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Clinical NLP Lab 23

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 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 .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Astaxanthin modulates immune response , inhibits cancer cell growth , reduces bacterial load and gastric inflammation , and protects against UVA-induced oxidative stress in in vitro and rodent models . Similar clinical studies in humans are unavailable . Our objective is to study the action of dietary astaxanthin in modulating immune response , oxidative status and inflammation in young healthy adult female human subjects . METHODS Participants ( averaged 21.5 yr ) received 0 , 2 , or 8 mg astaxanthin ( n = 14/diet ) daily for 8 wk in a randomized double-blind , placebo-controlled study . Immune response was assessed on wk 0 , 4 and 8 , and tuberculin test performed on wk 8 . RESULTS Plasma astaxanthin increased ( P &lt ; 0.01 ) dose-dependently after 4 or 8 wk of supplementation . Astaxanthin decreased a DNA damage biomarker after 4 wk but did not affect lipid peroxidation . Plasma C-reactive protein concentration was lower ( P &lt ; 0.05 ) on wk 8 in subjects given 2 mg astaxanthin . Dietary astaxanthin stimulated mitogen-induced lymphoproliferation , increased natural killer cell cytotoxic activity , and increased total T and B cell subpopulations , but did not influence populations of Thelper , Tcytotoxic or natural killer cells . A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8 . Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects . There was no difference in TNF and IL-2 concentrations , but plasma IFN-gamma and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin . CONCLUSION Therefore , dietary astaxanthin decreases a DNA damage biomarker and acute phase protein , and enhances immune response in young healthy females .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE The cytotoxic effect of the combination treatment of TNF-alpha and hyperthermia on L929 and TNF-alpha-resistant L929 ( rL929 ) cells was investigated . MATERIALS AND METHODS L929 cells were treated with TNF-alpha ( 5 ng/mL ) , heating at 43 degrees C or the combination of TNF-alpha and heating . The cells were harvested at different time within the 24-hour period . The viability and the type of cell death of the harvested cells were examined . RESULTS When L929 cells were treated with a combination of TNF-alpha and heating the cells died quickly and apoptosis increased to an overwhelming extent , especially in the group pre-treated with TNF-alpha for 1 h prior to heating . Although rL929 cells were resistant to TNF-alpha alone , the cells became sensitive to TNF-alpha treatment when combined with heating . Similar to the L929 cell , the cells also died rapidly and exhibited apoptosis to a higher extent . Using an Annexin-V-FITC kit and flow cytometer , we found that both necrosis and apoptosis occurred . Agarose gel electrophoresis of DNA extracted from treated cells showed that the DNA fragments were multiples of approximately 200 bp . Furthermore , by studying the kinetics of cell death and apoptosis , we found that the loss of cell membrane integrity preceded the DNA fragmentation in both L929 and rL929 cells . CONCLUSION The results suggested that hyperthermia may enhance the necrotic and apoptotic effects of TNF-alpha on some tumour cells and overcome the resistance of some tumour cells to TNF-alpha .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Myxoid leiomyosarcoma is an extremely rare variant of leiomyosarcoma , masquerading almost to perfection as a benign lesion . For , indeed , the tumor lacks the defining features of high mitotic activity , cellular atypia or necrosis , and the microscopic picture is dominated by abundant myxoid stroma containing sparse spindle cells . We report here such a case occurring in the uterus and discuss the differential diagnosis . The relevant literature is reviewed .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Adoptive transfer of immunity against hepatitis B surface antigen ( HBsAg ) was previously shown to facilitate suppression of experimental human hepatocellular carcinoma ( HCC ) expressing HBsAg in athymic mice . We have shown that oral tolerance induces antigen-specific immune suppression of HBsAg by feeding hepatitis B virus ( HBV ) antigens . In the present study we evaluated the effect of oral tolerance induction toward HBV or HCC antigens on the growth of experimental HCC-expressing HBsAg in mice . Tolerance induction was induced in mice by 5 oral feedings of 1 microg HBV antigens or HCC-extracted proteins ( 50 microg protein ) before vaccination with recombinant HBsAg . Splenocytes ( 2 x 10(6) ) from these mice were transferred to sublethally irradiated athymic BALB/c mice previously transplanted subcutaneously with 10(7) human hepatoma Hep3B cells . Adoptive transfer of splenocytes immunized toward HBsAg prevented tumor growth . At 4 weeks after splenocyte transplantation , tumor volume and serum alpha-fetoprotein ( AFP ) levels in athymic mice transplanted with splenocytes immunized to HBsAg were undetectable as compared with 1,048 +/- 738 mm(3) and 2,500 +/- 1,431 ng/ml in recipients of na�ve splenocytes ( p &lt ; 0.0001 ) . Mice receiving splenocytes tolerized toward Hep3B cells , as manifested by reduced serum HBs antibody levels , reduced HBV-specific stimulation index and reduced HBV-specific-IFN gamma spot-forming cells , had early tumor growth evident by elevated AFP serum levels , weight loss and mortality , which were suppressed at 6 weeks . Mice transplanted with splenocytes tolerized toward HBV antigens did not have direct evidence of tumor growth . Induction of oral tolerance toward HCC-extracted proteins enabled transient tumor growth in this model . This effect was mediated through downregulation of the anti-HBV immune response .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Manganese , an essential trace nutrient in human beings , has been widely used in the steel industry to improve hardness , stiffness , and strength . With the increased applications of manganese compounds , discharge into the environment has rapidly increased and may exert adverse effects on human health . In this study , manganese toxicity was investigated using cultured T98G cells , which are derived from human glioblasts with the ability to differentiate into several different types of neuroglia . Cytotoxicity was shown in manganese-treated groups ( 100 , 200 , 400 , and 800microM of MnCl(2) ) , and cell viability was decreased to 58.8% of the control group at 2days after treatment with 800microM of MnCl(2) . When cells were treated with manganese for 24h , ROS dose-dependently increased while antioxidant intracellular GSH decreased . With the generation of ROS , the increased activity of caspase-3 was shown , and was followed by chromatin condensation and breakage , which is an indication of the cellular apoptotic process . ROS also triggered pro-inflammatory responses in cultured T98G cells , which were demonstrated by the increased gene expression and protein levels of IL-6 and IL-8 .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cell migration plays important roles in natural processes involving embryonic development , inflammation , wound healing , cancer metastasis and angiogenesis . Cell migration on various biomaterials is also believed to improve the rate of wound healing and implant therapies in the tissue-engineering field . This study measured the distance traversed , or mileage , of mouse fibroblasts on a silk fibroin surface . Fibroblasts on the fibroin surface moved with better progress during 24 h than cells on collagen or fibronectin surfaces . Results obtained by quantitative real-time reverse transcription-polymerase chain reaction ( qRT-PCR ) revealed that fibroblasts on the fibroin surface expressed transforming growth factor β-induced protein ( TGFBI ) , which is an extracellular matrix ( ECM ) protein , stronger than on other surfaces in the early cell-culture stages . These results demonstrate that the fibroin surface shows higher potential to enhance cell migration and the production of ECM than a collagen or fibronectin surface .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metastasis , commonly to the lung , is the major cause of mortality from testicular cancer . The aim of the present study was to examine the effect of a novel nutrient mixture ( NM ) containing ascorbic acid , amino acids and green tea extract on the inhibition of melanoma growth and metastasis using a model of intratesticular inoculation of B16FO cells into nude mice . Male athymic mice ( n=12 ) , 10-12 weeks of age , were inoculated with 5�10(5) B16FO melanoma cells in 100 μl of PBS into the right testis , while the left testis was left untreated . Following inoculation , the mice were randomly divided into two groups . The control group ( n=6 ) was fed a regular mouse chow diet and the NM 1% group ( n=6 ) the same diet , but supplemented with 1% NM . Four weeks later the mice were sacrificed and the abdominal cavity was opened . Mice in the control group exhibited extensive metastasis in the peritoneal cavity and severely enlarged right testes and necrotic seminiferous tubules . By contrast , in the NM 1% fed group there was no evidence of peritoneal metastasis in 50% of the animals and mild metastasis in the remaining 50% . The right testes were enlarged and seminiferous tubules in the area of invasion showed evidence of degeneration . No metastasis to the liver , kidney or spleen were evident in either group . However , severe lung metastasis was observed in 2 of 6 mice in the control group and mild metastasis in 2 of 6 mice in the NM 1% group . In conclusion , these results confirm earlier studies and verify the anti-metastatic potential of NM .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The role of estrogen receptor beta ( ERβ ) in breast cancer is unclear . ERβ is considered to have a protective role in breast cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer cells . We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells . To study the mechanisms of the ERβ-mediated G2 cell cycle arrest , we investigated its effects on the regulatory pathways responsible for the G2/M phase transition . We found that ERβ inhibits CDK1 activity , which is the critical determinant of the G2/M progression . CDK1 activity is modulated by both stimulatory and inhibitory factors . Cyclin B1 is the major activator of CDK1 . ERβ inhibited the cell cycle-dependent stimulation of cyclin B1 mRNA and protein . GADD45A and BTG2 are two major inhibitors of CDK1 , which have been implicated in breast tumor formation . Based on these findings , we explored if the expression pattern of GADD45A and BTG2 is affected by ERβ . We found that ERβ stimulates GADD45A and BTG2 mRNA levels . The induction of these two genes is caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2 . Our findings demonstrated that unliganded ERβ causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2 expression . These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new therapies to prevent breast cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Diffuse intrinsic pontine glioma ( DIPG ) is a fatal pediatric disease . Thus far no therapeutic agent has proven beneficial in the treatment of this malignancy . Hence , conventional DNA-damaging radiotherapy ( RT ) remains the standard treatment , providing transient neurological improvement without improving probability of overall survival . During RT , WEE1 kinase controls the G2 cell cycle checkpoint allowing for repair of irradiation ( IR)-induced DNA damage . Here we show that WEE1 kinase is one of the highest overexpressed kinases in primary DIPG tissues as compared to matching non-neoplastic brain tissues . Inhibition of WEE1 by MK-1775 treatment of DIPG cells inhibited the IR-induced WEE1-mediated phosphorylation of CDC2 , resulting in reduced G2/M arrest and decreased cell viability . Finally , we demonstrate that MK-1775 enhances the radiation response of E98-Fluc-mCherry DIPG mouse xenografts . Altogether , these results show that inhibition of WEE1 kinase in conjunction with RT holds potential as a therapeutic approach for the treatment of DIPG .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The new concept of keeping primary tumor under control in situ to suppress distant foci sheds light on the novel treatment of metastatic tumor . Hyperthermia is considered as one of the means for controlling tumor growth . In this study , a novel thermal modality was built to introduce hyperthermia effect on tumor to suppress its growth and progression using 4T1 murine mammary carcinoma , a common animal model of metastatic breast cancer . A mildly raised temperature ( i.e.39�C ) was imposed on the skin surface of the implanted tumor using a thermal heating pad . Periodic heating ( 12 hours per day ) was carried out for 3 days , 7 days , 14 days , and 21 days , respectively . The tumor growth rate was found significantly decreased in comparison to the control without hyperthermia . Biological evidences associated with tumor angiogenesis and metastasis were examined using histological analyses . Accordingly , the effect of mild hyperthermia on immune cell infiltration into tumors was also investigated . It was demonstrated that a delayed tumor growth and malignancy progression was achieved by mediating tumor cell apoptosis , vascular injury , degrading metastasis potential and as well as inhibiting the immunosuppressive cell myeloid derived suppressor cells ( MDSCs ) recruitment . Further mechanistic studies will be performed to explore the quantitative relationship between tumor progression and thermal dose in the near future .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction;resisting cell death" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND In this report , we explored the role of PKCalpha and PKCe as mediators of phorbol 12-myristate13-acetate ( PMA)-induced proliferation in pituitary tumor GH3B6 cells , and determined if the ERK1/2 and Akt pathways were activated . METHODS The GH3B6 cell proliferation was estimated by BrdU incorporation and the cell cycle progression by flow cytometric cell cycle analysis . We determined the expression of PKCalpha and PKCe in membrane and cytosolic fractions by western blotting . The subcellular redistribution of both PKC isozymes was analyzed by confocal microscopy . RESULTS Incubation with PMA for 15 min stimulated PKCalpha and PKCe activation , which was correlated with the phosphorylation of ERK1/2 but not Akt . The activation of both these PKC isozymes was closely associated with the stimulation of proliferation and the cell cycle progression induced by PMA in GH3B6 cells , an effect that was blocked by the inhibitors of PKCalpha ( Gö6976 ) and PKCe ( eV1-2 ) . In addition , the pretreatment with the inhibitor of ERK1/2 ( PD98059 ) prevented the mitogenic activity induced by treatment with PMA for 15 min . CONCLUSION We demonstrated that the activation of PKCalpha and PKCe by phorbol ester in tumor pituitary GH3B6 cells led to cell proliferation and cell cycle progression , effects that involved ERK1/2 activation .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The molecular mechanism mediating expression of senescent cell antigen-aggregated or cleaved band 3 and externalized phosphatidylserine ( PS ) on the surface of aged erythrocytes and their premature expression in certain anemias is not completely elucidated . The erythrocytes with these surface modifications undergo macrophage-mediated phagocytosis . In this study , the role of protein kinase C ( PKC ) isoforms in the expression of these surface modifications was investigated . Inhibition of PKC α by 30 μM rottlerin ( R30 ) and 2.3 nM G� 6976 caused expression of both the senescent cell marker-externalized PS measured by FACS analysis and aggregated band 3 detected by western blotting . In contrast to this observation , but in keeping with literature , PKC activation by phorbol-12-myristate-13-acetate ( PMA ) also led to the expression of senescence markers . We explain this antithesis by demonstrating that PMA-treated cells show reduction in the activity of PKC α , thereby simulating inhibition . The reduction in PKC α activity may be attributed to the known downregulation of PMA-activated PKC α , caused by its membrane translocation and proteolysis . We demonstrate membrane translocation of PKC α in PMA-treated cells to substantiate this inference . Thus loss of PKC α activity either by inhibition or downregulation can cause surface modifications which can trigger erythrophagocytosis .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cells undergoing malignant transformation often exhibit a shift in cellular metabolism from oxidative phosphorylation to glycolysis . This glycolytic shift , called the Warburg effect , provides a mechanistic basis for targeting glycolysis to suppress carcinogenesis through the use of dietary caloric restriction and energy restriction-mimetic agents ( ERMA ) . We recently reported the development of a novel class of ERMAs that exhibits high potency in eliciting starvation-associated cellular responses and epigenetic changes in cancer cells though glucose uptake inhibition . The lead ERMA in this class , OSU-CG5 , decreases the production of ATP and NADH in LNCaP prostate cancer cells . In this study , we examined the effect of OSU-CG5 on the severity of preneoplastic lesions in male transgenic adenocarcinoma of the mouse prostate ( TRAMP ) mice . Daily oral treatment with OSU-CG5 at 100 mg/kg from 6 to 10 weeks of age resulted in a statistically significant decrease in the weight of urogenital tract and microdissected dorsal , lateral , and anterior prostatic lobes relative to vehicle controls . The suppressive effect of OSU-CG5 was evidenced by marked decreases in Ki67 immunostaining and proliferating cell nuclear antigen ( PCNA ) expression in the prostate . OSU-CG5 treatment was not associated with evidence of systemic toxicity . Microarray analysis indicated a central role for Akt , and Western blot analysis showed reduced phosphorylation and/or expression levels of Akt , Src , androgen receptor , and insulin-like growth factor-1 receptor in prostate lobes . These findings support further investigation of OSU-CG5 as a potential chemopreventive agent .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid ( EPA ) are able to suppress cell proliferation and inhibit tumor growth . The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated ( Atm)-deficient mice , a genetic cancer model that is associated with increased levels of oxidative stress . We analyzed toxicity , proliferation , cell-cycle progression , and apoptosis of EPA in vitro and latency to tumorigenesis in vivo . Because of the impact of reactive oxygen species ( ROS ) on the tumor incidence in ataxia telangiectasia ( AT ) , we further analyzed the effect of EPA on the generation of ROS and oxidative DNA damage ( ODD ) . EPA effectively inhibited proliferation , altered cell-cycle progression , and induced apoptosis of tumor cells ( AT-4 ) . EPA showed no effect on the latency to tumorigenesis in Atm-deficient mice . EPA treatment was accompanied by a significant increase of ROS and ODD . Our results demonstrate the antiproliferative effect of EPA on tumor cells by alteration of cell-cycle progression and induction of apoptosis in vitro . On the other hand , EPA treatment of Atm-deficient mice led to the formation of ROS and accumulation of ODD that might have abrogated the anticarcinogenic effect caused by EPA .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Genetic and epigenetic changes in the von Hippel-Lindau ( VHL ) tumour suppressor gene are common in sporadic conventional ( clear cell ) renal cell carcinoma ( ccRCC ) . The effects on VHL expression are unknown but increased understanding may be relevant clinically , either in terms of prognosis or in therapy selection . We have examined the expression of VHL mutant RNA in 84 ccRCC tumours previously screened for mutations in genomic DNA , 56 of which contained 52 unique mutations or polymorphisms . Based on the predicted change to the primary amino acid sequence , 24 of the mutations were missense , 11 resulted in frameshifts with premature truncation , 9 resulted in immediate truncation at the site of the mutation and 2 were frameshifts which extended the reading frame beyond the normal stop codon . Nine tumours had intronic variants , including substitution of invariant residues at splice sites , deletion of nucleotides spanning the exon-intron junction , an intronic variant of unknown function and the polymorphism c.463+43A>G . Four variants were identified which were present in genomic DNA but not in mRNA . Three of these , all encoding apparent missense changes to the primary amino acid sequence , were located close to the ends of exons , reduced the strength of the splice site and function as null rather than missense variants . One nonsense variant was not detectable in mRNA but all other mutations resulting in premature truncation codons ( PTCs ) were , suggesting truncating VHL mutations may potentially generate truncated VHL protein . An intronic variant , c.341‑11T>A , previously regarded as of unknown function , is associated with an increased level of skipping of exon 2 and may , therefore , reduce production of pVHL . Our data show that the biological consequences of VHL mutations are not necessarily predictable from the sequence change of the mutation and that for the majority of VHL mutations , the potential for the generation of mutant protein exists .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Epirubicin was developed as a semi-synthetic anthracycline derivative to circumvent the cardiotoxic limitations associated with the use of doxorubicin in the clinic . Anthracycline compounds have been demonstrated to form covalent drug-DNA adducts utilising endogenous and exogenous sources of formaldehyde ; however , previous investigations of the formation of epirubicin-DNA adducts provide conflicting evidence for adduct formation . This work provides evidence that epirubicin acts to form drug-DNA adducts at physiologically relevant concentrations and demonstrates that the rate of formation of epirubicin-DNA adducts is slower than that observed for other anthracycline compounds , explaining why they are only detectable under defined experimental conditions . Formation of covalent epirubicin-DNA adducts improves the apoptotic profile of epirubicin and provides opportunities to overcome drug resistance and cardiotoxic limitations .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In normal human cells , oncogene-induced senescence ( OIS ) depends on induction of DNA damage response . Oxidative stress and hyperreplication of genomic DNA have been proposed as major causes of DNA damage in OIS cells . Here , we report that down-regulation of deoxyribonucleoside pools is another endogenous source of DNA damage in normal human fibroblasts ( NHFs ) undergoing HRAS(G12V)-induced senescence . NHF-HRAS(G12V) cells underexpressed thymidylate synthase ( TS ) and ribonucleotide reductase ( RR ) , two enzymes required for the entire de novo deoxyribonucleotide biosynthesis , and possessed low dNTP levels . Chromatin at the promoters of the genes encoding TS and RR was enriched with retinoblastoma tumor suppressor protein and histone H3 tri-methylated at lysine 9 . Importantly , ectopic coexpression of TS and RR or addition of deoxyribonucleosides substantially suppressed DNA damage , senescence-associated phenotypes , and proliferation arrest in two types of NHF-expressing HRAS(G12V) . Reciprocally , short hairpin RNA-mediated suppression of TS and RR caused DNA damage and senescence in NHFs , although less efficiently than HRAS(G12V) . However , overexpression of TS and RR in quiescent NHFs did not overcome proliferation arrest , suggesting that unlike quiescence , OIS requires depletion of dNTP pools and activated DNA replication . Our data identify a previously unknown role of deoxyribonucleotides in regulation of OIS .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVE As we previously demonstrated , the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones , especially 6-iodo-5-hydroxy-eicosatrienoic acid ( delta-iodolactone ) . In this communication we compare the effect of iodide , molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines ( B-CPAP cells , FTC-133 cells and 8505C cells ) as well as on human breast cancer cells ( MCF 7 ) . METHODS Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium ( DMEM ) and MCF 7 cells in Rowswell Park Memorial Institute ( RPMI ) culture medium , both containing 10% ( v/v ) Fetal Calf Serum ( FCS ) , until they were confluent . Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM ( thyroid cancer cells ) or in RPMI medium ( MCF 7 cells ) both containing 5% FCS . Thereafter , different concentrations of iodide , iodine or delta-iodolactone were added for 24 h . Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells . Apoptosis was determined by a mitochondrial potential assay . RESULTS The growth rate of B-CPAP cells was unaffected by iodide , but was reduced by high concentreations of molecular iodine ( 100 and 500 microM ) . However , delta-iodolactone significantly reduced cell proliferation already with low concentrations ( 5 microM and 10 microM ) and further in a dose-dependent manner up to 82% . FTC-133 and 8505C cells were unaffected by iodide , iodine or delta-iodolactone . In contrast , in MCF 7 cells , molecular iodine ( 100 microM ) inhibited growth from 100% to 83% but delta-iodolactone ( 1 , 5 and 10 microM ) dose-dependently decreased growth rate from 100% to 82% and 62% , respectively . The inhibition of growth was through apoptosis , and not necrosis , as the amount of apoptotic cells corresponded to the growth inhibition . CONCLUSION delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metastatic breast tumors undergo epithelial-to-mesenchymal transition ( EMT ) , which renders them resistant to therapies targeted to the primary cancers . The mechanistic link between mtDNA ( mitochondrial DNA ) reduction , often seen in breast cancer patients , and EMT is unknown . We demonstrate that reducing mtDNA content in human mammary epithelial cells ( hMECs ) activates Calcineurin ( Cn)-dependent mitochondrial retrograde signaling pathway , which induces EMT-like reprogramming to fibroblastic morphology , loss of cell polarity , contact inhibition and acquired migratory and invasive phenotype . Notably , mtDNA reduction generates breast cancer stem cells . In addition to retrograde signaling markers , there is an induction of mesenchymal genes but loss of epithelial markers in these cells . The changes are reversed by either restoring the mtDNA content or knockdown of CnAα mRNA , indicating the causal role of retrograde signaling in EMT . Our results point to a new therapeutic strategy for metastatic breast cancers targeted to the mitochondrial retrograde signaling pathway for abrogating EMT and attenuating cancer stem cells , which evade conventional therapies . We report a novel regulatory mechanism by which low mtDNA content generates EMT and cancer stem cells in hMECs.Oncogene advance online publication , 4 November 2013 ; doi:10.1038/onc.2013.467 .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Placental Growth Factor ( PGF ) is a key molecule in angiogenesis . Several studies have revealed an important role of PGF primarily in pathological conditions ( e.g. : ischaemia , tumour formation , cardiovascular diseases and inflammatory processes ) suggesting its use as a potential therapeutic agent . However , to date , no information is available regarding the genetics of PGF variability . Furthermore , even though the effect of environmental factors ( e.g. : cigarette smoking ) on angiogenesis has been explored , no data on the influence of these factors on PGF levels have been reported so far . Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors : a study sample from two isolated villages in the Cilento region , South Italy ( N=871 ) and a replication sample from the general Danish population ( N=1,812 ) . A significant difference in PGF mean levels was found between the two cohorts . However , in both samples , we observed a strong correlation of PGF levels with ageing and sex , men displaying PGF levels significantly higher than women . Interestingly , smoking was also found to influence the trait in the two populations , although differently . We have then focused on genetic risk factors . The association between five single nucleotide polymorphisms ( SNPs ) located in the PGF gene and the plasma levels of the protein was investigated . Two polymorphisms ( rs11850328 and rs2268614 ) were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample . These results , for the first time , support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Retinoic acid ( RA)-induced differentiation therapy is partially successful in neuroblastoma treatment . We found that a novel combination of vanadium-based PTP inhibitors with RA induced extensive differentiation in neuroblastoma cells . In contrast to RA alone , this led to either permanent differentiation or senescence after 14days of combined treatment followed by chemical removal . Senescence was dependent in part on synergistic AKT and ERK activation. p21 was also strongly induced , but in contrast to oncogene-induced senescence , p53 was not activated . Vanadium-based inhibitors thus serve strongly to enhance RA's ability to drive differentiation and a novel form of senescence in neuroblastoma cells .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Testicular Germ Cell Tumors ( TGCT ) and patient-derived cell lines are extremely sensitive to cisplatin and other interstrand cross-link ( ICL ) inducing agents . Nevertheless , a subset of TGCTs are either innately resistant or acquire resistance to cisplatin during treatment . Understanding the mechanisms underlying TGCT sensitivity/resistance to cisplatin as well as the identification of novel strategies to target cisplatin-resistant TGCTs have major clinical implications . Herein , we have examined the proficiency of five embryonal carcinoma ( EC ) cell lines to repair cisplatin-induced ICLs . Using γH2AX staining as a marker of double strand break formation , we found that EC cell lines were either incapable of or had a reduced ability to repair ICL-induced damage . The defect correlated with reduced Homologous Recombination ( HR ) repair , as demonstrated by the reduction of RAD51 foci formation and by direct evaluation of HR efficiency using a GFP-reporter substrate . HR-defective tumors cells are known to be sensitive to the treatment with poly(ADP-ribose) polymerase ( PARP ) inhibitor . In line with this observation , we found that EC cell lines were also sensitive to PARP inhibitor monotherapy . The magnitude of sensitivity correlated with HR-repair reduced proficiency and with the expression levels and activity of PARP1 protein . In addition , we found that PARP inhibition strongly enhanced the response of the most resistant EC cells to cisplatin , by reducing their ability to overcome the damage . These results point to a reduced proficiency of HR repair as a source of sensitivity of ECs to ICL-inducing agents and PARP inhibitor monotherapy , and suggest that pharmacological inhibition of PARP can be exploited to target the stem cell component of the TGCTs ( namely ECs ) and to enhance the sensitivity of cisplatin-resistant TGCTs to standard treatments .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks ( DSBs ) in genomic DNA in cycling cells . These DSBs are often covalently bound with polypeptides at the 3 ' and 5 ' ends . Such modifications must be eliminated before DSB repair can take place , but it remains elusive which nucleases are involved in this process . Previous studies show that CtIP plays a critical role in the generation of 3 ' single-strand overhang at \" clean \" DSBs , thus initiating homologous recombination ( HR)-dependent DSB repair . To analyze the function of CtIP in detail , we conditionally disrupted the CtIP gene in the chicken DT40 cell line . We found that CtIP is essential for cellular proliferation as well as for the formation of 3 ' single-strand overhang , similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex . We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332 , which is required for interaction with BRCA1 . Although the resulting CtIP(S332A/-/-) cells exhibited accumulation of RPA and Rad51 upon DNA damage , and were proficient in HR , they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP(+/-/-) cells . Finally , CtIP(S332A/-/-)BRCA1(-/-) and CtIP(+/-/-)BRCA1(-/-) showed similar sensitivities to these reagents . Taken together , our data indicate that , in addition to its function in HR , CtIP plays a role in cellular tolerance to topoisomerase inhibitors . We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs , thereby facilitating subsequent DSB repair .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Epidermal growth factor receptor ( EGFR ) gene amplification and overexpression are commonly present in glioblastoma , and confer advantages of growth , invasiveness and radio/chemotherapy-resistance for tumour cells . Here , we assessed the role of EGFR activation for downstream mitogenic signalling in the commonly used glioblastoma cell line U251 . Despite the high expression level , activation of EGFR under standard culture conditions was low . Intact EGFR function was verified by the rapid phosphorylation of EGFR and downstream mitogen-activated protein(MAP) kinase ERK1/2 upon addition of exogenous EGF to serum-starved cells . By contrast , addition of fetal bovine serum ( FBS ) activated downstream ERK1/2 via the MAP kinase kinase without phosphorylating EGFR . A phosphoreceptor tyrosine kinase array showed FBS-induced activation of insulin-like growth factor-1 receptor ( IGF-1R),and the IGF-1R inhibitor AG1024 inhibited FBS-induced phosphorylation of ERK1/2 , implying IGF-1R as the major driver of FBS-associated mitogenic signalling in the absence of exogenous EGF . These findings have important implications for in vitro drug testing in glioblastoma . Moreover , activation of ERK1/2 was also strongly influenced by growth state and cell density of U251 cultures . Re-seeding exponentially growing cultures at high cell density induced p27/CDKN1B expression and suppressed P-ERK1/2 indicating a certain regulation of proliferation by contact inhibition . Strikingly , highly activated ERK1/2 signalling and cell cycle progression occurred when cells were released from plateau phase regardless of high seeding density . This phenomenon might implicate a proliferation response in the early recurrence observed after clinical therapy in glioblastoma patients . However , whether it will recapitulate in vivo remains to be demonstrated .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metformin is a well-established diabetes drug that prevents the onset of most types of human cancers in diabetic patients , especially by targeting cancer stem cells . Metformin exerts its protective effects by functioning as a weak \" mitochondrial poison, \" as it acts as a complex I inhibitor and prevents oxidative mitochondrial metabolism ( OXPHOS ) . Thus , mitochondrial metabolism must play an essential role in promoting tumor growth . To determine the functional role of \" mitochondrial health \" in breast cancer pathogenesis , here we used mitochondrial uncoupling proteins ( UCPs ) to genetically induce mitochondrial dysfunction in either human breast cancer cells ( MDA-MB-231 ) or cancer-associated fibroblasts ( hTERT-BJ1 cells ) . Our results directly show that all three UCP family members ( UCP-1/2/3 ) induce autophagy and mitochondrial dysfunction in human breast cancer cells , which results in significant reductions in tumor growth . Conversely , induction of mitochondrial dysfunction in cancer-associated fibroblasts has just the opposite effect . More specifically , overexpression of UCP-1 in stromal fibroblasts increases β-oxidation , ketone body production and the release of ATP-rich vesicles , which \" fuels \" tumor growth by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells . Hence , the effects of mitochondrial dysfunction are truly compartment-specific . Thus , we conclude that the beneficial anticancer effects of mitochondrial inhibitors ( such as metformin ) may be attributed to the induction of mitochondrial dysfunction in the epithelial cancer cell compartment . Our studies identify cancer cell mitochondria as a clear target for drug discovery and for novel therapeutic interventions .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO(2) and H(2)O ( oxidative phosphorylation ) even in the presence of oxygen ( Warburg effect ) . Dichloroacetate ( DCA ) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA ( tricarboxylic acid cycle ) by indirect activation of pyruvate dehydrogenase ( PDH ) . This can subsequently lead to an increased flow of oxygen in the respiratory chain , associated with enhanced generation of reactive oxygen species ( ROS ) which may cause apoptosis . In order to investigate if DCA may be suitable for neuroblastoma therapy , it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption . The data show , that DCA ( in the low millimolar range ) is able to reduce lactate production , but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality , proliferation and apoptosis of the three cell lines investigated . Therefore , DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma treatment .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Mutations in the Nf2 tumor suppressor gene lead to tumor formation in humans and mice and cellular overproliferation phenotypes in Drosophila . The Nf2 encoded protein , merlin , shares close sequence similarity in its amino terminus to members of the band 4.1 family of membrane-cytoskeletal linkers . Similarities between merlin and this family suggest a role for merlin in regulating cytoskeletal function . However , the mechanism of the tumor suppressing activity of merlin is not yet understood . Mutational analysis of Nf2 in flies has led to the identification of a dominant-negative allele , which harbors mutations in the amino terminus of the protein . Here , we report that expression of a murine analog of this amino-terminal mutant of Nf2 leads to complete transformation of NIH3T3 fibroblasts in culture . Cells that express this Nf2 mutant allele display disruptions of the actin cytoskeleton , lack of contact inhibition of growth , and anchorage-independent growth . Finally , fibroblasts that express this mutant Nf2 allele form tumors when injected into nude mice .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs ) show dramatic antitumor activity in a subset of patients with non-small cell lung cancer who have an active mutation in the epidermal growth factor receptor ( EGFR ) gene . On the other hand , some lung cancer patients with wild type EGFR also respond to EGFR-TKIs , suggesting that EGFR-TKIs have an effect on host cells as well as tumor cells . However , the effect of EGFR-TKIs on host microenvironments is largely unknown . A multiple organ metastasis model was previously established in natural killer cell-depleted severe combined immunodeficient mice using human lung cancer cells . This model was used to investigate the therapeutic efficacy of erlotinib , an EGFR-TKI , on multiple organ metastases induced by human small cell lung cancer cells ( SBC-5 cells ) that did not express EGFR . Although erlotinib did not have any effect on the proliferation of SBC-5 cells in vitro , it significantly suppressed bone and lung metastases in vivo , but not liver metastases . An immunohistochemical analysis revealed that , erlotinib significantly suppressed the number of osteoclasts in bone metastases , whereas no difference was seen in microvessel density . Moreover , erlotinib inhibited EGF-induced receptor activator of nuclear factor kappa-B expression in an osteoblastic cell line ( MC3T3-E1 cells ) . These results strongly suggested that erlotinib prevented bone metastases by affecting host microenvironments irrespective of its direct effect on tumor cells .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Pterostilbene , a polyphenolic compound present in grapes and other fruits , has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types . We found that pterostilbene at the IC90 concentration of 44 �M inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells . Treatment with pterostilbene resulted in a transient accumulation of cells in the G0/G1-cell cycle phase followed by the S-phase arrest . Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential , phosphatidylserine externalization and internucleosomal DNA fragmentation . Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Current antibody-based immunotherapeutic approaches under evaluation for breast carcinoma are limited in target scope . For example , administration of the human epidermal growth factor receptor ( EGFR ) antibody , alone or in combination with a chemotherapeutic drug , is thought to primarily inhibit tumor cell proliferation . The aim of this study was to assess the effects of a combined blockade designed to inhibit tumor growth by inhibition of proliferation rate and the proinflammatory effects of interleukin ( IL ) 8 . EXPERIMENTAL DESIGN A human breast carcinoma cell line that produces high levels of IL-8 was injected s.c. into severe combined immunodeficient mice . IL-8 has been reported to augment the progression of some human tumors ; thus , we used a human IL-8 antibody , ABXIL8 , in combination with anti-EGFR , ABXEGFR , to inhibit the metastasis of MDA231 tumors . RESULTS Whereas anti-IL-8 alone had no appreciable antimetastatic effect , the combination of ABXIL8 significantly enhanced the antitumor effects of ABXEGFR , resulting in greater survival of SCID tumor-bearing mice . This effect on survival was correlated with decreased metastatic spread and decreased tumor size in mice receiving both antibodies . Intriguingly , in vitro studies indicate that this antibody combination markedly inhibited matrix metalloproteinase activity associated with MDA-231 cells to a greater degree than either antibody alone . CONCLUSION Combined administration of these two human antibodies using growth factor blockade in conjunction with chemokine blockade may thus provide a more effective approach for treatment of metastatic human breast carcinoma .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity . Since sesamin inhibits the metabolic degradation of tocotrienols , studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse ( +SA ) and human ( MCF-7 and MDA-MB-231 ) mammary cancer cells . Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition , whereas combination treatment with these agents synergistically inhibited the growth of +SA , MCF-7 and MDA-MB-231 mammary cancer cells , while similar treatment doses were found to have little or no effect on normal ( mouse CL-S1 and human MCF-10A ) mammary epithelial cell growth or viability . However , sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism . Rather , combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest , and a corresponding decrease in cyclin D1 , CDK2 , CDK4 , CDK6 , phospho-Rb , and E2F1 levels , and increase in p27 and p16 levels . Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability . Taken together , these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic , not cytotoxic , and results from G1 cell cycle arrest .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: To search for potential biomarkers used to monitor the process of immortalization , we investigated the relative level of telomerase activity and other immortal phenotypes in the SHEE esophageal epithelial cell line . This human fetal esophageal epithelial cell line , induced by human papilloma virus ( HPV ) 18 E6E7 , was continually propagated over 100 passages . Fourteenth passage cells ( SHEE14 ) were cultured in a flask with a serum-free medium and continually cultured to the 30th passage ( SHEE30 ) . Cells of SHEE14 , SHEE20 and SHEE30 were examined according to cell morphology , cell cycle , apoptosis , contact-inhibition growth , anchorage- dependency , dose-dependency to epithelial growth factors ( EGF ) , telomerase activity and tumorigenicity . The SHEE14 cells exhibited good differentiation with contact-inhibition and anchorage-dependent growth . The SHEE20 cells exhibited increase of senescent and apoptotic cells , and difficulty in propagation . The SHEE30 cells exhibited a higher proliferative index and some undifferentiated cells , with weakened contact-inhibition and anchorage-dependent growth . The telomerase was activated in cells of SHEE30 , but not in SHEE14 and SHEE20 cells . The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30 . Three groups of cells displayed lack of tumor formation in nude mice . Compared with SHEE14 and SHEE20 , SHEE30 cells were of immortalized status with immortal phenotype , which consisted of telomerase activity , increase of cell proliferation , weakened contact-inhibition and anchorage-dependent growth , dose dependency to EGF and lack of tumor formation . From passage 14 to 30th passage , SHEE cells went through cellular senescence , apoptosis and immortalization . With a view toward diagnostic and biological aspects , telomerase activity is a crucial step and a cardinal requirement for immortalization . The telomerase activity and other immortal phenotypes are potential markers for monitoring the process of immortalization .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Androgen deprivation is currently a standard-of-care , first-line therapy for prostate cancer in the United States . Although this regimen effectively regresses androgen-dependent disease , relapse often occurs in an androgen-independent manner and is associated with poor prognosis . Such castration-resistant prostate cancer represents a major clinical challenge , and the mechanisms underlying castration resistance are not fully understood . Epithelial-mesenchymal transition ( EMT ) is a key developmental process and has also been implicated in cancer metastasis and therapeutic resistance in recent years . However , the factors contributing to EMT in human cancers remain unclear . Here , we show that both normal mouse prostate tissue and human LuCaP35 prostate tumor explants display an EMT as well as increased stem cell-like features following androgen deprivation . Importantly , we observed similar changes in mesenchymal features in prostate tumors from patients treated with androgen-deprivation therapy . In addition , we have delineated a feedback loop involving the androgen receptor and the Zeb1 transcription factor that seems to mediate this transition . In summary , we show for the first time that androgen deprivation induces EMT in both normal prostate and prostate cancer , revealing a potentially important consequence of a standard-of-care treatment for prostate cancer . This finding could have significant implications for second-line treatment strategies in this clinical setting .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Regulation of adaptive immunity by innate immune cells is widely accepted . Conversely , adaptive immune cells can also regulate cells of the innate immune system . Here , we report for the first time the essential role of B cells in regulating macrophage ( Mφ ) phenotype . In vitro B cell/Mφ co-culture experiments together with experiments in transgenic mice models for B-cell deficiency or overexpression showed B1 cells to polarize Mφ to a distinct phenotype . This was characterized by downregulated TNF-α , IL-1β and CCL3 , but upregulated IL-10 upon LPS stimulation ; constitutive expression of M2 Mφ markers ( e.g . Ym1 , Fizz1 ) and overexpression of TRIF-dependent cytokines ( IFN-β , CCL5 ) . Mechanistically , this phenotype was linked to a defective NF-κB activation , but a functional TRIF/STAT1 pathway . B1-cell-derived IL-10 was found to be instrumental in the polarization of these Mφ . Finally , in vivo relevance of B1-cell-induced Mφ polarization was confirmed using the B16 melanoma tumor model where adoptive transfer of B1 cells induced an M2 polarization of tumor-associated Mφ . Collectively , our results define a new mechanism of Mφ polarization wherein B1 cells play a key role in driving Mφ to a unique , but M2-biased phenotype . Future studies along these lines may lead to targeting of B1 cells to regulate Mφ response in inflammation and cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: CEACAM1 , CEA/CEACAM5 , and CEACAM6 are cell adhesion molecules ( CAMs ) of the carcinoembryonic antigen ( CEA ) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers . However , little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression . Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated , contact-inhibited cell growth . Interestingly , CEACAM1-L , but not CEACAM1-S , negatively regulates proliferation via its ITIM domain , while in proliferating cells no CEACAM expression is detectable . Furthermore , we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells , likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L , leading to undifferentiated anchorage-independent cell growth . We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6 , representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients . Taken together , our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L , but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype . Carbon monoxide ( CO ) , one of the products of the cytoprotective molecule heme oxygenase-1 ( HO-1 ) in cancer cells , has been implicated in carcinogenesis and therapeutic resistance . However , the functional contributions of CO and HO-1 to these processes are poorly defined . In human prostate cancers , we found that HO-1 was nuclear localized in malignant cells , with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes . Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy , with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe . CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption , free radical generation , and mitochondrial collapse . Collectively , our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics , ultimately resulting in metabolic exhaustion .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;cellular energetics" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Stannous chloride ( SnCl(2) ) and UVA induce DNA lesions through ROS . The aim of this work was to study the toxicity induced by UVA preillumination , followed by SnCl(2) treatment . E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents . The survival assays showed ( i ) The nfo mutant was the most sensitive to SnCl(2) ; ( ii ) lethal synergistic effect was observed after UVA pre-illumination , plus SnCl(2) incubation , the nfo mutant being the most sensitive ; ( iii ) wild type and nfo mutants , transformed with pBW21 plasmid ( nfo(+) ) had their survival increased following treatments . The alkaline agarose gel electrophoresis assays pointed that ( i ) UVA induced DNA breaks and fpg mutant was the most sensitive ; ( ii ) SnCl(2)-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics ; ( iii ) UVA + SnCl(2) promoted an increase in DNA breaks than SnCl(2) and , again , nfo mutant displayed the slowest repair kinetics . In summary , Nfo protects E. coli cells against damage induced by SnCl(2) and UVA + SnCl(2) .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Accumulating data suggest arsenic may be an endocrine disruptor and tentatively linked to breast cancer by some studies . Therefore , we tested the effects of chronic inorganic arsenic exposure on the normal estrogen receptor ( ER)-negative breast epithelial cell line , MCF-10A . Cells were chronically exposed to a low-level arsenite ( 500nM ) for up to 24weeks . Markers of cancer cell phenotype and the expression of critical genes relevant to breast cancer or stem cells ( SCs ) were examined . After 24weeks , chronic arsenic-exposed breast epithelial ( CABE ) cells showed increases in secreted MMP activity , colony formation , invasion , and proliferation rate , indicating an acquired cancer cell phenotype . These CABE cells presented with basal-like breast cancer characteristics , including ER-α , HER-2 , and progesterone receptor negativity , and overexpression of K5 and p63 . Putative CD44(+)/CD24(-/low) breast SCs were increased to 80% over control in CABE cells . CABE cells also formed multilayer cell mounds , indicative of loss of contact inhibition . These mounds showed high levels of K5 and p63 , indicating the potential presence of cancer stem cells ( CSCs ) . Epithelial-to-mesenchymal transition occurred during arsenic exposure . Overexpression of aromatase , a key rate-limiting enzyme in estrogen synthesis , occurred with arsenic starting early on in exposure . Levels of 17β-estradiol increased in CABE cells and their conditioned medium . The aromatase inhibitor letrozole abolished arsenic-induced increases in 17β-estradiol production and reversed cancer cell phenotype . Thus , chronic arsenic exposure drives human breast epithelia into a cancer cell phenotype with an apparent overabundance of putative CSCs . Arsenic appears to transform breast epithelia through overexpression of aromatase , thereby activating oncogenic processes independent of ER .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma-associated herpesvirus ( KSHV ) . It is prevalent among the elderly in the Mediterranean , inhabitants of sub-Saharan Africa , and immunocompromised individuals such as organ transplant recipients and AIDS patients . Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host . When the host's immune system weakens , KSHV begins to replicate again , and active tumor growth ensues . New therapeutic approaches are needed . Cannabidiol ( CBD ) , a plant-derived cannabinoid , exhibits promising antitumor effects without inducing psychoactive side effects . CBD is emerging as a novel therapeutic for various disorders , including cancer . In this study , we investigated the effects of CBD both on the infection of endothelial cells ( ECs ) by KSHV and on the growth and apoptosis of KSHV-infected ECs , an in vitro model for the transformation of normal endothelium to Kaposi sarcoma . While CBD did not affect the efficiency with which KSHV infected ECs , it reduced proliferation and induced apoptosis in those infected by the virus . CBD inhibited the expression of KSHV viral G protein-coupled receptor ( vGPCR ) , its agonist , the chemokine growth-regulated protein α ( GRO-α ) , vascular endothelial growth factor receptor 3 ( VEGFR-3 ) , and the VEGFR-3 ligand , vascular endothelial growth factor C ( VEGF-C ) . This suggests a potential mechanism by which CBD exerts its effects on KSHV-infected endothelium and supports the further examination of CBD as a novel targeted agent for the treatment of Kaposi sarcoma .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Endothelial cells respond to hypoxic changes with resultant accumulation of several metabolites and switch over to angiogenic phenotype . Although certain intermediates of glycolytic and oxidative metabolic pathways have been known to affect angiogenesis , the effect of citrate , which accumulates in certain tumors , on angiogenesis is not known . Therefore , the effect of citrate on angiogenesis was studied using different model systems . Increased vascularization in chorioallantoic membrane assay , increased endothelial sprouting in rat aortic rings , and increased expression of CD31 , E-selectin in endothelial cells suggested a possible proangiogenic effect of citrate . Upregulation of angiogenic factors such as vascular endothelial growth factor and fibroblast growth factor suggested that the effect of citrate involves modulation of expression of angiogenic growth factors . LY 294002 , an inhibitor of PI3K-Akt pathway , and wortmannin , an inhibitor of Akt pathway , reversed the effect of citrate in human umbilical vein endothelial cells . Citrate induced significant upregulation and activation of Akt in endothelial cells . Rapamycin , an inhibitor of mTOR , also reversed the effect of citrate in human umbilical vein endothelial cells and sprouting of aortic rings suggesting that the angiogenic effect of citrate involves activation of PI3K-Akt-mTOR pathway .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: LewisY ( LeY ) antigen is an oligosaccharide that is highly expressed at the cell surface in various human cancers . Increased LeY expression activates epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2 ) and promotes cell proliferation in EGFR-overexpressing cells . However , the effect of downregulation of LeY expression on cell proliferation in HER2-overexpressing cells remains unknown . FUT1 encodes α1,2-fucosyltransferase , a key enzyme for LeY synthesis . We knocked down FUT1 by short interfering RNA ( siRNA ) in four HER2-overexpressing human cancer cell lines , including NCI-N87 , MKN7 , SKBr3 and BT474 . We investigated whether downregulation of LeY and alteration in the glycosylation status of these cells affect cell proliferation and HER2 activation . Knocking down FUT1 expression markedly inhibited proliferation of NCI-N87 , which highly expressed EGFR and was sensitive to EGFR deprivation . Furthermore , FUT1 siRNA downregulated the total amount of HER2 protein , phosphorylation of HER2 and EGFR , and phosphorylation of extracellular signal-regulated kinase ( ERK ) in this cell line . Moreover , the marked downregulation of phosphorylation of HER2 and ERK was observed following short-time EGF-stimulation . These effects were not observed in the other three cell lines . Our results suggest that knockdown of FUT1 downregulates HER2 signaling via EGFR downregulation . FUT1 may serve as a new molecular target for HER2-overexpressing human cancers with activated EGFR signaling .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cyclin E2 , but not cyclin E1 , is included in several gene signatures that predict disease progression in either tamoxifen-resistant or metastatic breast cancer . We therefore examined the role of cyclin E2 in antiestrogen resistance in vitro and its potential for therapeutic targeting through cyclin-dependent kinase ( CDK ) inhibition . High expression of CCNE2 , but not CCNE1 , was characteristic of the luminal B and HER2 subtypes of breast cancer and was strongly predictive of shorter distant metastasis-free survival following endocrine therapy . After antiestrogen treatment of MCF-7 breast cancer cells , cyclin E2 mRNA and protein were downregulated and cyclin E2-CDK2 activity decreased . However , this regulation was lost in tamoxifen-resistant ( MCF-7 TAMR ) cells , which overexpressed cyclin E2 . Expression of either cyclin E1 or E2 in T-47D breast cancer cells conferred acute antiestrogen resistance , suggesting that cyclin E overexpression contributes to the antiestrogen resistance of tamoxifen-resistant cells . Ectopic expression of cyclin E1 or E2 also reduced sensitivity to CDK4 , but not CDK2 , inhibition . Proliferation of tamoxifen-resistant cells was inhibited by RNAi-mediated knockdown of cyclin E1 , cyclin E2 , or CDK2 . Furthermore , CDK2 inhibition of E-cyclin overexpressing cells and tamoxifen-resistant cells restored sensitivity to tamoxifen or CDK4 inhibition . Cyclin E2 overexpression is therefore a potential mechanism of resistance to both endocrine therapy and CDK4 inhibition . CDK2 inhibitors hold promise as a component of combination therapies in endocrine-resistant disease as they effectively inhibit cyclin E1 and E2 overexpressing cells and enhance the efficacy of other therapeutics .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Extensive biochemical and structural analyses have been performed on the putative DNA repair proteins of hyperthermophilic archaea , in contrast to the few genetic analyses of the genes encoding these proteins . Accordingly , little is known about the repair pathways used by archaeal cells at high temperature . Here , we attempted to disrupt the genes encoding the potential repair proteins in the genome of the hyperthermophilic archaeon Thermococcus kodakaraensis . We succeeded in isolating null mutants of the hjc , hef , hjm , xpb , and xpd genes , but not the radA , rad50 , mre11 , herA , nurA , and xpg/fen1 genes . Phenotypic analyses of the gene-disrupted strains showed that the xpb and xpd null mutants are only slightly sensitive to ultraviolet ( UV ) irradiation , methyl methanesulfonate ( MMS ) and mitomycin C ( MMC ) , as compared with the wild-type strain . The hjm null mutant showed sensitivity specifically to mitomycin C. On the other hand , the null mutants of the hjc gene lacked increasing sensitivity to any type of DNA damage . The Hef protein is particularly important for maintaining genome homeostasis , by functioning in the repair of a wide variety of DNA damage in T. kodakaraensis cells . Deletion of the entire hef gene or of the segments encoding either its nuclease or helicase domain produced similar phenotypes . The high sensitivity of the Δhef mutants to MMC suggests that Hef performs a critical function in the repair process of DNA interstrand cross-links . These damage-sensitivity profiles suggest that the archaeal DNA repair system has processes depending on repair-related proteins different from those of eukaryotic and bacterial DNA repair systems using homologous repair proteins analyzed here .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk , but these studies produced inconsistent results . In this pilot , randomized , double-blind , placebo-controlled clinical trial ( n = 47 ) , we assessed the effects of an antioxidant micronutrient combination ( 800 mg dl-alpha-tocopherol acetate , 24 mg beta-carotene , 1.0 g vitamin C , 200 microg l-selenomethionine , 7.2 mg riboflavin , 80 mg niacin , 60 mg zinc , 5 mg manganese ) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma . Plasma tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 , and F2-isoprostane concentrations were measured using ELISAs , and cystine ( CySS ) was measured using high-performance liquid chromatography . Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group ( P = 0.002 ) , and CySS decreased by 19% ( P = 0.03 ) ; however , interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers , although these findings were not statistically significant . The decreases of TNF-alpha and CySS were more pronounced in nonsmokers . These data suggest that ( a ) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and ( b ) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 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 .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Annexin II is secreted into the extracellular environment , where , via interactions with specific proteases and extracellular matrix proteins , it participates in plasminogen activation , cell adhesion , and tumor metastasis and invasion . However , mechanisms regulating annexin II transport across the cellular membrane are unknown . In this study , we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 ( IGF-1 ) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin ( NIH-3T3(IR) ) or IGF-1 receptor ( NIH-3T3(IGF-1R) ) . Stimulation of insulin and IGF-1 receptors by insulin caused a temporary dissociation of annexin II from these receptors , which was accompanied by an increased amount of extracellular annexin II detected in the media of PC12 , NIH-3T3(IR) , and NIH-3T3(IGF-1R) cells but not in that of untransfected NIH-3T3 cells . Activation of a different growth factor receptor , the platelet-derived growth factor receptor , did not produce such results . Tyrphostin AG1024 , a tyrosine kinase inhibitor of insulin and IGF-1 receptor , was shown to inhibit annexin II secretion along with reduced receptor phosphorylation . Inhibitors of a few downstream signaling enzymes including phosphatidylinositol 3-kinase , pp60c-Src , and protein kinase C had no effect on insulin-induced annexin II secretion , suggesting a possible direct link between receptor activation and annexin II secretion . Immunocytochemistry revealed that insulin also induced transport of the membrane-bound form of annexin II to the outside layer of the cell membrane and appeared to promote cell aggregation . These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cancer cells preferentially metabolize glucose by aerobic glycolysis , characterized by increased lactate production . This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase , in contrast to the M1 isozyme normally expressed in differentiated cells , and it confers a proliferative advantage to tumor cells . The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons . We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues , tumor cell lines , and during terminal differentiation of muscle cells , and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms . We further show that the M1-specific exon is actively repressed in cancer-cell lines--although some M1 mRNA is expressed in cell lines derived from brain tumors--and demonstrate that the related splicing repressors hnRNP A1 and A2 , as well as the polypyrimidine-tract-binding protein PTB , contribute to this control . Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production . These findings extend the links between alternative splicing and cancer , and begin to define some of the factors responsible for the switch to aerobic glycolysis .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The ATM kinase and p53 are key tumor suppressor factors that control the genotoxic stress response pathway . The ATM substrate Mdm2 controls p53 activity by either targeting p53 for degradation or promoting its synthesis by binding the p53 mRNA . The physiological role and regulation of Mdm2's dual function toward p53 is not known . Here we show that ATM-dependent phosphorylation of Mdm2 at Ser395 is required for the p53 mRNA-Mdm2 interaction . This event also promotes SUMO-conjugation of Mdm2 and its nucleoli accumulation . Interfering with the p53 mRNA-Mdm2 interaction prevents p53 stabilization and activation following DNA damage . These results demonstrate how ATM activity switches Mdm2 from a negative to a positive regulator of p53 via the p53 mRNA .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: It is well established that aberrant production of inflammatory mediators has been associated with most the toxic manifestations and the genesis of different chronic diseases including cancer . The basic aim of the present study is to investigate the effects of soy isoflavones ( SIF ) on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced cutaneous inflammatory responses and to explore the underlying molecular mechanisms . We have studied the protective effects of SIF against TPA induced oxidative stress , pro-inflammatory cytokines level , activation of NF-κB , expression of COX-2 and ki-67 in mouse skin . Animals were divided into five groups I-V ( n=6 ) . Groups II , III and IV received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day , for 2 days . Animals of the groups III and IV were pre-treated with SIF 1.0 μg ( D1 ) and 2.0 μg ( D2 ) topically 30 min prior to each TPA administration , while groups I and V were given acetone ( 0.2 ml ) and SIF ( D2 ) , respectively . We have found that SIF pretreatment significantly inhibited TPA induced oxidative stress , proinflammatory cytokines production and activation of NF-κB . SIF also inhibited the expression of COX-2 and ki-67 . Histological findings further supported the protective effects of SIF against TPA-induced cutaneous damage . Thus , our results suggest that inhibitory effect of SIF on TPA-induced cutaneous inflammation includes inhibition of proinflammatory cytokines , attenuation of oxidative stress , activation of NF-κB and expression of COX-2 .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cancer can be envisioned as a metabolic disease driven by pressure selection and intercellular cooperativeness . Together with anaerobic glycolysis , the Warburg effect , formally corresponding to uncoupling glycolysis from oxidative phosphorylation , directly participates in cancer aggressiveness , supporting both tumor progression and dissemination . The transcription factor hypoxia-inducible factor-1 ( HIF-1 ) is a key contributor to glycolysis . It stimulates the expression of glycolytic transporters and enzymes supporting high rate of glycolysis . In this study , we addressed the reverse possibility of a metabolic control of HIF-1 in tumor cells . We report that lactate , the end-product of glycolysis , inhibits prolylhydroxylase 2 activity and activates HIF-1 in normoxic oxidative tumor cells but not in Warburg-phenotype tumor cells which also expressed lower basal levels of HIF-1α . These data were confirmed using genotypically matched oxidative and mitochondria-depleted glycolytic tumor cells as well as several different wild-type human tumor cell lines of either metabolic phenotype . Lactate activates HIF-1 and triggers tumor angiogenesis and tumor growth in vivo , an activity that we found to be under the specific upstream control of the lactate transporter monocarboxylate transporter 1 ( MCT1 ) expressed in tumor cells . Because MCT1 also gates lactate-fueled tumor cell respiration and mediates pro-angiogenic lactate signaling in endothelial cells , MCT1 inhibition is confirmed as an attractive anticancer strategy in which a single drug may target multiple tumor-promoting pathways .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 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 .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Pyruvate kinase isoenzyme M2 ( PKM2 ) is a key enzyme in aerobic glycolysis ; inhibition of PKM2 leads to the tumor growth inhibition . In this study , the effects of combined treatment with cisplatin ( DDP ) and a plasmid that expresses a short hairpin RNA ( shRNA ) targeting PKM2 on the growth of human A549 xenograft lung cancer model were investigated . METHODS The expression of PKM2 in A549 cells was determined by immunofluorescence . PKM2 expression levels were evaluated by Western blot analysis . In a human A549 lung cancer xenograft model , the effects of treatment with shRNA , with or without cisplatin , on tumor volume were determined . Apoptosis and cell proliferation status were examined to determine the mechanisms of tumor growth inhibition . RESULTS Expression of shRNA targeting PKM2 resulted in inhibition of PKM2 expression in A549 cells . In the lung cancer xenograft model , average tumor volume in the group treated with both cisplatin and shRNA was statistically lower than those of other groups ( P &lt ; 0.05 ) . The levels of apoptotic cells were significantly higher in samples from animals in the combined treatment group than those from untreated animals ( P &lt ; 0.05 ) . The cell proliferation rate , as determined by counting cells labeled with an anti-phospho-histone H3 , a marker for mitosis , was lower in samples from animals treated with both cisplatin and shRNA than in samples from other groups ( P &lt ; 0.05 ) . CONCLUSIONS Use of RNA interfering ( RNAi ) targeting PKM2 significantly inhibited tumor growth when combined with cisplatin in a human A549 lung cancer xenograft model . The enhanced antitumor activity of the combined treatment compared to treatment with shRNA alone may result in part from increased induction of apoptosis and augmented inhibition of cancer cell proliferation .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Tissue factor ( TF ) , an initiator of blood coagulation , participates in cancer progression and metastasis . We recently found that inhibition of MAPK/ERK upregulated both full length TF ( flTF ) and soluble isoform TF ( asTF ) gene expression and cell-associated TF activity in breast cancer MDA-MB-231 cells . We explored the possible mechanisms , especially the possible interaction with EGFR and PI3K/Akt pathways . METHODS A plasmid containing TF promoter -2174  plus luciferase reporter gene was introduced into MDA-MB-231 cells to evaluate TF promoter activity . In order to study the interaction of these pathways , ERK inhibitor ( PD98059 ) , PI3K inhibitors ( LY294002 , wortmannin ) , Akt inhibitor ( A6730 ) , and EGFR inhibitor ( erlotinib ) as well as the corresponding siRNAs were used to treat MDA-MB-231 cells , and ovarian cancer OVCAR-3 and SKOV-3 cells . Quantitative PCR and western blot were used to determine TF expression . One stage clotting assays were used to measure pro-coagulation activity of the MDA-MB-231 cells . RESULTS We show that PI3K inhibitors LY294002 , wortmannin and A6730 significantly inhibited TF promoter activity , and reduced TF mRNA and protein levels due to the inhibition of Akt phosphorylation . In contrast , ERK inhibitor PD98059 and ERK siRNA enhanced TF promoter activity by 2.5 fold and induced an increase in TF mRNA and protein levels in a dose dependent manner in these cells . The PI3K/Akt pathway was shown to be involved in PD98059-induced TF expression because the induction was inhibited by PI3K/Akt inhibitors . Most interestingly , the EGFR inhibitor erlotinib and EGFR siRNA also significantly suppressed PD98059- or ERK siRNA-induced TF promoter activity and TF protein expression . Similar results were found with ovarian cancer cells SKOV-3 and OVCAR-3 . Furthermore , in MDA-MB-231 , mRNA levels of asTF were regulated in a similar way to that of TF in response to the cell treatment . CONCLUSIONS This study showed a regulatory mechanism in which MAPK/ERK signals inhibit EGFR/PI3K/Akt-mediated TF expression in breast cancer MDA-MB-231 cells . The same regulation was observed in ovarian cancer OVCAR-3 and SKOV-3 cells . Interestingly , we observed that both flTF and asTF could be regulated in a parallel manner in MDA-MB-231 . As the PI3K/Akt pathway and EGFR regulate TF expression in cancer cells , targeting these signaling components is expected to potentially inhibit TF expression-associated tumor progression .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics , although only coronin 3 has been shown to be related to cancer cell migration . In glioblastoma cells , the knockdown of coronin 3 inhibits cell proliferation and invasion . Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma . In this paper , we analyze the migration , invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3 , and explore the mechanism of coronin 3 in the process of gastric cancer metastasis . RESULTS The expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M , which we established in our laboratory . We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues , and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis . Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines . Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells . In contrast , up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells . In addition , knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells . The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3 , and the results suggested that , following the knockdown of coronin 3 , the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K. CONCLUSION Coronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells , including their migration and invasion .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The orphan receptor TR3 is an important regulator of cell proliferation and apoptosis . However , whether TR3 is involved in regulating the stem-like properties of cancer cells remains unknown . The present study shows that TR3 expression is increased in gastric tumorsphere cells and is positively correlated with cancer stem cell ( CSC ) characteristics . Knocking down TR3 leads to the suppression of its stem-like properties in both gastric cancer cells and tumorsphere cells . This process involves the decreased expression of the stemness-related genes Oct-4 and Nanog and the invasion-related gene MMP-9 . We further identify Nanog as a new target for the transcription factor TR3 . Together , these data demonstrate for the first time that TR3 is essential for the maintenance of stem-like properties in human gastric cancer cells and implicate TR3 as a new therapeutic target for gastric cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The purpose of the study was to evaluate Sorafenib ( BAY 43-9006 ) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors . Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors . Rip1Tag2 mice were treated in two different groups according to the model of tumor progression : the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death . Tumor surface , tumor cell proliferation , and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib . Survival was recorded for the late treatment group . In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group . Apoptosis was significantly augmented and cell proliferation was inhibited . As a single therapy Sorafenib significantly improved survival in the late treatment group . Conclusion . Sorafenib may provide a new paradigm for the therapy of islet cell tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A key issue in the development of the central nervous system ( CNS ) is understanding the molecular mechanisms regulating cell number . The present study examines the role of CD81 ( previously known as TAPA , the target of the antiproliferative antibody ) in the control of brain size and glial cell number . CD81 is a member of the tetraspanin family of proteins . This group of small membrane proteins is associated with the regulation of cell migration and mitotic activity . Glial cells express CD81 , and antibodies directed against this protein suppress the mitotic activity of cultured cells . In this study , we examine the effects of the CD81 -/- mutation on the CNS of mature mice . These mice have extremely large brains , as much as 30% larger than the brains of wild-type ( +/+ ) littermates . The increase in brain weight is accompanied by an increase in the number astrocytes and microglia , whereas the number of neurons and oligodendrocytes in the CD81 -/- animals appears to be normal . When the CD81 -/- mutation is placed on different genetic backgrounds , there is a remarkable range in the penetrance of the null allele phenotype , demonstrating that the mutation can be affected by modifier loci . This work provides support for the role of CD81 in the regulation of astrocyte and microglial number , perhaps by regulating cell proliferation by a contact inhibition-dependent mechanism .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Helicobacter hepaticus-infected Rag2(-/-) mice emulate many aspects of human inflammatory bowel disease , including the development of colitis and colon cancer . To elucidate mechanisms of inflammation-induced carcinogenesis , we undertook a comprehensive analysis of histopathology , molecular damage , and gene expression changes during disease progression in these mice . Infected mice developed severe colitis and hepatitis by 10wk post-infection , progressing into colon carcinoma by 20wk post-infection , with pronounced pathology in the cecum and proximal colon marked by infiltration of neutrophils and macrophages . Transcriptional profiling revealed decreased expression of DNA repair and oxidative stress response genes in colon , but not in liver . Mass spectrometric analysis revealed higher levels of DNA and RNA damage products in liver compared to colon and infection-induced increases in 5-chlorocytosine in DNA and RNA and hypoxanthine in DNA . Paradoxically , infection was associated with decreased levels of DNA etheno adducts . Levels of nucleic acid damage from the same chemical class were strongly correlated in both liver and colon . The results support a model of inflammation-mediated carcinogenesis involving infiltration of phagocytes and generation of reactive species that cause local molecular damage leading to cell dysfunction , mutation , and cell death . There are strong correlations among histopathology , phagocyte infiltration , and damage chemistry that suggest a major role for neutrophils in inflammation-associated cancer progression . Further , paradoxical changes in nucleic acid damage were observed in tissue- and chemistry-specific patterns . The results also reveal features of cell stress response that point to microbial pathophysiology and mechanisms of cell senescence as important mechanistic links to cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVE To analyze the profiles of interleukin-2 ( IL-2 ) , IL-6 , IL-8 , IL-10 , tumor necrosis factor-alpha ( TNF-alpha ) , transforming growth factor-beta1 ( TGF-beta1 ) and interferon-gamma ( IFN-gamma ) in serum and the tumor microenvironment ( cyst fluid , ascites ) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status . We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors . DESIGN Prospective study . SETTING Tertiary referral hospital . POPULATION 51 women with epithelial ovarian cancer , 26 with benign ovarian tumors of epithelial origin and 21 healthy controls . METHODS The levels of cytokines were measured using ELISA sets . RESULTS We did not found differences in the levels of IFN-gamma , TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors . Women with advanced cancer had significantly higher serum IL-6 , IL-10 and TGF-beta1 levels than women with early stages or benign tumors . Moreover , women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10 , TGF-beta1 and IL-8 . The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors . The areas under curves constructed for the selected cutoff serum cytokines levels ( AUC-ROC ) showed good predictive values for IL-6 ( 0.87 ) , IL-10 ( 0.836 ) and IL-8 ( 0.797 ) . CONCLUSIONS Our results indicate on intensified inflammatory process in women with ovarian cancer ( accompanied by their immunosuppression ) . Preoperative analysis of serum IL-6 , IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Treatment of cells with the anti-cancer drug camptothecin ( CPT ) induces topoisomerase I ( Top1)-mediated DNA damage , which in turn affects cell proliferation and survival . In this report , we demonstrate that treatment of the wild-type HCT116 ( wt HCT116 ) human colon cancer cell line and the isogenic p53(-/-) HCT116 and p21(-/-) HCT116 cell lines with a high concentration ( 250 nm ) of CPT resulted in apoptosis , indicating that apoptosis occurred by a p53- and p21-independent mechanism . In contrast , treatment with a low concentration ( 20 nm ) of CPT induced cell cycle arrest and senescence of the wt HCT116 cells , but apoptosis of the p53(-/-) HCT116 and p21(-/-) HCT116 cells . Further investigations indicated that p53-dependent expression of p21 blocked apoptosis of wt HCT116 cells treated with 20 nm , but not 250 nm CPT . Interestingly , blocking of the apoptotic pathway , by Z-VAD-FMK , in p21(-/-) HCT116 cells following treatment with 20 nm CPT did not permit the cells to develop properties of senescence . These observations demonstrated that p21 was required for senescence development of HCT116 cells following treatment with low concentrations of CPT .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Folate ( vitamin B9 ) is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate ( dTMP ) and s-adenosylmethionine ( AdoMet ) . The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance , but still unclear . We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis , which is prominent in prostate cells . We , therefore , hypothesized that prostate cells might be highly susceptible to genetic , epigenetic and phenotypic changes consequent to folate restriction . RESULTS We studied the consequences of long-term , mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate ( TRAMP ) model , recapitulating different stages of prostate cancer ; benign , transformed and metastatic . High-performance liquid chromatography analysis demonstrated that mild folate depletion ( 100 nM ) sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines . Random oligonucleotide-primed synthesis ( ROPS ) revealed a significant increase in uracil misincorporation and DNA single strand breaks , while spectral karyotype analysis ( SKY ) identified five novel chromosomal rearrangements in cells grown with mild folate depletion . Using global approaches , we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine , indicating a broad effect of folate depletion on epigenetic regulation . These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion . CONCLUSIONS This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with supraphysiological amounts of folate ( 2 microM ) routinely used in tissue culture . In addition , we elucidate for the first time the contribution of these aspects to consequent phenotype changes in epithelial cells . These results provide a strong rationale for studying the effects of folate manipulation on the prostate in vivo , where cells might be more sensitive to changes in folate status resulting from folate supplementation or antifolate therapeutic approaches .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Head and neck squamous cell carcinoma ( HNSCC ) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies . Targeting epidermal growth factor receptor ( EGFR ) is attractive in that it is an early critical event in HNSCC pathogenesis . However , current agents lack efficacy or have unacceptable toxicity . Several groups have demonstrated that the over-the-counter medication , polyethylene glycol ( PEG ) has remarkable chemopreventive efficacy against colon carcinogenesis . Importantly , we reported that this effect is mediated through EGFR internalization/degradation . In the current study , we investigated the chemopreventive efficacy of this agent against HNSCC , using both the well validated animal model 4-NQO ( 4-nitroquinoline 1-oxide ) rat model and cell culture with the human HNSCC cell line SCC-25 . We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity ( tongue and cavity wall ) post 4NQO initiation resulted in a significant reduction in tumor burden ( both , tumor size and tumors/tumor bearing rat ) without any evidence of toxicity . Immunohistochemical studies depicted decreased proliferation ( number of Ki67-positive cells ) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG . We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest , which was potentially mediated through upregulated p21(cip1/waf1) . In conclusion , we demonstrate , for the first time , that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Ginkgolic acids ( GAs ) , extracted from the seed coat of Ginkgo biloba L. Our previous study has shown that GA monomer could inhibit the growth of Hep-2 significantly and induce the fragmentation of the chromosomal DNA . To further assess the antitumor potential and turn it into a candidate new antitumor drug , the antitumor mechanism of GA was investigated . METHOD The cytotoxicity and antitumor effect of GA monomer were assayed by MTT colorimetric assay with nontumorogenic MC-3T3-E1 as well as tumorogenic Hep-2 and Tac8113 cell lines . The effect of GA monomer on the proliferation of tumor cell lines was analyzed with MTT colorimetric and CFSE labeled assay . Cell cycle distribution and measurement of the percentage of apoptotic cells were performed by flow cytometry following stained with propidium iodide , annexin V-FITC . The expression of apoptotic proteins Bcl-2 , Bax and caspase-3 was analyzed with Western blot . RESULT GA only inhibited the growth of tumorogenic cell lines in a both dose- and time-dependent manner . Tumor cells were treated with GA for 72 h , 70.53 ± 4.54% Hep-2 and 63.5 ± 7.2% Tca8113 cells were retarded at GO/G1 phase , and the percentage of apoptosis was 40.4 ± 1.58 and 38.4 ± 1.7% , respectively . GA-treated activated caspase-3 downregulated the expression of anti-apoptotic Bcl-2 protein and upregulated the expression of pro-apoptotic Bax protein , eventually leading to a decrease in the Bcl-2/Bax ratio in tumor cells . CONCLUSIONS The antitumor action of GA was due to inhibiting the proliferation in a manner of inhibiting division , retarding the progress of cell cycle and inducing apoptosis , making GA a candidate as new antitumor drug .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The biological activities of tocotrienols are receiving increasing attention . Herein , we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate ( TRAMP ) mouse model . Male TRAMP mice , 8 wk old , were fed 0.1% , 0.3% , or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old . Likewise , a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old . Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus . Furthermore , mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls . This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD ( Bcl(2) antagonist of cell death ) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27 . In contrast , the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups . Taken together , our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins , mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma . Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism . A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin ( AFB1-albumin adducts ) . A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan , were employed in this study . Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay , hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay , as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction . The detection rate of AFB1-albumin adducts was significantly higher in males ( 42.5% ) than in females ( 21.6% ) ( multivariate-adjusted odds ratio=2.6 , 95% confidence interval=1.4-5.0 ) . The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers ( 42.8% ) than in non-carriers ( 36.6% ) ( multivariate-adjusted odds ratio=1.4 , 95% confidence interval=1.0-2.1 ) . In addition , the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1 . In conclusion , this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population . This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Telomerase is a ribonucleoprotein enzyme that functions to maintain telomeres , the terminal DNA that protects chromosomal integrity , regulating cellular replicative life span . Telomerase is not expressed in most normal human somatic cells but is active in stabilizing telomeres of certain self-renewing cell populations and most malignant cells , making the enzyme an appealing target for anticancer therapy . We describe here a novel cross-species approach to telomerase inhibition . Ectopic expression of the human telomerase catalytic reverse transcriptase component in murine cells inhibited endogenous murine telomerase activity . Using this approach , telomerase inhibition in immortal murine fibroblasts resulted in critical telomere shortening , leading to slowed proliferation , abnormal morphology , altered cell cycle , and telomere dysfunction with cytogenetic instability , followed by apoptotic cell death . Subpopulations of two telomerase-inhibited clones escaped widespread apoptosis , showing proliferative recovery in culture despite persistently inhibited telomerase activity with progressive telomere shortening and dysfunction . This study , by targeting immortal murine cells for telomerase inhibition , demonstrates the importance of telomerase to murine cell immortalization and telomere maintenance . Moreover , the murine model used here should prove useful in further evaluating telomerase inhibition as an anticancer therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Many tumors contain heterogeneous populations of cells , only some of which exhibit increased tumorigenicity and resistance to anticancer therapies . Evidence suggests that these aggressive cancer cells , often termed \" cancer stem cells \" or \" cancer stem-like cells \" ( CSCs ) , rely upon developmental signaling pathways that are important for survival and expansion of normal stem cells . Here we report that , in analogy to embryonic mammary epithelial biology , estrogen signaling expands the pool of functional breast CSCs through a paracrine FGF/FGFR/Tbx3 signaling pathway . Estrogen or FGF9 pretreatment induced CSC properties of breast cancer cell lines and freshly isolated breast cancer cells , whereas cotreatment of cells with tamoxifen or a small molecule inhibitor of FGFR signaling was sufficient to prevent the estrogen-induced expansion of CSCs . Furthermore , reduction of FGFR or Tbx3 gene expression was able to abrogate tumorsphere formation , whereas ectopic Tbx3 expression increased tumor seeding potential by 100-fold . These findings demonstrate that breast CSCs are stimulated by estrogen through a signaling pathway that similarly controls normal mammary epithelial stem cell biology .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 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 .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metastatic cancer cells typically fail to halt migration on contact with non-cancer cells . This invasiveness is in contrast to normal mesenchymal cells that retract on contact with another cell . Why cancer cells are defective in contact inhibition of locomotion is not understood . Here , we analyse the dynamics of prostate cancer cell lines co-cultured with fibroblasts , and demonstrate that a combinatorial code of Eph receptor activation dictates whether cell migration will be contact inhibited . The unimpeded migration of metastatic PC-3 cells towards fibroblasts is dependent on activation of EphB3 and EphB4 by ephrin-B2 , which we show activates Cdc42 and cell migration . Knockdown of EphB3 and EphB4 restores contact inhibition of locomotion to PC-3 cells . Conversely , homotypic collisions between two cancer cells results in contact inhibition of locomotion , mediated by EphA-Rho-Rho kinase ( ROCK ) signalling . Thus , the migration of cancer cells can switch from restrained to invasive , depending on the Eph-receptor profile of the cancer cell and the reciprocal ephrin ligands expressed by neighbouring cells .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cancer cells constantly adapt to oxidative phosphorylation ( OXPHOS ) suppression resulting from hypoxia or mitochondria defects . Under the OXPHOS suppression , AMP-activated protein kinase ( AMPK ) regulates global metabolism adjustments , but its activation has been found to be transient . Whether cells can maintain cellular ATP homeostasis and survive beyond the transient AMPK activation is not known . Here , we study the bioenergetic adaptation to the OXPHOS inhibitor oligomycin in a group of cancer cells . We found that oligomycin at 100 ng/ml completely inhibits OXPHOS activity in 1 h and induces various levels of glycolysis gains by 6 h , from which we calculate the bioenergetic organizations of cancer cells . In glycolysis-dominant cells , oligomycin does not induce much energy stress as measured by glycolysis acceleration , ATP imbalance , AMPK activation , AMPK substrate acetyl-CoA carboxylase phosphorylation at Ser(79) , and cell growth inhibition . In OXPHOS-dependent LKB1 wild type cells , oligomycin induces 5-8% ATP drops and transient AMPK activation during the initial 1-2 h . After AMPK activation is completed , oligomycin-induced increase of acetyl-CoA carboxylase phosphorylation at Ser(79) is still detected , and cellular ATP is back at preoligomycin treatment levels by sustained elevation of glycolysis . Cell growth , however , is inhibited without an increase in cell death and alteration in cell cycle distribution . In OXPHOS-dependent LKB1-null cells , no AMPK activation by oligomycin is detected , yet cells still show a similar adaptation . We also demonstrate that the adaptation to oligomycin does not invoke activation of hypoxia-induced factor . Our data suggest that cancer cells may grow and survive persistent OXPHOS suppression through an as yet unidentified regulatory mechanism .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Autophagy , or autophagocytosis , is a selective intracellular degradative process involving the cell's own lysosomal apparatus . An essential component in cell development , homeostasis , repair and resistance to stress , autophagy may result in either cell death or survival . The targeted region of the cell is sequestered within a membrane structure , the autophagosome , for regulation of the catabolic process . A key factor in both autophagosome formation and autophagosome maturation is a protein encoded by the ultraviolet irradiation resistance-associated gene ( UVRAG ) . Conversely , the serine/threonine-specific protein kinase B ( PKB , also known as Akt ) , which regulates survival in various cancers , inhibits autophagy through mTOR activation . We found that Akt1 may also directly inhibit autophagy by down-regulating UVRAG both in a 293T transient transfection system and breast cancer cells stably expressing Akt1 . The UVRAG with mutations at putative Akt1-phosphorylation sites were still inhibited by Akt1 , and dominant-negative Akt1 also inhibited UVRAG expression , suggesting that Akt1 down-regulates UVRAG by a kinase activity-independent mechanism . We showed that Akt1 overexpression in MDA-MB-231 breast cancer cells down-regulated UVRAG transcription . Cells over-expressing Akt1 were more resistant than control cells to ultraviolet light-induced autophagy and exhibited the associated reduction in cell viability . Levels of the autophagosome indicator protein LC3B-II and mRFP-GFP-LC3 were reduced in cells that over-expressing Akt1 . Inhibiting Akt1 by siRNA or reintroducing UVRAG gene rescued the level of LC3B-II in UV-irradiation . Altogether , these data suggest that Akt1 may inhibit autophagy by decreasing UVRAG expression , which also sensitizes cancer cells to UV irradiation .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Sorafenib is a multi-targeted agent and has been reported to have potent antitumor effects against various types of tumors , including human non-small cell lung cancer ( NSCLC ) . In this study , we explored in vitro the antitumor effects of sorafenib alone and in combination with gemcitabine in epidermal growth factor receptor-tyrosine kinase inhibitor ( EGFR-TKI)-resistant human lung cancer cell lines and the related molecular mechanisms . The NSCLC cell lines A549 ( mutant KRAS ) , H1666 ( mutant BRAF ) and H1975 ( mutant EGFR-T790M ) were treated with sorafenib and gemcitabine alone and in combination . The cytotoxicity was assessed by MTT assay , cell cycle distribution was analyzed by flow cytometry , and alterations in signaling pathways were analyzed by western blotting . We found that sorafenib exhibited dose-dependent growth inhibition in all three EGFR-TKI-resistant NSCLC cell lines . When sorafenib was combined with gemcitabine , synergistic activity was observed in the A549 and H1666 cells and antagonistic activity was observed in the H1975 cells . Sorafenib arrested the cell cycle at the G1 phase , whereas gemcitabine arrested the cell cycle at the S phase . Sorafenib inhibited C-RAF and p-ERK in the A549 cells and B-RAF and p-ERK in the H1666 and H1975 cells . The molecular mechanism of this synergism is that RAF/MEK/ERK which are activated by gemcitabine are efficiently suppressed by simultaneously administered sorafenib . By contrast , the mechanism of antagonism may be due to mutual interference with the cell cycle in the H1975 cells . In conclusion , we found that sorafenib exhibits antiproliferative effects in EGFR-TKI-resistant NSCLC cell lines and when combined with gemcitabine demonstrates synergistic activity in A549 and H1666 cells but antagonistic activity in H1975 cells .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Cholangiocarcinoma , a type of malignant tumor , originates from epithelial cells of the bile duct . Perineural invasion is common path for cholangiocarcinoma metastasis , and it is highly correlated with postoperative recurrence and poor prognosis . It has been reported that muscarinic acetylcholine receptor M3 ( mAChR M3 ) is widely expressed in digestive tract cancer , and may play an important role in the proliferation , differentiation , transformation and carcinogenesis of tumors . This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma . METHODS Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas ( 40 cases ) and normal bile duct tissues ( 9 ) , as well as to investigate nerve infiltration . The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation . The experimental data were analyzed by the Chi-square test . RESULTS The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated ( 69% , 9/13 ) than in well- and moderately-differentiated cholangiocarcinomas ( 30% , 8/27 ) ( X2=5.631 , P<0.05 ) . The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma ( 50% , 14/28 ) was higher than that in cholangiocarcinomas from the middle and lower common bile duct ( 25% , 3/12 ) ( X2=2.148 , P<0.05 ) . Cholangiocarcinomas with distant metastasis had a strongly-positive expression rate ( 75% , 9/12 ) , which was much higher than those without distant metastasis ( 29% , 8/28 ) ( X2=7.410 , P<0.01 ) . The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group . CONCLUSIONS The expression of mAChR M3 is influenced by the extent of differentiation , distant metastasis and the site of cholangiocarcinoma . It also plays a key role in the proliferation and metastasis of cholangiocarcinoma .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors . Consequently , the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types . In addition to host immune responses , intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance , metastatic dissemination and the induction of immune suppression . Cancer stem cells are far from a static cell population ; rather , their presence appears to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma . However , the impact immune responses have on tumor stem cell differentiation or expansion is not well understood . In this study , we demonstrate that targeting tumor-infiltrating macrophages and inflammatory monocytes by inhibiting either the myeloid cell receptors CSF1R or CCR2 decreases the number of tumor-initiating cells in pancreatic tumors . Targeting CCR2 or CSF1R improves chemotherapeutic efficacy , inhibits metastasis and increases antitumor T-cell responses . Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3 , thereby facilitating macrophage-mediated suppression of CD8+ T lymphocytes . Together , our findings show how targeting tumor-infiltrating macrophages can effectively overcome therapeutic resistance mediated by tumor-initiating cells .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;activating invasion and metastasis;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The glutathione peroxidases , a family of selenocysteine-containing redox enzymes , play pivotal roles in balancing the signaling , immunomodulatory , and deleterious effects of reactive oxygen species ( ROS ) . The glutathione peroxidase GPX3 is the only extracellular member of this family , suggesting it may defend cells against ROS in the extracellular environment . Notably , GPX3 hypermethylation and underexpression occur commonly in prostate , gastric , cervical , thyroid , and colon cancers . We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis , a process characterized by oxidative stress and inflammation , comparing Gpx3(-/-) mice in an established two-stage model of inflammatory colon carcinogenesis . Gpx3-deficient mice exhibited an increased tumor number , though not size , along with a higher degree of dysplasia . In addition , they exhibited increased inflammation with redistribution toward protumorigenic M2 macrophage subsets , increased proliferation , hyperactive WNT signaling , and increased DNA damage . To determine the impact of acute gene loss in an established colon cancer line , we silenced GPX3 in human Caco2 cells , resulting in increased ROS production , DNA damage and apoptosis in response to oxidative stress , combined with decreased contact-independent growth . Taken together , our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The beneficial effect of yoghurt consumption on health and on the improvement of the mucosal immune system is well established , as is the diet-associated risk of colon cancer . In an experimental model in BALB/c mice we demonstrated that yoghurt added to the diet for 10 consecutive days , with the procedure repeated each 10 days for 6 months , inhibited the development of a colorectal carcinoma induced by 1,2 dimethylhydrazine ( DMH ) . The immunoregulatory mechanisms involved in the inhibition of tumour growth by yoghurt were also examined in these studies . We determined B lymphocytes IgA(+) and IgG(+) , as well as CD4(+) and CD8(+) T cells in the large intestine . We measured cellular apoptosis and the cytokines TNF-alpha , IFN-gamma and IL-10 . An increase in the number of IgA(+) ( P<0.01 ) was observed , but not in IgG(+) ( P<0.01 ) , or in the CD4(+) population ( P<0.01 ) in the mice treated with DMH and yoghurt . While in the group with the carcinogen there was an enhancement in the IgG(+) B cells ( P<0.01 ) and CD8(+) T cells ( P<0.01 ) . Yoghurt increased the number of apoptotic cells and induced IFN-gamma and TNF-alpha cytokine release , their production being regulated by an increase in IL-10 ( P<0.001 ) . We demonstrated that yoghurt may exert antitumour activity by a decrease in the inflammatory immune response mediated by IgA(+) increase , apoptosis induction and IL-10 release .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVE The signalling molecule protein kinase B ( Akt ) modulates many cellular processes . Phosphatidylinositol 3-kinase ( PI3K)/Akt signalling pathways play important roles in tumour angiogenesis . The aim of this study was to determine the role of phosphorylated Akt ( pAkt ) in angiogenesis and its correlation with vascular endothelial growth factor ( VEGF)-A in gastric adenocarcinoma . METHODS Tumour tissue and matched healthy gastric mucosa were obtained from patients undergoing surgical resection of gastric adenocarcinoma . Akt and pAkt were detected via Western blotting . VEGF-A , pAkt and CD34 were examined by immunohistochemistry . RESULTS Akt and pAkt protein levels were significantly higher in gastric cancer tissue than in normal tissue ( n = 48 patients ) . Positive VEGF-A immunostaining was significantly associated with pAkt immunostaining . Microvessel density was correlated with both VEGF-A and pAkt positivity . CONCLUSIONS Phosphorylated Akt and VEGF-A are involved in angiogenesis of gastric adenocarcinoma , and Akt activation may contribute to angiogenesis via VEGF-A upregulation . The PI3K/Akt/VEGF signalling pathway may be involved in gastric adeno carcinoma .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Whole body hyperthermia ( WBH ) has been used as an adjunct to radio-/chemotherapy in patients with various malignant diseases . Although clear evidence is still missing , it has been hypothesized that an activation of the immune system might contribute to the therapeutic effect of WBH . To examine whether a treatment with 60-minute 41.8 degrees C WBH as an adjunct to chemotherapy ( WBH-CT ) induces an activation of T cells , blood samples were collected at numerous time points before and up to 48 h post-treatment . The aim of this study was to examine the effect of WBH-CT on the expression of a broad range of activation markers on peripheral blood lymphocytes ( PBL ) , on serum cytokines and intracellular cytokine levels in T cells , and the capacity of these cells to proliferate . Immediately after 41.8 degrees C WBH-CT treatment , a drastic increase in peripheral natural killer ( NK ) cells ( P<0.05 ) and CD56+ cytotoxic T lymphocytes ( CTL ; P<0.01 ) in the patients ' peripheral blood was observed . At 5 h post-treatment , the percentages of both effector cell types had returned to baseline levels . This transient phenomenon was accompanied by a short period of reduced T cell activity , indicated by diminished serum levels of soluble interleukin-2 receptors ( sIL-2R ) at 3 h post-WBH-CT ( P<0.05 ) and decreased lymphocytic proliferation at the same point in time . This first phase was followed by a marked but short-lived increase in the patients ' serum levels of interleukin-6 ( IL-6 ; P<0.01 ) during the first 5 h following treatment , with a subsequent decrease to baseline levels at 24 h and significantly increased serum levels of tumor necrosis factor-alpha ( TNF-alpha ) at 0 h ( P<0.01 ) , 3 h ( P<0.05 ) , 5 h ( P<0.05 ) and 24 h ( P<0.01 ) post-WBH-CT . The third phase of the immunological consequences of WBH-CT consisted of an increase in the percentage of peripheral cytotoxic T lymphocytes ( CTL ) expressing CD56 , reaching a maximum at 48 h post-WBH ( P<0.01 ) . Furthermore , the percentage of CD4+ T cells expressing the T cell activation marker CD69 increased nearly two-fold over time , reaching its maximum at 48 h ( P<0.05 ) . As an additional marker for T cell activation , serum levels of sIL-2R increased markedly ( P<0.01 ) , reaching maximum levels at the same point in time . Elevated intracellular concentrations of interferon-gamma ( IFN-gamma ) and/or TNF-alpha in CD8+ T cells were found in 4 out of 5 patients at 24 h post-WBH-CT . Since similar changes were not observed in patients receiving chemotherapy alone , this is the first study to provide evidence for prolonged WBH-CT-induced activation of human T cells .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Ceramide induces cell cycle arrest and apoptotic cell death associated with increased levels of p27(kip1) . The aim of this study was to examine the effects of ceramide on p27(kip1) protein levels as a measure of cell cycle arrest and apoptosis . Results showed that ceramide increased p27(kip1) protein levels through activation of protein phosphatase 2A ( PP2A ) in PC-3 prostate cancer cells . Treatment of cells with the PP2A inhibitor okadaic acid or with PP2A-Cα siRNA inhibited ceramide-induced enhanced p27(kip1) protein expression and Akt dephosphorylation , and prevented Skp2 downregulation . Overexpression of constitutively active Akt attenuated ceramide-induced Skp2 downregulation and p27(kip1) upregulation . In addition , ceramide stimulated binding of the PP2A catalytic subunit PP2A-Cαβ to Akt as assessed by immunoprecipitation experiments , indicating that PP2A is involved in the induction of p27(kip1) via inhibition of Akt pathway . Finally , whether PP2A can regulate p27(kip1) expression independently of Akt pathway was determined . Knockdown of PP2A-Cα with siRNA reduced p27(kip1) levels in the presence of Akt inhibitor . These data reveal that PP2A is a regulator of ceramide-induced p27(kip1) expression via Akt-dependent and Akt-independent pathways .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metastasis is the most lethal attribute of human malignancy . High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer . Previous studies indicate that a mutation of the threonine residue at position 34 ( Thr34Ala ) of survivin generates a dominant-negative mutant that induces apoptosis , inhibits angiogenesis , and suppresses highly metastatic breast carcinoma in mouse models . We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis . The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages . We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A ( Lip-mS ) , Lip-plasmid ( Lip-P ) , or normal saline ( NS ) . Eight days after the last dose , five randomly chosen mice from each group were sacrificed . We detected the apoptotic index , microvessel density ( MVD ) , lymphatic microvessel density ( LMVD ) , and the expression of VEGF-D with immunohistochemistry . After the remaining animals were sacrificed , we compared the tumor-infiltrated lymph nodes in each group . Administration of mSurvivinT34A plasmid complexed with cationic liposome ( DOTAP/chol ) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model . These responses were associated with tumor cell apoptosis , and angiogenesis and lymphangiogenesis inhibition . Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis , thus suppressing tumor growth and lymphatic metastasis . The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVES Epidermal growth factor ( EGF ) stimulates cell proliferation by binding to its receptor ( epidermal growth factor receptor ) , and the overexpression of this receptor is associated with poorer prognosis . The EGF gene presents a polymorphism at position 61 ( A/G ) , associated with higher EGF production . We examined the association between this polymorphism and cervical cancer through a case-control study . METHODS This study used the PCR-restriction fragment length polymorphism method on a sample of 384 women with cervical lesions and 500 controls of white ethnicity . RESULTS In cases of cervical cancer , we found an increased risk of progression to advanced disease ( The International Federation of Gynecology and Obstetrics stage IIb/IV ) ( odds ratios=2.05 ; 95% confidence intervals=1.11 to 3.79 ; P=0.021 ) , and this risk was particularly evident in G carriers for younger women ( odds ratios=2.96 ; 95% confidence intervals=1.41-6.20 , P=0.003 ) . CONCLUSIONS We hypothesize the onset of an advanced disease-driven selective pressure due to the effect of oncogenic human papillomavirus types in a favorable genetic background observed in G carrier women . These results suggest that EGF functional polymorphism may influence cervical cancer prognosis through an EGF/epidermal growth factor receptor pathway .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND : To quantify tumour angiogenesis , microvessel density ( MVD ) has been widely used . We here present a novel angiogenesis marker , microvessel proliferation ( MVP ) , based on dual immunohistochemical staining of nestin and Ki-67 . Immature endothelial cells express nestin , and when co-expressed with the proliferation marker Ki-67 , the number of proliferating immature blood vessels can be measured . MATERIALS AND METHODS : Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index ( VPI ) , the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels . RESULTS : High VPI was strongly associated with several markers of aggressive breast cancer , such as negative oestrogen receptor ( ER ) status ( p=0.003 ) , high tumour cell proliferation by Ki-67 ( p=0.004 ) , high p53 expression ( p=0.001 ) , and five profiles for the basal-like phenotype ( odds ratios ( OR ) ; range 3.4-6.3 ) . Also , high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions ( p<0.0005 ) , and adverse outcome in univariate and multivariate survival analysis ( p=0.034 and p=0.022 , respectively ) . CONCLUSION : Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features , basal-like phenotypes , interval presentation , and prognosis in this series of breast cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: An epithelial cell line , referred to as A163 , was established from breast carcinoma derived from a patient with a strong family history of breast cancer but no known breast cancer susceptibility mutation . A163 was propagated in a serum-free culture medium including the epidermal growth factor . Immunophenotypic characterization demonstrated a mixed luminal and basal-like phenotype . When epidermal growth factor was excluded from the culture medium , A163 entered a quiescent period followed by a period of increased cell proliferation in a subpopulation of the cells . The epidermal growth factor-independent subpopulation retained the basal-like phenotype of the parental cell line . Karyotype and fluorescent in situ hybridization analysis showed an amplification of epidermal growth factor receptor on 7q in A163-S1 only , resulting in high expression of total and phosphorylated epidermal growth factor receptor . The A163-S1 sub-line piles up in culture , indicating a loss of contact inhibition . When grown on transwell filters , A163 shows basal expression of P63 and cytokeratin 14 , whereas A163-S1 expresses P63 ubiquitously , and has lost the basal specific expression of cytokeratin 14 , indicating a loss of polarity . Furthermore , when cultured in reconstituted basement membrane matrix , A163 form polarized normal like acini . In contrast , A163-S1 form large disorganized structures with lack of polarity . These cell lines may prove useful to understand molecular changes in breast cancer progression , in particular basal-like breast cancer subtype with bad prognosis and no current treatment options .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A novel compound 2-arylidene-4,7-dimethyl indan-1-one synthesized was screened for anticancer effect against the human breast adenocarcinoma cell line , MCF-7 . An IC50 value of &gt ; or = 80 microM , nontoxic to the normal breast cell line HBL-100 , showed complete inhibition of the MCF-7 cells . Analysis of mechanisms showed nuclear fragmentation and DNA laddering in gel electrophoresis . GSH and GR levels were found to be reduced after the compound treatment . Cell cycle analysis using fluorescent cytometry revealed G2/M phase arrest , which indicates the compound deserves consideration for further studies against cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Nucling is a stress-inducible protein associated with apoptosomes . The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis . We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well . Here we show that hepatocellular carcinoma ( HCC ) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout ( KO ) mice than wild-type ( WT ) mice . Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males . In the background of Nucling-KO mice , we observed the up-regulation of TNFalpha , spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver . In addition , we observed a decrease in the number of Kupffer cells ( KCs ) in the KO mice . KCs are important for the hepatic immune system , acting as phagocytes or antigen-presenting cells ( APCs ) . We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha . These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver . We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Premature senescence , a key strategy used to suppress carcinogenesis , can be driven by p53/p21 proteins in response to various stresses . Here , we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability . Wig1 controls the association of Argonaute2 ( Ago2 ) , a central component of the RNA-induced silencing complex ( RISC ) , with target p21 mRNA via binding of the stem-loop structure near the microRNA ( miRNA ) target site . Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence . Wig1 plays an essential role in cell proliferation , as demonstrated in tumour xenografts in mice , and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues . Together , our data indicate a novel role of Wig1 in RISC target accessibility , which is a key step in RNA-mediated gene silencing . In addition , these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 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 .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND The current staging system provides an anatomical classification of lung tumors ; its secondary purpose is to allow the prognostic stratification of patients into homogeneous groups after surgery . In this work , intratumoral perineural invasion , lymphatic and blood vessel invasion together with the necrosis content of the tumor exclusive of the non-small cell cancer staging system were studied . METHODS During a 4-year period , 152 patients operated for non-small cell lung cancer ( NSCLC ) at our hospital were analyzed . Mean age of patients was 55.7 +/- 10.1 years . RESULTS Overall 5-year survival was 42.2 % . Mediastinal lymph node involvement , tumor size , incomplete resection , pneumonectomy , presence of necrosis and perineural invasion were significant prognosticators ( P = 0.03 , 0.04 , 0.0001 , 0.046 , 0.0246 , &lt ; 0.0001 , respectively ) . Multivariate analysis revealed that N status , perineural invasion , and the presence of necrosis were independent prognostic factors ( P = 0.006 , P = 0.001 , P = 0.001 , respectively ) . Patients who had stage I tumor with necrosis and perineural invasion had a lower survival rate than those with stage IIIA tumor without these histopathological features ( P = 0.04 ) . The presence of these histopathological characteristics in stage IIIA patients was a sign of a poorer prognosis ( P = 0.0001 ) . CONCLUSIONS Perineural invasion and the presence of necrosis independently indicated a dismal prognosis and their prognostic power is comparable to those of the TNM classification . These factors could be candidates for better survival stratification and the indicators of the need for adjuvant therapy in early stage lung cancer patients .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Pyruvate kinase M2 ( PKM2 ) is a key player in the Warburg effect of cancer cells . However , the mechanisms of regulating PKM2 are not fully elucidated . Here , we identified the protein-serine/threonine kinase PIM2 , a known oncogene , as a novel binding partner of PKM2 . The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells . Importantly , we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue , resulting in an increase of PKM2 protein levels . Compared with wild type , PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis , co-activating HIF-1α and β-catenin , and cell proliferation , while enhancing mitochondrial respiration of cancer cells . These findings demonstrate that PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer , highlighting PIM2 as a potential therapeutic target .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The insulin-like growth factor ( IGF ) pathway represents one of the most studied molecular regulatory networks in oncology . Clinical trials investigating the therapeutic value of anti-IGF1 receptor ( IGF1R ) therapies in cancer , including prostate cancer , are ongoing . However , the multiple functions of the IGF network in the prostate are not entirely known . To elucidate the effects of IGF and insulin ( INS ) on prostate cells , we stimulated prostate cancer ( PC3 , DU145 , LNCaP , DUCaP ) and noncancerous prostate cells ( EP156T , RWPE-1 ) and observed differing responses : whereas cancer cells responded to IGF and INS exposure by way of enhanced cell proliferation and glucose consumption , basal to luminal differentiation was induced in noncancerous cells . The same diverse responses were observed when the growth factor receptors IGF1R or INSR were overexpressed . Down-regulation of IGF1R or INSR isoform A ( INSRA ) also inhibited only proliferation of cancer cells . The proliferative response induced by the INSR in cancer cells was mediated solely by the INSRA . Moreover we observed that the receptors of the IGF network mutually influence their expression and exert redundant functions , thus underscoring the functional molecular network formed by IGF , INS , IGF1R , and INSR . Collectively we found that both IGF1R and INSRA have oncogenic effects in prostate cancer , but the IGF network also has important physiological functions in the noncancerous prostate . These data provide new insights into the biology of the IGF network in the prostate , thereby facilitating the design and interpretation of clinical studies investigating IGF1R targeting agents .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: AIM To assess the prognostic significance of nuclear factor-κB ( NF-κB ) and its target genes in gastric cancer . METHODS The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA . Preoperative serum levels of vascular endothelial growth factor ( VEGF ) , interleukin-6 ( IL-6 ) were assessed via enzyme-linked immuno-sorbent assay . C-reactive protein ( CRP ) and serum amyloid A ( SAA ) were measured via immunotrubidimetry . RESULTS Positive rate of NF-κB RelA was 42.6% . NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 ( P = 0.044 ) and CRP ( P = 0.010 ) . IL-6 , SAA , CRP were related to depth of invasion , VEGF and SAA were correlated with lymph node metastasis . IL-6 , VEGF , SAA and CRP were related to the stage . Univariate analysis demonstrated that immunostaining of NF-κB RelA , levels of IL-6 , VEGF , SAA were significantly related with both disease free survival and overall survival ( OS ) . Multivariate analysis verified that NF-κB RelA [ hazard ratio ( HR ) : 3.40 , P = 0.024 ] and SAA ( HR : 3.39 , P = 0.045 ) were independently associated with OS . CONCLUSION Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: It is prevailingly thought that the antiestrogens tamoxifen and ICI 182 , 780 are competitive antagonists of the estrogen-binding site of the estrogen receptor-alpha ( ER-α ) . However , a plethora of evidence demonstrated both antiestrogens exhibit agonist activities in different systems such as activation of the membrane-initiated signaling pathways . The mechanisms by which antiestrogens mediate estrogen-like activities have not been fully established . Previously , a variant of ER-α , EP-α36 , has been cloned and showed to mediate membrane-initiated estrogen and antiestrogen signaling in cells only expressing ER-α36 . Here , we investigated the molecular mechanisms underlying the antiestrogen signaling in ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells that express high levels of endogenous ER-α36 . We found that the effects of both 4-hydoxytamoxifen ( 4-OHT ) and ICI 182 , 780 ( ICI ) exhibited a non-monotonic , or biphasic dose response curve ; antiestrogens at low concentrations , elicited a mitogenic signaling pathway to stimulate cell proliferation while at high concentrations , antiestrogens inhibited cell growth . Antiestrogens at l nM induced the phosphorylation of the Src-Y416 residue , an event to activate Src , while at 5 �M induced Src-Y527 phosphorylation that inactivates Src . Antiestrogens at 1 nM also induced phosphorylation of the MAPK/ERK and activated the Cyclin D1 promoter activity through the Src/EGFR/STAT5 pathways but not at 5 �M . Knock-down of ER-α36 abrogated the biphasic antiestrogen signaling in these cells . Our results thus indicated that ER-α36 mediates biphasic antiestrogen signaling in the ER-negative breast cancer cells and Src functions as a switch of antiestrogen signaling dependent on concentrations of antiestrogens through the EGFR/STAT5 pathway .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Elevated phosphorylation of estrogen receptor α ( ERα ) at serines 118 ( S118 ) and 167 ( S167 ) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer . It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling , resulting in aggressive ERα-independent breast cancer cells . To this end , MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα . The resulting cell line was stably transfected with wild-type ERα ( ER-AB cells ) , or ERα containing serine to alanine mutation at S118 or S167 ( S118A cells and S167A cells , respectively ) . These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth , morphology , migration/invasion , and ERα-regulated gene expression . S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro . Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size , and both S118A and S167A cells exhibited less cellular complexity . S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin , indicating retention of epithelial lineage markers . Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells . In summary , attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells , resulting in increased growth , migration/invasion , compromised expression of ERα target genes , and markedly altered gene expression patterns .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: FMS-like tyrosine kinase 3 ( FLT3 ) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells , but its constitutive activation by internal tandem duplication ( ITD ) mutations correlates with a poor prognosis in AML . The development of FLT3 tyrosine kinase inhibitors ( TKI ) is a promising strategy , but resistance that arises during the course of treatment caused by secondary mutations within the mutated gene itself poses a significant challenge . In an effort to predict FLT3 resistance mutations that might develop in patients , we used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI . We identified F621L , A627P , F691L and Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI . Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3 autophosphorylation and signaling through MAP kinase , STAT5 and AKT in some mutants . Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed resistance to sorafenib in vivo but not to lestaurtinib . These results indicate a growing number of FLT3 mutations that are likely to be encountered in patients . Such knowledge , combined with known remaining sensitivity to other FLT3 TKI , will be important to establish as secondary drug treatments that can be substituted when these mutants are encountered .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling" } ]