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clinicalnlplab

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Clinical NLP Lab 29

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A new cell line of human ovarian clear cell adenocarcinoma ( CCC ) , TU-OC-1 , was established and characterized . The cells showed a polygonal-shaped morphology and grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle . The chromosome numbers ranged from 64 to 90 . A low rate of proliferation was observed , similar to other CCC cell lines tested ( OVTOKO , RMG-I , and OVAS ) , and the doubling time was 38.4h . The respective IC50 values of cisplatin and paclitaxel were 12.2μM and 58.3nM . Mutational analysis revealed that TU-OC-1 cells harbored a PIK3CA mutation at codon 542 ( E542K ) in exon 9 , which is a mutation hot spot on this gene . We observed that phosphorylated Akt protein was overexpressed in TU-OC-1 cells by western blot analysis . Heterotransplantation to nude mice produced tumors that reflected the original . This cell line may be useful to study the chemoresistant mechanisms of CCC and contribute to novel treatment strategies .\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: Epigenetic changes in pediatric neuroblastoma may contribute to the aggressive pathophysiology of this disease , but little is known about the basis for such changes . In this study , we examined a role for the DNA methyltransferase DNMT3B , in particular , the truncated isoform DNMT3B7 , which is generated frequently in cancer . To investigate if aberrant DNMT3B transcripts alter DNA methylation , gene expression , and phenotypic character in neuroblastoma , we measured DNMT3B expression in primary tumors . Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas , suggesting that expression of DNMT3B7 may induce a less aggressive clinical phenotype . To test this hypothesis , we investigated the effects of enforced DNMT3B7 expression in neuroblastoma cells , finding a significant inhibition of cell proliferation in vitro and angiogenesis and tumor growth in vivo . DNMT3B7-positive cells had higher levels of total genomic methylation and a dramatic decrease in expression of the FOS and JUN family members that comprise AP1 transcription factors . Consistent with an established antagonistic relationship between AP1 expression and retinoic acid receptor activity , increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all-trans retinoic acid ( ATRA ) compared to controls . Our results indicate that DNMT3B7 modifies the epigenome in neuroblastoma cells to induce changes in gene expression , inhibit tumor growth , and increase sensitivity to ATRA .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity that mainly targets vascular endothelial growth factor receptors , and recently , it has been shown to be an active agent for the treatment of malignant pheochromocytomas . Previously , we demonstrated that sunitinib directly inhibited mTORC1 signaling in rat pheochromocytoma PC12 cells . Although autophagy is a highly regulated cellular process , its relevance to cancer seems to be complicated . It is of note that inhibition of mTORC1 is a prerequisite for autophagy induction . Indeed , direct mTORC1 inhibition initiates ULK1/2 autophosphorylation and subsequent Atg13 and FIP200 phosphorylation , inducing autophagy . Here , we demonstrated that sunitinib significantly increased the levels of LC3-II , concomitant with a decrease of p62 in PC12 cells . Following sunitinib treatment , immunofluorescent imaging revealed a marked increased punctate LC3-II distribution . Furthermore , Atg13 knockdown significantly reduced its protein level , which in turn abolished sunitinib-induced autophagy . Moreover , inhibition of autophagy by siRNAs targeting Atg13 or by pharmacological inhibition with ammonium chloride , enhanced both sunitinib-induced apoptosis and anti-proliferation . Thus , sunitinib-induced autophagy is dependent on the suppression of mTORC1 signaling and the formation of ULK1/2-Atg13-FIP200 complexes . Inhibition of autophagy may be a promising therapeutic option for improving the anti-tumor effect of sunitinib .\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 As a highly conserved system , the activation of the Notch pathway has been implicated in the tumorigenesis of various hematologic diseases , including leukemias , lymphomas , and multiple myeloma . The Notch3 receptor is frequently expressed in T-cell acute lymphoblastic leukemia ( T-ALL ) . METHODS To explore its possibility as a therapeutic target for T-ALL , we investigated the effect of Notch3 silencing on Jurkat and SupT1 cells using a novel tumor-specific short hairpin RNA ( shRNA ) driven by survivin promoters . RESULTS We found that downregulated expression of Notch3 correlated with significant apoptosis and inhibition of proliferation . CONCLUSION These facts suggest that downregulating expression of Notch3 could attenuate the Notch signaling activity in T-ALL . All these results indicate that inhibition of Notch3 expression can result in potent antitumor activity in T-ALL .\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: Glutathione S-transferase ( GST ) class Mu activity was determined in 145 unrelated hospital patients in Berlin by measuring their conjugation activity towards the specific substrate trans-stilbene oxide ( TSO ) with two substrate concentrations ( 50 and 250 microM ) in homogenates prepared from lymphocytes . Eighty individuals ( 55.2% ) had an activity lower than 10 pmol/min/10(6) lymphocytes and were classified as GST class Mu deficient . In 142 of 145 cases , phenotype was confirmed by the results of a genotyping procedure using the polymerase chain reaction technique . Two fragments of 273 and about 650 bp including one and two introns , respectively , could always be amplified from genomic DNA in individuals with high GST class Mu activity and could not be amplified in persons with impaired glutathione-TSO conjugation activity . This indicates that persons with low activity carry a large deletion mutation within the GST class Mu gene . The enzymatically determined antimode between low and high activity determined as 10 pmol/min/1 million lymphocytes in the assay with 50 microM TSO could be clearly confirmed by genotyping .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We have investigated the cytotoxic activity , the induction of apoptosis , and the interstrand cross-linking efficiency in the A2780cisR ovarian tumor cell line , after replacement of the two NH3 nonleaving groups in trans-[PtCl2(NH3)2] ( trans-DDP ) by dimethylamine and isopropylamine . The data show that trans-[PtCl2(NH(CH)2)(NHCH(CH3)2)] is able to circumvent resistance to cis-[PtCl2(NH3)2] ( cis-DDP , cisplatin ) in A2780cisR cells . In fact , trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] shows a cytotoxic potency higher than that of cis-DDP and trans-DDP , with the mean IC50 values being 11 , 58 , and 300 microM , respectively . In addition , at equitoxic doses ( concentrations of the platinum drugs equal to their IC50 values ) and after 24 hours of drug treatment , the level of induction of apoptosis by trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] is twice that produced by cis-DDP . Under the same experimental conditions , trans-DDP does not induce significant levels of apoptosis in A2780cisR cells . After 24 hours of incubation of A2780cisR cells at concentrations equal to the IC0o value of the platinum drugs , the level of DNA interstrand cross-links ( ICLs ) induced by trans-[PtCI2(NH(CH)2)(NHCH(CH3)] is two and three times higher , respectively , than those induced by cis-DDP and trans-DDP . We also found that trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] formed DNA ICLs between guanine and complementary cytosine . We propose that , in A2780cisR cells , the induction of apoptosis by trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] is related to its greater ability ( relative to cis-DDP and trans-DDP ) to form DNA ICLs .\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: BACKGROUND &amp ; AIMS Hepatocellular carcinoma ( HCC ) is an aggressive malignancy with few treatment options . As the status of the tumour immune microenvironment can affect progression of established tumours , we evaluated potential immune mechanisms associated with survival in HCC . METHODS Immune gene expression profiles were analyzed in tumour and non-tumour liver tissues from resected HCC patients using quantitative PCR and immunohistochemistry . Tumour-infiltrating leukocytes ( TILs ) were isolated to verify the expression of immune genes and to identify proliferating TILs . These parameters were analyzed statistically in relation with patient survival and tumour phenotype ( apoptosis and proliferation ) . RESULTS The immune microenvironment within tumours was found to be heterogeneous , although globally more inert compared to the adjacent non-tumour liver tissue . Univariate analysis in 61 patients identified a group of innate immune genes whose expression within tumours is positively associated with patient survival . TNF , IL6 and CCL2 are the most significant genes , with TNF being an independent predictor of survival in multivariate analysis . The gene set includes macrophage and NK-associated molecules such as TLR4 , TLR3 , CCR2 , NCR3 . Most of these molecules are expressed by TILs . Importantly , proliferating immune cells , predominantly NK and T cells , are present in tumours of patients with longer survival , and exclusively in areas devoid of proliferating tumour cells . NK and CD8(+) T cell densities are correlated positively with tumour apoptosis , and negatively with tumour proliferation . CONCLUSIONS Hence , an inflammatory immune microenvironment within HCC tumours could be an important means to control tumour progression via TIL activation and proliferation .\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: OBJECTIVES To evaluate the impact of the category of unclassified renal cell carcinoma ( URCC ) on survival following nephrectomy . METHODS Patients with clear cell RCC ( ccRCC , n = 3048 ) and URCC ( n = 38 ) were identified . Patients with URCC were matched 4:1 with ccRCC patients based on year of surgery , symptoms at presentation , tumor size , stage , regional lymph node involvement , metastases , grade , coagulative tumor necrosis , and sarcomatoid differentiation . Survival was estimated using the Kaplan-Meier method and compared between ccRCC and URCC patients using log-rank tests . RESULTS Patients with URCC were more likely to have regional lymph node involvement ( P <.001 ) , higher grade ( P <.001 ) , tumor necrosis ( P <.001 ) , and sarcomatoid differentiation ( P <.001 ) as compared to patients with ccRCC . Overall survival was not significantly different between URCC and ccRCC patients in either the unmatched ( P = .337 ) or matched ( P = .345 ) cohorts . Cancer-specific survival was significantly worse for URCC patients compared with unmatched ccRCC patients ( P = .020 ) . However , this difference was not statistically significant when the URCC patients were compared with the matched cohort ( P = .688 ) . Distant metastases-free survival was somewhat worse for M0 URCC patients compared with unmatched M0 ccRCC patients ( P = .063 ) , but not in the matched cohort ( P = .788 ) . CONCLUSIONS Although URCC is more likely to present with advanced clinicopathologic features compared with ccRCC , no statistically significant differences in outcome were noted after adjusting for these features in a matched analysis .\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: Interleukin-23 ( IL-23 ) plays an essential role in the mucosal immune system . It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells . However , neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed . The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells . We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry . Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer . ELISA and real-time PCR were used to evaluate the transforming growth factor ( TGF)-β production due to IL-23 stimulation . All of the TNM stage IV patients were positive for IL-23R . IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases . The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation , whereas no change was observed in the activities of MIP101 and KM12c cells . IL-23 directly enhanced the malignancy of the colon carcinoma cells . An autocrine mechanism via TGF-β production may underlie these effects . IL-23 is therefore a potential target for cancer immunotherapy . However , the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered .\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: Clear cell renal cell carcinoma ( ccRCC ) is the most common pathological subtype of kidney cancer . Here , we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease . One of the most potent survival regulators , the monocarboxylate transporter MCT4 ( SLC16A3 ) , impaired ccRCC viability in all eight ccRCC lines tested and was the seventh most overexpressed gene in a meta-analysis of five ccRCC expression datasets . MCT4 silencing impaired secretion of lactate generated through glycolysis and induced cell cycle arrest and apoptosis . Silencing MCT4 resulted in intracellular acidosis , and reduction in intracellular ATP production together with partial reversion of the Warburg effect in ccRCC cell lines . Intra-tumoural heterogeneity in the intensity of MCT4 protein expression was observed in primary ccRCCs . MCT4 protein expression analysis based on the highest intensity of expression in primary ccRCCs was associated with poorer relapse-free survival , whereas modal intensity correlated with Fuhrman nuclear grade . Consistent with the potential selection of subclones enriched for MCT4 expression during disease progression , MCT4 expression was greater at sites of metastatic disease . These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;resisting cell death;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Recent evidence indicates that the estrogen receptor-α-negative , androgen receptor ( AR)-positive molecular apocrine subtype of breast cancer is driven by AR signaling . The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype ; its proliferation is stimulated by androgens such as 5α-dihydrotestosterone ( DHT ) but inhibited by the progestin medroxyprogesterone acetate ( MPA ) via AR-mediated mechanisms . We report here that the AR gene in MDA-MB-453 cells contains a G-T transversion in exon 7 , resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 ( Q865H ) in the ligand binding domain . Compared with wild-type AR , the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists . Ligand binding , molecular modeling , mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation , AR intramolecular interactions , and receptor stability . Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells . Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway . These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant . This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype .\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 Hepatocellular carcinoma ( HCC ) is the most common liver cancer . Therapeutic results are usually unsatisfactory because liver tumors recur often . Immunologic factors may be related to the recurrence of HCC ; however , this possibility is mentioned only rarely . METHODS Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs : group A ( n = 8 ) , diameter ≤3 cm ; group B ( n = 8 ) , diameter >3 cm and ≤5 cm ; and group C ( n = 14 ) , diameter >5 cm . T-lymphocytes from peripheral blood , nontumor liver tissue , and the HCC were analyzed . RESULTS The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups . CD25+ cells were increased in the tumor tissue in group C patients ( range , 6-41% ; median , 22.9% ; P = .003 ) , compared to group A patients . The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes ( r = 0.556 ) . These CD4+ CD25+ lymphocytes produced transforming growth factor-β and interferon-γ but not interleukin-10 , and were anergic to plate-coated monoclonal antibodies ( anti-CD3/anti-CD28 ) . The characteristics of these antibodies were comparable to those of regulatory T cells . When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells , the proliferation of lymphocytes was inhibited . CONCLUSION The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes . These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells .\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: Epidemiological studies have indicated that females may be at greater risk of smoking associated lung cancer compared with males . Several lines of biochemical evidence support these observations . A possible role of circulating steroid hormones in the etiology of lung cancer has been hypothesized . In the present paper , we have studied the expression of the estrogen receptors ( ER)-alpha and ER beta in histologically normal human lung tissue and lung tumor cell lines . Relative ER mRNA levels were measured by reverse transcriptase-PCR and normalized to the level of expression of the glyceraldehyde 3-phosphate dehydrogenase gene ( GAPDH ) . In lung tissue , an ER alpha transcript was found at various levels in 38 out of 46 cases ( 83% ) . ER beta was expressed in all cases . The ERs were expressed at similar levels in females and males , and the levels of ER alpha and ER beta mRNA were significantly related ( P<0.0001 ) . Compared with the lung tissue , ER expression levels were lower in 16 human lung tumor cell lines and two immortalized human bronchial epithelial cell lines . Five of the tumor cell lines ( 31% ) expressed detectable levels of ER alpha and both of the immortalized cell lines showed a weak ER alpha expression level . All cell lines expressed the ER beta . The lung cell lines BEAS-2B and DB354 showed significantly reduced cell proliferation in response to tamoxifen and a minor increased growth in response to 17 beta-estradiol . In conclusion , ER genes are abundantly expressed in both histologically normal human lung and lung tumor cell lines . This indicates a possible role of ERs in lung carcinogenesis .\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: Chromatographic , peptide mapping and mass spectrometric analysis were used to examine hemoglobin ( Hb ) from heavy drinkers and abstainers for alcohol consumption-related modifications . Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different ( p &lt ; 0.05 ) amounts of \" fast \" hemoglobin . The presence of higher amounts of \" fast \" Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications . To further examine Hb for modifications , tryptic peptides of the \" fast \" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry ( PDMS). [ 14C]acetaldehyde ( AcH)-Hb was synthesized in vivo for use as a standard . Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [ 14C]acetaldehyde-Hb . The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides ; the two pairs of peptides co-migrated on HPLC . A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb . The modified peptides were found in five of six heavy drinker samples . This is the first description of site-specific AcH-Hb adducts occurring in vivo . The routine detection of such adducts has potential for characterizing usual alcohol intake .\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: Although anticancer effect of gambogic acid ( GA ) and its potential mechanisms were well documented in past decades , limited information is available on the anticancer effect of gambogenic acid ( GNA ) , another major active component of Gamboge . Here we performed a study to determine whether GNA possesses anticancer effect and find its potential mechanisms . The results suggested that GNA significantly inhibited the proliferation of several tumor cell lines in vitro and in vivo . Treatment with GNA dose and time dependently induced A549 cells apoptosis , arrested the cells to G0/G1 phase in vitro and down-regulated the expression of cyclin D1 and cyclooxygenase ( COX)-2 in mRNA level . In addition , anticancer effect was further demonstrated by applying xenografts in nude mice coupled with the characteristic of apoptosis in the GNA treated group . Taken together , these observations might suggest that GNA inhibits tumor cell proliferation via apoptosis-induction and cell cycle arrest .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;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: PURPOSE Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration ( AMD ) enables sensitive use of antiangiogenic drugs and reduces adverse side effects . So far , no in vivo imaging methods are available to specifically label active angiogenesis . Here , we report such a technique using fluorophore-labeled cationic liposomes ( CL ) detected with a standard clinical in vivo scanning laser ophthalmoscope ( SLO ) . METHODS C57Bl/6 mice underwent laser coagulations at day 0 ( d0 ) to induce choroidal neovascularization ( CNV ) . Liposomes labeled with Oregon green , rhodamine ( Rh ) , or indocyanine green ( ICG ) were injected into the tail vein at various time points after laser coagulation , and their fluorescence was observed in vivo 60 min later using an SLO , or afterwards in choroidal flatmounts or cryosections . RESULTS SLO detected accumulated fluorescence only in active CNV lesions with insignificant background noise . The best signal was obtained with CL-ICG . Choroidal flatmounts and cryosections of the eye confirmed the location of retained CL in CNV lesions . Neutral liposomes , in contrast , showed no accumulation . CONCLUSIONS These results establish fluorophore-labeled CL as high affinity markers to selectively stain active CNV . This novel , non-invasive SLO imaging technique could improve risk assessment and indication for current intraocular antiangiogenic drugs in neovascular eye diseases , as well as monitor therapeutic outcomes . Labeling of angiogenic vessels using CL can be of interest not only for functional imaging in ophthalmology but also for other conditions where localization of active angiogenesis is desirable .\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 UT-7 cell line was established from a patient with a megakaryoblastic leukemia ( Komatsu et al , Cancer Res 51 : 341 , 1991 ) . Its proliferation is strictly dependent on the presence of hematopoietic growth factors including erythropoietin ( Epo ) , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , and interleukin-3 ( IL-3 ) . We investigated the differentiation capacities of this cell line under the action of several growth factors , using immunomarkers , flow cytometry , and ultrastructural techniques . In the presence of GM-CSF and IL-3 , eosinophil and basophil promyelocytes were detected , as well as a few cells with erythroid and megakaryocytic ( MK ) differentiation features . In contrast , Epo induced a marked erythroid differentiation with an increase of glycophorin A expression , accompanied by a few hemoglobinized cells . Differentiation induced by the growth factors took 24 to 48 hours to begin , and increased with cell passages to a plateau at 2 weeks of culture . However , this was not only due to a cell selection because the differential effects of Epo and GM-CSF were observed from a single cell clone and the phenotype could be reversed by opposite growth factors , even after a long period of culture . We subsequently investigated the phenotype of UT-7 in the presence of combinations of Epo , IL-3 , and GM-CSF , and showed that GM-CSF and IL-3 act predominantly over Epo . This effect was mediated by a rapid downmodulation of Epo receptors by GM-CSF at messenger RNA and binding sites levels , without a change in receptor affinities . On the other hand , Epo had no effect on number and affinity of GM-CSF receptors . This study shows that UT-7 is a growth factor-dependent pluripotent cell line in which commitment may be directed by a hierarchical action of growth factors through an early and rapid transmodulation of growth factor receptors .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The involvement of signal transduction systems in the initial attachment of two murine B16 melanoma clones of differing metastatic potential to extracellular matrix components was examined to learn more of the early events in cell-matrix interaction . Clones of high and low metastatic capacity attached similarly in the absence of any stimulators , exhibiting a two phase time course of attachment with 100% attachment by 60 min . A slight difference in attachment characteristics between the clones was seen in response to phorbol ester stimulation , which significantly inhibited attachment of the low metastatic clone but which had no effect on the highly metastatic clone . Total protein kinase C activity and distribution was similar for both clones . Attachment of both clones was severely reduced , however , if intracellular calcium was elevated or intracellular calmodulin inhibited . This study suggests that signal transduction mechanisms are involved in melanoma cell attachment to matrix proteins and offers an approach to pharmacological manipulation of these cell-matrix interactions which may be relevant to reducing metastatic spread .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The effect of peptides released during the fermentation of milk on the humoral immune system and on fibrosarcoma growth was studied . Lactobacillus helveticus was able to release peptidic compounds during milk fermentation due to its high proteolytic activity , as was shown by the degree of proteolysis and size-exclusion HPLC elution profiles . Three fractions of these compounds were separated and fed to mice during different periods ( 2 , 5 , and 7 d ) . The humoral immune response was assessed by following the number of IgA-secreting cells , and the antitumor activity was monitored by studying the regression of subcutaneously implanted fibrosarcomas . Feeding during 2 and 7 d with the medium-sized fraction ( Fraction II ) significantly increased the IgA-producing cells in the intestines , whereas feeding with the large compound fraction ( Fraction I ) during 5 d and the small compound fraction ( Fraction III ) during all three feeding periods provided similar increases . A double dose of Fraction II showed the highest IgA-producing cell count . The increase by Fraction III was shown to be caused by the presence of L-Tryptophan . Fraction II significantly decreased the size of fibrosarcoma when previously fed during 7 d , and feeding with Fraction I during 5 d decreased significantly its size after 35 d of growth . Although the mechanisms by which lactic acid bacteria enhance the immune system are not clear , this study clearly shows that bioactive compounds released in fermented milks contribute to the immunoenhancing and antitumor properties of these products . The release of bioactive peptides by lactic acid bacteria can have important implications on the modulation of the cellular immune response .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In cancer cells , glucose is often converted into lactic acid , which is known as the ' Warburg effect ' . The reason that cancer cells have a higher rate of aerobic glycolysis , but not oxidative phosphorylation , remains largely unclear . Herein , we proposed an epigenetic mechanism of the Warburg effect . Fructose-1,6-bisphosphatase-1 ( FBP1 ) , which functions to antagonize glycolysis was downregulated through NF-kappaB pathway in Ras-transformed NIH3T3 cells . Restoration of FBP1 expression suppressed anchorage-independent growth , indicating the relevance of FBP1 downregulation in carcinogenesis . Indeed , FBP1 was downregulated in gastric carcinomas ( P<0.01 , n=22 ) and gastric cancer cell lines ( 57% , 4/7 ) . Restoration of FBP1 expression reduced growth and glycolysis in gastric cancer cells . Moreover , FBP1 downregulation was reversed by pharmacological demethylation . Its promoter was hypermethylated in gastric cancer cell lines ( 57% , 4/7 ) and gastric carcinomas ( 33% , 33/101 ) . Inhibition of NF-kappaB restored FBP1 expression , partially through demethylation of FBP1 promoter . Notably , Cox regression analysis revealed FBP1 promoter methylation as an independent prognosis predicator for gastric cancer ( hazard ratio : 3.60 , P=0.010 ) . In summary , we found that NF-kappaB functions downstream of Ras to promote epigenetic downregulation of FBP1 . Promoter methylation of FBP1 can be used as a new biomarker for prognosis prediction of gastric cancer . Such an important epigenetic link between glycolysis and carcinogenesis partly explains the Warburg effect .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Gefitinib , the specific inhibitor of the epidermal growth factor receptor ( EGFR ) , may cause growth delay in cancer cell lines . Thorough understanding of the downstream cellular signaling of gefitinib will facilitate the discovery of biomarkers for predicting outcomes and monitoring anti-EGFR therapies , and provide information for key targets for therapeutic intervention . In this study , we investigated the role of transducer of erbB2.1 ( TOB1 ) in gefitinib therapy . Using the lung carcinoma cell lines A549 and NCI-H1975 , the results suggested that gefitinib might mediate cell cycle arrest in lung cancer cells at least by targeting TOB1 expression . Gefitinib treatment caused cell cycle arrest predominantly at the G1 phase , which is associated with TOB1 nuclear translocation and its interaction with cyclin D1 . We also showed that knockdown of TOB1 expression by RNAi rescued lung cancer cells from gefitinib-induced cell-proliferative arrest . These results suggest that TOB1 interaction with cyclin D1 and nuclear translocation is directly involved in the gefitinib-induced anti-proliferative cell cycle arrest .\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: AMPK is a metabolic sensor that helps maintain cellular energy homeostasis . Despite evidence linking AMPK with tumor suppressor functions , the role of AMPK in tumorigenesis and tumor metabolism isunknown . Here we show that AMPK negatively regulates aerobic glycolysis ( the Warburg effect ) in cancer cells and suppresses tumor growth invivo . Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis . Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis , increased allocation of glucose carbon into lipids , and biomass accumulation . These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α ( HIF-1α ) , as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling . Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation .\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 triterpenoid fraction ( 100 and 200 mg/kg ) of the fruit bodies of Ganoderma lucidum inhibited primary solid-tumor growth in the spleen , liver metastasis and secondary metastatic tumor growth in the liver in intrasplenic Lewis lung carcinoma ( LLC)-implanted mice . In addition , the triterpenoid fraction ( 800 micrograms/mL ) inhibited angiogenesis induced by Matrigel ( a soluble basement membrane extract of the Engelbreth-Holm-Swam ( EHS ) tumor ) supplemented with vascular endothelial growth factor ( VEGF ) and heparin in an in vivo model . This suggested that the antitumor and antimetastatic activities of the triterpenoid fraction of G. lucidum might be due to the inhibition of tumor-induced angiogenesis . Next , we attempted to isolate the active substance(s) using the in vivo assay system of Matrigel-induced angiogenesis . The acidic fraction of the triterpenoid fraction inhibited the Matrigel-induced angiogenesis . Compound I was isolated from the acidic fraction as an active substance that inhibited the Martigel-induced angiogenesis . Compound I was identified as ganoderic acid F based on the data of IR , 1H- and 13C-NMR and MS analyses .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Exposure to ultraviolet B ( UVB ) radiation ( 280-320 nm ) is the primary etiologic factor associated with the development of basal cell carcinoma ( BCC ) . The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise eliminate them . Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation . Humans , like mouse strains , display variations in dermal mast cell prevalence . In a study of Danish and South Australian BCC patients and control subjects , one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant . This skin site was investigated to avoid any changes in mast cell prevalence caused by sun exposure . Two sections ( 4 microm ) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells . Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total dermal area ( expressed as mast cells per square millimeter ) . This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations . We hypothesize that mast cells function in humans , as in mouse strains , by initiating immunosuppression following UV irradiation and , thereby , allowing a permissive environment for the development of BCC . Thus , a high dermal mast cell prevalence as demonstrable in buttock skin is a significant predisposing factor for development of BCC in humans .\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: A clinicopathological study of 41 cases of pituitary apoplexy in a series of 324 surgically treated pituitary adenomas is presented . In 23 patients , the predominant operative finding was hemorrhage with or without necrosis . However , there were 15 ( 37.7% ) cases where pale , necrotic tissue with no evidence of hemorrhage was found at surgery . Pale , necrotic material was particularly found when there was a long interval between the acute clinical event and surgery . It is concluded that the pale , necrotic debris represents one stage in the resorption process of blood after hemorrhagic necrosis of pituitary adenomas . This entity needs to be kept in mind especially since the material closely resemble the pultaceous material seen in craniopharyngiomas and epidermoid cysts .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The omega-3 long chain polyunsaturated fatty acids , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , elicit antiproliferative effects in cancer cell lines and in animal models . Dietary DHA and EPA can be converted to their ethanolamine derivatives , docosahexaenoyl ethanolamine ( DHEA ) and eicosapentaenoyl ethanolamine ( EPEA ) , respectively ; however , few studies are reported on their anticancer activities . Here , we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells . Since DHA and EPA are ligands of Peroxisome Proliferator-Activated Receptor ( PPAR ) γ , we sought to determine whether PPARγ may also mediate DHEA and EPEA actions . In MCF-7 cells , both compounds enhanced PPARγ expression , stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN , resulting in the inhibition of AKT-mTOR pathways . Besides , DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction . We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining . Finally , we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor . In summary , our data show that the two omega-3 ethanolamines exert antiproliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents . J. Cell . Physiol. © 2012 Wiley Periodicals , Inc .\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: Cellular senescence has emerged as a critical tumor suppressive mechanism in recent years , but relatively little is known about how senescence occurs . Here , we report that secreted Frizzled-related protein 1 ( SFRP1 ) , a secreted antagonist of Wnt signaling , is oversecreted upon cellular senescence caused by DNA damage or oxidative stress . SFRP1 is necessary for stress-induced senescence caused by these factors and is sufficient for the induction of senescence phenotypes . We present evidence suggesting that SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma ( Rb ) pathway and that cancer-associated SFRP1 mutants are defective for senescence induction .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;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: Although the expression of extracellular matrix protein-1 ( ECM1 ) has been documented in several tumor models , the function of ECM1 has remained unclear . In this study , expression of ECM1 was detected by real time PCR and immunohistochemistry . The role and mechanism of ECM1 overexpression in cholangiocarcinoma ( CCA ) cells were assessed by wound-healing , matrigel invasion assay and Western blotting . Expression of ECM1 was significantly elevated in CCA tissues than that in adjacent noncancerous , cholangitis and normal bile duct tissues . Its overexpression was associated with poor differentiation , lymph node metastasis , poor prognosis , and the level of CA199 , MMP-9 , estrogen receptor . Knockdown of ECM1 suppressed migration and invasion of CCA cells . Using PI3K or IKK inhibitor reduced the level of phospho-Akt or phospho-IκBα as well as ECM1 . Taken together , overexpression of ECM1 may contribute to CCA initiation and progression through promoting migration and invasion of CCA cells , its overexpression was associated with Akt/NF-κB signaling axis .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The development of targeted therapies and immunotherapies has markedly advanced the treatment of metastasized melanoma . While treatment with selective BRAF(V600E) inhibitors ( like vemurafenib or dabrafenib ) leads to high response rates but short response duration , CTLA-4 blocking therapies induce sustained responses , but only in a limited number of patients . The combination of these diametric treatment approaches may further improve survival , but pre-clinical data concerning this approach is limited . We investigated , using Tyr::CreER(T2)PTEN(F-/-)BRAF(F-V600E/+) inducible melanoma mice , whether BRAF(V600E) inhibition can synergize with anti-CTLA-4 mAb treatment , focusing on the interaction between the BRAF(V600E) inhibitor PLX4720 and the immune system . While PLX4720 treatment strongly decreased tumor growth , it did not induce cell death in BRAF(V600E)/PTEN(-/-) melanomas . More strikingly , PLX4720 treatment led to a decreased frequency of tumor-resident T cells , NK-cells , MDSCs and macrophages , which could not be restored by the addition of anti-CTLA-4 mAb . As this effect was not observed upon treatment of BRAF wild-type B16F10 tumors , we conclude that the decreased frequency of immune cells correlates to BRAF(V600E) inhibition in tumor cells and is not due to an off-target effect of PLX4720 on immune cells . Furthermore , anti-CTLA-4 mAb treatment of inducible melanoma mice treated with PLX4720 did not result in enhanced tumor control , while anti-CTLA-4 mAb treatment did improve the effect of tumor-vaccination in B16F10-inoculated mice . Our data suggest that vemurafenib may negatively affect the immune activity within the tumor . Therefore , the potential effect of targeted therapy on the tumor-microenvironment should be taken into consideration in the design of clinical trials combining targeted and immunotherapy .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease ( GVHD ) . However , optimal dosage is still under debate . Thirty-one consecutive children , mainly with haematological malignancies , were transplanted in a single institution with such donors , selected by HLA-A -B compatibility by serology and DRB1* by DNA typing . Antithymocyte globulin ( Thymoglobuline ; Sangstat ) was infused at days -3 , -2 , -1 . Total dosage varied : 16 patients received a median of 7.5 mg/kg ( 2.5 to 10.5 : low-dose group ) , and 15 a median of 15.5 mg/kg ( 14.4 to 19.4 : high-dose group ) . Post-transplant GVHD prophylaxis consisted of cyclosporine , short-course methotrexate and steroids . CD3(+) , CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group . Median time to reach 100 CD4(+) cells was 8 months vs 4 months ( P = 0.03 ) . Median time to normal CD19(+) cells was 16 months vs 8 months ( P = 0.01 ) . CD16(+)CD56(+) and CD8(+) cell reconstitution was similar . Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections ( P = 0.009 ) . Although obtained from a limited number of patients , our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution .\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: Given the important role of CXCR4 in cancer metastasis , microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion . Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior . CXCR4 is upregulated in several cancer cells under hypoxic conditions , suggesting a relationship between tumor hypoxia and CXCR4 . However , the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood . KATO III gastric cancer cells were exposed to hypoxia or normoxia . CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry . Wound healing , migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12 , a major CXCR4 ligand . CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATOIII cells following exposure to hypoxia . This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses ( migration and invasion ) to CXCL12 treatment in vitro . The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA . Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner , and that upregulation of CXCR4 plays a role in cancer cell migration and invasion . Thus , disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A novel series of N(4)-(3-chlorophenyl)-5-(oxazol-2-yl)pyrimidine-4,6-diamines were synthesized and evaluated as dual inhibitors of HER-1/HER-2 tyrosine kinases . In contrast to the currently approved HER-2-targeted agent ( lapatinib , 1 ) , our irreversible HER-1/HER-2 inhibitors have the potential to overcome the clinically relevant and mutation-induced drug resistance . The selected compound ( 19a ) showed excellent inhibitory activity toward HER-1/HER-2 tyrosine kinases with selectivity over 20 other kinases and inhibited the proliferation of both cancer cell types : lapatinib-sensitive cell lines ( SK-Br3 , MDA-MB-175 , and N87 ) and lapatinib-resistant cell lines ( MDA-MB-453 , H1781 , and H1975 ) . The excellent pharmacokinetic profiles of 19a in mice and rats led us to further investigation of a novel therapeutic agent for HER-2-targeting treatment of solid tumors , especially HER-2-positive breast/gastric cancer and HER-2-mutated lung 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: Focal inflammation causes systemic fever . Cancer hyperthermia therapy results in shrinkage of tumors by various mechanisms , including induction of adaptive immune response . However , the physiological meaning of systemic fever and mechanisms of tumor shrinkage by hyperthermia have not been completely understood . In this study , we investigated how heat shock influences the adaptive immune system . We established a cytotoxic T lymphocyte ( CTL ) clone ( #IM29 ) specific for survivin , one of the tumor-associated antigens ( TAAs ) , from survivin peptide-immunized cancer patients ' peripheral blood , and the CTL activities were investigated in several temperature conditions ( 37-41�C ) . Cytotoxicity and IFN-γ secretion of CTL were greatest under 39�C condition , whereas they were minimum under 41�C . To address the molecular mechanisms of this phenomenon , we investigated the apoptosis status of CTLs , expression of CD3 , CD8 , and TCRαβ by flow cytometry , and expression of perforin , granzyme B , and Fas ligand by western blot analysis . The expression of perforin and granzyme B were upregulated under temperature conditions of 39 and 41�C . On the other hand , CTL cell death was induced under 41�C condition with highest Caspase-3 activity . Therefore , the greatest cytotoxicity activity at 39�C might depend on upregulation of cytotoxic granule proteins including perforin and granzyme B. These results suggest that heat shock enhances effector phase of the adaptive immune system and promotes eradication of microbe and tumor 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: Glycol ethers are known reproductive and developmental toxins in laboratory animals , but little is known about their genotoxic effects in humans . In the current article , the authors tested the hypothesis that human in utero exposure to ethylene glycol monomethyl ether ( EGME ) is associated with the development of specific congenital anomalies and elevated levels of chromosome aberrations . The authors conducted a clinical and cytogenetic evaluation of 41 offspring of 28 females occupationally exposed to EGME for an average duration of 4.6 yr . Six offspring of 5 women who were occupationally exposed to EGME during pregnancy exhibited characteristic dysmorphic features that were not observed in 35 offspring of 23 women who worked in the same facility , but who were not pregnant at the time of exposure . Persistent cytogenetic damage was observed exclusively in all 6 in-utero-exposed offspring , but not in their 12 match non-in-utero-exposed controls . The study characterizes EGME as a human teratogen , as indicated by the prevalence of characteristic dysmorphic features and persistent cytogenetic damage in individuals exposed in utero to this chemical .\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: Proline- , glutamic acid- and leucine-rich protein-1/modulator of non-genomic activity of estrogen receptor ( ER ) ( PELP1/MNAR ) is a novel nuclear receptor ( NR ) co-activator that plays an essential role in the actions of ER . Emerging findings suggest that PELP1/MNAR is a novel proto-oncogene , whose expression is deregulated in several hormone-responsive cancers , including endometrial cancer . In this study , we demonstrate that PELP1/MNAR is widely expressed in endometrial carcinoma cell lines . To investigate its possible role in endometrial carcinoma progression , we adopted an RNA interference technology to downregulate PELP1/MNAR expression in Ishikawa endometrial carcinoma cells . PELP1/MNAR downregulation substantially reduced cell proliferation , and the cells in which PELP1/MNAR expression was knocked down also exhibited a decreased migration and invasion ability , as shown by Boyden chamber and invasion assays . The results showed that the expression of MMP-2 and MMP-9 was also decreased . These results suggest that PELP1/MNAR plays a role in endometrial cancer progression and metastasis , and that PELP1/MNAR may be a potential therapeutic target for endometrial cancer .\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: A 39-year-old male without contributory medical history had sustained progressive double vision , ptosis , and trigeminal pain for 2 weeks . Physical examination revealed total ophthalmoplegia and visual field defect with normal blood examination and chest radiography . Cranial computed tomography revealed a hyperdense mass in the left frontotemporal fossae with bony erosion . Magnetic resonance imaging confirmed a broad-based , intensely enhanced extraaxial tumor of 4x4x4 cm diameter with dural tail sign . Cerebral angiography demonstrated insignificant blood supply both from the internal carotid and middle meningeal arteries . Nearly total tumor resection was achieved via orbitofrontotemporal craniotomy . Intraoperative findings revealed the extraaxial tumor with broad attachment to the dura mater and invasion to the optic and oculomotor nerves . Histological examination revealed hypercellular tumor with significant cell atypism , mitotic activity , and focal necrosis . Immunohistochemical staining was positive for AE1/3 and c-kit , but negative for glial fibrillary acidic protein . Systemic examination performed postoperatively revealed a thymic tumor without additional remote lesions . The final diagnosis was metastatic brain tumor from thymic carcinoma . Rapid progression of neurological impairment inconsistent with a benign extraaxial tumor needs prompt surgical intervention .\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: Interactions of CD70 , a tumor necrosis factor-related cell surface ligand and its receptor , CD27 , are thought to play an important role for T- , B- , and natural killer-cell activation . However , ligation of CD27 can also induce apoptosis . Human glioblastoma is paradigmatic for cancer-associated immunosuppression . We identified CD70 as a radioinducible gene in U87 MG glioma cells . A screening of a panel of human glioma cell lines revealed that 11 of 12 cell lines expressed CD70 mRNA and protein . Two human neuroblastoma cell lines did not express CD70 . CD70 mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53-independent manner . No alteration in CD70 expression was observed after glioma cell exposure to cytotoxic drugs such as lomustine . CD70 protein was also detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic astrocytomas in vivo . CD27 expression was not detected in any glioma cell line , and there was no evidence for autocrine or backward signaling of the CD70 system in human glioma cells . Unexpectedly , CD70 expressed on glioma cells did not increase the immunogenicity of glioma cells in vitro . In contrast , CD70-positive glioma cells induced apoptosis in peripheral blood mononuclear cells ( PBMCs ) in a CD70-dependent manner . Neutralization of CD70 expressed on glioma cells prevented apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures of glioma cells and PBMCs . The effects of CD70-expressing glioma cells on PBMCs were mimicked by agonistic CD27 antibodies . Conversely , the shedding of CD27 by PBMCs was identified as a possible escape mechanism from glioma cell-induced CD70-dependent apoptosis . Thus , induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Sonodynamic therapy ( SDT ) has shown great potential in target cancer therapy , but it induced cell death modes hasn't been fully investigated . This study was to examine autophagic and apoptotic responses to protoporphyrin IX ( PpIX ) mediated SDT in murine leukemia L1210 cells . After SDT , the occurrence of autophagy was identified by morphological observation and biochemical analysis . Meanwhile , the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death . The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies , which indicated that impairment of autophagy enhanced the anti-tumor effect of SDT through induction of apoptosis and necrosis , while caspase inhibition didn't affect autophagic vacuoles formation or protect SDT induced cytotoxicity . The findings supported that autophagic vacuoles formed upstream and independently from caspase-dependent cell death . Additionally , the possible mechanism of SDT-induced autophagy was evaluated by measurement of ROS ( reactive oxygen species ) formation . Result suggested ROS play important role in initiating autophagy , possibly through the sono-damaged mitochondria being enclosed by autophagic vacuoles . All together , these data indicate that autophagy may be cytoprotective in our experimental system , and point to an important insight into how autophagy inhibitors , in combination with SDT may contribute a regimen for cancer therapy .\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: SET and MYND domain-containing protein 3 ( SMYD3 ) is a histone methyltransferase that plays an important role in transcriptional regulation in human carcinogenesis . It can specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes , including several oncogenes ( e.g. , N-myc , CrkL , Wnt10b , RIZ and hTERT ) and genes involved in the control of cell cycle ( e.g. , CyclinG1 and CDK2 ) and signal transduction ( e.g. , STAT1 , MAP3K11 and PIK3CB ) . To determine the effects of SMYD3 over-expression on cell proliferation , we transfected SMYD3 into MDA-MB-231 cells and found that these cells showed several transformed phenotypes as demonstrated by colony growth in soft agar . Besides , we show here that down-regulation of SMYD3 could induce G1-phase cell cycle arrest , indicating the potent induction of apoptosis by SMYD3 knockdown . These results suggest the regulatory mechanisms of SMYD3 on the acceleration of cell cycle and facilitate the development of strategies that may inhibit the progression of cell cycle in breast cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Primary fibroblasts respond to activated H-RAS(V12) by undergoing premature arrest , which resembles replicative senescence . This irreversible ' fail-safe mechanism ' requires p19(ARF) , p53 and the Retinoblastoma ( Rb ) family : upon their disruption , RAS(V12)-expressing cells fail to undergo senescence and continue to proliferate . Similarly , co-expression of oncogenes such as c-MYC or E1A rescues RAS(V12)-induced senescence . To identify novel genes that allow escape from RAS(V12)-induced senescence , we designed an unbiased , retroviral complementary DNA library screen . We report on the identification of DRIL1 , the human orthologue of the mouse Bright and Drosophila dead ringer transcriptional regulators . DRIL1 renders primary murine fibroblasts unresponsive to RAS(V12)-induced anti-proliferative signalling by p19(ARF)/p53/p21(CIP1) , as well as by p16(INK4a) . In this way , DRIL1 not only rescues RAS(V12)-induced senescence but also causes these fibroblasts to become highly oncogenic . Furthermore , DRIL1 immortalizes mouse fibroblasts , in the presence of high levels of p16(INK4a) . Immortalization by DRIL1 , whose product binds the pRB-controlled transcription factor E2F1 ( ref. 8 ) , is correlated with induction of E2F1 activity . Correspondingly , DRIL1 induces the E2F1 target Cyclin E1 , overexpression of which is sufficient to trigger escape from senescence . Thus , DRIL1 disrupts cellular protection against RAS(V12)-induced proliferation downstream of the p19(ARF)/p53 pathway .\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: OBJECTIVE To study the effect of necrostatin ( Nec-1 ) on apoptosis induced by aluminum ( Al ) , and approach the mechanism . METHODS Neural cell death model was made by 4 mmol/L Al treated neuroblastoma cells ( SH-SY5Y ) . Cell viabilities were detected at different concentrations of Al and/or Nec-1 . Hoechst 33342/PI double staining was used to observe apoptosis and ( or ) necrosis that were quantified by flow cytometry using Annexin V/PI double staining . Apoptotic pathway was tested by activities of Caspase-3 , Caspase-8 and Caspase-9 . In addition , the expression of NF-kappa B and Cyt-c was measured by immunocytochemistry . RESULTS Cell viabilities were significantly decreased with the increasing concentrations of Al ( P &lt ; 0.05 ) , which could be significantly upregulated by 60 micromol/L Nec-1 ( P &lt ; 0.05 ) and were correlated with the concentrations of Nec-1 ( P &lt ; 0.05 , P &lt ; 0.01 ) . Apoptosis and necrosis were observed under fluorescent microscope and quantified by flow cytometry , which suggested an increasing trend of apoptotic and necrotic rates ( P &lt ; 0.05 , P &lt ; 0.01 ) . Whereas , Nec-1 could not only decrease the necrotic rate but also apoptotic rate as well ( P &lt ; 0.05 , P &lt ; 0.01 ) . Data of Nec-1 on caspases activities showed that Nec-1 could not affect Caspase-9 activity ( P &gt ; 0.05 ) and Cty-c protein expression as well ( P &gt ; 0.05 ) . However , Nec-1 could reduce Caspase-8 activity significantly ( P &lt ; 0.05 , P &lt ; 0.01 ) and increase NF-kappa B protein expression ( P &lt ; 0.05 , P &lt ; 0.01 ) and finally decrease Caspase-3 activity ( P &lt ; 0.05 ) . CONCLUSION Nec-1 could reduce cell apoptosis induced by Al , through Caspase-8 pathway , and up-regulate the expression of NF-kappa B protein .\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 Tamoxifen , a selective oestrogen receptor modulator ( SERM ) , and brivanib alaninate , a vascular endothelial growth factor receptor 2 ( VEGFR-2 ) inhibitor , are two target specific agents that result in a substantial decrease in tumour growth when given alone . Tamoxifen activates SERM stimulated breast and endometrial tumour growth . Tamoxifen and brivanib alaninate have side-effects that can affect therapeutic outcomes . The primary goal of the current study was to evaluate the therapeutic effects of lower doses of both agents when given in combination to mice with SERM sensitive , oestrogen stimulated tumour xenografts ( MCF-7 E2 tumours ) . Experiments were conducted to evaluate the response of SERM stimulated breast ( MCF-7 Tam , MCF-7 Ral ) and endometrial tumours ( EnCa 101 ) to demonstrate the activity of brivanib alaninate in SERM resistant models . EXPERIMENTAL DESIGN In the current study , tumour xenografts were minced and bi-transplanted into the mammary fat pads of athymic , ovariectomised mice . Preliminary experiments were conducted to determine an effective oral dose of tamoxifen and brivanib alaninate that had minimal effect on tumour growth . Doses of 125 microg of tamoxifen and 0.05 mg/g of brivanib alaninate were evaluated . An experiment was designed to evaluate the effect of the two agents together when started at the time of tumour implantation . An additional experiment was done in which tumours were already established and then treated , to obtain enough tumour tissue for molecular analysis . RESULTS Brivanib alaninate was effective at inhibiting tumour growth in SERM sensitive ( MCF-7 E2 ) and SERM stimulated ( EnCa 101 , MCF-7 Ral , MCF-7 Tam ) models . The effect of the low dose drug combination as an anti-tumour strategy for SERM sensitive ( MCF-7 E2 ) in early treatment was as effective as higher doses of either drug used alone . In established tumours , the combination is successful at decreasing tumour growth , while neither agent alone is effective . Molecular analysis revealed a decreased phosphorylation of VEGFR-2 in tumours that were treated with brivanib alaninate and an increase in VEGFA transcription to compensate for the blockade of VEGFR-2 by increasing the transcription of VEGFA . Tamoxifen increases the phosphorylation of VEGFR-2 and this effect is abrogated by brivanib alaninate . There was also increased necrosis in tumours treated with brivanib alaninate . CONCLUSION Historically , tamoxifen has a role in blocking angiogenesis as well as the blockade of the ER . Tamoxifen and a low dose of an angiogenesis inhibitor , brivanib alaninate , can potentially be combined not only to maximise therapeutic efficacy but also to retard SERM resistant tumour growth .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In our study we investigated the level of apoptosis in PBMCs and the serological level of sFas ( CD95/APO-1 ) in 22 patients with malignant melanoma ( 12 patients with unique cutaneous primary tumour and 10 patients with unique brain metastasis ) . The first determination was performed before tumour excision and the second at 6-7 months after excision . Results in patients with primary tumour in the first determination : 6 patients with over normal values in PBMCs apoptosis and 5 patients with increased values of sFas . In the second determination : apoptosis was increased in 5 patients and sFas level was increased in 4 cases . In patients with metastases in the first determination apoptosis of PBMC was increased in 7 cases and sFas in 5 cases . In the second determination apoptosis was increased in 4 cases and sFas was increased in 4 cases . Our results show that half of the investigated patients presented elevated values of PBMCs apoptosis and Fas receptor both before and 6-7 months after tumour excision . Apoptosis values for PBMCs and sFas values were with 1/4 higher than normals . There was no difference in clinical evolution of the patients with normal or increased values for studied parameters . Clinical evolution was performed for 1 year . The presence of increased values for PBMCs and sFas after tumour excision , primary or metastasis is surprising and hard to explain . It is possible that tumoral evolution induces a disregulation at PBMCs level or other cells level that persists unexpectedly , after tumour excision or apoptotic processes , in a certain level to be independent and anterior to tumour development .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A 34-year-old Japanese woman presented with left supraclavicular lymph node swelling . Computed tomography scans revealed a mass on the left lower lobe , pulmonary nodules , and pleural effusion . A lymph node biopsy revealed large-cell carcinoma with an epidermal growth factor receptor ( EGFR ) deletion mutation , L747-T751 in exon 19 . Although malignant pleural effusions carried the same EGFR mutation , progressive pleural effusions after treatment with chemotherapy , gefitinib , and erlotinib did not show any EGFR mutation . A cell line established from the pleural effusion 3 days before the patient expired also did not harbor the EGFR mutation . Histological sections of the lymph node of the patient were similar to those of the xenograft tumor of the cell line . There may be genetic heterogeneity in EGFR mutant tumors .\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: Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma ( LGNPPA ) is extremely rare ; only four cases have been reported . Herein are presented the case reports of two Japanese male patients with thyroid-like LGNPPA . Macroscopically , these tumors were pedunculated polypoid masses on the roof of the nasopharynx . Microscopically , they were characterized by papillary and glandular epithelial proliferation . The papillae were complex and tightly packed with hyalinized fibrovascular cores and lined by columnar and pseudostratified cells with intervening spindle-shaped cells . Both cell types had round to oval vesicular nuclei with tiny nucleoli and mildly eosinophilic cytoplasm . Mitotic figures were not evident and necrosis was not observed . Psammoma bodies were seen focally in one of the patients . Transition from normal surface epithelium to tumor cells was identified in both cases . On immunohistochemistry the tumor cells were positive for cytokeratin ( CK)7 , CK19 , thyroid transcription factor-1 ( TTF-1 ) and vimentin . They were negative for CK5/6 , CK20 , thyroglobulin , S-100 protein and CD15 . In situ hybridization for EBV was negative . Nasopharyngeal tumors with similar morphological appearance should be examined for TTF-1 immunoreactivity , and patients should be clinically followed to determine the course of this unusual disease and the significance of TTF-1 expression .\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: Prostate cancer is the most frequent and second most lethal cancer in men in the United States . Innate immunity and inflammation may increase the risk of prostate cancer . To determine the role of innate immunity and inflammation in advanced prostate cancer , we investigated the association of 320 single nucleotide polymorphisms , located in 46 genes involved in this pathway , with disease risk using 494 cases with advanced disease and 536 controls from Cleveland , Ohio . Taken together , the whole pathway was associated with advanced prostate cancer risk ( P = 0.02 ) . Two sub-pathways ( intracellular antiviral molecules and extracellular pattern recognition ) and four genes in these sub-pathways ( TLR1 , TLR6 , OAS1 , and OAS2 ) were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk . Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects .\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: AMP-activated protein kinase ( AMPK ) has been implicated in anti-proliferative actions in a range of cell systems . Recently , it was observed that Compound C , an inhibitor of AMPK , also reduced the cell viability in human diploid fibroblasts ( HDFs ) . Compound C-induced growth arrest was associated with a decrease in the cell cycle regulatory proteins , such as proliferating cell nuclear antigen , phosphorylated pRB , cyclin-dependent protein kinases ( Cdk 2 and 4 ) , cyclins ( D and E ) , and the Cdk inhibitors ( p21 , p16 , and p27 ) . Therefore , the present study examined the molecular mechanism of the antiproliferative effects of Compound C. Although Compound C inhibited serum-induced phosphorylation of Akt and its substrate , glycogen synthase kinase-3β , it did not affect the Akt activity in vitro . Compound C significantly inhibited the receptor tyrosine phosphorylation and the activity of downstream signaling molecules , such as p85 phosphoinositide 3-kinase , phospholipase C-γ1 , and extracellular signal-regulated kinase 1/2 , induced by platelet-derived growth factor ( PDGF ) but not by epidermal growth factor- and insulin-like growth factor . In vitro growth factor receptor tyrosine kinase activity profiling revealed the IC(50) for PDGF receptor-β ( PDGFRβ ) to be 5.07 μM , whereas the IC(50) for the epidermal growth factor receptor and insulin-like growth factor receptor was ≥100 μM . The inhibitory effect of Compound C on PDGFRβ and Akt was also observed in AMPKα(1)/α(2)-knockout mouse embryonic fibroblasts , indicating that its inhibitory effect is independent of the AMPK activity . The inhibitory effect of Compound C on cell proliferation and PDGFRβ tyrosine phosphorylation was also demonstrated in various PDGFR-expressing cells , including MRC-5 , BEAS-2B , rat aortic vascular smooth muscle cells , and A172 glioblastoma cells . These results indicate that Compound C can be used as a potential antiproliferative agent for PDGF- or PDGFR-associated diseases , such as cancer , atherosclerosis , and fibrosis .\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: Spindle cell oncocytoma ( SCO ) of the pituitary gland is a relatively recently established , very rare subtype of adenohypophysis tumours that was introduced as a distinct clinicopathological entity in the fourth edition of WHO classification of the central nervous system tumours ( 2007 ) . It is non-endocrine neoplasm of the anterior pituitary that occurs in adults and usually follows a benign clinical course , corresponding to WHO grade I. Up to now , pituitary SCO have been reported occasionally and only 14 cases of SCO have been documented in the literature . Because of their rarity , the pathogenesis and natural history of these tumours have not been fully characterized . We report two additional cases of SCO occurring in females aged 63 years ( Case 1 ) and 65 years ( Case 2 ) , who presented with pan-hypopituitarism , headache and visual field defect . In both cases , the magnetic resonance imaging showed solid sellar mass of moderate size with suprasellar extension . The clinical and radiological features suggested non-functioning pituitary macroadenomas without evidence of invasive growth . One patient presented with tumour recurrence 3 years after undergoing the previous surgical removal of tumour , which was initially misdiagnosed as schwannoma . The first tumour was removed by transsphenoidal surgery and the second one by frontal craniotomy . Histologically and immunohistochemically , both tumours displayed the features typical for SCO of the pituitary . They were composed of interwoven fascicles of spindle cells exhibiting abundant eosinophilic cytoplasm of oncocytic or granular appearance . Mitoses were rarely observed and necrosis was absent . In one case , the advanced lymphocytic infliltration was observed within neoplastic tissue . The tumour cells exhibited immunoreactivity for S-100 protein , galectin-3 , vimentin and epithelial membrane antigen but they were negative for GFAP , anterior pituitary neuroendocrine markers ( prolactin , growth hormone , TSH , ACTH , FSH , LH ) , chromogranin , synaptophysin , cytokeratin CK ( AE1/AE3 ) , smooth muscle actin , desmin , CD34 and CD68 . MIB1 labeling index did not exceed 10% . Ultrastructurally , the tumour cells were rich in mitochondria with lamellar cristae . Moreover , in Case 2 some tumour cells showed a number of giant mitochondria with severely destructed internal matrix . Spindle cell oncocytoma of the anterior pituitary is often misdiagnosed entity of uncertain histogenesis . It should be considered in the differential diagnosis of various sellar-region lesions of oncocytic morphology .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The identification of molecular markers related to critical biological processes during carcinogenesis may aid in the evaluation of carcinogenic potentials of chemicals and chemical mixtures . Work from our laboratory demonstrated that a single treatment with N-methyl-N'-nitro-N-nitrosoguanidine ( MNNG ) enhanced spontaneous malignant transformation of the human keratinocyte cell line RHEK-1 . In contrast , chronic low-level exposure of cells to arsenic alone or in a mixture containing arsenic , cadmium , chromium , and lead inhibited malignant conversion . To identify changes in gene expression that influence these different outcomes , cDNA microarray technology was used . Analysis of multiple human arrays in MNNG-transformed RHEK-1 cells , designated OM3 , and those treated with arsenic or the arsenic-containing metal mixture showed unique patterns of gene expression . Genes that were overexpressed in OM3 included oncogenes , cell cycle regulators , and those involved in signal transduction , whereas genes for DNA repair enzymes and inhibitors of transformation and metastasis were suppressed . In arsenic-treated cells , multiple DNA repair proteins were overexpressed . Mixture-treated cells showed increased expression of a variety of genes including metallothioneins and integrin 4 . These cells showed decreased expression of oncogenes , DNA repair proteins , and genes involved in the mitogen-activated protein kinase pathway . For comparison we are currently analyzing gene expression changes in RHEK-1 cells transformed by other means . The goal of these studies is to identify common batteries of genes affected by chemical modulators of the carcinogenic process . Mechanistic studies may allow us to correlate alterations in their expression with sequential stages in the carcinogenic process and may aid in the risk assessment of other xenobiotics .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;evading growth suppressors;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: Mitochondrial uncoupling protein 2 ( UCP2 ) can moderate oxidative stress by favoring the influx of protons into the mitochondrial matrix , thus reducing electron leakage from respiratory chain and mitochondrial superoxide production . Here , we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly increases reactive oxygen species ( ROS ) production inhibiting pancreatic adenocarcinoma cell growth . We also show that UCP2 inhibition triggers ROS-dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase ( GAPDH ) , formation of autophagosomes , and the expression of the autophagy marker LC3-II . Consistently , UCP2 over-expression significantly reduces basal autophagy confirming the anti-autophagic role of UCP2 . Furthermore , we demonstrate that autophagy induced by UCP2 inhibition determines a ROS-dependent cell death , as indicated by the apoptosis decrease in the presence of the autophagy inhibitors chloroquine ( CQ ) or 3-methyladenine ( 3-MA ) , or the radical scavenger NAC . Intriguingly , the autophagy induced by genipin is able to potentiate the autophagic cell death triggered by gemcitabine , the standard chemotherapeutic drug for pancreatic adenocarcinoma , supporting the development of an anti-cancer therapy based on UCP2 inhibition associated to standard chemotherapy . Our results demonstrate for the first time that UCP2 plays a role in autophagy regulation bringing new insights into mitochondrial uncoupling protein field .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The down-regulation of dominant oncogenes , including C-MYC , in tumor cells often leads to the induction of senescence via mechanisms that are not completely identified . In the current study , we demonstrate that MYC-depleted melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase ( TS ) and ribonucleotide reductase ( RR ) and subsequent depletion of deoxyribonucleoside triphosphate pools . Simultaneous genetic inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones caused by MYC-depletion . Reciprocally , overexpression of TS and RR in melanoma cells or addition of deoxyribo-nucleosides to culture media substantially inhibited DNA damage and senescence-associated phenotypes caused by C-MYC depletion . Our data demonstrate the essential role of TS and RR in C-MYC-dependent suppression of senescence in melanoma cells .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;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: INTRODUCTION HER2 and estrogen receptor ( ER ) are important in breast cancer and are therapeutic targets of trastuzumab ( Herceptin ) and tamoxifen , respectively . Retinoids inhibit breast cancer growth , and modulate signaling by HER2 and ER . We hypothesized that treatment with retinoids and simultaneous targeting of HER2 and/or ER may have enhanced anti-tumor effects . METHODS The effects of retinoids combined with trastuzumab or tamoxifen were examined in two human breast cancer cell lines in culture , BT474 and SKBR3 . Assays of proliferation , apoptosis , differentiation , cell cycle distribution , and receptor signaling were performed . RESULTS In HER2-overexpressing/ER-positive BT474 cells , combining all-trans retinoic acid ( atRA ) with tamoxifen or trastuzumab synergistically inhibited cell growth , and altered cell differentiation and cell cycle . Only atRA/trastuzumab-containing combinations induced apoptosis . BT474 and HER2-overexpressing/ER-negative SKBR3 cells were treated with a panel of retinoids ( atRA , 9-cis-retinoic acid , 13-cis-retinoic acid , or N-(4-hydroxyphenyl) retinamide ( fenretinide ) ( 4-HPR) ) combined with trastuzumab . In BT474 cells , none of the single agents except 4-HPR induced apoptosis , but again combinations of each retinoid with trastuzumab did induce apoptosis . In contrast , the single retinoid agents did cause apoptosis in SKBR3 cells ; this was only modestly enhanced by addition of trastuzumab . The retinoid drug combinations altered signaling by HER2 and ER . Retinoids were inactive in trastuzumab-resistant BT474 cells . CONCLUSIONS Combining retinoids with trastuzumab maximally inhibits cell growth and induces apoptosis in trastuzumab-sensitive cells . Treatment with such combinations may have benefit for breast cancer patients .\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 effect of polychlorinated biphenyls ( PCBs ) on Vero cell proliferation was investigated , with the attempts to assess the possible hormetic dose-response and to compare their structure-dependent toxicity . Both PCB congeners revealed low doses stimulation in our experiment . However , significant cytotoxicity was only observed in PCB 52 concentrations larger than 0.1 microg ml(-1) , while there was no significant inhibition in PCB 77-treated cells at concentrations selected . Furthermore , the time-dependent cytotoxic trends were different . The comparison between PCB 52 and PCB 77 indicated that the cytotoxic mechanisms involved in coplanar or non-coplanar PCB congener exposure were different , and this difference might be associated with individual genotoxicity and the release of contact inhibition , respectively .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aberrant expression of human epidermal growth factor receptor-2 ( HER-2 ) has been detected in ovarian cancer . However , the role of HER-2 in the development of ovarian cancer has not been sufficiently elucidated . The objective of this study was to determine the role of HER-2 in the apoptosis and metastasis of SKOV-3 ovarian cancer cells . SKOV-3 cells were transfected with three double‑stranded small interfering RNA ( siRNA ) molecules that target HER-2 . Various sequences were synthesized by T7 transcription invitro to select the most effective HER-2‑silencing siRNA . SKOV-3 cells were examined for growth inhibition using the MTT proliferation assay and apoptosis was assessed using flow cytometry and TUNEL assay . The Matrigel basement memebrane matrix was used to assess invasion and chemotactic mobility , as a model of tumor cell metastasis . Western blot analysis was used to detect the expression of matrix metallopeptidase-9 ( MMP-9 ) , E-cadherin , N-cadherin and vimentin. siRNA interference in HER-2 resulted in decreased cell proliferation and invasion and increased apoptosis . Western blot analysis demonstrated a marked increase in E-cadherin and MMP-9 and a reduction in N-cadherin and vimentin protein levels in the SKOV-3 cells . The suppression of HER-2 expression resulted in apoptosis and the inhibition of metastasis of SKOV-3 cells . Therefore , the overexpression of the HER-2 gene can enhance the metastatic potential of SKOV-3 cells by increasing the protein levels of MMP-9 . Epithelial-mesenchymal transition may be involved in the HER-2 siRNA-induced invasion and migration of SKOV-3 cells . Taken together , these results suggest that HER-2 functions as an oncogene and may thus be an attractive therapeutic target in SKOV-3 ovarian cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: Neuroblastoma ( NB ) , a common pediatric neoplasm , consists of two main cell populations : neuroblastic/ganglionic cells and Schwann cells . NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors . Recent studies suggest that Schwann cells influence NB tumor growth via secreted factors that induce differentiation , suppress proliferation , and inhibit angiogenesis . Two angiogenesis inhibitors , pigment epithelium-derived factor and tissue inhibitor of metalloproteinase-2 , have been detected in Schwann cell secretions . Here , we isolated another Schwann cell-derived secreted inhibitor of angiogenesis , a 43-kDa protein identified as SPARC ( secreted protein acidic and rich in cysteine ) , an extracellular matrix protein . We found SPARC to be critical for the antiangiogenic phenotype of cultured Schwann cells . We also show that purified SPARC potently inhibits angiogenesis and significantly impairs NB tumor growth in vivo . SPARC may be an effective candidate for the treatment of children with clinically aggressive , Schwannian stroma-poor NB tumors .\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: Depression is the most common psychiatric syndrome in cancer patients and adversely affects anti-cancer immune system and life quality of patients . Antidepressant desipramine ( DMI ) is clinically prescribed in the auxiliary treatment of cancer patients . Increasing evidences suggest that DMI has a broad spectrum of target-off biological effects , such as anticancer properties . Our previous study revealed that DMI at the clinical relevant concentrations could induce CHOP-dependent apoptotic death in C6 glioma cells . In this study , we further explored the pro-autophagic effect of DMI in C6 glioma cells and its underlying mechanism . Treatment with DMI could induce autophagic cell death characterized by the formation of autophagosome and the elevated level of autophagic protein Beclin-1 and cellular redistribution of marker LC3 . Meanwhile , DMI inhibited the activation of PI3K-AKT-mTOR pathway which is considered as a negative regulator of autophagy . Furthermore , DMI activated PERK-eIF2α and ATF6 of endoplasmic reticulum ( ER ) stress pathway , while knockdown of PERK with the PERK-specific short interfering RNA ( siRNA ) could obviously attenuate the autophagy . The results strongly suggested that DMI could induce autophagy through the PERK-ER stress pathway in C6 glioma cells . Our findings provided new insights into another beneficial potential of antidepressant DMI in the adjuvant therapy of cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines ( LCLs ) . EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation , which facilitates G1 to S transition controlled by the major transcriptional activator E2F1 . E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways . In this study , we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis , as a possible consequence of both p53- and E2F1-mediated activities . Importantly , EBNA3C was previously shown to suppress p53-induced apoptosis . Now , we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis , as well as its anti-proliferative effects in a p53-independent manner , in response to DNA damage . The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis . Mechanistically , we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes , and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion . Moreover , in response to DNA damage , E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability . In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired ; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis . This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas .\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: Lung cancers express the cholinergic autocrine loop , which facilitates the progression of cancer cells . The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers ( SCLCs ) . In this study we intended to investigate the growth inhibitory effect of R2HBJJ , a novel muscarinic antagonist , on non-small cell lung cancer ( NSCLC ) cells and the possible mechanisms . The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs . R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea . R2HBJJ markedly suppressed the growth of NSCLC cells , such as H1299 , H460 and H157 . In H1299 cells , both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin . Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition . Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection , respectively . Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb . Therefore , the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells . R2HBJJ , as a novel mAChRs antagonist , can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth , which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC .\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: INTRODUCTION The insulin-like growth factor I receptor ( IGF-IR ) pathway plays a major role in cancer growth , tumor cell survival and resistance to therapy . BACKGROUND Preclinical evidence that targeting the IGF-IR is effective in cancer treatment has been accumulating for almost 2 decades . Early clinical trials revealed an acceptable safety profile together with pharmacodynamic evidence that the receptor can be targeted successfully . It is premature to draw conclusions regarding the therapeutic potential of this class of compounds but well-documented single-agent activity was noted during phase I evaluations , and recent evidence from a phase-II study suggests that co-administration of an anti-IGF-1R antibody with chemotherapy for non-small-cell lung cancer ( NSCLC ) improves objective response rate and progression-free survival . VIEWPOINTS These early results are a strong indication for continued research on the targeting of IGF-R , particularly in the treatment of NSCLC . CONCLUSIONS Today , IGF-1R targeting appears a promising approach , more than two dozen compounds have been developed and clinical trials are underway .\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: Objective . The present study was performed to investigate the effect of N-desulfated heparin on basic fibroblast growth factor ( bFGF ) expression , tumor angiogenesis and metastasis of gastric carcinoma . Methods . Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of NOD SCID mice . Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution ( normal saline group ) or 10 mg/kg N-desulfated heparin ( N-desulfated heparin group ) twice weekly for three weeks . In vitro , human gastric carcinoma SGC-7901 cells were treated with N-desulfated heparin in different concentration ( 0.1 mg/mL , 1 mg/mL , N-desulfated heparin group ) , and treated with medium ( control group ) . Results . In vivo , the tumor metastasis rates were 9/10 in normal saline group and 2/10 in N-desulfated heparin group ( P &lt ; 0.05 ) . The intratumoral microvessel density was higher in normal saline group than in N-desulfated heparin group ( P &lt ; 0.05). bFGF expression in gastric tissue was inhibited by N-desulfated heparin ( P &lt ; 0.05 ) . There was no bleeding in N-desulfated heparin group . In vitro , N-desulfated heparin inhibited significantly bFGF protein and mRNA expression of gastric carcinoma cells ( P &lt ; 0.05 ) . Conclusions . N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF expression and tumor angiogenesis with no obvious anticoagulant activity .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Deregulation of D-type cyclin-dependent kinases ( CDK4 and 6 ) is widely observed in various human cancers , illustrating their importance in cell cycle control . Like other cyclin-dependent kinases ( CDKs ) , assembly with cyclins is the most critical step for activation of CDK4/6 . As previously reported elsewhere , we observed that the level of cyclinD1-CDK4 complex and its associated kinase activity were significantly low in asynchronously proliferating mouse embryo fibroblasts lacking both p21(Cip1) and p27(Kip1) ( p21/p27-null MEFs ) . These evidences imply that p21(Cip1) and p27(Kip1) CDK inhibitors are ' essential activators ' of cyclin D-kinases . We , however , discovered here that both the assembly and activation of cyclin D1-CDK4 complex occur when quiescent p21/p27-null MEFs were stimulated to re-enter the cell cycle . This mitogen-induced cyclin D1-kinase activity was blocked by overexpression of p16(INK4a) and resulted in the inhibition of S phase entry in p21/p27-null MEFs . Furthermore , ectopic expression of p34(SEI-1) , a mitogen-induced CDK4 binding protein , increased the levels of active cyclinD1-CDK4 complex in asynchronously proliferating p21/p27-null MEFs . Together , our results suggest that there are several independent ways to stimulate the assembly of cyclin D1-CDK4 kinases . Although p21(Cip1) and p27(Kip1) play a role in this process , our results demonstrate that additional mechanisms must occur in G0 to S phase transition .\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: A distinct group of breast cancers , called \" basal \" or \" triple-negative \" ( TN ) cancers express both basal cytokeratins and the epidermal growth factor receptor , but fail to express estrogen receptors , progesterone receptors or HER2 and have stem-like or mesenchymal features . They are particularly aggressive , are frequently chemo-resistant , with p53 mutation , up-regulation of IL-6 and Stat3 . Because TN cells are particularly sensitive to the anti-diabetic agent metformin , we hypothesized that it may target JAK2/Stat3 signaling . The effects of metformin upon Stat3 expression and activation were examined in four human TN cell lines . Metformin's effects were also studied in sublines with forced over-expression of constitutively active ( CA ) Stat3 , as well as lines with stable knockdown of Stat3 . Metformin inhibited Stat3 activation ( P-Stat3 ) at Tyr705 and Ser727 and downstream signaling in each of the four parental cell lines . CA-Stat3 transfection attenuated , whereas Stat3 knockdown enhanced , the effects of metformin upon growth inhibition and apoptosis induction . A Stat3 specific inhibitor acted synergistically with metformin in reducing cell growth and inducing apoptosis . An mTOR inhibitor showed no significant interaction with metformin . In summary , Stat3 is a critical regulator of metformin action in TN cancer cells , providing the potential for enhancing metformin's efficacy in the clinical setting .\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: Fifty-six previously untreated stage-I ( according to Rai ) chronic lymphocytic leukemia ( CLL ) patients were examined for their clinical data , immunological characteristics , and hormonal values . Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin ( PHA ) , concanavalin A ( ConA ) , pisum sativatum agglutinin ( PSA ) , wheat germ agglutinin ( WGA ) , recombinant interleukin 2 ( IL 2 ) , and dextran sulfate ( DxS ) ; also by decreased immunoglobulin levels ( IgG , IgA , IgE ) and increased beta 2-microglobulin ( beta 2-M ) values . Simultaneously , dysregulation of the hypothalamic-pituitary-adrenal axis , immune system integration , imbalance of sex hormones , and changes in thyroid hormones were observed in the same group of patients . Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy .\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: INTRODUCTION Necrosis at the tumor center is a common feature of aggressive breast cancers and has been associated with poor prognosis . It is commonly identified by means of invasive histopathology , which often correlates with morbidity and potential tumor cell dissemination , and limits the reconstruction of the whole necrotic domain . In this study we hypothesized that non covalent association to serum albumin ( SA ) and covalent binding to ligands for tumor-abundant cell receptors should synergistically drive selective accumulation and prolonged retention of imaging and therapeutic agents in breast tumor necrotic domains enabling in vivo identification , imaging and possibly treatment of such tumors . METHODS Cyclo-Arg-Gly-Asp-D-Phe-Lys ( c(RGDfK) ) were conjugated to bacteriochlorophyll-derivatives ( Bchl-Ds ) , previously developed as photodynamic agents , fluorescent probes and metal chelators in our lab . The c(RGDfK) component drives ligation to alphaVbeta3 integrin receptors over-expressed by tumor cells and neo-vessels , and the Bchl-D component associates to SA in a non-covalent manner . STL-6014 , a c(RGDfK)-Bchl-D representative , was i.v. injected to CD-1 , nude female mice bearing necrotic and non-necrotic human MDA-MB-231-RFP breast cancer tumors . The fluorescence signals of the Bchl-Ds and RFP were monitored over days after treatment , by quantitative whole body imaging and excised tumor/tissue samples derived thereof . Complementary experiments included competitive inhibition of STL-6014 uptake by free c(RGDfK) , comparative pharmacokinetics of nonconjugated c(RGDfK) Bchl-D ( STL-7012 ) and of two human serum albumin ( HSA ) conjugates : HSA-STL-7012 and HSA-STL-6014 . RESULTS STL-6014 and STL-7012 formed complexes with HSA ( HSA/STL-6014 , HSA/STL-7012 ) . STL-6014 , HSA-STL-7012 and HSA-STL-6014 , selectively accumulated at similar rates , in tumor viable regions over the first 8 h post administration . They then migrated into the necrotic tumor domain and presented tumor half lifetimes ( T1/2 ) in the range of days where T1/2 for HSA-STL-6014 &gt ; STL-6014 &gt ; HSA-STL-7012 . No accumulation of STL-7012 was observed . Pre-injection of c(RGDfK) excess , prevented the uptake of STL-6014 in the small , but not in the large tumors . CONCLUSIONS Non-covalent association to SA and covalent binding to c(RGDfK) , synergistically enable the accumulation and prolonged retention of Bchl-Ds in the necrotic regions of tumors . These findings provide novel guidelines and strategy for imaging and treatment of necrotic tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Ruthenium(II) methylimidazole complexes , with the general formula [ Ru(MeIm)(4)(N⌢N)](2+) ( N⌢N=tip ( RMC1 ) , iip ( RMC2 ) , dppz ( RMC3 ) , dpq ( RMC4 ) ; MeIm=1-methylimidazole , tip=2-(thiophene-2-yl)-1H-imidazo [ 4,5-f ] [ 1,10]phenanthroline , iip=2-(1H-imidazol-4-yl)-1H-imidazo [ 4,5-f ] [ 1,10]phenanthroline , dppz=dipyrido[3,2-a:2',3'-c]phenazine , dpq=pyrazino [ 2,3-f ] [ 1,10]phenanthroline ) , were synthesized and characterized . As determined by MTT ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) assay , these complexes displayed potent anti-proliferation activity against various cancer cells . RMC1 inhibited the growth of A549 ( human lung adenocarcinoma ) lung cells through induction of apoptotic cell death , as evidenced by the accumulation of cell population in sub-G1 phase . RMC1 also induced the depletion of mitochondrial membrane potential in A549 cells by regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members . Another experiment showed that Bid protein was also activated by RMC1 , which implied that RMC1 could existed two pathways crosstalk , namely , have exogenous death receptor signaling pathway . These results demonstrated that RMC1 induced cancer cell death by acting on both mitochondrial and death receptor apoptotic pathways , suggesting that RMC1 could be a candidate for further evaluation as a chemotherapeutic agent against human cancers .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The main feedback loop driving circadian rhythm in mice is controlled , in part , by the genes encoding the cryptochromes Cry1 and Cry2 . Targeted mutation of both Cry1 and Cry2 delay the early onset of tumor formation in p53-null mutant mice . Furthermore , Ras-transformed p53- and Cry-null mouse skin fibroblasts are more sensitive than p53 mutants to apoptotic cell death initiated by agents that activate either the intrinsic or the extrinsic apoptosis pathways . Here , we investigated the effect of Cry1 and Cry2 mutations on cell death by other genotoxic agents that generate alkylated bases , interstrand crosslinks , DNA-protein crosslinks , and double-strand breaks . Both ultraviolet ( UV ) and the UV mimetic compound oxaliplatin and the radiomimetic compound doxorubicin promoted apoptosis by upregulating the tumor suppressor p73 . However , only the UV and oxaliplatin-induced upregulation of p73 mediated by the transcription factor Egr1 , but not the doxorubicin-induced upregulation mediated by the transcription factor E2F1 , was enhanced by Cry1/Cry2 double mutation . Accordingly , Egr1 downregulation reduced oxaliplatin-induced apoptosis , whereas E2F1 downregulation reduced doxorubicin-induced apoptosis . Our findings establish distinct roles for cryptochromes in intrinsic apoptosis induced by UV mimetic and radiomimetic agents .\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: Silver nanoparticles ( Ag-np ) have been used in medicine and commercially due to their anti-microbial properties . Therapeutic potentials of these nanoparticles are being explored extensively despite the lack of information on their mechanism of action at molecular and cellular level . Here , we have investigated the DNA damage response and repair following Ag-np treatment in mammalian cells . Studies have shown that Ag-np exerts genotoxicity through double-strand breaks ( DSBs ) . DNA-PKcs , the catalytic subunit of DNA dependent protein kinase , is an important caretaker of the genome which is known to be the main player mediating Non-homologous End-Joining ( NHEJ ) repair pathway . We hypothesize that DNA-PKcs is responsible for the repair of Ag-np induced DNA damage . In vitro studies have been carried out to investigate both cytotoxicity and genotoxicity induced by Ag-np in normal human cells , DNA-PKcs proficient , and deficient mammalian cells . Chemical inhibition of DNA-PKcs activity with NU7026 , an ATP-competitive inhibitor of DNA-PKcs , has been performed to further validate the role of DNA-PKcs in this model . Our results suggest that Ag-np induced more prominent dose-dependent decrease in cell viability in DNA-PKcs deficient or inhibited cells . The deficiency or inhibition of DNA-PKcs renders the cells with higher susceptibility to DNA damage and genome instability which in turn contributed to greater cell cycle arrest/cell death . These findings support the fact that DNA-PKcs is involved in the repair of Ag-np induced genotoxicity and NHEJ repair pathway and DNA-PKcs particularly is activated to safeguard the genome upon Ag-np exposure .\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: DNA damage checkpoints in the cell cycle may be important barriers against cancer progression in human cells . Fanconi anemia ( FA ) is an inherited DNA instability disorder that is associated with bone marrow failure and a strong predisposition to cancer . Although FA cells experience constitutive chromosomal breaks , cell cycle arrest at the G2 DNA damage checkpoint , and an excess of cell death , some patients do become clinically stable , and the mechanisms underlying this , other than spontaneous reversion of the disease-causing mutation , are not well understood . Here we have defined a clonal phenotype , termed attenuation , in which FA patients acquire an abrogation of the G2 checkpoint arrest . Attenuated cells expressed lower levels of CHK1 ( also known as CHEK1 ) and p53 . The attenuation could be recapitulated by modulating the ATR/CHK1 pathway , and CHK1 inhibition protected FA cells from cell death . FA patients who expressed the attenuated phenotype had mild bone marrow deficiency and reached adulthood , but several of them eventually developed myelodysplasia or leukemia . Better understanding of attenuation might help predict a patient's clinical course and guide choice of treatment . Our results also highlight the importance of evaluating the cellular DNA damage checkpoint and repair pathways in cancer therapies in general .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: TGF-β derived from bone fuels melanoma bone metastases by inducing tumor secretion of prometastatic factors that act on bone cells to change the skeletal microenvironment . Halofuginone is a plant alkaloid derivative that blocks TGF-β signaling with antiangiogenic and antiproliferative properties . Here , we show for the first time that halofuginone therapy decreases development and progression of bone metastasis caused by melanoma cells through the inhibition of TGF-β signaling . Halofuginone treatment of human melanoma cells inhibited cell proliferation , phosphorylation of SMAD proteins in response to TGF-β , and TGF-β-induced SMAD-driven transcription . In addition , halofuginone reduced expression of TGF-β target genes that enhance bone metastases , including PTHrP , CTGF , CXCR4 , and IL11 . Also , cell apoptosis was increased in response to halofuginone . In nude mice inoculated with 1205Lu melanoma cells , a preventive protocol with halofuginone inhibited bone metastasis . The beneficial effects of halofuginone treatment were comparable with those observed with other anti-TGF-β strategies , including systemic administration of SD208 , a small-molecule inhibitor of TGF-β receptor I kinase , or forced overexpression of Smad7 , a negative regulator of TGF-β signaling . Furthermore , mice with established bone metastases treated with halofuginone had significantly less osteolysis than mice receiving placebo assessed by radiography . Thus , halofuginone is also effective in reducing the progression of melanoma bone metastases . Moreover , halofuginone treatment reduced melanoma metastasis to the brain , showing the potential of this novel treatment against cancer metastasis . Cancer Res ; 72(23) ; 6247-56. �2012 AACR .\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: Neurofibromatosis type 2 patients develop schwannomas , meningiomas and ependymomas resulting from mutations in the tumor suppressor gene , NF2 , encoding a membrane-cytoskeleton adapter protein called merlin . Merlin regulates contact inhibition of growth and controls the availability of growth factor receptors at the cell surface . We tested if microtubule-based vesicular trafficking might be a mechanism by which merlin acts . We found that schwannoma cells , containing merlin mutations and constitutive activation of the Rho/Rac family of GTPases , had decreased intracellular vesicular trafficking relative to normal human Schwann cells . In Nf2-/- mouse Schwann ( SC4 ) cells , re-expression of merlin as well as inhibition of Rac or its effector kinases , MLK and p38(SAPK) , each increased the velocity of Rab6 positive exocytic vesicles . Conversely , an activated Rac mutant decreased Rab6 vesicle velocity . Vesicle motility assays in isolated squid axoplasm further demonstrated that both mutant merlin and active Rac specifically reduce anterograde microtubule-based transport of vesicles dependent upon the activity of p38(SAPK) kinase . Taken together , our data suggest loss of merlin results in the Rac-dependent decrease of anterograde trafficking of exocytic vesicles , representing a possible mechanism controlling the concentration of growth factor receptors at the cell surface .\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: The immune system of vertebrates is able to detect bacterial DNA based on the presence of unmethylated CpG motifs . We examined the therapeutic potential of oligodeoxynucleotides with CpG motifs ( CpG ODN ) in a colon carcinoma model in BALB/c mice . Tumors were induced by s.c. injection of syngeneic C26 cells or Renca kidney cancer cells as a control . Injection of CpG ODN alone or in combination with irradiated tumor cells did not protect mice against subsequent tumor challenge . In contrast , weekly injections of CpG ODN into the margin of already established tumors resulted in regression of tumors and complete cure of mice . The injection site was critical , since injection of CpG ODN at distant sites was not effective . Mice with two bilateral C26 tumors rejected both tumors upon peritumoral injection of one tumor , indicating the development of a systemic immune response . The tumor specificity of the immune response was demonstrated in mice bearing a C26 tumor and a Renca tumor at the same time . Mice that rejected a tumor upon peritumoral CpG treatment remained tumor free and were protected against rechallenge with the same tumor cells , but not with the other tumor , demonstrating long term memory . Tumor-specific CD8 T cells as well as innate effector cells contributed to the antitumor activity of treatment . In conclusion , peritumoral CpG ODN monotherapy elicits a strong CD8 T cell response and innate effector mechanisms that seem to act in concert to overcome unresponsiveness of the immune system toward a growing tumor .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors . Agro-industrial wastes , such as cotton and curaua fibers , are used to prepare nanofibers for use in thermoplastic films , where they are combined with polymeric matrices , and in biomedical applications such as tissue engineering , amongst other applications . The development of products containing nanofibers offers a promising alternative for the use of agricultural products , adding value to the chains of production . However , the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated . This has resulted in the creation of the new area of nanotoxicology , which addresses the toxicological aspects of these materials . PURPOSE AND METHODS Contributing to these developments , the present work involved a genotoxicological study of different nanofibers , employing chromosomal aberration and comet assays , as well as cytogenetic and molecular analyses , to obtain preliminary information concerning nanofiber safety . The methodology consisted of exposure of Allium cepa roots , and animal cell cultures ( lymphocytes and fibroblasts ) , to different types of nanofibers . Negative controls , without nanofibers present in the medium , were used for comparison . RESULTS The nanofibers induced different responses according to the cell type used . In plant cells , the most genotoxic nanofibers were those derived from green , white , and brown cotton , and curaua , while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua . An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed . CONCLUSION This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental impacts .\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: A number of cancer chemotherapeutic drugs designed to have cytotoxic actions on tumor cells have recently been shown to also have antiangiogenic activities . Endothelial cell migration and proliferation are key components of tumor angiogenesis , and agents that target the microtubule cytoskeleton can interfere with these processes . In this study , the effect on endothelial cell functions of the microtubule-stabilizing drugs Taxotere and Taxol were evaluated in three in vitro assays : a chemokinetic migration assay , an angiogenesis factor-mediated chemotactic migration assay , and a three-dimensional Matrigel tubule formation assay , using rat fat pad endothelial cells ( RFPECs ) and/or human umbilical vein endothelial cells ( HUVECs ) . Taxotere was active in all three assays at concentrations that were not cytotoxic and did not inhibit endothelial cell proliferation . In the RFPEC chemokinetic migration and in vitro tubule formation assays , the IC50 values were approximately 10(-9) M for both Taxotere and Taxol . HUVEC migration , however , was more sensitive to Taxotere , with an observed IC50 of 10(-12) M in a chemokinetic assay . In a Boyden chamber assay , HUVEC chemotaxis stimulated by either of two angiogenic factors , thymidine phosphorylase or vascular endothelial growth factor , was inhibited by Taxotere with an IC50 of 10(-11) M and was ablated at 10(-9) M. Taxotere was also up to 1000-fold more potent than Taxol in inhibiting either chemokinetic or chemotactic migration . When the microtubule cytoskeleton was visualized using immunofluorescence staining of alpha-tubulin , there were no gross morphological changes observed in HUVECs or RFPECs treated with Taxotere at concentrations that inhibited endothelial cell migration but not proliferation . The effects of Taxotere on migration were associated with a reduction in the reorientation of the cell's centrosome , at concentrations that did not affect gross microtubule morphology or proliferation . Reorientation of the centrosome , which acts as the microtubule organizing center , in the intended direction of movement is a critical early step in the stabilization of directed cell migration . These data indicate that endothelial cell migration correlates more closely with changes in microtubule plasticity than with microtubule gross structure . The antiangiogenic activity of Taxotere in vivo was assessed in a Matrigel plug assay . In this assay , the angiogenic response to fibroblast growth factor 2 was inhibited in vivo by Taxotere with an ID50 of 5.4 mg/kg when injected twice weekly over a 14-day period , and angiogenesis was completely blocked in mice that received 10 mg/kg Taxotere . The in vivo data further suggested that Taxotere had selectivity for endothelial cell migration and/or microvessel formation because infiltration of inflammatory cells into the Matrigel plug was much less sensitive to inhibition by Taxotere . In conclusion , Taxotere is a potent and potentially specific inhibitor of endothelial cell migration in vitro and angiogenesis in vitro and in vivo .\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: Homologous recombination ( HR ) is essential for repair of meiotic DNA double-strand breaks ( DSBs ) . Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized , the subsequent steps of HR are less well defined . Here , we describe a synthetic lethal interaction between the C. elegans helicase helq-1 and RAD-51 paralog rfs-1 , which results in a block to meiotic DSB repair after strand invasion . Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics in helq-1 , rfs-1 double mutants , persistence of RAD-51 foci and genetic interactions with rtel-1 suggest a failure to disassemble RAD-51 from strand invasion intermediates . Indeed , purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from double-stranded , but not single-stranded , DNA filaments via distinct mechanisms in vitro . These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly , which are collectively essential for completion of meiotic DSB repair .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The neurofibromatosis type 2 ( NF2 ) tumor suppressor gene encodes merlin , a membrane/cytoskeleton protein necessary for the maintenance of contact inhibition of growth in cells . Bi-allelic inactivation of NF2 is known to cause multiple cancers in both humans and mice . However , the mechanism through which merlin exerts its tumor-suppressive function remains obscure . In this report , we show that NF2 knockout mouse embryonic fibroblasts lost contact inhibition of cell proliferation and contained significantly increased canonical Wnt signaling . Inhibition of Rac1 , the activity of which is inversely regulated by NF2 , through the use of a dominant-negative mutant , small hairpin RNA or a small molecule inhibitor in NF2-deficient cells , was able to suppress elevated Wnt signals as shown by reduced activity of the T-cell factor 4 ( TCF4 ) transcription factor . Dominant-negative TCF4 or Rac1 mutant , as well as a small molecule inhibition of Wnt , were able to curb NF2 deficiency-elicited cell proliferation at the confluent state . Thus , Rac1-mediated canonical Wnt signaling is essential for the loss of contact inhibition in NF2-deficient 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: Construction industry workers are exposed to many known carcinogens in their complex occupational environment . Since there are no past studies on genotoxicity among this group in the Indian subcontinent , workers engaged in different construction sites at Coimbatore , Tamil Nadu , India , were assessed here . We enrolled 96 workers and 68 control subjects with similar mean age , smoking , tobacco chewing prevalence and alcohol consumption , for analysis of DNA damage in blood leucocytes by micronucleus ( MN ) and comet assays . DNA repair inhibition was also analyzed by assessing the XPD gene . Construction workers showed a significant increase in MN and comet tail length compared to controls with adjustment for smoking habits , tobacco chewing , alcohol consumption and years of exposure ( P<0.05 ) . The results indicated that chronic occupational exposure to cement during construction work could lead to increased levels of DNA damage and repair inhibition .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Epidemiological studies have indicated that obesity is associated with colorectal cancer . The obesity hormone leptin is considered as a key mediator for cancer development and progression . The present study aims to investigate regulatory effects of leptin on colorectal carcinoma . The expression of leptin and its receptor Ob-R was examined by immunohistochemistry in 108 Chinese patients with colorectal carcinoma . The results showed that leptin/Ob-R expression was significantly associated with T stage , TNM stage , lymph node metastasis , distant metastasis , differentiation and expression of p-mTOR , p-70S6 kinase , and p-Akt . Furthermore , the effects of leptin on proliferation and apoptosis of HCT-116 colon carcinoma cells were determined . The results showed that leptin could stimulate the proliferation and inhibit the apoptosis of HCT-116 colon cells through the PI3K/Akt/mTOR pathway . Ly294002 ( a PI3K inhibitor ) and rapamycin ( an mTOR inhibitor ) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated PI3K/Akt/mTOR pathway . All these results indicated that leptin could regulate proliferation and apoptosis of colorectal carcinoma through the PI3K/Akt/ mTOR signalling pathway .\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: Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis , or the Warburg effect . As in ovarian cancer cells , increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer . However , it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis . In the present research , we found that EF24 , a HIF-1α inhibitor , could significantly block glucose uptake , the rate of glycolysis , and lactate production compared with vehicle treatment in SKOV-3 , A2780 and OVCAR-3 cells . These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays . Furthermore , as an important mediator of glucose metabolism , glucose transporter 1 ( Glut1 ) was found to contribute to the function of EF24 in both energy metabolism and metastasis . To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model , intraperitoneal metastasis and lung metastasis model were introduced . Our results indicated that EF24 treatment could inhibit tumor growth , intraperitoneal metastasis and lung metastasis of SKOV-3 cells , and Glut1 is a possible mediator for the role of EF24 . In conclusion , our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis , and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Dendritic cells ( DCs ) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system . Ductal pancreatic adenocarcinoma ( PDAC ) , the most common pancreatic cancer , is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence . METHODS We examined the systemic influence ductal pancreatic adenocarcinoma ( PDAC ) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors , chronic pancreatitis , and age-matched controls . RESULTS All groups examined , including PDAC , had decreased levels of myeloid DCs ( MDC ) and plasmacytoid DCs ( PDC ) and enhanced apoptosis in these cells as compared to controls . We found elevated levels of PGE2 and CXCL8 in subjects with PDAC , and chronic pancreatitis . Levels of these inflammatory factors were in part restored in PDAC after tumor resection , whereas the levels of DCs were impaired in the majority of these patients approximately 12 weeks after tumor removal . Our results prove that solid pancreatic tumors , including PDAC , systemically affect blood DCs . The impairments do not seem to be tumor-specific , since similar results were obtained in subjects with chronic pancreatitis . Furthermore , we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival . CONCLUSIONS Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs . Furthermore , the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and 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: It was proved that nuclear factor-kappa B play an important role in the activation of immune cell , anti-virus , various stress reaction , and regulation of apoptosis , etc . The objective of this study was to investigate the effect of NF-kappa B signal-transduction pathway on apoptosis of hepatic carcinoma cell line-7721 induced by TNF-alpha .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Pyruvate kinase M2 ( PKM2 ) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms . Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 Ile429/Leu431 through the ERK2 docking groove and phosphorylates PKM2 at Ser37 , but does not phosphorylate PKM1 . Phosphorylated PKM2 Ser37 recruits PIN1 for cis-trans isomerization of PKM2 , which promotes PKM2 binding to importin α5 and translocating to the nucleus . Nuclear PKM2 acts as a coactivator of β-catenin to induce c-Myc expression , resulting in the upregulation of GLUT1 , LDHA and , in a positive feedback loop , PTB-dependent PKM2 expression . Replacement of wild-type PKM2 with a nuclear translocation-deficient mutant ( S37A ) blocks the EGFR-promoted Warburg effect and brain tumour development in mice . In addition , levels of PKM2 Ser37 phosphorylation correlate with EGFR and ERK1/2 activity in human glioblastoma specimens . Our findings highlight the importance of nuclear functions of PKM2 in the Warburg effect and tumorigenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Ataxia-telangiectasia mutated ( ATM ) is a cellular damage sensor that coordinates the cell cycle with damage-response checkpoints and DNA repair to preserve genomic integrity . However , ATM also has been implicated in metabolic regulation , and ATM deficiency is associated with elevated reactive oxygen species ( ROS ) . ROS has a central role in many physiological and pathophysiological processes including inflammation and chronic diseases such as atherosclerosis and cancer , underscoring the importance of cellular pathways involved in redox homeostasis . We have identified a cytoplasmic function for ATM that participates in the cellular damage response to ROS . We show that in response to elevated ROS , ATM activates the TSC2 tumor suppressor via the LKB1/AMPK metabolic pathway in the cytoplasm to repress mTORC1 and induce autophagy . Importantly , elevated ROS and dysregulation of mTORC1 in ATM-deficient cells is inhibited by rapamycin , which also rescues lymphomagenesis in Atm-deficient mice . Our results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy , identifying an integration node for the cellular damage response with key pathways involved in metabolism , protein synthesis , and cell survival .\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: Each year , more than 700,000 people undergo cancer surgery in the United States . However , more than 40% of those patients develop recurrences and have a poor outcome . Traditionally , the medical community has assumed that recurrent tumors arise from selected tumor clones that are refractory to therapy . However , we found that tumor cells have few phenotypical differences after surgery . Thus , we propose an alternative explanation for the resistance of recurrent tumors . Surgery promotes inhibitory factors that allow lingering immunosuppressive cells to repopulate small pockets of residual disease quickly . Recurrent tumors and draining lymph nodes are infiltrated with M2 ( CD11b(+)F4/80(hi)CD206(hi) and CD11b(+)F4/80(hi)CD124(hi) ) macrophages and CD4(+)Foxp3(+) regulatory T cells . This complex network of immunosuppression in the surrounding tumor microenvironment explains the resistance of tumor recurrences to conventional cancer vaccines despite small tumor size , an intact antitumor immune response , and unaltered cancer cells . Therapeutic strategies coupling antitumor agents with inhibition of immunosuppressive cells potentially could impact the outcomes of more than 250,000 people each year .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND &amp ; OBJECTIVE Altered cell adhesion has a critical role in the development of epithelial cancers . E-cadherin act on the maintenance of cell-cell adhesion and its function was thought to be regulated by associated cytoplasmic proteins , such as alpha-catenin and beta-catenin . This study was designed to examine the expression of beta-catenin in gastric carcinoma and to determine the relationship between tumor characteristics and survival . METHODS Immunohistochemical staining of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was performed in 148 patients with gastric carcinoma . RESULTS Abnormal expression of beta-catenin and E-cadherin was demonstrated in 43.2% and 44.6% of tumors respectively . Up to 63% of tumors stained abnormally for one or two components of the cadherin-catenin complex ( beta-catenin , E-cadherin ) . Abnormal beta-catenin and E-cadherin staining occurred more frequently in poor differentiated tumor than in good differentiated tumors ( P &lt ; 0.005 , respectively ) . There was a significant correlation between abnormal beta-catenin expression and depth of invasion(P &lt ; 0.025 ) . Moreover , abnormal beta-catenin expression was more frequent in tumors with positive lymph node metastasis ( 45/84 , 53.6% ) and distance metastasis(21/31 , 67.7% ) than in tumors without lymph node metastasis ( 19/64 , 29.7% ) ( P &lt ; 0.005 ) and distance metastasis ( 43/117 , 36.8% ) ( P &lt ; 0.005 ) . A survival advantage was noted in tumors retaining normal membranous expression of beta-catenin , independent of type , grade , or stage ( P &lt ; 0.005 ) . CONCLUSIONS Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma . The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The relationship between DNA damage and repair of peripheral blood leukocytes , liver , kidney and brain cells was investigated in Swiss albino mice ( Mus musculus L. ) after exposure to sevoflurane ( 2.4 vol% for 2 h daily , for 3 days ) . Genetic damage of mouse cells was investigated by the comet assay and micronucleus test . To perform the comet assay , mice were divided into a control group and 4 groups of exposed mice sacrificed on day 3 of the experiment , at 0 , 2 , 6 or 24 h after the last exposure to sevoflurane . Mean tail length ( TL ) , tail moment ( TM ) , and tail intensity ( TI ) values were significantly higher in exposed mice ( all examined organs ) than in the control group . Significant DNA damage immediately after exposure to sevoflurane was observed in leukocytes . Damage induction in the liver , kidney , and brain occurred 6 h later than in leukocytes , as expected according to the toxicokinetics of the drug , where blood is the first compartment to absorb sevoflurane . However , none of the tested tissues revealed signs of repair until 24 h after the exposure . To distinguish the unrepaired genome damage in vivo , the micronucleus test was applied . Number of micronuclei in reticulocytes showed a statistically significant increase , as compared with the control group at all observed times after the treatment .\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 oncogenic potential of a human papillomavirus type 16 ( HPV16 ) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes . The HPV16 variant was able to extend the lifespan of , but failed to immortalize , human keratinocytes . It could however cooperate with an activated ras oncogene to transform primary rodent cells . Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein . DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional , but a deletion in the viral E2 open reading frame was detected . This truncated E2 only weakly stimulated transcription of the viral regulatory region . Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency . These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A glycolytic profile unifies a group of pheochromocytomas and paragangliomas ( PHEOs/PGLs ) with distinct underlying gene defects , including von Hippel-Lindau ( VHL ) and succinate dehydrogenase B ( SDHB ) mutations . Nevertheless , their tumor aggressiveness is distinct : PHEOs/PGLs metastasize rarely in VHL- , but frequently in SDHB-patients . To date , the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown . Recently , however , an excellent model to study aggressive PHEOs ( mouse tumor tissue ( MTT ) cells ) has been developed from mouse PHEO cells ( MPC ) . We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness , which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs . The increase of glucose transporter 1 in VHL , and of hexokinase 2 in VHL and SDHB , confirmed their glycolytic profile . In agreement with the cell model and in support of decoupling of glycolysis , the Krebs cycle and oxidative phosphorylation ( OXPHOS ) , SDHB tumors showed increased lactate dehydrogenase levels . In SDHB-PGLs OXPHOS complex activity was increased at complex III and , as expected , decreased at complex II . Moreover , protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors . Although there was no direct evidence for increased reactive oxygen species production , elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs . For the first time , we show that despite dysfunction in complex II and evidence for a glycolytic phenotype , the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS . In addition , we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs , proteins that have been proposed as promising therapeutic targets in other cancers . This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs , which may lead to identifying new diagnostic and prognostic markers in the near future .\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: Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with β(2)-adrenergic receptor ( β(2)-AR ) stimulation . However , the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear . Here , we compare the effect of the β(2)-AR agonists ( R,R')-fenoterol ( Fen ) and ( R,R')-4-methoxy-1-naphthylfenoterol ( MNF ) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [ (3)H]thymidine incorporation assays . Despite the expression of β(2)-AR , no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen , although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation . Unexpectedly , isoproterenol and Fen promoted HepG2 cell growth , but MNF reduced proliferation together with increased apoptosis . The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol ( ICI 118,551 ) , a β(2)-AR antagonist , whereas those of MNF were unaffected . Because of the coexpression of β(2)-AR and cannabinoid receptors ( CBRs ) and their impact on HepG2 cell proliferation , these Gα(i)/Gα(o)-linked receptors may be implicated in MNF signaling . Cell treatment with ( R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone ( WIN 55,212-2 ) , a synthetic agonist of CB(1)R and CB(2)R , led to growth inhibition , whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling . MNF responses were sensitive to pertussis toxin . The β(2)-AR-deficient U87MG cells were refractory to Fen , but responsive to the antiproliferative actions of MNF and WIN 55,212-2 . The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway , providing one of the first examples of a dually acting β(2)-AR-CBR ligand .\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: This study intended to investigate the expression of the ZEB1 and E-cadherin proteins in lung squamous cell carcinoma ( LSCC ) tissues and to examine the clinicopathological correlation between protein levels and LSCC . RT-PCR and Western blot were used to examine the expression of ZEB1 and E-cadherin mRNAs and proteins in LSCC tissues as well as in adjacent normal tissues , and then analyze the relationship between the clinicopathological characteristics and the expression changes of ZEB1 and E-cadherin mRNAs in LSCC . In addition , RNAi was used to knockdown the expression of the ZEB1 gene in Human HCC827 cells ; subsequently , changes in the invasive ability of the resultant cells were studied . The positive rates of ZEB1 and E-cadherin mRNAs in LSCC tissues were 69.2 and 38.5% , respectively . They differed significantly from the corresponding positive rates in the adjacent normal lung tissues ( 15.4 and 80.8% , p<0.05 ) . There was a negative correlation between the protein levels of ZEB1 and E-cadherin in LSCC tissues ( r=-0.714 , p<0.001 ) ; in addition , it was found that ZEB1 protein expression in LSCC tissues was significantly higher than that in the neighboring normal lung tissues ( p<0.05 ) , and its expression was also significantly higher in patients with lymph node metastases and distant metastases compared to those patients without metastatic disease ( p<0.05 ) . On the contrary , E-cadherin expression was significantly lower in LSCC tissues than that in the neighboring normal tissue ( p<0.05 ) . It was lower in patients with lymph node metastasis and distant metastasis compared to patients without metastatic disease ( p<0.05 ) . However , the expression of ZEB1 and E-cadherin was independent of gender , age , tumor size , or tumor differentiation level ( p>0.05 ) . Transfection of ZEB1 siRNA into HCC827 cells significantly reduced the ZEB1 protein level ( p<0.01 ) and significantly elevated E-cadherin levels ( p<0.01 ) . Moreover , significantly less ZEB1 siRNA-transfected cells migrated through Transwell chambers in the LSCC tissue than that in the control groups ( untransfected or transfected with control siRNA , p<0.01 ) . The expression of the ZEB1 gene in LSCC tissues is downregulated with the expression of E-cadherin . On the other hand , the expression of siRNA against ZEB1 promotes E-cadherin expression and suppresses the invasive ability conferred by E-cadherin . In conclusion , our data suggested that overexpression of the ZEB1 gene is possibly associated with the occurrence , development , invasion of LSCC .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Background:Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma ( HCC ) . The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance , but such correlation is unclear in sorafenib resistance of HCC.Methods:Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line ( Huh-7R ; derived from sorafenib-sensitive Huh-7 ) were used . The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin . Dichloroacetate ( DCA ) , a pyruvate dehydrogenase kinase ( PDK ) inhibitor , and siRNA of hexokinase 2 ( HK2 ) were used to target relevant pathways of cancer metabolism . Cell viability , mitochondrial membrane potential , and sub-G1 fraction were measured for in vitro efficacy . Reactive oxygen species ( ROS ) , adenosine triphosphate ( ATP ) and glucose uptake were also measured . A subcutaneous xenograft mouse model was used for in vivo efficacy.Results:The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity ( R(2)=0.9067 , among sorafenib-naive cell lines ; P=0.003 , compared between Huh-7 and Huh-7 R ) . DCA reduced lactate production and increased ROS and ATP , indicating activation of oxidative phosphorylation ( OXPHOS ) . DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis ( sub-G1 ( combination vs sorafenib ) : Hep3B , 65.4±8.4% vs 13±2.9% ; Huh-7 R , 25.3± 5.7% vs 4.3±1.5% ; each P<0.0001 ) , whereas siRNA of HK2 did not . Sorafenib ( 10 mg kg(-1) per day ) plus DCA ( 100 mg kg(-1) per day ) also resulted in superior tumour regression than sorafenib alone in mice ( tumour size : -87% vs -36% , P<0.001).Conclusion:The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity , and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.British Journal of Cancer advance online publication , 20 December 2012 ; doi:10.1038/bjc.2012.559 www.bjcancer.com .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: It is still difficult to decide on the treatment modalities for advanced esophageal carcinoma when the prognostic factors of T4 esophageal cancer are not fully understood . In this article , we report that among 71 patients with T4 thoracic esophageal cancer , 49 underwent esophagectomy , 9 had curative resection ( R0 group ) , and 40 had palliative resection ( R1/2 group ) . A total of 22 patients had palliative treatments : bypass in 5 ( bypass group ) , gastrostomy or jejunostomy in 6 ( stoma group ) , and radiochemotherapy alone in 11 ( nonoperation group ) . Clinicopathologic characteristics were retrospectively investigated . Treatment-related deaths occurred in 7 ( 10% ) : none in R0 , 3 ( 8% ) in R1/2 , 3 ( 60% ) in bypass , and 1 ( 17% ) in stoma group . Swallowing was improved in 50 ( 70% ) patients : 9 ( 100% ) in R0 , 30 ( 75% ) in R1/2 , 1 ( 20% ) in bypass , 3 ( 50% ) in stoma , and 7 ( 64% ) in the nonoperation group . One- , two- , and three-year overall survival rates were 56% , 22% , and 22% in the R0 group and 35% , 19% and 6% in the R1/2 group , respectively ( p = 0.19 ) . In the bypass , stoma , and nonoperation groups , none survived 1.6 years . The factors influencing the survival rate of the 49 patients undergoing esophagectomy were grade of lymph node metastasis , amount of perioperative blood transfusion , lymph vessel , and blood vessel invasion . Among these , independent prognostic factors for survival were amount of blood transfusion ( -6 units vs. -7 units , p <0.0001 ) and grade of lymph node metastasis [ none- or peritumoral [ lymph nodes adjacent to the main tumor or at a nearby location ( <3 cm ) from the tumor ] metastasis vs. more distant metastasis [ lymph nodes at a distant location ( &gt ; 3 cm) ] , p = 0.016 ] . Bypass and stoma operation neither prolonged the survival nor improved the difficulty of swallowing compared with radiochemotherapy alone . Esophagectomy can achieve the best improvement of swallowing and the longest survival with an acceptable mortality rate . Esophageal carcinoma patients with T4 disease and distinct metastasis in the lymph nodes at a distant location ( >3 cm ) from the primary tumor may not benefit from an esophageal resection .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: UNLABELLED Hepatocellular carcinoma ( HCC ) is a major liver malignancy . We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC . Suppressor of variegation 3-9 homolog 1 ( SUV39H1 ) , the prototype of histone methyltransferase , is the major enzyme responsible for histone H3 lysine 9 trimethylation , which , essentially , is involved in heterochromatin formation , chromosome segregation , and mitotic progression . However , the implication of SUV39H1 in hepatocarcinogenesis remains elusive . In this study , we found that SUV39H1 was frequently up-regulated in human HCCs and was significantly associated with increased Ki67 expression ( P &lt ; 0.001 ) and the presence of venous invasion ( P = 0.017 ) . To investigate the role of SUV39H1 in HCC development , both gain- and loss-of-function models were established . SUV39H1 overexpression remarkably enhanced HCC cell clonogenicity , whereas knockdown of SUV39H1 substantially suppressed HCC cell proliferation and induced cell senescence . In addition , ectopic expression of SUV39H1 increased the migratory ability of HCC cells , whereas a reduced migration rate was observed in SUV39H1 knockdown cells . The significance of SUV39H1 in HCC was further demonstrated in a nude mice model ; SUV39H1 knockdown drastically inhibited in vivo tumorigenicity and abolished pulmonary metastasis of HCC cells . We also identified microRNA-125b ( miR-125b ) as a post-transcriptional regulator of SUV39H1 . Ectopic expression of miR-125b inhibited SUV39H1 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SUV39H1 expression at both messenger RNA and protein levels . We have previously reported frequent down-regulation of miR-125b in HCC . Interestingly , miR-125b level was found to be inversely correlated with SUV39H1 expression ( P = 0.001 ) in clinical specimens . Our observations suggested that miR-125b down-regulation may account for the aberrant SUV39H1 level in HCC . CONCLUSION Our study demonstrated that SUV39H1 up-regulation contributed to HCC development and metastasis . The tumor-suppressive miR-125b served as a negative regulator of SUV39H1 .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;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: AIM Colorectal cancer is the third most common form of cancer in the industrial countries . Due to advances regarding the treatments , primarily development of improved surgical methods and the ability to make the earlier diagnosis , the mortality has remained constant during the past decades even though the incidence in fact has increased . To improve chemotherapy and enable personalised treatment , the need of biomarkers is of great significance . In this study , we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38 , the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis . MATERIAL AND METHODS The study included 3 colon cancer cell lines : KM12C , KM12SM and KM12l4a . The 3 cell lines were treated with SN-38 , and samples were obtained after 24 and 48 hour treatments . The gene expression analyses were performed using oligonucleotide microarrays comprising of approximately 27,000 spots where the untreated controls were compared to the SN-38-treated samples . RESULTS Unsupervised clustering clearly distinguished the treated cell lines from the untreated . Supervised analysis identified 3,974 significant genes ( p = 0.05 ) differentiating the treated samples from the untreated , majority of which were down-regulated after treatment . The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity , signal transduction , apoptosis , RNA processing , protein metabolism and transport , cell cycle and transcription . A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis , transcription , development and differentiation . CONCLUSIONS These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA , DNA and protein metabolism were affected by SN-38 . The impact of certain genes on colorectal cancer development needs to be further evaluated ; however , these results could serve as a basis for further studies in order to find targets for irinotecan treatment .\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: Cantharidin is an active constituent of mylabris , a traditional Chinese medicine . It is a potent and selective inhibitor of protein phosphatase 2A ( PP2A ) that plays an important role in control of cell cycle , apoptosis , and cell-fate determination . Owing to its antitumor activity , cantharidin has been frequently used in clinical practice . In the present study , we investigated the therapeutic potential of cantharidin in pancreatic cancer . Cantharidin efficiently inhibited the growth of pancreatic cancer cells , but presented a much lighter toxicity effect against normal pancreatic duct cells . It caused G2/M cell-cycle arrest that was accompanied by the down-regulation of cyclin-dependent kinase 1 ( CDK1 ) and up-regulation of p21 expression . It induced apoptosis and elevated the expressions of pro-apoptotic factors tumor necrosis factor-alpha ( TNF-alpha ) , TNF-related apoptosis inducing receptor 1 ( TRAILR1 ) , TRAILR2 , Bad , Bak , and Bid , and decreased the expression of anti-apoptotic Bcl-2 . Activation of caspase-8 and caspase-9 suggested that both extrinsic and intrinsic pathways are involved in the induction of apoptosis . Interestingly , unlike previous studies on other cancer cells , we found that the inhibitory role of cantharidin is independent of oxidative stress in pancreatic cancer cells . Mitogen-activated protein kinases ( MAPKs ) , including ERK , JNK , and p38 , were activated after treatment with cantharidin . Inhibition of JNK , but not ERK or p38 , alleviated the cytotoxity effect of cantharidin , suggesting cantharidin exerted its anticancer effect through the JNK-dependent way . Hence , in addition to being an attractive candidate compound with therapeutic potential , cantharidin also highlighted the possibility of using PP2A as a therapeutic target for pancreatic cancer treatment .\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: Glioblastoma multiforme is the most aggressive primary brain tumor in adults . Overexpression of the EGF receptor ( EGFR ) is recognized as a widespread oncogenic signature in glioblastoma multiforme , but the complexity of its contributions is not fully understood , nor the most effective ways to leverage anti-EGFR therapy in this setting . Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria ( OXPHOS ) , a phenomenon termed the Warburg effect , which is a general feature of oncogenesis . In this study , we report that hypoxia drives expression of the pyruvate dehydrogenase kinase ( PDK1 ) and EGFR along with the hypoxia-inducing factor ( HIF)-1α in human glioblastoma multiforme cells . PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation , initiating a feed-forward loop that can sustain malignant progression . RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1α expression , shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation . In clinical specimens of glioblastoma multiforme , we found that immunohistochemical expression of PDK1 , EGFR , and HIF-1α were elevated in glioblastoma multiforme specimens when compared with normal brain tissues . Collectively , our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: Using standard culture conditions , primary human mammary epithelial cells ( HMECs ) undergo a premature , transient growth arrest termed M0 ( mortality stage 0 ) after 10-15 population doublings in vitro . It has been reported that emergence from this growth arrest by the abrogation of p16(INK4a) , a cyclin-dependent kinase inhibitor , and expression of the catalytic component of human telomerase ( hTERT ) are necessary for HMEC immortalization . Here we show that primary HMECs , grown on feeder layers , do not undergo this growth arrest and can be immortalized without abrogating p16 . These findings support the concept that the so-called M0 stage represents a cell culture stress-induced growth arrest and that hTERT is sufficient to immortalize HMECs when cultured under adequate conditions .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Rho GTPases are signaling molecules known to control cell motility . Several recent studies have suggested a role for Rho proteins in mediating tumor metastasis independent of their affects on cell proliferation . As Rho proteins require post-translational modification with a geranlygeranyl moiety for full activity , we tested the affect of blocking geranylation on localization , downstream signaling , and stimulation of invasion . Expression of a constitutively active Rho construct in A375 melanoma cells dramatically stimulated invasion through Matrigel membranes ; however , a constitutively active RhoA mutated so that it cannot be geranylated , failed to stimulate invasion . Moreover , expression of epitope or GFP tagged modifications of this nongeranylatable constitutively active Rho demonstrated that geranylation is necessary for correct cellular localization of Rho . Geranylation was also found to be necessary for full downstream activation of serum response factor mediated transcription . Pharmacologic inhibition of Rho geranylation produced similar inhibition of Rho localization , signaling , and invasion . Our results suggest that inhibition of Rho geranylation may be an attractive pharmacologic target for inhibiting melanoma metastasis .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Widespread changes in gene expression drive tumorigenesis , yet our knowledge of how aberrant epigenomic and transcriptome profiles arise in cancer cells is poorly understood . Here , we demonstrate that metabolic transformation plays an important role . Butyrate is the primary energy source of normal colonocytes and is metabolized to acetyl-CoA , which was shown to be important not only for energetics but also for HAT activity . Due to the Warburg effect , cancerous colonocytes rely on glucose as their primary energy source , so butyrate accumulated and functioned as an HDAC inhibitor . Although both mechanisms increased histone acetylation , different target genes were upregulated . Consequently , butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring , whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect . These findings link a common metabolite to epigenetic mechanisms that are differentially utilized by normal and cancerous cells because of their inherent metabolic differences .\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: Tumor cells are elusive targets for immunotherapy due to their heterogeneity and genetic instability . Here we describe a novel , oral DNA vaccine that targets stable , proliferating endothelial cells in the tumor vasculature rather than tumor cells . Targeting occurs through upregulated vascular-endothelial growth factor receptor 2 ( FLK-1 ) of proliferating endothelial cells in the tumor vasculature . This vaccine effectively protected mice from lethal challenges with melanoma , colon carcinoma and lung carcinoma cells and reduced growth of established metastases in a therapeutic setting . CTL-mediated killing of endothelial cells indicated breaking of peripheral immune tolerance against this self antigen , resulting in markedly reduced dissemination of spontaneous and experimental pulmonary metastases . Angiogenesis in the tumor vasculature was suppressed without impairment of fertility , neuromuscular performance or hematopoiesis , albeit with a slight delay in wound healing . Our strategy circumvents problems in targeting of genetically unstable tumor cells . This approach may provide a new strategy for the rational design of cancer therapies .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction;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 cellular mechanisms of anti-androgen-induced tumor regression have not been investigated in great detail . We have compared the induction of cell death in the androgen-dependent , non-invasive LNCaP prostate cancer cell line by Casodex and TNF-alpha . Both agents induce a dose and time-dependent decrease in cell viability in vitro . However , Casodex does not induce classical DNA fragmentation to oligonucleosomes typically induced by TNF-alpha , but rather induces cleavage to form intermediate 60 kb DNA fragments . RT-PCR based analysis demonstrates that in LNCaP cells Casodex coordinately alters the expression of steady-state level of mRNAs of several matrix metalloproteases and their cognate inhibitors ( most notably MMP2 and TIMP1 ) . Zymography and reverse zymography confirm that the ratio of metalloprotease(s) to inhibitor(s) is altered in favor of activation of the proteases . In a small percentage of the treated LNCaP cells , the activation of the extracellular matrix ( ECM)-proteases by Casodex also induces an invasive phenotype . The acquisition of an invasive phenotype is not seen when LNCaP cells are treated with TNF-alpha , and is not seen when the LNCaP cells are treated with both compounds simultaneously , suggesting that the phenomenon may be specific to particular classes of compounds . These observations have significant implications in the treatment of prostate cancer , since the appearance of a more aggressive phenotype following treatment is clearly undesirable .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;activating invasion and metastasis" } ]