultraviolet , especially the longer wavelength light , using Drosophila . Recently , we have demonstrated that light of wavelength up to 340 nm is mutagenic on Drosophila larvae . Using an excision repair-deficient Drosophila strain ( mus201 ) , we have obtained results suggesting that the lesion caused in larvae by the 320 nm-light irradiation may be similar to the damage induced by irradiation at 310 nm , and that light of 330 and 340 nm may induce damage different from that induced by 310 and 320 nm-light . To examine the difference in DNA damage induced by light of a particular wavelength , we performed monochromatic irradiation on larvae of two Drosophila strains ; one excision repair-deficient ( mei-9 ) and another postreplication repair-deficient ( mei-41). 310 and 320 nm-light was more mutagenic in the mei-9 strain than in mei-41 , whereas 330 and 340 nm-light was more mutagenic in mei-41 than in mei-9 . It is demonstrated that the mei-41 gene is a homologue of the human atm gene which is responsible for a cell cycle checkpoint . This result suggests that 310-320 nm-light induces DNA damage that is subject to nucleotide excision repair ( NER ) and that 330-360 nm-light causes damage to be recognized by the cell cycle checkpoint but it is not repairable by NER . OUTPUT:

evading growth suppressors;genomic instability and mutation

HoC_1shot177

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 the course of a medicinal chemistry program aimed at discovering novel tumour-active rebeccamycin derivatives targeting DNA and/or topoisomerase I , a series of analogues with the sugar residue linked to the two indole nitrogens was recently developed . Two promising drug candidates in this staurosporine-rebeccamycin hybrid series were selected for a DNA-binding study reported here . The DNA interaction of the cationic indolocarbazole glycosides MP059 bearing a N,N-diethylaminoethyl side chain and MP072 containing a sugar bearing an amino group was compared with that of the uncharged analogue MP024 . The results show that the addition of a cationic substituent , either directly on the indolocarbazole chromophore or on the carbohydrate residue , significantly reinforces the interaction of the drugs with nucleic acids . The two cationic molecules MP059 and MP072 recognise preferentially sequences containing GpT.ApC and TpG.CpA steps but they do not inhibit topoisomerase I , in contrast to the parent uncharged derivative MP024 which stimulates DNA single strand breaks by topoisomerase I. The cytotoxic activity of the indolocarbazole derivatives bearing positively charged groups is one order of magnitude higher than that of the neutral compound MP024 . The high cytotoxic potential can be attributed to the enhanced DNA binding and sequence recognition capacity of the cationic compounds . The study provides useful information for further structure-activity relationship studies in the indolocarbazole series . OUTPUT:

genomic instability and mutation

HoC_1shot178

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Acetyl-11-keto-beta-boswellic acid ( AKBA ) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata ( frankincense ) . AKBA has been recently identified as a novel , orally active , non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro . Because natural pentacyclic triterpenes have an antiproliferative effect against different tumor types , we investigated the effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas , common central nervous system tumors . Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2-8 microM . At similar , physiologically achievable concentrations , AKBA rapidly ( within minutes ) and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 ( Erk-1 and Erk-2 ) in meningioma cells stimulated with platelet-derived growth factor BB . High expression level of 5-LO was detected in primary meningioma cells and surgical specimens by immunoblotting analysis , suggesting the possible role of 5-LO in meningioma tumorigenesis . Considering the critical importance of the Erk-1/2 signal transduction pathway not only in meningiomas but in other human neoplasms , the interruption of signaling through this evolutionarily conserved pathway might be one of the mechanisms by which AKBA induces suppression of proliferation and apoptosis of different tumor types . OUTPUT:

sustaining proliferative signaling

HoC_1shot179

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Common use of antimutagens and anticarcinogens in everyday life is an effective measure for preventing human cancer and genetic diseases . Antioxidant properties of tea have vast potential as protective agents against diverse toxic effects . The present study was aimed to evaluate the role of aqueous clonal tea extracts ( green tea , oolong tea and black tea ) in modulating the genotoxic damage induced by cyclophosphamide ( CP ) , a commonly used chemotherapeutic drug and a well-known mutagen and clastogen . All the three tea extracts at 1 and 2% concentration did not increase the frequency of micronucleated polychromatic erythrocytes ( MPE ) in bone marrow cells of mice when administered individually . The tea extracts decreased the micronuclei ( MN ) induced by CP . Therefore , regular intake of tea may improve the antioxidant status in in vivo and thereby reduce the risk of cancer and coronary heart disease . OUTPUT:

genomic instability and mutation

HoC_1shot180

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: To investigate whether the Bcl-2 gene family is involved in modulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60 cell line and primary acute myelogenous leukemic cells , the Bcl-2 family member Mcl-1 , Bax and Bak and cell cycle proteins including P27kipl , P21wafl , cyclin D3 and pRbp- were selected and their expression detected by SABC immuno-histochemical stain method . The attitude of sub-G1 peak in DNA histogram was determined by FCM . The TUNEL positive cell percentage was identified by terminal deoxynucleotidyl transferase ( TdT)-mediated Biotin dUNP end labeling technique . It was found that when HL-60 cells were treated with 25 mumol/L curcumin for 24 h , the expression level of Mcl-1 was down-regulated , but that of Bax and Bak up-regulated time-dependently . There was significant difference in the expression level of Mcl-1 , Bax and Bak between the curcumin-treated groups and control group ( P &lt ; 0.05-0.01 ) . At the same time , curcumin had no effect on progress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis , but could increase the peak of Sub-G1 ( P &lt ; 0.05 ) , and down-regulate the expression of Mcl-1 and up-regulate the expression of Bax and Bak with the difference being statistically significant . The expression of P27kipl , P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin . These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process of apoptosis induced by curcumin in HL-60 cells and AML cells . Curcumin can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells . The mechanism appeared to be mediated by perturbing G0/G1 phases checkpoints which associated with up-regulation of P27kipl , P21wafl and pRbp- expression , and down-regulation of cyclin D3 . OUTPUT:

sustaining proliferative signaling;evading growth suppressors;resisting cell death

HoC_1shot181

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 evaluate the effects of adenovirus ( Ad)-mediated transfer of p53 and p16 on human bladder cancer cells EJ , EJ were transfected with Ad-p53 and Ad-p16 . Cell growth , morphological change , cell cycle , apoptosis were measured using MTT assay , flow cytometry , cloning formation , immunocytochemical assays . Ad-p16 or Ad-p53 alone could inhibit the proliferating activity of EJ cells in vitro . Ad-p53 could induce apoptosis of partial EJ cells . G1 arrest was observed 72 h after infection with Ad-p16 , but apoptosis was not obvious . The transfer of Ad-p16 and Ad-p53 could significantly inhibit the growth of EJ cells , decrease the cloning formation rate and induce apoptosis of large number of EJ cells . The occurrence time of subcutaneous tumor was delayed and the tumor volume in 4 weeks was diminished by using Ad-p53 combined with Ad-p16 and the difference was significant compared with using Ad-p53 or Ad-p16 alone . It was suggested that the transfer of wild-type p53 and p16 could significantly inhibit the growth of human bladder cancer in vitro and in vivo . OUTPUT:

resisting cell death;evading growth suppressors

HoC_1shot182

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 comparative study was undertaken between cancer of the uterine cervix ( n = 50 ) and female breast cancer ( n = 50 ) with reference to the expression of c-erbB-2 oncoprotein ( HER-2/neu ) and that of epidermal growth factor receptor ( EGF-R ) , both being highly homologous structurally . Expressions of EGF-R and c-erbB-2 oncoprotein were viewed in breast and cervical cancer tissues by immunochemical staining . Cervical cancer cases showed much higher expression of EGF-R which also revealed significant association with the expression of c-erbB-2 oncoprotein and tumour grading . Among breast cancer cases , over-expression of EGF-R correlated significantly with metastasis of lymph node ; and expression of c-erbB-2 oncoprotein showed a significant relationship with histological grading of the tumour . Moreover , an association was noticed between the tumour grade and the concomitant immuno positive expression of EGF-R and c-erbB-2 . Our study revealed an existence of a conflicting pattern in the expression of EGF-R and c-erbB-2 oncoprotein between carcinomas of the breast and uterine cervix . OUTPUT:

sustaining proliferative signaling;activating invasion and metastasis

HoC_1shot183

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Transforming growth factor-beta1 ( TGF-beta1 ) exerts potent immunosuppressive effects . In this study , we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma ( HCC ) cell lines in immunosuppression mechanisms . Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay ( ELISA ) , we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5 , Hep3B , and HepG2 . To determine the biological activity of TGF-beta1 in the supernatants , we examined the effects of the culture supernatants on the production of interferon ( IFN)-gamma induced during the culture of peripheral blood mononuclear cells ( PBMCs ) stimulated with interleukin ( IL)-12 . IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5 , Hep3B , and HepG2 reduced to 14.7 +/- 0.8 , 17.3 +/- 9.0 , and 35.9 +/- 14.6% , respectively , compared with the value in the culture with control medium ( complete culture medium ) . These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes ( CTL ) and natural killer ( NK ) cells , and thus could enhance their ability to escape immune-mediated surveillance . OUTPUT:

avoiding immune destruction

HoC_1shot184

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: INTRODUCTION Cell-cell interaction is an essential component of atherosclerotic plaque development . Activated monocytes appear to play a central role in the development of atherosclerosis , not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development . Using serum free co-culture method , we determined the effect of monocytes on endothelial cell proliferation . METHODS Endothelial cell proliferation is determined by the amount of [ 3H]thymidine incorporated in to the DNA . Basic fibroblast growth factor ( b-FGF ) , vascular endothelial growth factor ( VEGF ) and interleukin-8 ( IL-8 ) levels in the conditioned medium were determined by ELISA . RESULTS Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation , whereas conditioned medium from activated monocytes promoted endothelial cell proliferation . The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF , VEGF and IL-8 . Neutralizing antibodies against b-FGF , VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes . When b-FGF , VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes , it is less mitogenic to endothelial cells . CONCLUSION Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors . OUTPUT:

inducing angiogenesis

HoC_1shot185

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 experiments have shown that emodin is highly active in suppressing the proliferation of several tumor cell lines . However , it is not clear that emodin can induce growth inhibition of hepatoma cells . We have found that emodin induces apoptotic responses in the human hepatocellular carcinoma cell lines ( HCC ) Mahlavu , PLC/PRF/5 and HepG2 . The addition of emodin to these three cell lines led to inhibition of growth in a time- and dose-dependent manner . Emodin generated reactive oxygen species ( ROS ) in these cells which brought about a reduction of the intracellular mitochondrial transmembrane potential ( DeltaPsim ) , followed by the activation of caspase-9 and caspase-3 , leading to DNA fragmentation and apoptosis . Our findings demonstrate that ROS and the resulting oxidative stress play a pivotal role in apoptosis . Preincubation of hepatoma cell lines with the hydrogen peroxide-scavenging enzyme , catalase ( CAT ) and cyclosporin A ( CsA ) , partially inhibited apoptosis . These results demonstrate that enhancement of generation of ROS , DeltaPsim disruption and caspase activation may be involved in the apoptotic pathway induced by emodin . OUTPUT:

resisting cell death;tumor promoting inflammation

HoC_1shot186

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Tea ( Camellia sinensis ) is one of the most popular beverages , consumed worldwide . The health promoting properties of tea have been attributed to its antioxidative polyphenolic constituents and their oxidative products . The aim of the present study was to evaluate the chemopreventive efficacy of a black tea infusion on azoxymethane induced colonic preneoplastic lesions , the aberrant crypt foci in Sprague-Dawley rats . Rats were injected with azoxymethane ( 15mg/kg.b.w. ) and received oral administration of 1% and 2% ( w/v ) tea infusions from the 1(st)day of carcinogen application . The treatment was continued for 12 weeks . The colons were then assessed for aberrant crypt foci and compared with the untreated carcinogen control group . In situ cell proliferation and in situ apoptosis were also estimated using Brdu incorporation and the TUNEL method , respectively . Aberrant crypt foci were reduced significantly ( by 44% in the 1% tea-treated and by about 40% in 2% tea-treated group ) . Significant decrease in proliferation and increase in apoptosis suggest a possible interplay between the two processes resulting in inhibition of colon carcinogenesis by black tea . OUTPUT:

resisting cell death

HoC_1shot187

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 the present study we examined the effects of menadione , a redox cycling agent , on structural changes of human osteosarcoma line 143B cells . It has been previously reported that menadione can cause necrotic or apoptotic cell death in a concentration- depending manner . In our experimental model , cells were treated with 100 microM menadione for 24 hours . Using electron microscopy technique cells carrying three kinds of morphological changes were detected : necrotic cells , apoptotic cells and those demonstrating a co-existence of apoptotic and necrotic features in one single cell . OUTPUT:

resisting cell death

HoC_1shot188

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: Resveratrol , a phytoalexin found in grapes and wine , has been shown to exhibit a wide range of pharmacological properties and is believed to play a role in the chemoprevention of human cancer . Resveratrol has also been shown to induce antiproliferation and apoptosis of several leukemia cell lines . In the present study , we investigated the effect of resveratrol in adult T cell leukemia . Our present observations showed that resveratrol induced growth inhibition in all five human T cell lymphotrophic virus-1-infected cell lines examined , with 50% effective dose of 10.4-85.6 mM . In the resveratrol-treated cells , induction of apoptosis was confirmed by annexin V-based analyses and morphological changes . The most surprising observation was that resveratrol treatment resulted in a gradual decrease in the expression of survivin , an antiapoptotic protein , during cell apoptosis . These findings indicate that resveratrol inhibits the growth of human T cell lymphotrophic virus-1-infected cell lines , at least in part , by inducing apoptosis mediated by downregulation in survivin expression . In view of the accumulating evidence that survivin may be an important determinant of a clinical response in adult T cell leukemia , our present findings have led to the suggestion that resveratrol , a common constituent of the human diet , merits further investigation as a potential therapeutic agent for this incurable disease . OUTPUT:

resisting cell death

HoC_1shot189

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Intra-arterial infusion with cisplatin ( CDDP ) and bleomycin ( BLM ) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone . Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM . Two to four courses of the infusion therapy were given to each patient , and the response rate , the tumor and serum drug concentrations , and the cell kinetics in tumor tissue were evaluated . The response rate ( CR+PR ) was 71.4% according to the WHO criteria . There was no difference , in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders . Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment , both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors . These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy . OUTPUT:

sustaining proliferative signaling

HoC_1shot190

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 isolated rabbit kidney proximal tubular epithelial cell lines . The selection was based on their ability to form confluent monolayers on porous supports and to maintain receptor-mediated signal transduction and ion transport , characteristic of the proximal tubule . The isolation method consisted of several steps : ( 1 ) superficial cortical proximal tubule segments were microdissected and cultured on a matrix-coated porous support until cells formed a confluent monolayer ; ( 2 ) primary cultures showing hormone-regulated ion transport typical for the proximal tubule were selected and co-cultured with irradiated fibroblasts ; and ( 3 ) the epithelial cells surviving after several passages were expanded and passaged on porous substrates . Most of the cell lines developed in this manner were obtained by co-culture with irradiated fibroblasts producing a recombinant retrovirus encoding SV40 large T antigen and G418 resistance . However , SV40 T antigen expression was not essential for immortalization , since neither T antigen nor G418 resistance was detected in the isolated cell lines and co-culture with non-producing 3T3 cells gave similar results . One cell line ( vEPT ) has been characterized in some detail with respect to morphological , biochemical , and ion transport properties . This line forms confluent monolayers with apical microvilli , tight junctions , and convolutions of the basolateral plasma membrane . Once confluent , monolayers maintain conductances of 25 to 32 mS/cm2 for several weeks in culture and possess phlorizin-sensitive short-circuit current ( Isc ) in glucose containing media , indicative of apical Na(+)-glucose co-transport. vEPT cells also retain receptor and signaling mechanisms for angiotensin II ( Ang II ) . Apical and basal Ang II and 5,6-epoxy-eicosatrienoic acid ( 5,6-EET ) modulate the Isc in a manner similar to primary cultures . The cell lines share with primary cultures expression of the cytokeratins K8 , K10/K11 , and K19 ( "nomenclature " [ 21] ) . They also retain several receptor and signal transduction mechanisms . For example , Ang II , arachidonate , bradykinin , 5,6-EET , parathyroid hormone ( residues 1 through 34 ) , and purine nucleotides increase cytosolic Ca2+ , PTH elevates cAMP levels , and Ang II enhances proximal tubule-specific arachidonic acid metabolism . OUTPUT:

enabling replicative immortality

HoC_1shot191

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 human fibroblasts , the expression of SV40 large T antigen is known to cause a variety of chromosomal aberrations and especially dicentric chromosomes . In some cases , the later aberrations have been reported to be reversible telomeric associations . We report here aberration and chromosome number studies of twenty-nine T antigen positive lineages , studied from their initiation by transfection of T antigen sequences into human diploid fibroblasts , until crisis or immortalization occurred or , in some cases until the lines became tumorigenic in nude mice . The data show that T antigen consistently produced chromosomal instability of both number and structure by an active process that began before transformation indicators were positive and continued throughout neoplastic progression . The most frequently observed aberrations were dicentric chromosomes , which were shown to be true dicentrics by examination by in situ hybridization with telomeric sequences . These data are consistent with the hypothesis that T antigen causes human fibroblasts to become neoplastically transformed by successive rounds of chromosomal mutation and lineage evolution . OUTPUT:

enabling replicative immortality;genomic instability and mutation

HoC_1shot192

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Basal cell hyperplasia classically has been described as having bland cytologic features . During the past 2 years , we have seen 12 cases ( 11 in consultation ) with atypical features that were confused with adenocarcinoma of the prostate . Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma ; in the 12th case , nuclei were enlarged , hyperchromatic , and moderately pleomorphic . Immunohistochemistry with antibodies against high-molecular-weight cytokeratin ( 34 beta E12 ) was performed in nine of the cases , verifying their basal cell nature . Additional findings in these cases were necrotic intraluminal secretions ( two cases ) , immature squamous metaplasia ( two cases ) , peculiar hyaline cytoplasmic globules ( two cases ) , adenosis ( one case ) , markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen ( one case ) , and intraluminal blue mucin ( two cases ) . We analyzed nine cases of typical basal cell hyperplasia , all of which showed classic features of basal cell hyperplasia with benign cytology . Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation . Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate , prostatic intraepithelial neoplasia , and basaloid carcinoma ( adenoid cystic carcinoma ) of the prostate . OUTPUT:

tumor promoting inflammation

HoC_1shot193

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 telomerase activity and the senescence profile of cultured breast fibroblasts from normal human interstitial and malignant stromal tissue were studied in comparison with their proliferation and differentiation pattern . Fibroblasts were grown either in the presence or absence of a conditioned medium ( CM ) obtained from cultures of the oestrogen receptor-positive breast cancer MCF-7 cell line . At different passages ( from the 2nd up to the 48th ) , fibroblasts were examined for the telomerase activity by the Telomerase Repeats Amplification Protocol ( TRAP ) assay , for proliferation profile by Ki-67 antigen expression , and the myofibroblast or smooth muscle cell-like differentiation pattern by immunofluorescence with monoclonal antibodies specific for smooth muscle markers . Serial passages of fibroblasts from normal or tumour breast reveal that the relationship between the levels of telomerase activity and phenotypic/proliferation profile changes with cell subcultivation in a different manner in the two cell populations . The fibroblasts from normal tissue completed 12 passages in a CM-independent way prior to senescence whereas fibroblasts from tumour stroma senescence were attained after 48 passages . These cells showed a marked decrease of telomerase activity , growth rate and smooth muscle alpha-actin expressing myofibroblasts after the 32nd passage . CM treatment of this fibroblast population induces a decline in the myofibroblast content , which precedes the changes in telomerase activity . Passaged fibroblasts from normal breast tissue can be converted to myofibroblasts upon CM treatment whereas those from tumour stroma were CM-insensitive . Taken together our data suggest that a heterogeneous fibroblast population with different life span is activated/recruited in the breast interstitium and poses the problem of a unique activation/recruitment of fibroblasts in neoplastic conditions . OUTPUT:

enabling replicative immortality

HoC_1shot194

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Contradictory results have been reported regarding the association between vascularity ( used as an index of angiogenesis ) and thrombospondin-1 ( TSP-1 ) in human tumours . In previous studies , the reported association was based on the estimated average TSP-1 value per tumour , with a sufficient number of specimens collectively analysed per tumour type . Given the extent of intra-tumour heterogeneity , we determined the association between TSP-1 and vascularity within individual specimens , based on the average values of TSP-1 and vascularity in 10-20 pre-selected areas per tumour . Cells expressing TSP-1 mRNA were visualised by in situ hybridisation and quantified by point counting . Vascularity was quantified by point counting and vessel density of von Willebrand Factor-positive vessels . In 10 ductal breast carcinomas , a direct correlation between TSP-1 and vascularity was found in 4 tumours , no correlation in 3 and an inverse correlation in 3 . The effect of TSP-1 on endothelial cell migration in vitro was assessed in the Boyden chamber assay . TSP-1 stimulated cell migration at low concentrations ( 0.1-10 microg/ml ) and was inhibitory at high concentrations ( 25-100 microg/ml ) . These results suggest that TSP-1 may elicit a concentration-dependent , bi-phasic , effect on angiogenesis . OUTPUT:

inducing angiogenesis;activating invasion and metastasis

HoC_1shot195

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis . The possibility was tested that interleukin-8 ( IL-8 ) , which is a cytokine that is chemotactic for lymphocytes and neutrophils , is also angiogenic . Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells . Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha . An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity . These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis , tumor growth , and wound repair . OUTPUT:

inducing angiogenesis

HoC_1shot196

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 observed previously that treatment of plateau-phase L5178Y murine lymphoblasts in vitro with 2'-deoxycoformycin plus deoxyadenosine ( dCF/dAdo ) can inhibit the repair of X-irradiation-induced DNA single-strand breaks ( SSB ) in these cells and that this effect is associated with synergistic cell kill . In this study we examined the effect of a combination treatment of plateau-phase L5178Y cells with bleomycin ( BLM ) plus dCF/dAdo . Incubation of BLM-treated cells with dCF/dAdo resulted in significant inhibition of the repair of BLM-induced DNA SSB . However , an additive , but not a synergistic , increase in cell kill was observed when cells were treated with a combination of BLM plus dCF/dAdo . OUTPUT:

genomic instability and mutation;resisting cell death

HoC_1shot197

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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: There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo . In this study , we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo . The human pancreatic cancer cell line Hs-776T ( HS-W ) produces slow-growing tumors in SCID mice . Cells of a variant form ( HS-R ) of Hs-776T produced faster-growing tumors compared to HS-W . Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) . Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2 , but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R . Cell proliferation was similar in both tumor types in vivo , whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells ( EC ) . Subsequently , VEGF was over-expressed in Hs-776T cells ( HS-VF ) , resulting in rapidly growing tumors and lowering tumor and EC apoptosis . Collectively , our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors . OUTPUT:

inducing angiogenesis;resisting cell death;sustaining proliferative signaling

HoC_1shot198

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related 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 examined the effect of FK506 on the Adriamycin sensitivity of the multidrug resistant human chronic myelocytic leukemia cell line ( K562/ADM ) . In K562/ADM cells , 1.0 microgram/ml FK506 reversed the resistance of Adriamycin , and increased the IC50 value for Adriamycin up to 17 fold . However , IC50 value for the parent cells ( K562 ) increased only 1.5 fold . By cell cycle analysis , the accumulation in late S-G2M phase was confirmed on K562/ADM cells , treated with 1.0 microgram/ml FK506 and low-dose of Adriamycin . Cyclosporin A ( CsA ) could also restored the Adriamycin sensitivity in the K562/ADM cells , as previously reported. 1.0 microgram/ml FK506 as well as CsA significantly increased radioactive Adriamycin accumulation in K562/ADM cells and blocked [ 3H]azidopien photoaffinity labeling of P-glycoprotein . These results suggest that 1.0 microgram/ml FK506 could reverse the Adriamycin resistance in a MDR human leukemia cells through the interaction with P-glycoprotein . OUTPUT:

sustaining proliferative signaling

HoC_1shot199

The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics. ### INPUT: Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis. OUTPUT: sustaining proliferative signaling;resisting cell death INPUT: OBJECTIVES Epiphyseal cartilage is a barrier to osteosarcoma invasion , however the mechanisms behind this resistance remain unclear . The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage . METHODS We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression . We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis ; proangiogenic vascular endothelial growth factor ( VEGF ) and antiangiogenic pigment epithelium-derived factor ( PEDF ) . RESULTS Epiphyseal cartilage remained intact across its entire length in all sections examined , despite increasing tumor size as well as intra- and extraosseous destruction . In the most advanced cases , only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded . This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF . In contrast , the resting , proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases . This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF . CONCLUSION Epiphyseal cartilage is resistant to local invasion by osteosarcoma . The balance of angiogenesis , influenced by pro- and antiangiogenic factors , is likely to play an important role in this resistance . OUTPUT:

inducing angiogenesis;activating invasion and metastasis