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: BACKGROUND &amp ; OBJECTIVE Hereditary non-polyposis colorectal cancer ( HNPCC or Lynch syndrome ) , is a genetically heterogeneous disorder that is believed to account for 2-10 per cent of all the colorectal cancer cases . The disease follows autosomal dominant inheritance pattern with high penetrance ( 85% ) and younger age of onset when compared to patients with sporadic tumours . HNPCC is associated with germ-line mutations in the DNA mismatch repair ( MMR ) genes namely MLH1 , MSH2 , MSH6 , and PMS2 . The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria , and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed . METHODS A total 12 members of the HNPCC family were studied for genetic investigation . Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/polymorphisms at population level . RESULTS The analysis resulted in identification of a 1975C>T mutation in exon 17 , resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed , resulting in replacement of isoleucine with valine at codon 219 . Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation , while I219V variant was found in 9.8 per cent of the controls . INTERPRETATION &amp ; CONCLUSION R659X mutation correlates with disease phenotype , and 655A>G locus is highly polymorphic . Our study suggested that R659X substitution was prime cause for the disease phenotype in this family . I219V substitution is a polymorphism having no association with the disease onset or segregation . The family members harbouring this mutation were advised to be under regular medical surveillance .\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 prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians . The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival . This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread . In this study , we used one- and two-dimensional gel electrophoresis , mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas . Using a refinement for classifying oral carcinomas in regard to prognosis , we analyzed small but lymph node metastasis-positive versus large , lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination . Specific protein patterns favoring metastasis were observed in the \" more-aggressive \" group defined by the present study . This group displayed upregulation of proteins involved in migration , adhesion , angiogenesis , cell cycle regulation , anti-apoptosis and epithelial to mesenchymal transition , whereas the \" less-aggressive \" group was engaged in keratinocyte differentiation , epidermis development , inflammation and immune response . Besides the identification of several proteins not yet described as deregulated in oral carcinomas , the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death;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: Neural stem cells ( NSCs ) are considered to be the cell of origin of glioblastoma multiforme ( GBM ) . However , the genetic alterations that transform NSCs into glioma-initiating cells remain elusive . Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture , followed by additional rounds of mutagenesis to generate tumors in vivo , we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells . Mobilization of Sleeping Beauty transposons in NSCs induced the immortalization of astroglial-like cells , which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation , consistent with a potential astroglial origin for mesenchymal GBM . Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes , including human GBM-associated genes , such as Met and Nf1 , and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development . We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method . Finally , we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development , suggesting that tumor formation in this model system involves competition among genetically variant cells , which is similar to the Darwinian evolutionary processes now thought to generate many human cancers . This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Senescence , an inherent tumor suppressive mechanism , is a critical determinant for chemotherapy . In the present study , we show that the monocarboxylate transporter 2 ( MCT2 ) protein was tumor-selectively expressed in human colorectal malignancies and knockdown of MCT2 induces mitochondrial dysfunction , cell-cycle arrest , and senescence without additional cellular stress in colorectal cancer cell lines . Moreover , the reactive oxygen species ( ROS ) scavenger , N-acetylcysteine , blocked MCT2 knockdown-induced growth arrest and cellular senescence , indicating a pivotal role of ROS in this pathway . Dramatic induction of mitochondrial superoxide generation and decrease in ATP production was observed , indicating that mitochondrial dysfunction is the major mechanism underlying MCT2 knockdown-induced ROS generation . Senescence-associated DNA damage was also evident from the increase in promyelocytic leukemia bodies , γH2AX foci , and SAHF . Conversely , overexpression of MCT2 prevented doxorubicin-induced ROS accumulation ( P = 0.0002 ) and cell growth inhibition ( P = 0.001 ) . MCT2 knockdown suppressed KRAS mutant colorectal tumor growth in vivo . In addition , MCT2 knockdown and cytostatic drug combination further enhanced the antitumor effect . These findings support the use of MCT2 as a promising target for inhibition of colorectal cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling;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: BACKGROUND Human Barrett's cancer cell lines have numerous , poorly-characterized genetic abnormalities and , consequently , those lines have limited utility as models for studying the early molecular events in carcinogenesis . Cell lines with well-defined genetic lesions that recapitulate various stages of neoplastic progression in Barrett's esophagus would be most useful for such studies . METHODOLOGY/PRINCIPAL FINDINGS To develop such model cell lines , we started with telomerase-immortalized , non-neoplastic Barrett's epithelial ( BAR-T ) cells , which are spontaneously deficient in p16 , and proceeded to knock down p53 using RNAi , to activate Ras by introducing oncogenic H-Ras(G12V) , or both . BAR-T cells infected with either p53 RNAi or oncogenic H-Ras(G12V) alone maintained cell-to-cell contact inhibition and did not exhibit anchorage-independent growth in soft agar . In contrast , the combination of p53 RNAi knockdown with expression of oncogenic H-Ras(G12V) transformed the p16-deficient BAR-T cells , as evidenced by their loss of contact inhibition , by their formation of colonies in soft agar , and by their generation of tumors in immunodeficient mice . CONCLUSIONS/SIGNIFICANCE Through these experiments , we have generated a number of transformed and non-transformed cell lines with well-characterized genetic abnormalities recapitulating various stages of carcinogenesis in Barrett's esophagus . These lines should be useful models for the study of carcinogenesis in Barrett's esophagus , and for testing the efficacy of chemopreventive and chemotherapeutic agents .\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: Prostate cancer ( PCA ) is the most common histological malignancy and the second leading cause of cancer deaths among North American men . There has been considerable interest in the chemopreventative properties of selenium . In this study , we assessed whether selenium inhibits cell growth and associated cell cycle regulatory proteins . Human PCA cells ( LNCaP , PC3 , PC3-AR2 , and PC3-M ) were incubated with and without selenium ( Seleno-DL-methionine , 150 microM ) for 24 , 48 , and 72 h . Cells were fixed and stained with propidium iodide for flow cytometry analysis . In parallel experiments , total protein was extracted , immunoprecipitated with cyclin E antibody , and analyzed by Western blot for the expression of cell cycle markers . Treatment with selenium caused G1 arrest and an 80% reduction in the S phase of LNCaP with no effect on PC3 . However , PC3 cells transfected with the androgen receptor ( PC3-AR2 ) exhibited a G2/M arrest and a marked reduction ( 57% ) in the S phase during cell cycle progression . In the analysis of cell cycle regulatory molecules , selenium-treated cells demonstrated a significant induction of cyclin-dependent kinase inhibitors Cip1/p21 and Kip1/p27 . These data suggest that selenium possesses strong antiproliferative properties in regard to human PCA . This effect appears to be dependent on the presence of a functioning androgen receptor . This provides a theoretical basis for Phase III studies of selenium in PCA prevention .\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: ABSTRACT : BACKGROUND : Survivin , a member of the family of inhibitor of apoptosis proteins , functions as a key regulator of mitosis and programmed cell death . YM155 , a novel molecular targeted agent , suppresses survivin , which is overexpressed in many tumor types . The aim of this study was to determine the antitumor activity of YM155 in SK-NEP-1 cells . METHODS : SK-NEP-1 cell growth in vitro and in vivo was assessed by MTT and nude mice experiments . Annexin V/propidium iodide staining followed by flow cytometric analysis was used to detect apoptosis in cell culture . Then gene expression profile of tumor cells treated with YM155 was analyzed with real-time PCR arrays . We then analyzed the expression data with MEV ( Multi Experiment View ) cluster software . Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis tool . RESULTS : YM155 treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner . Annexin V assay , cell cycle , and activation of caspase-3 demonstrates that YM155 induced apoptosis in SK-NEP-1 cells . YM155 significantly inhibited growth of SK-NEP-1 xenografts ( YM155 5 mg/kg : 1.45 +/- 0.77 cm3 ; YM155 10 mg/kg : 0.95 +/- 0.55 cm3 ) compared to DMSO group ( DMSO : 3.70 +/- 2.4 cm3 ) or PBS group cells ( PBS : 3.78 +/- 2.20 cm3 , ANOVA P &lt ; 0.01 ) . YM155 treatment decreased weight of tumors ( YM155 5 mg/kg : 1.05 +/- 0.24 g ; YM155 10 mg/kg : 0.72 +/- 0.17 g ) compared to DMSO group ( DMSO : 2.06 +/- 0.38 g ) or PBS group cells ( PBS : 2.36 +/- 0.43 g , ANOVA P &lt ; 0.01 ) . Real-time PCR array analysis showed between Test group and control group there are 32 genes significantly up-regulated and 54 genes were significantly down-regulated after YM155 treatment . Ingenuity pathway analysis ( IPA ) showed cell death was the highest rated network with 65 focus molecules and the significance score of 44 . The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to cell death , cellular function maintenance , cell morphology , carbohydrate metabolism and cellular growth and proliferation . Death receptor signaling ( 3.87E-19 ) , TNFR1 signaling , induction of apoptosis by HIV1 , apoptosis signaling and molecular mechanisms of cancer came out to be the top four most significant pathways . IPA analysis also showed top molecules up-regulated were BBC3 , BIRC3 , BIRC8 , BNIP1 , CASP7 , CASP9 , CD5 , CDKN1A , CEBPG and COL4A3 , top molecules down-regulated were ZNF443 , UTP11L , TP73 , TNFSF10 , TNFRSF1B , TNFRSF25 , TIAF1 , STK17A , SST and SPP1 , upstream regulator were NR3C1 , TP53 , dexamethasone , TNF and Akt . CONCLUSIONS : The present study demonstrates that YM155 treatment resulted in apoptosis and inhibition of cell proliferation of SK-NEP-1cells . YM155 had significant role and little side effect in the treatment of SK-NEP-1 xenograft tumors . Real-time PCR array analysis firstly showed expression profile of genes dyes-regulated after YM155 treatment . IPA analysis also represents new molecule mechanism of YM155 treatment , such as NR3C1 and dexamethasone may be new target of YM155 . And our results may provide new clues of molecular mechanism of apoptosis induced by YM155 .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Metabolic dependence on glucose utilisation has been described for different tumours characterised by activation of Akt , upregulation of GLUT1 , M2PK and TKTL1 . To date , however , little is known about glucose metabolism in breast cancer tissue . METHODS We analysed 55 breast cancer specimens , 26 adjacent ductal carcinomas in situ ( DCIS ) and 23 adjacent normal breast tissues for expression of glycolytic markers by immunohistochemistry . RESULTS We found expression of pAkt in 49% , GLUT1 in 25% , M2PK in 68% and TKTL1 in 31% of the tumours investigated . Expression of pAkt and Her2neu are positively correlated with borderline significance ( P = 0.055 ) . Expression of pAkt , GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue . Surprisingly , M2PK expression was highest in normal breast tissue . CONCLUSIONS We found a glycolytic phenotype in a high percentage of breast cancer samples . Inhibition of glycolysis might evolve as a future option for breast cancer therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We have constructed plasmids pS3G-1 and pSG4 that contain single acetylaminofluorene adducts within contiguous runs of three ( 5'-CCCG1G2G3-3' ) and four ( 5'-CG1GGG4T-3' ) guanine residues , respectively . In Escherichia coli , the frequency of induced -1 frameshift mutations was strongly dependent on the position of modification : pS3G-G3 was approximately 100-fold and 10-fold more mutagenic than pS3G-G1 and pS3G-G2 , respectively ; pSG4-G4 was approximately 600-fold more mutagenic than pSG4-G1 . Mutagenesis was SOS-dependent and was markedly reduced in bacteria that were proficient in nucleotide excision repair as compared to a repair-deficient uvrA6 mutant . DNA sequencing showed that -1 frameshift events in pS3G-1 consisted of either targeted mutations ( greater than 90% of induced mutations ) within the guanine sequence or semitargeted mutations ( greater than 10% ) in the 5 ' flanking repetitive cytosine sequence . Semitargeted events , which were observed when acetylaminofluorene modification was at G1 and G2 , show that a lesion can reduce the fidelity of replication at positions 5 ' to its location on the template strand . No semitargeted frameshifts were observed in plasmid pSG4 , which lacks a repetitive sequence 5 ' to the adduct . Our results are consistent with a model for frameshift mutagenesis in which the acetylaminofluorene adduct ( i ) allows accurate incorporation of cytosine opposite the bulky lesion during DNA synthesis and ( ii ) impedes elongation of primer/template termini formed opposite the adduct or 5 ' to the adduct on the template strand , providing increased opportunity for the formation of slipped frameshift intermediates .\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: Prostaglandin E(2) ( PGE(2) ) receptor subtype EP(2) , which is coupled to cAMP metabolism , is known to mediate proliferation of primary human keratinocytes in vitro . The effect of gain or loss of EP(2) receptors in immortalized human keratinocytes ( HaCat cells ) was examined . HaCat keratinocytes were transfected with sense or anti-sense constructs of the EP(2) receptor . Loss or gain of EP(2) expression was documented by immunoblot and associated changes in agonist-stimulated cAMP production . Loss or gain of EP(2) receptor expression correlated with alterations in plating efficiencies but with modest affects on growth . When cell lines were studied in an organ culture model , anti-sense clones were highly invasive compared with vector controls and sense transfectants . A marked increase in prostaglandin production is commonly seen in malignant lesions . Because prostaglandin receptors are known to undergo ligand-induced receptor down-regulation , we sought to determine whether EP(2) receptor down-regulation results in increased invasiveness . In vector controls , invasiveness was reproduced by ligand-dependent EP(2) receptor down-regulation as assessed by immunohistochemistry . In addition , loss of EP(2) receptor expression was associated with decreased paxillin expression , a critical component of focal adhesion assembly . Thus , down-regulation of EP(2) receptors represents a potential mechanism for neoplastic progression to an invasive phenotype .\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: Epigenetic deregulation of gene expression has a role in the initiation and progression of prostate cancer ( PCa ) . The histone methyltransferase MMSET/WHSC1 ( Multiple Myeloma SET domain ) is overexpressed in a number of metastatic tumors , but its mechanism of action has not been defined . In this work , we found that PCa cell lines expressed significantly higher levels of MMSET compared with immortalized , non-transformed prostate cells . Knockdown experiments showed that , in metastatic PCa cell lines , dimethylation of lysine 36 and trimethylation of lysine 27 on histone H3 ( H3K36me2 and H3K27me3 , respectively ) depended on MMSET expression , whereas depletion of MMSET in benign prostatic cells did not affect chromatin modifications . Knockdown of MMSET in DU145 and PC-3 tumor cells decreased cell proliferation , colony formation in soft agar and strikingly diminished cell migration and invasion . Conversely , overexpression of MMSET in immortalized , non-transformed RWPE-1 cells promoted cell migration and invasion , accompanied by an epithelial-mesenchymal transition ( EMT ) . Among a panel of EMT-promoting genes analyzed , TWIST1 expression was strongly activated in response to MMSET . Chromatin immunoprecipitation analysis demonstrated that MMSET binds to the TWIST1 locus and leads to an increase in H3K36me2 , suggesting a direct role of MMSET in the regulation of this gene . Depletion of TWIST1 in MMSET-overexpressing RWPE-1 cells blocked cell invasion and EMT , indicating that TWIST1 was a critical target of MMSET , responsible for the acquisition of an invasive phenotype . Collectively , these data suggest that MMSET has a role in PCa pathogenesis and progression through epigenetic regulation of metastasis-related genes .\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: Methyleugenol ( MEG ) , a constituent of plants used in the human diet , is hepatocarcinogenic in rodents . In an experiment to elucidate its mode of action in rat liver , male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase , after which half the rats were fed 500 ppm phenobarbital ( PB ) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks . At 8 and 16 week interim terminations , ( 32)P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups . The hepatocellular replicating fractions , measured by proliferating cell nuclear antigen immunohistochemistry , were doubled or more in all MEG groups . Hepatocellular altered foci , detected by glutathione S-transferase-placental type ( π ) immunohistochemistry , were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks . At the end of maintenance/promotion phase , the incidences , multiplicity and size of foci was similar between control and low dose groups , while those of mid and high dose groups were increased . Hepatocellular adenomas occurred in the mid and high dose groups , attaining higher multiplicity and size with PB . Thus , MEG had rapid initiating activity , reflecting the formation of DNA adducts and possibly cell proliferation .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cancer vaccines based on human tumor-associated antigens ( TAA ) have been tested in patients with advanced or recurrent cancer , in combination with or following standard therapy . Their immunogenicity and therapeutic efficacy has been difficult to properly evaluate in that setting characterized by multiple highly suppressive effects of the tumor and the standard therapy on the patient's immune system . In animal models of human cancer , vaccines administered in the prophylactic setting are most immunogenic and effectively prevent cancer development and progression . We report results of a clinical study that show that in patients without cancer but with a history of premalignant lesions ( advanced colonic adenomas , precursors to colon cancer ) , a vaccine based on the TAA MUC1 was highly immunogenic in 17 of 39 ( 43.6% ) of vaccinated individuals , eliciting high levels of anti-MUC1 immunoglobulin G ( IgG ) and long-lasting immune memory . Lack of response in 22 of 39 individuals was correlated with high levels of circulating myeloid-derived suppressor cells ( MDSC ) prevaccination . Vaccine-elicited MUC1-specific immune response and immune memory were not associated with significant toxicity . Our study shows that vaccines based on human TAAs are immunogenic and safe and capable of eliciting long-term memory that is important for cancer prevention . We also show that in the premalignant setting , immunosuppressive environment ( e.g. , high levels of MDSC ) might already exist in some individuals , suggesting an even earlier premalignant stage or preselection of nonimmunosuppressed patients for prophylactic vaccination . Cancer Prev Res ; 6(1) ; 18-26. �2012 AACR .\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: Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica . Rats were exposed to crystalline silica by inhalation ( 15 mg m(-3) , 6 h per day , 5 days ) and global gene expression profile was determined in the lungs by microarray analysis at 1 , 2 , 4 , 8 and 16 weeks following termination of silica exposure . The number of significantly differentially expressed genes ( >1.5-fold change and <0.01 false discovery rate P-value ) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats . Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings . The number of biological functions , canonical pathways and molecular networks significantly affected by silica exposure , as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals , also exhibited a steady increase similar to the silica-induced pulmonary toxicity . Genes involved in oxidative stress , inflammation , respiratory diseases , cancer , and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs ; however , unresolved inflammation was the single most significant biological response to pulmonary exposure to silica . Excessive mucus production , as implicated by significant overexpression of the pendrin coding gene , SLC26A4 , was identified as a potential novel mechanism for silica-induced pulmonary toxicity . Collectively , the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat . Published 2012 . This article is a US Government work and is in the public domain in the USA .\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: Objective To investigate the effect of bufalin on nucleus-mitochondria localization of human telomerase reverse transcriptase(hTERT) by exploring its effect on proliferation and apoptosis in human esophageal squamous carcinoma EC9706 cells . Methods EC9706 cells were treated with bufalin at various concentrations , and then the cell growth inhibition of EC9706 cells was examined by CCK-8 assay and the 50% inhibitory concentration ( IC(50) ) was calculated.Cell cycle analysis was performed by flow cytometry with PI staining , and nucleus morphology of apoptosis were observed by fluorescence microscopy with Hoechst 33342 staining . The apoptotic index was measured by flow cytometry with Annexin V-FITC/PI double staining. hTERT subcellular localization and protein expression were determined by Western blotting and multiple immunofluorescence labling combined with laser confocal scanning microscopy . Results The proliferation of EC 9706 cells was significantly inhibited by bufalin along with the increase of processing time and concentrations ( p<0.01 ) . After the EC9706 cells were exposed to 100 nmol/L bufalin,the number of cells gradually decreased in G(1) phase and increased in S and G(2)/M phases(p<0.05) . The typical nucleus morphological changes of apoptosis were observed and the apoptotic index was increased(p<0.01) . The expression of hTERT decreased in nucleus but increased in mitochondria(p<0.05) . Conclusions Bufalin can inhibit the proliferation of human esophageal squamous carcinoma EC9706 cells in a time- and dose-dependent manner . It can arrest cell cycle in S and G(2)/M phases and induce the apoptosis of EC 9706 cells. hTERT is localized in both nucleus and mitochondria,and can be partially translocated from nucleus to mitochondria during the bufalin-induced apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Progression of breast cancer is associated with remodeling of the extracellular matrix , often involving a switch from estrogen dependence to a dependence on EGF receptor ( EGFR)/HER-2 and is accompanied by increased expression of the main binding protein for insulin-like growth factors ( IGFBP-3 ) . We have examined the effects of IGFBP-3 on EGF responses of breast epithelial cells in the context of changes in the extracellular matrix . On plastic and laminin with MCF-10A normal breast epithelial cells , EGF and IGFBP-3 each increased cell growth and together produced a synergistic response , whereas with T47D breast cancer cells IGFBP-3 alone had no effect , but the ability of EGF to increase cell proliferation was markedly inhibited in the presence of IGFBP-3 . In contrast on fibronectin with MCF-10A cells , IGFBP-3 alone inhibited cell growth and blocked EGF-induced proliferation . With the cancer cells , IGFBP-3 alone had no effect but enhanced the EGF-induced increase in cell growth . The insulin-like growth factor-independent effects of IGFBP-3 alone on cell proliferation were completely abrogated in the presence of an EGFR , tyrosine kinase inhibitor , Iressa . Although IGFBP-3 did not affect EGFR phosphorylation [ Tyr(1068) ] , it was found to modulate receptor internalization and was associated with activation of Rho and subsequent changes in MAPK phosphorylation . The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor .\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: Centrosome overduplication or amplification has been observed in many human cancers and in premalignant tissue , but the mechanisms leading to such centrosome aberrations are not fully understood . We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human fibroblasts , especially in a polyploid subpopulation . This study examines localization of p53 protein at centrosomes in mitotic cells , which is often observed in association with DNA damage response , to investigate a possible association between p53 localization and numerical centrosome aberrations induced by cellular senescence . Cultures at later passages or the 4th day after exposure to H(2)O(2) showed increased frequencies of mitotic cells with supernumerary centrosomes , especially in a polyploid subpopulation . Immunohistochemical analysis frequently showed p53-positive foci in mitotic cells , and some were localized at centrosomes . The number of p53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence . Supernumerary centrosomes showed higher frequencies of p53 localization compared to normally duplicated centrosomes . Centrosome-associated p53 protein was phosphorylated at Ser15 . These data suggest a possible association between localization of p53 protein and numerical centrosome aberrations in replicatively or prematurely senescent 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: Metabolic reprogramming in cancer is manifested by persistent aerobic glycolysis and suppression of mitochondrial function and is known as the Warburg effect . The Warburg effect contributes to cancer progression and is considered to be a promising therapeutic target . Understanding the mechanisms used by cancer cells to suppress their mitochondria may lead to development of new approaches to reverse metabolic reprogramming . We have evaluated mitochondrial function and morphology in poorly respiring LM7 and 143B osteosarcoma ( OS ) cell lines showing the Warburg effect in comparison with actively respiring Saos2 and HOS OS cells and noncancerous osteoblastic hFOB cells . In LM7 and 143B cells , we detected markers of the mitochondrial permeability transition ( MPT ) , such as mitochondrial swelling , depolarization , and membrane permeabilization . In addition , we detected mitochondrial swelling in human OS xenografts in mice and archival human OS specimens using electron microscopy . The MPT inhibitor sanglifehrin A reversed MPT markers and increased respiration in LM7 and 143B cells . Our data suggest that the MPT may play a role in suppression of mitochondrial function , contributing to the Warburg effect in cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The t(10;11)(p12;q23) chromosomal translocation in human acute myeloid leukemia results in the fusion of the MLL and AF10 genes . The latter codes for a novel leucine zipper protein , one of many MLL fusion partners of unknown function . In this report , we demonstrate that retroviral-mediated transduction of an MLL-AF10 complementary DNA into primary murine myeloid progenitors enhanced their clonogenic potential in serial replating assays and led to their efficient immortalization at a primitive stage of myeloid differentiation . Furthermore , MLL-AF10-transduced cells rapidly induced acute myeloid leukemia in syngeneic or severe combined immunodeficiency recipient mice . Structure/function analysis showed that a highly conserved 82-amino acid portion of AF10 , comprising 2 adjacent alpha-helical domains , was sufficient for immortalizing activity when fused to MLL . Neither helical domain alone mediated immortalization , and deletion of the 29-amino acid leucine zipper within this region completely abrogated transforming activity . Similarly , the minimal oncogenic domain of AF10 exhibited transcriptional activation properties when fused to the MLL or GAL4 DNA-binding domains , while neither helical domain alone did . However , transcriptional activation per se was not sufficient because a second activation domain of AF10 was neither required nor competent for transformation . The requirement for alpha-helical transcriptional effector domains is similar to the oncogenic contributions of unrelated MLL partners ENL and ELL , suggesting a general mechanism of myeloid leukemogenesis by a subset of MLL fusion proteins , possibly through specific recruitment of the transcriptional machinery .\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: Contact inhibition of locomotion ( CIL ) is the process by which cells stop the continual migration in the same direction after collision with another cell . Highly invasive malignant cells exhibit diminished CIL when they contact stromal cells , which allows invasion of the tissue by tumors . We show that Nm23-H1 is essential for the suppression of Rac1 through inactivation of Tiam1 at the sites of cell-cell contact , which plays a pivotal role in CIL . U87MG cells show CIL when they contact normal glia . In spheroid confrontation assays U87MG cells showed only limited invasion of the glial population , but reduction of Nm23-H1 expression in U87MG cells abrogated CIL resulting in invasion . In U87MG cells , Nm23-H1 is translocated to the sites of contact with glia through association with α-catenin and N-cadherin . Mutants of Nm23-H1 , which lacked the binding ability with Tiam1 , or α-catenin did not restore CIL . Moreover , the expression of ephrin-B1 in tumor cells disrupted CIL and promoted invasion . As one mechanism , ephrin-B1 inhibits the association of Nm23-H1 with Tiam1 , which contributes for activation of Rac1 . These results indicate a novel function of Nm23-H1 to control CIL , and its negative regulation by ephrin-B1 .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The pancreatic stellate cells ( PSCs ) have complex roles in pancreas , including tissue repair and fibrosis . PSCs surround ATP releasing exocrine cells , but little is known about purinergic receptors and their function in PSCs . Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability . The number of PSCs isolated from wild type ( WT ) mice was 50% higher than those from the Pfizer P2X7 receptor knock out ( KO ) mice . The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs , while KO PSCs only expressed truncated versions of the receptor . In culture , the proliferation rate of the KO PSCs was significantly lower . Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs , indicating importance of endogenous ATP . Exogenous ATP had a two-sided effect . Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM . At high ATP concentration ( 5 mM ) , WT PSCs , but not the KO PSCs died . The intracellular Ca(2+) signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120 . The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations . This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death , and therefore might be potential targets for treatments of pancreatic fibrosis and cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The cytotoxic activity of cyclosporin A ( CsA ) and the three non-immuno-suppressive CsA analogues B3-243 , WO-039 and B3-665 were studied in tumor cell lines representing both classical and atypical forms of multidrug resistance ( MDR ) : T-ALL GM3639 L100 cells selected for vincristine ( vcr ) resistance and displaying characteristics of classical MDR , including P-glycoprotein ( pgp ) expression and increased drug efflux which can be inhibited by pgp blockers ( e.g. verapamil ) , and U-1285/ADR , a small cell lung cancer ( SCLC ) cell line selected for doxorubicin resistance which lacks pgp , is insensitive to pgp-blockers and shows cross resistance to cis-platinum . At 1 micrograms/ml CsA was the most active agent in reversing Vcr resistance in L100 cells followed by B3-243 and WO-039 , with no effect of B3-665 . Parental LO cells were only marginally sensitized to Vcr by these agents . No reversing effect of any cyclosporin was observed in the U-1285/ADR or its parental cell line . Compared to LO cells , L100 cells showed a marked hypersensitivity to CsA &gt ; B3-243 &gt ; WO-039 with B3-665 being inactive . No collateral sensitivity was observed for cyclosporins in U-1285/ADR cells . Although of different magnitude , the pattern of cytotoxic activity for the different cyclosporins alone closely parallelled that of L100 cells for U-1285 , U1285/ADR and LO cells . The results indicate that not only the collateral sensitivity in classical MDR but also the cytotoxic actions of cyclosporins per se on tumor cells alone are independent of immunosuppressive activity . The results also suggest a structure-activity relationship for cyclosporin-induced cytotoxicity similar to , but independent of , MDR reversing activity .\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: PURPOSE BMP-6 , which belongs to the TGF-β superfamily , is a multifunctional molecule with distinct abilities in embryogenesis and organogenesis . Our recent research has implied that BMP-6 may suppress breast cancer metastasis . In the present study , we extended to elucidate the molecular mechanism by which BMP-6 exerts its anti-tumorigenic effect . METHODS The Boyden chamber assay was used to examine the ability of BMP-6 and HO-1 in MCF-7 malignant progress . RT-PCR , western blot , luciferase assay , and quantitative CHIP were used to determine the potential mechanism and signaling pathways by which BMP-6 and HO-1 function as anti-metastatic factors in MCF-7 cells . RESULTS The Boyden chamber assay showed that BMP-6 inhibited the migration and invasion of MCF-7 cells , which effect was significantly deprived by knockdown of HO-1 . We further demonstrated that BMP-6 treatment resulted in an activation of HO-1 transcription through the recruitment of Smad1/5 to the Smad-responsive element on its promoter . In addition , BMP-6-induced up-regulation of HO-1 exhibited an inhibitory effect on MMP-9 secretion in a paracrine action in MCF-7 cells . Overexpression of BMP-6 and HO-1 synergistically suppressed MMP-9 transcription , which effect was specifically mediated via the MAPK/p38/AP-1 signaling . However , blockade of HO-1 using ZnPPIX totally abolished BMP-6-regulated MMP-9 activation in MCF-7 cells . CONCLUSIONS These observations suggest a novel role of BMP-6/HO-1 cascade to relieve breast cancer metastasis by regulating the secretion of growth factors in tumor microenvironment .\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: BACKGROUND Elevated levels of air pollution are associated with increased risk of lung cancer . Particulate matter ( PM ) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation , a lung cancer risk factor . Vanadium pentoxide ( V2O5 ) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans . In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage ( initiation-promotion ) model of pulmonary neoplasia in mice . RESULTS A/J , BALB/cJ ( BALB ) , and C57BL/6J ( B6 ) mice were treated either with the initiator 3-methylcholanthrene ( MCA ; 10 microg/g ; i.p. ) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment . Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid ( BALF ) , and chemokines , transcription factor activity , and MAPK signaling were quantified in lung homogenates . We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J ( 10.3 +/- 0.9 tumors/mouse ) and BALB ( 2.2 +/- 0.36 ) mice significantly above that observed with MCA/PBS or V2O5 alone ( P &lt ; 0.05 ) . No tumors were observed in the B6 mice in any of the experimental groups . Mice sensitive to tumor promotion by V2O5 were also found to be more susceptible to V2O5-induced pulmonary inflammation and hyperpermeability ( A/J>BALB>B6 ) . Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1 , higher NFkappaB and c-Fos binding activity , as well as sustained ERK1/2 activation in lung tissue . CONCLUSIONS In this study we demonstrate that V2O5 , an occupational and environmentally relevant metal oxide , functions as an in vivo lung tumor promoter among different inbred strains of mice . Further , we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation . These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways .\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: An efficent antitumor and antiviral cellular immune response requires optimal interferon-gamma ( IFN-gamma ) secretion and perforin expression in CD8(+) T cells . The aim of this study was to define whether CD4(+) and CD8(+) T cells from patients with undifferentiated carcinoma of nasopharyngeal type ( UCNT ) , a tumor regularly associated with the Epstein-Barr virus ( EBV ) , have abnormal phenotype profiles , cytokine production , perforin and CD3-zeta expressions . Our data showed that CD4 and CD8 subset distribution was not grossly altered in the peripheral blood of UCNT patients , while tumor biopsies contained an increased proportion of CD8(+) T cells . The analysis of the CD4(+) subset showed a defect in interleukin-2 ( IL-2 ) production and a moderate increase of IL-10 production , a situation consistent with a Th1/Th2 imbalance . We have also demonstrated that CD8(+) lymphocytes from UCNT patients had a marked impairment of IFN-gamma secretion and perforin expression . This impairment was not related to the presence of detectable EBV DNA in the plasma . In UCNT patients , the blockade of the perforin pathway and of IFN-gamma production may constitute important mechanisms for immune escape by the tumor and for impaired control of EBV replication .\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 β2-adrenergic receptor ( β2AR ) mediates the effects of chronic stress in several neoplasms , however , β2AR signaling is impaired by hypoxia in various tissues . While hypoxia is a common feature significant in the progression of solid tumors , little is known about the effect of hypoxia on β2AR signaling in the tumor microenvironment . Previously , it has been reported that the systemic administration of mesenchymal stem cells ( MSCs ) increased the engraftment and metastatic colonization of rat osteosarcoma ( OS ) cells . In the current study , the effect of MSCs on the hypoxia-induced desensitization of the β2AR in OS cells was investigated . Epinephrine , norepinephrine and isoproterenol increased the cellular proliferation of the rat OS cell line COS1NR and rat MSCs in a dose-dependent and β2AR antagonist-sensitive manner . While isoproterenol had significant proliferative effects on MSCs under normoxic and hypoxic conditions , COS1NR cells did not respond under hypoxic conditions . A sensitivity assay for the β2AR revealed that hypoxia impaired the sensitivity of COS1NR cells , whereas hypoxia did not affect MSCs . An immunoassay revealed no significant change in the expression of hypoxia-inducible factor-1α ( HIF1α ) in COS1NR cells , whilst an immunoassay demonstrated a 15% increase in MSCs following isoproterenol stimulation . In COS1NR cells co-cultured with MSCs under hypoxic conditions , isoproterenol caused a significant increase in proliferation and this effect was inhibited by an anti-interleukin ( IL)-6 antibody . A tumor formation assay in syngeneic rats revealed that the systemic administration of MSCs enhances the growth of OS and the effect of MSCs was inhibited by IL-6 neutralization . In conclusion , MSCs are resistant to the hypoxia-induced desensitization to β2AR . Hypoxia caused a siginificant desensitization of the β2AR in COS1NR cells alone , whereas MSCs may support tumor progression through cellular interactions .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND/AIMS We investigated whether the anticancer drug Ukrain ( UK ) is able to modulate the expression of some of the key markers of tumor progression in pancreatic cell carcinoma , in order to assess its potential therapeutic effect . METHODS Three cell lines ( HPAF-II , PL45 , HPAC ) were treated with UK ( 5 , 10 and 20 μM ) for 48 h , or left untreated . Secreted protein acidic and rich in cysteine ( SPARC ) mRNA levels were assessed by real-time PCR . Matrix metalloproteinases ( MMP)-2 and -9 activity was analyzed by SDS zymography ; SPARC protein levels in cell lysates and supernatants were determined by Western blot . Cell cycle was determined by flow cytometric analysis , and invasion by matrigel invasion assay . RESULTS UK down-regulated MMP-2 and MMP-9 , suggesting that UK may decrease pancreatic cancer cell invasion , as confirmed by the matrigel invasion assay . SPARC protein down-regulation in supernatants points to an inhibition by UK of extracellular matrix remodeling in the tumor microenvironment . At the same time , SPARC mRNA and cellular protein level up-regulation suggests that UK can affect cell proliferation by cell cycle inhibition , showing a cell cycle G2/M arrest in UK-treated cells . CONCLUSION Our results suggest that UK modulates two major aspects involved in tumorigenesis of pancreatic cancer cells , such as extracellular matrix remodeling and cell proliferation .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In mammalian cells more than 90% of double-strand breaks are repaired by NHEJ . Impairment of this pathway is associated with cell cycle arrest , cell death , genomic instability and cancer . Human diseases such as Nijmegen breakage syndrome , due to mutations in the NBS1 gene , produce defects in resection of double-strand breaks . NBS1 hypomorphic mutant mice are viable , and cells from these mice are defective in S phase and G2/M checkpoints . NBS1 polymorphisms have been associated with increased risk of breast cancer . We previously demonstrated that estradiol protected estrogen receptor ( ER)-positive ( + ) breast cancer cell lines against double-strand breaks and cell death . We now demonstrate that protection from double-strand break damage in ER+ cells is mediated via regulation by c-myc , p53 , CBP and SRC1 coactivators in intron 1 of the NBS1 gene . We concluded that NBS1 is responsible for estradiol-mediated protection from double-strand breaks in ER+ breast cancer cells .\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: Normal human lung fibroblast diploid cells , WI-38 , become senescent after a definite number of divisions . VA-13 is a line of immortalized cells established by transformation of WI-38 cells by SV40 virus . To determine whether SV40 large T ( SV40-T ) antigen is essential for this immortalization of WI-38 cells we introduced an antisense gene for T antigen into VA-13 . Two morphologically different types of antisense transformant ( VA-AS5-8 and VA-AS37-8 ) were obtained . In both antisense transformants the expression of T antigen was reduced by more than 70% as compared to that in the parent cells . The morphology of the antisense transformants indicated a partial conversion to the senescent phenotype of WI-38 . The relative number of cells in the S phase of the antisense transformants was decreased as compared to that in cultures of VA-13 and about 50% of cells were at G1/0 . The doubling time of the transformants was prolonged to close to the doubling time of WI-38 . The level of expression of retinoblastoma protein ( pRB ) complexed with SV40-T antigen of the antisense transformants was significantly decreased although the level of total pRB was much higher than that in VA-13 . The pRB was present exclusively in the underphosphorylated form . Thus , the decreased level of formation of the complex between SV40-T and pRB or the underphosphorylation of pRB may explain the suppression of growth of antisense transformants . Together , these results show that an antisense gene for SV40-T antigen can efficiently block the cell proliferation and the cell immortalization of VA-13 cells .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aryl hydrocarbon receptor ( AHR ) is a ligand-activated transcription factor that mediates the effects of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) . Recently , AHR has emerged as a potential therapeutic target for breast cancer by virtue of its ability to modulate estrogen receptor-α ( ERα ) signalling and/or its ability to block cell proliferation . Our previous studies identified cyclin G2 ( CCNG2 ) , an inhibitor of cell-cycle progression , as an AHR target gene ; however , the mechanism of this regulation is unknown . Chromatin immunoprecipitation assays in T-47D human breast cancer cells revealed a TCDD-dependent recruitment of AHR , nuclear co-activator 3 ( NCoA3 ) and the transcription factor forkhead box A1 ( FOXA1 ) , a key regulator of breast cancer cell signaling , to CCNG2 resulting in increases in CCNG2 mRNA and protein levels . Mutation of the AHR response element ( AHRE ) and forkhead-binding sites abolished TCDD-induced CCNG2-regulated reporter gene activity . RNA interference-mediated knockdown of FOXA1 prevented the TCDD-dependent recruitment of AHR and NCoA3 to CCNG2 and reduced CCNG2 mRNA levels . Interestingly , knockdown of FOXA1 also caused a marked decrease in ERα , but not AHR protein levels . However , RNA interference-mediated knockdown of ERα , a negative regulator of CCNG2 , had no effect on TCDD-dependent AHR or NCoA3 recruitment to or expression of CCNG2 . These findings show that FOXA1 , but not ERα , is essential for AHR-dependent regulation of CCNG2 , assigning a role for FOXA1 in AHR action .\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 identified REDD1 as a novel transcriptional target of p53 induced following DNA damage . During embryogenesis , REDD1 expression mirrors the tissue-specific pattern of the p53 family member p63 , and TP63 null embryos show virtually no expression of REDD1 , which is restored in mouse embryo fibroblasts following p63 expression . In differentiating primary keratinocytes , TP63 and REDD1 expression are coordinately downregulated , and ectopic expression of either gene inhibits in vitro differentiation . REDD1 appears to function in the regulation of reactive oxygen species ( ROS ) ; we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress , which are both increased following ectopic expression of either TP63 or REDD1 . Thus , REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation .\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: Kinins and their receptors have been recently implicated in cancer . Using functional and molecular approaches , we investigated the relevance of kinin B(1) and B(2) receptors in bladder cancer . Functional studies were conducted using bladder cancer cell lines , and human biopsies were employed for molecular studies . Both B(1) des-Arg(9)-BK and B(2) BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells . Furthermore , treatment with B(1) and B(2) receptor antagonists ( SSR240612 and HOE140 ) markedly inhibited the proliferation of T24 cells . Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4 , while des-Arg(9)-BK completely failed to induce its proliferation . Real-time PCR revealed that the mRNA expression of kinin receptors , particularly B(1) receptors , was increased in T24 cells relative to RT4 cells . Data from bladder cancer human biopsies revealed that B(1) receptor expression was increased in all tumor samples and under conditions of chronic inflammation . We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ ( phosphatidylinositol 3-kinase ) with AS252424 , concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK . Finally , the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways , whereas p38 MAP kinase remained unaffected . Kinin receptors , especially B(1) receptors , appear to be implicated in bladder cancer progression . It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Nonmelanoma skin cancer ( NMSC ) is by far the most frequent type of cancer in humans . NMSC includes several types of malignancies with different clinical outcomes , the most frequent being basal and squamous cell carcinomas . We have used the Sleeping Beauty transposon/transposase system to identify somatic mutations associated with NMSC . Transgenic mice bearing multiple copies of a mutagenic Sleeping Beauty transposon T2Onc2 and expressing the SB11 transposase under the transcriptional control of regulatory elements from the keratin K5 promoter were treated with TPA , either in wild-type or Ha-ras mutated backgrounds . After several weeks of treatment , mice with transposition developed more malignant tumors with decreased latency compared with control mice . Transposon/transposase animals also developed basal cell carcinomas . Genetic analysis of the transposon integration sites in the tumors identified several genes recurrently mutated in different tumor samples , which may represent novel candidate cancer genes . We observed alterations in the expression levels of some of these genes in human tumors . Our results show that inactivating mutations in Notch1 and Nsd1 , among others , may have an important role in skin 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: We report that all-trans retinoic acid ( ATRA ) in combination with zoledronic acid has strong synergistic cytotoxic and apoptotic effects against human hormone- and drug-refractory prostate cancer cells , PC-3 and DU-145 , in a time- and dose-dependent manner . We further investigated the effect of the combination treatment on the apoptotic process by both oligoarray and protein array analysis in DU-145 cells , in which the drug combination shows much more strong synergistic effects , as compared to PC-3 cells . Moreover , we have also performed real time-PCR array analysis to validate oligoarray results . We demonstrated that the combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in human androgen-and drug refractory prostate cancer cells DU-145 , at either transcriptional or translational levels . While expression of proapoptotic genes such as tumor necrosis factor receptor superfamily ( TNFRSF ) , Bad , Bax , Fas , FADD are induced with the exposure of the combination , expression of antiapoptotic genes or proteins such as members of inhibitor apoptosis family ( IAPs ) , MCL-1 , LTBR , p53 and bcl-2 are reduced . Because this novel combination treatment has fewer side effects than is generally the case with conventional cytotoxic agents , this regimen may be a good option for treatment of elderly prostate cancer patients .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: AIM The goal of this study was to characterize the AFP receptor , its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402 . METHODS Cell proliferation enhanced by AFP was detected by MTT assay , 3H-thymidine incorporation and S-stage percentage of cell cycle analysis . With radioactive labeled 125I-AFP for receptor binding assay ; cAMP accumulation , protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium ( Ca2+i ) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope . The expression of oncogenes N- ras , p 53 , and p21( ras ) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively . RESULTS It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay , ( 3)H-thymidine incorporation and S-phase percentage up to 2-fold . Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9 x10(-8)mol . ( -1)L respectively . Pretreatment of cells with AFP resulted in a significant increase ( 625% ) in cAMP accumulation . The activity of protein kinase A activity were increased up to 37.5 , 122.6 , 73.7 and 61.2% at treatment time point 2 , 6 , 12 and 24 hours . The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204% at 4 min . The results also showed that AFP(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells . In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control . CONCLUSION These results demonstrate that AFP is a potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells . Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium to regulate the expression of oncogenes .\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 studies have shown that genistein inhibits the growth of PC3 prostate cancer cells and induces apoptosis by inhibiting nuclear factor kappaB ( NF-kappaB ) and Akt signaling pathways . To better understand the precise molecular mechanism(s) by which genistein exerts its effects on PC3 cells , we utilized cDNA microarray to interrogate 12,558 known genes to determine the gene expression profiles altered by genistein treatment . We found a total of 832 genes that showed a greater than twofold change after genistein treatment from two independent experiments with a high degree of concordance . Among these genes , 774 genes were down-regulated and 58 genes were up-regulated with genistein treatment . Cluster analysis showed nine different types of expression alternations . These genes were also subjected to cluster analysis according to their biological functions . We found that genistein regulated the expression of genes that are critically involved in the regulation of cell growth , cell cycle , apoptosis , cell signaling transduction , angiogenesis , tumor cell invasion and metastasis . Reverse transcription-polymerase chain reaction ( RT-PCR ) analysis was used to confirm the results of cDNA microarray , and the results of RT-PCR were consistent with the microarray data . We conclude that genistein affected the expression of a large number of genes that are related to the control of cell survival and physiologic behaviors . The gene expression profiles provide comprehensive molecular mechanism(s) by which genistein exerts its pleiotropic effects on cancer cells . Genistein-induced regulation of these genes may be further exploited for devising chemopreventive and/or therapeutic strategies for prostate cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Gamma-radiation , tetrandrine , bistratene A , and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human BM13674 cell line 8 h after treatment . Apoptosis induced in BM13674 cells by these diverse agents was markedly inhibited by 1 microM okadaic acid , a tumour promoter that inhibits protein phosphatases 1 and 2A . This compound also inhibited the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation . The inhibition of apoptosis was confirmed using fluorescence microscopy and DNA gel electrophoresis . Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations . Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells . The present data provides further support that posttranslational modification of proteins , in particular , phosphorylation/dephosphorylation status , plays an important role in inhibition/activation of programmed cell death in different human cells after exposure to several cytotoxic agents .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We show that sufficient concentrations of gold nanoparticles produced by an original synthesis method in EMT-6 and CT-26 cancer cells make it possible to detect the presence , necrosis and proliferation of such cells after inoculation in live mice . We first demonstrated that the nanoparticles do not interfere with the proliferation process . Then , we observed significant differences in the tumor evolution and the angiogenesis process after shallow and deep inoculation . A direct comparison with pathology optical images illustrates the effectiveness of this approach .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Proliferation of non-transformed cells is regulated by cell-cell contacts , which are referred to as contact-inhibition . Vice versa , transformed cells are characterised by a loss of contact-inhibition . Despite its generally accepted importance for cell-cycle control , little is known about the intracellular signalling pathways involved in contact-inhibition . Unravelling the molecular mechanisms of contact-inhibition and its loss during tumourigenesis will be an important step towards the identification of novel target genes in tumour diagnosis and treatment . To better understand the underlying molecular mechanisms we identified the transcriptional programme of contact-inhibition in NIH3T3 fibroblast using high-density microarrays . Setting the cut off : >or=1.5-fold , P <or= 0.05 , 853 genes and 73 cDNA sequences were differentially expressed in confluent compared to exponentially growing cultures . Importing these data into GenMAPP software revealed a comprehensive list of cell-cycle regulatory genes mediating G0/G1 arrest , which was confirmed by RT-PCR and Western blot . In a narrow analysis ( cut off : >or=2-fold , P <or= 0.002 ) , we found 110 transcripts to be differentially expressed representing 107 genes and 3 cDNA sequences involved , for example , in proliferation , signal transduction , transcriptional regulation , cell adhesion and communication . Interestingly , the majority of genes was upregulated indicating that contact-inhibition is not a passive state , but actively induced . Furthermore , we confirmed differential expression of eight genes by semi-quantitative RT-PCR and identified the potential tumour suppressor transforming growth factor-beta ( TGF-beta)-1-induced clone 22 ( TSC-22 ; tgfb1i4 ) as a novel protein to be induced in contact-inhibited 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: Bone marrow transplantation ( BMT ) , used to treat severe hematological malignancies , often leads to potentially fatal acute graft-versus-host disease ( GVHD ) , despite attempts for better matching and/or use of immune suppressive agents . We reported that embryo-derived PreImplantation-Factor plays a determining role in developing maternal/host tolerance towards the semi/allogenic embryo and regulating systemic immune response . Synthetic PIF ( PIF ) treatment is effective preventing immune attack in non-pregnant models of autoimmunity . Herein , we test PIF ability to prevent acute GVHD development in semi or totally allogenic murine models . We examine PIF's regulatory effect in vivo and in vitro , to control deleterious GVHD while maintaining its ability to preserve beneficial graft vs. leukemia ( GVL effect ) . Bone marrow and spleen cells from C57BL/6 donors were transplanted to semi-allogenic ( C57BL/6�BALB/c ) F1 or allogenic ( BALB/c ) recipients , and then treated with PIF1mg/kg/day/2weeks . Short-term PIF administration reduced acute GVHD in both models and increased survival for up to four months after semi-(or totally ) allogenic BMT . The obtained effect was coupled with lessened skin ( semi-allogenic ) and decreased liver inflammation ( both models ) as well as reduced colon ulceration ( allogenic ) . Both GVHD associated cytokines and chemokines gene expression were decreased in the liver . PIF further lowered circulating interleukin-17 , but not interferon-γ levels . PIF treatment was demonstrated in vivo and in vitro to lead to decreased iNOS expression and in LPS-activated macrophages to lower nitric oxide secretion . Significantly , PIF did not impair the beneficial GVL effect in the B-cell leukemia model . PIF primarily acts by inducing regulatory phenotype on monocytes/APC , which controls T-cell proliferation . Overall our data demonstrates that PIF protects against semi/allogenic GVHD long-term by reducing both target organ and systemic inflammation and by lowering oxidative stress , all while preserving the beneficial GVL effect .\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: Environmental or occupational exposure to low doses of arsenic induces a series of health problems including cancer . The molecular events in arsenic-induced carcinogenicity remain to be defined . In the NuLi-1 immortalized human lung epithelial cell line with p53 and pRb deficiency , exposure to low doses of arsenic trioxide for 72 h promoted cell proliferation and upregulated the gene transcription levels of FOXM1 , CDC6 , CDC25A , and cyclin D1 , which are both critical cell cycle regulatory genes and proto-oncogenes . Continuous in vitro exposure to 1 �M arsenic trioxide for 34 wks induced malignant cell transformation , as evidenced by enhanced anchorage-independent cell growth . The expression of FOXM1 , CDC6 , CDC25A , and Cyclin D1 was dynamically elevated at the gene transcription and protein levels in the process of cell transformation . The carcinogenic ability of transformed cell colonies coincides with the expression levels of FOXM1 in in vitro anchorage-independent growth assays and in vivo tumor xenograft formation assays . In reverse , the knockdown of FOXM1 in lung adenocarcinoma A549 cells or arsenic-transformed NuLi-1 cells significantly decreased anchorage-independent cell growth and tumor xenograft formation . The transformed NuLi-1 cells showed genomic instability in the form of copy number variation ( CNV ) at chromosome 1 , 5 , 6 , 18 , and 20 , but not loss of heterozygosity ( LOH ) . These results showed for the first time that chronic exposure to low doses of arsenic trioxide promoted lung carcinogenicity , in part by aberrantly upregulating FOXM1 and its associated oncogenes , when the tumor suppressor genes p53 and pRb were inactivated. � 2012 Wiley Periodicals , Inc .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cytokine-dependent cell lines have been used to analyze the cytokine-induced cellular signaling and the mechanism of oncogenesis . In the current study , we analyzed MOTN-1 and PLT-2 cell lines established from different stages of a T-cell large granular lymphocyte leukemia patient ( Daibata et al. 2004 ) . MOTN-1 is IL-2-dependent derived from the chronic phase , whereas IL-2-independent PLT-2 is from the aggressive and terminal stage . They shared considerable chromosome abnormalities and the pattern of T-cell receptor rearrangement , presuming that the cytokine independence of PLT-2 was due to the additive genetic abnormality . Besides IL-2 , IL-15 supported MOTN-1 cell growth , because these receptors share beta- and gamma-subunits . IL-2 activated ERK , AKT and STAT pathway of MOTN-1 . STAT3 pathway of PLT-2 was also activated by IL-2 , suggesting intact IL-2 induces signal transduction of PLT-2 . However , ERK1/2 but not AKT , was continuously activated in PLT-2 , consistent with the increased Ras-activity of PLT-2 . Sequence analysis revealed KRAS G12A mutation but not NRAS and HRAS mutation of PLT-2 but not MOTN-1 . Another signaling molecule affecting Ras-signaling pathway , SHP2 , which has been frequently mutated in juvenile myelomonocytic leukemia ( JMML ) , did not show mutation . Moreover , MEK inhibitor , PD98059 , as well as farnesylation inhibitor inhibited PLT-2 cell growth . Using NIH3T3 and MOTN-1 , ERK activation , increased cell proliferation and survival by KRAS G12A were shown , suggesting the important role of KRAS G12A in IL-2-independent growth of PLT-2 . Taken together , KRAS G12A is important for IL-2-independent growth of PLT-2 cells and suggests the possibility of involvement of KRAS mutation with disease progression .\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: Cancer development is associated with genetic instability . Identification of specific loci altered during carcinogenesis in a particular tissue gives scope for early detection and predicting the progressive nature of the tissue pathology . Instability at microsatellite loci is widely attributed to mismatch repair errors due to epigenetic alterations . Using three dinucleotide markers , D3S1313 , D9S171 , D17S250 and two mononucleotide markers BAT25 , BATRII , we evaluated MSI in 97 cases enrolled for endoscopy of upper GI tract with symptoms of dyspepsia , reflux or dysphagia . We aimed at evaluating markers that reflect instability in esophageal malignancies , examine the prevalence of MSI in cancers and other pathologies of the esophagus , and determine the methylation status of hMLH1 gene in relation to MSI. 42% ( 21/50 ) cancers and 15.4%(2/13) precancers exhibited MSI where 85.7% cancers and 50% precancers with MSI , showed a hypermethylated hMLH1 promoter . Increased number of cases with repair gene methylation were seen with increasing severity of the esophageal pathology suggesting epigenetic progression parallels histologic changes . BAT25 and D3S1313 markers exhibited instability frequently and cases with MSI using these markers showed an abnormal hMLH1 promoter . Thus these markers were useful in identifying the mismatch repair phenotype . These two markers may be useful to screen cases for early cancer related changes , after validation on a larger sample .\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: OBJECTIVES Epiphyseal cartilage is a barrier to osteosarcoma invasion , however the mechanisms behind this resistance remain unclear . The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage . METHODS We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression . We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis ; proangiogenic vascular endothelial growth factor ( VEGF ) and antiangiogenic pigment epithelium-derived factor ( PEDF ) . RESULTS Epiphyseal cartilage remained intact across its entire length in all sections examined , despite increasing tumor size as well as intra- and extraosseous destruction . In the most advanced cases , only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded . This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF . In contrast , the resting , proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases . This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF . CONCLUSION Epiphyseal cartilage is resistant to local invasion by osteosarcoma . The balance of angiogenesis , influenced by pro- and antiangiogenic factors , is likely to play an important role in this resistance .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling . Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase ( MMP ) activity , we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng ( Panax ginseng C.A. Meyer ) . Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet , a high fat diet ( HFD ) , or HFD supplemented with 0.5% or 5% Korean red ginseng extract . We measured body weight , adipose tissue mass , food intake , MMP activity , and the expression of genes involved in angiogenesis and MMPs . Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts . Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues . Ginseng also reduced mRNA levels of angiogenic factors ( e.g. , VEGF-A and FGF-2 ) and MMPs ( e.g. , MMP-2 and MMP-9 ) , whereas it increased mRNA levels of angiogenic inhibitors ( e.g. , TSP-1 , TIMP-1 , and TIMP-2 ) in adipose tissues . These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines , A2780 and CP70 , induced by a novel curcumin analogue , B19 . The proliferation of cells was detected with methyl thiazolyl tetrazolium ( MTT ) assay and apoptosis was examined by flow cytometry . Reactive oxygen species ( ROS ) were assessed by the fluorescent indicator DCF-DA . The protein expression of the endoplasmic reticulum ( ER ) stress pathways , GRP78 , XBP-1 , ATF-4 and CHOP , was examined with Western blotting . A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin . At 20 �M , B19 induced significant apoptosis in CP70 cells . Furthermore , B19 induced the ER stress response , while curcumin had no effect on ER stress . These results suggest that B19 has more effective antitumor properties than curcumin , and is associated with the activation of ER stress and ROS in ovarian cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In this study , we compared the effects of SKI-606 with Iressa , Src/Abl and EGF-R kinase inhibitors , respectively , on selected parameters in HeLa and SiHa cervical cancer cell lines , which express E6/E7 oncoproteins of high-risk HPV types 18 and 16 , respectively . Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G(0)-G(1) cell cycle arrest and reduction of S and G(2)-M phase using 2 and 5 μM concentrations of these inhibitors . In contrast , SKI-606 induces differentiation to an epithelial phenotype \" mesenchymal-epithelial transition \" ; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells , in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected . These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins . The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of β-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule . Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via β-catenin alteration , suggesting that Src inhibitor , in comparison to EGF-R , is a promising therapeutic agent for human cervical cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The tumor suppressor p27(Kip1) is an inhibitor of cyclin/cyclin-dependent kinase ( CDK ) complexes and plays a crucial role in cell cycle regulation . Nevertheless , p27 function in the tumorigenesis of the uterine cervix has been poorly defined . Some phenomenon hints that HPV E7 protein can enhance p27 expression , which is contradictory to HPV E7's property of increasing cell proliferation rate . So , in the present study , we have examined the effect of E7 on p27 expression . Though the levels of p27 are increased after HPV E7 expression , most of the p27 protein localized in the cytoplasm and have no function on cell cycle arrest and contact inhibition . The cell migration rate is elevated when p27 is high expression and located in cytoplasm . The results indicated that E7-p27 interaction not only abolished the p27's cell cycle inhibitory function by sequestering it to the cytoplasm , but also endow the cell with invasive property which is the feature of malignant 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: Diarylquinoline compounds are newly synthesized derivatives of the new anti-tuberculosis drug , TMC207 . In this study , nine diarylquinoline compounds were screened for cytotoxic activity against human tumor cells , and their mechanisms of action were investigated . Among the nine compounds , STM-57 [ N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methl)-N-(3,4-dichlorophenyl)-3-(4 -methylpiperazin-1-yl)propanamide ] showed potent cytotoxic activity . STM-57 induced caspase-independent cell death in the human nasopharyngeal carcinoma cell line , CNE-2 . Further investigation showed that STM-57 induced autophagy , as determined with the increased expression of green fluorescent protein-light chain3 ( GFP-LC3 ) and increased LC3-II levels . STM-57 inhibited the phosphorylation of Akt and the mammalian target of rapamycin ( mTOR ) in CNE-2 cells . The intracellular calcium concentration and reactive oxygen species levels were increased in CNE-2 cells following treatment with STM-57 , whereas the mitochondrial transmembrane potential ( ΔΨm ) and ATP concentrations were decreased .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Arsenic trioxide ( ATO ) is a novel agent to treat acute promyelocytic leukemia ( APL ) . ATO can degrade chimeric PML-RAR proteins and induce apoptosis in various cancer cells . However , its effects on primary hematopoietic CD34+ have not been examined . In this study , we compared the effects of ATO on HL60 leukemic cells and primary umbilical cord blood ( UCB ) CD34+ cells . HL60 cells and UCB CD34+ cells were cultured with different concentrations of ATO for up to three weeks and examined for changes of cell cycle . We found that ATO ( &lt ; or = 5 microM ) caused prolongation of G1/S and G2/M phase in a dose-dependent manner . The percentage of cells in G2/M increased significantly ( from 8.6 to 53.8% ) . High-dose ATO ( &gt ; or = 25 microM ) caused non-specific cell death in HL60 cells without any changes in cell cycle . In contrast to HL60 cells , UCB CD34+ cells were more resistant to high-dose ATO and most ATO-resistant CD34+ cells remained in G0/G1 phase . Primary cells that were resistant to ATO were rich in CD34+ cells . We further show that the ATO resistance was not related to the expression of P-glycoprotein ( MDR-1 ) . Our results suggest that the resistance to ATO in primitive UCB CD34+ cells is most likely related to its cell-cycle status . These results could be useful to design treatments for non-APL malignancies and to enrich hematopoietic stem cells in clinically applicable settings .\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: Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype . The expressions of two tumor suppressor genes , the retinoblastoma ( Rb ) gene and the p53 gene , were investigated during senescence , crisis , and cell line establishment . In temperature-sensitive ( ts)-v-erb B erythroblasts and ts-v-src fibroblasts ( as well as in v-myc macrophages ) , loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization . In contrast , expression of the Rb gene was unchanged at all stages of immortalization . Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts , even in lines that were immortal and lacked p53 . The results demonstrate that the process of immortalization is distinct from cell transformation , probably requiring different mutational events .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Abstract Purpose : Cell death is one of the most important endpoints of radiosensitivity . The tumor suppressor p53 participates not only in regulation of apoptosis , but also in autophagy mechanism . In this study , H1299-P53 ( with wild-type p53 ) and H1299-175H ( with mutant 175H ) were used , and the effects of p53 on radiosensitivity were analyzed . Methods : Cell models with different p53 status were established by gene engineering , and cell viability was examined by colony formation assay , and cell counting kit-8 ( CCK-8 ) , 3-Methyladenine , and Z-VAD were used to block autophagy and apoptosis , respectively . Western blot was used to detect protein expression ; monodansylcadaverine ( MDC ) staining was used to analyze autophagy rate ; DAPI/Propidium Iodide ( PI ) staining and flow cytometry were used to assess apoptosis and necrosis . Results : In parental H1299 , H1299-P53 , and H1299-175H cells , radiosensitivity exhibited different by colony formation and CCK-8 assay ( D0 : 1.764 Gy , 1.407 Gy and 1.695 Gy ; Dq : 2.977 Gy , 1.199 Gy and 2.312 Gy in turn ) . The radiosensitization of p53 was associated with the increase of MDM2 and P21 expression . The ionizing radiation ( IR)-induced apoptosis was significant in H1299-P53 compared with in H1299 and H199-175H ( p<0.05 ) by flow cytometry , and the expression of cleaved-caspase3 was increased in H1299-P53 cells . While the IR-induced autophagy was significant in H1299 cells ( p<0.01 ) and decreased in H1299-P53 and H1299-175H cells ( p<0.01 ) by MDC staining , the expression of MAPLC3II and Beclin-1 increased in H1299 , but not in H1299-p53 and H199-175H cells . The IR-induced cell survival was significantly increased by Z-VAD-FMK and decreased by 3MA in H1299-P53 cells ; IR- induced autophagy was significantly increased by Z-VAD-FMK in H1299-P53 cells ( p<0.01 ) , but not changed in H1299 cells . Conclusion : p53 could regulate radiosensitivity by inhibiting autophagy and activating apoptosis ; autophagy provides a prosurvival mechanism , and p53 potently abrogated the IR-induced autophagy , while mutant 175H shown no effect on radiosensitivity , suggesting that individual treatment strategies should be based on p53 status in patients .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas . METHODOLOGY/PRINCIPAL FINDINGS To address intertumoral heterogeneity we investigated non-microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors . To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence , and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components . All tumors and tumor components were analyzed for allelic loss of 1p/19q ( LOH 1p/19q ) , for TP53- mutations and for R132 mutations in the IDH1 gene . The investigation of non-microdissected tumor tissue revealed clonality in 75% ( 38/51 ) . Aberrant molecular alterations upon recurrence were detected in 25% ( 13/51). 64% ( 9/14 ) of these were novel and associated with tumor progression . Loss of previously detected alterations was observed in 36% ( 5/14 ) . One tumor pair ( 1/14 ; 7% ) was significant for both . Intratumoral clonality was detected in 57% ( 4/7 ) of the microdissected tumor pairs and in 75% ( 3/4 ) of single microdissected tumors. 43% ( 3/7 ) of tumor pairs and one single tumor ( 25% ) revealed intratumoral heterogeneity . While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status , all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components . CONCLUSIONS/SIGNIFICANCE The majority of recurrent gliomas are of monoclonal origin . However , the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas .\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: NKX3.1 is a homeodomain protein that functions as a dosage sensitive prostate-specific transcription factor . Diminished NKX3.1 expression is associated with prostate epithelial cell proliferation in vitro and with increasing Gleason grade in patient samples . Mouse Nkx3.1 also functions as a negative regulator of prostate cell growth in prostate cancer models . Identifying biological and environmental factors that modulate NKX3.1 accumulation is therefore central to efforts aimed at elucidating prostate growth control mechanisms . To determine the effect of inflammation on Nxk3.1 accumulation , bacterial prostatitis was induced by intraurethral inoculation of a uropathogenic E. coli strain in mice . Nkx3.1 expression was profoundly reduced in infected prostate lobes and correlated with increased expression of a proliferation marker . Androgen receptor levels were also reduced in concert with Nkx3.1 , and a marked increase in the basal cell marker p63 was observed . Analyses of the inflammatory infiltrate revealed a classic acute inflammatory response that attained characteristics of a chronic state within fourteen days postinoculation . Comparison of the four prostate lobes revealed clear differences in the extent of inflammation . These data demonstrate that acute inflammation in response to a bacterial agent in the prostate is associated with a significant diminution in the level of a key regulator of prostate cell proliferation . These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Piceatannol has potent anti-inflammatory , immunomodulatory , anticancer and antiproliferative effects . However , little is known about the mechanism by which piceatannol inhibits invasion and metastasis . The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 ( MMP-9 ) in DU145 human prostate cancer cells . The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α ( TNF-α ) . However , treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression . In addition , a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells . Nuclear factor-κ B ( NF-κB ) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis . Therefore , whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed . The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity . Using a specific NF-κB inhibitor , pyrrolidine dithiocarbamate , it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation . Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits . Furthermore , TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol . The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression . Overall , these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate 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: We compared gadolinium diethylenetriaminepentaacetic acid ( Gd-DTPA ) enhanced T1-weighted images ( T1-Gd ) with the histopathological findings in 13 patients with bone or soft tissue sarcomas . Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients . The necrotic or cystic areas in the tumor were not enhanced , rendering them distinctly . The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients . Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced . Thus , the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd . Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The development and progression of esophageal cancer is associated with multiple alterations in the genome , including loss of the tumor suppressor phosphatase and tensin homolog deleted from the chromosome 10 ( PTEN ) gene . The purpose of this study was to determine the effects of adenovirus-mediated MMAC/PTEN expression on the growth and survival of human esophageal cancer cells in vitro and in vivo . We found that compared to control cells , overexpression of PTEN significantly suppressed growth and induced apoptosis in esophageal cancer cell lines Eca-109 and TE-1 via downregulation of Bcl-2 expression and changes in cell-cycle progression . Adenovirus PTEN also inhibited the growth of subcutaneous tumor xenografts by significantly reducing tumor size in vivo . Thus our results confirm the proposed functional role of MMAC/PTEN as a regulator of esophageal cancer progression in vivo and in vitro . PTEN might be an important biological marker and potential therapeutic target in the treatment of human esophageal cancer .\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: Squamous cell carcinoma ( SCC ) is the most frequent cancer in organ transplant recipients ( OTRs ) . The immune system plays a major role in the fight against SCC , however , little is known about the local inflammatory response in SCC at all . We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs . RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis . SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4 , CD8 , TBET , GATA-3 , FOXP3 , RORC , IFN-gamma , IL-4 , TGF-beta , IL-10 , and IL-17A mRNA expression . Immunohistochemistry was carried out in SCC for CD3 , CD4 , CD8 , and FOXP3 expression . Considerable inflammation was seen in both patient groups . SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature . CD4(+) mRNA was diminished in immunosuppression . Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients . T-BET and IFN-gamma mRNA expression were decreased in the OTR group . Although Th17-weighted inflammation was unchanged , IL-17A mRNA level was markedly decreased with immunosuppression . Regulatory T cells , characterized by FOX-P3 and TGF-beta mRNA level , were decreased in OTRs . Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients .\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: When the cell cycle is arrested , even though growth-promoting pathways such as mTOR are still active , then cells senesce . For example , induction of either p21 or p16 arrests the cell cycle without inhibiting mTOR , which , in turn , converts p21/p16-induced arrest into senescence ( geroconversion ) . Here we show that geroconversion is accompanied by dramatic accumulation of cyclin D1 followed by cyclin E and replicative stress . When p21 was switched off , senescent cells ( despite their loss of proliferative potential ) progressed through S phase , and levels of cyclins D1 and E dropped . Most cells entered mitosis and then died , either during mitotic arrest or after mitotic slippage , or underwent endoreduplication . Next , we investigated whether inhibition of mTOR would prevent accumulation of cyclins and loss of mitotic competence in p21-arrested cells . Both nutlin-3 , which inhibits mTOR in these cells , and rapamycin suppressed geroconversion during p21-induced arrest , decelerated accumulation of cyclins D1 and E and decreased replicative stress . When p21 was switched off , cells successfully progressed through both S phase and mitosis . Also , senescent mouse embryonic fibroblasts ( MEFs ) overexpressed cyclin D1 . After release from cell cycle arrest , senescent MEFs entered S phase but could not undergo mitosis and did not proliferate . We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: BACKGROUND Hesperidin , a flavanone present in citrus fruits , has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells . However , the precise mechanisms of action are not entirely understood . AIM The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma ( PPARγ ) in hesperidin's anticancer actions in human pre-B NALM-6 cells , which expresses wild-type p53 . METHODS The effects of hesperidin on cell-cycle distribution , proliferation , and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662 . The expression of peroxisome proliferator-activated receptor-gamma ( PPARγ ) , p53 , phospho-IκB , Bcl-2 , Bax , and XIAP proteins were focused on using the immunoblotting assay . The transcriptional activities of PPARγ and nuclear factor-kappaB ( NF-κB ) were analyzed by the transcription factor assay kits . The expression of PPARγ and p53 was analyzed using the RT-PCR method . RESULTS Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner . The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin . CONCLUSIONS The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells . These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies .\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: Radix of Asiasarum heterotropoides var. mandshuricum F. Maekawa ( A. radix ) has been prescribed for treating pain , allergies and inflammatory disorders in traditional oriental medicine . However , only limited information on the anticancer effects of A. radix is currently available . The aim of this study was to determine the anticancer effect of the ethanol extract of A. radix ( EEAR ) on HCT-116 human colon cancer cells and to investigate its underlying mechanisms of action . EEAR significantly induced G2/M cell cycle arrest and apoptosis in HCT-116 cells . EEAR-induced apoptosis was observed in parallel with activation of caspases and an increased ratio of Bax ( pro-apoptotic)/Bcl2 ( anti-apoptotic ) . Western blot analyses revealed that EEAR elevated the expression of p53 and p21(Waf/Cip1) and decreased the expression of the regulator proteins of G2/M phase progression , such as cdc2 and cyclin B. The upregulation of p53 by EEAR was due to the increased levels of p53 mRNA without a similar increase in proteasome-mediated p53 degradation . EEAR-induced apoptosis in HCT-116 cells was dependent on p53 expression , as determined by siRNA-mediated p53 knockdown . Taken together , these results suggest that EEAR inhibits the growth of the HCT-116 cells through induction of G2/M cell cycle arrest and apoptosis , which are mediated by p53 expression .\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: Hormone replacement therapy , which is a common menopausal treatment , is contraindicated in women with breast cancers due to concerns regarding the potential for breast cell proliferation . As such , there is a need for alternative methods for treating menopausal symptoms . To determine the influence of one such alternative , black cohosh ( Cimicifuga racemosa [ CR] ) , on estrogen-dependent mammary cancers , we conducted an in vitro investigation of the effect of an isopropanolic CR-extract on the proliferation of estrogen receptor-positive breast cancer cells . The experiments were performed using the human breast adenocarcinoma ( MCF-7 ) cell test system , an established in vitro model for estrogen-dependent tumors . The influence of CR-extract on the proliferation of the MCF-7 cells was determined by measuring the incorporation of radioactively labeled thymidine . Under estrogen-deprived conditions , the CR-extract ( 10(-3)-10(-5) dilutions ) significantly inhibited MCF-7 cell proliferation . Additionally , application of the CR-extract inhibited estrogen-induced proliferation of MCF-7 cells . Moreover , the proliferation-inhibiting effect of tamoxifen was enhanced by the CR-extract . Such data that suggest a non-estrogenic , or estrogen-antagonistic effect of CR on human breast cancer cells lead to the conclusion that CR treatment may be a safe , natural remedy for menopausal symptoms in breast cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Anthracyclines have been widely used as antitumor agents , playing a crucial role in the successful treatment of many types of cancer , despite some side effects related to cardiotoxicity . New anthracyclines have been designed and tested , but the first ones discovered , doxorubicin and daunorubicin , continue to be the drugs of choice . Despite their extensive use in chemotherapy , little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines . The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis , characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene . METHODS We assessed the induction of apoptosis ( Sub-G1 ) by cosmomycin D in nucleotide excision repair-deficient fibroblasts ( XP-A and XP-C ) as well as the levels of DNA damage ( alkaline comet assay ) . RESULTS Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner , with highest apoptosis levels observed 96 h after treatment . The effects of cosmomycin D were equivalent to those obtained with doxorubicin . The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells , and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay . CONCLUSIONS Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts . Despite similar apoptosis levels , cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin . This may be related to differences in structure between cosmomycin D and doxorubicin .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The metastatic spread of malignant neoplasms is associated with active migration of cancer cells . The migration of neoplastic cells during the metastatic process may be affected by various extracellular factors , including chemoattractants , haptotactic signals , electric fields , substrate anisotropy , and cell-to-cell contacts . We examined the effect of homotypic collisions and heterotypic interactions with normal human skin fibroblasts on the motile activity of Walker carcinosarcoma cells . It was found that Walker carcinosarcoma cells moving in a dense population neither show contact inhibition of movement when colliding with one another nor increase their motile activity as a result of contact stimulation of motility . On the other hand , when plated onto the surface of aligned fibroblasts , Walker carcinosarcoma cells migrated mainly along the long axes of underlying fibroblasts as a result of contact guidance . The directional character of movement ( but not the speed of migration ) of Walker carcinosarcoma cells on the surface of aligned fibroblasts was completely effaced by RGD-containing synthetic peptide at a concentration of 1 mg/ml but not by 5 microM verapamil ( selective voltage-gated calcium channel inhibitor ) or 10 microM gadolinium chloride ( non-specific blocker of mechanosensitive ion channels ) . The suppression of directional character of migration of tumour cells by RGD-containing peptide was associated with the decrease in the amount of fibronectin macromolecules attached to fibroblasts . This suggests that alignment and anisotropic distribution of fibronectin macromolecules may be responsible for contact guidance of tumour cells moving on the surface of fibroblasts .\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: Tumors are infiltrated by macrophages , T and B-lymphocytes , which may favor tumor development by promoting angiogenesis , growth and invasion . The aim of this study was to investigate the clinical relevance of the relative amount of macrophages ( CD68⁺ ) , T-cells ( CD3⁺ and B-cells ( CD20⁺ ) at the invasive front of breast carcinomas , and the expression of matrix metalloproteases ( MMPs ) and their inhibitors ( TIMPs ) either at the invasive front or at the tumor center . We performed an immunohistochemical study counting CD3 , CD20 and CD68 positive cells at the invasive front , in 102 breast carcinomas . Also , tissue sections were stained with MMP-2 , -9 , -11 , -14 and TIMP-2 antibodies , and immunoreactivity location , percentage of reactive area and intensity were determined at the invasive front and at the tumor center . The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center ( p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio , respectively for MMP-11 and TIMP-2 ) . In addition , a high CD68/(CD3+CD20) ratio ( >0.05 ) was directly associated with a higher probability of shortened relapse-free survival . Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival ( RR : 2.54 , CI : ( 1.23-5.24 ) , p<0.01 ) . Therefore , CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Νuclear factor-κB ( NF-κB ) and activator protein-1 ( AP-1 ) are major transcription factors that have been associated with breast cancer metastasis by inducing matrix metalloproteinase-9 ( MMP-9 ) expression . In this study , we investigated the inhibitory effects of guggulsterone isomers ( cis or trans ) on 12-O-tetradecanoylpho-bol-13-acetate ( TPA)-induced MMP-9 expression . Cis-guggulsterone inhibited TPA-induced MMP expression by blocking IκB kinase ( IKK)/NF-κB signaling , whereas trans-guggulsterone blocked mitogen-activated protein kinase ( MAPK)/AP-1 signaling . Cis-guggulsterone was more potent than trans-guggulsterone in the inhibition of TPA-induced MMP-9 expression and invasion of MCF-7 cells . Furthermore , we found that the combination of these isomers exerted an additive effect on the inhibition of MCF-7 cell invasion . These results suggest that guggulsterone isomers downregulate MMP-9 expression and tumor cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1 activation . In addition , the suppression of MMP-9 expression correlated well with the inhibition of cell invasion .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Semiconductor nanoparticles ( NPs ) became important and wide-used tool for cell imaging because of their unique remarkable properties . Nevertheless , all previous investigations in this area were done on proliferating cells . For the first time , this work demonstrates strong influence of cell active proliferation/contact inhibition of proliferation on uptake of NPs . In addition , we show that cell division plays key-role in penetration of silicon carbide based NPs ( SiC NPs ) inside the cell nucleus . This may very likely concern other types of NPs able to reach the cell nuclei . In particular , observed effect of cell division gives perspectives for future selective cancer treatment with NPs .\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: BACKGROUND Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands . Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects . It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function . In an effort to recapitulate the effects of IGF-1 , as well as increase the likelihood of translating these findings to the clinic , the small molecule therapeutic Roscovitine , is being tested . Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues . METHODOLOGY/PRINCIPAL FINDINGS Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2)/M phase , as demonstrated by flow cytometry . In contrast , mice treated with radiation exhibit no differences in the percentage of cells in G(2)/M when compared to unirradiated controls . Similar to previous studies utilizing IGF-1 , pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells . Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells , which is suppressed by pretreatment with Roscovitine . Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands , both acutely and chronically , as measured by salivary output . CONCLUSIONS/SIGNIFICANCE These studies suggest that induction of transient G(2)/M cell cycle arrest by Roscovitine allows for suppression of apoptosis , thus preserving normal salivary function following targeted head and neck irradiation . This could have an important clinical impact by preventing the negative side effects of radiation therapy in surrounding normal tissues .\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: PURPOSE Although the adrenal gland is a common site of extrahepatic metastasis from hepatocellular carcinoma ( HCC ) , there are no definitive guidelines for the treatment of adrenal metastasis . This study examines the effectiveness of various treatments for this disease . METHODS We retrospectively analyzed 20 patients treated for adrenal metastasis of HCC by adrenalectomy ( n = 13 ) , transarterial chemoembolization ( TACE ) , or percutaneous ethanol injection therapy ( PEIT ) ( n = 7 ) . RESULTS There were no significant differences in cumulative survival rates between patients given adrenalectomy and those given TACE or PEIT , either after completing treatment for primary HCC or after the first treatment for adrenal metastasis . Six of seven patients with tumor thrombi in the inferior vena cava ( IVC ) from adrenal metastasis underwent adrenalectomy combined with intracaval thrombectomy , five of whom survived for more than 1 year after surgery , and two of whom are still alive without any recurrence more than 3 years after surgery . PEIT showed good results for small adrenal metastasis . CONCLUSION These findings suggest that therapeutic modalities should be chosen according to the clinical features of each individual , including the size of the metastatic tumor , whether there is invasion into the IVC , the function of the remaining liver , and the existence of intra- and/or nonadrenal extrahepatic lesions . Furthermore , intracaval tumor thrombectomy could be indicated for patients with IVC thrombus if they are suitable candidates for surgery .\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: OBJECTIVE The HER2 receptor is involved in pathways essential for cell proliferation , and is an important predictive and prognostic factor in breast cancer . HER2 probably plays a critical role in many types of cancer , including urothelial carcinoma of the bladder ( UCB ) . Stage T1 UCB exhibits heterogeneous clinical behaviour , and the frequency of HER2 expression in such disease has not been thoroughly examined . The aim of this study was to use an immunohistochemical technique to evaluate the frequency of HER2 expression in a defined population-based cohort of patients registered as having primary stage T1 UCB . MATERIAL AND METHODS The initial study population comprised 285 patients registered as having primary stage T1 UCB . The original histological specimens were re-evaluated with regard to T stage and World Health Organization grade . Hospital records provided information on tumour size , multiplicity , possible presence of histologically proven recurrence and progression . The patients were followed for at least 5 years or until death . In tumours still considered stage T1 after re-evaluation , HER2 was investigated by immunohistochemistry of paraffin-embedded material and scored according to the guidelines used in breast cancer . RESULTS After histopathological re-evaluation , 201 patients were still T1 UCB and could be investigated regarding HER2 expression . HER2 overexpression was observed in 25 of those patients ( 12.4% ) . HER2 status was not significantly associated with recurrence or progression . CONCLUSIONS HER2 was overexpressed in 12.4% of the present cohort of patients with primary stage T1 UCB . There was no significant association between tumour HER2 status and prognosis .\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: Systemic oxidative stress is associated with a wide range of pathological conditions . Oxidative DNA damage is frequently measured in circulating lymphocytes . Mitochondrial DNA ( mtDNA ) is known to be more sensitive to oxidative damage than nuclear DNA but is rarely used for direct measurement of DNA damage in clinical studies . Based on the supercoiling-sensitive real-time PCR method , we propose a new approach for the noninvasive monitoring of systemic oxidative stress by quantifying the mtDNA structural damage and copy number change in isolated lymphocytes in a single test . We show that lymphocytes have significantly less mtDNA content and relatively lower baseline levels of damage than cancer cell lines . In an ex vivo challenge experiment , we demonstrate , for the first time , that exogenous H2O2 induces a significant increase in mtDNA damage in lymphocytes from healthy individuals , but no repair activity is observed after 1 h recovery . We further demonstrate that whole blood may serve as a convenient alternative to the isolated lymphocytes in mtDNA analysis . Thus , the blood analysis with the multiple mtDNA end-points proposed in the current study may provide a simple and sensitive test to interrogate the nature and extent of systemic oxidative stress for a broad spectrum of clinical investigations .\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: Keratinocyte growth factor ( KGF , fibroblast growth factor-7 ) is a fibroblast-derived mitogen , which stimulates proliferation of epithelial cells . The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair . However , the role of KGF in cutaneous carcinogenesis and cancer progression is not known . We have examined the role of KGF in progression of squamous cell carcinoma ( SCC ) of the skin . The expression of KGF receptor ( KGFR ) mRNA was lower in cutaneous SCCs ( n = 6 ) than in normal skin samples ( n = 6 ) . Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF . KGF did not stimulate SCC cell proliferation , but it reduced invasion of SCC cells through collagen . Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes , including genes with tumor suppressing properties ( SPRY4 , DUSP4 , DUSP6 , LRIG1 , PHLDA1 ) . KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes , including genes associated with tumor progression ( MMP13 , MATN2 , CXCL10 , and IGFBP3 ) . Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2 . Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression . These results provide evidence , that KGF does not promote progression of cutaneous SCC , but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells , as compared to normal keratinocytes .\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: Because PRL has growth factor activities in several tissues , we have asked whether it also has autocrine growth factor activity in pituitary GH3 cells . GH3 cells were grown at increasing densities in the presence or absence of antirat PRL ( polyclonal and monoclonal ) or nonspecific antibodies . Cell proliferation increased with increasing cell density , as did the concentration of PRL in the medium . Antirat PRL , but not control antibody , markedly inhibited but did not eliminate cell proliferation , and this effect was diminished with increasing PRL concentration in the medium . PRL receptors were demonstrated on 40-50% of the cells by indirect immunofluorescence using a specific antirat PRL receptor monoclonal antibody . Cell surface PRL was colocalized to the same 40-50% of the cells and copatched or cocapped along with the receptors . Absence or presence of PRL receptors did not correlate with stage of the cell cycle , as judged by ethidium bromide dual labeling . Cell surface PRL was found to be on PRL-containing cells . These data have fulfilled four criteria necessary for establishment of a substance as a secreted autocrine growth factor : 1 ) the factor must be secreted ; 2 ) in log growth phase , increased cell proliferation should occur at increased cell densities ; 3 ) the cells must display a receptor for the factor ; and 4 ) there must be a growth response to the factor . Thus we have established that PRL is an autocrine growth factor for at least 40-50% of the GH3 cell population . This , to our knowledge , is the first example of autocrine growth factor activity of a major hormone normotopically expressed .\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: PTEN , a phosphoinositide-3-phosphatase , serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism . Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation , especially reactive carbonyl species , which are commonly occurring by-products of arachidonic acid peroxidation . Using MCF7 and HEK-293 cells , we report that several reactive aldehydes and ketones , e.g. electrophilic α,β-enals ( acrolein , 4-hydroxy-2-nonenal ) and α,β-enones ( prostaglandin A(2) , Δ12-prostaglandin J(2) and 15-deoxy-Δ-12,14-prostaglandin J(2) ) covalently modify and inactivate cellular PTEN , with ensuing activation of PKB/Akt kinase ; phosphorylation of Akt substrates ; increased cell proliferation ; and increased nuclear β-catenin signaling . Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation , oxidative stress , or aging .\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 have developed fluorescent probes for the detection of strand scission in the excision repair of oxidatively damaged bases . They were hairpin-shaped oligonucleotides , each containing an isomer of thymine glycol or 5,6-dihydrothymine as a damaged base in the center , with a fluorophore and a quencher at the 5'- and 3'-ends , respectively . Fluorescence was detected when the phosphodiester linkage at the damage site was cleaved by the enzyme , because the short fragment bearing the fluorophore could not remain in a duplex form hybridized to the rest of the molecule at the incubation temperature . The substrate specificities of Escherichia coli endonuclease III and its human homolog , NTH1 , determined by using these probes agreed with those determined previously by gel electrophoresis using ( 32)P-labeled substrates . Kinetic parameters have also been determined by this method . Since different fluorophores were attached to the oligonucleotides containing each lesion , reactions with two types of substrates were analyzed separately in a single tube , by changing the excitation and detection wavelengths . These probes were degraded during an incubation with a cell extract . Therefore , phosphorothioate linkages were incorporated to protect the probes from nonspecific nucleases , and the base excision repair activity was successfully detected in HeLa cells .\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: Caveolin-1 ( -/- ) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts . Here , we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 ( -/- ) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers . More specifically , the transcriptional profiles of Cav-1 ( -/- ) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node ( LN ) metastasis . This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein ( by immuno-histochemical staining in the fibroblast compartment ) is significantly associated with increased LN-metastasis . We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress , DNA damage/repair , inflammation , hypoxia , and aerobic glycolysis , consistent with the \" Reverse Warburg Effect \" . Finally , the tumor stroma of \" metastasis-prone \" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease . This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress . These processes may include oxidative stress , NO over-production ( peroxynitrite formation ) , inflammation , hypoxia , and mitochondrial dysfunction , which are thought to occur in Alzheimer?s disease pathology . Thus , a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress , aerobic glycolysis , and inflammation , driving the \" Reverse Warburg Effect \" in the tumor micro-environment and cancer cell metastasis .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;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: Anal canal cancer is a rare tumor without clear treatment evidence in the metastatic setting . In terms of the bad prognosis of patients with metastatic anal cancer , further therapeutic options are urgently needed . In this paper we present the case of a 64-year-old man suffering from undifferentiated squamous cell carcinoma with liver metastases . After progression on cisplatin and fluorouracil , tumor tissue was analyzed with respect to anti-EGFR therapy with cetuximab . There was no KRAS mutation and the EGFR expression level in the tumor tissue was 2+ ; ideal conditions for the immunotherapy . Encouraged by these results we started a therapy using FOLFIRI in combination with cetuximab . Fortunately the patient showed a partial response after 6 cycles . On patient's preference we did a therapy break of 6 weeks . Within this time period the disease was progressive indicating its aggressiveness . However , the same immunotherapy was able to stabilize the disease for a further 3 months . The patient died 21 months after diagnosis because of liver failure . Nevertheless , from our perspective the combination of FOLFIRI and cetuximab is quite a promising therapeutic option for patients with metastatic anal cancer . Potential predictive factors of the immunochemotherapy are discussed in this paper .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Breast cancer includes high number of molecular entities targetable by specific agents . In this study , array CGH and PIK3CA/AKT1 mutations were used to drive patients into targeted therapy . A prospective molecular analysis was offered to metastatic breast cancer patients for whom samples were collected prospectively or retrospectively either from frozen or paraffin-embedded tissue . Analyses were performed using array CGH ( Agilent platform ) and PIK3CA ( exon 10 and 21 ) and AKT1 mutations were explored by standard Sanger sequencing . One hundred and eight patients were included . Good quality CGH was obtained in 79% cases and was better for frozen samples . Genomic alterations were identified in 50% of patients including 11 PIK3CA and 8 AKT1 mutations . Eighteen treatments ( 17 patients ) were administered according to their molecular profile with evidence of activity in nine . Reasons for not providing a genomic-driven treatment included absence of progressive disease ( 38% ) , investigator's choice ( 9% ) , rapid PD ( 19% ) , and no drug access ( 21% ) . Array CGH correctly identified Her2 status in 97% cases ; failures were related to low % of tumour cells . Our study showed that array CGH is feasible in the context of daily practice and , in combination with PIK3CA/AKT1 mutations , identifies a significant number of actionable molecular alterations that allow driving patients into specific targeted agents .\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 explore the inhibitory effect of sulfated polysaccharide from Masson pine ( Pinus massoniana ) pollen ( SPPM60 ) on G(2)/M phase of human liver cancer HepG2 cells and its mechanism . METHODS : The proliferation rate of HepG2 cells was evaluated by methyl thiazolyl tetrazolium ( MTT ) colorimetric assay . The cycles of HepG2 cells were measured by flow cytometry when 200μg/ml concentration of SPPM60 was adopted , the expression of the genes related to cell cycle was detected by real-time PCR . RESULTS : SPPM60 inhibited the proliferation of HepG2 cells and the inhibition rate was elevated with increase of SPPM60 concentration . After treatment with 200μg/ml of SPPM60 , the percentage of S phase cells was decreased , but that of G(2)/M phase was significantly increased ( 72h vs control : 32.96�0.33% vs 18.59�0.04% , 3.44�0.05% vs 18.30�0.08% , P<0.01 ) . The results of real-time PCR showed that SPPM60 could down-regulate the mRNA levels of CDK1 and CyclinB ( P<0.01 ) , and up-regulate the expression of p53 and p21 ( P<0.05 ) . CONCLUSION : SPPM60 causes arrest of HepG2 cells at G(2)/M phase , and the mechanism is related to the down-regulation of CDK1 and CyclinB and up-regulation of p53 and p21 expression .\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: Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells ( the Warburg Effect ) . Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems , and the molecular mechanisms underlying the shifts remain unknown . With proteomics , we observed increased glycolysis in disused human diaphragm muscle . In disused muscle , lung cancer , and H(2)O(2)-treated myotubes , we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase ( PFKm , >2 fold , P<0.05 ) and accumulation of lactate ( >150% , P<0.05 ) . Using microRNA profiling , we identify miR-320a as a regulator of PFKm expression . Reduced miR-320a levels ( to ∼50% of control , P<0.05 ) are associated with the increased PFKm in each of these diverse systems . Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions . Further , miR-320a appears to regulate oxidative stress-induced PFKm expression , and reduced miR-320a allows greater induction of glycolysis in response to H(2)O(2) treatment . We show that this microRNA-mediated regulation occurs through PFKm's 3 ' untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a . These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Many different cellular pathways have evolved to protect the genome from the deleterious effects of DNA damage that result from exposure to chemical and physical agents . Among these is a process called transcription-coupled repair ( TCR ) that catalyzes the removal of DNA lesions from the transcribed strand of expressed genes , often resulting in a preferential bias of damage clearance from this strand relative to its non-transcribed counterpart . Lesions subject to this type of repair include cyclobutane pyrimidine dimers that are normally repaired by nucleotide excision repair ( NER ) and thymine glycols ( TGs ) that are removed primarily by base excision repair ( BER ) . While the mechanism underlying TCR is not completely clear , it is known that its facilitation requires proteins used by other repair pathways like NER . It is also believed that the signal for TCR is the stalled RNA polymerase that results when DNA damage prevents its translocation during transcription elongation . While there is a clear role for some NER proteins in TCR , the involvement of BER proteins is less clear . To explore this further , we studied the removal of 7-methylguanine ( 7MeG ) and 3-methyladenine ( 3MeA ) from the dihydrofolate reductase ( dhfr ) gene of murine cell lines that vary in their repair phenotypes. 7MeG and 3MeA constitute the two principal N-methylpurines formed in DNA following exposure to methylating agents . In mammalian cells , alkyladenine DNA alkyladenine glycosylase ( Aag ) is the major enzyme required for the repair of these lesions via BER , and their removal from the total genome is quite rapid . There is no observable TCR of these lesions in specific genes in DNA repair proficient cells ; however , it is possible that the rapid repair of these adducts by BER masks any TCR . The repair of 3MeA and 7MeG was examined in cells lacking Aag , NER , or both Aag and NER to determine if rapid overall repair masks TCR . The results show that both 3MeA and 7MeG are removed without strand bias from the dhfr gene of BER deficient ( Aag deficient ) and NER deficient murine cell lines . Furthermore , repair of 3MeA in this region is highly dependent on Aag , but repair of 7MeG is equally efficient in the repair proficient , BER deficient , and NER deficient cell lines . Strikingly , in the absence of both BER and NER , neither 7MeG nor 3MeA is repaired . These results demonstrate that NER , but not TCR , contributes to the repair of 7MeG , and to a lesser extent 3MeA .\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: Group VIB Phospholipase A(2) ( iPLA(2)γ ) is distributed in membranous organelles in which β-oxidation occurs , that is , mitochondria and peroxisomes , and is expressed by insulin-secreting pancreatic islet β-cells and INS-1 insulinoma cells , which can be injured by inflammatory cytokines , for example , IL-1β and IFN-γ , and by oxidants , for example , streptozotocin ( STZ ) or t-butyl-hydroperoxide ( TBHP ) , via processes pertinent to mechanisms of β-cell loss in types 1 and 2 diabetes mellitus . We find that incubating INS-1 cells with IL-1β and IFN-γ , with STZ , or with TBHP causes increased expression of iPLA(2)γ mRNA and protein . We prepared INS-1 knockdown ( KD ) cell lines with reduced iPLA(2)γ expression , and they proliferate more slowly than control INS-1 cells and undergo increased membrane peroxidation in response to cytokines or oxidants . Accumulation of oxidized phospholipid molecular species in STZ-treated INS-1 cells was demonstrated by LC/MS/MS scanning , and the levels in iPLA(2)γ-KD cells exceeded those in control cells. iPLA(2)γ-KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1β and IFN-γ . These findings suggest that iPLA(2)γ promotes β-cell proliferation and that its expression is increased during inflammation or oxidative stress as a mechanism to mitigate membrane injury that may enhance β-cell survival .\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 immune status of spleen and the effect of surgical treatment in advanced gastric cancer ( AGC ) patients were evaluated by means of testing NK cell activity , T-lymphocyte subsets and circulating immune complex ( CIC ) . The results showed ( 1 ) the significant impairment of NK cell activity and T-lymphocyte subsets , were decreased in CD3+ , CD4+ cells and increased in CD6+ cells resulting in CD4+/CD8+ cell ratio decrease in peripheral blood lymphocytes ( PBL ) , splenic venous blood lymphocytes ( SVL ) and spleen cells ( SC ) of AGC , as compared with PBL of normal population ; ( 2 ) NK cell activity or CD4+/CD8+ cell ratio of SVL and SC were significantly lower than those of PBL in AGC patients , mainly caused by marked decrease of CD4+ cells in SC ; ( 3 ) NK cell activity , CD4+ cells and CD4+/CD8+ cell ratio were significantly elevated in most of AGC cases receiving either radical gastrectomy ( R2+ ) or extensive radical gastrectomy ( R3 ) . A striking declination in CD8+ cells were found only after R3 operation ; ( 4 ) after a short period ( 10-14 days ) or a long period ( 2-4 years ) of radical gastrectomy , NK cell activity and T-lymphocyte subsets showed no significant differences between R2+ and R3 operation . As a rule , AGC would weaken immune function of patients , and along with the development of the tumor , the immunosuppression in the spleen would be generated gradually . For these reasons , a complete tumor resection would be necessary to improve the immunocompetence , and the combined splenectomy might be advisable if indicated .\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 immune system has an important role in tumor appearance and spreading . One of the most efficient subpopulations of cytotoxic cells in the destruction of tumors are NK cells . NK cells are activated and increase their cytotoxic potential and modulate their cytokine production after treatment with IFNgamma , IL-12 , TNFalpha and IL-2 . The investigation of the activity of NK cells was performed on peripheral blood lymphocytes ( PBL ) of 16 healthy controls and of 40 patients with metastatic breast carcinoma . Modulation of NK cells was performed with IL-2 , IL-7 , IL-12 , TNFalpha , monoclonal antibodies ( mAb ) for TNFalpha and TNFalpha receptors type I and II , as well as with sera of healthy controls and patients with breast cancer in different clinical stages . Modulating effect of the applied factors after in vitro treatment of PBL was evaluated by the cytotoxic assay using 51chromium . Our results indicate that IL-2 significantly increased the activity of NK cells of controls and breast cancer patients . The sera of patients with advanced breast cancer significantly reduced NK cell activity . IL-7 , IL-12 and mAb for TNFalpha do not significantly change the activity of NK cells . The presence of anti-TNFalpha mAb did not change the inhibitory effect of the sera of breast cancer patients with advanced disease on the activity of NK cells of controls and patients with breast cancer . Blocking of TNFalpha Rcs with mAbs decrease the reactivity of NK cells for IL-2 . The treatment of breast cancer patients with advanced clinical stage of breast cancer with IL-2 , as an additional therapy , could be advantageous , as NK cells after this treatment increase their cytotoxic activity against tumor cells and can improve therapeutical results .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: This study aimed to observe the effects of octreotide ( OCT ) on cisplatin resistance reversal of cancer cells in vitro and in nude mice in vivo . MTT method and flow cytometry were used to investigate the effect of cisplatin , OCT or the combination of these two compounds on the proliferation and apoptosis of SKOV3-DDP cells . The size and weight of xenograft tumors from the nude mice model were measured . Real-time PCR was used to detect the mRNA expression of SSTR2 , MDR1 , MRP2 , GST-pi and EGFR in SKOV3/DDP cells following the different treatment . At the concentration of 2.5-20 g/ml , OCT significantly reduced IC50 ( p &lt ; 0.05 ) and promoted apoptosis ( p &lt ; 0.05 ) of SKOV3-DDP cells ' response to cisplatin . Unchanged expression was found in SSTR2 on the SKOV3/DDP cell in vitro after OCT treatment , but increased expression in vivo ( p &lt ; 0.05 ) . OCT increased GST-pi expression ( p &lt ; 0.05 ) and reduced MRP2 and EGFR expression ( p &lt ; 0.05 ) in a dose-dependent manner . The similar results were obtained in mice in vivo experiment , except the reduced expression of GST-pi . It is suggested that OCT could inhibit ovarian cancer proliferation and promote apoptosis , via the cell surface SSTR2 , and reverse cisplatin resistance through inhibition of MRP2 , EGFR , and even GST-pi expressions .\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: Hepatocellular carcinoma ( HCC ) is the most prevalent liver tumor and a deadly disease with limited therapeutic options . Dysregulation of cell signaling pathways is a common denominator in tumorigenesis , including hepatocarcinogenesis . The epidermal growth factor receptor ( EGFR ) signaling system is commonly activated in HCC , and is currently being evaluated as a therapeutic target in combination therapies . We and others have identified a central role for the EGFR ligand amphiregulin ( AR ) in the proliferation , survival and drug resistance of HCC cells . AR expression is frequently up-regulated in HCC tissues and cells through mechanisms not completely known . Here we identify the β-catenin signaling pathway as a novel mechanism leading to transcriptional activation of the AR gene in human HCC cells . Activation of β-catenin signaling , or expression of the T41A β-catenin active mutant , led to the induction of AR expression involving three specific β-catenin-Tcf responsive elements in its proximal promoter . We demonstrate that HCC cells expressing the T41A β-catenin active mutant show enhanced proliferation that is dependent in part on AR expression and EGFR signaling . We also demonstrate here a novel cross-talk of the EGFR system with fibroblast growth factor 19 ( FGF19 ) . FGF19 is a recently identified driver gene in hepatocarcinogenesis and an activator of β-catenin signaling in HCC and colon cancer cells . We show that FGF19 induced AR gene expression through the β-catenin pathway in human HCC cells . Importantly , AR up-regulation and EGFR signaling participated in the induction of cyclin D1 and cell proliferation elicited by FGF19 . Finally , we demonstrate a positive correlation between FGF19 and AR expression in human HCC tissues , therefore supporting in clinical samples our experimental observations . These findings identify the AR/EGFR system as a key mediator of FGF19 responses in HCC cells involving β-catenin signaling , and suggest that combined targeting of FGF19 and AR/EGFR may enhance therapeutic efficacy .\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 report the formation , detection , quantitation and structural characterization of products resulting from the adduction of deoxynucleosides ( deoxyadenosine , deoxyguanosine , deoxycytidine and 5-methyldeoxycytidine ) to the catechol estrogens ( CE ) of estrone , estradiol-17beta and estradiol-17 alpha . The crude products are obtained in a one-pot synthesis through oxidation of catechols to quinones and subsequent Michael-type reaction with the deoxynucleosides in acidic medium . In all experiments , adducts are detected by electrospray ionization mass spectrometry analysis after HPLC separation ( LC/ESI/MS(n) ) . The two pyrimidines deoxycytidine and 5-methyldeoxycytidine yield only CE adducts to deoxynucleosides , which correspond to stable adducts on DNA . For purines , the results depend on the CE ( 2,3- or 3,4-catechols ) used , the function and configuration on carbon 17 ( ketone for estrone , alcohol for alpha and beta isomers of estradiol ) , and on the purine itself ( deoxyadenosine or deoxyguanosine ) . Both stable adducts and deglycosylated adducts are formed , and therefore formation of stable adducts on DNA as well as the loss of purines from the DNA strands could be possible . MS(2) and MS(3) experiments prove to be relevant for further structural determinations , enabling in some cases the elucidation of the regiochemistry of adduction on the A and B rings of the steroid moiety .\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: Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors . When two cells touch , an adhesion link is created between them by means of transmembrane E-cadherin proteins . Simultaneously , their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links . Here , we propose a detailed quantitative model of the role of cytoplasmic beta-catenin and alpha-catenin proteins in this process , treated as a reaction-diffusion system . Upon cell-cell contact the concentration in alpha-catenin dimers increases , inhibiting actin branching and thereby reducing cellular motility and expansion pressure . This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin , beta-catenin , and alpha-catenin in the cellular phenotype and in tumorigenesis . In particular , we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene . Potential direct tests of our model are discussed .\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: Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors . Based on high throughput technologies data , this disease is currently classified according to the molecular expression of estrogen ( ER ) , progesterone ( PR ) and human epidermal growth factor ( HER-2 ) receptors . In this study , we defined the inflammatory profile of the main molecular subtypes of breast cancer patients : luminal ( ER and PR positive , HER-2 negative ) , HER-2 enriched ( HER-2 positive ) and triple negative ( ER , PR and HER-2 negative ) . Cytokines panel was assessed by measurement of TNF-α , TGF-β , IL-1 , IL-10 and IL-12 plasmatic levels . Oxidative profile was assessed by determination of lipid peroxidation , total antioxidant capacity of plasma , malondialdehyde levels , carbonyl content and nitric oxide ( NO ) . Clinical data were correlated with inflammatory findings . Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α , TGF-β and enhanced oxidative stress levels associated with reduced IL-12 . HER-2-enriched group exhibited higher levels of TNF-α , IL-12 and TGF-β associated with enhanced oxidative stress . Triple-negative subtype exhibited the most aggressive profile of disease behavior , with reduction in both TNF-α and TGF-β , with high levels of lipid peroxidation and NO . The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer , opening potential therapeutic targets to future therapies .\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 anti-tumor antibiotic salinomycin ( Sal ) was recently identified as a selective inhibitor of breast cancer stem cells ; however , the effect of Sal on hepatocellular carcinoma ( HCC ) is not clear . This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC . HCC cell lines ( HepG2 , SMMC-7721 , and BEL-7402 ) were treated with Sal . Cell doubling time was determinated by drawing growth curve , cell viability was evaluated using the Cell Counting Kit 8 . The fraction of CD133(+) cell subpopulations was assessed by flow cytometry . We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+)cell subpopulations in HCC cells . Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases . Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining . Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio . Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays . Compared to control , β-catenin expression is significantly down-regulated upon Sal addition . The Ca(2+) concentration in HCC cells was examined by flow cytometry and higher Ca(2+) concentrations were observed in Sal treatment groups . The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls . Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo . Finally , the role of Sal on in vivo Wnt/β-catenin signaling was evaluated by Western blot and immunohistochemistry . This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/β-catenin signaling via increased intracellular Ca(2+) levels .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: New molecularly targeted therapies are needed for childhood ependymoma . Angiogenesis and the PDGFR pathway could be potential therapeutic targets . This study aimed to screen ependymomas for the expression and clinicopathological correlates of angiogenic factors and potential therapeutic targets including VEGFR , endoglin ( CD105 ) , CD34 , CD31 , c-Kit , PDGFR-α and PDGFR-β . Immunohistochemistry for angiogenesis factors and PDGFR-α and β was performed in 24 archival tumor samples from children and adults treated for ependymoma at our institution . CD31 density , CD105 density and pericyte coverage index ( PCI ) were calculated . These findings were correlated with clinical outcome . VEGFR2 was overexpressed in tumor cells in only one out of 24 cases , but was found overexpressed in the vessels in 6 cases . PDGFR-α and β were found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases ( 29.2 % ) . CD31 density , CD105 density and PCI did not correlate with expression of PDGFRs . Overexpression of PDGFR-α and β in tumor cells and overexpression of PDGFR-α in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFR-α in tumor cells ( 2 year progression free survival was 16.7 ± 15.2 for cases with overexpression of PDGFR-α in the tumor vs. 74.5 ± 15.2 for those with low/no expression , hazard ratio = 5.78 , p = 0.04 ) . A number of angiogenic factors are expressed in ependymoma tumor cells and tumor endothelium . Preliminary evidence suggests that the expression of PDGFRs could have a prognostic significance in ependymoma . This data suggests that PDGFRs should be further evaluated as targets using novel PDGFR inhibitors .\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: BACKGROUND The pTalpha/preTCR regulates the beta-selection , a crucial T-cell developmental checkpoint , providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck) . METHODS To define the relevance of pTalpha in human T-cell lymphoblastic leukemia ( T-ALL ) , we analyzed in T-ALL cell lines ( n=14 ) pTalpha and p56(Lck) mRNA and protein expression as also the tyrosine-phosphorylation . The p56(Lck) specific src-protein-tyrosine kinase inhibitor ( PTK-I ) PP1 was used in growth inhibition assays . IC(50) value determination , cell cycle- and apoptosis analyses were performed in T-ALL- , non-T-ALL- and murine transgenic cell lines . RESULTS pTalpha expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts . PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G(1/0) phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2 , respectively . PP1 sensitive cell lines expressed the target protein p56(Lck) and showed a corresponding P-Tyr signal . CONCLUSION Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTalpha mediated proliferation in this leukemic sub-type . In addition , p56(Lck) represents also independently of pTalpha a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases .\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: PURPOSE Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative ( gemtuzumab ozogamicin , GO ) are a novel therapy option for acute myeloid leukaemia ( AML ) . Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies , including drug efflux or other mechanisms decreasing apoptosis . Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks ( DSBs ) accompanied by decreased DNA repair . METHODS We labelled anti-CD33 antibodies with the alpha-emitter ( 211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the ( 211)At-labelled antibodies , GO or unlabelled antibodies as controls . We also measured caspase-3/7 activity , DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free ( 211)At . RESULTS The mean labelling ratio of ( 211)At-labelled antibodies was 1:1,090 +/- 364 ( range : 1:738-1:1,722 ) in comparison to 2-3:1 for GO . Tumour cell binding of ( 211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33 . ( 211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution ( 1:1,000 ) . No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after ( 211)At-anti-CD33 ( 1:1,090 ) versus GO ( 1:1 ) treatment . CONCLUSION Our results suggest that ( 211)At is a promising , highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody . Labelling techniques leading to higher chemical yield and specific activities must be developed to increase ( 211)At-anti-CD33 therapeutic effects .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Maintaining the integrity of the cell cycle is critical for ensuring that cells only undergo DNA replication and proliferation under controlled conditions in response to discrete stimuli . One mechanism by which the fidelity of this process is guaranteed is through the activation of cell cycle checkpoints . The mitotic spindle checkpoint , which is regulated by Aurora B kinase , ensures proper kinetochore attachment to chromosomes leading to equal distribution of chromosomes to daughter cells . We demonstrated that the mitogen-activated protein kinase ( MAPK ) cascade regulates mitotic progression and the spindle checkpoint . As demonstrated by immunofluorescence at kinetochores , depletion of Raf Kinase Inhibitory Protein ( RKIP ) , an inhibitor of Raf/MEK/ERK signaling , causes an increase in MAPK activity that inhibits Aurora B kinase activity . By monitoring mitotic index and transit time from nuclear envelope breakdown to anaphase , we demonstrated that RKIP depletion leads to a defective spindle checkpoint and genomic instability , particularly in response to drugs that disrupt microtubule function .\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: Thrombospondin-1 is a matricellular protein with potent antitumour activities , the levels of which determine the fate of many different tumours , including renal carcinomas . However , the factors that regulate this protein remain unclear . In renal carcinomas , hypoxic conditions enhance the expression of angiogenic factors that help adapt tumour cells to their hostile environment . Therefore , we hypothesized that anti-angiogenic factors should correspondingly be dampened . Indeed , we found that hypoxia decreased the thrombospondin-1 protein in several clear cell renal carcinoma cell lines ( ccRCC ) , although no transcriptional regulation was observed . Furthermore , we proved that hypoxia stimulates multiple signals that independently contribute to diminish thrombospondin-1 in ccRCC , which include a decrease in the activity of oxygen-dependent prolylhydroxylases ( PHDs ) and activation of the PI3K/Akt signalling pathway . In addition , thrombospondin-1 regulation in hypoxia proved to be important for ccRCC cell migration and invasion .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

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

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The progression of prostate cancers ( PCs ) to locally invasive , androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse . The present study was undertaken to establish the possibility of using a combination of specific oncogenic products , including epidermal growth factor receptor ( EGFR ) , pAkt , nuclear factor-kappaB ( NF-κB ) and macrophage inhibitory cytokine-1 ( MIC-1 ) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages . The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR , Ser(473)-pAkt , NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of 76 cases of prostatic adenocarcinoma specimens during the disease progression and these biomarkers were expressed in a small subpopulation of CD133(+) PC cells and the bulk tumor mass of CD133(-) PC cells . Importantly , all of these biomarkers were also overexpressed in 80-100% of 30 PC metastasis bone tissue specimens . Moreover , the results have indicated that the EGF-EGFR signaling pathway can provide critical functions for the self-renewal of side population ( SP ) cells endowed with stem cell-like features from highly invasive WPE1-NB26 cells . Of therapeutic interest , the targeting of EGFR , pAkt , NF-κB or MIC-1 was also effective at suppressing the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells , inducing disintegration of SP cell-derived prostaspheres and decreasing the viability of SP and non-SP WPE1-NB26 cell fractions . Also , the targeting of these oncogenic products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26 cells and enhanced their sensibility to the cytotoxic effects induced by docetaxel . These findings suggest that the combined use of EGFR , pAkt , NF-κB and/or MIC-1 may represent promising strategies for improving the accuracy of current diagnostic and prognostic methods and efficacy of treatments of PC patients in considering the disease heterogeneity , thereby preventing PC progression to metastatic and lethal disease states .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: Multiple myeloma ( MM ) is classically illustrated by a desynchronized cytokine system with rise in inflammatory cytokines . There are recent reports which emphasized the potential role of angiogenesis in the development of MM. Role of cyclooxygenase 2 ( COX-2 ) is well documented in the pathogenesis of solid tumors , but little is known about its occurrence and function in hematologic neoplasms . Involvement of neoangiogenesis is reported in the progression of MM , and angiopoietins probably contribute to this progression by enhancing neovascularization . Circulatory and mRNA levels of angiogenic factors and cyclooxygenase were determined in 125 subjects ( 75 MM patients and 50 healthy controls ) by using enzyme-linked immunosorbent assay and quantitative PCR . We observed significant increase for angiogenic factors ( Ang-1 , Ang-2 , hepatocyte growth factor , and vascular endothelial growth factor ) and cyclooxygenase at circulatory level , as well as at mRNA level , as compared to healthy controls except insignificant increase for Ang-1 at circulatory level . We have also observed the significant positive correlation of all angiogenic factors with cyclooxygenase . The strong association found between angiogenic factors and COX-2 in this study may lead to the development of combination therapeutic strategy to treat MM. Therefore , targeting COX-2 by using its effective inhibitors demonstrating antiangiogenic and antitumor effects could be used as a new therapeutic approach for treatment of MM .\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: In order to determine the in vivo immune response in glioblastoma , monoclonal and polyclonal antibodies specific for inflammatory leukocytes and immunoregulatory products were utilized to stain tissue from four surgical specimens . The more activated the inflammatory cells , the more activated the tumors appeared to be . In the tumor with the largest infiltration ( Case 3 ) , inflammatory cells were stained for interferon-gamma , interleukin-2 , interleukin-1 beta , lymphotoxin , tumor necrosis factor-alpha , and transforming growth factor-beta . The tumor cells also expressed interleukin-1 beta , interleukin-6 , transforming growth factor-beta , tumor necrosis factor-alpha , and prostaglandin E. In contrast , in the tumor with the least inflammatory response ( Case 1 ) , the tumor cells did not express any cytokines . Expression of cytokines by glioma cells was modest in the two cases with modest inflammatory responses . Cellular inflammation , primarily consisting of T cells and macrophages with few or no B cells or natural killer cells , was two- to 15-fold greater outside the tumor than within . In contrast to leukocytes outside the tumor , which were activated and expressing class II major histocompatibility antigens , leukocytes within the tumor parenchyma or at the tumor's edge were negative for these antigens . In the four specimens studied here , the tumor cells themselves were also negative for class II major histocompatibility antigens . These findings , although preliminary , suggest that inflammatory cells within gliomas are inactivated and that glioma cells may increase the expression of immunosuppressive cytokines in response to an increased lymphocyte infiltrate . This observation , if corroborated by more extensive studies , may help to explain the failure of immune treatments in glioblastoma multiforme .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Both the deregulation of microRNAs and epidermal growth factor receptor ( EGFR ) are emerging as important factors in non-small-cell lung cancer ( NSCLC ) . Here , miR-133b was found to be associated with tumor stage , the extent of regional lymph node involvement , stage , visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC . Bioinformatic analysis and luciferase reporter assay revealed that miR-133b can interact specifically with the 3'-UTR of EGFR mRNA . Functionally , miR-133b transfection showed regulatory activity in translationally repressing EGFR mRNA . Moreover , miR-133b transfection may modulate apoptosis , invasion and sensitivity to EGFR-TKI through the EGFR signaling pathways , especially in EGFR-addicted NSCLC cells . Taken together , our findings show that miR-133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway . This finding has important implications for the development of targeted therapeutics for a number of EGFR-addicted cancers .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis;resisting cell death" } ]