Datasets:

clinicalnlplab

/

HoC_train

like 0

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input 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 single-strand breaks and associated growth inhibition induced by the thymidylate synthase inhibitor N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazoline-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid ( ICI D1694 ) were quantitated using the human ileocecal adenocarcinoma cell line , HCT-8 . The effects of different concentrations and schedules of [ 6R,S]-5-formyltetrahydrofolate ( [ 6RS]LV ) and 2'-deoxy-thymidine ( dThd ) on drug growth inhibition and DNA damage were also evaluated . The drug concentrations for 50% inhibition of cell growth in culture following 2-h and 72-h exposures were 0.073 and 0.003 microM , respectively . After a 2-h drug exposure , the occurrence of DNA single-strand breaks ( SSBs ) was time dependent . It was detectable at 8 h and reached a maximum at about 24 h , 34 +/- 3 ( SD ) and 305 +/- 34 rad equivalents with 0.1 microM ( 50% inhibition concentration ) and 1.0 microM ( 90% inhibition concentration ) ICI D1694 , respectively . A significant level of DNA SSBs ( 101 +/- 13 rad equivalents ) was still detectable at 72 h after the 2-h treatment with 1 microM ICI D1694 . No significant level of DNA SSBs was detected when cells were exposed simultaneously to ICI D1694 and 20 microM [ 6RS]LV . Complete rescue of drug-induced DNA SSBs could be achieved when cells were exposed to 10 microM dThd starting no later than 4 h after drug treatment . The growth inhibition of ICI D1694 was abrogated by [ 6RS]LV in a concentration-dependent manner . Complete protection was achieved when cells were exposed simultaneously to 1 microM ICI D1694 and 5 microMs [ 6RS]LV or to 3 microMs dThd immediately after drug treatment . The results demonstrate that : ( a ) the growth inhibition of ICI D1694 is a function of time and schedule ; ( b ) the growth inhibition is accompanied by extensive DNA single-strand breaks and slow repair ; ( c ) at 1 microM ICI D1694 , 3 microMs dThd and 5 microMs [ 6RS]LV can completely rescue cells from drug effects when dThd is added up to 4 h following drug treatment or when [ 6RS]LV is given in combination with the drug ; ( d ) interference of [ 6RS]LV with ICI D1694 action may be occurring at the level of drug uptake and at intracellular targets , while dThd interferes with the drug action at intracellular targets .\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: UNLABELLED Activation of beta-catenin , the central effector of the canonical Wnt pathway and a recognized oncogene , has been implicated in hepatocellular carcinoma . We examined N-nitrosodiethylamine ( DEN)-induced tumorigenesis in hepatic beta-catenin conditional knockout mice ( beta-cat KO ) . Male beta-cat KO and age- and sex-matched littermate controls were given a single intraperitoneal DEN injection and followed for 6-12 months for hepatic tumors . Hepatic tumors were characterized for histology , proliferation , apoptosis , oxidative stress , and specific proteins by way of western blot , immunohistochemistry , and coprecipitation studies . For in vivo tumor intervention studies , specific inhibitors were administered intraperitoneally or through drinking water . Intriguingly , beta-cat KO mice showed a paradoxical increase in susceptibility to DEN-induced tumorigenesis . This accelerated tumorigenesis is due to increased injury and inflammation , unrestricted oxidative stress , fibrosis , and compensatory increase in hepatocyte proliferation secondary to platelet-derived growth factor receptor alpha ( PDGFRalpha)/phosphoinositide 3-kinase ( PIK3CA)/Akt activation and c-Myc overexpression . In vitro suppression of beta-catenin expression in hepatoma cells led to enhanced PDGFRalpha expression , which was abrogated in the presence of nuclear factor kappaB ( NF-kappaB ) inhibitor . Daily treatment of 6-month-old DEN-exposed beta-cat KO with PDGFRalpha inhibitor dramatically reduced tumor numbers and size . Inclusion of N-acetyl-L-cysteine , a known antioxidant and NF-kappaB inhibitor , in the drinking water led to complete abolition of tumorigenesis in DEN-exposed beta-cat KO . CONCLUSION Loss of beta-catenin impairs the liver's ability to counteract DEN-induced oxidative stress and enhances tumorigenesis through PDGFRalpha/PIK3CA/Akt signaling . Blockade of PDGFRalpha or oxidative stress dramatically affects beta-catenin-deficient tumorigenesis . Also , hepatoma cells use PDGFRalpha/PIK3CA signaling as an escape mechanism following beta-catenin suppression , and their sequential suppression profoundly impedes tumor proliferation .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The Salvador/Warts/Hippo ( Hippo ) signaling pathway defines a novel signaling cascade regulating cell contact inhibition , organ size control , cell growth , proliferation , apoptosis and cancer development in mammals . The upstream regulation of this pathway has been less well defined than the core kinase cassette . KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP , but functional consequences of these biochemical changes have not been previously addressed . We show that in MCF10A cells , loss of KIBRA expression displays epithelial-to-mesenchymal transition ( EMT ) features , which are concomitant with decreased LATS and YAP phosphorylation , but not MST1/2 . In addition , ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA , Willin and Merlin differentially regulate genes controlled by YAP . Finally , reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype , an aggressive sub-group with EMT features and a poor prognosis .\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: Biomaterials such as polyetherurethans ( PEUs ) are the scaffolding , which is indispensable for the development of the bio-artificial organs . However , PEUs can induce tumors in subcutaneous implantation sites in rat . We have shown that the different inhibitory potential of gap junctional intercellular communication ( GJIC ) on the surface of the biomaterials , including PEUs , is a key step in determining the tumorigenic potential . Here we show that suppression of a gap junctional protein connexin 43 ( Cx43 ) plays an important role in in vivo tumorigenesis induced by PEUs for the first time and that Cx43 transfection may be an effective strategy for preventing tumorigenesis induced by biomaterials . Rat tumor cell line U41 is derived from tumors in the subcutaneous implantation of PEU films . The GJIC and the expression of Cx43 were suppressed in U41 . The restoration of normal phenotype , such as reduction of growth rate , recovery of contact inhibition and loss of colony formation ability in soft agar , was achieved by Cx43 transfection . These results strongly suggest that suppression of Cx43 expression plays an important role in the development of rat malignant fibrous histiocytoma ( MFHC ) caused by PEUs and that Cx43 transfection is effective for prevention of tumorigenesis induced by PEUs .\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: At present , isoniazid ( INH ) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer , although it is not clear whether or not this reduces the antitumor efficacy of BCG . In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs . INH was given on the 3 days around each BCG instillation . We found that the administration of INH severely impaired the immunological effects of BCG . The induction of mononuclear cell infiltration in the bladder wall was reduced . Enlargement of the regional lymph nodes ( weight and number of cells ) , and increase of MHC Class II expression on the lymph node cells , normally observed after intravesical BCG administration , were inhibited by INH . Systemic immunity , measured by the DTH reaction in the skin to PPD , was also diminished due to the combined treatment of BCG with INH . When INH was administered during the last 4 of 6 BCG instillations , the immune response to BCG was still impaired . A five-fold increase of the dose of BCG did not overcome the effect of INH . INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced . Although INH concentrations in the urine were high at the onset of the instillation , in vitro experiments indicated that the effect of INH may not be caused by killing of the BCG organisms shortly after application in the bladder . In conclusion , our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG . As this response may be important for the antitumor effect of BCG , urologists should be cautious with the prophylactic use of INH . The influence on the antitumor efficacy is now investigated in man .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene ( DMBA)-induced rat mammary tumors , by simultaneously investigating the expression of estrogen receptor-alpha ( ERalpha ) , estrogen receptor-beta ( ERbeta ) , progesterone receptor ( PR ) , apoptosis , neu , and markers of cell proliferation , such as proliferating cell nuclear antigen ( PCNA ) by immunohistochemistry . The percentage of ERalpha positive tumors was 65.8% in masses from control animals , and significantly dropped to 36.8% in tumors from soy treated rats ( P=0.010 ) . The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals ( P=0.066 ) . Moreover , the percentage of cases which were both ERalpha and ERbeta positive was significantly lower ( 17.6% ) in soy treated than in control animals ( 51.3% ) ( P=0.006 ) . The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats ( P=0.0006 ) . There were no statistically significant differences in the percentage of tumors positively stained for neu , apoptosis , or PCNA , in control vs. soy treated rats . However , when analyzing the reciprocal correlation among the different biochemical parameters we showed that , in treated animals , the majority of ERalpha positive tumors ( 91.7% ) were also PCNA positive ( P=0.036 ) . The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors ( 25 vs. 5% ) ( P=0.0031 ) . Moreover , an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive ( P=0.011 ) .\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: Many human cellular and tissue compartments are supersaturated with respect to calcium oxyanion salts . In order to prevent the formation of injurious crystals efficient anti-crystallization protective mechanisms must be necessary . We suggest that depletion of such systems , particularly in ageing organisms and under conditions of oxidative stress , plays an important role in degenerative and inflammatory diseases , including cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Prostate cancer ( PCa ) progression is often associated with transactivation of the androgen receptor ( AR ) by endogenous hormones/growth factors . One such factor affecting growth , proliferation , and apoptostis ( pro-/anti- ) in various cancers is the adipokine leptin . This research studied leptin-induced signaling and apoptosis in androgen sensitive ( LNCaP , PC3/AR ) and insensitive ( PC3 , DU145 ) PCa cell lines . METHODS Signaling was studied by immunoblotting in cells overexpressing leptin receptors ( LRb ) , Janus kinase 2 ( JAK2 ) , and kinase negative-HER2-YFP cDNAs . Apoptosis was measured by immunoblotting of apoptotic proteins and by Hoechst staining of condensed DNA . RESULTS Leptin rapidly induced activation of JAK2 , STAT3 , and MAPK ( ERK1/2 ) signaling cascades ; it may also induce HER2 transactivation via leptin-induced phospho-JAK2 . Leptin was then shown to exert clear pro-apoptotic effects , increasing levels of caspase 3 , cleavage of its substrate , poly ( ADP-ribose ) polymerase ( PARP ) to cleaved PARP(89) , levels of CK 18 , a cytoskeletal protein formed during apoptosis , and DNA condensation . Kinase inhibitors indicated that leptin-induced apoptosis is probably mediated by balanced activation of JAK2/STAT3 , p38 MAPK , and PKC pathways in PCa cells . A human leptin mutein LRb antagonist , L39A/D40A/F41A , fully inhibited leptin-induced phosphorylation of JAK2 , ERK1/2 , and Akt/PKB , and partially abrogated effects on apoptotic proteins . In LNCaP and PC3/AR cells , leptin increased AR protein levels in correlation with raised apoptotic markers . Thus , AR may mediate , at least partly , the leptin-induced apoptotic response . CONCLUSIONS Leptin can clearly induce apoptosis in human PCa cell lines . These findings could lead to development of new leptin agonists with enhanced pro-apoptotic effects and targeted for use in human PCa .\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: Trabecular meshwork ( TM ) cells have widely been used as an invitro model for glaucoma research . However , primary TM cells suffer the disadvantages of limited cell numbers and slow rates of proliferation . We discovered a spontaneously transformed bovine TM ( BTM ) cell line , BTM-28T . This cell line proliferated rapidly in low-glucose culture medium but also demonstrated contact inhibition in high-glucose culture medium . BTM-28T cells expressed key TM cell markers including α-smooth muscle actin ( α-SMA ) , laminin and collagen IV ( col IV ) . Also , 100nM dexamethasone ( DEX ) enhanced the formation of cross-linked actin networks ( CLANs ) in confluent BTM-28T cell cultures . Transforming growth factor beta 2 ( TGFβ2 ) induced the expression of fibronectin ( FN ) , plasminogen activator inhibitor-1 ( PAI-1 ) , and connective tissue growth factor ( CTGF ) in our cell cultures . This cell line will be helpful to better understand the aqueous humor outflow pathway as related to the pathophysiology of glaucoma .\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: Nitric oxide ( NO ) shows tumoricidal activity . We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway , but upregulates the MEK/ERK pathway downstream of growth factor signaling . We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone . We determined the effects of S-nitrosoglutathione ( GSNO , NO-donor ) and U0126 ( MEK inhibitor ) on insulin-like growth factor-I ( IGF-I ) and epidermal growth factor ( EGF ) signaling , proliferation and invasion in cancer cell lines . GSNO inhibits phosphorylation of IGF-I receptor ( IGF-IR ) , EGF receptor ( EGFR ) and Akt , but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF . On the other hand , U0126 inhibits phosphorylation of ERK1/2 , but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells . The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR , EGFR , Akt and ERK1/2 after stimulation by IGF-I and EGF . GSNO as well as U0126 , inhibits the proliferation of MIAPaCa-2 , HCT-116 , Panc-1 , MCF-7 , HT-29 and AGS cells in a dose-dependent manner . GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells . These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The telomerase activity and the senescence profile of cultured breast fibroblasts from normal human interstitial and malignant stromal tissue were studied in comparison with their proliferation and differentiation pattern . Fibroblasts were grown either in the presence or absence of a conditioned medium ( CM ) obtained from cultures of the oestrogen receptor-positive breast cancer MCF-7 cell line . At different passages ( from the 2nd up to the 48th ) , fibroblasts were examined for the telomerase activity by the Telomerase Repeats Amplification Protocol ( TRAP ) assay , for proliferation profile by Ki-67 antigen expression , and the myofibroblast or smooth muscle cell-like differentiation pattern by immunofluorescence with monoclonal antibodies specific for smooth muscle markers . Serial passages of fibroblasts from normal or tumour breast reveal that the relationship between the levels of telomerase activity and phenotypic/proliferation profile changes with cell subcultivation in a different manner in the two cell populations . The fibroblasts from normal tissue completed 12 passages in a CM-independent way prior to senescence whereas fibroblasts from tumour stroma senescence were attained after 48 passages . These cells showed a marked decrease of telomerase activity , growth rate and smooth muscle alpha-actin expressing myofibroblasts after the 32nd passage . CM treatment of this fibroblast population induces a decline in the myofibroblast content , which precedes the changes in telomerase activity . Passaged fibroblasts from normal breast tissue can be converted to myofibroblasts upon CM treatment whereas those from tumour stroma were CM-insensitive . Taken together our data suggest that a heterogeneous fibroblast population with different life span is activated/recruited in the breast interstitium and poses the problem of a unique activation/recruitment of fibroblasts in neoplastic conditions .\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: It is well established that hyperplasia and decreased apoptosis of airway smooth muscle cells ( ASMCs ) play an important role in the asthmatic airway remodeling . Tumor suppressor PTEN gene with phosphatase activity plays an important regulatory role in embryonic development , cell proliferation , and apoptosis , cell cycle regulation , migration ( invasion ) of the cytoskeleton . We hypotheses that PTEN gene could affect the growth and viability of ASMCs through the regulation of PI3K/Akt , MAPK , and cell cycle-related gene expression . We constructed a recombinant adenovirus to transfect ASMCs . Cells were divided into the overexpression of PTEN gene group ( Ad-PTEN-GFP ) , negative control group ( Ad-GFP ) , and blank control group ( DMEM ) . The cell apoptosis of ASMCs were evaluated by Hoechst-33342 staining and PE-7AAD double-labeled flow cytometry . The cell cycle distribution was observed by flow cytometry with PI staining . The expression of PTEN , p-Akt , total-Akt , p-ERK1/2 , total-ERK1/2 , cleaved-Caspases-3 , Caspases-9 , p21 , and Cyclin D1 were tested by the Western blotting . Our study revealed that overexpression of PTEN gene did not induce apoptosis of human ASMCs cultured in vitro . However , overexpression of PTEN inhibited proliferation of human ASMCs cultured in vitro and was associated with downregulation of Akt phosphorylation levels , while did not affect ERK1/2 phosphorylation levels . Moreover , overexpression of PTEN could induce ASMCs arrested in the G0/G1 phase through the downregulation of Cyclin D1 and upregulation of p21 expressions .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The multi-kinase inhibitor dasatinib induced a variable but significant decrease of viability in both p53(wild-type) ( EHEB , JVM-2 , JVM-3 ) and p53(mutated) ( MEC-1 , MEC-2 , BJAB ) prolymphocytic B leukemic cells , due to a combination of cell cycle block in G1 and apoptosis . Antibody phospho-kinase array analysis revealed that dasatinib inhibited the phosphorylation of various kinases , including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors , in both p53(wild-type) and p53(mutated) cells . Therefore , dasatinib might offer a novel therapeutic strategy not only for p53(wild-type) , but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches .\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: The aryl hydrocarbon receptor ( AhR ) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds . Several reports have shown that the AhR plays an important role in the control of cell-cycle progression , and this function is thought to be partly associated with the tumor promotion activity of dioxin . However , the underling mechanisms are not fully understood . We have previously shown that overexpression of AhR , as well as AhR ligand treatment , stimulates cell proliferation of human lung cancer A549 cells . In AhR-activated cells , the expression levels of DNA synthesis-related genes such as proliferating cell nuclear antigen ( PCNA ) and RFC38 are notably increased . Expression of these genes is mainly regulated by E2F1 , a transcription factor that is crucial for transition of the cell cycle from G1 to S phase . We show here that the transcriptional activity of E2F1 is increased by the AhR agonist treatment and that this effect depends on the presence of AhR . Functional mapping of AhR showed that the Per-Arnt-Sim ( PAS ) B domain is required for promotion of E2F1 activity . The mechanism involves formation of a complex of AhR and E2F1 on the regulatory region in the E2F1 target gene , followed by recruitment of coactivator activator for thyroid hormone and retinoid receptors ( ACTR ) . Consequently , the results in this study indicate the physiological function of AhR as a potent transcriptional coactivator of E2F1-dependent transcription and implicate the AhR-E2F1 interaction as a part of the mechanism by which AhR/Arnt promotes cell proliferation .\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: Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix . The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion , metastasis , and angiogenesis . However , the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer ( NSCLC ) cells still remain unclear . In the present study , the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide . Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo . Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells , which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo . These findings demonstrate that heparanase plays essential roles in regulating the invasion , proliferation , and angiogenesis of A549 cells .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Patients with invasive breast ductal carcinoma ( IBDC ) with metastasis have a very poor prognosis . Little is known about the synergistic action of growth and inflammatory factors in IBDC metastases . METHODS The expression of activated extracellular signal-regulated kinase1/2 ( phosphorylated or p-ERK1/2 ) was analyzed by immunohistochemistry in IBDC tissue samples from 80 cases . BT474 IBDC cell migration and invasion were quantified using the Transwell assay . Matrix metalloproteinase ( MMP)-9 expression and activity were analyzed by RT-PCR , Western blotting and zymography . Activator protein ( AP)-1 activity was measured with a luciferase reporter gene assay . The Wilcoxon signed-rank test , Chi-square test , the partition of Chi-square test , independent t-test , and Spearman's method were used for the statistical analysis . RESULTS Phosphorylated ERK1/2 was detected in 58/80 ( 72.5% ) IBDC tissues , and was associated with higher TNM stage and lymph node metastasis , but not patient age or tumor size . Individually , epidermal growth factor ( EGF ) , and interleukin ( IL)-1β activated ERK1/2 , increased cell migration and invasion , MMP-9 expression and activity , AP-1 activation in vitro and the expression of p-ERK1/2 was positively correlated with EGF expression levels , as well as IL-1β , MMP-9 and c-fos in IBDC tissue samples . Co-stimulation with EGF and IL-1β synergistically increased ERK1/2 and AP-1 activation , cell migration and invasion , and MMP-9 expression and activity . Inhibition of ERK1/2 using U0126 or siRNA abolished EGF and/or IL-1β-induced cell migration and invasion in a dose-dependent manner . CONCLUSION Activated ERK1/2 was associated with higher TNM stage and lymph node metastasis in IBDC . Both in vitro and in vivo studies indicated that ERK-1/2 activation may increase the metastatic ability of IBDC cells . Growth and inflammatory factors synergistically induced IBDC cell migration and invasion via ERK1/2 signaling , AP-1 activation and MMP-9 upregulation .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Chronic inflammation is a critical component in breast cancer progression . Pro-inflammatory mediators along with growth/survival factors within the tumor microenvironment potentiate the expression of pro-inflammatory cytokines ( IL-1 , IL-6 , TNF-α ) , chemotactic cytokines and their receptors ( CXCR4 , CXCL12 , CXCL8 ) and angiogenic factors ( VEGF ) that often overcome the effect of anti-inflammatory molecules ( IL-4 , IL-10 ) thus evading the host's antitumor immunity . Detailed knowledge , therefore , of the regulatory mechanisms determining cytokine levels is essential to understand the pathogenesis of breast cancer . HIF-1α and NF-κB transcription factors are important players for the establishment of a pro-inflammatory and potentially oncogenic environment . HIF-1α is the key mediator of the cellular response to oxygen deprivation and induces the expression of genes involved in survival and angiogenesis within solid hypoxic tumors . The expression of these genes is often modulated by the p53 tumor suppressor protein that induces apoptosis or cell cycle arrest in neoplastic cells . Functional crosstalk between HIF-1α and p53 pathways mediated by modulators shared between the two transcription factors such as SRC-1 and SIRT-1 differentially regulate the expression of distinct subsets of their target genes under variable stress conditions . In an attempt to shed light on the complex regulatory mechanisms involved in cancer-related inflammation , we investigated the role of the two common p53 and HIF-1α co-regulators SRC-1 and SIRT-1 , in the expression of the highly potent metastatic chemokine receptor CXCR4 . Both SRC-1 and SIRT-1 overexpression in DSFX-treated MCF-7 cells reduced CXCR4 cellular levels implying that both co-regulators are crucial factors in the determination of the metastatic potential of breast cancer cells .\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: Mice defective in the mismatch repair ( MMR ) gene Msh2 manifest an enhanced predisposition to skin cancer associated with exposure to UVB radiation . This predisposition is further heightened if the mice are additionally defective for the nucleotide excision repair gene Xpc . To test the hypothesis that the predisposition of Msh2 mutant mice to skin cancer reflects a mutator phenotype associated with increased proliferation of skin cells following exposure to UV radiation , Msh2 mutant mice were exposed to the tumor promoter TPA . Such mice showed a robust proliferative response in the skin , but did not manifest evidence of dysplasia or neoplasia . We conclude that the predisposition of Msh2 mice to UVB radiation-induced skin cancer reflects an interaction between the processes of mismatch repair and some other excision repair mode , the exact nature of which remains to be established .\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: TP53 mutations compromising p53 transcriptional function occur in more than 50% of human cancers , including pancreatic adenocarcinoma , and render cancer cells more resistant to conventional therapy . In the last few years , many efforts have been addressed to identify p53-reactivating molecules able to restore the wild-type transcriptionally competent conformation of the mutated proteins . Here , we show that two of these compounds , CP-31398 and RITA , induce cell growth inhibition , apoptosis , and autophagy by activating p53/DNA binding and p53 phosphorylation ( Ser15 ) , without affecting the total p53 amount . These effects occur in both wild-type and mutant p53 pancreatic adenocarcinoma cell lines , whereas they are much less pronounced in normal human primary fibroblasts . Furthermore , CP-31398 and RITA regulate the axis SESN1-2/AMPK/mTOR by inducing AMPK phosphorylation on Thr172 , which has a crucial role in the autophagic response . The protective role of autophagy in cell growth inhibition by CP-31398 and RITA is supported by the finding that the AMPK inhibitor compound C or the autophagy inhibitors chloroquine or 3-methyladenine sensitize both pancreatic adenocarcinoma cell lines to the apoptotic response induced by p53-reactivating molecules . Our results demonstrate for the first time a survival role for autophagy induced by p53-reactivating molecules , supporting the development of an anti-cancer therapy based on autophagy inhibition associated to p53 activation .\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 yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity . Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms . Here , we show that SIRT1 , the human Sir2 homolog , is recruited to the promyelocytic leukemia protein ( PML ) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras ( Ha-rasV12 ) . SIRT1 binds and deacetylates p53 , a component of PML nuclear bodies , and it can repress p53-mediated transactivation . Moreover , we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation . When overexpressed in primary mouse embryo fibroblasts ( MEFs ) , SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence . Taken together , our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Many reports have emphasized the role of gastrin as a growth factor for normal gastrointestinal mucosa and gastrointestinal cancers . Recent studies have pointed out that this peptide acts also as a growth factor for the pancreatic cancer cell line AR42J . This effect is mediated by gastrin [ cholecystokinin ( CCK)-B ] receptors . In the present study , we investigated gastrin ( CCK-B ) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6 , comparing it to normal rat pancreas , and we also characterized CCK receptor subtypes in this tumor . The results showed that there is extensive gastrin binding to the DSL-6 pancreatic carcinoma . No evidence of specific gastrin binding to normal pancreas was found . Analysis of the ability of gastrin-17-I to inhibit 125I-gastrin-I binding demonstrated that gastrin bound to a single class of receptors with a Kd of 0.21 +/- 0.04 nM and a binding capacity of 184 +/- 29 fmol/mg protein. 125I-Gastrin-I binding was inhibited by the specific CCK-B receptor antagonist L365,260 approximately 40 times more effectively than by the specific CCK-A receptor antagonist L364,718 . Analysis of the ability of cholecystokinin octapeptide ( CCK-8 ) to inhibit 125I-Bolton-Hunter-CCK-8 binding revealed two CCK binding sites , i.e. , a high affinity site and a low affinity site . The observed binding affinities of CCK-8 were then introduced into the computer analysis of the dose-inhibition curve of the ability of gastrin-17-I to inhibit binding of 125I-Bolton-Hunter-CCK-8 , which was significantly better fit by a three-site model than by a two-site model . The three sites meet the criteria for CCK-B , high affinity CCK-A , and low affinity CCK-A receptors . The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites . This study demonstrated that DSL-6 pancreatic carcinoma expresses three subtypes of CCK receptors . Gastrin ( CCK-B ) receptors , which were not detected in normal rat pancreas , constitute about one third of the total high affinity CCK receptors . We suggest that novel expression of gastrin ( CCK-B ) receptors may be generated by gene mutation or amplification during carcinogenesis and may play an important role in promoting tumor growth .\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: Integrin αvβ3 plays a role in insulin-like growth factor 1 ( IGF1 ) signaling ( integrin-IGF1 receptor ( IGF1R ) cross-talk ) in non-transformed cells in anchorage-dependent conditions . We reported previously that IGF1 directly binds to αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation in these conditions . The integrin-binding defective IGF1 mutant ( R36E/R37E ) is defective in inducing ternary complex formation and IGF signaling , whereas it still binds to IGF1R . We studied if IGF1 can induce signaling in anchorage-independent conditions in transformed Chinese hamster ovary cells that express αvβ3 ( β3-CHO ) cells . Here we describe that IGF1 signals were more clearly detectable in anchorage-independent conditions ( polyHEMA-coated plates ) than in anchorage-dependent conditions . This suggests that IGF signaling is masked by signals from cell-matrix interaction in anchorage-dependent conditions . IGF signaling required αvβ3 expression , and R36E/R37E was defective in inducing signals in polyHEMA-coated plates . These results suggest that αvβ3-IGF1 interaction , not αvβ3-extracellular matrix interaction , is essential for IGF signaling . Inhibitors of IGF1R , Src , AKT , and ERK1/2 did not suppress αvβ3-IGF-IGF1R ternary complex formation , suggesting that activation of these kinases are not required for ternary complex formation . Also , mutations of the β3 cytoplasmic tail ( Y747F and Y759F ) that block β3 tyrosine phosphorylation did not affect IGF1R phosphorylation or AKT activation . We propose a model in which IGF1 binding to IGF1R induces recruitment of integrin αvβ3 to the IGF-IGF1R complex and then β3 and IGF1R are phosphorylated . It is likely that αvβ3 should be together with the IGF1-IGF1R complex for triggering IGF signaling .\n OUTPUT:\n" }, { "from": "agent", "value": "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: Increasing evidence shows that estrogens are involved in lung cancer proliferation and progression , and most human lung tumors express estrogen receptor β ( ERβ ) as well as aromatase . To determine if the aromatase inhibitor anastrozole prevents development of lung tumors induced by a tobacco carcinogen , alone or in combination with the ER antagonist fulvestrant , ovariectomized female mice received treatments with the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone ( NNK ) along with daily supplements of androstenedione , the substrate for aromatase . Placebo , anastrozole and/or fulvestrant were administered in both an initiation and a promotion protocol of lung tumorigenesis . The combination of fulvestrant and anastrozole given during NNK exposure resulted in significantly fewer NNK-induced lung tumors ( mean = 0.5 ) compared with placebo ( mean = 4.6 , P &lt ; 0.001 ) , fulvestrant alone ( mean = 3.4 , P &lt ; 0.001 ) or anastrozole alone ( mean = 2.8 , P = 0.002 ) . A significantly lower Ki67 cell proliferation index was also observed compared with single agent and control treatment groups . Beginning antiestrogen treatment after NNK exposure , when preneoplastic lesions had already formed , also yielded maximum antitumor effects with the combination . Aromatase expression was found mainly in macrophages infiltrating preneoplastic and tumorous areas of the lungs , whereas ERβ was found in both macrophages and tumor cells . Antiestrogens , especially in combination , effectively inhibited tobacco carcinogen-induced murine lung tumorigenesis and may have application for lung cancer prevention . An important source of estrogen synthesis may be inflammatory cells that infiltrate the lungs in response to carcinogens , beginning early in the carcinogenesis process . ERβ expressed by inflammatory and neoplastic epithelial cells in the lung may signal in response to local estrogen production .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The colon carcinoma cell line CC531 is metastatic to liver after splenic injection in syngeneic rats . After repeated in vivo passages , a subline was selected that produced liver metastases at a considerably higher rate than the original cell line . These cells were characterized by increased intracellular glutathione , proliferation and ability to restore glutathione after exposure to oxidative stress , thus indicating an elevated resistance to oxidative stress . Furthermore , the increased metastatic ability was also accompanied by increased proliferation rate , adhesion to extracellular matrix proteins and endothelial cells , and secretion of a 60 kD matrix metalloproteinase . When cultured in vitro for a prolonged time ( more than 30 trypsinizations ) , the cells showed a reduced in vivo metastatic ability , reduced secretion of three metalloproteinases including the 60 kD proteinase , and reduced intracellular glutathione . These results indicate that metastatic ability can be influenced through several adaptive mechanisms , and that the cell's ability to resist oxidative stress and maintain intracellular glutathione are of central importance .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: c-myc , c-erbB-2 , and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas . The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues . Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors , while the level of expression in normal breast tissue was much less than that in breast cancer . Membrane staining of the c-erbB-2 protein was demonstrated in 29% ( 4 of 14 ) of noninvasive ductal carcinomas and in 45% ( 19 of 42 ) of invasive breast carcinomas . None of the 11 normal breast tissue samples was positive . The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue , 4.57 +/- 1.36% for noninvasive ductal carcinoma , and 12.76 +/- 2.18% for invasive breast cancer . In 42 invasive breast carcinomas , the expression of c-myc , c-erbB-2 , and Ki-67 proliferation marker were compared with lymph node status , estrogen receptor status , progesterone receptor status , and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status . We concluded that they might be additional prognostic factors for breast carcinoma .\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: p53 plays an important role in regulating a wide variety of cellular processes , such as cell cycle arrest and/or apoptosis . Dysfunction of p53 is frequently associated with several pathologies , such as cancer and neurodegenerative diseases . In recent years substantial progress has been made in developing novel p53-activating molecules . Importantly , modulation of p53 interaction with its main inhibitor , Mdm2 , has been highlighted as a promising therapy target . In this regard , bimolecular fluorescence complementation ( BiFC ) analysis , by providing direct visualization of protein interactions in living cells , offers a straightforward method to identify potential modulators of protein interactions . In this study , we developed a simple and robust Venus-based BiFC system to screen for modulators of p53-p53 and p53-Mdm2 interactions in live mammalian cells . We used nutlin-3 , a well-known disruptor of p53-Mdm2 interaction , to validate the specificity of the assay . The reduction of BiFC signal mediated by nutlin-3 was correlated with an increase in Puma transactivation , PARP cleavage , and cell death . Finally , this novel BiFC approach was exploited to identify potential modulators of p53-Mdm2 complex formation among a commercially available chemical library of 33 protein phosphatase inhibitors . Our results constitute \" proof-of-concept \" that this model has strong potential as an alternative to traditional target-based drug discovery strategies . Identification of new modulators of p53-p53 and p53-Mdm2 interactions will be useful to achieve synergistic drug efficacy with currently used anti-tumor therapies .\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 epidemiologic association between asbestos exposure and human malignant mesothelioma is well established . However , the molecular mechanisms linking asbestos exposure of humans and the subsequent mesothelioma formation is not well understood . The most frequent genetic changes found so far in human malignant mesothelioma ( HMM ) are deletions and point mutations in the tumor suppressor genes p16INK4a and NF2 . Whereas homozygous deletions appear to be the predominant mechanism leading to p16/CDKN2A inactivation , inactivating point mutations coupled with allelic loss mainly occur at the NF2 locus . In the present study , asbestos-treated human mesothelial cells ( HMC ) , SV40-transformed human mesothelial cells ( MeT-5A ) and a human mesothelioma cell line ( COLO ) were investigated for genetic changes of cell cycle genes ( cyclin D1 , p16INK4a , RB1 , CDK2 ) using multicolor fluorescence in situ hybridization ( mFISH ) in interphase cells . The results show that cyclin D1 is unaffected in all investigated cells . The p16INK4a gene locus was shown to be mutated in COLO cells but not in HMC . After labeling of CDK2 and RB1 , hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells . Our data indicate that disarrangement of the RB1 dependent pathway seems to be involved in mesothelioma formation .\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: Overexpression of cyclin D1 is believed to endow mammary epithelial cells ( MEC ) with a proliferative advantage by virtue of its contribution to pRB inactivation . Accordingly , abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2 . Here , we report that mouse cyclin D1(KE/KE) MECs ( deficient in cyclin D1 activity ) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo . In addition , immortalized cyclin D1(KE/KE) MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro . However , highlighting its dual role during tumorigenesis , downregulation of autophagy led to an increase in senescence in cyclin D1(KE/KE) MECs . Autophagy upregulation was also confirmed in human mammary epithelial cells ( HMEC ) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and , similar to our murine system , simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response . Collectively , our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium . Cancer Res ; 72(24) ; 6477-89. �2012 AACR .\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: Colorectal cancer ( CRC ) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor , and thus is an useful model for studying metabolic shift . In the present study , we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry ( GC/MS ) and liquid chromatography tandem mass spectrometry ( LC/MS/MS ) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC . Colonic tissues including tumor , polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study . The metabolic profiles were obtained using GC/MS and LC/MS/MS . Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues . Various amino acids and lipids in the polyps and tumors were elevated , suggesting higher energy needs for increased cellular proliferation . In contrast , significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis . In addition , the accumulation of hypoxanthine and xanthine , and the decrease of uric acid concentration , suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC . Further , there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors . It appears that to gain a growth advantage , cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Low-dose cyclophosphamide ( CP ) therapy induces immunogenic tumor cell death and decreases regulatory T cell ( Treg ) numbers in mice with transplantable tumors . Using the ret transgenic murine melanoma model that resembles human melanoma , we detected no beneficial antitumor effects with such treatment , despite a decrease in Tregs . On the contrary , low-dose CP enhanced the production of chronic inflammatory mediators in melanoma lesions associated with increased accumulation of Gr1(+)CD11b(+) myeloid-derived suppressor cells ( MDSCs ) , which exhibit elevated suppressive activity and nitric oxide ( NO ) production as well as inhibition of T-cell proliferation . Moreover , the frequencies of CD8(+) T cells in the tumors and their ability to produce perforin were decreased . To study whether the observed CP-induced MDSC expansion and activation also occurs under chronic inflammatory tumor-free conditions , mice exhibiting chronic inflammation were treated with CP . Similar to tumor-bearing mice , CP-treated inflamed mice displayed elevated levels of MDSCs with enhanced production of NO , reactive oxygen species , and a suppressed in vivo natural killer ( NK ) cell cytotoxic activity indicating CP effects on the host immune system independent of the tumor . We suggest that melanoma therapy with low-dose CP could be efficient only when combined with the neutralization of MDSC immunosuppressive function and chronic inflammatory microenvironment.Journal of Investigative Dermatology advance online publication , 6 December 2012 ; doi:10.1038/jid.2012.444 .\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: We report a case of recurrent gastric cancer successfully treated by a combination of CPT-11 and CDDP as the third- line chemotherapy . A 78-year-old man with advanced gastric cancer underwent a curative distal gastrectomy . Three years later , the tumor marker level began to rise and computed tomography ( CT ) revealed lymph node metastasis invading the pancreas resulting in pancreatic duct dilatation . S-1 treatment was initiated but was discontinued because of a systemic exanthem . Paclitaxel was administrated as secondary chemotherapy . But , after 2 courses , a further increase in the tumor marker level and portal vein invasion were observed . Combination therapy of CPT-11 and CDDP was administered as the third-line chemotherapy . After 3 courses , the tumor marker level normalized , tumor size decreased , and the invasion was eliminated . Third-line chemotherapy against recurrent gastric cancer should be considered if patient performance status ( PS ) is maintained .\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: AIMS AND BACKGROUND To investigate a six-drug combination in patients with nonmetastatic Ewing sarcoma , focusing on chemotherapy-induced necrosis and chemotherapy toxicity in adult and pediatric patients . METHODS AND STUDY DESIGN Alternating cycles of vincristine ( 1.5 mg/m2 ) , doxorubicin ( 80 mg/m2 ) and cyclophosfamide ( 1200 mg/m2 ) ( weeks 0 , 6 , 13 , 22 and 31 ) , ifosfamide ( 9 g/m2 ) , vincristine ( 1.5 mg/m2 ) , and actinomycin D ( 1.5 mg/m2 ) ( weeks 3 , 16 , 25 and 34 ) , and ifosfamide ( 9 g/m2 ) and etoposide ( 450 mg/m2 ) ( weeks 9 , 19 , 28 and 37 ) were administered . Primary chemotherapy-induced necrosis was graded : G3 ( complete necrosis ) , G2 ( microfoci of tumor cells ) and G1 ( macrofoci of tumor cells ) . RESULTS From 1996 to 1999 , 50 patients with Ewing sarcoma were enrolled . The median age was 23.5 years ( range , 4-56 ) . Chemotherapy-induced necrosis ( in 28 patients ) was G3 in 36% , G2 in 21% and G1 in 43% . At a median follow-up of 110 months ( range , 36-129 ) , 5-year overall survival and event-free survival were 72% and 66% , respectively . According to histologic response , 5-year event-free survival was 90% in G3 , 83% in G2 , and 42% in G1 ( P = 0.02 ) . In adult and pediatric ( <18 years ) patients , the incidence of G4 leukopenia was 62% and 74% , respectively , with febrile neutropenia in 13% and 21% , respectively . G4 thrombocytopenia occurred in 3% of cycles in adults and in 7% in pediatric patients . Platelet and red blood cell transfusions were required respectively in 1% and 11% of cycles in adults and in 6% and 24% of cycles in pediatric patients . CONCLUSIONS The six-drug combination can be administered safely in adult and pediatric populations . About 40% of patients have a poor chemotherapy-induced tumor necrosis , leading to poor probability of survival . New strategies are recommended to improve survival of poor responders to the six-drug combination .\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: Therapy-induced senescence ( TIS ) , a cytostatic stress response in cancer cells , is induced inefficiently by current anticancer agents and radiation . The mechanisms that mediate TIS in cancer cells are not well defined . Herein , we characterize a robust senescence response both in vitro and in vivo to the quinone diaziquone ( AZQ ) , previously identified in a high-throughput senescence-induction small-molecule screen . Using AZQ and several other agents that induce senescence , we screened a series of cyclin-dependent kinase inhibitors and found that p27(Kip1) was induced in all investigated prostate cancer cell lines . The ubiquitin-ligase Skp2 negatively regulates p27(Kip1) and , during TIS , is translocated to the cytoplasm before its expression is decreased in senescent cells . Overexpression of Skp2 blocks the effects of AZQ on senescence and p27(Kip1) induction . We also find that stable long-term short hairpin RNA knockdown of Skp2 decreases proliferation but does not generate the complete senescence phenotype . We conclude that Skp2 participates in regulating TIS but , alone , is insufficient to induce senescence in cancer 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: Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc . We investigate the effect of zinc deficiency on DNA damage , expression of DNA-repair enzymes , and downstream signaling events in a cell-culture model . Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress . Low intracellular zinc increased DNA single-strand breaks ( comet assay ) . Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease ( APE ) . Repletion with zinc restored cell growth and reversed DNA damage . APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression . The ability of the transcription factors p53 , nuclear factor kappaB , and activator protein 1 ( AP1 ) to bind to consensus DNA sequences was decreased markedly with zinc deficiency , as assayed by electrophoretic mobility-shift assays . Thus , low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression , but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Peptide 11 , CDPGYIGSR-NH2 , is a segment of laminin which blocks tumor cell invasion . A high affinity laminin receptor in tumor cells is thought to be blocked by the carboxyl-terminal YIGSR , and conformational energy calculations suggest that the glycine in YIGSR allows an important conformational bend . We replaced the YIGSR glycine residue in peptide 11 with either D-alanine or L-alanine to allow or disfavor the proposed glycine bend . We found the Gly7-->D-Ala7 analog to be equal to peptide 11 in inhibiting tumor cell invasion of basement membrane matrix . The Gly7-->L-Ala7 analog was much less capable of invasion inhibition . Two-dimensional 1H-1H NMR was used to study the solution conformations of the peptide 11 analogs . NOESY experiments revealed close NH-NH contacts in peptide 11 and the D-Ala7 analog , but not in the L-Ala7 analog . Molecular dynamics generated low energy structures with excellent NOE agreement for peptide 11 and its analogs . Both peptide 11 and the D-Ala7 analog , but not the less active L-Ala7 analog , were predicted to have similar bends around Gly7 or D-Ala7 . These results suggest that a bend in the YIGSR region of peptide 11 may be important for the binding of laminin to its metastasis-associated receptor .\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: NK1 is a tachykinin receptor highly relevant to tumorigenesis and metastasis development in breast cancer and other carcinomas . Despite the substantial efforts done to develop potent NK1 receptor antagonists , none of these antagonists had shown good antitumor activity in clinical trials . Now , we have tested the effect of inhibition of the neuropeptide Substance P ( SP ) , a NK1 ligand , as a potential therapeutic approach in cancer . We found that the inhibition of SP with antibodies strongly inhibit cell growth and induce apoptosis in breast , colon , and prostate cancer cell lines . These effects were accompained by a decrease in the mitogen-activated kinase singaling pathway . Interestingly , in some cell lines SP abrogation decreased the steady state of Her2 and EGFR , suggesting that SP-mediated signaling is important for the basal activity of these ErbB receptors . In consequence , we observed a blockade of the cell cycle progression and the inhibition of several cell cycle-related proteins including mTOR . SP inhibition also induced cell death in cell lines resistant to Lapatinib and Trastuzumab that have increased levels of active Her2 , suggesting that this therapeutic approach could be also effective for those cancers resistant to current anti-ErbB therapies . Thus , we propose a new therapeutic strategy for those cancers that express NK1 receptor and/or other tachykinin receptors , based in the immuno-blockade of the neuropeptide SP .\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: Elevated serum levels of vasoactive intestinal peptide ( VIP ) are associated with some cases of neuroblastoma and correlate with a favorable prognosis . VIP has previously been shown in our laboratory to cause the in vitro growth inhibition and morphological differentiation of the human neuroblastoma cell line , LA-N-5 . It is now shown that LA-N-5 cells express immunoreactive VIP and bear specific VIP receptors . Antagonism of endogenous VIP , either by competitive inhibition or receptor blockade , increased cell proliferation , suggesting that VIP is operative in normal growth regulation . Intracellular and extracellular levels of VIP were also shown to increase significantly during the retinoic acid-induced differentiation of these cells . Furthermore , a concomitant marked increase in VIP receptor expression was demonstrated with cellular differentiation . These receptors remain functional as evidenced by a matching increase in the level of detectable cAMP generated in response to exogenous VIP . It is concluded that VIP is a normal autoregulator of neuroblastoma cell growth and differentiation , and that retinoic acid-mediated differentiation may be , in part , due to endogenous VIP .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The tumor suppressors Lats1 and Lats2 are mediators of the Hippo pathway that regulates tissue growth and proliferation . Their N-terminal non-kinase regions are distinct except for Lats conserved domains 1 and 2 ( LCD1 and LCD2 ) , which may be important for Lats1/2-specific functions . Lats1 knockout mice were generated by disrupting the N-terminal region containing LCD1 ( Lats1(ΔN/ΔN) ) . Some Lats1(ΔN/ΔN) mice were born safely and grew normally . However , mouse embryonic fibroblasts ( MEFs ) from Lats1(ΔN/ΔN) mice displayed mitotic defects , centrosomal overduplication , chromosomal misalignment , multipolar spindle formation , chromosomal bridging and cytokinesis failure . They also showed anchorage-independent growth and continued cell cycles and cell growth , bypassing cell-cell contact inhibition similar to tumor cells . Lats1(ΔN/ΔN) MEFs produced tumors in nude mice after subcutaneous injection , although the tumor growth rate was much slower than that of ordinary cancer cells . Yap , a key transcriptional coactivator of the Hippo pathway , was overexpressed and stably retained in Lats1(ΔN/ΔN) MEFs in a cell density independent manner , and Lats2 mRNA expression was downregulated . In conclusion , N-terminally truncated Lats1 induced Lats2 downregulation and Yap protein accumulation , leading to chromosomal instability and tumorigenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "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: Numerous scientific studies have examined the relationship between coffee consumption and an array of medical conditions , including cancer , and yet the direct effect of commercially brewed coffee on cancer cells has not been evaluated . The purpose of this study was to evaluate the antiproliferation effect of 4 different regular and decaffeinated coffee brews and 3 of coffee's bioactive ingredients-caffeine , chlorogenic acids , and caffeic acid-on 2 human ovarian cancer cell lines alone and in combination with cisplatin ( CDDP ) . Antiproliferation IC(50) for Brand A regular and decaffeinated coffee on A2780 cells was 1:70.79 ± 5.66 and 1:55.68 ± 2.00 dilution ( vol/vol ) in tissue culture medium ( mean ± standard error of the mean ; N = 12 ) , respectively , and slightly lower on A2780CP70 cells . Three other brands showed lower antiproliferation activity . Antiproliferation IC(50) concentrations of chlorogenic acids and caffeic acid are many folds lower than caffeine . In combination with CDDP , both Brand A coffee brews , and the 3 bioactive compounds , showed additive antiproliferation effect on both cancer cell lines . Flow cytometry analysis showed that coffee treatment induced apoptosis of A2780 and A2780CP70 cells . To our knowledge , this is the first report showing the antiproliferation activity and the additive effect with CDDP of commercially prepared coffee brews on human cancer cell lines .\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: Aberrant glucose metabolism characterized by high levels of glycolysis , even in the presence of oxygen , is an important hallmark of cancer . This metabolic reprogramming referred to as the Warburg effect is essential to the survival of tumor cells and provides them with substrates required for biomass generation . Molecular mechanisms responsible for this shift in glucose metabolism remain elusive . As described herein , we found that aberrant expression of the proinflammatory protein transglutaminase 2 ( TG2 ) is an important regulator of the Warburg effect in mammary epithelial cells . Mechanistically , TG2 regulated metabolic reprogramming by constitutively activating nuclear factor ( NF)-κB , which binds to the hypoxia-inducible factor ( HIF)-1α promoter and induces its expression even under normoxic conditions . TG2/NF-κB-induced increase in HIF-1α expression was associated with increased glucose uptake , increased lactate production and decreased oxygen consumption by mitochondria . Experimental suppression of TG2 attenuated HIF-1α expression and reversed downstream events in mammary epithelial cells . Moreover , downregulation of p65/RelA or HIF-1α expression in these cells restored normal glucose uptake , lactate production , mitochondrial respiration and glycolytic protein expression . Our results suggest that aberrant expression of TG2 is a master regulator of metabolic reprogramming and facilitates metabolic alterations in epithelial cells even under normoxic conditions . A TG2-induced shift in glucose metabolism helps breast cancer cells to survive under stressful conditions and promotes their metastatic competence .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;tumor promoting inflammation;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: Polycyclic aromatic hydrocarbons ( PAH ) such as dibenzo[a,l]pyrene ( DBP ) are wide-spread environmental pollutants most probably mutagenic and carcinogenic to humans . Detailed data on the cytogenetic effects of anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene ( DBPDE ) in mammalian cells are not available in the literature . The aim of this study is to elucidate the mechanisms involved in the induction of chromosomal aberrations and sister chromatid exchanges ( SCEs ) by DBPDE in mammalian cells . In order to achieve this a parental ( AA8 ) and different DNA repair-deficient Chinese hamster ovary cell lines such as UV4 , UV5 , UV61 ( nucleotide excision repair , NER ) , EM9 ( base excision repair , BER ) , irs1SF ( homologous recombination repair , HRR ) and V3-3 ( non-homologous end joining , NHEJ ) were used . The most sensitive cell lines for DBPDE-induced chromosome aberrations were EM9 and irs1SF , while EM9 and V3-3 cell lines were the most sensitive in terms of SCEs induction . It can be suggested that the BER pathway plays an important role in the repair of lesions induced by DBPDE , affecting both chromosomal aberrations and SCEs induction . Moreover , the HRR pathway seems to play a role in cellular resistance to DBPDE mainly in terms of chromosomal aberration induction while the NHEJ pathway takes part affecting only the induction of SCEs .\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 the immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene , with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor antigen ( TA ) . Slow progressor melanomas contained no activated T lymphocytes ( TL ) . In contrast , \" aggressive \" melanomas were infiltrated by activated TLs lacking effector molecules and expressing high levels of PD-1 , indicating an exhausted phenotype . Aggressive melanomas were also infiltrated by immature myeloid cells ( IMC ) . Infiltration was associated with local inflammation and systemic Th2/Th17-oriented chronic inflammation that seemed to impair further activation of TLs , as tumor-specific T cells adoptively transferred into mice bearing aggressive melanomas were poorly activated and failed to infiltrate the melanoma . This immunosuppression also led to the incapacity of these mice to reject inoculated TA-positive tumors , in contrast to slow-progressing melanoma-bearing mice , which were responsive . To test the role of adaptive immunity in tumor progression , we induced melanomas in immunodeficient RagKO compound mice . These mice developed aggressive but not slow-progressing melanomas at a higher frequency and with a shorter latency than immunocompetent mice . Immunodeficient mice also developed abnormal inflammation and infiltration of IMCs in a manner similar to immunocompetent mice , indicating that this phenotype was not dependent on adaptive immunity . Therefore , tumor-intrinsic factors distinguishing the two melanoma types control the initiation of inflammation , which was independent of adaptive immunity . The latter delayed development of aggressive melanomas but was overridden by inflammation .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Angiogenesis is critical for cancer growth and metastasis . Steps of angiogenesis are energy consuming , while vascular endothelial cells are highly glycolytic . Glioblastoma multiforme ( GBM ) is a highly vascular tumor and this enhances its aggressiveness . D-amino acid oxidase ( DAO ) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates . Oxidative stress-energy depletion ( OSED ) therapy was recently reported ( El Sayed et al. , Cancer Gene Ther , 19 , 1-18 , 2012 ) . OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate ( 3BP ) , a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate ( El Sayed et al. , J Bioenerg Biomembr , 44 , 61-79 , 2012 ) . Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase . Here , we report that DAO , 3BP and citrate significantly inhibited angiogenesis , decreased the number of vascular branching points and shortened the length of vascular tubules . OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar . Human GBM cells ( U373MG ) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside , while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells .\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: Aberrant expression and polymorphism of fibroblast growth factor receptor 4 ( FGFR4 ) has been linked to tumor progression and anticancer drug resistance . We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to membrane-type 1 matrix metalloproteinase ( MT1-MMP , MMP-14 ) induction at the edge of tumors expressing the FGFR4-R388 risk variant . Both FGFR4 and MT1-MMP were upregulated in tissue biopsies from several human cancer types including breast adenocarcinomas , where they were partially coexpressed at the tumor/stroma border and tumor invasion front . The strongest overall coexpression was found in prostate carcinoma . Studies with cultured prostate carcinoma cell lines showed that the FGFR4-R388 variant , which has previously been associated with poor cancer prognosis , increased MT1-MMP-dependent collagen invasion . In this experimental model , knockdown of FGFR4-R388 or MT1-MMP by RNA interference blocked tumor cell invasion and growth in collagen . This was coupled with impaired phosphorylation of FGFR substrate 2 and Src , upregulation of E-cadherin , and suppression of cadherin-11 and N-cadherin . These in vitro results were substantiated by reduced MT1-MMP content and in vivo growth of prostate carcinoma cells after the FGFR4-R388 gene silencing . In contrast , knockdown of the alternative FGFR4-G388 allele enhanced MT1-MMP and invasive tumor cell growth in vivo and within three-dimensional collagen . These results will help to explain the reported association of the FGFR4-R388 variant with the progression and poor prognosis of certain types of tumors .\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: In spite of numerous advances , the 5-year survival rate for head and neck squamous cell cancer has remained largely stagnant and few new anti-tumor drugs have been developed . PCH4 , a derivative of n-butylidenephthalide , has been investigated for its anti-tumor effects on oral squamous cell carcinoma ( OSCC ) . The aim of this study was to investigate the anti-tumor mechanism of a potential target gene , Nur77 , in OSCC cells , which can be induced by PCH4 treatment . Data show that PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and induced cell apoptosis in OSCC cells . When Nur77 translocation was blocked , the degree of tumor apoptosis caused by PCH4 was significantly inhibited ( p < 0.05 ) . Within the MAPK pathway , PCH4 only induced JNK phosphorylation . Furthermore , treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis ( p < 0.05 ) and decreased PCH4-induced Nur77 expression ( p < 0.05 ) . In a xenograft animal model , administration of PCH4 also showed anti-tumor effects . We have demonstrated that OSCC cells are sensitive to PCH4 and that Nur77 protein translocation from the nucleus to the cytoplasm might be associated with the induction of apoptosis by PCH4 . These results indicate that PCH4 may serve as a potential anti-tumor drug for OSCC therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVES : Cigarette smoking is a major risk factor for pancreatic cancer ( PaCa ) . However , the mechanisms of smoking-induced PaCa remain unknown . Here we investigated the effect of smoking compounds on cell death pathways in pancreatic ductal cells , precursors of PaCa . METHODS : Human pancreatic ductal cells ( HPDE6-c7 ) were cultured with cigarette smoke extract ( CSE ) or smoking compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ( NNK ) . Apoptosis and autophagy were assessed by DNA fragmentation and immunofluorescence , respectively . RESULTS : Exposure to CSE or NNK decreased DNA fragmentation and up-regulated BclXL . Akt kinase was activated by smoking compounds through reactive oxygen species-dependent mechanism . Specifically , Akt activation was prevented by inhibition of nicotinamide adenine dinucleotide oxidase . Molecular or pharmacologic inhibitions of Akt prevented the antiapoptotic effect of smoking compounds . Smoking compounds stimulated rapid ( 1 hour ) and transient activation of 5'-adenosine monophosphate-activated protein kinase and formation of autophagic vacuoles , indicating stimulation of autophagy . Repeated exposure to CSE/NNK ( 48 hours or longer ) abolished the early activation of autophagic markers . Inhibition of Akt prevented the antiautophagic effect of long exposure to smoking compounds , indicating that smoking-induced late activation of Akt prevents autophagy . CONCLUSIONS : Long exposure of pancreatic ductal cells to smoking compounds inhibited apoptosis and autophagy . The results revealed a central role for Akt kinase in mediating key procarcinogenic effects of smoking compounds .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Gliomas are aggressive and almost incurable glial brain tumors which frequently display abnormal platelet-derived growth factor ( PDGF ) signaling . Evidence gained from studies on several in vivo animal models has firmly established a causal connection between aberrant PDGF signaling and the formation of some gliomas . However , only recently has significant knowledge been gained regarding crucial issues such as the glioma cell of origin and the relationship between the transforming stimulus and the cellular characteristics of the resulting tumor . Based on recent evidence , we propose that PDGF can bias cell-fate decisions , driving the acquisition of cell type-specific features by the progeny of multipotent neural progenitors , thus determining the shape and direction of the transformation path . Furthermore , recent data about the cellular mechanisms of PDGF-driven glioma progression and maintenance indicate that PDGF may be required , unexpectedly , to override cell contact inhibition and promote glioma cell infiltration rather than to stimulate cell proliferation .\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: Nitric oxide ( NO)-releasing non-steroidal anti-inflammatory drugs ( NO-NSAIDs ) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs , possess anti-proliferative , pro-apoptotic and anti-cancer activities . Here , we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice . Topical application of NO-sulindac reduced tumor incidence , number ( p<0.05 ) and volume ( p<0.005 ) as compared to UVB ( alone)-irradiated vehicle-treated mice . An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio . The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced . However , proliferation was identified as the major target of NO-sulindac in this study . A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed . The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway . UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2 , p38 and JNK1/2 . In this regard , NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2 , the direct NFκB transcription target proteins . NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial-mesenchymal transition . A marked decrease in the expression of mesenchymal markers such as Fibronectin , N-cadherin , SNAI , Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors . Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;tumor promoting inflammation;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: Acrolein ( Acr ) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust . It can also be produced endogenously by oxidation of polyunsaturated fatty acids . The Acr-derived 1,N(2)-propanodeoxyguanosine ( Acr-dG ) adducts in DNA are mutagenic lesions that are potentially involved in human cancers . In this study , monoclonal antibodies were raised against Acr-dG adducts and characterized using ELISA . They showed strong reactivity and specificity toward Acr-dG , weaker reactivity toward crotonaldehyde- and trans-4-hydroxy-2-nonenal-derived 1,N(2)-propanodeoxyguanosines , and weak or no reactivity toward 1,N(6)-ethenodeoxyadenosine and 8-oxo-deoxyguanosine . Using these antibodies , we developed assays to detect Acr-dG in vivo : first , a simple and quick FACS-based assay for detecting these adducts directly in cells ; second , a highly sensitive direct ELISA assay for measuring Acr-dG in cells and tissues using only 1 μg of DNA without DNA digestion and sample enrichment ; and third , a competitive ELISA for better quantitative measurement of Acr-dG levels in DNA samples . The assays were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA , and the results were confirmed by LC-MS/MS-MRM . An immunohistochemical assay was also developed to detect and visualize Acr-dG in HT29 cells as well as in human oral cells . These antibody-based methods provide useful tools for the studies of Acr-dG as a cancer biomarker and of the molecular mechanisms by which cells respond to Acr-dG as a ubiquitous DNA lesion .\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 functional and therapeutic importance of the Warburg effect is increasingly recognized , and glycolysis has become a target of anticancer strategies . We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation-like mechanism . We hypothesized that the compounds target Glut1 and are efficacious in vivo as anticancer agents . Here , we report that a novel representative compound WZB117 not only inhibited cell growth in cancer cell lines but also inhibited cancer growth in a nude mouse model . Daily intraperitoneal injection of WZB117 at 10 mg/kg resulted in a more than 70% reduction in the size of human lung cancer of A549 cell origin . Mechanism studies showed that WZB117 inhibited glucose transport in human red blood cells ( RBC ) , which express Glut1 as their sole glucose transporter . Cancer cell treatment with WZB117 led to decreases in levels of Glut1 protein , intracellular ATP , and glycolytic enzymes . All these changes were followed by increase in ATP-sensing enzyme AMP-activated protein kinase ( AMPK ) and declines in cyclin E2 as well as phosphorylated retinoblastoma , resulting in cell-cycle arrest , senescence , and necrosis . Addition of extracellular ATP rescued compound-treated cancer cells , suggesting that the reduction of intracellular ATP plays an important role in the anticancer mechanism of the molecule . Senescence induction and the essential role of ATP were reported for the first time in Glut1 inhibitor-treated cancer cells . Thus , WZB117 is a prototype for further development of anticancer therapeutics targeting Glut1-mediated glucose transport and glucose metabolism .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;enabling replicative immortality;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: Thrombopoietin ( TPO ) receptor agonists represent a new approach for the treatment of thrombocytopenia , which may develop as a consequence of immune thrombocytopenia , chemotherapy treatment , chronic hepatitis C infection , or myelodysplastic syndromes . There are concerns that use of certain growth factors can hasten disease progression in some types of hematologic malignancies and solid tumors . In this study , expression of MPL ( TPO-R ) mRNA was examined in tumor cell lines , patient tumor samples ( renal cell carcinoma , prostatic carcinoma , soft tissue and bony/cartilage sarcoma , colon cancer , and lymphoma ) , and normal tissues using microarray analysis and qRT-PCR . MPL mRNA is expressed at very low or undetectable levels compared with erythropoietin receptor ( EPOR ) , human epidermal growth factor ( ERBB2 ; HER2 ) , and insulin-like growth factor-1 receptor ( IGF1R ) in these patient samples . These data suggest TPO-R agonists will likely preferentially stimulate proliferation and differentiation of cells of megakaryocytic lineage , potentially demonstrating their utility for correcting thrombocytopenia in clinical settings .\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 investigated the effectiveness of continuous hyperthermic peritoneal perfusion ( CHPP ) for the peritoneal dissemination of gastric cancer . A total 124 patients with advanced gastric cancer were enrolled in this study . Prophylactic CHPP ( P-CHPP ) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination , and 79 patients without CHPP were a control group . Therapeutic CHPP ( T-CHPP ) was performed in 21 patients with peritoneal dissemination , and 52 patients without CHPP were a control group . There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP . Univariate analysis showed that location of tumor , tumor diameter , and lymph node metastasis influenced prognosis , but there was no prognostic factor in the Cox proportional regression hazard model . There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP . Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis , and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis . In the patients with CHPP , the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP .\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: Thyroid hormone ( T(3) ) mediates cellular growth , development , and differentiation by binding to the nuclear thyroid hormone receptor ( TR ) . Recent studies suggest that long-term hypothyroidism is associated with human hepatocellular carcinoma ( HCC ) independent from other major HCC risk factors . Dickkopf ( DKK ) 4 , a secreted protein , antagonizes the Wnt signal pathway . In this study , we demonstrate that T(3) may play a suppressor role by inducing DKK4 expression in HCC cells at both the messenger RNA ( mRNA ) and protein levels . DKK4 was down-regulated in 67.5% of HCC cancerous tissues . The decrease in DKK4 levels was accompanied by a concomitant decrease in TR protein levels in the matched cancerous tissues in 31% of tissues compared by immunoblotting with the adjacent noncancerous tissues . Further , TR and DKK4 expression levels were positively correlated in both normal and cancerous specimens by tissue array analysis . In function assays , stable DKK4 transfected into J7 or HepG2 cells decreased cell invasion in vitro . Conversely , knocking down DKK4 restores cell invasiveness . DKK4-expressing J7 clones showed increased degradation of β-catenin , but down-regulation of CD44 , cyclin D1 , and c-Jun . To investigate the effect of DKK4 and TR on tumor growth in vivo , we established a xenograft of J7 cells in nude mice . J7-DKK4 and J7-TRα1 overexpressing mice , which displayed growth arrest , lower lung colony formation index , and smaller tumor size than in control mice , supporting an inhibitory role of DKK4 in tumor progression . CONCLUSION : Taken together , these data suggest that the TR/DKK4/Wnt/β-catenin cascade influences the proliferation and migration of hepatoma cells during the metastasis process and support a tumor suppressor role of the TR .\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: Genotoxic stress induces cell cycle arrest and DNA repair which may enable tumor cells to survive radiation therapy . Here , we defined the role of Ca(2+) signaling in the cell cycle control and survival of chronic myeloid leukemia ( CML ) cells subjected to ionizing radiation ( IR ) . To this end , K562 erythroid leukemia cells were irradiated ( 0-10 Gy ) . Tumor survival was analyzed by clonogenic survival assay and cell cycle progression via flow cytometry . Plasma membrane cation conductance was assessed by patch-clamp whole-cell recording and the cytosolic free Ca(2+) concentration ( [ Ca(2+)](i) ) was measured by fura-2 Ca(2+) imaging . Nuclear activity of Ca(2+)/calmodulin-dependent kinase II ( CaMKII ) was defined by Western blotting . In addition , the effect of IR ( 5 Gy ) on the cation conductance of primary CML cells was determined . The results indicated that IR ( 10 Gy ) induced a G(2)/M cell cycle arrest of K562 cells within 24 h post-irradiation ( p.i. ) and decreased the clonogenic survival to 0.5 % of that of the control cells . In K562 cells , G(2)/M cell cycle arrest was preceded by activation of TRPV5/6-like nonselective cation channels in the plasma membrane 1-5 h p.i. , resulting in an elevated Ca(2+) entry as evident from fura-2 Ca(2+) imaging . Similarly , IR stimulated a Ca(2+)-permeable nonselective cation conductance in primary CML cells within 2-4 h p.i. . Ca(2+) entry , into K562 cells was paralleled by an IR-induced activation of nuclear CaMKII . The IR-stimulated accumulation in G(2) phase was delayed upon buffering [ Ca(2+)](i) with the Ca(2+) chelator BAPTA-AM or inhibiting CaMKII with KN93 ( 1 nM ) . In addition , KN93 decreased the clonogenic survival of irradiated cells but not of control cells . In conclusion , the data suggest that IR-stimulated cation channel activation , Ca(2+) entry and CaMKII activity participate in control of cell cycle progression and survival of irradiated CML cells .\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: Tumour cells primarily utilize aerobic glycolysis for energy production , a phenomenon known as the Warburg effect . Its mechanism is not well understood . The tumour suppressor gene p53 is frequently mutated in tumours . Many tumour-associated mutant p53 ( mutp53 ) proteins not only lose tumour suppressive function but also gain new oncogenic functions that are independent of wild-type p53 , defined as mutp53 gain of function ( GOF ) . Here we show that tumour-associated mutp53 stimulates the Warburg effect in cultured cells and mutp53 knockin mice as a new mutp53 GOF . Mutp53 stimulates the Warburg effect through promoting GLUT1 translocation to the plasma membrane , which is mediated by activated RhoA and its downstream effector ROCK . Inhibition of RhoA/ROCK/GLUT1 signalling largely abolishes mutp53 GOF in stimulating the Warburg effect . Furthermore , inhibition of glycolysis in tumour cells greatly compromises mutp53 GOF in promoting tumorigenesis . Thus , our results reveal a new mutp53 GOF and a mechanism for controlling 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: Protein tyrosine kinase 6 ( PTK6 ) is a non-receptor tyrosine kinase expressed in epithelial cancers . Disruption of Ptk6 decreases azoxymethane-induced colon tumorigenesis in mice by preventing signal transducer and activator of transcription 3 activation . Relocalization of PTK6 in prostate cancers contributes to increased growth . Although not expressed in normal breast or ovary , PTK6 promotes anchorage-independent survival of breast and ovarian tumor cells . We identified several potential PTK6 substrates in the human SW620 colon cancer cell line using mass spectrometry , including FAK ( focal adhesion kinase ) . We show that FAK is a direct substrate of PTK6 in vitro and in vivo . Expression of membrane-targeted active PTK6 ( Palm-PTK6-YF ) induces constitutive activation of FAK and cell morphology changes , which are independent of SRC family kinases in Src-/- , Yes-/- , Fyn-/- ( SYF ) mouse embryonic fibroblasts ( MEFs ) . Palm-PTK6-YF expressing SYF cells are transformed and overcome contact inhibition , form colonies in transformation assays , proliferate in suspension and form tumors in a xenograft model . Expression of FAK and Palm-PTK6-YF in Fak-/- MEFs synergistically activates AKT and protects cells against anoikis . However , expression of Palm-PTK6-YF in Akt1/2-/- MEFs fails to protect cells from anoikis , indicating AKT is critical in PTK6 and FAK-mediated survival signaling . In a conditional Pten knockout murine prostate cancer model , we identify prostate epithelial cells with enhanced activation of endogenous PTK6 and FAK at the plasma membrane . Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis , which can be rescued by exogenous expression of FAK . Our data reveal important roles for a PTK6-FAK-AKT signaling axis in promoting anchorage-independent cell survival .\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: Ovarian hormones have a pivotal role in the control of proliferation in the mammary gland , and cumulative life-time exposure to ovarian hormones is known to be a determinant of breast cancer risk . We have shown previously that a p.o.-active , long-acting butyrate analogue , sodium phenylbutyrate ( PB ) , reduced proliferation in normal and malignant human breast cells in culture and reduced expression of ovarian hormone receptors , suggesting that PB had cellular effects consistent with decreasing breast cancer risk . The aim of this study was to determine the in vivo effects of PB in the normal mammary gland on epithelial cell proliferation , estrogen receptor alpha ( ER alpha ) expression , and cyclin D1 expression . BALB/c mice were treated with PB , delivered by mini-osmotic pumps , for 7 days . Moderate ( 250 mg/kg/day ) and high ( 500 mg/kg/day ) PB treatment resulted in a decrease in proliferation in mammary epithelial cells ( P &lt ; 0.001 ) , determined by bromodeoxyuridine incorporation . Analysis of ER alpha immunostaining revealed a significant reduction in moderate- and high-treatment groups ( P = 0.01 and P = 0.02 ) , and expression of cyclin D1 was virtually ablated ( P &lt ; 0.001 ) . Histone deacetylase inhibition is a known mechanism of butyrate action , and consistent with this , PB increased levels of acetylated histone H3 in the mammary gland . In summary , PB decreased proliferation in the mammary gland in vivo at clinically achievable doses . Decreased proliferation was accompanied by changes in the levels of ER alpha and cyclin D1 . These data show that PB modulates parameters thought to be involved in the carcinogenic process in the normal mammary gland , and compounds in this class may therefore be useful candidates for breast cancer chemoprevention .\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: A rare immunohistochemical study using 28 surgical sections of human chondrosarcoma revealed that 67.9% of tumour cells had weak ( 10-40% ) or strong ( >40% ) positive immunoreaction for peroxisome proliferator-activated receptor-gamma . The expression of peroxisome proliferator-activated receptor-gamma mRNA and protein in human chondrosarcoma cell line OUMS-27 was also determined by reverse transcription-polymerase chain reaction and immunocytochemistry , respectively . Furthermore , the effects of peroxisome proliferator-activated receptor-gamma ligands on cell proliferation and survival were investigated in OUMS-27 cells . Pioglitazone , a selective ligand for peroxisome proliferator-activated receptor-gamma , and 15-deoxy-Delta(12,14)-prostaglandin J(2) ( 15d-PGJ(2) ) , a putative endogenous ligand for peroxisome proliferator-activated receptor-gamma , inhibited the proliferation of OUMS-27 cells in a dose-dependent manner . The mechanism of cytotoxic effects of 15d-PGJ(2) was via apoptosis as shown by DNA fragmentation using TUNEL stain and DNA ladder formation , and by ultrastructural analysis using transmission electron microscopy . Flow-cytometric analysis using annexin-V-fluorescein and propidium iodide detected the early change of apoptosis , as well as necrosis of OUMS-27 cells at 4 h after co-incubation with 15d-PGJ(2) . These results suggest that peroxisome proliferator-activated receptor-gamma may play a significant role in the pathogenesis of chondrosarcoma , and peroxisome proliferator-activated receptor-gamma ligands , especially 15d-PGJ(2) , may be of therapeutic value in the treatment of human chondrosarcoma .\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: Bladder cancer is one of the most common tumors of the genitourinary tract ; however , the molecular events underlying growth and invasion of the tumor remain unclear . Here , role of the CXCR7 receptor in bladder cancer was further explored . CXCR7 protein expression was examined using high-density tissue microarrays . Expression of CXCR7 showed strong epithelial staining that correlated with bladder cancer progression . In vitro and in vivo studies in bladder cancer cell lines suggested that alterations in CXCR7 expression were associated with the activities of proliferation , apoptosis , migration , invasion , angiogenesis and tumor growth . Moreover , CXCR7 expression was able to regulate expression of the proangiogenic factors IL-8 or VEGF , which may involve in the regulation of tumor angiogenesis . Finally , we found that signaling by the CXCR7 in bladder cancer cells activates AKT , ERK and STAT3 pathways . The AKT and ERK pathways may reciprocally regulate , which are responsible for in vitro and in vivo epithelial to mesenchymal transition ( EMT ) process of bladder cancer . Simultaneously targeting the two pathways by using U0126 and LY294002 inhibitors or using CCX733 , a selective CXCR7 antagonist drastically reduced CXCR7-induced EMT process . Taken together , our data show for the first time that CXCR7 plays a role in the development of bladder cancer . Targeting CXCR7 or its downstream-activated AKT and ERK pathways may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for bladder cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;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: OBJECTIVE To study the effect of Zilongjin ( ZLJ , a composite Chinese drug ) on proliferation and apoptosis of human breast carcinoma cell line MCF-7 . METHODS MCF-7 cells were randomly divided into four groups depending on the culture solution used , the control group , cultured with 1640 medium not contained ZLJ ; and the three ZJL groups cultured with medium contained low ( 1.5 mg/mL ) , moderate ( 3 mg/mL ) and high ( 6 mg/mL ) dosage of ZLJ crude drug respectively . The changes of cell proliferation were assessed by cell growth curve assay and methyl thiazolyl tetrazolium ( MTT ) assay . And the cell apoptosis was analyzed by flow cytometry , Hoechst 33342 staining and DNA ladder assay . RESULTS Compared with that in the normal control , the counts of cells in the three ZLJ groups were decreased significantly ( P<0.05 ) at such time point as 24 , 48 , 72 , 96 , 120 , and 144 h . Furthermore , apart from the comparison of the growth inhibition rate between the low and moderate dosage group at 24 and 72 h which were found to be no significant difference ( P>0.05 ) , the comparison f that among the three ZLJ groups appeared to be significant difference ( P<0.05 ) . The inhibitory effect of ZLJ on cell proliferation of MCF-7 was time- and dose-dependent ; it could retard cells in G0/G1 cell phase ; apoptosis of MCF-7 cell was induced by moderate and high dosage of ZLJ with revealing of apoptotic body and DNA ladder formation . CONCLUSION ZLJ shows cell proliferation inhibitory and apoptosis inducing effects on human breast cancer cell line MCF-7 , and thus to realize its anti-tumor action .\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: BACKGROUND The most deadly form of cancer is not lung or colon , breast or prostate ; it is any cancer that has become metastatic . Mortality due to metastatic melanoma , one of the most aggressive and deadly cancers , has increased steadily over the last several decades . Unfortunately , the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals . We sought to identify an effective and nontoxic agent against metastatic melanoma . METHODOLOGY/PRINCIPAL FINDINGS We chose to study Cloudman S-91 mouse melanoma cells ( sub-clone M3 , CCL53.1 ) because these cells are highly aggressive and metastatic , representing one of the deadliest types of cancer . Melanoma cells also had an experimental advantage because their morphology , which is easily monitored , relates to the physiology of metastatic cells and normal melanocytes . We chose to test methyl sulfone as a chemotherapeutic agent for two reasons . Because of its chemical structure , we speculated a potential anti-cancer activity by targeting microtubules . Equally important , methyl sulfone has a well-established safety profile in humans . Surprisingly , we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells , and the reemergence of phenotypes characteristic of healthy melanocytes . Briefly , over time methyl sulfone induced contact inhibition , loss of ability to migrate through an extracellular matrix , loss of anchorage-independent growth , proper wound healing followed by contact inhibition , irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes . CONCLUSIONS/SIGNIFICANCE Methyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma . Additionally , methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration , contact inhibition , wound healing and cellular senescence .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: HGF signaling induces epithelial cells to disassemble cadherin-based adhesion and increase cell motility and invasion , a process termed epithelial-mesenchymal transition ( EMT ) . EMT plays a major role in cancer metastasis , allowing individual cells to detach from the primary tumor , invade local tissue , and colonize distant tissues with new tumors . While invasion of vascular and lymphatic networks is the predominant route of metastasis , nerves also can act as networks for dissemination of cancer cell to distant sites in a process termed perineual invasion ( PNI ) . Signaling between nerves and invasive cancer cells remains poorly understood , as does cellular decision making that selects the specific route of invasion . Here we examine how HGF signaling contributes to PNI using reductionist culture model systems . We find that TGFβ , produced by PC12 cells , enhances scattering in response to HGF stimulation , increasing both cell-cell junction disassembly and cell migration . Further , gradients of TGFβ induce migratory mesenchymal cells to undergo chemotaxis towards the source of TGFβ . Interestingly , VEGF suppresses TGFβ-induced enhancement of scattering . These results have broad implications for how combinatorial growth factor signaling contributes to cancer metastasis , suggesting that VEGF and TGFβ might modulate HGF signaling to influence route selection during cancer progression .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Proliferator-activated receptor gamma ( PPARgamma ) is a nuclear receptor , which mainly associates with adipogenesis , but also appears to facilitate cell differentiation or apoptosis in certain malignant cells . This apoptosis induction by PPARgamma is increased by co-stimulation with tumor necrosis factor ( TNF)-alpha-related apoptosis-inducing ligand ( TRAIL ) , a member of the TNF family . In this study , we investigated the effect of PPARgamma on Fas-mediated apoptosis in hepatocellular carcinoma ( HCC ) cell lines . PPARgamma was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-Delta-12,14-prostaglandin J2 ( 15d- PGJ2 ) , a PPARgamma ligand , inhibited cellular proliferation in HepG2 , SK-Hep1 or HLE cells , unlike pioglitazone , another PPARgamma ligand , which did not have a significant influence on proliferation of these cells . However , 15d-PGJ2 facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone . These results suggest that PPARgamma can augment TNF-family-induced apoptosis .\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: Epidemiological data and animal models have provided evidence that nonsteroidal antiinflammatory drugs ( NSAIDs ) have an anticancer effect . However , the molecular mechanisms underlying these antineoplastic effects are not well understood . We described previously that expression levels of the chemokine receptor , CCR5 , and the beta2-integrin , Mac-1 , were down-regulated on primary monocytes after incubation in supernatants from human carcinoma cell lines , and that this down-regulation resulted in impaired monocyte function with respect to migration and adhesion . We now demonstrate that these impairments are also present in vivo . Monocytes from cancer patients displayed significantly reduced CCR5 levels and migration capacities in comparison to cells from healthy donors . Because migration is necessary for the antitumor activity of monocytes/macrophages , these deficits may contribute to the suppressed immune system seen in cancer patients . In a clinical study , we analyzed the effect of a selective COX-2 inhibitor , Rofecoxib , on the migration of monocytes derived from cancer patients . The results revealed significant improvement in migration equal to those levels seen in healthy donors . We conclude that in patients with cancer , the intake of Rofecoxib for 3 wk leads to significant restoration of monocyte function . These data may , at least in part , help explain the anticancer effects of NSAIDs .\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: Chromosomal DNA must be in single-strand form for important transactions such as replication , transcription , and recombination to occur . The single-strand DNA ( ssDNA ) is more prone to damage than double-strand DNA ( dsDNA ) , due to greater exposure of chemically reactive moieties in the nitrogenous bases . Thus , there can be agents that damage regions of ssDNA in vivo while being inert toward dsDNA . To assess the potential hazard posed by such agents , we devised an ssDNA-specific mutagenesis reporter system in budding yeast . The reporter strains bear the cdc13-1 temperature-sensitive mutation , such that shifting to 37°C results in telomere uncapping and ensuing 5 ' to 3 ' enzymatic resection . This exposes the reporter region , containing three closely-spaced reporter genes , as a long 3 ' ssDNA overhang . We validated the ability of the system to detect mutagenic damage within ssDNA by expressing a modified human single-strand specific cytosine deaminase , APOBEC3G . APOBEC3G induced a high density of substitutions at cytosines in the ssDNA overhang strand , resulting in frequent , simultaneous inactivation of two reporter genes . We then examined the mutagenicity of sulfites , a class of reactive sulfur oxides to which humans are exposed frequently via respiration and food intake . Sulfites , at a concentration similar to that found in some foods , induced a high density of mutations , almost always as substitutions at cytosines in the ssDNA overhang strand , resulting in simultaneous inactivation of at least two reporter genes . Furthermore , sulfites formed a long-lived adducted 2'-deoxyuracil intermediate in DNA that was resistant to excision by uracil-DNA N-glycosylase . This intermediate was bypassed by error-prone translesion DNA synthesis , frequently involving Pol ζ , during repair synthesis . Our results suggest that sulfite-induced lesions in DNA can be particularly deleterious , since cells might not possess the means to repair or bypass such lesions accurately .\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: INTRODUCTION A subpopulation of cancer cells , tumor-initiating cells , is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy . The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins , as well as a reduced propensity to undergo apoptosis or senescence . METHODS To test this hypothesis , we isolated CD24-/low/CD44+ tumor-initiating cells ( as mammospheres ) from MCF-7 breast cancer cells grown in adherent monolayer culture , and carried out a comprehensive comparison of cell death and DNA damage response pathways prior to and after exposure to ionizing radiation in mammospheres and monolayer MCF-7 cells . Single and double-strand break repair was measured by single-cell gel electrophoresis . The latter was also examined by phosphorylation of histone H2AX and formation of 53BP1 and Rad51 foci . Apoptosis was quantified by flow-cytometric analysis of annexin V-binding and senescence was analyzed on the basis of cellular beta-galactosidase activity . We employed the telomeric repeat amplification protocol to quantify telomerase activity . Expression of key DNA repair and cell cycle regulatory proteins was detected and quantified by western blot analysis . RESULTS Our data demonstrate that in comparison to the bulk population of MCF-7 cells ( predominantly CD24+/CD44+ ) , the MCF-7 mammosphere cells benefit from a multifaceted approach to cellular protection relative to that seen in monolayer cells , including a reduced level of reactive oxygen species , a more active DNA single-strand break repair ( SSBR ) pathway , possibly due to a higher level of expression of the key SSBR protein , human AP endonuclease 1 ( Ape1 ) , and a significantly reduced propensity to undergo senescence as a result of increased telomerase activity and a low level of p21 protein expression . No significant difference was seen in the rates of double-strand break repair ( DSBR ) between the two cell types , but DSBR in mammospheres appears to by-pass the need for H2AX phosphorylation . CONCLUSIONS Enhanced survival of MCF-7 tumor-initiating cells in response to ionizing radiation is primarily dependent on an inherent down-regulation of the senescence pathway . Since MCF-7 cells are representative of cancer cells that do not readily undergo apoptosis , consideration of senescence pathways may play a role in targeting stem cells from such tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;evading growth suppressors;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Induced pluripotent stem ( iPS ) cells share some basic properties , such as self-renewal and pluripotency , with cancer cells , and they also appear to share several metabolic alterations that are commonly observed in human tumors . The cancer cells ' glycolytic phenotype , first reported by Otto Warburg , is necessary for the optimal routing of somatic cells to pluripotency . However , how iPS cells establish a Warburg-like metabolic phenotype and whether the metabolic pathways that support the bioenergetics of iPS cells are produced by the same mechanisms that are selected during the tumorigenic process remain largely unexplored . We recently investigated whether the reprogramming-competent metabotype of iPS cells involves changes in the activation/expression status of the H ( + ) -ATPase , which is a core component of mitochondrial oxidative phosphorylation that is repressed at both the activity and protein levels in human carcinomas , and of the lipogenic switch , which refers to a marked overexpression and hyperactivity of the acetyl-CoA carboxylase ( ACACA ) and fatty acid synthase ( FASN ) lipogenic enzymes that has been observed in nearly all examined cancer types . A comparison of a starting population of mouse embryonic fibroblasts and their iPS cell progeny revealed that somatic cell reprogramming involves a significant increase in the expression of ATPase inhibitor factor 1 ( IF1 ) , accompanied by extremely low expression levels of the catalytic β-F1-ATPase subunit . The pharmacological inhibition of ACACA and FASN activities markedly decreases reprogramming efficiency , and ACACA and FASN expression are notably upregulated in iPS cells . Importantly , iPS cells exhibited a significant intracellular accumulation of neutral lipid bodies ; however , these bodies may be a reflection of intense lysosomal/autophagocytic activity rather than bona fide lipid droplet formation in iPS cells , as they were largely unresponsive to pharmacological modulation of PPARgamma and FASN activities . The AMPK agonist metformin , which endows somatic cells with a bioenergetic infrastructure that is protected against reprogramming , was found to drastically elongate fibroblast mitochondria , fully reverse the high IF1/β-F1-ATPase ratio and downregulate the ACACA/FASN lipogenic enzymes in iPS cells . The mitochondrial H ( + ) -ATP synthase and the ACACA/FASN-driven lipogenic switch are newly characterized as instrumental metabolic events that , by coupling the Warburg effect to anabolic metabolism , enable de-differentiation during the reprogramming of somatic cells to iPS 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: The role of T cells in eradicating leukemic cells has been well demonstrated for chronic myeloid leukemia ( CML ) . Type 1 ( T1 ) T-cell cytokines play a major role in this antileukemic immune effect . Studies in cancer patients have demonstrated a decreased T1 cytokine production , measured by enzyme-linked immunosorbent assay ( ELISA ) , in cultures of peripheral blood mononuclear cells . This observation of malignancy-related suppressed T1 cytokines also occurs in untreated chronic-phase ( CP ) CML , raising the question of the influence of different CML treatment regimens on this immunosuppression . Intracellular flow cytometry ( ICF ) has facilitated the evaluation of cytokines on a single-cell level . This study analyzed T1 ( interferon-gamma ) cytokine production in purified peripheral blood T cells by ICF , comparing different therapy approaches for CML . Twenty-one newly diagnosed CP CML patients were compared with 24 patients treated with interferon-alpha ( IFN-alpha ) and to 30 allogeneic bone marrow transplant ( BMT ) recipients ( BCR-ABL negative by reverse-transcriptase polymerase chain reaction , and free of , or having only limited graft-versus-host disease at the time of study ) . Thirty-seven healthy controls were included . Our results showed a significantly decreased T-cell IFN-gamma synthesis in CP CML patients in relation to healthy controls ( P = 0.0007 ) . Treatment with IFN-alpha resulted in a shift from immunosuppression--documented for the group of untreated patients--to immunopotentiation , with an increase of T-cell IFN-gamma production ( P = 0.0266 ) . Notably , BMT enhanced IFN-gamma production of T cells to a level not only exceeding untreated patients ( P &lt ; 0.0001 ) but also healthy volunteers ( P &lt ; 0.0001 ) . The observation of T1 cytokine up-regulation with IFN-alpha therapy indicates that enhanced T-cell function may be achievable in patients with CML , even in the absence of an allo-response .\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: An aqueous extract of Kefir , fermented milk originally produced in the Caucasus mountains , suppressed morphological changes of human melanoma HMV-1 and SK-MEL cells and human normal fibroblastTIG-1 cells caused by UVC-irradiation , suggesting that UV damage can be suppressed by the Kefir extract . The addition of the Kefir extract after UVC-irradiation of HVM-1 cells resulted in a remarkable decrease in intracellular reactive oxygen species ( ROS ) which had been increased by UVC irradiation . The Kefir extract also stimulated unscheduled DNA synthesis and suppressed UVC-induced apoptosis of HMV-1 cells . A colony formation assay revealed that the Kefir extract rescued HMV-1 cells from cell death caused by UVC irradiation . The Kefir extract , as well as methyl methanethiosulfonate which is known to enhance the nucleotide excision repair ( NER ) activity , exhibited strong thymine dimer repair-enhancing activity . Epigalocatechin exhibited a weak NER activity but vitamins A , C , and E and catechin showed no NER activity . The thymine dimer repair-enhancing factors in the Kefir extract were heat-stable and assumed to be molecules with a molecular weight of less than 5000 . The treatment of HMV-1 cells with the Kefir extract during or before UVC- irradiation also prevented the generation of ROS and thymine dimmer , and suppressed the apoptosis of HMV-1 cells , suggesting that application of Kefir can prevent UV damage .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVE Chronic generation of inflammatory cytokines and reactive oxygen species are implicated in atherosclerosis , aging , cancers , and other chronic diseases . We hypothesized that zinc induces A20 in premonocytic , endothelial , and cancer cells , and A20 binds to tumor necrosis factor ( TNF)-receptor associated factor , and inhibits Iκ kinase-α ( IKK-α)/nuclear factor-κB ( NF-κB ) , resulting in downregulation of TNF-α and interleukin-1β ( IL-1β ) . METHODS To test this hypothesis , we used HL-60 , human umbilical vein endothelial cells , and SW480 cell lines under zinc-deficient and zinc-sufficient conditions in this study . We measured oxidative stress markers , inflammatory cytokines , A20 protein and mRNA , A20-FRAF-1 complex , and IKK-α/NF-κB signaling in stimulated zinc-deficient and zinc sufficient cells . We also conducted antisense A20 and siRNA studies to investigate the regulatory role of zinc in TNF-α and IL-1β via A20 . RESULTS We found that zinc increased A20 and A20-tumor necrosis factor-receptor associated factor-1 complex , decreased the IKK-α/NF-κB signaling pathway , oxidative stress markers , and inflammatory cytokines in these cells compared with zinc-deficient cells . We confirmed that zinc-induced A20 contributes to downregulation of TNF-α and IL-1β by antisense and short interfering RNA A20 studies . CONCLUSION Our studies suggest that zinc suppresses generation of NF-κB-regulated inflammatory cytokines by induction of A20 .\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: Recent surveys indicate that Pi intake has increased steadily as Pi-containing foods have increased . Our previous study demonstrated that high dietary Pi strongly stimulated lung tumorigeneis . In order to answer the issue whether low Pi may be chemopreventive , we examined the effects of low Pi on lung cancer . Eighteen 5-wk-old male K-ras(LA1) lung cancer model mice were randomly allocated to 2 groups . One group was fed a normal diet ( 0.5% Pi ) and other group was fed low Pi ( 0.1% Pi ) diet for 4 wk . Lung cancer development was evaluated by histopathological examination , Western blot , kinase assay , and immunohistochemistry . Low Pi increased the expression of sodium-dependent phosphate co-transporter 2b , and activated Akt signal with decreased PTEN expression in the lungs of K-ras(LA1) mice . Low Pi increased the Akt/mTOR-mediated protein translation through upregulating the phosphorylation of p70S6K and 4E-BP1 . In addition , low Pi stimulated cell cycling as evidenced by altered cell cycle regulators such as cyclin D1 and D3 . Finally , low Pi increased lung tumorigenesis in K-ras(LA1) mice compared to the normal diet group . Our results clearly demonstrated that low Pi also promoted lung tumorigenesis , thus suggesting that an appropriate intake of dietary Pi may be critical for lung cancer prevention as well as treatment .\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: Transcriptional coactivator amplified in breast cancer 1 ( AIB1 ) plays important roles in the progression of several cancers such as prostate cancer , breast cancer , and hepatocellular carcinoma . However , its role in cholangiocarcinoma ( CCA ) , a chemoresistant bile duct carcinoma with a poor prognosis , remains unclear . In this study we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines . Down-regulation of AIB1 induced the G2/M arrest and decreased the expression of mitosis-promoting factors including Cyclin A , Cyclin B , and Cdk1 through suppressing the Akt pathway , which resulted in inhibiting CCA cell proliferation . In addition , AIB1 enhanced the chemoresistance of CCA cells at least in part through up-regulating the expression of antiapoptotic protein Bcl-2 . AIB1 regulated the expression of Bcl-2 in CCA cells through activating the Akt pathway as well as suppressing intracellular reactive oxygen species ( ROS ) . AIB1 suppressed ROS by up-regulating antioxidants such as glutathione synthetase and glutathione peroxidase , which are targets of the NF-E2-related factor 2 ( Nrf2 ) , a critical transcription factor that regulates antioxidants , detoxification enzymes , and drug efflux proteins . AIB1 also increased the expression of another two Nrf2 targets , ABCC2 and ABCG2 , to enhance drug efflux . AIB1 served as an essential coactivator for Nrf2 activation by physically interacting with Nrf2 to enhance its transcriptional activity . Conclusion : AIB1 plays an important role in proliferation and chemoresistance of CCA through simultaneous activation of Akt and Nrf2 pathways , suggesting that AIB1 is a potential molecular target for CCA treatment .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;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: PRL induces quiescent Nb2 rat T-lymphoma cells to undergo mitogenesis . Upon PRL stimulation , the transcription factor interferon regulatory factor-1 ( IRF-1 ) is induced as a novel T-cell activation gene in Nb2 cells . Surprisingly , IRF-1 is expressed twice during a single PRL-induced growth cycle : first during the early G1 phase , in an immediate transient peak from 15 min to 2 h , and second during the G1/S phase transition , in a broader peak beginning at 8 h . The unusual biphasic expression of IRF-1 mRNA is accompanied both times by de novo IRF-1 protein synthesis . However , the rate of IRF-1 protein turnover appears to be different in G1 and S phases . IRF-1 protein expressed in G1 exhibits a half-life of about 25 min , whereas in the S phase , the half-life is about 60 min . By washing out PRL at various times during G1 , we found a direct correlation among the length of PRL exposure , the second peak of IRF-1 mRNA expression , and DNA synthesis . Our data suggest that PRL and one putative nuclear mediator , IRF-1 , may be important in two distinct phases of the cell cycle : first in cell cycle activation , and then in S phase progression .\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: Genomic instability has long been recognized as the main feature of neoplasia and a factor modulating individual cancer susceptibility . There are attempts to find effective assays of both individual DNA repair capacity and genetic instability , and their relation to the cancer risk . Genetic predisposition plays an important role in the etiology and development of head and neck squamous cell carcinoma ( HNSCC ) . The aim of our study was to search for a correlation between chromosomal instability and DNA repair capacity in HNSCC patients and healthy controls . The chromosomal instability was measured by the number of bleomycin ( BLM)-induced chromosomal aberrations and diepoxybutane ( DEB)-induced sister chromatid exchanges . The DNA repair capacity was assessed using the DEB-induced adaptive response ( AR ) . The HNSCC patients in our study showed a significant increase in chromosomal instability after a preterminal exposure of their lymphocytes to either BLM for the last 5 h or DEB for the last 24 h of incubation . However , the AR was higher in HNSCC patients than in the control group , suggesting an increase in the DNA repair capacity in the cancer patients as compared to the control . There is no correlation between the DNA repair capacity estimated on the basis of preterminal exposures to BLM and DEB and the DNA repair capacity estimated on the basis of the adaptive response to DEB . The preterminal exposure and the adaptive response test may activate different DNA repair mechanisms .\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: Onions ( Allium cepa L. ) are widely used in the food industry for its nutritional and aromatic properties . Our studies showed that ethyl acetate extract of onion ( EEO ) had potent inhibitory effects on animal fatty acid synthase ( FAS ) , and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells . Furthermore , this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids , the final product of FAS catalyzed synthesis . These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS . We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes , which was also related to its inhibition of intracellular FAS activity . Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers , these findings suggested that onion might be useful for preventing obesity-related malignancy .\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: Blind mole rats Spalax ( BMR ) are small subterranean rodents common in the Middle East . BMR is distinguished by its adaptations to life underground , remarkable longevity ( with a maximum documented lifespan of 21 y ) , and resistance to cancer . Spontaneous tumors have never been observed in spalacids . To understand the mechanisms responsible for this resistance , we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani . BMR cells proliferated actively for 7-20 population doublings , after which the cells began secreting IFN-β , and the cultures underwent massive necrotic cell death within 3 d . The necrotic cell death phenomenon was independent of culture conditions or telomere shortening . Interestingly , this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat , Heterocephalus glaber , the naked mole rat in which cells display hypersensitivity to contact inhibition . Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death . Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways , and triggered by the release of IFN-β . Thus , we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;enabling replicative immortality;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND/AIMS The use of chemotherapy in hepatocellular carcinoma is still controversial . The aim of this study was to investigate whether the combined use of epirubicin and progesterone has a synergistic effect on cell proliferation and apoptosis in HepG2 cells . METHODOLOGY Different concentrations of epirubicin ( 0.1 microg/ml , 0.25 microg/ml and 0.5microg/ml ) or progesterone ( 12.5 microM , 25 microM and 50 microM ) were added to HepG2 cells either alone or in combinations consisting of different concentrations of the two . Their effects on HepG2 cells were studied by ( 1 ) XTT assay for analysis of cell proliferation , ( 2 ) 3H-Thymidine incorporation for DNA synthesis , ( 3 ) annexin V-FITC/ propidium iodide ( PI ) flowcytometery for cell apoptosis , ( 4 ) flowcytometry for cell cycle distributions , and ( 5 ) reverse transcription-polymerase chain reaction for expression of cell cycle modulator , cyclin D1 . RESULTS 50 microM progesterone increased both the cytotoxic and apoptotic effects of 0.1 microg/ml epirubicin on HepG2 cells at 48 hr culture due to 50 microM progesterone accumulated cells in S phase of the cell cycle and subsequently reduced cyclin D1 expression . These effects on HepG2 cells induced by this combination were comparable to those induced by 0.5 microg/ml epirubicin alone . CONCLUSIONS In vitro , progesterone can increase the cytotoxicity and apoptosis induced by epirubicin on HepG2 cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A common metabolic change in cancer is the acquisition of glycolytic phenotypes . Increased expression of glycolytic enzymes is considered as one contributing factor . The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial . Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-Ras(Q61L) transformation , even though the mitochondrial contents or mass was not reduced in the transformed cells . First , mitochondrial respiration , as measured by mitochondrial oxygen consumption , was suppressed in NIH-3T3 cells transformed with H-Ras(Q61L) . Second , oligomycin or rotenone did not reduce the cellular ATP levels in the H-Ras(Q61L) transformed cells , suggesting a diminished role of mitochondrial respiration in the cellular energy metabolism . Third , inhibition of glycolysis with iodoacetic acid reduced ATP levels at a much faster rate in H-Ras(Q61L) transformed cells than in the vector control cells . The reduction of cellular ATP levels was reversed by exogenously added pyruvate in the vector control cells but not in H-Ras(Q61L) transformed cells . Finally when compared to the HRas(Q61L) transformed cells , the vector control cells had increased resistance toward glucose deprivation . The increased resistance was dependent on mitochondrial oxidative phosphorylation since rotenone or oligomycin abolished the increased survival of the vector control cells under glucose deprivation . The results also suggest an inability of the H-Ras(Q61L) transformed cells to reactivate mitochondrial respiration under glucose deprivation . Taken together , the data suggest that mitochondrial respiration can be impaired during transformation of NIH-3T3 cells by oncogeneic H-Ras(Q61L) .\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: Epithelial-mesenchymal transition ( EMT ) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites . Recently , EMT was shown to be associated with the cancer stem cell ( CSC ) phenotype in breast cancer . Snail is a transcription factor that mediates EMT in a number of tumor types , including colorectal cancer ( CRC ) . Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC . Human CRC specimens were stained for Snail expression , and human CRC cell lines were transduced with a retroviral Snail construct or vector control . Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT ( colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) assay . Migration and invasion were determined in vitro using modified Boyden chamber assays . EMT and putative CSC markers were analyzed using Western blotting . Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice . Snail was overexpressed in human CRC surgical specimens . This overexpression induced EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration and invasion ( P &lt ; 0.002 vs. control ) . Snail overexpression also led to an increase in metastasis formation in vivo ( P &lt ; 0.002 vs. control ) . Furthermore , the Snail-overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells . Increased Snail expression induces EMT and the CSC-like phenotype in CRC cells , which enhance cancer cell invasion and chemoresistance . Thus , Snail is a potential therapeutic target in metastatic CRC .\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: PTEN loss of function enhances proliferation , but effects on cellular energy metabolism are less well characterized . We used an inducible PTEN expression vector in a PTEN-null glioma cell line to examine this issue . While proliferation of PTEN-positive cells was insensitive to increases in glucose concentration beyond 2.5mM , PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to approximately 10mM , coinciding with a shift to glycolysis and \" glucose addiction \" . This demonstrates that the impact of loss of function of PTEN is modified by glucose concentration , and may be relevant to epidemiologic results linking hyperglycemia to cancer risk and cancer mortality .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The innate immune response involves a variety of inflammatory reactions that can result in inflammatory disease and cancer if they are not resolved and instead are allowed to persist . The effective activation and resolution of innate immune responses relies on the production and posttranscriptional regulation of mRNAs encoding inflammatory effector proteins . The RNA-binding protein HuR binds to and regulates such mRNAs , but its exact role in inflammation remains unclear . Here we show that HuR maintains inflammatory homeostasis by controlling macrophage plasticity and migration . Mice lacking HuR in myeloid-lineage cells , which include many of the cells of the innate immune system , displayed enhanced sensitivity to endotoxemia , rapid progression of chemical-induced colitis , and severe susceptibility to colitis-associated cancer . The myeloid cell-specific HuR-deficient mice had an exacerbated inflammatory cytokine profile and showed enhanced CCR2-mediated macrophage chemotaxis . At the molecular level , activated macrophages from these mice showed enhancements in the use of inflammatory mRNAs ( including Tnf , Tgfb , Il10 , Ccr2 , and Ccl2 ) due to a lack of inhibitory effects on their inducible translation and/or stability . Conversely , myeloid overexpression of HuR induced posttranscriptional silencing , reduced inflammatory profiles , and protected mice from colitis and cancer . Our results highlight the role of HuR as a homeostatic coordinator of mRNAs that encode molecules that guide innate inflammatory effects and demonstrate the potential of harnessing the effects of HuR for clinical benefit against pathologic inflammation and cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Dietary antioxidants , such as the carotenoids , may protect DNA from oxidative damage . This has been proposed to explain the epidemiological association between higher consumption of fruits and vegetables , which are rich in antioxidants , and lower incidence of cancer . However , this remains to be demonstrated conclusively . The effects of carotenoid supplementation on 1 ) baseline DNA damage , 2 ) susceptibility of cellular DNA to oxidative attack , and 3 ) DNA repair were measured in the human lymphocyte cell line Molt-17 . Baseline DNA damage , susceptibility to oxidant attack ( 100 mumol/l H2O2 for 5 min at 4 degrees C ) , and disappearance of DNA single-strand breaks ( SSB ) after oxidative challenge were monitored by single-cell gel electrophoresis . DNA repair patch synthesis activity in cell extracts was determined using assays that measure nucleotide incorporation during repair of oxidative lesions in template DNA . Unlike single-cell gel electrophoresis , the parameters measured with these assays are not dependent on strand break religation . There was no evidence that beta-carotene , lutein , or beta-cryptoxanthin supplementation protected cellular DNA from oxidation under basal conditions or after oxidative challenge . However , only carotenoid-supplemented cells exhibited a significant decrease in numbers of SSB over a 2-h period after treatment with H2O2 . Carotenoid supplementation did not provoke any detectable change in repair patch synthesis activity . We conclude that supplementation with carotenoids at 8 mumol/l does not provide significant antioxidant protection for DNA in Molt-17 lymphocytes but may enhance recovery of cells from oxidative challenge , as measured by loss of SSB . We argue that these data are most consistent with carotenoids acting to enhance DNA strand break repair .\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: Recent research has shown that the Na(+)/K(+)-ATPase alpha1 subunit is a novel anti-cancer target , which plays pivotal roles in malignant cell ion transport , metabolism , migration and signal transduction . The purpose of the present study was to investigate the anti-cancer effects of ouabain and Na(+)/K(+)-ATPase alpha1 small interfering ribonucleic acid ( siRNA ) on HepG2 cell proliferation , apoptosis and cell cycle , and to explore the molecular mechanisms . The expression of Na(+)/K(+)-ATPase alpha1 subunit in human hepatocellular carcinoma ( HCC ) , normal liver tissues and human HCC line ( HepG2 , SMMC-7721 and Bel-7402 ) has been investigated . Using the ouabain and Na(+)/K(+)-ATPase alpha1 subunit siRNA , which target the Na(+)/K(+)-ATPase , we have evaluated the effects of inhibiting Na(+)/K(+)-ATPase alpha1 in human HepG2 cells with respect to cell proliferation , morphology , cell cycle , impact on intracellular Ca2++ , reactive oxygen species ( ROS ) concentration , and correlated gene expression level on messenger ribonucleic acid ( mRNA ) and protein . Our data showed that the expression Na(+)/K(+)-ATPase alpha1 subunit in HCC tissues is higher than that in normal liver tissues . Ouabain and Na(+)/K(+)-ATPase alpha1 siRNA could inhibit HepG2 cell proliferation . Ouabain could induce HepG2 cell apoptosis and generate S phase arrest , and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated , and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 ( CDK2)/proliferating cell nuclear antigen ( PCNA ) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A ( P21(CIP1) ) . We believe that targeting of the Na(+)/K(+)-ATPase alpha1 subunit in human HCC cells could provide new sight into the treatment of HCC .\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: Olfactomedin 4 ( OLFM4 ) is highly expressed in gastrointestinal cancers and has an anti-apoptotic function . The roles of OLFM4 in tumor growth and metastasis and how it functions in these processes remain elusive . We investigated the function of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an experimental system . Our results showed that OLFM4 had no positive effect on cell viability or cell cycle progression in B16F10 cells . However , it significantly suppressed the tumorigenicity of B16F10 cells , i.e. , intradermal primary tumor growth and lung metastasis . OLFM4 also suppressed the migration and invasion of B16F10 cells in vitro . For further insight into the mechanisms underlying OLFM4-mediated suppression of tumor progression , we examined the effect of OLFM4 on the expression of integrin and matrix metalloproteinase ( MMP ) , both of which are involved in tumor progression . Overexpression of OLFM4 clearly reduced the expression levels of integrin α1 , integrin α4 , integrin α5 , integrin α6 , and MMP9 . Moreover , forced expression of MMP9 attenuated the inhibitory activity of OLFM4 on migration and invasiveness . Our findings provide the experimental evidence that OLFM4 may function as a tumor suppressor and an anti-metastatic gene during tumor progression .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Hormone-independent tumor growth and metastasis are associated with increased mortality in human prostate cancer . In this study , we evaluate a potential role for ligand-mediated activation of HER2 receptor tyrosine kinase in androgen-independent prostate cancers . HER2 , HER3 , and epidermal growth factor receptor were detected in the androgen-independent cell line 22Rv1 . Heregulin stimulation results in receptor phosphorylation and cell proliferation that is inhibited by increasing concentrations of anti-HER2 recombinant humanized monoclonal antibody ( rhuMAb ) 2C4 . Furthermore , inhibition of tumor growth was observed in xenografts derived from 22Rv1 cells when treated with rhuMAb 2C4 in a dose-dependent manner . These studies provide a framework , both in vitro and in vivo , to examine the molecular mechanisms of ligand-driven HER2 activation in androgen-independent 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: Elevated insulin-like growth factor binding protein-related protein 1 ( IGFBP-rP1 ) mRNA in senescent human mammary epithelial cells suggested that the IGFBP-3 gene product may inhibit cell proliferation . To test this hypothesis , we used a retroviral vector to express IGFBP-rP1 cDNA in the IGFBP-rP1-deficient MCF-7 breast cancer cell line . Compared with control vector-transduced cells , cumulative cell numbers for IGFBP-rP1-transduced polyclonal or clonal cell cultures were reduced by 39 and 74% , respectively , after 1 week . Medium conditioned by IGFBP-rP1-producing cultures reduced cumulative cell numbers in parental MCF-7 cultures by 20% compared with medium from cultures of a control vector-transduced cell line . Nuclear fragmentation analysis and cell proliferation assays completed in the presence of the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone excluded apoptosis as the responsible mechanism . The percentage of cells containing senescence-associated beta-galactosidase activity was doubled compared with control cell cultures . Flow cytometry analysis indicated that twice as many noncycling cells were present in the IGFBP-rP1-transduced MCF-7 cell cultures compared with controls . These findings indicate that IGFBP-rP1 is an inhibitor of MCF-7 breast cancer cell proliferation and may act via a cellular senescence-like mechanism .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The ARF locus is frequently inactivated in human cancer . The oncosuppressor ARF has indeed been described as a general sensor for different situation of cellular stress . We have previously demonstrated that ARF deficiency severely impairs inflammatory responses in vitro and in vivo , establishing a role for ARF in the regulation of innate immunity . The aim of the present work was to get further insights into the immune functions of ARF and to evaluate its possible contribution to the polarization of macrophages toward the M1 or M2 phenotype . Our results demonstrate that resting Arf(-/-) macrophages express high levels of Ym1 and Fizz-1 , two typical markers of alternatively-activated macrophages ( M2 ) . Additionally , Arf(-/-) peritoneal macrophages showed an impaired response to lipopolysaccharide ( a classical inducer of M1 polaryzation ) and a reduced production of pro-inflammatory cytokines/chemokines . Moreover , upon stimulation with interleukin-4 ( IL-4 ) , an inducer of the M2 phenotype , well established M2 markers such as Fizz-1 , Ym1 and arginase-1 were upregulated in Arf(-/-) as compared with wild type macrophages . Accordingly , the cytokine and chemokine profile associated with the M2 phenotype was significantly overexpressed in Arf(-/-) macrophages responding to IL-4 . In addition , multiple pro-angiogenic factors such as VEGF and MMP-9 were also increased . In summary , these results indicate that ARF contributes to the polarization and functional plasticity of macrophages .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;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: Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan , China . The potent apoptotic activities of bigelovin in human leukemia U937 cells were shown in our previous study . The present study investigated the anti-angiogenic and immunomodulatory effects of bigelovin using transgenic zebrafish Tg(fli1a:EGFP)y1 with fluorescent blood vessels and human peripheral blood mononuclear cells ( PBMCs ) , respectively . Furthermore , the inhibitory activities of bigelovin on the human endothelial cell adhesion molecules ( CAMs ) were also examined . Our results showed that the growth of subintestinal vessels of the bigelovin-treated zebrafish embryos was significantly inhibited and the gene expressions in angiogenesis signaling pathways ( e.g . Ang2 and Tie2 ) of the zebrafish were down-regulated after bigelovin treatment . Besides , the proliferation and Th1 cytokines productions ( e.g . IFN-γ , IL-2 and IL-12 ) were suppressed in bigelovin-treated PBMCs . On the other hand , bigelovin was shown to significantly inhibit the human monocyte adhesion to human endothelial cells and the gene expressions of inflammation-related CAMs ( e.g . ICAM-1 , VCAM-1 and E-selectin ) were significantly down-regulated in bigelovin-treated human endothelial cells . In summary , our data provide the first evidence that bigelovin possesses anti-angiogenic and immunomodulatory activities , suggesting bigelovin may exert multi-target functions against cancer in animal models .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor , and this is typically seen as a failure of treatment . We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53 . We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo . Our results suggest that p53 and p21 play a central role in the onset of senescence , whereas p16(INK4a) function may be involved in maintaining senescence . Thus , like apoptosis , senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Telomerase is a ribonucleoprotein consisting of a catalytic subunit , the telomerase reverse transcriptase , TERT , and an integrally associated RNA , TR , which contains a template for the synthesis of short repetitive G-rich DNA sequences at the ends of telomeres . Telomerase can repetitively reverse transcribe its short RNA template , acting processively to add multiple telomeric repeats onto the same DNA substrate . The contribution of enzyme processivity to telomere length regulation in human cells is not well characterized . In cancer cells , under homeostatic telomere length-maintenance conditions , telomerase acts processively , while under nonequilibrium conditions , telomerase acts distributively on the shortest telomeres . To investigate the role of increased telomerase processivity on telomere length regulation in human cells with limited lifespan that are dependent on human TERT ( hTERT ) for lifespan extension and immortalization , we mutated the leucine at position 866 in the reverse transcriptase C motif of hTERT to a tyrosine ( L866Y ) , which is the amino acid found at a similar position in HIV-1 reverse transcriptase . We report that , similar to the previously reported ' gain of function ' Tetrahymena telomerase mutant ( L813Y ) , the human telomerase variant displays increased processivity. hTERT-L866Y , like wild-type hTERT can immortalize and extend the lifespan of limited lifespan cells . Moreover , hTERT-L866Y expressing cells display heterogenous telomere lengths , telomere elongation , multiple telomeric signals indicative of fragile sites and replicative stress , and an increase in short telomeres , which is accompanied by telomere trimming events . Our results suggest that telomere length and homeostasis in human cells may be regulated by telomerase enzyme processivity .\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: XRCC4 , in association with DNA ligase IV , is thought to play a critical role in the ligation of two DNA ends in DNA double-strand break ( DSB ) repair through non-homologous end-joining ( NHEJ ) pathway . In the present study , we captured radiation-induced chromatin-recruitment of XRCC4 by biochemical fractionation using detergent Nonidet P-40 . A subpopulation of XRCC4 changed into a form that is resistant to the extraction with 0.5% Nonidet P-40-containing buffer after irradiation . This form of XRCC4 was liberated by micrococcal nuclease treatment , indicating that it had been tethered to chromatin DNA . This chromatin-recruitment of XRCC4 could be seen immediately ( &lt ; 0.1 hr ) after irradiation and remained up to 4 hr after 20 Gy irradiation . It was seen even after irradiation of small doses , i.e. , 2 Gy , but the residence of XRCC4 on chromatin was very transient after 2 Gy irradiation , returning to near normal level in 0.2-0.5 hr after irradiation . The chromatin-bound XRCC4 represented only approximately 1% of total XRCC4 molecules even after 20 Gy irradiation and the quantitative analysis using purified protein as the reference suggested that only a few XRCC4-DNA ligase IV complexes were recruited to each DNA end . We further show that the chromatin-recruitment of XRCC4 was not attenuated by wortmannin , an inhibitor of DNA-PK , or siRNA-mediated knockdown of the DNA-PK catalytic subunit ( DNA-PKcs ) , indicating that this process does not require DNA-PKcs . These results would provide us with useful experimental tools and important insights to understand the DNA repair process through NHEJ pathway .\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: Ferric nitrilotriacetate ( Fe-NTA ) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress . The present study was undertaken to explore protective effect of silymarin , a flavonolignan from milk thistle ( Silybum marianum ) , against Fe-NTA mediated renal oxidative stress , inflammation and tumor promotion response along with elucidation of the implicated mechanism(s) . Administration of Fe-NTA ( 10 mg/kg bd wt , i.p. ) to Swiss albino mice induced marked oxidative stress in kidney , evident from augmentation in renal metallothionein ( MT ) expression , depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes , and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal . Fe-NTA also significantly activated nuclear factor kappa B ( NFkappaB ) and upregulated the expression of downstream genes : cyclooxygenase 2 and inducible nitric oxide synthase and enhancing the production of proinflammatory cytokines : tumor necrosis factor alpha ( TNF-alpha ) and interleukin-6 ( IL-6 ) . However , feeding of 0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA induced oxidative stress and inflammation . It further augmented MT expression , restored the antioxidant armory , ameliorated NFkappaB activation and decreased the expression of proinflammatory mediators . Silymarin also suppressed Fe-NTA induced hyperproliferation in kidney , ameliorating renal ornithine decarboxylase activity and DNA synthesis . From these results , it could be concluded that silymarin markedly protects against chemically induced renal cancer and acts plausibly by virtue of its antioxidant , anti-inflammatory and antiproliferative activities .\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: Malignant mesothelioma ( MM ) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested . Three different primary cultures ( MMGe-1 , MES MM 98 , and MES 1 ) and one immortalized cell line ( MSTO 211 H ) of human MM were studied in order to evaluate the HER-2/neu expression . Three out of four cell lines showed a different level of c-erbB-2 expression , the highest being detected on the MSTO 211 H cell line ( fibroblastic phenotype ) , whereas MMGe-1 resulted negative . The effect of the anti-HER-2/neu antibody ( Trastuzumab ) alone , and in combination with cisplatin ( CDDP ) at different doses ( ranging from 0.1 to 100 microg/ml ) , was studied on all the c-erB-2 positive cell lines . Trastuzumab was able to inhibit cell proliferation in a time-dependent manner , with growth inhibition also obtained at low concentrations ( 0.1-1 microg/ml ) . Combined treatment with Trastuzumab ( 10 microg/ml ) and CDDP ( 1 microg/ml ) showed synergism . Our results were encouraging , and suggest a rationale for further investigations in a clinical setting .\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: Our previous study demonstrated that 5-aminolevulinic acid ( ALA ) administered to mice stimulates oxidative phosphorylation by upregulation of the mitochondrial respiratory chain complex IV enzyme cytochrome c oxidase ( COX ) . The present study investigated whether ALA disrupts the Warburg effect , which represents a shift in ATP generation from oxidative phosphorylation to glycolysis , protecting tumor cells against oxidative stress-mediated apoptosis . The human lung carcinoma cell line A549 exposed to ALA exhibited enhanced oxidative phosphorylation , which was indicated by an increase in COX protein expression and oxygen consumption . Furthermore , ALA suppressed glycolysis-mediated acidosis . This normalization of the ATP metabolic pathways significantly increased the generation of superoxide anion radical ( O2•- ) and the functional expression of active caspase-3 , leading to caspase-dependent apoptosis . These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death . Use of this endogenous compound might constitute a novel approach to cancer therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Food-derived heterocyclic aromatic amines ( HCAs ) have proved to be carcinogenic in both rodents and nonhuman primates . Two different metabolic pathways are suggested for the metabolic activation of HCA . The hepatic pathway proceeds via a two-step process involving N-hydroxylation by cytochrome P4501A2 and subsequent O-acetylation by N-acetyltransferase-2 . An alternative pathway may be of particular interest in extrahepatic tissues and proceeds via one-electron oxidation catalyzed by prostaglandin H synthase ( PHS ) , rendering free-radical metabolites . In this study , we investigated the metabolic activation of two HCAs , 2-amino-3-methylimidazo[4,5-f]quinoline ( IQ ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , by two different enzyme systems in vitro , generating different primary and secondary reactive metabolites . Rat liver S9 mix and PHS were used as the activating system and represent the hepatic and extrahepatic pathways , respectively . Electron-spin resonance spectroscopy showed that both IQ and PhIP exerted inhibiting effects on PHS-mediated formation of hydroxyl radicals during the conversion of arachidonic acid to prostaglandins . Evidence for the formation of HCA free radicals was presented in an indirect way by the formation of glutathione-derived thiyl radicals , with purified PHS as the activating system . Activation by S9 mix did not result in the formation of detectable radical metabolites , showing that the two metabolic routes primarily led to the formation of different metabolites . In all electron-spin resonance experiments , IQ appeared to be more effective than PhIP . In contrasts , DNA adduct analysis by means of ( 32)P-postlabeling showed similar adduct patterns for S9 and PHS in single-stranded and double-stranded salmon testes DNA after incubation with PhIP , indicating the ultimate formation of a common reactive intermediate . For IQ , activation by PHS led to an additional adduct spot that was not present after S9 activation . Furthermore , activation of IQ resulted in higher adduct levels compared with PhIP for both activation pathways . Overall , adduct levels were higher in single-stranded DNA than double-stranded DNA . Our results showed that the hepatic and extrahepatic pathways resulted in different primary metabolites , while the ultimate formation of a similar reactive intermediate for PhIP , possibly an arylnitrenium ion , suggested that both pathways could play an important role in the onset of carcinogenesis .\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: AIM To investigate the progressive transformation of immortal cells of human fetal esophageal epithelium induced by human papillomavirus , and to examine biological criteria of sequential passage of cells , including cellular phenotype , proliferative rate , telomerase , chromosome and tumorigenicity . METHODS The SHEE cell series consisted of immortalized embryonic esophageal epithelium which was in malignant transformation when cultivated over sixty passages without co-carcinogens . Cells of the 10th , 31st , 60th and 85th passages were present in progressive development after being transfected with HPV . Cells were cultivated in a culture flask and 24-hole cultural plates . Progressive changes of morphology , cell growth , contact-inhibition , and anchorage-dependent growth characteristics were examined by phase contrast microscopy . The cell proliferation rate was assayed by flow cytometry . The modal number of chromosomes was analyzed . HPV18E(6)E(7) was detected by Western blot methods and activities of telomerase were analyzed by TRAP . Tumorigenicity of cells was detected with soft agar plates cultivated and with tumor formation in SCID mice . RESULTS In morphological examination the 10th passage cells were in good differentiation , the 60th and 85th passages cells were in relatively poor differentiation , and the 31st passage cells had two distinct differentiations . The characteristics of the 85th and 60th passage cells were weakened at contact-inhibition and anchorage-dependent growth . Karyotypes of four stages of cells belonged to hyperdiploid or hypotriploid , and bimodal distribution of chromosomes appeared in the 31st and 60th passage cells . All of these characteristics combined with a increasing trend . The activities of telomerase were expressed in the latter three passages . Four fourths of SCID mice in the 85th passage cells and one fourth of SCID mice in the 60th passage cells developed tumors , but the cells in the 10th and 31st passage displayed no tumor formation . CONCLUSION In continual cultivation of fetal esophageal epithelial cells with transduction of HPV18E(6)E(7) , cells from the 10th to the 85th passage were changed gradually from preimmortal , immortal , precancerous to malignantly transformed stages . All of these changes were in a dynamic progressive process . The establishment of a continuous line of esophageal epithelium may provide a in vitro model of carcinogenesis induced by HPV .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;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: Tobacco-induced oxidative stress leads to chronic inflammation and is implicated in the development of many human epithelial cancers , including head and neck cancer . Cigarette smoke exposure was shown to induce the expression of the ΔNp63α and nitric oxide synthase ( NOS)-2 in head and neck squamous cell carcinoma cells and immortalized oral keratinocytes . The NOS2 promoter was found to contain various cognate sequences for several transcription factors including interferon regulatory factor ( IRF)-6 and p63 , which were shown in vivo binding to the NOS2 promoter in response to smoke exposure . Small interfering ( si)-RNAs against both ΔNp63α and IRF6 decreased the induction of NOS2 promoter-driven reporter luciferase activity and were shown to inhibit NOS2 activity . Furthermore , both mainstream ( MSE ) and sidestream ( SSE ) smoking extracts induced changes in expression of autophagic marker , LC3B , while siRNA against ΔNp63α , IRF6 and NOS2 modulated these autophagic changes . Overall , these data support the notion that ΔNp63α/IRF6 interplay regulates NOS2 transcription , thereby underlying the autophagic-related cancer cell response to tobacco exposure .\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: Tricyclic antidepressants , such as amitriptyline ( Elavil ) , and the nontricyclic agent , fluoxetine ( Prozac ) , bind to growth-regulatory intracellular histamine receptors , associated with anti-estrogen binding sites in microsomes and nuclei . The prototype anti-estrogen binding site/intracellular histamine receptor ligand , N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl , inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo . Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl , we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression ( equivalent human dose range , approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine ) . All experiments were performed blinded . In studies of growth stimulation of transplantable syngeneic tumors , groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells , followed 24 h later by daily i.p. injections of saline , amitriptyline , or fluoxetine . Tumor latency ( fibrosarcoma ) , aggregate tumor weight ( s.c. injected melanoma ) , or time to death from pulmonary metastasis ( i.v. injected melanoma ) was determined ; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo . In a mammary carcinogenesis model , the effects of chronic saline , amitriptyline , or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene ( DMBA ) were compared . Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5 , as compared to none of 20 saline controls ( P less than 0.002 ) . Similarly , 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline ( P less than 0.001 ) . For both models , tumor latency decreased 30-40% and , in the DMBA model , tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls . Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro . While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells , a significant ( P less than 0.01 ) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS )\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Pam3CSK4 , a synthetic TLR2 ligand , has been shown to expand CD4+ regulatory T cells ( Treg cells ) . Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy ( IT ) . This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population . PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times : before IT and 6 mo and 1 y after the maximum-tolerated dose . This study was performed without a placebo-controlled group . D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production . Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition . TUNEL revealed that CD8+CD25+ Treg cells , but not CD4+CD25+ Treg cells , directly induced CD4+CD45ROhi+ apoptosis . Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells ; therefore , it may be a good adjuvant for the treatment of mite allergies .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death" } ]