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Clinical NLP Lab 28

[ { "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: BRIT1 protein ( also known as MCPH1 ) contains 3 BRCT domains which are conserved in BRCA1 , BRCA2 , and other important molecules involved in DNA damage signaling , DNA repair , and tumor suppression . BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients . Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways . To investigate its physiological role and dissect the underlying mechanisms , we generated BRIT1(-/-) mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability . Both BRIT1(-/-) mice and mouse embryonic fibroblasts ( MEFs ) were hypersensitive to gamma-irradiation . BRIT1(-/-) MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation . Notably , BRIT1(-/-) mice were infertile and meiotic homologous recombination was impaired . BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis , and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis . In mutant spermatocytes , DNA double-strand breaks ( DSBs ) were formed , but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired . In addition , we found that BRIT1 could bind to RAD51/BRCA2 complexes and that , in the absence of BRIT1 , recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered , indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site . Collectively , our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages , and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Reactive oxygen species ( ROS ) such as hydrogen peroxide ( H(2)O(2) ) , O(*-)(2) and OH(*) participate in the pathogenesis of ischemia/reperfusion injury , inflammation and atherosclerosis . Our previous studies have suggested that increased angiotensin II ( Ang II)-forming chymase may be involved in the development of atherosclerosis . However , the regulatory mechanism of chymase expression has not yet been clarified . In this study , we tested whether oxidative stress upregulates mouse mast cell proteinase chymase , mouse mast cell proteinase ( MMCP)-5 or MMCP-4 . We also examined the expression and activity of these proteins after treatment . Cultured mouse mastocytoma cells ( MMC ) displaying chymase-dependent Ang II-forming activity were treated with H(2)O(2) and several aminothiols with or without anti-oxidants . The levels of MMCP-5 and MMCP-4 expression were determined by quantitative RT-PCR ; the level of chymase-dependent Ang II-forming activity was measured by high performance liquid chromatography using Ang I as a substrate . Treatment of MMC with homocysteine ( 0.1-3 mmol l(-1) ) significantly increased MMCP-5 and MMCP-4 expression , as well as Ang II-forming activity . These effects were significantly inhibited by the addition of catalase and further suppressed by the combination of catalase and superoxide dismutase . Incubation with hydrogen peroxide alone caused a significant increase in Ang II-forming activity , which was completely suppressed by co-treatment with catalase . Furthermore , MMCP-5 and MMCP-4 expression levels were drastically suppressed and chymase induction by homocysteine was diminished under the GATA-inhibited condition . Homocysteine increased mast cell chymase expression and activity through the mechanism of oxidative stress . Our results suggest that there is a biochemical link between oxidative stress and the local Ang II-forming system .\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: Human esophageal adenocarcinoma ( EAC ) develops in a sequence from gastroesophageal reflux disease ( GERD ) , columnar-lined esophagus ( CLE ) , dysplasia , and eventually to EAC . We established a rat surgical EAC model with esophagogastroduodenal anastomosis ( EGDA ) to mimic the staged process of esophageal adenocarcinogenesis . Profiling of the AA metabolites with mass spectrometry showed that prostaglandin E2 ( PGE2 ) , leukotriene B4 ( LTB4 ) , 15-hydroeicosatetraenoic acid ( HETE ) , 12-HETE , 8-HETE and 5-HETE all increased at the esophagoduodenal junction after EGDA as compared with the proximal esophagus , with PGE2 as the major metabolite . Consistent with this profile , cyclooxygenase 2 ( Cox2 ) was overexpressed in the basal cell layer of esophageal squamous epithelium , CLE cells and EAC tumor cells of the EGDA rats , as compared with the normal esophageal epithelium . Sulindac ( a Cox inhibitor ) , nordihydroguaiaretic acid ( NDGA , a lipoxygenase inhibitor ) and alpha-difluoromethylornithine ( DFMO , an ornithine decarboxylase inhibitor ) were tested for their possible inhibitory actions against the formation of EAC in the rat EGDA model . In a short-term study ( for 4 weeks after surgery ) , dietary administration of both sulindac ( 300 and 600 p.p.m. ) and NDGA ( 100 p.p.m. ) effectively reduced the EGDA-induced inflammation . In a long-term chemoprevention study ( for 40 weeks after surgery ) , 300 p.p.m. sulindac , alone or in combination with 100 p.p.m . NDGA or 0.5% DFMO , decreased the tumor incidence from 57.7 to 26.9% , or 16.7 or 20% , respectively ( P &lt ; 0.05 ) . NDGA alone ( 100 and 200 p.p.m. ) slightly decreased the tumor incidence to 52.4 and 37% , respectively , although the difference was not statistically significant . DFMO alone did not show significant effects on tumor incidence . Inhibition of tumor formation by sulindac was correlated with lowered levels of PGE2 . In conclusion , sulindac exerted its chemopreventive effect against the formation of EAC in the rat EGDA model possibly through its inhibition of Cox .\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: Chronic inflammation is a risk factor for the development of colon cancer , providing genotoxic insults , growth and pro-angiogenic factors that can promote tumorigenesis and tumor growth . Immunomodulatory agents can interfere with the inflammation that feeds cancer , but their impact on the transformed cell is poorly understood . The calcium/calcineurin signaling pathway , through activation of NFAT , is essential for effective immune responses , and its inhibitors cyclosporin A ( CsA ) and FK506 are used in the clinics to suppress immunity . Moreover , the kinases GSK3β and mTOR , modulated by PI-3K/Akt , can inhibit NFAT activity , suggesting a cross-talk between the calcium and growth factor signaling pathways . Both NFAT and mTOR activity have been associated with tumorigenesis . We therefore investigated the impact of calcineurin and PI-3K/mTOR inhibition in growth of human colon carcinoma cells . We show that despite the efficient inhibition of NFAT1 activity , FK506 promotes tumor growth , whereas CsA inhibits it due to a delay in cell cycle progression and induction of necroptosis . We found NFκB activation and mTORC1 activity not to be altered by CsA or FK506 . Similarly , changes to mitochondrial homeostasis were equivalent upon treatment with these drugs . We further show that , in our model , NFAT1 activation is not modulated by PI3K/mTOR . We conclude that CsA slows cell cycle progression and induces necroptosis of human carcinoma cell lines in a TGFβ- , NFAT- , NFκB- and PI3K/mTOR-independent fashion . Nevertheless , our data suggest that CsA , in addition to its anti-inflammatory capacity , may target transformed colon and esophagus carcinoma cells without affecting non-transformed cells , promoting beneficial tumoristatic effects .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: Cigarette smoke ( CS ) is a rich source of radicals , predisposing the cell to oxidative stress resulting in inflammation . Chronic inflammation is a recognized risk factor for carcinogenesis . Cyclooxygenase-2 ( COX-2 ) is a mediator of inflammatory pathway and may , therefore , contribute to carcinogenesis . There are several reports that suggest the association between CS and COX-2 associated risk to cancer . In the present study , we examined the role of celecoxib ( a selective COX-2 inhibitor ) in modulating the oxidative stress caused by CS inhalation in mice . CS exposure for a period of 10 weeks caused oxidative stress in the pulmonary and hepatic tissues , as evident from the increase in lipid peroxidation levels ( LPO ) and decrease in reduced glutathione ( GSH ) levels . Celecoxib ( 125 mg/kg body weight for 8 weeks ) administration to CS inhaling mice reduced the oxidative stress by decreasing the LPO levels and enhancing the GSH levels in comparison to the CS-exposed group . CS exposure repressed the enzymatic antioxidant defense system , as evident from the decrease in catalase ( CAT ) and superoxide dismutase ( SOD ) activities . Co-adminstration of celecoxib considerably reversed the changes in the enzymatic antioxidant defense system . Histopathological studies of lungs showed that CS exposure induced alveolar wall destruction and air space enlargement . In co-treated group , the alveolar septa were thicker than normal with apparent infiltration of inflammatory cells . In CS-exposed group , hepatic tissue exhibited vacuolization and macrophage infiltration . Co-treatment with celecoxib restored the normal histoarchitechture in hepatic tissues of CS inhaling mice . Thus , the present study demonstrated that celecoxib adminstration reduced the oxidative stress-mediated risk to carcinogenesis , due to its ability to boost the antioxidant defense system .\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: Lentinula edodes mycelia ( L.E.M. ) is a dried powder extracted from shiitake mushrooms ( Lentinula edodes ) . We previously demonstrated that it has immunomodulatory effects . In this paper , the direct cytotoxic effects of the polysaccharide-rich fraction of L.E.M . ( L.E.M. ethanol precipitate ; LEP ) on HepG2 human hepatocellular carcinoma ( HCC ) cells were investigated . LEP directly killed the HepG2 cells efficaciously , but had only minor effects on normal rat hepatocytes and normal mouse dermal cells under the same conditions . Characteristic morphological changes associated with apoptosis such as shrinkage , rounding , and floating as well as chromatin condensation were confirmed ; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling ( TUNEL ) staining was positive as determined by fluorescence microscopy analyses . The caspase-3 and -8 death receptor pathway was found largely responsible for the apoptotic death of HepG2 cells treated with LEP . In conclusion , LEP can directly induce apoptosis of HepG2 cells , and thus may have potential chemotherapeutic applications for the treatment of HCC .\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 Surgical procedures such as liver resection and liver transplantation are the first-line treatments for hepatocellular carcinoma ( HCC ) patients . However , the high incidence of tumor recurrence and metastasis after liver surgery remains a major problem . Recent studies have shown that hepatic ischemia-reperfusion ( I/R ) injury and endothelial progenitor cells ( EPCs ) contribute to tumor growth and metastasis . We aim to investigate the mechanism of FTY720 , which was originally applied as an immunomodulator , on suppression of liver tumor metastasis after liver resection and partial hepatic I/R injury . METHODOLOGY/PRINCIPAL FINDINGS An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777 . Two weeks after orthotopic liver tumor implantation , the rats underwent liver resection for tumor-bearing lobe and partial hepatic I/R injury . FTY720 ( 2 mg/kg ) was administered through the inferior caval vein before and after I/R injury . Blood samples were taken at days 0 , 1 , 3 , 7 , 14 , 21 and 28 for detection of circulating EPCs ( CD133+CD34+ ) . Our results showed that intrahepatic and lung metastases were significantly inhibited together with less tumor angiogenesis by FTY720 treatment . The number of circulating EPCs was also significantly decreased by FTY720 treatment from day 7 to day 28 . Hepatic gene expressions of CXCL10 , VEGF , CXCR3 , CXCR4 induced by hepatic I/R injury were down-regulated in the treatment group . CONCLUSIONS/SIGNIFICANCE FTY720 suppressed liver tumor metastasis after liver resection marred by hepatic I/R injury in a rat liver tumor model by attenuating hepatic I/R injury and reducing circulating EPCs .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Engineered zinc-finger nucleases ( ZFN ) represented an innovative method for the genome manipulation in vertebrates . ZFN introduced targeted DNA double strand breaks ( DSB ) and initiated non-homologous end joining ( NHEJ ) after pronuclear or cytoplasmatic microinjection into zygotes . Resulting frame shift mutations led to functional gene ablations in zebra fish , mice , pigs and also in laboratory rats . Therefore , we targeted the rat Rag1 gene essential for the V(D)J recombination within the immunoglobulin production process and for the differentiation of mature B and T lymphocytes to generate an immunodeficient rat model in the LEW/Ztm strain . RESULTS After microinjection of Rag1 specific ZFN mRNAs in 623 zygotes of inbred LEW/Ztm rats 59 offspring were born from which one carried a 4 bp deletion . This frame shift mutation led to a premature stop codon and a subsequently truncated Rag1 protein confirmed by the loss of the full-length protein in Western Blot analysis . Truncation of the Rag1 protein was characterized by the complete depletion of mature B cells . The remaining T cell population contained mature CD4+/CD3+/TCRαβ+ as well as CD8+/CD3+/TCRαβ+ positive lymphocytes accompanied by a compensatory increase of natural killer cells in the peripheral blood . Reduction of T cell development in Rag1 mutant rats was associated with a hypoplastic thymus that lacked follicular structures . Histological evaluation also revealed the near-complete absence of lymphocytes in spleen and lymph nodes in the immunodeficient Rag1 mutant rat . CONCLUSION The Rag1 mutant rat will serve as an important model for transplantation studies . Furthermore , it may be used as a model for reconstitution experiments related to the immune system , particularly with respect to different populations of human lymphocytes , natural killer cells and autoimmune phenomena .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;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: Hepatocellular carcinoma ( HCC ) is the fifth most common cancer worldwide . Major risk factors of HCC include infection with hepatitis B or C viruses , alcohol and non-alcoholic fatty liver disease . HCC is difficult to diagnose at early stage , and has a very poor survival rate when diagnosed at a late stage . The majority of HCC-related deaths result from local invasion ( to cause liver failure ) or distant metastases . There is an urgent need to identify effective molecular targets for the treatment of the disease . As the target of an established class of therapeutic agent thiazolidinediones ( TZDs ) , peroxisome-proliferator-activated receptor γ ( PPARγ ) has been widely studied for its role in the development of HCC . A substantial body of evidence based on in vitro and in vivo models indicates that the activation of PPARγ is able to inhibit HCC cell proliferation and tumor growth through inducing cell cycle arrest and apoptosis via the regulation of a panel of downstream effector molecules . PPARγ activation also induces an inhibitory effect on HCC metastasis . Meanwhile , there is new evidence suggesting that PPARγ inhibition could also be anti-tumorigenic . In the present review , we summarize the available information on the role of PPARγ in HCC development and spread , and discuss whether PPARγ activation by TZDs could play a role in the treatment of HCC , summarizing both in vitro and in vivo . Considering the available data , PPARγ seems to exert beneficial effects against HCC and may therefore represent as a therapeutic target .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;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: Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin ( TCDD ) . TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial , viral , and parasitic infections in exposed animals . Nearly 20 years after the Seveso , Italy , accident , we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones ( n = 62 ) and in the surrounding noncontaminated area ( n = 58 ) . Plasma IgG levels decreased with increasing TCDD plasma concentration ( r = -0.35 , p = 0.0002 ) . Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest ( &lt ; 3.5 ppt ) TCDD levels to 1,163 mg/dL in the group with the highest ( 20.1-89.9 ppt ) TCDD levels ( p = 0.002 ) . The association was significant ( p = 0.0004 ) after adjusting for age , sex , smoking , and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs . IgM , IgA , C3 , and C4 plasma concentrations did not exhibit any consistent association with TCDD levels . We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components . The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse . Methodologic issues , results , and possible sources of variation between studies are discussed . The possible long-term immunologic effects of TCDD exhibited by the participants of the present study , coupled with the increased incidence of lymphatic tumors in the area of the accident , warrant further investigation .\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: Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas ( ccRCCs ) are poorly understood . A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau ( VHL ) gene , which contributes to cancer progression and metastasis . We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells . VIP increased adhesion but decreased expression of metalloproteinases , MMP2 and MMP9 , as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells . VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells , suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma . VIP effects in A498 cells were blocked by the VPAC(1/2)-receptor antagonist JV-1-53 . In conclusion , present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;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 response to DNA double strand breaks , the histone variant H2AX at the break site is phosphorylated at serine 139 by DNA damage sensor kinases such as ataxia telangiectasia-mutated , forming gamma-H2AX . This phosphorylation event is critical for sustained recruitment of other proteins to repair the break . After repair , restoration of the cell to a prestress state is associated with gamma-H2AX dephosphorylation and dissolution of gamma-H2AX-associated damage foci . The phosphatases PP2A and PP4 have previously been shown to dephosphorylate gamma-H2AX . Here , we demonstrate that the wild-type p53-induced phosphatase 1 ( WIP1 ) also dephosphorylates gamma-H2AX at serine 139 in vitro and in vivo . Overexpression of WIP1 reduces formation of gamma-H2AX foci in response to ionizing and ultraviolet radiation and blocks recruitment of MDC1 ( mediator of DNA damage checkpoint 1 ) and 53BP1 ( p53 binding protein 1 ) to DNA damage foci . Finally , these inhibitory effects of WIP1 on gamma-H2AX are accompanied by WIP1 suppression of DNA double strand break repair . Thus , WIP1 has a homeostatic role in reversing the effects of ataxia telangiectasia-mutated phosphorylation of H2AX .\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: We have previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than nonstressed ones . Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells ( BCR-ABL(+) ) express HSP60 and HSP72 on their surface . To explore how the immune system distinguishes stressed from nonstressed apoptotic tumor cells , we analyzed the responses of dendritic cells to these 2 types of apoptotic cells . We found that nonstressed and heat-stressed apoptotic 12B1-D1 cells were taken up by dendritic cells in a comparable fashion . However , when stressed apoptotic 12B1-D1 cells were coincubated with immature dendritic cells for 24 hours , this resulted in greater up-regulation of costimulatory molecules ( CD40 , CD80 , and CD86 ) on the surface of dendritic cells . Moreover , stressed apoptotic 12B1-D1 cells were more effective in stimulating dendritic cells to secrete interleukin-12 ( IL-12 ) and in enhancing their immunostimulatory functions in mixed leukocyte reactions . Furthermore , we demonstrated that immunization of mice with stressed apoptotic 12B1-D1 cells induced the secretion of T helper-1 ( T(H)1 ) profile of cytokines by spleen cells . Splenocytes from mice immunized with stressed apoptotic cells , but not nonstressed ones , were capable of lysing 12B1-D1 and the parental 12B1 line , but not a B-cell leukemia line , A20 . Our data indicate that stressed apoptotic tumor cells are capable of providing the necessary danger signals , likely through increased surface expression of heat shock proteins ( HSPs ) , resulting in activation/maturation of dendritic cells and , ultimately , the generation of potent antitumor T-cell responses .\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: The effects of glucocorticoid ( GC ) on the proliferation of Dunn Osteosarcoma ( OS ) cells were examined under in vitro culture conditions . Dexamethasone ( Dex ) inhibited the proliferation of Dunn OS cells in a dose-dependent manner , while the addition of anti-GC , RU486 , to the culture medium in part recovered Dex-induced growth inhibition . The number of maximum binding sites ( Bmax ) and the dissociation constant ( Kd ) value of glucocorticoid receptor ( GR ) in Dunn OS cells were 19,560 sites/cell and 5.2 +/- 0.8 nM , respectively . RU486 competed with labeled Dex against GR at a concentration of 10(-6) M. Western blot analysis of [ 3H]Dex-mesylate-labeled cell homogenate and immunohistochemical staining against GR further confirmed the presence of GR . Dex treatment of Dunn OS cells resulted in apoptosis with the characteristic internucleosomal DNA cleavage shown by the DNA ladder pattern in agarose gel electrophoresis . These data demonstrate that GC inhibits the proliferation of Dunn OS cells via GR , for which one possible mechanism in vitro is induction of apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "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: The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells ( MECs ) . One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence . However , the precise genetic changes that are responsible for this event in MECs is largely unknown . Here , we report that Bmi-1 , originally identified as a c-Myc cooperating oncoprotein , can bypass senescence , extend the replicative life span , and immortalize MECs . Furthermore , Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines . Overexpression of Bmi-1 in MECs led to activation of human telomerase reverse transcriptase ( hTERT ) transcription and induction of telomerase activity . Telomerase induction by Bmi-1 was an early event in the extension of the replicative life span and immortalization . Bmi-1 was not overexpressed in hTERT-immortalized MECs , suggesting that Bmi-1 functions upstream of hTERT . Although , c-Myc has been reported to induce telomerase in MECs , Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT promoter . Deletion analysis of the Bmi-1 protein suggested that the RING finger , as well as a conserved helix-turn-helix-turn domain , were required for its ability to induce telomerase and immortalize MECs . These data suggest that Bmi-1 regulates telomerase expression in MECs and plays a role in the development of human breast cancer .\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: Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers . As chronic inflammations are associated with malignancies , it is important to prevent inflammation-mediated neoplastic formation , promotion and/or progression . One possible intervention will be using cancer chemopreventive agents such as curcumin ( CUR ) , a potent anti-inflammatory and anti-oxidative stress compound . Polyunsaturated fatty acids ( PUFA ) such as docosahexaenoic acid ( DHA ) or eicosapentaenoic acid ( EPA ) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids , cytokines , and reactive oxygen species ( ROS ) . The present study aims at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory effects in RAW 264.7 cells . Non-toxic concentrations of single and combination of the compounds were investigated at 6 , 12 and 24h . The nitric oxide ( NO ) suppression effects were most prominent at 24h . All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 microM and 25 microM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels . Importantly , very low doses of CUR 2.5 microM and DHA or EPA of 0.78 microM could synergistically suppress the LPS-induced prostaglandin E(2) ( PGE(2) ) . The combinations were also found to suppress iNOS , COX-2 , 5-lipoxygenase ( 5-LOX ) and cPLA(2) but induce HO-1 . Taken together , the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA .\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: Comparative mutagenesis studies of N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene ( dG-AAF ) and N-(2'-deoxyguanosin-8-yl)-2-aminofluorene ( dG-AF ) adducts positioned in the Nar I restriction enzyme site were performed using Escherichia coli ( E. coli ) and simian kidney ( COS-7 ) cells . Oligodeoxynucleotides ( (5)(')TCCTCG(1)G(2)CG(3)CCTCTC ) containing a recognition sequence for the Nar I restriction enzyme were modified site-specifically with dG-AAF or dG-AF . Modified and unmodified oligomers inserted into single-stranded phagemid shuttle vectors were used to transform E. coli or to transfect COS-7 cells . Following replication in host cells , progeny plasmids were recovered and analyzed for mutations . In SOS-induced E. coli , dG-AAF primarily induced one- and two-base deletions . The mutational frequency varied , depending on the position modified in the Nar I site ; 91% two-base deletions were observed at G(3) , while 8.4% and 2.8% deletions were detected at G(2) and G(1) , respectively . In contrast , dG-AF at any position in the Nar I site failed to produce deletions , generating primarily G --&gt ; T transversions ( mutational frequency , 7.6-8.4% ) . In COS-7 cells , both dG-AAF and dG-AF primarily induced G --&gt ; T transversions . Mutation frequencies for dG-AAF were 9.4-24% , the highest values being at G(1) and G(3) . Mutation frequencies for dG-AF were 9.3-21% , the higher value at G(2) . We conclude from this study that the mutation potential of dG-AAF and dG-AF depends on the structure of the adduct , the sequence context of the lesion , and the host cell used for the experiment .\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: Regulation of poly(ADP-ribose) ( PAR ) synthesis and turnover is critical to determining cell fate after genotoxic stress . Hyperactivation of PAR synthesis by poly(ADP-ribose) polymerase-1 ( PARP-1 ) occurs when cells deficient in DNA repair are exposed to genotoxic agents ; however , the function of this hyperactivation has not been adequately explained . Here , we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β ( pol β ) . The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent , methyl methanesulfonate ( MMS ) , or to low energy laser-induced DNA damage . There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells , but not in wild-type cells . In the case of MMS treatment , PAR synthesis did not lead to cell death in the pol β null cells , but instead resulted in increased PARylation of the nonhomologous end-joining ( NHEJ ) protein Ku70 and increased association of Ku70 with PARP-1 . Inhibition of the NHEJ factor DNA-PK , under conditions of MMS-induced PARP-1 hyperactivation , enhanced necrotic cell death . These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised .\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: To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process , methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M . All transformants examined revealed an alteration in DNA methylation in some of the genes , although these changes were variable among them . A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes , whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes . Resultant data indicate that the alteration of DNA methylation is closely related to transformation process , yet how this involvement occurs is complex and remains unclear .\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: We have evaluated DNA damage ( DNA adduct formation ) after feeding benzo[a]pyrene ( BP ) to wild-type ( WT ) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53 . DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry ( HPLC/ES-MS/MS ) , which measures r7,t8,t9-trihydroxy-c-10-(N ( 2)-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene ( BPdG ) , and a chemiluminescence immunoassay ( CIA ) , using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ( BPDE)-DNA antiserum , which measures both BPdG and the other stable BP-DNA adducts . When mice were fed 100 ppm BP for 28 days , BP-induced DNA damage measured in esophagus , liver and lung was typically higher in Xpa(-/-)p53(+/-) mice , compared with WT mice . This result is consistent with the previously observed tumor susceptibility of Xpa(-/-)p53(+/-) mice . BPdG , the major DNA adduct associated with tumorigenicity , was the primary DNA adduct formed in esophagus ( a target tissue in the mouse ) , whereas total BP-DNA adducts predominated in higher levels in the liver ( a non-target tissue in the mouse ) . In an attempt to lower BP-induced DNA damage , we fed the WT and Xpa(-/-)p53(+/-) mice 0.3% chlorophyllin ( CHL ) in the BP-containing diet for 28 days . The addition of CHL resulted in an increase of BP-DNA adducts in esophagus , liver and lung of WT mice , a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-)p53(+/-) mice and an increase of BPdG in livers of WT mice . Therefore , the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect , indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs .\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 O(6) -methylguanine-DNA methyltransferase ( MGMT ) is a DNA repair enzyme that can protect cells from carcinogenic effects of alkylating agents by removing adducts from the O(6) position of guanine . Evidences indicated that areca quid chewing may increase the risk of oral squamous cell carcinoma ( OSCC ) . This study was to investigate the role of MGMT expression in OSCCs and the normal oral tissues . METHODS Thirty-two OSCCs from areca quid chewers and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by the immunohistochemistry for MGMT . Primary human oral keratinocytes ( HOKs ) were challenged with arecoline , the major alkaloid of areca nut , by Western blot . Nicotine , an important component of cigarette smoke , was added to find the possible regulatory mechanisms . RESULTS Significant association was observed between low MGMT expression and advanced clinical stage of OSCCs and lymph node metastasis ( P=0.03 ) . MGMT expression was significantly higher in patients only chewing areca quid than patients both chewing areca quid and smoking ( P=0.028 ) . Arecoline was found to elevate MGMT expression in a dose- and time-dependent manner . The addition of nicotine was found to enhance arecoline-induced MGMT expression . CONCLUSION Our results indicate that MGMT could be used clinically as a predictive marker for tumor processing , the potential for lymph node metastasis as well as advanced clinical stage . MGMT expression was significantly upregulated by arecoline in HOKs . Nicotine has a synergistic effect of arecoline-induced MGMT expression . The cigarette smoking may act synergistically in the pathogenesis of OSCC in areca quid chewers via the upregulation of MGMT .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication . Simultaneously , however , it may also enhance antitumor therapy through initiation of proinflammatory , antiviral cytokine responses at the tumor site . The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus . In this respect , injection of oncolytic vesicular stomatitis virus ( VSV ) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression , but it is not associated with viral replicative burst in the tumor . In contrast , intratumoral delivery of VSV induces an acute proinflammatory reaction , which quickly resolves concomitantly with virus clearance . Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication , a single-cycle VSV is equally effective as a fully replication-competent VSV , whereas inactivated viruses do not generate therapy . Even though therapy is dependent on host CD8+ and natural killer cells , these effects are not associated with interferon-gamma-dependent responses against either the virus or tumor . There is , however , a strong correlation between viral gene expression , induction of proinflammatory reaction in the tumor and in vivo therapy . Overall , our results suggest that acute innate antiviral immune response , which rapidly clears VSV from B16ova tumors , is associated with the therapy observed in this model . Therefore , the antiviral immune response to an oncolytic virus mediates an intricate balance between safety , restriction of oncolysis and , potentially , significant immune-mediated antitumor therapy .\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: A better understanding of the underlying mechanisms of DNA repair after exposure to ionizing radiation represents a research priority aimed at improving the outcome of clinical radiotherapy . Because of the close association with DNA double strand break ( DSB ) repair , phosphorylation of the histone H2AX protein ( γH2AX ) , quantified by immunodetection , has recently been used as a method to study DSB induction and repair at low and clinically relevant radiation doses . However , the lack of consistency in literature points to the need to further validate the role of H2AX phosphorylation in DSB repair and the use of this technique to determine intrinsic radiosensitivity . In the present study we used human mammary epithelial MCF10A cells , characterized by a radiosensitive phenotype due to reduced levels of the Ku70 and Ku80 repair proteins , and investigated whether this repair-deficient cell line displays differences in the phosphorylation pattern of H2AX protein compared to repair-proficient MCF10A cells . This was established by measuring formation and disappearance of γH2AX foci after irradiating synchronized cell populations with ( 60)Co γ-rays . Our results show statistically significant differences in the number of γH2AX foci between the repair-deficient and -proficient cell line , with a higher amount of γH2AX foci present at early times post-irradiation in the Ku-deficient cell line . However , the disappearance of those differences at later post-irradiation times questions the use of this assay to determine intrinsic radiosensitivity , especially in a clinical setting .\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: The therapeutic principle of allogeneic haematopoietic cell transplantation ( allo-HCT ) is based on an active donor immune system that eliminates host-derived tumour cells . We hypothesized that in addition to the alloantigen-driven anti-tumour response , disruption of the immunological microenvironment within the tumour is responsible for its elimination after allo-HCT . We observed that induction of graft-versus-host disease ( GvHD ) significantly reduced the abundance of luc(+) FoxP3(+) regulatory T ( Treg ) cells in the tumour tissue , which is indicative of impaired or over-ridden tumour recruitment signals towards Treg cells . Analysis of the intestines and liver revealed chemokines and purine nucleotides as candidates for attracting Treg to these sites of inflammation . Despite its expression on tissue-residing Treg cells , the chemokine receptor CCR3 was not critical for Treg-cell function following allo-HCT . Extracellular ATP can attract immune cells via P2Y2 . P2Y2 was found to be expressed on Treg cells , and we found a partial reduction of GvHD prevention when P2Y2(-/-) rather than P2Y2(+/+) Treg cells were given . Exogenous local inflammation reduced Treg-cell accumulation in the tumour , suggesting a potential clinical approach to prevent Treg-cell-mediated tumour escape . In conclusion , we demonstrate that GvHD-related inflammation reduced Treg-cell numbers at the tumour sites , which may in turn help to explain the observation that patients with GvHD have a lower risk of tumour relapse .\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: INTRODUCTION AND AIMS The survival of pancreatic cancer patients with portal vein resection is extremely poor due to the high incidence of liver metastasis . The occurrence of liver metastasis is decreased by locoregional arterial infusion after pancreatic surgery . Chemosensitivity tests can provide the basis for individualized chemotherapy in each patient and predict the clinical response . Therefore , the current study was designed to clarify whether locoregional chemotherapy based on the results of chemosensitivity tests has the clinical effects of preventing liver metastasis and improving survival for patients with portal vein resection . METHODOLOGY The resected specimens from 40 of 47 patients with resection of pancreatic cancer were assessed for chemosensitivity to various anticancer drugs . Fourteen patients underwent portal vein resection due to direct invasion , and nine of these patients received intra-arterial adjuvant chemotherapy on the basis of the results of MTT assay to prevent liver metastasis . The remaining five patients received no chemotherapy . RESULTS None of the patients who received intra-arterial chemotherapy had liver metastasis , and this group of patients had improved survival . The mean survival of patients with intra-arterial chemotherapy was significantly longer than that of patients without chemotherapy ( 25.6 months with chemotherapy versus 9.4 months without chemotherapy ) . CONCLUSION A pilot study of postoperative intra-arterial chemotherapy showed the reduction of liver metastasis and improvement of survival among pancreatic cancer patients with portal vein resection .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide ( H2O2 ) in murine Hepa-1c1c7 cells . Oxidative DNA damage was estimated by nuclear condensation assessment , fluorescence-activated cell sorting analysis , and Comet assay . Rutaecarpine inhibited cell death induced by 500 μM H2O2 , as assessed by 4',6-diamidino-2-phenylindole ( DAPI ) staining . Treatment with rutaecarpine reduced the number of DNA strand breaks induced by H2O2 , as assessed by DAPI staining and Comet assay , and increased quinone reductase , phosphatidylinositol 3-kinase , and pAkt protein levels , as assessed by western blotting .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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 growth-inhibitory effects of ketoconazole , an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes , were tested in human colon and breast cancer cell lines . In the serum independent HT29-S-B6 colon cell clone , ketoconazole reduced cell proliferation and [ 3H]thymidine incorporation in a dose-dependent fashion , with a 50% inhibitory concentration of approximately 2.5 microM . Flow cytometry showed an accumulation of cells in the G0-G1 phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase . Ketoconazole also inhibited [ 3H]thymidine incorporation in the hormone-independent breast cancer cells MDA-MB-231 and Evsa-T , with respective 50% inhibitory concentration of approximately 13 and 2 microM . The mechanism of action of ketoconazole is unknown . However , another lipoxygenase inhibitor , BW755C , inhibited only weakly [ 3H]-thymidine incorporation and accumulated the cells in S and G2 . Conversely , clotrimazole and SKF525A , inhibitors of cytochrome P-450 enzymes , had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole , other azole derivatives which do not inhibit cytochrome P-450 enzymes , had no effect . The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole .\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: Diallyl disulfide ( DADS ) is a major organo-sulfur compound derived from garlic ( Allium sativum ) , which inhibits the proliferation of various types of cancer cells . In this study we investigated the effect of DADS on the induction of apoptosis , as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells . Treatment of B16F-10 cells with nontoxic concentrations of DADS resulted in the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner . Cell-cycle analysis revealed that the occurrence of the sub-G1 peak was significantly elevated in DADS-treated cells . DADS treatment also down-reguated Bcl-2 expression and up-regulated p53 , caspase-9 , and caspase-3 expression in B16F-10 melanoma cells . The study also reveals that DADS inhibited the activation and nuclear translocation of p65 , p50 , and c-Rel subunits of nuclear factor ( NF)-B and other transcription factors , such as c-fos , activated transcription factor-2 , and cyclic adenosine monophosphate response element-binding protein , in B16F-10 melanoma cells The pro-inflammatory cytokine production and gene expression of tumor necrosis factor ( TNF)-α , interleukin ( IL)-1β , IL-6 , and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) were down-regulated in DADS-treated cells compared with control B16F-10 metastatic melanoma cells . DADS induces caspase-dependent apoptosis through a mitochondria-mediated intrinsic pathway in B16F-10 melanoma cells by activating p53 and caspase-3 gene expression and suppressing pro-inflammatory cytokines and NF-B-mediated Bcl-2 activation .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND/PURPOSE Although angiogenic factors may play an important role in the biology of neuroblastoma , which frequently spreads hematogenously , the mechanism remains unclear . The authors studied tumor progression and invasion from the perspective of angiogenesis and sought to understand the features of this type of tumor . METHODS Thirty-one specimens were resected from patients with neuroblastoma and the expression of vascular endothelial growth factor ( VEGF ) , and its receptor ( Flk-1 ) was examined using immunohistochemistry . The authors looked for correlations among the expressions of VEGF and its receptor with various clinicopathologic factors . In addition , they examined the expression and location of VEGF and Flk-1 mRNA in 10 primary neuroblastoma using in situ hybridization . RESULTS Both in situ hybridization and immunohistochemistry showed the presence of VEGF expression within the neuroblastoma cells . We found VEGF mRNA in neuroblastoma cells but not vascular endothelial cells according to in situ hybridization . Further , Flk-1 mRNA was present both in neuroblastoma cells and vascular endothelial cells . The level of VEGF expression was higher in unfavorable histology , using the criteria of Shimada , than in favorable histology . CONCLUSION The authors suggest that paracrine and autocrine systems are involved in the angiogenesis of neuroblastoma , and the expression of VEGF correlates with the prognosis in neuroblastoma .\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: The Hippo signaling pathway inhibits cell growth and regulates organ size through a kinase cascade that leads to the phosphorylation and nuclear exclusion of the growth-promoting transcriptional coactivator Yes-associated protein ( YAP)/Yorkie . It mediates contact inhibition of cell growth downstream of cadherin adhesion molecules and other cell surface proteins . Contact inhibition is often antagonized by mitogenic growth factor signaling . We report an important mechanism for this antagonism , inhibition of Hippo pathway signaling by mitogenic growth factors . EGF treatment of immortalized mammary cells triggers the rapid translocation of YAP into the nucleus along with YAP dephosphorylation , both of which depend on Lats , the terminal kinase in the Hippo pathway . A small-molecule inhibitor screen of downstream effector pathways shows that EGF receptor inhibits the Hippo pathway through activation of PI3-kinase ( PI3K ) and phosphoinositide-dependent kinase ( PDK1 ) , but independent of AKT activity . The PI3K-PDK1 pathway also mediates YAP nuclear translocation downstream of lysophosphatidic acid and serum as a result of constitutive oncogenic activation of PI3K . PDK1 associates with the core Hippo pathway-kinase complex through the scaffold protein Salvador . The entire Hippo core complex dissociates in response to EGF signaling in a PI3K-PDK1-dependent manner , leading to inactivation of Lats , dephosphorylation of YAP , and YAP nuclear accumulation and transcriptional activation of its target gene , CTGF . These findings show that an important activity of mitogenic signaling pathways is to inactivate the growth-inhibitory Hippo pathway and provide a mechanism for antagonism between contact inhibition and growth factor action .\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: Momordica charantia has been found to exhibit anticancer activity , in addition to its well-known therapeutic functions . We have demonstrated that the leaf extract of Momordica charantia ( MCME ) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways . In this study , a different susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability , leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells . MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities . We proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt , β-catenin , and MMPs .\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: More effective treatments for metastatic lung cancer remain a pressing clinical need . In this study , we identified migration inducting gene-7 ( MIG-7 ) protein as critical for COX-2/prostaglandin E2 ( PGE2)- and Akt/GSK-3β-dependent tumor invasion/metastasis . COX-2/PGE2 activated EP4 to enhance Akt and GSK-3β phosphorylation and β-catenin/T-cell factor/lymphoid enhancer factor signaling leading to MIG-7 upregulation . RNAi-mediated attenuation of MIG-7 blocked COX-2/PGE2- and Akt/GSK-3β-mediated migration/invasion effects . Furthermore , MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK-3β phosphorylation and cancer-cell migration/invasion . Cancer cells overexpressing MIG-7 exhibited increased expression of ZEB-1 and Twist in parallel with epithelial-mesenchymal transition , metastasis and cancer lethality . MIG-7 protein level positively correlated with advanced stages of human lung cancers . MIG-7 thus offers a theranostic target for cancer metastases arising from aberrant activation of the cellular COX-2/PGE2 and Akt/GSK-3β signaling pathways .\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: UNLABELLED Oxygen free radicals and their reactive derivatives participate in formation of chronic inflammation states , which facilitate development of gastrointestinal tract tumors . Oxidative stress is one of the main causes of damage to cell membranes in result of exacerbated lipid peroxidation process . End products of lipid peroxidation ( aldehydes , organic peroxides ) react with important biological macromolecules such as DNA and proteins , cause changes in cell membrane structure and properties leading to loss of its integrity . Intensification of the lipid peroxidation process is a factor which may also lead to a malfunction in the antioxidant barrier , which further weakens the defense of cells against oxygen free radicals and promotes the onset and development of cancer . The aim of the study was the determination of lipid peroxidation level in gastrointestinal tract tumors ( stomach , liver , colon , and colorectal cancer to liver metastases ) . MATERIAL AND METHODS Materials for studies were obtained from 150 patients with gastrointestinal tract tumors : 10 with stomach cancer , 30 with malignant and benign liver cancers , 60 with primary colorectal cancer , and 50 with metachronous colorectal cancer liver metastases . We also investigated 25 patients with liver cirrhosis , which was treated as a pre-cancerous condition . In total , 175 patients were examined . Tumor specimens , and normal adjacent tissues ( 6-7 cm from the edge of the tumor ) , which served as control tissue in studies , were collected from patients ( with their consent ) during surgery . Additionally , liver specimens were collected from patients with liver cirrhosis . Lipid peroxidation level was determined spectrophotometrically as a concentration of final lipid peroxidation products , which in reaction with tiobarbituric acid ( TBA ) form colour complex ( thiobarbituric acid-reactive substances - TBARS ) . RESULTS The study showed the highest concentration of TBARS in benign , and the lowest in malignant liver tumors . Other types of gastrointestinal tumors studied , were characterized by similar levels of lipid peroxidation . TBARS concentration in these tumors was approximately 2-fold higher than in malignant liver tumors and much lower than in benign tumors . In all cancers of the digestive tract with the exception of malignant liver tumors increased level of TBARS was found , comparing with control tissue . The concentration of TBARS in cirrhotic liver was lower than in control . The level of lipid peroxidation in liver cirrhosis and malignant liver tumors was similar . There were no significant differences in TBARS concentration in the tumors of particular sections of the intestine and normal colon . The highest concentration of TBARS was found in G1 grade of colorectal cancer . In subsequent grades of cells differentiation ( G2 and G3 ) its concentration was lower . The highest level of lipid peroxidation , expressed as the concentration of TBARS was found in the I stage of colorectal cancer clinical advancement . The significantly lowest concentration of TBARS was shown for stage II ( UICC ) . CONCLUSIONS The level of lipid peroxidation in cancerous cells of gastrointestinal tract indicates increased oxidative stress . The changes of lipid peroxidation level--a marker of oxidative stress in gastrointestinal tumors appear to be closely associated with their development stages ( liver cirrhosis/malignant liver cancer ; colorectal cancer/colorectal cancer liver metastases ) and are likely to create such conditions , in which cancerous cells may proliferate , undergo gradual dedifferentiation and malignancy , and generate metastases .\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: Class switch recombination ( CSR ) in B lymphocytes is initiated by introduction of multiple DNA double-strand breaks ( DSBs ) into switch ( S ) regions that flank immunoglobulin heavy chain ( IgH ) constant region exons . CSR is completed by joining a DSB in the donor S mu to a DSB in a downstream acceptor S region ( e.g. , S gamma1 ) by end-joining . In normal cells , many CSR junctions are mediated by classical nonhomologous end-joining ( C-NHEJ ) , which employs the Ku70/80 complex for DSB recognition and XRCC4/DNA ligase 4 for ligation . Alternative end-joining ( A-EJ ) mediates CSR , at reduced levels , in the absence of C-NHEJ , even in combined absence of Ku70 and ligase 4 , demonstrating an A-EJ pathway totally distinct from C-NHEJ . Multiple DSBs are introduced into S mu during CSR , with some being rejoined or joined to each other to generate internal switch deletions ( ISDs ) . In addition , S-region DSBs can be joined to other chromosomes to generate translocations , the level of which is increased by absence of a single C-NHEJ component ( e.g. , XRCC4 ) . We asked whether ISD and S-region translocations occur in the complete absence of C-NHEJ ( e.g. , in Ku70/ligase 4 double-deficient B cells ) . We found , unexpectedly , that B-cell activation for CSR generates substantial ISD in both S mu and S gamma1 and that ISD in both is greatly increased by the absence of C-NHEJ . IgH chromosomal translocations to the c-myc oncogene also are augmented in the combined absence of Ku70 and ligase 4 . We discuss the implications of these findings for A-EJ in normal and abnormal 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: BACKGROUND To assess the potential mechanisms that may underlie increased local failure in triple negative ( TN ) breast cancers , an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors , including molecular phenotype . METHODS A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision . Data were collected on age ; tumor size , grade , and nodal stage ; estrogen receptor , progesterone receptor , and human endothelial growth factor receptor 2 ( Her2 ) ; extensive intraductal component ; lymphovascular invasion ; margins ; and reexcision findings . Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings . Molecular phenotypes were defined by conventionally used immunohistochemical pattern . RESULTS Data were collected on 369 patients with breast cancer . The median age was 57 years , median tumor size was 1.5 cm , 36% had positive margins , 32% had positive lymph nodes , 73.5% had the luminal A subtype , 9.5% had the luminal B subtype , 4.5% were Her2-enriched , and 12.5% were TN . Overall , 32% of patients had invasive cancer in their reexcision specimens , and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes . On univariate analysis , age , tumor size , margin status , lymphovascular invasion , nodal status , and TN subtype were associated with elevated risk of residual invasive cancer . On multivariate analysis using a forward stepwise model , TN subtype maintained significance , with an odds ratio of 3.28 ( P = .002 ) . CONCLUSION TN subtype has a statistically significant association with an increased risk of residual tumor . This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden .\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: Although the etiology of primary brain tumors is largely unknown , prior studies suggest that DNA repair polymorphisms may influence risk of glioma . Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma , but these tumors have not been well studied . We estimated the risk of glioma ( n = 362 ) , meningioma ( n = 134 ) , and acoustic neuroma ( n = 69 ) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based , case-control study conducted by the National Cancer Institute . We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 ( OR(CT/TT) = 3.5 ; 95% confidence interval : 1.8-6.9 ; P(trend) .0006 ) , which persisted after controlling for multiple comparisons ( P = .019 ) . Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 ( P(trend) .01 ) ; MUTYH rs3219466 ( P(trend) .02 ) , and PCNA rs25406 ( P(trend) .03 ) . The NBN rs1805794 minor allele variant was associated with decreased meningioma risk ( P(trend) .006 ) . Risk of acoustic neuroma was increased for the ERCC2 rs1799793 ( P(trend) .03 ) and ERCC5 rs17655 ( P(trend) .05 ) variants and decreased for the PARP1 rs1136410 ( P(trend) .03 ) . Decreased glioma risk was observed with the XRCC1 rs1799782 variant ( P(trend) .04 ) . Our results suggest that common DNA repair variants may affect the risk of adult brain tumors , especially meningioma .\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: ABSTRACT : BACKGROUND : Chemokine receptor CXCR4 , together with its ligand CXCL12 , plays critical roles in cancer progression , including growth , metastasis and angiogenesis . Ewing sarcoma is a sarcoma with poor prognosis despite current therapies , particularly for patients with advanced-stage disease . Lungs and bone ( marrow ) , organs of predilection for ( primary/metastatic ) Ewing sarcoma , represent predominant CXCL12 sources . METHODS : To gain insight into the role of the CXCR4-CXCL12 axis in Ewing sarcoma , CXCR4 , CXCL12 and hypoxia-inducible factor-1alpha protein expression was studied in therapy-naive and metastatic tumors by immunohistochemistry . CXCR4 function was assessed in vitro , by flow cytometry and proliferation/ cell viability assays , in the presence of recombinant CXCL12 and/or CXCR4-antagonist AMD3100 or under hypoxic conditions . RESULTS : Whereas CXCR4 was predominantly expressed by tumor cells , CXCL12 was observed in both tumor and stromal areas . Survival analysis revealed an ( expression level-dependent ) negative impact of CXCR4 expression ( p &lt ; 0.04 ) . A role for the CXCR4-CXCL12 axis in Ewing sarcoma growth was suggested by our observations that i ) CXCR4 expression correlated positively with tumor volume at diagnosis ( p = 0.013 ) , ii ) CXCL12 was present within the microenvironment of virtually all cases , iii ) CXCL12 induced proliferation of CXCR4-positive Ewing sarcoma cell lines , which could be abrogated by AMD3100 . CXCR4 expression was not correlated with occurrence of metastatic disease . Also , therapy-naive tumors demonstrated higher CXCR4 expression as compared to metastases ( p = 0.027 ) . Evaluation of in vivo hypoxia-inducible factor-1alpha expression and culture of cells under hypoxic conditions revealed no role for hypoxia in CXCR4 expression . CONCLUSIONS : Together , our results imply a crucial role for the CXCR4-CXCL12 axis in auto- and/or paracrine growth stimulation . Integration of CXCR4-targeting strategies into first- and/or second-line treatment regimens may represent a promising treatment option for Ewing sarcoma .\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: Many breast cancers are estrogen independent , and even in patients who initially respond to estrogen suppression therapy , the regression is often temporary . We have recently shown that antagonists of bombesin and gastrin-releasing peptide , including RC-3095 , inhibit the growth of pancreatic , colonic , and prostatic cancers in experimental animals . This effect was associated with a substantial decrease in epidermal growth factor ( EGF ) receptor levels in pancreatic and colon cancers .\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: Alterations of the epidermal growth factor receptor ( EGFR ) gene are common in some forms of cancer and the most frequent is a deletion of exons 2-7 . We have previously shown that this mutant receptor , called DeltaEGFR , confers enhanced tumorigenicity to glioblastoma cells through elevated proliferation and reduced apoptotic rates of the tumor cells in vivo . To understand the molecular mechanisms that underlie DeltaEGFR-enhanced proliferation , we examined the gene products that control cell cycle progression . We found that levels of the cyclin-dependent kinase ( CDK ) inhibitor , p27 , were lower in U87MG.DeltaEGFR tumors than in parental U87MG or control U87MG.DK tumors . Consequently , CDK2-cyclin A activity was also elevated , concomitant with the RB protein hyperphosphorylation . In addition , activated phosphatidylinositol 3-kinase ( PI3-K ) and phosphorylated Akt levels were also elevated in the U87MG.DeltaEGFR tumors . U87MG.DeltaEGFR cells failed to arrest in G(1) in response to serum starvation in vitro and while maintaining high levels of PI3-K activity and hyperphosphorylated RB . Treatment of U87MG.DeltaEGFR cells with LY294002 , a PI3-K inhibitor , caused reduced levels of phosphorylated Akt and concomitantly up-regulated levels of p27 . Expression of a kinase dead dominant-negative Akt mutant in the U87MG.DeltaEGFR cells similarly resulted in up-regulation of p27 and down-regulation of tumorigenicity in vivo . These results suggest that the constitutively active DeltaEGFR can enhance cell proliferation in part by down-regulation of p27 through activation of the PI3-K/Akt pathway . This pathway may represent another therapeutic target for treatment of those aggressive glioblastomas expressing DeltaEGFR .\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: High concentrations of lactic acid ( LA ) are found under various pathophysiological conditions and are accompanied by an acidification of the environment . To study the impact of LA on TNF secretion , human LPS-stimulated monocytes were cultured with or without LA or the corresponding pH control . TNF secretion was significantly suppressed by low concentrations of LA ( &lt ; or = 10 mM ) , whereas only strong acidification had a similar effect . This result was confirmed in a coculture model of human monocytes with multicellular tumor spheroids . Blocking synthesis of tumor-derived lactate by oxamic acid , an inhibitor of lactate dehydrogenase , reversed the suppression of TNF secretion in this coculture model . We then investigated possible mechanisms underlying the suppression . Uptake of [ 3-(13)C]lactate by monocytes was shown by hyphenated mass spectrometry . As lactate might interfere with glycolysis , the glycolytic flux of monocytes was determined . We added [ 1,2-(13)C(2)]glucose to the culture medium and measured glucose uptake and conversion into [ 2,3-(13)C(2)]lactate . Activation of monocytes increased the glycolytic flux and the secretion of lactate , whereas oxygen consumption was decreased . Addition of unlabeled LA resulted in a highly significant decrease in [ 2,3-(13)C(2)]lactate secretion , whereas a mere corresponding decrease in pH exerted a less pronounced effect . Both treatments increased intracellular [ 2,3-(13)C(2)]lactate levels . Blocking of glycolysis by 2-deoxyglucose strongly inhibited TNF secretion , whereas suppression of oxidative phosphorylation by rotenone had little effect . These results support the hypothesis that TNF secretion by human monocytes depends on glycolysis and suggest that LA and acidification may be involved in the suppression of TNF secretion in the tumor environment .\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: UVB from solar radiation is both an initiating and promoting agent for skin cancer . We have found that primary human keratinocytes undergo an apoptotic response to UVB . To determine whether these responses are altered during the course of immortalization , we examined markers of apoptosis in primary human foreskin keratinocytes ( HFK ) transduced with either a retroviral vector expressing the E6 and E7 genes of HPV-16 or with empty vector alone ( LXSN-HFK ) . Whereas LXSN-HFK as well as early passage keratinocytes expressing HPV-16 E6 and E7 ( p7 E6/7-HFK ) were both moderately responsive to UVB irradiation , late passage-immortalized keratinocytes ( p27 E6/7-HFK ) were exquisitely sensitive to UVB-induced apoptosis . After exposure to UVB , enhanced annexin V-positivity and internucleosomal DNA fragmentation were observed in p27 E6/7-HFK compared with either LXSN- or p7 E6/7-HFK . Caspase-3 fluorometric activity assays as well as immunoblot analysis with antibodies to caspase-3 and poly(ADP-ribose) polymerase revealed elevated caspase-3 activity and processing at lower UVB doses in p27 E6/7-HFK compared with LXSN- or p7 E6/7-HFK . In addition , the caspase inhibitor DEVD-CHO reduced the apoptotic response and increased survival of all three HFK types . Immunoblot analysis revealed that caspase-8 was activated in all three cell types , but caspase-9 was only activated in p27 E6/7-HFK . Cell cycle analysis further showed that only p27 E6/7-HFK exhibit G(2)/M accumulation that is enhanced by UVB treatment . This accumulation was associated with a rapid down-regulation of Bcl-2 in these cells . The immortalization process subsequent to the expression of HPV E6 and E7 may therefore determine UVB sensitivity by switching the mode of apoptosis from a caspase-8 to a Bcl-2-caspase-9-mediated pathway of apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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: Steroid hormone receptors , including estrogen receptor-alpha ( ERalpha ) , are ligand-activated transcription factors , and hormone binding leads to depletion of receptor levels via preteasome-mediated degradation . NEDD8 ( neural precursor cell-expressed developmentally down-regulated ) is an ubiquitin-like protein essential for protein processing and cell cycle progression . We recently demonstrated that ubiquitin-activating enzyme ( Uba)3 , the catalytic subunit of the NEDD8-activating enzyme , inhibits ERalpha transcriptional activity . Here we report that Uba3-mediated inhibition of ERalpha transactivation function is due to increased receptor protein turnover . Coexpression of Uba3 with ERalpha increased receptor degradation by the 26S proteasome . Inhibition of NEDD8 activation and conjugation diminished polyubiquitination of ERalpha and blocked proteasome-mediated degradation of receptor protein . The antiestrogen ICI 182,780 is known to induce ER degradation . In human MCF7 breast cancer cells modified to contain a disrupted NEDD8 pathway , ICI 182,780 degradation of ERalpha was impaired , and the antiestrogen was ineffective at inhibiting cell proliferation . This study provides the first evidence linking nuclear receptor degradation with the NEDD8 pathway and the ubiquitin-proteasome system , suggesting that the two pathways can act together to modulate ERalpha turnover and cellular responses to estrogens . Based on our observation that an intact NEDD8 pathway is essential for the antiproliferation activity of the ICI 182,780 in ERalpha positive breast cancer cells , we propose that disruptions in the NEDD8 pathway provide a mechanism by which breast cancer cells acquire antiestrogen resistance while retaining expression of ERalpha .\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: We have modelled multiple stages of malignant transformation of human endothelial cells ( ECs ) by overexpressing the catalytic subunit of human telomerase ( hTERT ) , together with SV40 T antigen ( SV40T ) and oncogenic N-ras . Transfection with hTERT alone , led to the immortalization of two out of three cultures of bone marrow-derived ECs ( BMECs ) . One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation . BMECs transfected with hTERT alone were functionally and phenotypically normal . BMECs transfected with SV40T ( BMSVTs ) had an extended lifespan , but eventually succumbed to crisis . BMSVTs exhibited a partially transformed phenotype , demonstrating growth factor independence , altered antigen expression and forming tiny , infrequent colonies in vitro . Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures . BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo . BMECs co-expressing SV40T , hTERT and N-ras exhibited an overtly transformed phenotype ; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo . These investigations demonstrate transformation of human ECs to an overtly malignant phenotype . This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias , as well as for testing drugs designed to curtail aberrant EC growth .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The role of regulatory T cells ( T(regs) ) in human colon cancer ( CC ) remains controversial : high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study . In mouse models of cancer , T(regs) have been reported to suppress inflammation and protect the host , suppress T cells and protect the tumor , or even have direct cancer-promoting attributes . These different effects may result from the presence of different T(reg) subsets . We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive , but compromised anti-inflammatory , properties ; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt . T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis . Indeed , ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions , suppressed inflammation , improved polyp-specific immune surveillance , and severely attenuated polyposis . Ablation of interleukin-6 ( IL-6 ) , IL-23 , IL-17 , or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt . Surprisingly , loss of IL-17A had a dual effect : IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer . Thus , we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation , potency of immune surveillance , and severity of disease outcome .\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: Mast cells ( MC ) are key effector cells in allergic reactions but also involved in host defence , tissue remodeling , angiogenesis , and fibrogenesis . Here , we show that human intestinal fibroblasts ( FB ) suppress apoptosis in human intestinal MC dependent on IL-6 . Intestinal FB produced IL-6 upon direct stimulation by intestinal MC in co-culture or by MC mediators such as TNF-α , IL-1β , tryptase or histamine . MC incubated with IL-6 survived for up to 3 weeks similar to MC co-cultured with FB and MC survival could be blocked by neutralizing anti-IL-6 Abs . Moreover , FB stimulated by MC mediators upregulated their expression of matrix metalloproteinase-1 ( MMP-1 ) , a key fibrolytic enzyme . Noteworthy , FB co-cultured with MC or treated with MMP-1 lost confluence and showed increased numbers of apoptotic cells . Our data indicate an intimate cross talk between mucosal MC and FB resulting in MC survival and induction of a fibrolytic rather than a profibrotic state in FB .\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: OBJECTIVES To evaluate and compare the incidence , TNM staging and the current strate- gy for the surgical treatment of renal cell carcinoma ( RCC ) in two European urologic institutions , situated in Varna , Bulgaria and in Bari , Italy . Both clinics have sound experience of RCC surgery , and modern laparoscopic equipment . A retrospective chart review of all patients with RCC diagnosed and treated in the last year was conducted at the two sites . MATERIALS AND METHODS In total , 88 patients ( 66 males and 22 females , mean age 58 years , range 24-81 years ) were enrolled in the study . Comparisons were made between some clinical and pathologic parameters with an established prognostic and therapeutic impact . The type of surgery perormed at both sites was analyzed as well . All these comparative studies were performed in relation to the 2008 EAU guidelines on the current management of RCC . Commercially available statistical software was used for the purpose . RESULTS The results showed no difference between the two sites regarding the RCC incidence and the patients ' age and gender . Significant differences ( p value &lt ; 0.0001 ) emerged in terms of : the median size of the tumors at surgery ( 8.5 cm in Varna , SD + 4.04 vs. 4.4 cm in Bari , SD _ 2.02 ) ; T-stage of the tumor ( Varna T T2-30% , T3-22% , T4-15% vs. Bari T1-64% , T2-12% , T3-24% , T4-0% ) ; N-positive disese ( 24% vs. 2% ) ; distant metastases ( 20% vs. 2% ) and presence of necrosis in the renal masses ( 37% vs. 19% ) . Thus , 85% of Varna patients underwent open radical nephrectomy , 11% nephron-sparing surgery and 4% explorative laparotomy , due to inoperability of the renal mass . Only 29% of Bari patients were treated by open radical nephrectomy , 12% underwent laparoscopic nephrectomy , 57% open partial nephrectomy and 2% laparoscopic partial tumor resection . Conclusions : These numbers demonstrate more advantageous tumour features at the Italian clinic in terms of organ-sparing surgical options ( open and laparoscopic ) , whereas in the Bulgarian clinic the tumour features pose certain limitations to the application of modern surgical techniques . This difference is due to early diagnosis of RCC in Italy , allowing treatment of smaller volume tumors .\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: We previously reported that hepatic stellate cells ( HSCs ) activated by angiotensin II ( AngII ) facilitate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma ( ICC ) . AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition ( EMT ) in renal epithelial cells , alveolar epithelial cells and peritoneal mesothelial cells . However , in the past , the relationship between AngII and stromal cell-derived factor-1 ( SDF-1 ) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail . SDF-1 and its specific receptor , CXCR4 , are now receiving attention as a mechanism of cell progression and metastasis . In this study , we examined whether activated HSCs promote tumor fibrogenesis , tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor ( AT-1 ) and the SDF-1/CXCR4 axis . Two human ICC cell lines and a human HSC line , LI-90 , express CXCR4 . Significantly higher concentration of SDF-1α was released into the supernatant of LI-90 cells to which AngII had been added . SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor . Furthermore , addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression , reduced E-cadherin expression , and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells . Co-culture with HSCs also enhanced the migratory capability of ICC cells . These findings suggest that SDF-1α , released from activated HSCs and AngII , play important roles in cancer progression , tumor fibrogenesis , and migration in autocrine and paracrine fashion by mediating EMT . Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma , tumor progression and meta-stasis of tumor cells expressing AT-1 and CXCR4 .\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: Telomerase activity , a cardinal requirement for immortalization , is a crucial step in the development of cancer and has been studied in many kinds of malignant tumours for clinical diagnostic and/or prognostic utilities . Using a PCR-based TRAP assay , we investigated telomerase activity in 8 adenomatous polyps , 9 dysplastic polyps , and in 36 paired cancer-normal mucosa specimens , one liver and one spleen metastasis from patients resected for sporadic colorectal cancer . Telomerase was absent or very low in normal mucosa and in adenomatous polyps . Dysplastic polyps and adenocarcinoma samples showed telomerase activity , with higher levels in cancer tissues compared to dysplastic lesions . A high telomerase activity was shown to be associated with late-staged cancers and metastasis , providing arguments supporting the role of telomerase not only in the development but also in the progression of colorectal carcinoma . Moreover , telomerase evaluation may help to confirm the malignant transformation in polypoid colorectal lesions with different levels of dysplastic alterations .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer is the malignant neoplasia with the highest incidence in women worldwide . Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression . Human studies have not considered the complexity of tumor biology during the stages of cancer advance , limiting their clinical application . The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early ( ED ; TNM I and II ) and advanced disease ( AD ; TNM III and IV ) of patients diagnosed with infiltrative ductal carcinoma breast cancer . Oxidative stress parameters were evaluated by plasmatic lipoperoxidation , carbonyl content , thiobarbituric reactive substances ( TBARS ) , nitric oxide levels ( NO ) , total radical antioxidant parameter ( TRAP ) , superoxide dismutase , and catalase activities and GSH levels . Immune evaluation was determined by TNF-α , IL-1β , IL-12 , and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence . Tissue damage analysis included heart ( total CK and CKMB ) , liver ( AST , ALT , GGT ) , and renal ( creatinine , urea , and uric acid ) plasmatic markers . C-reactive protein ( CRP ) and iron metabolism were also evaluated . Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages . ED was characterized by reduction in catalase , 8-isoprostanes , and GSH levels , with enhanced lipid peroxidation and TBARS levels . AD exhibited more pronounced oxidative status , with reduction in catalase activity and TRAP , intense lipid peroxidation and high levels of NO , TBARs , and carbonyl content . ED patients presented a Th2 immune pattern , while AD exhibited Th1 status . CRP levels and ferritin were increased in both stages of disease . Leukocytes burst impairment was observed in both the groups . Plasma iron levels were significantly elevated in AD . The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators .\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: The contribution that mitochondrial bioenergetics could have in cancer development is debated . Here , we have generated HCT116-derived colocarcinoma cell lines expressing different levels of the beta catalytic subunit of the mitochondrial H+-adenosine triphosphate synthase to assess the contribution of mitochondrial bioenergetics in colon cancer progression . The generated cells exhibit large ultrastructural , transcriptomic , proteomic and functional differences in their mitochondria and in their in vivo tumor forming capacity . We show that the activity of oxidative phosphorylation defines the rate of glucose utilization by aerobic glycolysis . The aggressive cellular phenotype , which is highly glycolytic , is bound to the deregulated expression of genes involved in metabolic processes , the regulation of the cell cycle , apoptosis , angiogenesis and cell adhesion . Remarkably , the molecular and ultrastructural analysis of the tumors derived from the three HCT116 cell lines under study highlight that tumor promotion inevitably requires the selection of cancer cells with a repressed biogenesis and functional activity of mitochondria , i.e. the highly glycolytic phenotype is selected for tumor development . The tumor forming potential of the cells is a non-genetically acquired condition that provides the cancer cell with a cell-death resistant phenotype . An abrogated mitochondrial respiration contributes to a diminished potential for reactive oxygen species signaling in response to 5-fluorouracil treatment . Treatment of cancer cells with dichloroacetate partially restores the functional differentiation of mitochondria and promotes tumor regression , emphasizing the reversible nature of the metabolic trait of cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVES/HYPOTHESIS Head and neck squamous cell carcinoma ( HNSCC ) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells . We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor ( FGFR ) . STUDY DESIGN Preclinical investigation . METHODS HNSCC cell lines ( FADU , OSC19 , Cal27 , SCC1 , SCC5 , SCC22A ) , fibroblast ( HS27 ) , and endothelial cells ( human umbilical vascular endothelial cell ) were cultured individually or in coculture . Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074 . Mice bearing established HNSCC xenografts were treated with PD173074 ( 12 mg/kg ) , and tumor histology was analyzed for stromal composition , proliferation ( Ki67 staining ) , and apoptosis ( TUNEL [ terminal deoxynucleotidyl transferase dUTP nick end labeling ] staining ) . RESULTS In vitro , inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls . However , HNSCC cell proliferation was not affected by inhibition of FGFR . When cocultured with fibroblasts , HNSCC cells proliferation increased by 15% to 80% ( P &lt ; .01 ) . Furthermore , this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition . Additionally , treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition ( P &lt ; .001 ) . Additionally , those tumors from mice treated with PD173074 had a smaller stromal component , decreased proliferation , and increased apoptosis . CONCLUSIONS Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro .\n OUTPUT:\n" }, { "from": "agent", "value": "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: We have examined the effect of FK506 on the Adriamycin sensitivity of the multidrug resistant human chronic myelocytic leukemia cell line ( K562/ADM ) . In K562/ADM cells , 1.0 microgram/ml FK506 reversed the resistance of Adriamycin , and increased the IC50 value for Adriamycin up to 17 fold . However , IC50 value for the parent cells ( K562 ) increased only 1.5 fold . By cell cycle analysis , the accumulation in late S-G2M phase was confirmed on K562/ADM cells , treated with 1.0 microgram/ml FK506 and low-dose of Adriamycin . Cyclosporin A ( CsA ) could also restored the Adriamycin sensitivity in the K562/ADM cells , as previously reported. 1.0 microgram/ml FK506 as well as CsA significantly increased radioactive Adriamycin accumulation in K562/ADM cells and blocked [ 3H]azidopien photoaffinity labeling of P-glycoprotein . These results suggest that 1.0 microgram/ml FK506 could reverse the Adriamycin resistance in a MDR human leukemia cells through the interaction with P-glycoprotein .\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: DNA damage signaling and repair take place in a chromatin context . Consequently , chromatin-modifying enzymes , including adenosine triphosphate-dependent chromatin remodeling enzymes , play an important role in the management of DNA double-strand breaks ( DSBs ) . Here , we show that the p400 ATPase is required for DNA repair by homologous recombination ( HR ) . Indeed , although p400 is not required for DNA damage signaling , DNA DSB repair is defective in the absence of p400 . We demonstrate that p400 is important for HR-dependent processes , such as recruitment of Rad51 to DSB ( a key component of HR ) , homology-directed repair , and survival after DNA damage . Strikingly , p400 and Rad51 are present in the same complex and both favor chromatin remodeling around DSBs . Altogether , our data provide a direct molecular link between Rad51 and a chromatin remodeling enzyme involved in chromatin decompaction around DNA DSBs .\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: Sarcomatoid renal cell carcinomas of the kidney are rare neoplasms constituting about 1-5% of all renal malignant neoplasms . These are aggressive tumors and are commonly associated with conventional ( clear cell ) renal cell carcinomas , but cases associated with chromophobe renal cell carcinomas are sparse . Cytological features of such lesions have rarely been reported . Here , we report a unique case of a 48-year-old male patient who presented with right flank lump and pain . A fine needle aspiration was performed from the lesion under ultrasound guidance and a cytological diagnosis of pleomorphic sarcoma was made . A right-sided radical nephrectomy was carried out and subsequent histopathology revealed a sarcomatoid renal cell carcinoma with wide areas of necrosis coexisting with chromophobe renal cell carcinoma with calcification . Differentiation of pleomorphic sarcoma from a sarcomatoid renal cell carcinoma is , thus , challenging from cytopathology smears and the differential diagnoses should always be borne in mind while giving a cytopathological opinion .\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: Even when patients with nonsmall cell lung cancer undergo surgical resection at an early stage , recurrent disease often impairs the clinical outcome . There are numerous causes potentially responsible for a relapse of the disease , one of them being extensive angiogenesis . The balance of at least two systems , VEGF VEGFR and Ang Tie , regulates vessel formation . The aim of this study was to determine the impact of surgery on the plasma levels of the main angiogenic factors during the first month after surgery in nonsmall cell lung cancer patients . The study group consisted of 37 patients with stage I nonsmall cell lung cancer . Plasma concentrations of Ang1 , Ang2 , sTie2 , VEGF , and sVEGF R1 were evaluated by ELISA three times : before surgical resection and on postoperative days 7 and 30 . The median of Ang2 and VEGF concentrations increased on postoperative day 7 and decreased on day 30 . On the other hand , the concentration of sTie2 decreased on the 7th day after resection and did not change statistically later on . The concentrations of Ang1 and sVEGF R1 did not change after the surgery . Lung cancer resection results in proangiogenic plasma protein changes that may stimulate tumor recurrences and metastases after early resection .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;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: E6-associated protein ( E6-AP ) is a dual function protein . It acts as an E3 ubiquitin-protein ligase enzyme and coactivator of steroid hormone receptors such as estrogen ( ERα ) and progesterone ( PR ) receptors . It promotes the degradation of ERα and PR through the ubiquitin-proteasome pathway . Furthermore , it has been shown that the levels of E6-AP are inversely associated with that of ERα in human breast tumors . But the role of wild-type human E6-AP and its ubiquitin-protein ligase activity in mammary tumorigenesis is still unknown . To investigate this role , the authors utilized transgenic mice lines that specifically overexpress either the wild-type human E6-AP ( E6-AP(WT) ) or the ubiquitin-protein ligase defective E6-AP that contains C833S mutation ( E6-AP(C833S) ) in the mammary gland . To further substantiate the role of E6-AP in the development of breast tumorigenesis , it was also examined the expression of E6-AP in a large cohort of human breast cancer samples . The transgenic mice that overexpress wild-type E6-AP ( E6-AP(WT) ) fail to develop mammary tumors . Unlike the E6-AP(WT) mice , the E6-AP(C833S) mice that overexpress ubiquitin-protein ligase defective E6-AP protein develop mammary hyperplasia with a median latency of 18months . These observations suggest that the inactivation of the ubiquitin-protein ligase function of E6-AP is sufficient to initiate the process of mammary tumor development . Furthermore , the data also suggests that E6-AP exerts its effects on target cells by modulating the protein levels and functions of ERα and PR . In addition , it was found in human breast cancer patients that the level of E6-AP is decreased in invasive breast tumors compared to normal breast tissue . Moreover , the authors also show that the survival patterns for E6-AP negative patients were worse compared to E6-AP positive patients . Taken together , these data suggests that E6-AP may act as a tumor suppressor in breast .\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: We have isolated rabbit kidney proximal tubular epithelial cell lines . The selection was based on their ability to form confluent monolayers on porous supports and to maintain receptor-mediated signal transduction and ion transport , characteristic of the proximal tubule . The isolation method consisted of several steps : ( 1 ) superficial cortical proximal tubule segments were microdissected and cultured on a matrix-coated porous support until cells formed a confluent monolayer ; ( 2 ) primary cultures showing hormone-regulated ion transport typical for the proximal tubule were selected and co-cultured with irradiated fibroblasts ; and ( 3 ) the epithelial cells surviving after several passages were expanded and passaged on porous substrates . Most of the cell lines developed in this manner were obtained by co-culture with irradiated fibroblasts producing a recombinant retrovirus encoding SV40 large T antigen and G418 resistance . However , SV40 T antigen expression was not essential for immortalization , since neither T antigen nor G418 resistance was detected in the isolated cell lines and co-culture with non-producing 3T3 cells gave similar results . One cell line ( vEPT ) has been characterized in some detail with respect to morphological , biochemical , and ion transport properties . This line forms confluent monolayers with apical microvilli , tight junctions , and convolutions of the basolateral plasma membrane . Once confluent , monolayers maintain conductances of 25 to 32 mS/cm2 for several weeks in culture and possess phlorizin-sensitive short-circuit current ( Isc ) in glucose containing media , indicative of apical Na(+)-glucose co-transport. vEPT cells also retain receptor and signaling mechanisms for angiotensin II ( Ang II ) . Apical and basal Ang II and 5,6-epoxy-eicosatrienoic acid ( 5,6-EET ) modulate the Isc in a manner similar to primary cultures . The cell lines share with primary cultures expression of the cytokeratins K8 , K10/K11 , and K19 ( \"nomenclature \" [ 21] ) . They also retain several receptor and signal transduction mechanisms . For example , Ang II , arachidonate , bradykinin , 5,6-EET , parathyroid hormone ( residues 1 through 34 ) , and purine nucleotides increase cytosolic Ca2+ , PTH elevates cAMP levels , and Ang II enhances proximal tubule-specific arachidonic acid metabolism .\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: Results generated by the immunohistochemical staining with PC10 , a new monoclonal antibody recognizing PCNA ( a nuclear protein associated with cell proliferation ) in formalin-fixed and paraffin-embedded tissue were compared with those of Ki-67 labeling and DNA flow cytometry in 47 consecutive non-small cell lung cancer ( NSCLC ) . PCNA reactivity was observed in all samples and confined to the nuclei of cancer cells . Its frequency ranged from 0 to 80% ( 37.7 +/- 23.6 ) and larger sized , early-staged and DNA aneuploid tumors expressed a significant higher number of PCNA-reactive cells . The PCNA and Ki-67 labeling rates were closely correlated ( r = 0.383 , P = 0.009 ) . By flow cytometry , we observed a good correlation among PCNA labeling and S-phase fraction ( r = 0.422 , P = .0093 ) and G1 phase ( r = 0.303 , P = .051 ) of the cell cycle . Results indicate that PCNA labeling with PC10 is a simple method for assessing the proliferative activity in formalin-fixed , paraffin-embedded tissue of NSCLC and correlates well with Ki-67 labeling and S-phase fraction of the cell cycle .\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: PURPOSE Germline mutations in BRCA1 result in a strong predisposition to breast cancer , with frequent loss of heterozygosity of the remaining wild-type allele . The development of BRCA1 tumors is likely to depend on additional genetic alterations and gene expression changes which follow growth and DNA repair defects associated with BRCA1 deficiency . The identification of these modifications offers an opportunity to find surrogate markers of BRCA1 tumors . Here , we sought to identify differentially expressed proteins related to BRCA1 depletion . EXPERIMENTAL DESIGN We used isogenic HeLa cells either stably knocked-down or not for BRCA1 ( BRCA1(KD) ) and compared protein profiles of these cells by DIGE . RESULTS We detected increased levels of Replication protein A2 ( RPA2 ) in BRCA1(KD) cells as compared to control cells . RPA2 is an essential protein required for DNA replication and repair . We further demonstrated that depletion of RPA2 subunit delays growth of BRCA1(KD) respect to isogenic control cells . Strikingly , elevated levels of RPA2 were more frequently observed in BRCA1 tumors when triple-negative tumors from BRCA1 mutation carriers ( n=13 ) and non-carriers ( n=36 ) were stained in situ for RPA2 . CONCLUSIONS AND CLINICAL RELEVANCE RPA2 up-regulation may thus be involved in the growth and/or survival of BRCA1 tumor cells and useful in immunohistochemical discrimination of triple-negative BRCA1 tumors .\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: Estrogen receptor α ( ERα ) expression in breast cancer is predictive of response to endocrine therapy ; however , resistance is common in ERα-positive tumors that overexpress the growth factor receptor ERBB2 . Even in the absence of estrogen , ERα can be activated by growth factors , including the epidermal growth factor ( EGF ) . EGF induces a transcriptional program distinct from estrogen ; however , the mechanism of the stimulus-specific response is unknown . Here we show that the EGF-induced ERα genomic targets , its cistromes , are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1 . The EGF-induced ERα cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers . This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that overexpress ERBB2 . These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα , as opposed to blocking its estrogen responsiveness alone .\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: Abstract The use of immunotherapeutics in melanoma has received much attention , and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation . Cytotoxic T lymphocyte-associated antigen 4 ( CTLA-4 ) serves as a negative regulator of immunity . Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses . Treatment with CTLA-4 blocking antibodies , however , is not without potential toxicities . Autoimmune side-effects , the most common being colitis-associated diarrhea , are frequently associated with clinical responses . In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities , we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor ( GVAX ; Cell Genesys , South San Francisco , CA , USA ) with periodic infusions of CTLA-4 blocking antibodies . This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients . Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells ( T(regs) ) . Effective anti-tumor immunity and serious autoimmunity can be disassociated . Further targeting of anti-tumor T(regs)in combinatorial therapy approaches may be a rich avenue of future investigation .\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: BACKGROUND Peritoneal transport status is important not only for prescription , but also as a prognostic index . Flt-1 and Flk-1 , the major vascular endothelial growth factor receptors involved in angiogenesis and hyperpermeability , may play a potent role in determining peritoneal transport characteristics . However , the relationship between them has not been studied to date . We hypothesized that Flt-1 and Flk-1 expression in the peritoneal vasculature of uremic patients could be closely related to baseline peritoneal transport status . METHODS Thirty-six new patients without a previous history of peritonitis were enrolled . Clinical parameters such as age , sex , height , weight , causes of renal failure , and residual renal function were assessed . Parietal peritoneal biopsies were obtained during implantation of peritoneal dialytic catheters . Flt-1 and Flk-1 were semi-quantitatively evaluated by immunohistochemical staining . Peritoneal microvascular density ( MVD ) was counted . Within 6 weeks after commencing peritoneal dialysis , a standard peritoneal equilibration test was performed , and the dialysate-to-plasma concentration ratio for creatinine at 4 h ( D4/P Cr ) was determined . The patients were divided into two groups based on the D4/P Cr : more than 0.65 ( Group H , n = 22 ) and less than or equal to 0.65 ( Group L , n = 14 ) . The 24-h peritoneal protein excretion ( PPE ) was assayed . Flt-1 and Flk-1 were correlated with peritoneal MVD , D4/P Cr , and PPE . RESULTS Flt-1 and Flk-1 were detected in the peritoneal vasculature of uremic patients . Flt-1 expression was similar between the two groups , but Flk-1 expression in Group H was significantly higher than that in Group L ( p = 0.001 ) . Flt-1 expression did not show significant correlations with peritoneal MVD , D4/P Cr , and PPE . However , Flk-1 expression showed significant correlations with the above three parameters ( p &lt ; 0.001 for all ) . CONCLUSIONS For the first time , the expressions of Flt-1 and Flk-1 in peritoneal vasculature of uremic patients were detected . Flk-1 expression in peritoneal vasculature of uremic patients is closely correlated with the number of peritoneal microvessels , peritoneal small solute transport rate , and PPE . Our findings strongly suggest that Flk-1 may be a crucial determinant of baseline peritoneal transport characteristics . Further interventional studies are needed .\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: The topoisomerase II ( topo II ) DNA incision-and-ligation cycle can be poisoned ( for example following treatment with cancer chemotherapeutics ) to generate cytotoxic DNA double-strand breaks ( DSBs ) with topo II covalently conjugated to DNA . Tyrosyl-DNA phosphodiesterase 2 ( Tdp2 ) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts . Here , X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 β-2-helix-β DNA damage-binding ' grasp ' , helical ' cap ' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove . The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing . Structural , mutational and functional analyses support a single-metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase ( EEP ) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs .\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: The \" high-risk \" human papillomavirus types 16 ( HPV-16 ) and 18 ( HPV-18 ) have been etiologically implicated in the majority of human cervical carcinomas . In these cancers , the viral DNAs are often integrated into the host genome so that expression of the E1 and the E2 genes is lost , suggesting that disruption of these regulatory genes plays an important role in carcinogenic progression . Previous studies defining the viral genes affecting HPV-16 transformation functions have used the \" prototype \" viral genome , which was cloned from a human cervical carcinoma and later discovered to harbor a mutation in the E1 gene . In this study , we have corrected this mutation and have evaluated the effect of mutations of either the E1 or the E2 gene on the efficiency of HPV-16 immortalization of human keratinocytes . Mutation of either the E1 gene or the E2 gene in the background of a \" wild-type \" HPV-16 genome markedly increased immortalization capacity . Mutations were also generated in the E2-binding sites located upstream of the P97 promoter , which directs synthesis of the viral E6 and E7 transforming genes . E2 negatively regulates the P97 promoter through binding at adjacent sites . Surprisingly , the mutation of these sites only partially relieved the negative effect of E2 on viral immortalization , implicating additional mechanisms in the E2 repression of viral immortalization functions . Our results provide genetic evidence that the E1 and E2 gene products each can repress HPV-16 immortalization and support the hypothesis that a selective growth advantage is provided by integration of the viral genome in a manner that causes the loss of expression of either E1 or E2 .\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: Radiation-induced carcinogenesis is a major concern both for astronauts on long-term space missions and for cancer patients being treated with therapeutic radiation . Exposure to radiation induces oxidative stress and chronic inflammation , which are critical initiators and promoters of carcinogenesis . Many studies have demonstrated that non-steroidal anti-inflammatory drugs and antioxidants can reduce the risk of radiation-induced cancer . In this study , we found that a synthetic triterpenoid , CDDO-Me ( bardoxolone methyl ) , was able to protect human colon epithelial cells ( HCECs ) against radiation-induced transformation . HCECs that were immortalized by ectopic expression of hTERT and cdk4 and exhibit trisomy for chromosome 7 ( a non-random chromosome change that occurs in 37% of premalignant colon adenomas ) can be transformed experimentally with one combined exposure to 2 Gy of protons at 1 GeV/nucleon followed 24 h later by 50 cGy of ( 56)Fe ions at 1 GeV/nucleon . Transformed cells showed an increase in proliferation rate and in both anchorage-dependent and independent colony formation ability . A spectrum of chromosome aberrations was observed in transformed cells , with 40% showing loss of 17p ( e.g. loss of one copy of p53 ) . Pretreatment of cells with pharmacological doses of CDDO-Me , which has been shown to induce antioxidative as well as anti-inflammatory responses , prevented the heavy-ion-induced increase in proliferation rate and anchorage-dependent and independent colony formation efficiencies . Taken together , these results demonstrate that experimentally immortalized human colon epithelial cells with a non-random chromosome 7 trisomy are valuable premalignant cellular reagents that can be used to study radiation-induced colorectal carcinogenesis . The utility of premalignant HCECs to test novel compounds such as CDDO-Me that can be used to protect against radiation-induced neoplastic transformation is also demonstrated .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Transforming growth factor beta ( TGF-β ) signaling has been implicated in driving tumor progression and metastasis by inducing stem cell-like features in some human cancer cell lines . In this study , we have utilized a novel murine cell line NMuMG-ST , which acquired cancer stem cell ( CSC ) phenotypes during spontaneous transformation of the untransformed murine mammary cell line NMuMG , to investigate the role of autocrine TGF-β signaling in regulating their survival , metastatic ability , and the maintenance of cancer stem cell characteristics . We have retrovirally transduced a dominant-negative TGF-β type II receptor ( DNRII ) into the NMuMG-ST cell to abrogate autocrine TGF-β signaling . The expression of DNRII reduced TGF-β sensitivity of the NMuMG-ST cells in various cell-based assays . The blockade of autocrine TGF-β signaling reduced the ability of the cell to grow anchorage-independently and to resist serum deprivation-induced apoptosis . These phenotypes were associated with reduced levels of active and phosphorylated AKT and ERK , and Gli1 expression suggesting that these pathways contribute to the growth and survival of this model system . More interestingly , the abrogation of autocrine TGF-β signaling also led to the attenuation of several features associated with mammary stem cells including epithelial-mesenchymal transition , mammosphere formation , and expression of stem cell markers . When xenografted in athymic nude mice , the DNRII cells were also found to undergo apoptosis and induced significantly lower lung metastasis burden than the control cells even though they formed similar size of xenograft tumors . Thus , our results indicate that autocrine TGF-β signaling is involved in the maintenance and survival of stem-like cell population resulting in the enhanced metastatic ability of the murine breast cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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 well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels . It is a complex process , involving both pro- and anti-angiogenic factors , and plays a significant role in physiological and pathophysiological processes such as embryonic development , atherosclerosis , post-ischemic vascularization of the myocardium , tumor growth and metastasis , rheumatoid arthritis etc . This is the first report of zinc oxide ( ZnO ) nanoflowers that show significant pro-angiogenic properties ( formation of new capillaries from pre-existing blood vessels ) , observed by in vitro and in vivo angiogenesis assays . The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation . Additionally , it helps to promote endothelial cell ( EA.hy926 cells ) migration in wound healing assays . Formation of reactive oxygen species ( ROS ) , especially hydrogen peroxide ( H(2)O(2))-a redox signaling molecule , might be the plausible mechanism for nanoflower-based angiogenesis . Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases , where angiogenesis plays a significant role .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;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: Aims : RAS-induced tumorigenesis has been suggested to follow a three-stage model consisting of an initial RAS activation , senescence induction , and evasion of p53-dependent senescence checkpoints . While reactive oxygen species ( ROS ) act as second messengers in RAS-induced senescence , they are also involved in oncogenic transformation by inducing proliferation and promoting mutations . In the current work , we investigated the role of extracellular superoxide dismutase ( SOD3 ) in RAS-induced senescence and immortalization in vitro and in vivo . We used a mouse embryonic fibroblast ( MEF ) primary cell model together with immortalized and transformed human cell lines derived from papillary and anaplastic thyroid cancer . Results : Based on our data , sod3 RNA interference in H-RasV12-transduced cells markedly inhibited cell growth , while sod3 over-expression in MEFs initially caused a proliferative burst followed by the activation of DNA damage checkpoints , induction of p53-p21 signal transduction , and senescence . Subsequently , sod3-transduced MEF cells developed co-operative p21-p16 down-regulation and acquired transformed cell characteristics such as increased telomerase activity , loss of contact inhibition , growth in low-nutrient conditions , and in vivo tumorigenesis . Interestingly , as reported previously with RAS , we showed a dose-dependent response to SOD3 in vitro and in vivo involving transcriptional and non-transcriptional regulatory mechanisms . Innovation : SOD3 may mediate H-RasV12-induced initiation of primary cell immortalization . Conclusions : Our results indicate that SOD3 influences growth signaling in primary and cancer cells downstream of the ras oncogene and could serve as a therapy target at an early tumorigenesis phase .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;genomic instability and mutation;tumor promoting inflammation;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 AND AIMS : Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity . We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism ( SNPs ) like TLR2 ( -196 to-174del ) , TLR3 ( C1377T ) , TLR4 ( Thr399Ile ) and TLR9 ( G2848A ) genes in patients with bladder cancer in a North Indian population . METHODS : SNPs were comprised of TLR2 ( -196 to -174 Del ) , TLR3(C1377T) , TLR4 ( Thr399Ile ) and TLR9 ( G2848A ) genes . Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer ( n=200 ) and unrelated healthy controls of similar ethnicity ( n=200 ) were genotyped by polymerase chain reaction restriction fragment length polymorphism ( PCR-RFLP ) analysis . RESULTS : In TLR2 I/D gene polymorphism , the combination of ID+DD showed a significant 3-fold increased risk ( p=0.001 ) . TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype ( ID+DD ) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer . The other genotypes of TLR3 , 4 and 9 did not exhibit any significant association with bladder cancer risk . CONCLUSIONS : Our results suggested the involvement of TLR2 ( -196 to-174 del ) in bladder cancer susceptibility ; however , TLR3 , 4 and 9 genes were not associated with risk of bladder cancer , implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer . Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma ( RCC ) patients , we compared autologous and allogeneic CD8(+) T cell responses against RCC line from RCC patients and their HLA-matched donors , using mixed lymphocyte/tumor cell cultures ( MLTCs ) . In addition , we analyzed the expression of molecules associated with cell cycle regulation . Autologous MLTC responder CD8(+) T cells showed cytotoxic activity against RCC cell lines ; however the analysis of the distribution of CD8(+) T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy . In RCC patients , a decreased proliferative response to tumor , associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle , was observed . These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8(+) effector cells . If validated , this may define a therapeutic target in the setting of patients with RCC .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

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

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Basal cell hyperplasia classically has been described as having bland cytologic features . During the past 2 years , we have seen 12 cases ( 11 in consultation ) with atypical features that were confused with adenocarcinoma of the prostate . Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma ; in the 12th case , nuclei were enlarged , hyperchromatic , and moderately pleomorphic . Immunohistochemistry with antibodies against high-molecular-weight cytokeratin ( 34 beta E12 ) was performed in nine of the cases , verifying their basal cell nature . Additional findings in these cases were necrotic intraluminal secretions ( two cases ) , immature squamous metaplasia ( two cases ) , peculiar hyaline cytoplasmic globules ( two cases ) , adenosis ( one case ) , markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen ( one case ) , and intraluminal blue mucin ( two cases ) . We analyzed nine cases of typical basal cell hyperplasia , all of which showed classic features of basal cell hyperplasia with benign cytology . Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation . Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate , prostatic intraepithelial neoplasia , and basaloid carcinoma ( adenoid cystic carcinoma ) of the prostate .\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: Dimethyl sulfoxide ( DMSO ) , a well-known differentiation inducer in several myeloid cells , also induces a reversible G(1) arrest in many cell lines . We recently showed that DMSO induces a G(1) phase arrest in Chinese hamster ovary ( CHO ) cells , by restoring contact inhibition and preventing high density-dependent apoptosis . CHO cells are frequently used in cell biology and mutagenesis studies due to their good growth capacity and ease of manipulation but are very difficult to synchronize by serum starvation since they detach from monolayers when they reach confluence . In this study we investigated the possibility of using DMSO to reversibly synchronize CHO cells in the G(1) phase of the cell cycle and analysed whether toxic effects follow the arrest using growth curve , sister chromatid exchange and micronuclei assays . We carried out a kinetic analysis of the arrest by DMSO and re-entry into the cell cycle after drug release by cytofluorimetric analysis of DNA content and bromodeoxyuridine incorporation . We show that CHO cells are efficiently and reversibly arrested in G(1) by DMSO in concentrations ranging between 1 and 2% . In our experiments , >90% of cells grown for 96 h in presence of the drug were arrested in G(1) and synchronously re-entered S phase approximately 8-12 h after release . Furthermore , expression levels of p27 were down-regulated during G(1) progression and cyclin D3 and E expression patterns were similar to those observed after serum starvation . No detectable cytotoxicity or genetic damage were induced in G(1) released cells as revealed by the tests employed . Our results show that DMSO is a very powerful inducer of G(1) synchronization in CHO cells without detectable cytotoxic or genetic effects in cell populations released from G(1) arrest . DMSO synchronization represents a model system in which to analyse protein activities regulating G(1) progression and investigate the response of G(1) cells to mutagen treatments .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors;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: p53 is a well-known transcription factor that controls cell cycle arrest and cell death in response to a wide range of stresses . Moreover , p53 regulates glucose metabolism and its mutation results in the metabolic switch to the Warburg effect found in cancer cells . Nucleotide biosynthesis is also critical for cell proliferation and the cell division cycle . Nonetheless , little is known about whether p53 regulates nucleotide biosynthesis . Here we demonstrated that p53-inducible microRNA-34a ( miR-34a ) repressed inosine 5'-monophosphate dehydrogenase ( IMPDH ) , a rate-limiting enzyme of de novo GTP biosynthesis . Treatment with anti-miR-34a inhibitor relieved the expression of IMPDH upon DNA damage . Ultimately , miR-34a-mediated inhibition of IMPDH resulted in repressed activation of the GTP-dependent Ras signaling pathway . In summary , we suggest that p53 has a novel function in regulating purine biosynthesis , aided by miR-34a-dependent IMPDH repression .\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 presence of distant metastases from colorectal cancer ( CRC ) does not preclude curative treatment . Early detection of pulmonary metastases at a potentially curable stage could improve survival . The aim of the present study was to assess the prognostic significance of commonly reported clinicopathologic features to identify high-risk patients who would likely benefit from more intensive chest surveillance for pulmonary metastases . MATERIAL AND METHOD A total of 351 consecutive patients , with surgical stages I-III colorectal cancer , who underwent curative resection at Phramongkutklao hospital from 1999 to 2005 , were followed regularly according to the established guidelines with routine physical examination , serum carcinoembryonic antigen ( CEA ) and colonoscopic surveillance . Imaging studies for detecting metastases were computed tomography ( CT ) , plain film radiography , and ultrasonograpy . Clinical and pathologic features were analyzed for their association with pulmonary metastasis . RESULTS There were 145 patients who had been operated for longer than five years after curative intent surgery . Of these , nineteen patients were lost to follow-up or died from other causes that were unrelated to colorectal cancer . Pulmonary metastases were detected in 26 patients by either CXR or CT scan . Median time to pulmonary metastasis was 19 months ( 95 percent CI , 12-35 ) . According to an univariate analysis , with log-rank test , identified four factors associated with pulmonary metastasis : Tumor stage T4 , Nodal stage N2 , elevation of serum CEA &gt ; 3.4 ng/ml and presence of lymphovascular invasion(LVI) . According to a multivariate analysis , with Cox regression , found an elevation of serum CEA &gt ; 3.4 ng/ml which was an independent factor that was significantly associated with pulmonary metastasis ( Hazard ratio ( HR ) , 8.9 ; 95 percent CI , 3.6-22 ; p &lt ; 0.01 ) . The present study revealed that 50 percent of patients who had more than one of these risk factors would eventually develop pulmonary metastases . CONCLUSION An elevation of serum CEA &gt ; or = 3.4 ng/ml was found as an independent factor that was significantly associated with pulmonary metastasis whereas tumor stage T4 , nodal stage N2 and presence of lymphovascular invasion ( LVI ) were not independent clinicopathologic features associated with subsequent pulmonary metastases . Chest CT scan has greater sensitivity than chest radiography in detection of pulmonary metastasis and should be considered as an imaging study of choice for intensive chest surveillance for patients who had more than one of these risk factors .\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: PURPOSE Recently , a new renal cell cancer syndrome has been linked to germline mutation of multiple subunits ( SDHB/C/D ) of the Krebs cycle enzyme , succinate dehydrogenase . We report our experience with the diagnosis , evaluation and treatment of this novel form of hereditary kidney cancer . MATERIALS AND METHODS Patients with suspected hereditary kidney cancer were enrolled on a National Cancer Institute institutional review board approved protocol to study inherited forms of kidney cancer . Individuals from families with germline SDHB , SDHC and SDHD mutations , and kidney cancer underwent comprehensive clinical and genetic evaluation . RESULTS A total of 14 patients from 12 SDHB mutation families were evaluated . Patients presented with renal cell cancer at an early age ( 33 years , range 15 to 62 ) , metastatic kidney cancer developed in 4 and some families had no manifestation other than kidney tumors . An additional family with 6 individuals found to have clear cell renal cell cancer that presented at a young average age ( 47 years , range 40 to 53 ) was identified with a germline SDHC mutation ( R133X ) Metastatic disease developed in 2 of these family members . A patient with a history of carotid body paragangliomas and an aggressive form of kidney cancer was evaluated from a family with a germline SDHD mutation . CONCLUSIONS SDH mutation associated renal cell carcinoma can be an aggressive type of kidney cancer , especially in younger individuals . Although detection and management of early tumors is most often associated with a good outcome , based on our initial experience with these patients and our long-term experience with hereditary leiomyomatosis and renal cell carcinoma , we recommend careful surveillance of patients at risk for SDH mutation associated renal cell carcinoma and wide surgical excision of renal tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: PURPOSE This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras ( KRAS ) gene on treatment efficacy in patients with metastatic colorectal cancer ( mCRC ) . PATIENTS Overall , 119 patients bearing a KRAS mutation in codon 12 were evaluated . All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group ( CECOG ) , AIO KRK-0104 or AIO KRK-0306 trials . RESULTS Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens . Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations ( overall survival 23.3 vs. 14-18 months ; hazard ratio 0.66 , range 0.43-1.03 ) . An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab . CONCLUSION The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy .\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: PURPOSE The epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ZD1839 ( Iressa ; AstraZeneca Pharmaceuticals , Alderley Park , United Kingdom ) is under development as an anticancer agent . We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin , an EGFR-dependent tissue , in cancer patients participating in ZD1839 phase I clinical trials . PATIENTS AND METHODS We studied 104 pre- and/or on-ZD1839 therapy ( approximately at day 28 of therapy ) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839 . We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated ( phosphorylated ) EGFR . Effects on receptor signaling ( activated mitogen-activated protein kinase [ MAPK] ) , proliferation , p27(KIP1) , and maturation were also assessed . RESULTS Histopathologically , the stratum corneum of the epidermis was thinner during therapy ( P <.001 ) . In hair follicles , prominent keratin plugs and microorganisms were found in dilated infundibula . ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells ( P <.001 ) . In addition , ZD1839 inhibited MAPK activation ( P <.001 ) and reduced keratinocyte proliferation index ( P <.001 ) . Concomitantly , ZD1839 increased the expression of p27(KIP1) ( P <.001 ) and maturation markers ( P <.001 ) and increased apoptosis ( P <.001 ) . These effects were observed at all dose levels , before reaching dose-limiting toxicities . CONCLUSION ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo . These effects were profound at doses well below the one producing unacceptable toxicity , a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: Gastrointestinal stromal tumor ( GIST ) is a prototype of mutant KIT oncogene-driven tumor . Prolonged tyrosine kinase inhibitor ( TKI ) treatment may result in a resistant phenotype through acquired secondary KIT mutation . Heat shock protein 90 ( HSP90AA1 ) is a chaperone protein responsible for protein maturation and stability , and KIT is a known client protein of HSP90AA1 . Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway . In this study , we demonstrated that NVP-AUY922 ( AUY922 ) , a new class of HSP90AA1 inhibitor , is effective in inhibiting the growth of GIST cells expressing mutant KIT protein , the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells . The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines . Surprisingly , AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway . The blockade of autophagy alone led to the accumulation of the KIT protein , highlighting the role of autophagy in endogenous KIT turnover . The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B- , acridine orange- or SQSTM1-labeled autophagosome , and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity . Therefore , the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs , but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion . The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined . Previous reports have suggested that MDSC may contribute to Treg induction in cancer . Herein , we provide evidence that tumor-induced gr-MDSCs , endowed with the potential of suppressing conventional T Lc , surprisingly impair TGF-β1-mediated generation of CD4(+)CD25(+)FoxP3(+) iTregs . Furthermore , gr-MDSCs impede the proliferation of nTregs without , however , affecting FoxP3 expression . Suppression of iTreg differentiation from na�ve CD4(+) cells by gr-MDSC occurs early in the polarization process , requires inhibition of early T cell activation , and depends on ROS and IDO but does not require arginase 1 , iNOS , NO , cystine/cysteine depletion , PD-1 and PD-L1 signaling , or COX-2 . These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;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 role of energy deregulation and altered/adapted metabolism in tumor cells is an increasingly important issue in understanding cancer . Hereditary leiomyomatosis and renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of fumarate hydratase ( FH ) , followed by somatic loss of the remaining wild-type allele and known to be a highly metastatic and lethal malignancy compared to other RCCs . The intrinsic loss of normal tricarboxylic acid ( TCA ) cycle presumably aids tumorigenesis due to the necessary metabolic alterations required and the enforced dependence on glycolysis derived energy , mimicking the Warburg effect . Thus , there is considerable utility in establishing a preclinical cell model from these tumors to study energy metabolism deregulation , as well as developing new targeted therapeutic approaches for TCA cycle enzyme-deficient cancers . Here , we describe a new immortalized cell line , UOK268 , derived from a patient's primary HLRCC-associated kidney cancer . This represents the first primary renal cell line to model TCA cycle gene loss and provides a perfect partner cell line to our previously described metastasis-derived HLRCC-associated cell line , UOK262 . We identified a novel germline FH missense mutation , p.His192Asp , and the subsequent loss of heterozygosity in UOK268 . The UOK268 cell line expressed mutant FH protein , which localized to the mitochondria , but with loss of almost all catalytic activity . The UOK268 cells had severely compromised oxidative phosphorylation and increased glycolytic flux . Ingenuity pathways analysis of human mitochondria-focused cDNA microarray ( hMitChip3 ) gene chip data confirmed the altered mRNA expression patterns of genes involved in several important pathways , such as lipid metabolism , apoptosis , and energy production/glycolysis . UOK268 provides a unique model of a primary cell line demonstrating an enforced , irreversible Warburg effect and , combined with UOK262 , provides a unique invitro preclinical model for studying the bioenergetics of the Warburg effect in human cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;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: The suppression of MAPK and oxidative stress could be an important anti-inflammatory mechanism . Fucoidan regulates MAPK activity in several cell lines . However , the mechanism for the anti-inflammatory and oxidative stress effect of low molecular weight fucoidan ( LMWF ) is poorly understood in RAW264.7 cells . The objective of this study was to examine the critical role of LMWF during LPS-induced inflammation in RAW264.7 cells . To determine the potential role of LMWF , we analysed pro-inflammatory cytokine , transcription factor , inflammation-related and oxidative stress related protein expression in vitro during LPS-induced inflammation in RAW264.7 cells . In this study , we demonstrated the anti-inflammatory effects of LMWF on LPS-induced inflammation in macrophages through the regulation of signalling pathways , including its effect on the attenuation of inflammatory cytokines , such as IL-1β , IL-1 and TNF-α , and the degradation of phosphorylated p38 MAPK , ERK1/2 and JNK . This study also demonstrates that LMWF might block NO as well as the expression of reactive oxygen species ( ROS ) , which subsequently inhibits the iNOS and COX-2 expression induced by LPS . Based on these findings , we suggest that LMWF might have great potential as an external pathogen prevention and intervention agent for inflammatory diseases .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "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 Epithelial mesenchymal transition ( EMT ) is known to be associated with chemoresistance as well as increased invasion/metastasis . However , the relationship between EMT and resistance to an epidermal growth factor receptor ( EGFR ) -targeting drug in head and neck squamous cell carcinoma ( HNSCC ) remains unknown . In this study , we investigated the acquisition of EMT by gefitinib in HNSCC cell line ( UMSCC81B ) . METHODS We isolated fibroblastoid variant ( 81B-Fb ) from gefitinib-resistant UMSCC81B-GR3 cells obtained after increasing the doses of gefitinib treatment in vitro and examined EMT and its underlying mechanism . RESULT 81B-Fb cells exhibited fibroblast-like morphology , increased motility , loss of E-cadherin , acquisition of vimentin and snail expression . In 81B-Fb cells , downregulation of EGFR , which is mediated by increased ubiquitination , and activation of downstream protein kinase B ( Akt ) , glycogen synthase kinase-beta ( GSK-3β ) signalling and upregulation of snail expression were observed compared with UMSCC81B cells . LY294002 , but not U0126 , suppressed foetal bovine serum or heregulin-β1-induced phosphorylation of Akt/GSK-3β and snail expression together with the inhibition of 81B-Fb cell motility . Furthermore , forced expression of EGFR resulted in partial restoration of gefitinib sensitivity and reversal of EMT . CONCLUSION These results suggest that EMT in the gefitinib-resistant cells is mediated by the downregulation of EGFR and compensatory activation of Akt/GSK-3β/snail pathway .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: Hypoxia–reoxygenation ( HR ) is a primary driver of angiogenesis in both atherogenesis and tumorigenesis . The main target of hypoxia-driven proangiogenic signaling is adherens junctions responsible for contact inhibition of endothelial cells . We analyzed the effects of hypoxia ( 8–12 hours ) followed by a brief period of reoxygenation ( 2 hours ) ( HR ) on angiogenesis and integrity of adherens junction in cultured human umbilical vein endothelial cells as well as the effects of aspirin on modulation of human umbilical vein endothelial cells ' response to HR . Cells exposed to HR displayed considerable enhancement of tube formation ( angiogenesis ) on matrigel . Immunocytostaining of near-confluent cells revealed that HR caused disruption of adherens junctions and internalization of their components VE-cadherin , p120 catenin , and b-catenin . Additionally , HR resulted in the appearance of binucleated cells , and VE-cadherin in colocalization with b-catenin was found to be positioned between the separating nuclei . Presence of aspirin ( acetylsalicylic acid , 1 mM ) resulted in preservation of adherens junctions on the cellular membrane and prevented angiogenesis as well as mitosis . HR caused upregulation LOX-1 , the p47(phox) subunit of NADPH , while reducing transcription of endothelial nitric oxide synthase . Aspirin had no effect on endothelial nitric oxide synthase and canceled the transcriptional activation of the LOX-1 and p47(phox) subunit of NADPH oxidase . Based on these data , we hypothesize that aspirin preserves the integrity of adherens junctions and thus blunts angiogenic response to HR through downregulation of LOX-1 and the LOX-1-mediated p47(phox) component of NADPH oxidase transcription , thus preventing NADPH oxidase assembly and function .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Dichlorvos , an organophosphate ( OP ) , is known to cause oxidative stress in the central nervous system ( CNS ) . Previously we have shown that dichlorvos treatment promoted the levels of proinflammatory molecules and ultimately induced apoptotic cell death in primary microglial cells . Here we studied the effect of dichlorvos on crucial cell cycle regulatory proteins and the DNA damage sensor ataxia-telangiectasia mutated ( ATM ) . We found a significant increase in p53 and its downstream target , p21 , levels in dichlorvos-treated microglial cells compared with control cells . Moreover , dichlorvos exposure promoted the levels of different cell cycle regulatory proteins . These results along with flow cytometry results suggested that primary microglial cells were arrested at G1 and G2/M phase after dichlorvos exposure . We have shown in a previous study that dichlorvos can induce DNA damage in microglia ; here we found that microglial cells also tried to repair this damage by inducing a DNA repair enzyme , i.e. , ATM . We observed a significant increase in the levels of ATM after dichlorvos treatment compared with control .\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: Reactive oxygen species ( ROS ) produced by phagocytic cells induce oxidative stress during chronic inflammation . ROS play a role in the pathogenesis of a broad range of diseases including autoimmune , cardiac and neoplastic abnormalities . We found that sera of patients with a variety of inflammatory dermatoses contain elevated levels of antibodies ( Ab ) binding to an oxidized DNA base derivative , 5-hydroxymethyl-2'deoxyuridine ( HMdU ) coupled to bovine serum albumin , as determined by the enzyme-linked immunosorbent assay . Patients with immune complex diseases and a history of neoplasm elaborated the highest titers of anti-HMdU Ab . Titers from sera of psoriatic subjects were lower than from the aforementioned groups but were still significantly elevated ( p &lt ; 0.001 ) above those of healthy controls . Treatment of inflammatory dermatoses with systemic antiinflammatory and cytotoxic drugs significantly lowered the titers [ p &lt ; 0.005 ( immune complex ) or p &lt ; 0.001 ( psoriasis and neoplastic ) diseases ] , suggesting that this assay may be of value in monitoring the response to therapy in these diseases .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: UNLABELLED BACKGROUND We aimed to develop a mouse spontaneous liver metastasis model from an orthotopically implanted human colon cancer cell line stably expressing a human sodium/iodide symporter ( NIS ) reporter gene , which can be imaged with single-photon emission computed tomography ( SPECT ) using 99mTcO4- . METHODS A recombinant plasmid containing a constitutively driven NIS gene ( pcDNA3-NIS ) was transfected into the human colon cancer cell line HCT116 , and stable cell lines were established . The stable cells were subcutaneously injected into the nude mice . When the diameter reached 10 mm , the xenografts were excised , cut into small fragments , and orthotopically implanted into the cecal walls of another nude mice. 99mTcO4- SPECT/CT imaging was initiated 8 weeks later and repeated every 1 to 2 weeks . RESULTS The production and function of NIS protein was confirmed in vitro by Western blotting and 99mTcO4- uptake assay . On SPECT/CT imaging , focal 99mTcO4- uptake was detected in the liver . Necropsy revealed local growth of the orthotopic colon xenografts with extensive invasion , microscopic serosal metastasis , and metastatic foci in the corresponding hepatic regions showing focal 99mTcO4- uptake . Immunohistochemistry revealed high levels of NIS expression in cells forming liver tumor , indicating that the liver tumor cells originated from the orthotopic colon xenografts . CONCLUSIONS The present proof-of-concept study provided a rationale for employing a radionuclide reporter gene for the specific visualization of spontaneous liver metastasis in living mice . This unique animal model of clinically relevant and externally detectable liver metastasis will be a powerful tool for investigating tumor biology and developing novel therapies for cancer metastasis .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Adenosine receptors ( A1 , A2A , A2B , A3 ) play an important role in the regulation of growth , proliferation and death of cancer and normal cells . We recently showed the expression profile of A2A and A2B receptors in normal and tumor breast tissues . In the present study , we used semiquantitative RT-PCR to measure the A1 and A3 gene expression levels in normal and tumor breast tissues . METHODS Breast tumors ( n = 18 ) and non-neoplastic mammary tissues ( n = 10 ) were collected and histologically confirmed to be neoplastic or non-neoplastic , respectively . Total RNA was extracted and reverse transcribed into cDNA , and PCR was performed under optimized condition for each receptor subtype . Amplification of beta-actin mRNA served as control for RT-PCR . The PCR products were separated on 1.7% agarose gels . The intensity of the bands was quantitated with ImageJ software after normalization against beta-actin expression . RESULTS All breast tumor and normal tissue specimens expressed A1 and A3 adenosine receptor transcripts . However , we observed that the expression level of the A3 receptor in tumor tissues was 1.27-fold that of normal tissues , whereas there was no significant difference between the expression levels of A1 in normal and tumor tissues . CONCLUSIONS Interestingly , the results of the present study indicate that breast tumors exhibit a higher level of A3 transcripts ( than normal tissues ) and support the possible key role of A3 adenosine receptor in tumor development . However , further studies based on real-time quantitative RT-PCR are needed to identify the exact gene expression levels .\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 phosphatidylinositol-3-kinase ( PI3K)/Akt oncogenic pathway is critical in glioblastomas . Loss of PTEN , a negative regulator of the PI3K pathway or activated PI3K/Akt pathway that drive increased proliferation , survival , neovascularization , glycolysis , and invasion is found in 70%-80% of malignant gliomas . Thus , PI3K is an attractive therapeutic target for malignant glioma . We report that a new irreversible PI3K inhibitor , PX-866 , shows potent inhibitory effects on the PI3K/Akt signaling pathway in glioblastoma . PX-866 did not induce any apoptosis in glioma cells ; however , an increase in autophagy was observed . PX-866 inhibited the invasive and angiogenic capabilities of cultured glioblastoma cells . In vivo , PX-866 inhibited subcutaneous tumor growth and increased the median survival time of animals with intracranial tumors . We also assessed the potential of proton magnetic resonance spectroscopy ( MRS ) as a noninvasive method to monitor response to PX-866 . Our findings show that PX-866 treatment causes a drop in the MRS-detectable choline-to-NAA , ratio and identify this partial normalization of the tumor metabolic profile as a biomarker of molecular drug action . Our studies affirm that the PI3K pathway is a highly specific molecular target for therapies for glioblastoma and other cancers with aberrant PI3K/PTEN expression .\n OUTPUT:\n" }, { "from": "agent", "value": "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: Hesperetin , a flavonoid from citrus fruits , has several bioactivities such as anti-inflammatory , antihypertensive , antiatherogenic effects . However , studies elucidating the role and the mechanism(s) of action of hesperetin in cervical cancer are sparse . In this study , we investigated the mechanism of the antiproliferative and apoptotic actions exerted by hesperetin on human cervical cancer SiHa cells . The viability of SiHa cells was evaluated using the MTT assay , apoptosis by acridine orange/ethidium bromide , propidium iodide , TUNEL assay , and Annexin V-Cy3 , cell cycle distribution and mitochondrial transmembrane potential using flow cytometry , and apoptotic marker genes using quantitative real-time PCR . The treatment of SiHa cells with hesperetin ( IC(50,) 650μm ) showed a marked concentration- and time-dependent inhibition of proliferation and induced the G2/M phase in a dose-dependent manner after 24h . There was an attenuation of mitochondrial membrane potential with increased expression of caspase-3 , caspase-8 , caspase-9 , p53 , Bax , and Fas death receptor and its adaptor protein Fas-associated death domain-containing protein ( FADD ) , indicating the participation of both death receptor- and mitochondria-related mechanisms . Furthermore , hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3 . This study shows that hesperetin exhibits a potential anticancer activity against human cervical cancer cell lines in vitro through the reduction in cell viability and the induction of apoptosis . Altogether , these data sustain our contention that hesperetin has anticancer properties and merits further investigation as a potential therapeutic agent .\n OUTPUT:\n" }, { "from": "agent", "value": "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: Infection by Opisthorchis viverrini , a risk factor for cholangiocarcinoma ( CCA ) may act through chronic inflammation , oxidative stress and lipid peroxidation ( LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine ( epsilondA ) , and 3,N4-etheno-2'-deoxycytidine ( epsilondC ) , markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients . In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model , in O. viverrini-infected hamsters that had received N-nitrosodimethylamine ( NDMA , 12.5 ppm in dw ) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method , from 21 up to 180 days post-O. viverrini-infection . In inflamed areas of the liver , etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct . Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters , treated with or w/o NDMA when compared with untreated controls . Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters . Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development . Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase ( ALP ) activity , bile duct hyperplasia , dysplasia , precancerous lesions , and CCA appearance . Also elevated expression of alkyladenine DNA glycosylase ( AAG ) , which excises 1,N6-ethenoadenine ( epsilonA ) was linked to higher adduct formation , suggesting imbalanced repair . Our results implicate accumulation of inflammation-related , promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence . Consistent with this role , p21 is a downstream target of several tumour suppressors and oncogenes , and it is downregulated in the majority of tumours , including breast cancer . Here , we report that protein arginine methyltransferase 6 ( PRMT6 ) , a type I PRMT known to act as a transcriptional cofactor , directly represses the p21 promoter . PRMT6 knock-down ( KD ) results in a p21 derepression in breast cancer cells , which is p53-independent , and leads to cell cycle arrest , cellular senescence and reduced growth in soft agar assays and in severe combined immunodeficiency ( SCID ) mice for all the cancer lines examined . We finally show that bypassing the p21-mediated arrest rescues PRMT6 KD cells from senescence , and it restores their ability to grow on soft agar . We conclude that PRMT6 acts as an oncogene in breast cancer cells , promoting growth and preventing senescence , making it an attractive target for cancer therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize ; they have been called metastasizing mixed tumor ( MZMT ) of salivary glands . We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT . At the time of discovery of metastatic disease , the patients , six women and five men , ranged in age from 20 to 83 years . Primary sites of involvement included the parotid gland ( eight cases ) , submandibular gland ( two cases ) , and the nasal septum ( one case ) . With one exception , all the patients had at least a single recurrences of their primary mixed tumor , but two or more recurrences were the norm before development of metastatic foci . The metastases were discovered from six to 52 years following the occurrence of the primary tumor . Metastatic deposits were identified in bone , lung , regional lymph nodes , skin , kidney , retroperitoneum , oral cavity , pharynx , calvarium , and central nervous system . The metastases either occurred simultaneously with an episode of recurrent mixed tumor ( n = 5 ) or from 5 to 29 years after a recurrence ( n = 6 ) . The treatment of the primary , recurrent , and metastatic neoplasms was surgical excision . Follow-up , ranging from 8 months to 16 years following the diagnosis of MZMT , revealed seven patients to be alive without disease ( 64% ) and two dead of causes unrelated to metastatic disease ( 18% ) . Two patients ( 18% ) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors . Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases . Aneuploid DNA cell content was identified in two of the cases . DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors . Retrospective analysis of histologic parameters ( mitotic rate , cellular pleomorphism , infiltrative growth , vascular or lymphatic invasion ) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease ( LPD ) secondary to organ/bone marrow transplant-related immunosuppression ( 30 : 11 liver , 10 heart/lung , 8 kidney and 1 bone marrow ) , other drug-induced immunosuppression ( 2 ) , congenital immunodeficiency ( 8 ) or human immunodeficiency virus ( HIV)-related immune dysfunction ( 2 ) . Ages ranged from 10 months to 17 years and there were 15 girls . Pathology was centrally reviewed and showed polymorphic features in 5 cases , monomorphic in 23 , mixed pattern in 5 patients and 9 other types . Using the Revised European-American Classification of Lymphoid Neoplasms , 5 were B lymphoblastoid , 24 were high-grade B and 14 were other subtypes . Using the Pittsburgh classification , 9 were lymphadenopathic , 10 were systemic , 25 were lymphomatous and , with the Murphy grouping for non-Hodgkin's lymphoma ( NHL ) , 10 were localized and 32 non-localized . Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive . Thirty-five patients were evaluable for clonality ; 24 were monoclonal and 11 were polyclonal . Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24 , which was sustained in 11 . Nineteen patients received chemotherapy , 14/18 evaluable responded , which was sustained in 8 cases . Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died . In the largest group of patients , solid organ transplants , no significant clinical or biological characteristics that predicted outcome were identified . In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective .\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: The number of renal cancers has increased over the last ten years and patient survival in advanced stages remains very poor . Therefore , new therapeutic approaches for renal cancer are essential . Englerin A is a natural product with a very potent and selective cytotoxicity against renal cancer cells . This makes it a promising drug candidate that may improve current treatment standards for patients with renal cancers in all stages . However , little is known about englerin A's mode of action in targeting specifically renal cancer cells . Our study is the first to investigate the biological mechanism of englerin A action in detail . We report that englerin A is specific for renal tumor cells and does not affect normal kidney cells . We find that englerin A treatment induces necrotic cell death in renal cancer cells but not in normal kidney cells . We further show that autophagic and pyroptotic proteins are unaffected by the compound and that necrotic signaling in these cells coincided with production of reactive oxygen species and calcium influx into the cytoplasm . As the first study to analyze the biological effects of englerin A , our work provides an important basis for the evaluation and validation of the compound's use as an anti-tumor drug . It also provides a context in which to identify the specific target or targets of englerin A in renal cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Anti-angiogenic treatment of glioblastoma characteristically results in therapy resistance and tumor progression via diffuse infiltration . Monitoring tumor progression in these patients is thwarted because therapy results in tumor invisibility in contrast-enhanced ( CE ) MRI . To address this problem , we examined whether tumor progression could be monitored by metabolic mapping using ( 1)H MR spectroscopic imaging ( MRSI ) . METHODS We treated groups of BALB/c nu/nu mice carrying different orthotopic diffuse-infiltrative glioblastoma xenografts with bevacizumab ( anti-vascular endothelial growth factor [ VEGF ] antibody , n = 13 ) , cabozantinib ( combined VEGF receptor 2/c-Met tyrosine kinase inhibitor , n = 11 ) , or placebo ( n = 15 ) and compared CE-MRI with MRS-derived metabolic maps before , during , and after treatment . Metabolic maps and CE-MRIs were subsequently correlated to histology and immunohistochemistry . RESULTS In vivo imaging of choline/n-acetyl aspartate ratios via multivoxel MRS is better able to evaluate response to therapy than CE-MRI . Lactate imaging revealed that diffuse infiltrative areas in glioblastoma xenografts did not present with excessive glycolysis . In contrast , glycolysis was observed in hypoxic areas in angiogenesis-dependent compact regions of glioma only , especially after anti-angiogenic treatment . CONCLUSION Our data present MRSI as a powerful and feasible approach that is superior to CE-MRI and may provide handles for optimizing treatment of glioma . Furthermore , we show that glycolysis is more prominent in hypoxic areas than in areas of diffuse infiltrative growth . The Warburg hypothesis of persisting glycolysis in tumors under normoxic conditions may thus not be valid for diffuse glioma .\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: Mesenchymal stem cells ( MSCs ) are generally used in tissue engineering , regenerative medicine and therapy for immune disorder disease . MSCs are also employed as drug carriers for tumor therapy due to their ability to migrate to tumor tissue . However , due to the immunosuppressive function of MSCs , the application of MSCs in prostate cancer therapy remains limited . In this study , we investigated the underlying mechanism by which MSCs enable prostate cancer cells to escape from immune surveillance in the inflammatory microenvironment . Firstly , we demonstrated that compared with the control groups , MSCs pretreated with IL-1α effectively promoted the growth of the mouse prostate cancer cell line RM-1 invivo . Furthermore , when RM-1 prostate cancer cells were co-injected with MSCs pretreated with IL-1α , tumor incidence significantly increased in allogeneic recipients . In addition , we investigated the mechanism through which MSCs promote the ability of RM-1 cells to escape from immune injury . The results revealed that IL-1α led to the upregulation of TGF-β in MSCs . The inflammatory cytokine-induced promotive effect of MSCs on RM-1 cells in vivo was inhibited by TGF-β siRNA . The results of our study suggest that inflammatory cytokines induce the immunosuppressive function of MSCs which enables prostate cancer cells to escape from immune injury .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;tumor promoting inflammation;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: When the prostate cancer cells become unresponsive to androgen therapy , resistance to chemotherapy becomes imminent , resulting in high mortality . To combat this situation , lycopodine , a pharmacologically important bioactive component derived from Lycopodium clavatum spores , was tested against hormone sensitive ( LnCaP ) and refractory ( PC3 ) prostate cancer cells in vitro . This study aims to check if lycopodine has demonstrable anti-cancer effects and if it has , to find out the possible mechanism of its action . The MTT assay was performed to evaluate the cytotoxic effect . Depolarization of mitochondrial membrane potential , cell cycle , EGF receptor activity and apoptosis were recorded by FACS ; profiles of different anti- and pro-apoptotic genes and their products were studied by semi-quantitative RT-PCR , indirect-ELISA , western blotting . Drug-DNA interaction was determined by CD spectroscopy . Administration of lycopodine down-regulated the expression of 5-lipoxygenase and the 5-oxo-ETE receptor ( OXE receptor1 ) and EGF receptor , and caused up-regulation of cytochrome c with depolarization of mitochondrial inner membrane potential , without palpable change in p53 activity , resulting in apoptosis , cell arrest at G0/G1 stage and ultimately reduced proliferation of cancer cells ; concomitantly , there was externalization of phosphotidyl serine residues . CD spectroscopic analysis revealed intercalating property of lycopodine with DNA molecule , implicating its ability to block cellular DNA synthesis . The overall results suggest that lycopodine is a promising candidate suitable for therapeutic use as an anti-cancer drug .\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: Genomic instability drives tumorigenesis , but how it is initiated in sporadic neoplasias is unknown . In early preneoplasias , alterations at chromosome fragile sites arise due to DNA replication stress . A frequent , perhaps earliest , genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus , leading to loss of Fhit protein expression . Because common chromosome fragile sites are exquisitely sensitive to replication stress , it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products . Here , we show in normal , transformed , and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks . Using DNA combing , we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse . The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels ; notably , restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells . Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest , allowing continued cell proliferation and ongoing chromosomal instability . This finding was in accord with in vivo studies , as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci . Furthermore , cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications , including amplification of the Mdm2 gene , suggesting that Fhit loss-induced genome instability facilitates transformation . We propose that loss of Fhit expression in precancerous lesions is the first step in the initiation of genomic instability , linking alterations at common fragile sites to the origin of genome instability .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling;enabling replicative immortality" } ]