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clinicalnlplab

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Clinical NLP Lab 29

[ { "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 widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment ( as well as their accumulation in human adipose tissue ) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity . A variety of musk fragrances were tested using the E-screen assay . A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks ( musk xylene , musk ketone ) , a major metabolite of musk xylene ( p-amino-musk xylene ) , and the polycyclic musk fragrance AHTN . This indicates that these substances do , in fact , demonstrate estrogenic activity . Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated . It must be noted , however , that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol . The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances , a group of substances that have not yet been well characterized in respect to their toxicological properties , has also been shown to be weakly estrogenically active in vitro . E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK , the macrocyclic musk fragrances ethylene brassylate , ethylene dodecandioate , and cyclopentadecanolide , are not estrogenically active .\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: Oxazaphosphorines are a class of DNA alkylating agents . The aim of the present study was to compare the possible influence of three new generation oxazaphosphorines , D-17272 ( mafosfamide cyclohexylamine salt ) , D-18864 ( 4-hydro-peroxy-cyclophosphamide ) , and D-19575 ( glufosfamide , beta-D-glucose-isophosphoramide mustard ) on DNA damage induction in the human histiocytic lymphoma U937 cells . The flow cytometry APO-BRDU assay , based on the TUNEL method , was used for the in situ detection of DNA strand breaks . After exposure of U937 cells to the oxazaphosphorines , the patterns of temporary changes in the frequency of TUNEL positive U937 cells , expressing DNA breakage , were determined . The effects of the oxazaphosphorines on U937 cells were dependent on the agent tested and its dose , and the time intervals after the drug application . The different potential of D-17272 , D-18864 and D-19575 to induce DNA strand breakage in the human histiocytic lymphoma U937 cells was shown .\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: Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity . Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled . Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profiles closely resembling mature human mammary luminal cell signatures . We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer . Chaos3 tumors underwent recurrent copy number alterations ( CNAs ) , particularly deletion of the RAS inhibitor Neurofibromin 1 ( Nf1 ) in nearly all cases . These overlap with human CNAs including NF1 , which is deleted or mutated in 27.7% of all breast carcinomas . Chaos3 mammary tumor cells exhibit RAS hyperactivation and increased sensitivity to RAS pathway inhibitors . These results indicate that spontaneous NF1 loss can drive breast cancer . This should be informative for treatment of the significant fraction of patients whose tumors bear NF1 mutations .\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: Epidemiological studies exploring the connection between hypertension and cancer incidence find a higher cancer mortality in hypertensive patients , particularly elevated in hypertension associated with a stimulation of the renin-angiotensin-aldosterone system . Primary aldosteronism , with plasma aldosterone levels between 0.5 and 1 nM ( 18-36 ng/dL ) and local aldosterone levels up to 500 nM ( 18,000 ng/dL ) , is now recognised as a more common cause for hypertension . We recently found angiotensin II to be genotoxic due to its induction of oxidative stress . Since aldosterone in higher concentrations also has oxidative effects , its potential genotoxic action in pig LLC-PK1 cells with properties of proximal tubules was analysed . DNA damage was evaluated by two test systems : the comet assay , and the micronucleus frequency test . The results showed that aldosterone concentrations starting from 10 nM ( 360 ng/dL ) caused a significant increase of DNA damage monitored with the comet assay in LLC-PK1 , while there was no change in cell vitality and proliferation . The micronucleus frequency test revealed that 10 nM aldosterone also leads to the formation of micronuclei . Furthermore , the formation of superoxide radicals in the cells by this aldosterone concentration could be detected with the superoxide-specific stain dihydroethidium . Further evidence for oxidative stress-induced DNA damage was its reversibility by the antioxidants tempol and catalase . Addition of the steroidal mineralocorticoid receptor antagonist spironolactone or the novel selective nonsteroidal antagonist ( R)-BR-4628 reduced the DNA damage and the amount of superoxide radicals indicating a receptor-dependent process .\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: Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis . The possibility was tested that interleukin-8 ( IL-8 ) , which is a cytokine that is chemotactic for lymphocytes and neutrophils , is also angiogenic . Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells . Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha . An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity . These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis , tumor growth , and wound repair .\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: Mitochondrial biogenesis , which depends on nuclear as well as mitochondrial genes , occurs in response to increased cellular ATP demand . The nuclear transcriptional factors , estrogen-related receptor alpha ( ERRalpha ) and nuclear respiratory factors 1 and 2 , are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis , whereas coactivators of the peroxisome proliferator-activated receptor gamma coactivator-1 ( PGC-1 ) family serve as mediators between the environment and this machinery . In the context of proliferating cells , PGC-1-related coactivator ( PRC ) is a member of the PGC-1 family , which is known to act in partnership with nuclear respiratory factors , but no functional interference between PRC and ERRalpha has been described so far . We explored three thyroid cell lines , FTC-133 , XTC.UC1 and RO 82 W-1 , each characterized by a different mitochondrial content , and studied their behavior towards PRC and ERRalpha in terms of respiratory efficiency . Overexpression of PRC and ERRalpha led to increased respiratory chain capacity and mitochondrial mass . The inhibition of ERRalpha decreased cell growth and respiratory chain capacity in all three cell lines . However , the inhibition of PRC and ERRalpha produced a greater effect in the oxidative cell model , decreasing the mitochondrial mass and the phosphorylating respiration , whereas the nonphosphorylating respiration remained unchanged . We therefore hypothesize that the ERRalpha-PRC complex plays a role in arresting the cell cycle through the regulation of oxidative phosphorylation in oxidative cells , and through some other pathway in glycolytic cells .\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: IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy . Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality . This study tested the ability of IL-15 to block apoptosis , prevent immunosuppression , and improve survival in sepsis . Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia . The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle . In addition to survival studies , splenic cellularity , canonical markers of activation and proliferation , intracellular pro- and antiapoptotic Bcl-2 family protein expression , and markers of immune cell apoptosis were evaluated by flow cytometry . Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo . IL-15 blocked sepsis-induced apoptosis of NK cells , dendritic cells , and CD8 T cells . IL-15 also decreased sepsis-induced gut epithelial apoptosis . IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA . IL-15 increased both circulating IFN-gamma , as well as the percentage of NK cells that produced IFN-gamma . Finally , IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia . In conclusion , IL-15 prevents two immunopathologic hallmarks of sepsis , namely , apoptosis and immunosuppression , and improves survival in two different models of sepsis . IL-15 represents a potentially novel therapy of this highly lethal disorder .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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: OBJECTIVE To study the effect of anandamide ( AEA ) on necrosis in HepG2 cells and to explore the role of AEA in progression of liver cancer . METHODS Localization of the fatty acid hydrolytic enzyme ( FAAH ) , cannabinoid receptors 1(CB1) and cannabinoid receptors 2 ( CB2 ) proteins was detected in L02 and HepG2 cells using immunofluorescence . L02 and HepG2 cells were treated with different concentrations of AEA and methyl-beta-cyclodextrin , and the rates of cells necrosis were examined by PI stain . Meanwhile , the expression levels of FAAH , CB1 and CB2 receptor proteins , as well as P38 mitogen-activated protein kinase ( p-P38 MAPK ) and c-Jun-NH2-terminal kinase ( p-JNK ) proteins , were analyzed by Western blot . RESULTS The FAAH , CB1 and CB2 receptor proteins were observed both in cytoplasm and on membrane in L02 and HepG2 cells . The expression level of FAAH protein was higher in HepG2 than in L02 cells . The expression level of CB1 receptor protein was very low in both L02 and HepG2 cells . The expression level of CB2 receptor protein was high in both L02 and HepG2 cells . AEA treatment induced necrosis in HepG2 cells but not in L02 cells . Methyl-beta-cyclodextrin treatment prevented necrosis in HepG2 cells ( t = 3.702 ; 5.274 ; 3.503 , P less than 0.05 ) . The expression patterns of FAAH , CB1 and CB2 receptor protein in L02 and HepG2 cells were confirmed by western blot , which were consistent with the immunofluorescence results . AEA treatment increased the levels of p-P38MAPK and p-JNK proteins in a dose-dependent manner in HepG2 cells ( F = 11.908 ; 26.054 , P less than 0.05 ) and the increase can be partially by prevented by MCD ( t = 2.801 ; t = 12.829 , P less than 0.05 ) . CONCLUSION AEA treatment induces necrosis in HepG2 cells via CB1 and CB2 receptors and lipid rafts .\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: Capillary endothelial cells can be induced to form capillary-like structures in vitro by plating on fibronectin-coated dishes ( Ingber , D. E. , and Folkman , J . ( 1989 ) J. Cell Biol. 109 , 317-330 ) , thereby mimicking angiogenesis . To assess the role of glycoproteins bearing asparagine-linked oligosaccharides in this process , we tested the effect of oligosaccharide processing inhibitors on the formation of capillary tubes . Deoxymannojirimycin , a compound that prevents synthesis of hybrid and complex-type oligosaccharides , inhibited the formation of capillary tubes . In contrast , swainsonine , an inhibitor that blocks synthesis of complex- but not hybrid-type oligosaccharides , did not inhibit tube formation . Lectin affinity chromatography of 2-[3H] mannose-labeled glycopeptides from endothelial cells induced to form tubes did not reveal a striking difference in the spectrum of oligosaccharides compared to uninduced cells . Since endothelial cells formed tubes normally in the presence of swainsonine , we analyzed glycopeptides from swainsonine-treated induced and uninduced cells . Cells induced to form tubes were enriched in monosialylated hybrid-type oligosaccharides sensitive to alpha-fucosidase , beta-galactosidase , and beta-N-acetylhexosaminidase , suggestive of sialyl Lewis-X determinants . We used an enzyme-linked immunoassay to measure sialyl Lewis-X epitopes on capillary endothelial cells and found that both induced and uninduced cells expressed sialyl Lewis-X epitopes . Deoxymannojirimycin and , to a lesser extent , swainsonine reduced the level of sialyl Lewis-X epitopes in cells induced to form capillary tubes , but neither compound affected the level of epitopes in cell monolayers . We conclude that synthesis of at least hybrid-type oligosaccharides is required for capillary tube formation in vitro and that an increase in monosialylated , fucosylated glycans on asparagine-linked oligosaccharides occurs during this process .\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: Cytokines are known to play an important role in host defense by regulating the function , growth , and differentiation of the cells of the immune system . We hypothesize that , in the tumor microenvironment , tumor cells and resident tissue cells ( e.g. , fibroblasts ) also produce cytokines that may regulate the local immune response to tumors . Initially , homogenates of eight head and neck squamous cell carcinomas ( HNSCC ) were assayed for the presence of interleukin-1 ( IL-1 ) , interleukin-4 ( IL-4 ) , interleukin-6 ( IL-6 ) , and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) to establish the presence of these cytokines in the tumors in vivo . We detected IL-1 in all tumor homogenates and IL-4 , IL-6 , and GM-CSF in some homogenates . To assess the ability of HNSCC to produce these cytokines , supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines . No IL-1 was detected , although baseline levels of IL-4 , IL-6 , and GM-CSF were present . However , the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 ( p &lt ; 0.01 ) , IL-6 ( p &lt ; 0.001 ) , and GM-CSF ( p &lt ; 0.02 ) . These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells . Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Endoplasmic reticulum ( ER ) stress induces both autophagy and apoptosis yet the molecular mechanisms and pathways underlying the regulation of these two cellular processes in cells undergoing ER stress remain less clear . We report here that eukaryotic elongation factor-2 kinase ( EEF2K ) is a critical controller of the ER stress-induced autophagy and apoptosis in tumor cells . DDIT4 , a stress-induced protein , was required for transducing the signal for activation of EEF2K under ER stress . We further showed that phosphorylation of EEF2K at Ser398 was essential for induction of autophagy , while phosphorylation of the kinase at Ser366 and Ser78 exerted an inhibitory effect on autophagy . Suppression of the ER stress-activated autophagy via silencing of EEF2K aggravated ER stress and promoted apoptotic cell death in tumor cells . Moreover , inhibiting EEF2K by either RNAi or NH125 , a small molecule inhibitor of the enzyme , rendered tumor cells more sensitive to curcumin and velcade , two anticancer agents that possess ER stress-inducing action . Our study indicated that the DDIT4-EEF2K pathway was essential for inducing autophagy and for determining the fate of tumor cells under ER stress , and suggested that inhibiting the EEF2K-mediated autophagy can deteriorate ER stress and lead to a greater apoptotic response , thereby potentiating the efficacy of the ER stress-inducing agents against cancer .\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 have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone ( DHC ) , a novel synthetic flavonoid , and fisetin , a naturally occurring flavonol-in prostate cancer cells . In this study , we further examine the mechanisms of these compounds on survival and proliferation pathways . DHC and fisetin ( 1-50 microM ) caused a dose-dependent reduction in viability , a concomitant increase in apoptosis in PC3 cells at 72 h , and a decrease in clonogenic survival at 24 h treatment . DHC was considerably more potent than fisetin in these cytotoxicity assays . The mechanism of accelerated cellular senescence was not activated by either compound in PC3 or lymph node carcinoma of the prostate ( LNCaP ) cells . Gene expression alterations in PC3 and LNCaP cells treated with 15 muM DHC and 25 microM fisetin for 6 to 24 h were determined by oligonucleotide array . Amongst the most highly represented functional categories of genes altered by both compounds was the cell cycle category . In total , 100 cell cycle genes were altered by DHC and fisetin including 27 genes with key functions in G2/M phase that were downregulated by both compounds . Other functional categories altered included chromosome organization , apoptosis , and stress response . These results demonstrate the multiple mechanisms of antitumor activity of DHC and fisetin in prostate cancer cells in vitro .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Induction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation . Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates . METHODOLOGY/PRINCIPAL FINDINGS We tested the effects of daily administered parathyroid hormone ( PTH ) on bone disease and myeloma growth , and we investigated molecular mechanisms by analyzing gene expression profiles of unique myeloma cell lines and primary myeloma cells engrafted in SCID-rab and SCID-hu mouse models . PTH resulted in increased bone mineral density of myelomatous bones and reduced tumor burden , which reflected the dependence of primary myeloma cells on the bone marrow microenvironment . Treatment with PTH also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts . In myelomatous bone , PTH markedly increased the number of osteoblasts and bone-formation parameters , and the number of osteoclasts was unaffected or moderately reduced . Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression . Human global gene expression profiling of myelomatous bones from SCID-hu mice treated with PTH or saline revealed activation of multiple distinct pathways involved in bone formation and coupling ; involvement of Wnt signaling was prominent . Treatment with PTH also downregulated markers typically expressed by osteoclasts and myeloma cells , and altered expression of genes that control oxidative stress and inflammation . PTH receptors were not expressed by myeloma cells , and PTH had no effect on myeloma cell growth in vitro . CONCLUSIONS/SIGNIFICANCE We conclude that PTH-induced bone formation in myelomatous bones is mediated by activation of multiple signaling pathways involved in osteoblastogenesis and attenuated bone resorption and myeloma growth ; mechanisms involve increased osteoblast production of anti-myeloma factors and minimized myeloma induction of inflammatory conditions .\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: Histone deacetylase inhibitors ( HDACi ) are promising epigenetic cancer chemotherapeutics rapidly approaching clinical use . In this study , we tested using in vitro and in vivo models the differential biological effects of a novel HDAC inhibitor [ belinostat ( PXD101) ] , in a wide panel of androgen-sensitive and androgen-independent tumor cells . Belinostat significantly increased acetylation of histones H3 and H4 . Belinostat potently inhibited the growth of prostate cancer cell lines ( IC50 range from 0.5 to 2.5 �M ) with cytotoxic activity preferentially against tumor cells . This agent induced G2/M arrest and increased significantly the percentage of apoptosis mainly in androgen-sensitive tumor cells confirming its growth-inhibitory effects . The cell death mechanisms were studied in three different prostate cancer cell lines with different androgen dependence and expression of androgen receptor ; LAPC-4 and 22rv1 ( androgen-dependent and expressing androgen receptor ) and PC3 ( androgen-independent not expressing androgen receptor ) . Belinostat induced the expression of p21 and p27 , acetylation of p53 and G2/M arrest associated with Bcl2 and Bcl-Xl downmodulation and significant reduction of survivin , IAPs and Akt/pAkt and increased caspase-8 and -9 expression/activity . Belinostat effectiveness was dependent on the androgen receptor ( AR ) , since the stable transfection of AR greatly increased the efficacy of this HDAC inhibitor . These observations were correlated using in vivo models . We demonstrated that belinostat preferentially resulted in antitumor effect in androgen-dependent tumor cells expressing AR . Our findings provide evidence that belinostat may be a promising anticancer drug for prostate cancer expressing AR , supporting its clinical role in prostate cancer .\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: Biallelic mutations in MCPH1 cause primary microcephaly ( MCPH ) with the cellular phenotype of defective chromosome condensation . MCPH1 encodes a multifunctional protein that notably is involved in brain development , regulation of chromosome condensation , and DNA damage response . In the present studies , we detected that MCPH1 encodes several distinct transcripts , including two major forms : full-length MCPH1 ( MCPH1-FL ) and a second transcript lacking the six 3 ' exons ( MCPH1Δe9-14 ) . Both variants show comparable tissue-specific expression patterns , demonstrate nuclear localization that is mediated independently via separate NLS motifs , and are more abundant in certain fetal than adult organs . In addition , the expression of either isoform complements the chromosome condensation defect found in genetically MCPH1-deficient or MCPH1 siRNA-depleted cells , demonstrating a redundancy of both MCPH1 isoforms for the regulation of chromosome condensation . Strikingly however , both transcripts are regulated antagonistically during cell-cycle progression and there are functional differences between the isoforms with regard to the DNA damage response ; MCPH1-FL localizes to phosphorylated H2AX repair foci following ionizing irradiation , while MCPH1Δe9-14 was evenly distributed in the nucleus . In summary , our results demonstrate here that MCPH1 encodes different isoforms that are differentially regulated at the transcript level and have different functions at the protein level .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;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: Topoisomerase 1 ( Top1)-DNA cleavage complexes induced by camptothecin ( CPT ) cause DNA strand breaks during DNA replication or transcription . Although the cellular responses to replication-mediated DNA double-strand breaks have been well studied , the responses to transcription-mediated DNA strand breaks have not . Here , we show that poly ( ADP-ribose ) polymerase ( PARP ) and cockayne syndrome group B protein ( CSB ) modulate the CPT-induced formation of discrete p53-binding protein 1 ( 53BP1 ) nuclear foci at sites of transcription-mediated DNA strand breaks . Inhibition of PARP activity enhanced the formation of these foci , while knockdown of essential components of the base excision repair ( BER ) pathway did not . These findings suggest that PARP suppresses transcription-mediated 53BP1 foci formation , but that this does not occur through the BER pathway . In addition , knockdown of CSB , one of the key factors of transcription-coupled repair , slowed the kinetics of 53BP1 foci formation . These data suggest that PARP and CSB modulate the formation of 53BP1 foci during the processing of transcription-mediated DNA strand breaks .\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: Chemoprevention is one feasible approach to decreasing morbidity and mortality of non-small cell lung cancer ( NSCLC ) . The present study aimed to explore the mechanisms of chemoprevention of NSCLC by Prunella vulgaris L . ( PV ) using a PV extract of 60% ethanol ( P-60 ) . In an A/J mouse model benzo[a]pyrene induction of lung tumors was significantly reduced difference by P-60 group . In addition , P-60 was found to have the ability to regulate cell cycle and induce apoptosis in SPC-A-1 cells . Therefore , we propose that P-60 has potential as a lung cancer chemopreventive agent .\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 present a new cell line , EJ established from an invasive endometrioid adenocarcinoma of the uterine corpus in a 56-year-old patient . The cells show rapid growth in culture with a doubling time of 16 h and high migration activity . Monolayer-cultured cells were polygonal in shape showing a tendency to pile up without contact inhibition . Subcutaneous transplantation of the EJ cells into nude mice formed solid tumors that were histologically diagnosed as adenocarcinoma , whereas no metastasis was observed . Cultured EJ cells produced tissue polypeptide antigen ( IPA ) . Genetic and molecular analyses revealed high telomerase activity but not estrogen receptor alpha expression . Using the DNA sequencing technique , we have screened EJ cells for p53 mutation in exon 5 to 8 but no mutation of p53 was observed . This cell line appears to represent the development of a more malignant clone with divergent receptor function and growth behavior , and provides us with an interesting new tool for the study of tumorigenesis in the human endometrium .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;evading growth suppressors;sustaining proliferative signaling;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: Bcl-2/E1B 19-kDa interacting protein 3 ( BNIP3 ) is a proapoptotic protein whose expression level is often low in colorectal cancer ( CRC ) cells due to the BNIP3 gene promoter DNA methylation by DNA methyltransferase ( DNMT ) . It is known that chemotherapy and radiotherapy suppress CRC through inducing tumor apoptosis . However , the molecular mechanisms underlying chemotherapy and radiotherapy-induced apoptosis of CRC cells are not well defined . In this study , we observed that the expression level of BNIP3 in colon cancer cells was significantly increased by treatment with therapeutic agents and radiation in vitro . The BNIP3 protein level in CRC tissues from patients who received preoperative concurrent chemotherapy was significantly higher than in those who received surgery alone . Furthermore , treatment with chemotherapeutic agents and radiation significantly decreased the DNMT1 expression level and enzymatic activity . Both expression level and activity of DNMT1 were inversely correlated with the expression level of BNIP3 in colon carcinoma cells after treatment with chemotherapeutic agents and radiation . Consistent with increased BNIP3 expression , chemotherapeutic agents and radiation induced colon carcinoma cell apoptosis in a dose-dependent manner . Based on these observations , we conclude that chemotherapy and radiotherapy inhibit DNMT1 expression to upregulate BNIP3 expression to promote CRC cell apoptosis . And , BNIP3 may play a role in the caspase-dependent apoptosis pathways , mainly during treatment with chemotherapy and radiotherapy .\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: An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists . In order to obtain large quantities of cells and reproducibility , human endothelial cells with extended life spans were developed by retroviral transfection . The resulting cells grown in a serum-free medium containing endothelial cell growth supplement ( ECGS ) have a telomerase activity , extended life spans of at least 21 passages , and an endothelial cell phenotype ( diI-acetylated-LDL upake , factor VIII-related antigen , VEGFR-1 and R-2 , and tissue-type plasminogen activator ( tPA) ) that resembled that of unaltered primary endothelial cells . Exceptions were ( i ) a higher expression of tPA , and ( ii ) a non-significant growth response to FGF-2 or VEGF stimulation . Within three-dimensional fibrin gels , specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells . Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS , respectively . Both cell types produced FGF-2 and VEGF cytokines . Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines . These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds .\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: INTRODUCTION The homeobox-containing transcription factor muscle segment homeobox 2 ( Msx2 ) plays an important role in mammary gland development . However , the clinical implications of Msx2 expression in breast cancer are unclear . The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro . METHODS Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients . Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray ( TMA ) containing 281 invasive breast tumours . Finally , to assess the functional role of Msx2 in vitro , Msx2 was ectopically expressed in a highly invasive breast tumour cell line ( MDA-MB-231 ) and an immortalised breast cell line ( MCF10a ) , and these cell lines were examined for changes in growth rate , cell death and cell signalling . RESULTS Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis ( P = 0.011 ) . Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm . Cytoplasmic Msx2 expression was associated with low grade tumours ( P = 0.012 ) and Ki67 negativity ( P = 0.018 ) . Nuclear Msx2 correlated with low-grade tumours ( P = 0.015 ) , estrogen receptor positivity ( P = 0.038 ) , low Ki67 ( P = 0.005 ) and high cyclin D1 expression ( P = 0.037 ) . Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival ( P = 0.049 ) , recurrence-free survival ( P = 0.029 ) and overall survival ( P = 0.019 ) . Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis . Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase ( ERK ) and decreased levels of Survivin and the ' split ends ' ( SPEN ) protein family member RBM15 . CONCLUSIONS We conclude that increased Msx2 expression results in improved outcome for breast cancer patients , possibly by increasing the likelihood of tumour cell death by apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death;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: The hypothesis that rodent cells can be immortalized by the direct induction of a single mutation-like event was tested by initiating cultures of benzo(a)pyrene treated Syrian hamster embryo cells with low inocula and expanding these few cells maximally until senescence prevented further culturing or immortalization took place . According to the mutation hypothesis immortalization is hardly to be expected under these conditions . However , immortalization was frequently observed . Therefore the induction of immortalization appears indirect . The progeny of benzo(a)pyrene treated cells immortalized with a rate of 3.9 x 10(-8)/cell/generation , which is 64 times higher than the spontaneous rate . The results are in line with the probabilistic theory developed in 1980 by both Fernandez et al . ( Proc . Natl . Acad . Sci . USA , 77 : 7272-7276 , 1980 ) and Kennedy et al . ( Proc . Natl . Acad . Sci . USA , 77 : 7262-7266 , 1980 ) , which states that treatment of cells with a carcinogen can result in a so-called activated state of the treated cells which is transmitted to the progeny and which results in an enhanced rate of transforming events .\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: MicroRNAs ( miRNAs ) are involved in cancer development and progression , acting as tumor suppressors or oncogenes . In this study , miRNA profiling was performed on 10 paired bladder cancer ( BC ) tissues using 20 GeneChipTM miRNA Array , and 10 differentially expressed miRNAs were identified in BC and adjacent noncancerous tissues of any disease stage/grade . After validated on expanded cohort of 67 paired BC tissues and 10 human BC cell lines by qRT-PCR , it was found that miR-100 was down-regulated most significantly in cancer tissues . Ectopic restoration of miR-100 expression in BC cells suppressed cell proliferation and motility , induced cell-cycle arrest in vitro , and inhibited tumorigenesis in vivo both in subcutaneous and intravesical passage . Bioinformatic analysis showed that mTOR gene was a direct target of miR-100. siRNA-mediated mTOR knockdown phenocopied the effect of miR-100 in BC cell lines . In addition , the cancerous metastatic nude mouse model established on the basis of primary BC cell lines suggested that miR-100/mTOR regulated cell motility and was associated with tumor metastasis . Both mTOR and p70S6K ( downstream messenger ) presented higher expression levels in distant metastatic foci such as in liver and kidney metastases than in primary tumor . Taken together , miR-100 may act as a tumor suppressor in BC , and reintroduction of this mature miRNA into tumor tissue may prove to be a therapeutic strategy by reducing the expression of target genes .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;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: Certain hexavalent chromium ( Cr(VI) ) compounds are well established occupational respiratory tract carcinogens . However , despite extensive studies , the cellular and molecular mechanisms underlying Cr(VI)-induced lung cancer remain poorly understood . In fact , the models used were often suboptimal and yielded conflicting results that were heavily dependent upon the system and experimental conditions employed . Here , we investigated the effects of chronic subcytotoxic and mildly cytotoxic ( 0.1-2 microM ) Cr(VI) exposures on cultures of human bronchial epithelial cells , the main targets of Cr(VI) carcinogenicity . Our studies with the nontumorigenic BEAS-2B cell line suggest that relatively short exposures ( h ) to sublethal Cr(VI) doses ( 0.1-1 microM ) may render these cells less sensitive to contact inhibition . We have also observed a reduced sensitivity to Cr(VI)-induced apoptosis shortly after the beginning of exposure to a mildly cytotoxic Cr(VI) dose ( 2 microM ) . Further studies are needed to determine whether these two phenotypes are involved in the Cr(VI)-induced carcinogenic process . Additionally , evidence gathered in this study strongly points to a Cr(VI) interference with cell adhesion to the substratum and with cell-cell interactions . Finally , by chronically exposing BEAS-2B cells to mildly cytotoxic Cr(VI) doses ( 1 and 2 microM ) , we were able to induce changes in cell morphology and pattern of growth characteristic of an early phase of pre-malignant progression .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A prominent feature of inflammatory diseases is endothelial dysfunction . Factors associated with endothelial dysfunction include proinflammatory cytokines , adhesion molecules , and matrix degrading enzymes . At the transcriptional level , they are regulated by the histone deacetylase sirtuin ( SIRT ) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB ( NF-κB ) . The role of SIRT6 , also a histone deacetylase , in regulating inflammation in endothelial cells is not known . The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells ( HUVECs ) in the presence of lipopolysaccharide ( LPS ) . LPS decreased expression of SIRT6 in HUVECs . Knockdown of SIRT6 increased the expression of proinflammatory cytokines ( IL-1β , IL-6 , IL-8 ) , COX-prostaglandin system , ECM remodelling enzymes ( MMP-2 , MMP-9 and PAI-1 ) , the adhesion molecule ICAM-1 , and proangiogenic growth factors VEGF and FGF-2 ; cell migration ; cell adhesion to leukocytes . Loss of SIRT6 increased the expression of NF-κB , whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity . Taken together , these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation , vascular remodelling , and angiogenesis . SIRT6 may be a potential pharmacological target for inflammatory vascular diseases .\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: The effect of transforming growth factor-beta 1 ( TGF-beta 1 ) and interleukin-1 beta ( IL-1 beta ) on LDL receptor in Hep G2 cells was investigated . A greater than two-fold stimulation of the binding and internalisation of [ 125I]-labelled LDL at 37 degrees C was observed after an 18-h incubation of the cells with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml compared with control cells . Scatchard analysis of the binding of [ 125I]-labelled LDL at 4 degrees C after an 18-h incubation of the cells with 1170 units/ml IL-1 beta and 5 ng/ml TGF-beta 1 showed that they were both acting primarily by increasing LDL receptor number . The increase in LDL receptor activity could not be attributed to an increase in cell proliferation as TGF-beta 1 at concentrations from 0.05 ng/ml to 50 ng/ml had no significant effect on either cell number or [ 3H]thymidine incorporation into DNA whilst IL-1 beta inhibited DNA synthesis by more than 80% at a concentration of 11,700 units/ml but had significant effect on cell number . Cholesterol biosynthesis from [ 14C]acetate , in contrast to the stimulation of LDL receptor activity , was inhibited by approximately two-fold by incubation with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml .\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: Properly regulated keratinocyte cell death is fundamentally important to maintain structural integrity and homeostatic function of epidermis . Moreover , from an oncological perspective , therapeutic approaches selectively targeting apoptosis of malignant cell types while sparing normal keratinocytes in surrounding skin is desirable . Apo2Ligand/tumor necrosis factor-related apoptosis-inducing ligand ( Apo2L/TRAIL ) has been observed to preferentially induce cytopathic effects on transformed/malignant cell types compared with their non-neoplastic counterparts . In this report , two different biologically active preparations of Apo2L/TRAIL , a non-tagged version , NT-Apo2L/TRAIL , and a leucine zipper fusion protein , LZ-Apo2L/TRAIL , were examined for their ability to trigger apoptosis in normal human keratinocytes , and in an immortalized cell line ( HaCaT cells ) . Differences between these preparations were observed , including : NT-Apo2L/TRAIL induced less keratinocyte apoptosis compared with LZ-Apo2L/TRAIL ; NT-Apo2L/TRAIL also induced less apoptosis of HaCaT cells compared with LZ-Apo2L/TRAIL ; LZ-Apo2L/TRAIL but not NT-Apo2L/TRAIL induced cytotoxic effects when keratinocytes became growth arrested due to undergoing spontaneous replicative senescence--a biological state previously observed to be resistant to UV-light-induced apoptosis . Similarities between preparations included : an enhanced ability for both Apo2L/TRAIL preparations to kill a greater relative percentage of HaCaT cells compared with keratinocytes ; enhanced cytotoxicity towards keratinocytes that had their NF-B activity inhibited ; a dependence of both Apo2L/TRAIL preparations on FADD and caspase activation ; triggering of the same caspase cascades including caspase 8 and 3 ; and an ability to induce apoptosis even when HaCaT cells and keratinocytes were transduced to overexpress either Bcl-2 or Bcl-x(L) ( survival factors that reduce susceptibility to UV-light-induced apoptosis ) . These results indicate that while both preparations of Apo2L/TRAIL possess biological activity , there are important differences as regards their ability to induce apoptosis in normal and immortalized keratinocytes . Moreover , the death receptor pathway triggered by LZ-Apo2L/TRAIL can overcome the apoptotic resistance normally observed in response to UV-light mediated by Bcl-2/Bcl-x(L) , as well as by the state of cellular senescence . Unraveling the molecular basis for these differential biological effects may reveal a new strategic role for these death receptor/ligands linked to apoptosis in maintaining the dynamic balance of keratinocyte proliferation , differentiation , and cell death necessary to achieve a homeostatic thickness and function of normal skin . In addition , it may be possible to utilize these Apo2L/TRAIL preparations for the treatment of various sun-induced skin cancers as they can differentially trigger apoptosis of transformed keratinocytes , or keratinocytes with abnormal NF-kappaB signaling , while sparing adjacent normal keratinocytes .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Dendritic cells ( DCs ) are key regulators of innate and acquired immunity . The maturation of DCs is directed by signal transduction events downstream of toll-like receptors ( TLRs ) and other pattern recognition receptors . Here , we demonstrate that , in mouse DCs , TLR agonists stimulate a profound metabolic transition to aerobic glycolysis , similar to the Warburg metabolism displayed by cancer cells . This metabolic switch depends on the phosphatidyl inositol 3'-kinase/Akt pathway , is antagonized by the adenosine monophosphate ( AMP)-activated protein kinase ( AMPK ) , and is required for DC maturation . The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10 . Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;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: Angiogenesis , the formation of new blood vessels from pre-existing vascular beds , is essential for tumor growth , invasion , and metastasis . Luteolin is a common dietary flavonoid found in fruits and vegetables . We studied the antiangiogenic activity of luteolin using in vitro , ex vivo , and in vivo models . In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation , migration , invasion and tube formation of endothelial cells , which are key events in the process of angiogenesis . Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay ( CAM ) and matrigel plug assay . Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9 . Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 in HUVECs . Proinflammatory cytokines such as IL-1β , IL-6 , IL-8 , and TNF-α level were significantly reduced by the treatment of luteolin in PC-3 cells . Luteolin ( 10 mg/kg/d ) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model , indicating that luteolin inhibited tumorigenesis by targeting angiogenesis . CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin . Moreover , luteolin reduced cell viability and induced apoptosis in prostate cancer cells , which were correlated with the downregulation of AKT , ERK , mTOR , P70S6K , MMP-2 , and MMP-9 expressions . Taken together , our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: DNA repair is an essential cellular process required to maintain genomic stability . Every cell is subjected to thousands of DNA lesions daily under normal physiological conditions . Ionizing radiation ( IR ) is a major DNA damaging agent that can be produced by both natural and man-made sources . A common source of radiation exposure is through its use in medical diagnostics or treatments such as for cancer radiotherapy where relatively high doses are received by patients . To understand the detailed DNA repair gene transcription response to high dose IR , gene expression exon array studies have been performed and the response to radiation in two divergent cell types , lymphoblastoid cell lines and primary fibroblasts , has been examined . These exon arrays detect expression levels across the entire gene , and have the advantage of high sensitivity and the ability to identify alternative transcripts . We found a selection of DNA repair genes , including some not previously reported , that are modulated in response to radiation . Detailed dose and time course kinetics of DNA repair transcription was conducted and results have been validated utilizing PCR methods . Alternative transcription products in response to IR were identified in several DNA repair genes including RRM2B and XPC where alternative initiation sites were found . These investigations have advanced the knowledge about the transcriptional response of DNA 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: HER-2/neu gene expression , DNA ploidy and proliferation index were studied in 250 cases of breast cancer . Expression of HER-2/neu was determined by using an antibody to the HER-2/neu receptor . Ki-67 antibody was used to determine the proliferation index of the breast cancers , and the Feulgen method was used to assess DNA amounts in the tumor cells . Histochemical staining was quantitated by image analysis . Of the cancers studied , 72 were positive for overexpression of HER-2/neu protein ; of these , 62 ( 86% ) possessed near-tetraploid DNA content , and 47 ( 65% ) had more than one G0G1 stem line ( polyploid ) of DNA distribution . Cells from the cases negative for HER/2-neu overexpression contained DNA amounts that ranged from diploid to varying degrees of aneuploid . A significant difference in the amounts of cellular proliferation in HER-2/neu overexpressing cancers was found between those that expressed the HER-2/neu receptor on their membranes and those that exhibited mainly cytoplasmic receptors .\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: PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands ( PD-L ) and is suggested to play a role in the maintenance of self-tolerance . In the present study , we examined possible roles of the PD-1/PD-L system in tumor immunity . Transgenic expression of PD-L1 , one of the PD-L , in P815 tumor cells rendered them less susceptible to the specific T cell antigen receptor-mediated lysis by cytotoxic T cells in vitro , and markedly enhanced their tumorigenesis and invasiveness in vivo in the syngeneic hosts as compared with the parental tumor cells that lacked endogenous PD-L . Both effects could be reversed by anti-PD-L1 Ab . Survey of murine tumor lines revealed that all of the myeloma cell lines examined naturally expressed PD-L1 . Growth of the myeloma cells in normal syngeneic mice was inhibited significantly albeit transiently by the administration of anti-PD-L1 Ab in vivo and was suppressed completely in the syngeneic PD-1-deficient mice . These results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 and PD-L may provide a promising strategy for specific tumor immunotherapy .\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: 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) is the most potent tumor promoter ever tested in rodents . Although it is known that most of TCDD actions are mediated by binding to the aryl hydrocarbon receptor ( AhR ) , the mechanisms leading to tumor promotion still remain to be elucidated . Loss of contact inhibition is one characteristic hallmark in tumorigenesis . In rat liver epithelial WB-F344 cells , TCDD induces a release from contact inhibition , which is manifested by a twofold increase in cell number when TCDD ( 1 nM for 48 h ) is added to confluent cells in the presence of serum , but not when given to exponentially growing or subconfluent , serum-deprived WB-F344 cells . Loss of G1 arrest was also shown by flow cytometric analysis . We demonstrate that TCDD treatment significantly increases cyclin D2 and cyclin A protein levels and show by immunofluorescence that these proteins accumulate in the nucleus . Although TCDD treatment leads to a strong increase in cyclin D2/cdk4 and cyclin A/cdk2 complex formation , we could only detect an elevation of cyclin A/cdk2 activity . In accordance with a lack of elevated cdk4 activity , no decrease in the amount of hypophosphorylated retinoblastoma protein could be shown after TCDD treatment . The importance of increased cyclin A/cdk2 activity for TCDD-dependent release from contact inhibition was shown by the fact that the cdk2/cdc2-specific inhibitor olomoucine ( 25 microM ) abolished TCDD response . These data indicate cyclin A-dependent loss of G1 arrest after TCDD treatment mainly downstream of the retinoblastoma protein .\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: We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model . It was suggested that the up-regulation of IL-10 production and IL-10 receptor ( IL-10R ) expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10 , besides its immunosuppressive activity , may act as a growth factor for metastatic L-TACB cells . The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production , reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth . Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells . Considering that cyclophosphamide is a prodrug , we used mafosfamide , a compound that yields in vitro the same active metabolites as cyclophosphamide does in vivo . Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and , concomitantly , inhibited metastatic cell proliferation . We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and , as a consequence , metastatic cell proliferation . These results may have a considerable impact on the design of new therapies for metastatic lymphomas .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In response to genotoxic stress , a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint ( DDC ) signalling pathway positively contributes to genome maintenance . Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest , cells must tightly regulate the activity of the kinases involved in this pathway . Despite their importance , the mechanisms for monitoring and modulating DDC signalling are not fully understood . Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae . On replication stress , cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53 , whereas activation of the upstream DDC kinase Mec1 remains normal . An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A , two positive regulators of Rad9-dependent Rad53 activation . A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107 . We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions . Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors .\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: Cell invasion is required for neoplastic metastasis . Matrix metalloproteinase-9 ( MMP-9 ) , which degrades the extracellular matrix , is a major component in the process of cancer cell invasion . Sulfuretin is one of the major flavonoids isolated from Rhus verniciflua . Sulfuretin has been used to reduce oxidative stress , platelet aggregation , the inflammatory response and mutagenesis . However , the effect of sulfuretin on breast cancer metastasis is unknown . In this study , we investigated the inhibitory effect of sulfuretin on 12-O-tetradecanoylphorbol-13-acetate ( TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells . Sulfuretin inhibited TPA-induced transcriptional activation of nuclear factor-κB ( NF-κB ) . We demonstrated that sulfuretin mediated the inhibition of TPA-induced MMP-9 expression and that cell invasion in MCF-7 cells involved suppression of the NF-κB pathway . Therefore , inhibiting MMP-9 expression by sulfuretin may have therapeutic potential for controlling breast cancer invasiveness .\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: Autophagy is activated in response to cellular stressors and mediates lysosomal degradation and recycling of cytoplasmic material and organelles as a temporary cell survival mechanism . Defective autophagy is implicated in human pathology , as disruption of protein and organelle homeostasis enables disease-promoting mechanisms such as toxic protein aggregation , oxidative stress , genomic damage , and inflammation . We previously showed that autophagy-defective immortalized mouse mammary epithelial cells are susceptible to metabolic stress , DNA damage , and genomic instability . We now report that autophagy deficiency is associated with endoplasmic reticulum ( ER ) and oxidative stress , and with deregulation of p62-mediated keratin homeostasis in mammary cells , allograft tumors , and mammary tissues from genetically engineered mice . In human breast tumors , high phospho(Ser73)-K8 levels are inversely correlated with Beclin 1 expression . Thus , autophagy preserves cellular fitness by limiting ER and oxidative stress , a function potentially important in autophagy-mediated suppression of mammary tumorigenesis . Furthermore , autophagy regulates keratin homeostasis in the mammary gland via a p62-dependent mechanism . High phospho(Ser73)-K8 expression may be a marker of autophagy functional status in breast tumors and , as such , could have therapeutic implications for breast cancer patients .\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: The DNA damage response ( DDR ) cascade and ROS ( reactive oxygen species ) signaling are both involved in the induction of cell death after DNA damage , but a mechanistic link between these two pathways has not been clearly elucidated . This study demonstrates that ROS induction after treatment of cells with neocarzinostatin ( NCS ) , an ionizing radiation mimetic , is at least partly mediated by increasing histone H2AX . Increased levels of ROS and cell death induced by H2AX overexpression alone or DNA damage leading to H2AX accumulation are reduced by treating cells with the antioxidant N-Acetyl-L-Cysteine ( NAC ) , the NADP(H) oxidase ( Nox ) inhibitor DPI , expression of Rac1N17 , and knockdown of Nox1 , but not Nox4 , indicating that induction of ROS by H2AX is mediated through Nox1 and Rac1 GTPase . H2AX increases Nox1 activity partly by reducing the interaction between a Nox1 activator NOXA1 and its inhibitor 14-3-3zeta . These results point to a novel role of histone H2AX that regulates Nox1-mediated ROS generation after DNA damage .\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: The metastasis-associated lung adenocarcinoma transcript 1 , MALAT1 , is a long non-coding RNA ( lncRNA ) that has been discovered as a marker for lung cancer metastasis . It is highly abundant , its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes , and it is associated with many RNA binding proteins and highly conserved throughout evolution . The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation , apoptosis , migration and invasion . Here , we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA . In human tumor cells , MALAT1 expression was abrogated using Zinc Finger Nucleases . Unexpectedly , the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells . Moreover , genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals . Thus , loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development .\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: Onconase ( Onc ) is an amphibian ribonuclease of the pancreatic RNase family that is cytostatic and cytotoxic to several tumor lines . It also shows anti-tumor activity in mouse tumor models and is currently in phase III clinical trials . In animal tests and clinical trials Onc shows lesser toxicity and fewer side effects compared to most chemotherapeutic drugs . Intriguingly , repeated infusions of this protein do not cause apparent immunological reactions in patients . The aim of the present study was to investigate sensitivity to Onc of human lymphocytes during their mitogenic stimulation in response to the polyvalent mitogen phytohemagglutinin ( PHA ) , and in mixed allogeneic lymphocyte cultures . Unexpectedly , we observed that frequency of cells undergoing activation-induced apoptosis was markedly increased in all cultures containing Onc . Apoptosis was measured by flow cytometry using markers that detect activation of caspases , the in situ presence of DNA strand breaks , and loss of fragmented DNA ( 'sub-G1 ' cell subpopulation ) . The enhancement of frequency of activation-induced apoptosis ( up to 244% ) was observed at 4.2-83 nM Onc concentration , which is at least an order magnitude lower than its minimal concentration reported to affect proliferation or induce apoptosis of leukemic and solid tumor cell lines . The cell cycle progression of lymphocytes that responded to PHA mitogenically was not affected at 8.3 or 83 nM Onc concentration . Because activation-induced apoptosis is the key mechanism regulating several in vivo immunological functions including induction of tolerance , the observed effects of Onc may explain the apparent lack of immune reactions to this protein in treated patients . The propensity of Onc to potentiate the activation-induced apoptosis suggests that this drug may have clinical utility as immunomodulating agent , e.g. , to suppress transplant rejection or treat autoimmune diseases .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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: Circulating tumour cells ( CTCs ) shed into blood from primary cancers include putative precursors that initiate distal metastases . Although these cells are extraordinarily rare , they may identify cellular pathways contributing to the blood-borne dissemination of cancer . Here , we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing , identifying Wnt2 as a candidate gene enriched in CTCs . Expression of WNT2 in pancreatic cancer cells suppresses anoikis , enhances anchorage-independent sphere formation , and increases metastatic propensity in vivo . This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 ( also known as TAK1 ) kinase . In humans , formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes , and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases . Thus , molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Dentin matrix protein 1 ( DMP1 ) is a member of the small integrin-binding ligand N-linked glycoprotein ( SIBLING ) family , a group of proteins initially described as mineralized extracellular matrices components . More recently , SIBLINGs have been implicated in several key steps of cancer progression , including angiogenesis . Although proangiogenic activities have been demonstrated for 2 SIBLINGs , the role of DMP1 in angiogenesis has not yet been addressed . We demonstrate that this extracellular matrix protein induced the expression of vascular endothelial cadherin ( VE-cadherin ) , a key regulator of intercellular junctions and contact inhibition of growth of endothelial cells that is also known to modulate vascular endothelial growth factor receptor 2 ( VEGFR-2 ) activity , the major high-affinity receptor for VEGF . DMP1 induced VE-cadherin and p27(Kip1) expression followed by cell-cycle arrest in human umbilical vein endothelial cells ( HUVECs ) in a CD44-dependent manner . VEGF-induced proliferation , migration , and tubulogenesis responses were specifically blocked on DMP1 pretreatment of HUVECs . Indeed , after VE-cadherin induction , DMP1 inhibited VEGFR-2 phosphorylation and Src-mediated signaling . However , DMP1 did not interfere with basic fibroblast growth factor-induced angiogenesis . In vivo , DMP1 significantly reduced laser-induced choroidal neovascularization lesions and tumor-associated angiogenesis . These data enable us to put DMP1 on the angiogenic chessboard for the first time and to identify this protein as a new specific inhibitor of VEGF-induced angiogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;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: The BLM helicase is a member of the RecQ DNA helicase family and is mutated in the cancer-prone disorder Bloom syndrome . BLM plays a role in a number of cellular processes including DNA double-strand break repair , Holliday junction dissolution , and chromosome segregation . In Drosophila melanogaster , the BLM ortholog ( DmBlm ) is encoded by the mus309 gene . To study the role of DmBlm in double-strand break repair , we utilized a genetic assay in which a targeted DNA double-strand gap is created through excision of a P transposable element . By recovering and molecularly analyzing individual repair products from wild-type and mus309 male pre-meiotic germline cells , we demonstrated that the DmBlm helicase is involved in homologous recombination downstream of strand invasion . This assay can be adapted to test the roles of numerous DNA metabolic factors in DNA double-strand gap 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: Monoclonal antibodies ( mAbs ) to HER2 are currently used to treat breast cancer , but low clinical efficacy , along with primary and acquired resistance to therapy , commonly limit clinical applications . We previously reported that combinations of antibodies directed at non-overlapping epitopes of HER2 are endowed with enhanced antitumor effects , probably due to accelerated receptor degradation . Here , we extend these observations to three-dimensional mammary cell models , and compare the effects of single mAbs with the effects of antibody combinations . Collectively , our in vitro assays and computational image analyses indicate that combining mAbs against different epitopes of HER2 better inhibits invasive growth . Importantly , while growth factors are able to reduce intraluminal apoptosis and induce an invasive phenotype , combinations of mAbs better than single mAbs can reverse the growth factor-induced phenotypes of HER2-overexpressing spheroids . In conclusion , our studies propose that mAb combinations negate the biological effects of growth factors on invasive growth of HER2-overexpressing cells . Hence , combining mAbs offers a therapeutic strategy , potentially able to enhance clinical efficacy of existing antireceptor immunotherapeutics .\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: Taxol ( Paclitaxel ) is an important natural product for the treatment of solid tumors such as ovarian , breast , non-small-cell lung tumors , and some head and neck carcinomas . Different concentrations of taxol trigger distinct effects on cell death forms . In present study , cell counting kit ( CCK-8 ) assay , confocal fluorescence microscopy imaging , flow cytometry ( FCM ) and western blotting ( WB ) analysis were used to analyze the characteristics of cell death induced by low ( 35 nM ) and high ( 70 microM ) concentration of taxol respectively in human lung adenocarcinoma ( ASTC-a-1 ) cells . Our results showed that low concentration of taxol induced cell death dominantly in apoptotic fashion associated with nuclear fragmentation , protein synthesis , phosphatidylserine ( PS ) externalization , G2/M cell cycle arrest , Bax translocation into mitochondria and caspase-3 activation , whereas high concentration of this drug induced significant cytoplasm vacuolization , mitochondria swelling and paraptosis-like cell death form without protein synthesis that is necessary for paraptosis . Although the mechanism of high concentration of taxol-induced paraptosis-like cell death has not been clear , this finding might have a potential implication for cancer therapy , especially for apoptosis-resistant cancer .\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: Epstein-Barr virus ( EBV ) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus . The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1 . However , the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression . Here , we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells . Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae . Using time-lapse microscopy , we found the fate of individual HeLa cells was determined by the expression level of BGLF4 . In addition to slight cell growth retardation , BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells . In Saos-2 cells , BGLF4 induced the hyperphosphorylation of co-transfected RB , while E2F1 was not released from RB-E2F1 complexes . The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner . Detection with phosphoamino acid specific antibodies revealed that , in addition to Ser780 , phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4 . Taken together , our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;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: Currently there is no good hepatocyte model for studying growth hormone ( GH ) function that reflects its normal physiological roles . Here we report the establishment of a functional hepatocyte cell line , SDRL-1 , from the liver of young male spontaneous dwarf rats ( SDR ) , with isolated GH deficiency . This line has been maintained in Dulbecco's Modified Eagle Medium ( DMEM)/F12 medium supplemented with 10% fetal bovine serum ( FBS ) with retention of a near diploid karyotype for extended periods of time . When grown as a monolayer sheet , it displayed a pavement-like appearance and contact inhibition . These cells have a poorly developed rough endoplasmic reticulum ( r-ER ) , few mitochondria and glycogen granules , and produce a small amount of albumin and α-fetoprotein , that is enhanced when grown on a collagen gel sponge . Human recombinant GH stimulated JAK2 and STAT5b tyrosine phosphorylation and IGF-I production in a concentration-dependent manner . When the cells were cultured with GH-supplemented medium , the number of mitochondria and glycogen granules increased together with the r-ER and Golgi apparatus . A number of microvilli were observed on the surface of the cultured cells , further suggesting that this cell line is composed of normally functioning hepatocytes . In summary , we established a novel hepatocyte cell line ( SDRL-1 ) , that appears to display normal function , which we propose can serve as a good in vitro model for studying GH-target organ interactions .\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: Signal transducers and activators of transcription 3 ( Stat3 ) is activated by cytokines and growth factors in lung cancers and regulates expression of genes implicated in cell growth , survival , and transformation . Previously , we found that mice with a deletion of the G protein-coupled receptor , family C , group 5 , member a ( Gprc5a ) gene develop lung tumors , indicating that Gprc5a is a tumor suppressor . Herein , we show that epithelial cells from Gprc5a knockout mouse lung ( Gprc5a(-/-) cells ) survive better in vitro in medium deprived of exogenous growth factors and form more colonies in semisolid medium than their counterparts from wild-type mice ( Gprc5a(+/+) cells ) . Stat3 tyrosine 705 phosphorylation and expression of several Stat3-regulated antiapoptotic genes were higher in Gprc5a(-/-) than in Gprc5a(+/+) cells . Both cell types secreted leukemia inhibitory factor ( Lif ) ; however , whereas Stat3 activation was persistent in Gprc5a(-/-) cells , it was transient in Gprc5a(+/+) cells . Lung adenocarcinoma cells isolated from Gprc5a(-/-) mice also exhibited autocrine Lif-mediated Stat3 activation . The level of Socs3 , the endogenous Stat3 inhibitory protein , was higher in Gprc5a(+/+) than in Gprc5a(-/-) cells , and expression of the tumor suppressor stabilized Socs3 . Inhibition of Stat3 signaling in Gprc5a(-/-) normal and cancer cells by the Janus-activated kinase 2 inhibitor AG490 or by a dominant negative Stat3(Y705F) increased starvation-induced apoptosis and inhibited colony formation . These results show that persistent Stat3 activation is important for the survival and transformation of Gprc5a(-/-) lung cells and suggest that the tumor suppressive effects of Gprc5a are mediated , at least in part , by inhibition of Stat3 signaling through Socs3 stabilization .\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: In the course of a medicinal chemistry program aimed at discovering novel tumour-active rebeccamycin derivatives targeting DNA and/or topoisomerase I , a series of analogues with the sugar residue linked to the two indole nitrogens was recently developed . Two promising drug candidates in this staurosporine-rebeccamycin hybrid series were selected for a DNA-binding study reported here . The DNA interaction of the cationic indolocarbazole glycosides MP059 bearing a N,N-diethylaminoethyl side chain and MP072 containing a sugar bearing an amino group was compared with that of the uncharged analogue MP024 . The results show that the addition of a cationic substituent , either directly on the indolocarbazole chromophore or on the carbohydrate residue , significantly reinforces the interaction of the drugs with nucleic acids . The two cationic molecules MP059 and MP072 recognise preferentially sequences containing GpT.ApC and TpG.CpA steps but they do not inhibit topoisomerase I , in contrast to the parent uncharged derivative MP024 which stimulates DNA single strand breaks by topoisomerase I. The cytotoxic activity of the indolocarbazole derivatives bearing positively charged groups is one order of magnitude higher than that of the neutral compound MP024 . The high cytotoxic potential can be attributed to the enhanced DNA binding and sequence recognition capacity of the cationic compounds . The study provides useful information for further structure-activity relationship studies in the indolocarbazole series .\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 Death receptors ( DR ) of the TNF family function as anti-tumor immune effector molecules . Tumor cells , however , often exhibit DR-signaling resistance . Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack . The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis . METHODOLOGY/PRINCIPAL FINDINGS The ability of radiation to modulate the expression of multiple death receptors ( Fas/CD95 , TRAILR1/DR4 , TRAILR2/DR5 , TNF-R1 and LTβR ) was examined in colorectal tumor cells . The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays . The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined . We found that radiation increased surface expression of Fas , DR4 and DR5 but not LTβR or TNF-R1 in these cells . Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation . Sub-lethal tumor cell irradiation alone exhibited minimal cell death , but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis , but not LTβR-induced death . Furthermore , radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation . Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L) and c-FLIP protein expression , this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types . CONCLUSIONS/SIGNIFICANCE Irradiation of tumor cells can overcome Fas and TRAIL resistance that is long lasting . Overall , results of these investigations suggest that non-lethal doses of radiation can be used to make human tumors more amenable to attack by anti-tumor effector molecules and cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Bisphenol A is a monomer used in the production of polycarbonate plastics , epoxy resins , and flame retardants . It is an endocrine disruptor with a variety of other effects , including genotoxicity . Oxidative metabolism of bisphenol A yields electophilic bisphenol A-3,4-quinone ( BPAQ ) , which may cause genotoxicity . To determine the genotoxic potential of bisphenol A , the mechanism of the reaction between the BPAQ and deoxyadenosine ( dA ) was studied in detail . The most probable reaction pathway was determined using quantum chemical methods . Our results demonstrate that the rate limiting step is Michael addition between BPAQ and dA , the main product being the unstable N7-modified adduct that rapidly undergoes depurination . In addition , our calculations provide strong evidence for protonation of the adducts prior to depurination , which indicates pH dependence of the reaction . The calculated activation barrier for Michael addition is 28.7 kcal/mol , indicating that the reaction with dA is very slow . Comparison with the activation energy of 23.1 kcal/mol for the corresponding deoxyguanosine reaction indicates that most of the DNA damage by BPAQ will occur at the guanine site . The detoxification reactions with glutathione compete with reactions between BPAQ and DNA . The calculated free energy of activation for the reaction with glutathione is significantly lower than that for the corresponding reaction with dA . This indicates that BPAQ will preferably react with glutathione and will only react with DNA when the level of glutathione in the cell is low .\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 Idarubicin is a synthetic anthracycline anticancer drug widely used in the treatment of some hematological malignancies . The studies in our laboratory have clearly demonstrated that idarubicin can undergo reductive bioactivation by NADPH-cytochrome P450 reductase to free radicals with resulting formation of DNA strand breaks , which can potentially contribute to its genotoxic effects [ Celik , H. , Arinç , E. , Bioreduction of idarubicin and formation of ROS responsible for DNA cleavage by NADPH-cytochrome P450 reductase and its potential role in the antitumor effect . J Pharm Pharm Sci , 11(4):68-82 , 2008 ] . In the current study , our aim was to investigate the possible protective effects of several phenolic antioxidants , quercetin , rutin , naringenin , resveratrol and trolox , against the DNA-damaging effect of idarubicin originating from its P450 reductase-catalyzed bioactivation . METHODS DNA damage was measured by detecting single-strand breaks in plasmid pBR322 DNA using a cell-free agarose gel method . RESULTS Our results indicated that , among the compounds tested , quercetin was the most potent antioxidant in preventing DNA damage . Quercetin significantly decreased the extent of DNA strand breaks in a dose-dependent manner ; 100 microM of quercetin almost completely inhibited the DNA strand breakage . Unlike quercetin , its glycosidated conjugate rutin , failed to provide any significant protection against idarubicin-induced DNA strand breaks except at the highest concentration tested ( 2 mM ) . The protective effects of other antioxidants were significantly less than that of quercetin even at high concentrations . Quercetin was found to be also an effective protector against DNA damage induced by mitomycin C. CONCLUSION We conclude that quercetin , one of the most abundant flavonoids in the human diet , is highly effective in reducing the DNA damage caused by the antitumor agents , idarubicin and mitomycin C , following bioactivation by P450 reductase .\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 aim of this work was to characterize the antitumoral activity of the plant compound 7-epi-nemorosone in prostate carcinoma cell lines . Prostate cancer is the most frequently diagnosed malignancy and the second-leading cause of cancer death in men . In spite of the current therapeutic options for this cancer entity , many patients die due to metastases in distant organs and acquired chemotherapy resistance . Thus , approaches to provide improvements in outcome and quality of life for such patients are urgently needed . Recently , the polyisoprenylated benzophenone 7-epi-nemorosone , originally collected by honeybees from Clusia rosea and Clusia grandiflora ( Clusiaceae ) , has been described to be a potent antitumoral agent . Here , its activity in prostate carcinoma is reported. 7-epi-nemorosone was isolated from Caribbean propolis employing RP-HPLC techniques . Its cytotoxicity was assessed using the MTT proliferation assay in human androgen-dependent prostate carcinoma LNCaP cells including an MDR1(+) sub-line . No cross-resistance was detected . FACS-based cell cycle analysis revealed a significant increase in the sub-G0/G1 , G1 , and depletion in the S phase populations . A concomitant down-regulation of cyclins D1/D3 and CDK 4/6 in LNCaP cells was detected by Western blot . Annexin-V-FITC labeling and caspase-3 cleavage assays showed that 7-epi-nemorosone induced apoptotic events . Major signal transduction elements such as p38 MAPK and Akt/PKB as well as androgen receptor AR and PSA production were found to be down-regulated after exposure to the drug . ERK1/2 protein levels and phosphorylation status were down-regulated accompanied by up-regulation but inhibition of the activity of their immediate upstream kinases MEK1/2 . Additionally , Akt/PKB enzymatic activity was effectively inhibited at a similar concentration as for MEK1/2 . Here , we demonstrate for the first time that 7-epi-nemorosone exerts cytotoxicity in an androgen-dependent prostate carcinoma entity by targeting the MEK1/2 signal transducer .\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: DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair . The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance . While activation of DNA damage checkpoints has been studied extensively , molecular mechanisms involved in sustaining and ultimately inactivating cell cycle checkpoints are largely unknown . Here , we explored feedback mechanisms that control the maintenance and termination of checkpoint function by computationally identifying an evolutionary conserved mitotic phosphorylation network within the DNA damage response . We demonstrate that the non-enzymatic checkpoint adaptor protein 53BP1 is an in vivo target of the cell cycle kinases Cyclin-dependent kinase-1 and Polo-like kinase-1 ( Plk1 ) . We show that Plk1 binds 53BP1 during mitosis and that this interaction is required for proper inactivation of the DNA damage checkpoint. 53BP1 mutants that are unable to bind Plk1 fail to restart the cell cycle after ionizing radiation-mediated cell cycle arrest . Importantly , we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells . Thus , a mitotic kinase-mediated negative feedback loop regulates the ATM-Chk2 branch of the DNA damage signaling network by phosphorylating conserved sites in 53BP1 and Chk2 to inactivate checkpoint signaling and control checkpoint duration .\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: Hypoxia-inducible factor-1 ( HIF-1 ) plays a critical role in reprogramming cancer metabolism toward aerobic glycolysis ( i.e. , the Warburg effect ) , which is critical to supplying cancer cells with the biomass needed for proliferation . Previous studies have shown that cetuximab , an EGF receptor-blocking monoclonal antibody , downregulates the alpha subunit of HIF-1 ( HIF-1α ) through the inhibition of EGF receptor downstream cell signaling and that downregulation of HIF-1α is required for cetuximab-induced antiproliferative effects . However , the mechanism underlying these actions has yet to be identified . In this study , we used the Seahorse XF96 extracellular flux analyzer to assess the effect of cetuximab treatment on changes in glycolysis and mitochondrial respiration , the two major energy-producing pathways , in live cells . We found that cetuximab downregulated lactate dehydrogenase A ( LDH-A ) and inhibited glycolysis in cetuximab-sensitive head and neck squamous cell carcinoma ( HNSCC ) cells in an HIF-1α downregulation-dependent manner . HNSCC cells with acquired cetuximab resistance expressed a high level of HIF-1α and were highly glycolytic . Overexpression of a HIF-1α mutant ( HIF-1α/ΔODD ) conferred resistance to cetuximab-induced G1 phase cell-cycle arrest , which could be overcome by knockdown of LDH-A expression . Inhibition of LDH-A activity with oxamate enhanced the response of cetuximab-resistant cells to cetuximab . Cetuximab had no noticeable inhibitory effect on glycolysis in nontransformed cells . These findings provide novel mechanistic insights into cetuximab-induced cell-cycle arrest from the perspective of cancer metabolism and suggest novel strategies for enhancing cetuximab response .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;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 &amp ; AIMS GUCY2C is the intestinal receptor for the paracrine hormones guanylin and uroguanylin that converts guanosine-5'-triphosphate to cyclic guanosine monophosphate ( cGMP ) . It functions as a tumor suppressor ; its loss disrupts intestinal homeostasis and promotes tumorigenesis . We investigated the effects of GUCY2C loss on intestinal cell proliferation , metabolism , signaling , and tumorigenesis in mice . METHODS Intestinal cell proliferation and metabolism were examined in Gucy2c(-/-) and colon cancer cells by microscopy , immunoblot , and functional analyses . Microarray analyses compared gene expression profiles of intestine cell from Gucy2c(-/-) and wild-type mice. v akt murine thymoma viral oncogene homolog ( AKT ) regulation and signaling were examined , and the role of AKT in GUCY2C-dependent tumorigenesis was defined in Gucy2c(-/-)Akt1(-/-) mice . RESULTS The size and number of intestinal crypts increased in Gucy2c(-/-) mice ; the associated epithelial cells showed accelerated proliferation , increased glycolysis , and reduced oxidative phosphorylation , which was reversed by oral administration of cGMP . Conversely , activating guanylyl cyclase C in human colon cancer cells delayed cell-cycle progression , decreased DNA synthesis and colony formation , reduced glycolysis , and increased mitochondrial adenosine triphosphate production . AKT signaling pathways were activated in intestines of Gucy2c(-/-) mice , associated with increased AKT phosphorylation . Disruption of AKT activity , pharmacologically or genetically , reduced DNA synthesis , proliferation , and glycolysis , and increased mitochondrial biogenesis . Intestinal tumorigenesis increased after administration of azoxymethane to Gucy2c(-/-) mice , compared with wild-type mice , but was eliminated in Gucy2c(-/-)Akt1(-/-) mice . CONCLUSIONS GUCY2C is a tumor suppressor that controls proliferation and metabolism of intestinal epithelial cells by inactivating AKT signaling . This receptor and its ligands , which are paracrine hormones , might be novel candidates for anticolorectal cancer therapy .\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: It is well known that cell-mediated immunity is suppressed in patients with neoplastic diseases . We have reported that soluble receptors for interleukin-2 ( sIL-2R ) and tumor necrosis factor ( sTNF-R1 ) are elevated in the serum of patients with advanced colorectal cancer . The presence of these soluble receptors and immunosuppressive cytokines , including interleukin-10 ( IL-10 ) , might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum ( cisplatin ) has been reported to immunomodulate , especially when used in low dose in combination with 5-Fluorouracil ( 5-FU ) . In this study , cisplatin and UFT , a form of uracil and tegafur which is a prodrug of 5-FU , were administered with immunomodulator Polysaccharide K ( PSK ) to ten patients with colorectal cancer , who showed distant metastasis in the liver or lung , and the serum levels of sIL-2R and sTNF-R1 and the production of gamma-interferon ( gamma-INF ) and interleukin-10 by peripheral blood mononuclear cells were measured . The serum concentrations of sIL-2R and the production of IL-10 were reduced ( p &lt ; 0.05 ) after 2 months of treatment . Thus , this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Purpose of this work was to synthesize several cis-/trans- isomer pairs of the platinum(II) complexes , and study the extent and the mode of their antiproliferative activity on HeLa cells . Six platinum(II) isomer pairs have a general formula cis-/trans-[PtA2X2] , where A is ligand : ammonia ( NH3 ) , pyridine ( Py ) ; and X is ligand : chloride ion ( Cl- ) , bromide ion ( Br- ) , iodide ion ( I- ) , thiocyanato ion ( SCN- ) ; four compounds have different structural formulas , and these are cis-/trans-[Pt(NH2OH)2(NH3)2]Cl2 , and cis-/trans-Pt(Gly)2 , where Gly is bidentate glycinato ligand . Results of the MTT assay , showed that six cis- and one trans-platinum(II) complexes exhibited cytotoxicity ( IC50 ) ranging between 5 and 33 microM . Most of the cis-platinum(II) isomers caused significant alteration of cell cycle phases progression , and induced apoptosis in degree that varied among different compounds , as evaluated using flowcytometry and morphological study . Spectrophotometric analysis ( AAS ) indicated that there is no correlation between intracellular platinum(II) accumulation and cytotoxicity of tested complexes .\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: Splenic haemangiosarcomas ( HSAs ) from 122 dogs were characterized and classified according to their patterns of growth , survival time post splenectomy , metastases and chemotherapy . The most common pattern of growth was a mixture of cavernous , capillary and solid tumour tissue . Survival time post splenectomy was independent of the growth pattern ; however , it was influenced by chemotherapy and metastases . Immunohistochemical assessment of the expression of angiogenic factors ( fetal liver kinase-1 , angiopoietin-2 , angiopoietin receptor-2 and vascular endothelial growth factor A ) and conventional endothelial markers ( CD31 , factor VIII-related antigen ) revealed variable expression , particularly in undifferentiated HSAs . Therefore , a combination of endothelial markers should be used to confirm the endothelial origin of splenic tumours .\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: DNA damage induced by benzene and its metabolites is thought of as an important mechanism underlying benzene genotoxicity in chronic benzene poisoning ( CBP ) . Therefore , genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population . Since benzene-induced DNA damages include DNA adducts , we hypothesized that the polymorphisms of ERCC1 ( Excision repair cross complementation group 1 ) and ERCC2/XPD ( Excision repair cross complementation group 2/xeroderma pigmentosum group D ) are associated with the risk of CBP . A case-control study involving 102 benzene-poisoned patients and 204 none-benzene-poisoned controls occupationally exposed to benzene was carried out in the Northeast region of China . The polymorphisms of codon 118 ( rs11615 ) and C8092A ( rs3212986 ) of ERCC1 , codon 751 ( rs13181 ) , 312 ( rs1799793 ) and 156 ( rs238406 ) of ERCC2/XPD were genotyped by TaqMan(®) Real-time PCR . The results showed that individuals carrying the ERCC1 codon 118 TT genotype had an increased risk of CBP ( OR(adj)=3.390 ; 95%CI : 1.393-8.253 ; P=0.007 ) comparing with its CC genotype . After stratified by smoking , gender and exposure duration we found that the increased risk of CBP associated with the ERCC1 codon 118 TT genotype confined to nonsmokers ( OR=3.214 ; 95% CI : 1.359-7.601 ; P=0.006 ) , female ( OR=3.049 ; 95% CI : 1.235-7.529 ; P=0.013 ) and exposure duration&gt ; 12 years ( OR=3.750 ; 95% CI : 1.041-13.513 ; P=0.035 ) . Since ERCC1 and ERCC2/XPD are both located on chromosome 19q13.3 , haplotype analysis of all 5 SNPs was also conducted . However no correlations between the risks of CBP and other genotypes or haplotypes were found . Therefore , our findings suggest an important role of ERCC1 codon 118 polymorphisms for a biomarker to CBP in the Chinese occupational population .\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: Human papillomavirus type 16 ( HPV16 ) E6 and E7 are selectively retained and expressed in HPV16-associated human genital tumors . E6 is active in several cell culture assays , including transformation of NIH 3T3 cells , trans activation of the adenovirus E2 promoter , and cooperation with E7 to immortalize normal human keratinocytes . Biochemically , the HPV16 E6 protein has been shown to bind to tumor suppressor protein p53 in vitro and induce its degradation in a rabbit reticulocyte lysate . To examine the relationship between the various biological activities of E6 and inactivation of p53 , we tested the abilities of dominant negative mutants of p53 to substitute functionally for E6 in the three cell culture assays . While wild-type p53 inhibited keratinocyte proliferation , both mouse and human mutant p53s , in conjunction with E7 , increased proliferation of the keratinocytes , resulting in generation of immortalized lines . However , in contrast to E6 , mutant p53 was unable to induce transformation or trans activate the adenovirus E2 promoter in NIH 3T3 cells . These results suggest that inactivation of wild-type p53 is necessary for HPV-induced immortalization of human keratinocytes and that different or additional activities are required for E6-dependent transformation and trans activation of NIH 3T3 cells .\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: Electronic properties of DNA are believed to play a crucial role in many phenomena in living organisms , for example the location of DNA lesions by base excision repair ( BER ) glycosylases and the regulation of tumor-suppressor genes such as p53 by detection of oxidative damage . However , the reproducible measurement and modelling of charge migration through DNA molecules at the nanometer scale remains a challenging and controversial subject even after more than a decade of intense efforts . Here we show , by analysing 162 disease-related genes from a variety of medical databases with a total of almost 20,000 observed pathogenic mutations , a significant difference in the electronic properties of the population of observed mutations compared to the set of all possible mutations . Our results have implications for the role of the electronic properties of DNA in cellular processes , and hint at the possibility of prediction , early diagnosis and detection of mutation hotspots .\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: Glioblastoma is one of the most lethal and common malignant human brain tumors , with aggressive proliferation and highly invasive properties . Honokiol derived from Magnolia officinalis is able to cross the blood-brain barrier ( BBB ) and the blood-cerebrospinal fluid barrier ( BCSFB ) , suggesting a strong possibility that it could be an effective drug for the treatment of brain tumors , including glioblastoma . Thus , we investigated the effects of honokiol on the expression of adhesion molecules in TNF-α-stimulated endothelial cells , and cancer growth and invasion were determined in T98G human glioblastoma cells . Honokiol dose-dependently inhibited the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) in human umbilical vein endothelial cells ( HUVECs ) stimulated with TNF-α for 6 h . Pretreatment with honokiol significantly reduced the adhesion of T98G cells to HUVECs . Moreover , honokiol inhibited the invasion of T98G cells , suggesting that honokiol has an anti-metastatic effect . In addition , honokiol increased the cytotoxicity of T98G cells in a dose- and time-dependent manner as assayed by MTT . TUNEL assay showed that honokiol significantly induced apoptosis in T98G cells at doses of 10 �M or more . The induction of apoptotic cell death was mediated by the downregulation of the anti-apoptotic protein Bcl-2 and the upregulation of the pro-apoptotic protein Bax . Taken together , the results of this study suggest that honokiol exerts an anticancer effect by preventing metastasis and inducing apoptotic cell death of brain tumor cells .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: AIM To elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib . METHODS The cell lines A549 , HeLa , and HepG2 were tested . The enzyme activity was examined under cell-free conditions using 384-well microplate assays . Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay . Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system . Protein expression analysis was performed using Western blotting . RESULTS Sorafenib potently suppressed the activities of cRAF , VEGFR2 , and RET with IC(50) values of 20.9 , 4 and 0.4 nmol/L , respectively . Sorafenib inhibited cRAF , VEGFR2 , and RET via non-ATP-competitive , ATP-competitive and mixed-type modes , respectively . In contrast , sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines . The IC(50) values for inhibition of A549 , HeLa , and HepG2 cells were 8572 , 4163 , and 8338 nmol/L , respectively . In the 3 cell lines , sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level , which in turn regulated related gene expression via a feed-back mechanism . CONCLUSION This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib .\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: Lung cancer is primarily caused by exposure to tobacco smoke . Tobacco smoke contains numerous carcinogens , including polycyclic aromatic hydrocarbons ( PAH ) . The most common PAH studied is benzo[a]pyrene ( B[a]P ) . B[a]P is metabolically activated through multiple routes , one of which is catalyzed by aldo-keto reductase ( AKR ) to B[a]P-7,8-dione ( BPQ ) . BPQ undergoes a futile redox cycle in the presence of NADPH to generate reactive oxygen species ( ROS ) . ROS , in turn , damages DNA . Studies with a yeast p53 mutagenesis system found that the generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because of similarities between the patterns ( types of mutations ) and spectra ( location of mutations ) and those seen in lung cancer . The patterns were dominated by G to T transversions , and the spectra in the experimental system have mutations at lung cancer hotspots . To address repair mechanisms that are responsible for BPQ induced damage we observed the effect of mutating two DNA repair genes OGG1 and APE1 ( APN1 in yeast ) and tested them in a yeast reporter system for p53 mutagenesis . There was an increase in both the mutant frequency and the number of G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1 yeast . Knocking out APN2 increased mutagenesis in the apn1 cells . In addition , we did not find a strand bias on p53 treated with BPQ in ogg1 yeast . These studies suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ , Apn1 and Apn2 have redundant functions and that the stand bias seen in lung cancer may not be due to impaired repair of oxidative lesions .\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 submandibular gland-derived tumor cell line SCA-9 is considered a useful tool to study the signaling pathways involved in proliferation , and their regulation , triggered by different stimuli . It is proposed that the non neuronal cholinergic system : acethylcholine , the enzymes that synthesize and degrade it , and the nicotinic and muscarinic receptors , play a key role in tumorigenesis . Here , we investigate the role of muscarinic receptors in SCA-9 cell proliferation , and the modulation of cholinergic signaling pathways exerted by the nuclear transcription factor κB ( NF-κB ) . The activation of cholinergic receptors by carbachol ( 10⁻⁹M ) increased cell proliferation ( P<0.001 ) . This was prevented by preincubating cells with the muscarinic antagonist atropine but not by mecamylamine , a nicotinic receptor blocker . Phospholipase C ( PLC)/nitric oxide synthase ( NOS)/arginase pathway is involved in this effect , since carbachol stimulated nitric oxide production , increased NOS2 and NOS3 expressions , urea production , and arginase II expression ( P<0.001 ) . Also , phospholipase A₂ ( PLA₂)/cyclooxygenase ( COX ) pathway is up-regulated in carbachol-induced SCA-9 cell proliferation , because prostaglandin E₂ liberation ( P<0.001 ) is increased and COX-1 expression is turned up ( P<0.001 ) . Interactions between PLC/NOS/arginases and PLA₂/COX pathways via its metabolites were detected . SCA-9 cells exhibit a constitutive activation of NF-κB , which regulates carbachol-induced NOS2 and 3 , arginase II and COX-1 expressions . In addition , protein kinase C is involved in the up-regulation of NOS2 and arginase II enzymes induced by carbachol via NF-κB . In conclusion , the activation of cholinergic receptors in SCA-9 tumor cells promotes proliferation via muscarinic effector enzymes , and reveals the participation of NF-κB at this step of tumorigenesis .\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: Therapy-induced cellular senescence ( TCS ) , characterized by prolonged cell cycle arrest , is an in vivo response of human cancers to chemotherapy and radiation . Unfortunately , TCS is reversible for a subset of senescent cells , leading to cellular reproliferation and ultimately tumor progression . This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer . We report the findings of a clinicopathological study in patients with locally advanced non-small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome . In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape , we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry . We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS . These polyploid senescent cells represent important transition states through which escape preferentially occurs . The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin-dependent kinase inhibitor family during TCS . Altogether , these studies underscore the importance of TCS in cancer therapeutics .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers ; however , therapies targeting this gene have not proved to be as effective as was initially hoped . Transcriptional profiling meta-analyses have shown that there are approximately 150 genes co-overexpressed with ERBB2 , suggesting that these genes may represent alternative factors influencing ERBB2-positive tumors . Here we describe an RNA interference-based analysis of these genes that identifies transcriptional regulators of fat synthesis and storage as being critical for the survival of these cells . These transcription factors , nuclear receptor subfamily 1 , group D , member 1 ( NR1D1 ) and peroxisome proliferator activated receptor gamma binding protein ( PBP ) , both reside on ERBB2-containing 17q12-21 amplicons and are part of the ERBB2 expression signature . We show that NR1D1 and PBP act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network , which is highly active in ERBB2-positive breast cancer cells . Malate dehydrogenase 1 and malic enzyme 1 , enzymes that link glycolysis and fatty acid synthesis , are also regulated by NR1D1 . The resulting high-level fat production from increased expression of these genes likely contributes to an abnormal cellular energy metabolism based on aerobic glycolysis . Together , these results show that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival .\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: Acute endothelial cell apoptosis and microvascular compromise couple gastrointestinal tract irradiation to reproductive death of intestinal crypt stem cell clonogens ( SCCs ) following high-dose radiation . Genetic or pharmacologic inhibition of endothelial apoptosis prevents intestinal damage , but as the radiation dose is escalated , SCCs become directly susceptible to an alternate cell death mechanism , mediated via ceramide synthase ( CS)-stimulated de novo synthesis of the proapoptotic sphingolipid ceramide , and p53-independent apoptosis of crypt SCCs . We previously reported that ataxia-telangiectasia mutated deficiency resets the primary radiation lethal pathway , allowing CS-mediated apoptosis at the low-dose range of radiation . The mechanism for this event , termed target reordering , remains unknown . Here , we show that inactivation of DNA damage repair pathways signals CS-mediated apoptosis in crypt SCCs , presumably via persistent unrepaired DNA double-strand breaks ( DSBs ) . Genetic loss of function of sensors and transducers of DNA DSB repair confers the CS-mediated lethal pathway in intestines of sv129/B6Mre11(ATLD1/ATLD1) and C57BL/6(Prkdc/SCID) ( severe combined immunodeficient ) mice exposed to low-dose radiation . In contrast , CS-mediated SCC lethality was mitigated in irradiated gain-of-function Rad50(s/s) mice , and epistasis studies order Rad50 upstream of Mre11 . These studies suggest unrepaired DNA DSBs as causative in target reordering in intestinal SCCs . As such , we provide an in vivo model of DNA damage repair that is standardized , can be exploited to understand allele-specific regulation in intact tissue , and is pharmacologically tractable .\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 protein toxins ricin , abrin , Shiga toxin , and diphtheria toxin were found to induce lysis of several cell lines in a manner characteristic for programmed cell death or apoptosis . The toxins induced DNA degradation , and light and electron microscopical studies revealed that lysis was preceded by reorganization of intracellular vacuoles , cell blebbing , and chromatin condensation both in Vero and in MDCK cells . Cell lysis was efficiently inhibited by cycloheximide and 3-methyladenine ( 3MA ) , a specific inhibitor of autophagy . Cycloheximide , which like 3MA inhibits autophagy , protected even when added at a time when the protein synthesis had been blocked by ricin , suggesting that the effect of cycloheximide on cell lysis is independent of its ability to inhibit protein synthesis . Also theophylline and dibutyryl-cGMP had some protective effect , whereas a number of compounds reported to protect against apoptosis in other systems were without protective effects . The data suggest that autophagy is important for the toxin-induced cell lysis .\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: Apoptosis , programmed cell death , was previously shown to be induced by the mAb anti-APO-1 ( IgG3 , kappa ) by binding to the APO-1 cell surface Ag , a new member of the nerve growth factor/TNF receptor superfamily . To investigate the role of the Ig H chain Fc regions we compared induction of apoptosis by the original mAb IgG3 anti-APO-1 with anti-APO-1 F(ab')2 fragments and different anti-APO-1 isotypes ( IgG1 , IgG2b , IgG2a , and IgA ) isolated by sequential sublining . We found that IgG3 was the most active isotype ; IgG1 , IgG2a , and IgA showed intermediate activity , and IgG2b and F(ab')2 were inactive . Cytotoxic activity of the inactive or less active antibody preparations was fully reconstituted by protein A , anti-mouse Ig , or anti-mouse Ig F(ab')2 , respectively . Thus , APO-1-mediated induction of apoptosis was dependent on efficient cross-linking of APO-1 cell surface Ag , indirectly augmented by anti-APO-1 Fc-Fc self-aggregation . Because of their different in vitro activity we selected IgG3- , IgG2b- , and IgA anti-APO-1 to test their antitumor activity against solid human B lymphoblastoid tumors in SCID mice . The isotypes showed a different serum half-life ( IgG3 : 9.2-10.4 days , IgG2b : 1.9-2.6 days , and IgA : 14.1-29.2 h ) and a different initial tumor localization 4 h after i.p. injection ( IgG3 around the blood vessels , IgG2b homogeneously , and IgA heterogeneously distributed in the tumor ) . All antibody preparations induced tumor regression by induction of apoptosis , even IgG2b anti-APO-1 inactive in vitro without cross-linking . The activity of IgA anti-APO-1 , which did not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity indicates that apoptosis may be used as the main if not the only mechanism of induction of tumor regression in vivo . As with in vitro , IgG3 anti-APO-1 was the most effective isotype also in vivo . This result suggests that cross-linking of APO-1 on the tumor cell surface may also be required for tumor regression by apoptosis in vivo . Taken together , our data show that selective targeting of apoptosis to tumors may be an efficient antitumor mechanism .\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 have extended our studies on the relationship between cisplatin/carboplatin-induced DNA damage in readily accessible tissue(s) and clinical response to therapy . Such an approach may assist in the study of cancer drug resistance and in establishing parameters for assessing human populations for sensitivity to DNA damaging agents in the environment . Platinum-DNA adduct levels were measured by atomic absorbance spectrometry . DNA repair capacity was assessed in human T-lymphocytes by the ability to repair cisplatin lesions in cellular DNA or in transfected plasmid DNA . In a \" blinded \" study of 21 patients receiving combination cisplatin/carboplatin drug therapy , there was a direct relationship between DNA damage in leukocytes and disease response ( summary two-sided p = 0.00011 ) . The cohort of patients had 15 different tumor types , suggesting that blood tissue and tumor tissue of an individual may process platinum-DNA damage similarly regardless of the tissue of origin of the tumor . In leukocytes in vivo , persistence and accumulation were prominent features of the cisplatin-DNA adduct profile . Functional DNA repair capacity has been studied in eight human leukocyte cell lines in vitro ( three , T-cells ; three , B-cells ; one , monocytic ; one , promyelocytic ) , using a host cell reactivation assay with cisplatin-damaged pRSVcat . In the three T cell lines studied , host cell reactivation efficiency was directly related to the cells ' abilities to repair cisplatin-damaged cellular DNA ( correlation coefficient = 0.993).(ABSTRACT TRUNCATED AT 250 WORDS )\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: Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types . Here we analysed polymorphisms in 5 genes involved in DNA repair ( XPD Asp312Asn and Lys751Gln , XRCC1 Arg399Gln , APE1 Asp148Glu , NBS1 Glu185Gln , and XPA G-4A ) and in a gene involved in regulation of the cell-cycle ( CCND1 A870G ) . We compared their frequencies in groups of colon , head and neck , and breast cancer patients , and 2 healthy control groups : ( 1 ) matched healthy Polish individuals and ( 2 ) a NCBI database control group . Highly significant differences in the distribution of genotypes of the APE1 , XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals . The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer ( OR = 1.9-2.3 and OR = 1.5-2.1 , respectively ) . Additionally , frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer . Importantly , no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients . The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses .\n OUTPUT:\n" }, { "from": "agent", "value": "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: Urokinase plasminogen activator receptor ( uPAR ) activates alpha5beta1 integrin and ERK signaling , inducing in vivo proliferation of HEp3 human carcinoma . Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin ( FN ) induced growth pathway . Its activation is ligand-independent and does not require high EGFR , but does require high uPAR expression . Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated . Domain 1 of uPAR is crucial for EGFR activation , and FAK links integrin and EGFR signaling . Inhibition of EGFR kinase blocks uPAR induced signal to ERK , implicating EGFR as an important effector of the pathway . Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo . These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling , providing cancer cells with proliferative advantage .\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 studied the mutagenic specificity of abasic sites using the yeast oligonucleotides transformation assay . We introduced oligonucleotide containing a natural abasic site and a tetrahydrofuran abasic site into Rev1 mutants , rev1AA , which contains mutations of Asp467 and Glu468 residues of Rev1p to Ala in order to inactivate dCMP transferase activity , and rev1 delta , which lacks its whole coding sequence . The transformation efficiencies of rev1AA with abasic-containing oligonucleotides were lower than those of B7528 , a strain proficient in REV1 gene , but much higher than rev1 delta mutant . Sequence analysis opposite the lesions showed that the mutation spectra were different among these three strains .\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 aryl hydrocarbon receptor ( AhR ) is a ligand-activated transcription factor . Recent studies have reported the anti-tumor effects of the AhR in breast cancer . In this study , we investigated the anti-tumor effect of AhR activation based on the cancer stem cell hypothesis . We show that AhR activation suppressed mammosphere formation of MCF-7 cells and decreased the proportion of cells with high ALDH-1 ( aldehyde dehydrogenase 1 ) activity . In addition , we also demonstrate that AhR activation regulates self-renewal signaling by down-regulating Wnt/β-catenin and Notch .\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: Bioenergetic profiling of tumors is a new challenge of cancer research and medicine as therapies are currently being developed . Meanwhile , methodological means must be proposed to gather information on tumor metabolism in order to adapt these potential therapies to the bioenergetic specificities of tumors . Studies performed on tumors and cancer cell lines have shown that cancer cells bioenergetics is highly variable . This profile changes with microenvironmental conditions ( eg. substrate availability ) , the oncogenes activated ( and the tumor suppressors inactivated ) and the interaction with the stroma ( i.e. reverse Warburg effect ) . Here , we assessed the power of metabolic footprinting ( MFP ) to unravel the bioenergetics and associated anabolic changes induced by three oncogenes , c-Myc , KLF4 and Oct1 . The MFP approach provides a quantitative analysis of the metabolites secreted and consumed by cancer cells . We used ultra performance liquid chromatography for quantifying the amino acid uptake and secretion . To investigate the potential oncogene-mediated alterations in mitochondrial metabolism , we measured oxygen consumption rate and ATP production as well as the glucose uptake and lactate release . Our findings show that c-Myc deficiency initiates the Warburg effect along with a reduction of mitochondrial respiration . KLF4 deficiency also stimulated glycolysis , albeit without cellular respiration impairment . In contrast , Oct1 deficiency reduced glycolysis and enhanced oxidative phosphorylation efficiency . MFP revealed that c-Myc , KLF4 and Oct1 altered amino acid metabolism with specific patterns . We identified isoleucine , α-aminoadipic acid and GABA ( γ-aminoisobutyric acid ) as biomarkers related . Our findings establish the impact of Oct1 , KLF4 and c-Myc on cancer bioenergetics and evidence a link between oncosecretomics and cellular bioenergetics profile .\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: Prostate cancer is the second most common cancer in elderly men worldwide and its incidence rate is rising continuously . Agents capable of inducing apoptosis in prostate cancer cells seem a promising approach to treat this malignancy . In this study we describe the synthesis of a number of novel N- and N,N'-substituted S-2,3,4,5,6-pentabromobenzylisothiouronium bromides and their activity against the human prostate adenocarcinoma PC3 cell line . All the compounds produced changes in mitochondrial transmembrane potential and cell cycle progression , showed a cytostatic effect and induced apoptosis in the tested cancer line in a concentration- and time-dependent manner . The most effective compounds ZKK-3 , ZKK-9 and ZKK-13 produced , at 20 microM concentration , apoptosis in 42 , 46 , and 66% of the cells , respectively , after 48 h incubation . Two selected S-2,3,4,5,6-pentabromobenzylisothiouronium bromides ( ZKK-3 , ZKK-9 ) showed also a synergic proapoptotic effect with the new casein kinase II inhibitor 2-(4-methylpiperazin-1-yl)-4,5,6,7-tetrabromo-1H-benzimidazole ( TBIPIP ) in the PC3 cell line .\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: Calcium ( Ca(2+) ) signals are involved in important checkpoints in cell death pathways and promote both apoptosis and autophagy . However , the relationship between autophagy and apoptosis in response to Ca(2+) level elevation is poorly understood . Here , we provided evidence that the influx of extracellular Ca(2+) triggered by Trichokonin VI ( TK VI ) , an antimicrobial peptide , induced calpain-dependent apoptosis and autophagy in hepatocellular carcinoma ( HCC ) cells . Remarkably , TK VI preferentially induced apoptosis that was associated with calpain-mediated Bax and Atg5 cleavage , which resulted in the collapse of the mitochondrial membrane potential and cytochrome c release . Interestingly , truncated , but not full-length Atg5 , associated with Bcl-xL and promoted the intrinsic pathway . Moreover , TK VI treatment induced reactive oxygen species ( ROS ) accumulation , an effect in which Bak might play a major role . This accumulation of ROS resulted in the subsequent disposal of damaged mitochondria within autophagosomes via Atg5-mediated and mitochondria-selective autophagy . Both the inhibition of calpain activity and Bax deficiency activated a switch that promoted an enhancement of autophagy . The inhibition of both apoptosis and autophagy significantly attenuated the TK VI cytotoxicity , indicating that the two processes had stimulatory effects during TK VI-meditated cell death . These results suggested that calpain , Bak and Atg5 were molecular links between autophagy and apoptosis and revealed novel aspects of the crosstalk between these two processes . The potential of TK VI is proposed as a promising anticancer agent for its well-characterized activity of Ca(2+) agonist and as a possible novel therapeutic strategy that acts on cancer cell mitochondria .\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: The expression of the angiogenic phenotype is regulated by a balance of pro-angiogenic and anti-angiogenic factors released into the tumor microenvironment . Nuclear protein 7 ( NOL7 ) , a novel tumor suppressor , acts as a master regulator of angiogenesis by downregulating pro-angiogenic factors and upregulating anti-angiogenic factors . Using cervical cancer as a model of investigation , we have previously shown that loss of NOL7 mRNA and protein expression is observed as early as the premalignant phase . Analysis of the gene failed to identify tumor-specific promoter methylation or coding region mutations , suggesting that NOL7 loss may be mediated by aberrant expression of its upstream regulators . In this study , we show that the RB tumor suppressor gene ( RB ) positively regulates NOL7 at the transcriptional level by recruiting transcription factors and transcription machinery proteins to its promoter region . Conversely , the loss of RB represses NOL7 transcription by inhibiting assembly of these proteins . This loss of NOL7 expression is also observed in RB-deficient human malignancies . Together , this work further characterizes the transcriptional activator function of RB and defines a potential role for RB in regulating angiogenesis through activation of NOL7 . Current anti-angiogenic therapies lack long-term efficacy , as they are unable to target the diverse angiogenic signals generated by tumors . Our data provide evidence to support the hypothesis that reactivation of pRB can potentially modulate the expression of the angiogenic phenotype through regulation of NOL7 . Therefore , this knowledge may be employed to design more comprehensive and effective therapies .\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: Many cells in mammals exist in the state of quiescence , which is characterized by reversible exit from the cell cycle . Quiescent cells are widely reported to exhibit reduced size , nucleotide synthesis , and metabolic activity . Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes . In contrast , we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition . By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data , we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells , with greater overflow flux from the pentose phosphate pathway back to glycolysis . Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts . By feeding the cells labeled glutamine , we also detected a \" backwards \" flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts ; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis . The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid , and in part toward excretion of extracellular matrix proteins . Thus , reduced metabolic activity is not a hallmark of the quiescent state . Quiescent fibroblasts , relieved of the biosynthetic requirements associated with generating progeny , direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;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: The HOX11 gene encodes a homeodomain transcription factor that is essential for spleen development during embryogenesis . HOX11 is also leukaemogenic , both through its clinical association with childhood T-cell acute lymphoblastic leukaemia , and its ability to immortalize other haematopoietic cell lineages experimentally . To examine the pathological role of HOX11 in tumorigenesis , we constitutively expressed HOX11 cDNA in J2E murine erythroleukaemic cells , which are capable of terminal differentiation . Enforced HOX11 expression was found to induce a profound alteration in J2E cellular morphology and differentiation status . Our analyses revealed that HOX11 produced clones with a preponderance of less differentiated cells that were highly adherent to plastic . Morphologically , the cells overexpressing HOX11 were larger and had decreased globin levels , as well as a reduction in haemoglobin synthesis in response to erythropoietin ( EPO ) . Immunocytochemical analysis confirmed the immature erythroid phenotype imposed by HOX11 , with clones transfected with HOX11 demonstrating expression of the c-Kit stem cell marker , while retaining EPO receptor expression . Taken together , these results show that HOX11 alters erythroid differentiation , favouring a less mature progenitor-like stage . This supports the notion that disrupted haematopoietic cell differentiation is responsible for pre-leukaemic immortalization by the HOX11 oncoprotein .\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: We have previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer . We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature . In the present study , we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases . We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998 , and analyzed the corresponding primary colorectal cancers clinicopathologically . Microscopic bile duct invasion was found in 89 of 217 cases ( 40.6% ) and , of these cases , 23 ( 10.6% ) had macroscopic intrabiliary extension . Histological sections of the corresponding primary colorectal cancer were available in eight ( group A ) of these 23 cases . These were compared with 20 cases , selected randomly , of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases . These patients underwent hepatectomy during the same period as group A and were used as a control ( group B ) . The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B ( P &lt ; 0.01 ) , while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups . These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases . Careful histological evaluation is important even for metastatic tumors .\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: Oncogene-induced senescence is now recognized as being an important mechanism in protecting against cancer . The phenotypic consequences , i.e. , the inhibition of cell proliferation , are well described in model systems and specific events/key players defined . However , there is still the need to understand , at a more global level , the network of events involved both in terms of cause and consequence . This paper shows the power of systematic proteomic analyses , both targeted and global , in addressing such biological questions , highlighting the widespread nature of histone acetylation changes , and the opposite metabolic changes to those seen in the Warburg effect .\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: BACKGROUND : CD81 is a transmembrane protein that serves as a putative receptor for hepatitis C virus . In addition , CD81 has been suggested to be involved in a broad range of other cellular functions . Its putative implication in tumorigenesis has so far , however , remained largely unexplored . To assess the candidacy of CD81 as a tumor suppressor in gastric cancer development , we investigated its expression and function in a series of primary gastric tumors and gastric tumor-derived cell lines . METHODS : The expression and concomitant methylation status of the CD81 gene and its effect on tumor development and cellular signaling were evaluated . RESULTS : CD81 mRNA levels were found to be low in 16 of 40 ( 40% ) primary tumors and 9 of 14 ( 64.2% ) cell lines , and these low expression levels were found to correlate with the stage and grade of the tumors . Genomic alterations of CD81 were not encountered , whereas its expression could be re-activated in low expressing cells upon 5-aza-dC treatment . Bisulfite DNA sequencing analysis of 10 CpG sites within the 5 ' proximal region of the CD81 gene promoter revealed that the observed transcriptional silencing was tightly associated with aberrant hypermethylation . Subsequent restoration of CD81 expression induced a G(1) cell cycle arrest and apoptosis , whereas siRNA-mediated CD81 down-regulation promoted cell proliferation and attenuated cellular responses to various apoptotic stress stimuli . Also the colony-forming ability of the tumor cells could be inhibited and enhanced through CD81 up- and down-regulation , respectively . CD81 was found to inhibit p38 ( but not ERK , JNK and AKT ) phosphorylation and its growth suppressive effect could be abolished through p38 up- and down-regulation . CONCLUSION : From our data we conclude that epigenetic inactivation of CD81 is a common feature of gastric tumors and that this inactivation may render growth and survival advantages to the tumor cells , at least partially through p38 signaling .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Epidemiologic studies have examined the association between fruit and vegetable ( F&V ) consumption and the risk of cancer . Several cancer-preventive mechanisms have been proposed , such as antioxidant properties and modulation of biotransformation enzyme activities ; both may be associated with reducing DNA damage and hence the mutation rate . We investigated , in a randomized , controlled , crossover feeding trial , the effect of 10 servings/day of botanically defined F&V for 2 wk on endogenous DNA damage ; resistance to gamma -irradiation damage ; and DNA repair capacity in lymphocytes , measured by the Comet assay . We also explored the association between the UGT1A1*28 polymorphism and serum bilirubin concentrations and DNA damage and repair measures . Healthy men ( n = 11 ) and women ( n = 17 ) , age 20 to 40 yr , provided blood samples at the end of each feeding period . Overall , F&V did not affect DNA damage and repair measures in lymphocytes . The number of UGT1A1*28 alleles was inversely associated with sensitivity to gamma -irradiation exposure and DNA repair capacity , but a biological mechanism to explain this association is unclear . A larger sample size is needed to investigate the association between bilirubin concentrations and endogenous DNA damage . With inconsistent findings in the literature , additional dietary intervention studies on the effect of F&V on DNA damage and repair are needed .\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: MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium . The effects on cell proliferation , glycolysis , and glutaminolysis were investigated . Of all adenosine derivatives tested , AMP was the most efficient inhibitor of cell proliferation . In AMP-treated cells , DNA synthesis decreased , whereas RNA and protein syntheses rose normally with time . In terms of carbohydrate metabolism , lactate production from glucose was drastically reduced ; therefore , most of lactate produced must have been derived from glutamine . Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed . In contrast , actual glycolytic flux rates declined , whereas key glycolytic enzyme activities increased . Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells . Based on the lowered NAD level in the AMP-treated cells , lactate dehydrogenase , but not malate dehydrogenase , was impaired ; thereby the whole of glycolysis was inhibited . In compensation , glutamine catabolism was increased . NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels . A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented .\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: OBJECTIVE To evaluate the risk factors for sentinel lymph node metastasis and validate the value of the Memorial Sloan-Kettering Cancer Center nomogram for the prediction of sentinel lymph node metastasis in breast cancer patients . METHODS A sentinel lymph node biopsy database containing 1227 consecutive breast cancer patients ( 416 patients with at least one positive sentinel lymph node ) was retrospectively analyzed . The predictive value of the Memorial Sloan-Kettering Cancer Center nomogram was calculated by the trend line and the area under the receiver-operator characteristic curve . Meanwhile , predictors for sentinel lymph node metastasis were also evaluated . RESULTS Tumor size , histological grade , lymphovascular invasion , mulifocality , estrogen receptor and progesterone receptor status were significant independent predictors for sentinel lymph node metastasis ( all P<0.01 ) . The Memorial Sloan-Kettering Cancer Center nomogram presented an area under the receiver-operator characteristic curve value of 0.730 . Patients with predictive value<16% had a frequency of sentinel lymph node metastasis of 0.9% . Those with values larger than 70% had a frequency of 96.2% . CONCLUSIONS The risk factors for sentinel lymph node metastasis in our study were consistent with those in the Memorial Sloan-Kettering Cancer Center nomogram . The Memorial Sloan-Kettering Cancer Center nomogram is a useful tool that could accurately predict the probability of sentinel lymph node metastasis in our breast cancer patients . Axillary surgical staging might be avoided in patients with a predictive value of <16% and axillary lymph node dissection might be done directly in those with a predictive value >70% , while other patients should still accept sentinel lymph node biopsy .\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 CDC4/FBXW7 , encoding a ubiquitin ligase , maps to 4q32 and has been implicated as a tumor suppressor gene and therapeutic target in many tumor types . Mutations in colonic adenomas , and the frequent losses on 4q described in gastric cancer prompt speculation about the role of CDC4/FBXW7 in gastric carcinogenesis . METHODS We assessed the role of CDC4/FBXW7 in gastric cancer , through loss of heterozygosity ( LOH ) and multiplex ligation-dependent probe amplification ( MLPA ) on 47 flow-sorted gastric carcinomas including early-onset gastric cancers ( EOGC ) and xenografted conventional gastric carcinomas . Ploidy analysis was carried out on 39 EOGCs and immunohistochemistry of CDC4/FBXW7 and its substrates c-myc , c-jun , Notch and cyclin E was performed on 204 gastric carcinomas using tissue microarrays ( TMAs ) . Sequence analysis of CDC4/FBXW7 was carried out on gastric carcinoma cell lines and xenografts . RESULTS Loss of heterozygosity of CDC4/FBXW7 occurred in 32% of EOGCs , and correlated with loss of expression in 26% . Loss of expression was frequent in both EOGC and conventional gastric cancers . No CDC4/FBXW7 mutations were found and loss of CDC4/FBXW7 did not correlate with ploidy status . There was a significant correlation between loss of CDC4/FBXW7 expression and upregulation of c-myc . CONCLUSION Loss of CDC4/FBXW7 appears to play a role in both EOGC and conventional gastric carcinogenesis , and c-myc overexpression is likely to be an important oncogenic consequence of CDC4/FBXW7 loss .\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 studied the effect of oxidative stress induced by hyperoxia , hydrogen peroxide , or menadione on mouse leukemia P388 cells at early ( 4 days ) and late ( 7 days ) stages of tumor growth . Oxidative stress proved to inhibit cell division and to induce apoptosis . Seven-day leukemia cells feature lower proliferative potential and higher sensitivity to oxidative stress and platidiam .\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: Zinc dyshomeostasis can induce cell death . However , the mechanisms involved have not been fully elucidated in prostate cancer ( PCa ) cells , which differ dramatically from normal cells in their zinc handling ability . Here , we studied the effects of the ionophore Zn-pyrithione ( ZP ) and the chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine ( TPEN ) . Both compounds induced cell death at micromolar concentrations when incubated with androgen-dependent ( LNCaP ) , androgen-independent ( PC3 , DU145 ) and androgen-sensitive ( C4-2 ) PCa cell-lines . Compared to PCa cells , RWPE1 prostate epithelial cells were less sensitive to ZP and more sensitive to TPEN , but total cellular zinc levels were changed similarly . ZnSO4 enhanced the toxicity of ZP , but inhibited the effects of TPEN as expected . The morphological/biochemical responses to ZP and TPEN differed . ZP decreased ATP levels and stimulated ERK , AKT and PKC phosphorylation . DNA laddering was observed only at low doses of ZP but all doses of TPEN . TPEN activated caspase 3/7 and induced PARP-cleavage , DNA-fragmentation , ROS-formation and apoptotic bodies . PKC and ERK-pathway inhibitors , and antioxidants protected against ZP-induced but not TPEN-induced death . Inhibitors of MPTP-opening protected both . Cell death in response to TPEN ( but not ZP ) was diminished by a calpain inhibitor and largely prevented by a caspase 3 inhibitor . Overall , the results indicated primarily a necrotic cell death for ZP and an apoptotic cell death for TPEN . The enhanced sensitivity of PCa cells to ZP and the apparent ability of ZP and TPEN to kill quiescent and rapidly dividing cells in a p53-independent manner suggest that ZP/TPEN might be used to develop adjunct treatments for PCa .\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: MD-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa ( an oriental edible mushroom ) . Intraperitoneal ( i.p. ) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system . In this study , we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models . After oral administration , MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells ( DCs ) present in the Peyer's patch . The captured MD-Fraction was then transported to the spleen , thereby inducing the systemic immune response . Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway . The therapeutic response of orally administered MD-Fraction was associated with ( i ) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs , ( ii ) increased infiltration of the activated T cells into the tumor , and ( iii ) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells . Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer. � 2012 Wiley Periodicals , Inc .\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: This study is to investigate the effects of bortezomib on the angiogenesis of mesenchymal stem cells ( MSCs ) . We examined the effects of bortezomib on the cellular proliferation , migration , and capillary network formation of HUVECs cocultured with CMs of MSCs . We found that Bortezomib inhibited the cellular proliferation and tube formation of HUVECs cocultured with CMs in a dose-dependent fashion . Bortezomib also prevented the migration of HUVECs cocultured with CMs . In addition , bortezomib dose-dependently inhibited the growth of MSCs and prevented the production of angiogenic factors including VEGF ( vascular endothelial growth factor ) , HGF ( hepatocyte growth factor ) , and bFGF ( basic fibroblast growth factor ) in MSCs . In conclusion , bortezomib prevented the angiogenesis mediated by MSCs .\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: Genetic immunotherapy with tumor antigen gene-modified dendritic cells ( DC ) generates robust immunity , although antitumor protection is not complete in all models . Previous experience in a model in which C57BL/6 mice immunized with DC transduced with adenoviral vectors expressing MART-1 demonstrated a 20-40% complete protection to a tumor challenge with B16 melanoma cells . Tumors that did develop in immunized mice had slower growth kinetics compared to tumors implanted in na�ve mice . In the present study , we wished to determine if the supraphysiological production of the Th1-skewing cytokine interleukin-12 ( IL-12 ) could enhance immune activation and antitumor protection in this model . In a series of experiments immunizing mice with DC cotransduced with MART-1 and IL-12 , antitumor protection and antigen-specific splenocyte cytotoxicity and interferon gamma production inversely correlated with the amount of IL-12 produced by DC . This adverse effect of IL-12 could not be explained by a direct cytotoxic effect of natural killer cells directed towards DC , nor the production of nitric oxide leading to down-regulation of the immune response - the two mechanisms previously recognized to explain immune-suppressive effects of IL-12-based vaccine therapy . In conclusion , in this animal model , IL-12 production by gene-modified DC leads to a cytokine-induced dose-dependent inhibition of antigen-specific antitumor protection .\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: BACKGROUND Although basal cell carcinoma ( BCC ) is the most common type of skin cancer , the incidence of metastasis is exceedingly low . OBJECTIVE Case presentation of a basal cell carcinoma arising on the dorsum of the foot with inguinal and pelvic lymph node metastases . METHOD Case presentation with literature review . RESULT On the basis of our review of Japanese literature , the risk factors for BCC metastasis are occurrence on the genitalia , diameter of more than 3 cm , deep invasion of tumor cells into extradermal structures , and infiltrative/morpheic histological type . CONCLUSION Although metastasis from BCC is extremely rare , the prognosis of metastatic BCC is often poor . Careful follow-up is recommended in cases with high 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: The secretin receptor ( SR ) , a G protein-coupled receptor , mediates the effects of the gastrointestinal hormone secretin on digestion and water homeostasis . Recently , high SR expression has been observed in pancreatic ductal adenocarcinomas , cholangiocellular carcinomas , gastrinomas , and bronchopulmonary carcinoid tumors . Receptor overexpression associates with enhanced secretin-mediated signaling , but whether this molecule plays an independent role in tumorigenesis is currently unknown . We recently discovered that pheochromocytomas developing in rats affected by the MENX ( multiple endocrine neoplasia-like ) syndrome express at very high-level Sctr , encoding SR . We here report that SR are also highly abundant on the membranes of rat adrenal and extraadrenal pheochromocytoma , starting from early stages of tumor development , and are functional . PC12 cells , the best characterized in vitro pheochromocytoma model , also express Sctr at high level . Thus , we used them as model to study the role of SR in neoplastic transformation . Small interfering RNA-mediated knockdown of Sctr decreases PC12 cells proliferation and increases p27 levels . The proproliferative effect of SR in PC12 cells is mediated , in part , by the phosphatidylinositol 3 kinase ( PI3K)/serine-threonine protein kinase ( AKT ) pathway . Transfection of Sctr in Y1 adrenocortical carcinoma cells , expressing low endogenous levels of Sctr , stimulates cell proliferation also , in part , via the PI3K/AKT signaling cascade . Because of the link between SR and PI3K/AKT signaling , tumor cells expressing high levels of the receptor ( MENX-associated primary pheochromocytoma and NCI-H727 human bronchopulmonary carcinoid cells ) respond well and in a SR-dependent manner to PI3K inhibitors , such as NVP-BEZ235 . The association between SR levels and response to PI3K inhibition might open new avenues for the treatment of tumors overexpressing this receptor .\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: Photodynamic therapy ( PDT ) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue . We therefore investigated interstitial tumour illumination as a means of selective PDT . A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats . Photofrin was administered ( 5 mg kg-1 i.v. ) 2 days before laser illumination . Tumours with a mean ( +/- s.e. ) diameter of 5.7 +/- 0.1 mm ( n = 106 , 20 days after implantation ) were illuminated with 625 nm light , at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100 , 200 , 400 , 800 or 1600 J cm-1 . Control groups received either laser illumination only , Photofrin only or diffuser insertion only . Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas . Long-term effects were studied on day 36 . To determine the biochemistry of liver damage and function , serum ASAT and ALAT levels were measured on day 1 and 2 , and antipyrine clearance on day 1 . Tumour and surrounding liver necrosis increased with light dose delivered ( P &lt ; 0.001 ) . Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals . No deterioration in liver function was found . The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage .\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: Dendritic cells ( DCs ) and natural killer ( NK ) cells are central components of innate immunity for controlling tumor growth . The therapeutic effects of certain anti-myeloma drugs are partially mediated by targeting the innate immune response . In addition , novel types of natural compounds have been developed that efficiently modulate the activity of both the cellular and humoral compartments of immunity . MGN-3 is known as an activator of natural killer cells , inducer of apoptosis and cytokine production , and modulator of dendritic cell maturation and differentiation in vitro . We have performed a randomized , placebo-controlled study to examine the effects of MGN-3 on innate immune system parameters in 48 multiple myeloma patients . We performed immunophenotypic analysis of peripheral blood samples , determined NK cell activity , and assessed the cytokine profiles of plasma before and during 3months of treatment . The results demonstrate a clear increase in NK activity in MGN-3-treated patients compared to the placebo group , an increased level of myeloid DCs in peripheral blood , and augmented concentrations of T helper cell type 1-related cytokines . The present study suggests that MGN-3 may represent an immunologically relevant product for activating innate immunity in multiple myeloma patients and warrants further testing to demonstrate clinical efficacy .\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: Colorectal cancer ( CRC ) is one of the leading causes of cancer deaths in Western countries . A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease . MicroRNAs ( miRNAs ) are aberrantly expressed in cancers and appear to have both diagnostic and prognostic significance . In this study , we identified novel miRNAs associated with recurrence of CRC , and their possible mechanism of action . TaqMan� Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosas and 46 microsatellite stable CRC tumors . Four miRNAs ( miR-362-3p , miR-570 , miR-148a* and miR-944 ) were expressed at a higher level in tumors from patients with no recurrence ( p &lt ; 0.015 ) , compared to tumors from patients with recurrence . A significant association with increased disease free survival was confirmed for miR-362-3p in a second independent cohort of 43 CRC patients , using single TaqMan� microRNA assays . In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability , and proliferation mainly due to cell cycle arrest . E2F1 , USF2 and PTPN1 were identified as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p . Subsequently , these genes were confirmed as direct targets by Luciferase reporter assays . Their knockdown in vitro phenocopied the effects of miR-362-3p over-expression . We conclude that miR-362-3p may be a novel prognostic marker in CRC , and hypothesize that the positive effects of augmented miR-362-3p expression may in part be mediated through the targets E2F1 , USF2 and PTPN1. � 2012 Wiley Periodicals , Inc .\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: Heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) is a member of the epidermal growth factor family and has a variety of physiological and pathological functions . Modulation of HB-EGF activity might have a therapeutic potential in the oncology area . We explored the therapeutic possibilities by characterizing the in vitro biological activity of anti-HB-EGF monoclonal antibody Y-142 . EGF receptor ( EGFR ) ligand and species specificities of Y-142 were tested . Neutralizing activities of Y-142 against HB-EGF were evaluated in EGFR and ERBB4 signaling . Biological activities of Y-142 were assessed in cancer cell proliferation and angiogenesis assays and compared with the anti-EGFR antibody cetuximab , the HB-EGF inhibitor CRM197 , and the anti-vascular endothelial growth factor ( VEGF ) antibody bevacizumab . The binding epitope was determined with alanine scanning . Y-142 recognized HB-EGF as well as the EGFR ligand amphiregulin , and bound specifically to human HB-EGF , but not to rodent HB-EGF . In addition , Y-142 neutralized HB-EGF-induced phosphorylation of EGFR and ERBB4 , and blocked their downstream ERK1/2 and AKT signaling . We also found that Y-142 inhibited HB-EGF-induced cancer cell proliferation , endothelial cell proliferation , tube formation , and VEGF production more effectively than cetuximab and CRM197 and that Y-142 was superior to bevacizumab in the inhibition of HB-EGF-induced tube formation . Six amino acids in the EGF-like domain were identified as the Y-142 binding epitope . Among the six amino acids , the combination of F115 and Y123 determined the amphiregulin cross-reactivity and that F115 accounted for the species selectivity . Furthermore , it was suggested that the potent neutralizing activity of Y-142 was derived from its recognition of R142 and Y123 and its high affinity to HB-EGF . Y-142 has a potent HB-EGF neutralizing activity that modulates multiple biological activities of HB-EGF including cancer cell proliferation and angiogenic activities . Y-142 may have a potential to be developed into a therapeutic agent for the treatment of HB-EGF-dependent cancers .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]