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Clinical NLP Lab 23

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input 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 During selective segregation of DNA , a cell asymmetrically divides and retains its template DNA . Asymmetric division yields daughter cells whose genome reflects that of the parents ' , simultaneously protecting the parental cell from genetic errors that may occur during DNA replication . We hypothesized that long-lived epithelial cells are present in immortal , premalignant cell populations , undergo asymmetric division , retain their template DNA strands , and cycle both during allometric growth and during pregnancy . METHODS The glands of 3-week old immune competent Balb/C female mice were utilized intact or cleared of host epithelium and implanted with ductal-limited , lobule-limited , or alveolar-ductal progenitor cells derived from COMMA-D1 pre-malignant epithelial cells. 5-bromo-2-deoxyuridine ( 5-BrdU ) was administered to identify those cells which retain their template DNA . Nulliparous mice were then either injected with [ (3)H]-thymidine ( (3)H-TdR ) to distinguish 5-BrdU-label retaining cells that enter the cell cycle and euthanized , or mated , injected with ( 3)H-TdR , and euthanized at various days post-coitus . Sections were stained for estrogen receptor-α(ER-α) or progesterone receptor ( PR ) via immunohistochemistry . Cells labelled with both 5-BrdU and ( 3)H-TdR were indicative of label-retaining epithelial cells ( LREC ) . RESULTS Cells that retained a 5-BrdU label and cells labelled with [ (3)H]-thymidine were found in all mice and were typically detected along the branching epithelium of mature mouse mammary glands . Cells containing double-labelled nuclei ( LREC ) were found in the intact mammary gland of both pregnant and nulliparous mice , and in mammary glands implanted with pre-malignant cells . Double-labelled cells ( (3)H-TdR/5-BrdU ) represent a small portion of cells in the mammary gland that cycle and retain their template DNA ( 5-BrdU ) . Some label-retaining cells were also ER-α or PR positive . LRECs distributed their second label ( (3)H-TdR ) to daughter cells ; and this effect persisted during pregnancy . LRECs , and small focal hyperplasia , were found in all immortalized premalignant mammary implant groups . CONCLUSIONS The results indicate that a subpopulation of long-lived , label-retaining epithelial cells ( LRECs ) is present in immortal premalignant cell populations . These LRECs persist during pregnancy , retain their original DNA , and a small percentage express ER-α and PR . We speculate that LRECs in premalignant hyperplasia represent the long-lived ( memory ) cells that maintain these populations indefinitely .\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 morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time . The apoptotic cancer cell contracted , became rounder and divorced from adjacent cells ; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane ; the endoplasmic reticulums ( ER ) expanded and fused with the cellular membrane ; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma . Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediatedin situ nick end labeling ( TUNEL ) . It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample . The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency ( ULF ) pulsed gradient magnetic field ; the nuclei DNA contents decreased , indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells . It was suggested that magnetic field could inhibit the metabolism of cancer cell , lower its malignancy , and restrain its rapid and heteromorphic growth . Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour , it could be used as a new method to treat 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: Background and Objective . The cell cycle is regulated by proteins at different checkpoints , and dysregulation of this cycle plays a role in carcinogenesis . Matrix metalloproteinases ( MMPs ) are enzymes that degrade collagen and promote tumour infiltration . The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder ( UCB ) . Patients and Methods . This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder . Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs . Results . Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence . Also , normal p16 expression was related to a lower risk of tumour progression . MMP2 , p21 , cyclin D1 , and pRb showed no significant results that could estimate progression or recurrence . Conclusions . Normal p16 expression is associated with a lower risk of tumour progression , but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The secretion of immunosuppressive factors like transforming growth factor-beta ( TGF-beta ) by tumor cells has been recognized as one of the mechanisms involved in tumor immunological escape . This study aimed to examine whether dendritic cell ( DC ) immunization could reverse TGF-beta-induced immunosuppression by simulating the in vivo interaction among infused DCs , host T cells , and tumor-secreted TGF-beta in an in vitro study . We found that both immature and mature DCs were relatively resistant to TGF-beta . The addition of TGF-beta to naive human CD4+ T cells , which are required by genetically modified DC to elicit antitumor immunity , resulted in their hyporesponsiveness to DC stimulation in a dose-dependent manner . When activated by allogeneic DCs in the presence of TGF-beta , CD4+ T cells displayed a reduced capacity to proliferate . More importantly , activated CD4+ T cells induced by DC stimulation were very sensitive to TGF-beta , and this susceptibility was enhanced by their previous exposure to TGF-beta . The underlying mechanism was linked to TGF-beta-induced apoptosis of activated T cells . However , the presence of stimulation from DC or antibodies to CD3 plus CD28 could partly reverse the immunosuppressive effect of TGF-beta on activated CD4+ T cells . Taken together , our results indicate that the efficacy of DC immunization may be impaired by tumor-derived TGF-beta .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;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: PURPOSE Genomic complexity is present in approximately 15% to 30% of all chronic lymphocytic leukemia ( CLL ) and has emerged as a strong independent predictor of rapid disease progression and short remission duration in CLL . We conducted this study to advance our understanding of the causes of genomic complexity in CLL . EXPERIMENTAL DESIGN We have obtained quantitative measurements of radiation-induced apoptosis and radiation-induced ATM autophosphorylation in purified CLL cells from 158 and 140 patients , respectively , and have used multivariate analysis to identify independent contributions of various biological variables on genomic complexity in CLL . RESULTS Here , we identify a strong independent effect of radiation resistance on elevated genomic complexity in CLL and describe radiation resistance as a predictor for shortened CLL survival . Furthermore , using multivariate analysis , we identify del17p/p53 aberrations , del11q , del13q14 type II ( invariably resulting in Rb loss ) , and CD38 expression as independent predictors of genomic complexity in CLL , with aberrant p53 as a predictor of approximately 50% of genomic complexity in CLL . Focusing on del11q , we determined that normalized ATM activity was a modest predictor of genomic complexity but was not independent of del11q . Through single nucleotide polymorphism array-based fine mapping of del11q , we identified frequent monoallelic loss of Mre11 and H2AFX in addition to ATM , indicative of compound del11q-resident gene defects in the DNA double-strand break response . CONCLUSIONS Our quantitative analysis links multiple molecular defects , including for the first time del11q and large 13q14 deletions ( type II ) , to elevated genomic complexity in CLL , thereby suggesting mechanisms for the observed clinical aggressiveness of CLL in patients with unstable genomes .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cell proliferation is known to be accompanied by activation of glycolysis . We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase , isoform 3 ( PFKFB3 ) , is degraded by the E3 ubiquitin ligase APC/C-Cdh1 , which also degrades cell-cycle proteins . We now show in two different cell types ( neoplastic and nonneoplastic ) that both proliferation and aerobic glycolysis are prevented by overexpression of Cdh1 and enhanced by its silencing . Furthermore , we have coexpressed Cdh1 with PFKFB3--either wild-type or a mutant form resistant to ubiquitylation by APC/C-Cdh1--or with the glycolytic enzyme 6-phosphofructo-1-kinase and demonstrated that whereas glycolysis is essential for cell proliferation , its initiation in the presence of active Cdh1 does not result in proliferation . Our experiments indicate that the proliferative response , regardless of whether it occurs in normal or neoplastic cells , is dependent on a decrease in the activity of APC/C-Cdh1 , which activates both proliferation and glycolysis . These observations have implications for cell proliferation , neoplastic transformation , and the prevention and treatment of cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE The difference in radiosensitivity between two isogenic tumour cell lines was evaluated to determine whether factors such as sublethal and potentially damage repair , DNA double-strand break repair and fidelity of repair can be related to differences in radiosensitivity . MATERIALS AND METHODS The cell lines used were the ovarian carcinoma A2780s and a radiation-resistant derivative A2780cp . Radiation response was measured in terms of cell survival , recovery of sublethal ( SLD ) and potentially lethal damage ( PLD ) , induction of and recovery of DNA strand breaks , and fidelity of DNA repair using a cell-free plasmid assay . RESULTS While A2780cp was more resistant to radiation than A2780s , it showed less ability for recovery of SLD and PLD . DNA strand-break induction was the same for both cell lines , while only at very high doses did A2780cp show greater DNA strand-break recovery than A2780s . Fidelity of rejoining DNA was significantly higher in the A2780cp cell line . CONCLUSION The difference in radiosensitivity between these two cell lines was not related to recovery of PLD or SLD or to the induction of DNA damage . It appears that fidelity of DNA rejoining , which was significantly higher in the resistant cell line , may be related to the difference in radiosensitivity .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVES Lymph node metastasis is among the most important prognostic factors for patients with esophageal squamous cell carcinoma after curative esophagectomy ; however , the extent of lymphadenectomy is still controversial . The objective of the present study was to determine the frequency of lymphatic metastases and to study the pattern of lymph node metastasis in a large study population . METHODS The data from 1361 patients with thoracic esophageal squamous cell carcinoma who underwent curative R0 esophagectomy were retrospectively examined . Logistic regression analysis was used to identify the factors associated with lymph node metastasis . RESULTS Of the 1361 patients , 714 ( 52.5% ) were found to have lymph node metastasis . The frequency of lymph node metastasis increased as the tumor invasion increased . Paratracheal nodes were the most frequent metastasis nodes ( 15.9% ) . The frequency of lymph node metastasis was 9.8% in the neck , 18.0% in the upper mediastinum , 18.9% in the middle mediastinum , 11.8% in the lower mediastinum , and 28.4% in the abdomen . Of these 714 patients , 424 ( 31.2% ) presented with 1 field involvement , 255 ( 18.7% ) with 2 fields , and 35 ( 2.6% ) with 3 fields involvement . Logistic regression analysis revealed tumor length ( P<.001 ) , tumor invasion ( P<.001 ) , tumor differentiation ( P=.003 ) , and lymphovascular invasion ( P<.001 ) were risk factors for lymph node metastasis . Tumor location ( P<.001 ) , tumor invasion ( P=.003 ) , lymphovascular invasion ( P=.004 ) , and paratracheal lymph node involvement ( P=.002 ) were identified as risk factors for cervical lymph node metastasis . CONCLUSIONS Metastases were more frequent in the abdomen than in the neck . Total mediastinal and upper abdominal lymphadenectomy should be carefully conducted . Certain factors , such as tumor location , depth of tumor invasion , lymphovascular invasion , and paratracheal lymph node involvement , might be helpful in determining the need to perform cervical lymphadenectomy in individual patients .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Although the p16(INK4a) and p21Waf1/Cip1 cyclin-dependent kinase ( CDK ) inhibitors are known to play key roles in cellular senescence in vitro , their roles in senescence remain rather poorly understood in vivo . This situation is partly due to the possibility of compensatory effect(s) between p16INK4a and p21Waf1/Cip1 or to the upregulation of functionally related CDK inhibitors . To directly address the cooperative roles of p16INK4a and p21Waf1/Cip1 in senescence in vivo , we generated a mouse line simply lacking both p16INK4a and p21Waf1/Cip1 genes [ double-knockout ( DKO) ] . Mouse embryonic fibroblasts ( MEF ) derived from DKO mice displayed no evidence of cellular senescence when cultured serially in vitro . Moreover , DKO MEFs readily escaped Ras-induced senescence and overrode contact inhibition in culture . This was not the case in MEFs lacking either p16INK4a or p21Waf1/Cip1 , indicating that p16(INK4a) and p21Waf1/Cip1 play cooperative roles in cellular senescence and contact inhibition in vitro . Notably , we found the DKO mice to be extremely susceptible to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis that involves oncogenic mutation of the H-ras gene . Mechanistic investigations suggested that the high incidence of cancer in DKO mice likely reflected a cooperative effect of increased benign skin tumor formation caused by p21Waf1/Cip1 loss , with increased malignant conversion of benign skin tumors caused by p16(INK4a) loss . Our findings establish an intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;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: Cytokeratin ( CK ) 19-positive hepatocellular carcinoma ( HCC ) has been reported to have a poor prognosis . The mechanism of the development of CK19-positive HCC remains to be studied . To clarify this , in vitro experiments were performed using human HCC cell lines ( PLC-5 , HepG2 ) , and the phenotypic changes after stimulation with several growth factors were examined using quantitative reverse transcriptase PCR , western blotting , and immunofluorescence staining . In vivo experiments using human HCC specimens obtained from a total of 78 patients and clinicopathological analysis were also performed . Among the growth factors tested , epidermal growth factor ( EGF ) had prominent effects on inducing CK19 expression in PLC-5 and HepG2 , which was accompanied by the reduced expression of α-fetoprotein in PLC-5 . The induction of CK19 expression after EGF stimulation was accompanied by the phosphorylation of c-Jun-N-terminal kinase ( JNK)/stress-activated protein kinase , which was blocked by the addition of JNK inhibitors . EGF also increased proliferative abilities and invasive properties of the HCC cell lines . In vivo , 9 ( 12% ) of 78 HCC cases showed positive immunohistochemical staining of CK19 . The extent of positive immunohistochemical signals of EGF , EGF receptor ( EGFR ) , and JNK expression was significantly intense in CK-19-positive HCC than those of CK19-negative HCC . Clinicopathological analysis showed that CK19-positive HCC had a high incidence of portal vein invasion , extrahepatic metastasis and an early relapse , which was associated with the worsened 2-year disease free survival . These results indicate that the activation of the EGF-EGFR signaling pathway is associated with the development of CK19-positive HCC , and the EGF-induced increase in growth abilities of HCC may account for the poor prognosis of the patients .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component ( a composite tumor ) rather than a pure rhabdoid tumor . Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin . Rhabdoid features in prostatic stromal sarcomas ( PSSs ) have never been described in the literature . Here , we report a case of a PSS with rhabdoid features . A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain . Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder . A needle biopsy was diagnosed as an unclassified spindle cell sarcoma , and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given , followed by radical prostatectomy . The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis . In areas , the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component . Both spindle and rhabdoid tumor cells were positive for vimentin , CD34 , and progesterone receptor and negative for desmin and cytokeratin immunostainings . The rhabdoid tumor cells retained INI1 expression . The tumor recurred in the bladder , and the patient died of sepsis . To the best of our knowledge , this is the first case of PSS with rhabdoid features . The tumor showed an aggressive clinical behavior with a short-term survival ( 7 months after diagnosis ) .\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: It is well known that ErbB2 , a receptor tyrosine kinase , localizes to the plasma membrane . Here we describe a novel observation that ErbB2 also localizes in mitochondria of cancer cells and patient samples . We found that ErbB2 translocates into mitochondria through association with mtHSP70 . Additionally , mitochondrial ErbB2 ( mtErbB2 ) negatively regulates mitochondrial respiratory functions . Oxygen consumption and activities of complexes of the mitochondrial electron transport chain were decreased in mtErbB2-overexpressing cells . Mitochondrial membrane potential and cellular ATP levels were also decreased . In contrast , mtErbB2 enhanced cellular glycolysis . The translocation of ErbB2 and its impact on mitochondrial function are kinase dependent . Interestingly , cancer cells with higher levels of mtErbB2 were more resistant to the ErbB2-targeting antibody trastuzumab . Our study provides a novel perspective on the metabolic regulatory function of ErbB2 and reveals that mtErbB2 has an important role in the regulation of cellular metabolism and cancer cell resistance to therapeutics .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Androgens and the androgen receptor ( AR ) play important roles in the development of male urogenital organs . We previously found that mice with total AR knockout ( ARKO ) and epithelial ARKO failed to develop normal prostate with loss of differentiation . We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate . However , AR roles of stromal fibroblasts in prostate development remain unclear . METHODS To further probe the stromal fibroblast AR roles in prostate development , we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts ( FSP-ARKO ) . We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development . RESULTS The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation , increased apoptosis , and decreased collagen composition . Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors . To further confirm these in vivo findings , we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells , as well as decrease of some stromal growth factors . CONCLUSIONS Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate , but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Nuclear factor kappa-B ( NF-κB ) activates multiple genes with overlapping roles in cell proliferation , inflammation and cancer . Using an unbiased approach we identified human CDK6 as a novel kinase phosphorylating NF-κB p65 at serine 536 . Purified and reconstituted CDK6/cyclin complexes phosphorylated p65 in vitro and in transfected cells . The physiological role of CDK6 for basal as well as cytokine-induced p65 phosphorylation or NF-κB activation was revealed upon RNAi-mediated suppression of CDK6 . Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-κB and TNF-induced gene expression . In complex with a constitutively active viral cyclin CDK6 stimulated NF-κB p65-mediated transcription in a target gene specific manner and this effect was partially dependent on its ability to phosphorylate p65 at serine 536 . Tumor formation in thymi and spleens of v-cyclin transgenic mice correlated with increased levels of p65 Ser536 phosphorylation , increased expression of CDK6 and upregulaton of the NF-κB target cyclin D3 . These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-κB to chronic inflammation and neoplasia .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Neuroblastoma ( NBL ) is a common pediatric solid tumor , and outcomes for patients with advanced neuroblastoma remain poor despite extremely aggressive treatment . Chemotherapy resistance at relapse contributes heavily to treatment failure . The poor survival of patients with high-risk NBL prompted this investigation into novel treatment options with the objective of gaining a better understanding of resistance mechanisms . On the basis of previous work and on data from publicly available studies , the authors hypothesized that human epidermal growth factor receptor 4 ( Her4 ) contributes to resistance . METHODS Her4 expression was reduced with small-hairpin RNA ( shRNA ) to over express intracellular HER4 , and the authors tested its impact on tumor cell survival under various culture conditions . The resulting changes in gene expression after HER4 knockdown were measured by using a messenger RNA ( mRNA ) array . RESULTS HER4 expression was up-regulated in tumor spheres compared with the expression in monolayer culture . With HER4 knockdown , NBL cells became less resistant to anoikis and serum starvation . Moreover , HER4 knockdown increased the chemosensitivity of NBL cells to cisplatin , doxorubicin , etoposide , and activated ifosfamide . In mRNA array analysis , HER4 knockdown predominately altered genes related to cell cycle regulation . In NBL spheres compared with monolayers , cell proliferation was decreased , and cyclin D expression was reduced . HER4 knockdown reversed cyclin D suppression . Overexpressed intracellular HER4 slowed the cell cycle and induced chemoresistance . CONCLUSIONS The current results indicated that HER4 protects NBL cells from multiple exogenous apoptotic stimuli , including anoikis , nutrient deficiency , and cytotoxic chemotherapy . The intracellular fragment of HER4 was sufficient to confer this phenotype . HER4 functions as a cell cycle suppressor , maintaining resistance to cellular stress . The current findings indicate that HER4 overexpression may be associated with refractory disease , and HER4 may be an important therapeutic target .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;evading growth suppressors;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Reactive or activated stroma characterizes many malignancies including breast cancers . Recently , we isolated a reactive mouse mammary gland stromal cell line called BJ3Z . These cells express alpha-smooth muscle actin and stromal cell-derived factor 1 ( SDF-1 ) and are tumorigenic when injected into mice . Here we show that , in vivo , BJ3Z cells influence the angiogenesis and proliferation of xenografted estrogen receptor ( ER)-positive MCF-7 human breast cancer cell-derived solid tumors . The growth-promoting effects of BJ3Z cells are equivalent to those of estradiol ( E(2) ) . BJ3Z cells also increase the proliferation of normal mouse mammary luminal cells adjacent to tumors . In vitro , BJ3Z cells reorganize and increase the proliferation of cocultured malignant MCF-7 and normal human breast MCF10A cells grown as organoids in three-dimensional culture . The effects of BJ3Z cells on MCF-7 cells are equivalent to those of E(2) . In contrast , BJ3Z cells do not alter the growth of highly aggressive ER-negative MDA-MB-231 human breast cancer cells . We show that BJ3Z cells secrete vascular endothelial growth factor ( VEGF ) . The growth of MCF-7 organoids induced by BJ3Z can be inhibited by antagonists of VEGF and SDF-1 . Conversely , recombinant VEGF stimulates the proliferation of MCF-7 , but not MDA-MB-231 , organoids . We conclude that , in addition to angiogenesis , VEGF released by activated stroma increases the growth of ER-positive malignant epithelial cells and of adjacent normal epithelium . Because activated stroma can substitute for E(2) and fosters hormone-independent growth of ER-positive tumors , we suggest that breast cancers exhibiting intrinsic hormone resistance may respond to antiangiogenic therapies .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Cellular and clinical sensitivity to ionizing radiation ( IR ) is determined by DNA double-strand breaks ( DSB ) repair . Here , we investigate the molecular mechanism underlying the extreme response of a head and neck tumor case ( SKX ) to standard radiotherapy . METHODS Immunofluorescence ( IF ) was used for the assessment of DSB repair , Western blot and real-time PCR for protein and mRNA expression , respectively . RESULTS SKX cells exhibited a pronounced radiosensitivity associated with numerous residual γ-H2AX foci after IR . This was not associated with lacking canonical repair proteins . SKX cells did not express any ATM protein . Accordingly , immunoblotting revealed no ATM kinase activity toward substrates such as p-SMC1 , p-CHK2 and p-KAP1 . Sequencing of all 66 exons of ATM showed no mutation . ATM mRNA level was moderately reduced , which could be reverted by 5'-Aza-C treatment but without restoring protein levels . Importantly , we demonstrated a post-transcriptional regulation in SKX cells via 6-fold enhanced levels of miR-421 , which targets the 3'-UTR of ATM mRNA . Transfection of SKX cells with either anti-miR-421 inhibitor or a microRNA-insensitive ATM vector recovered ATM expression and abrogated the hyper-radiosensitivity . CONCLUSION This is the first report describing microRNA-mediated down-regulation of ATM leading to clinically manifest tumor radiosensitivity .\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: Glioma tumors are refractory to conventional treatment . Glioblastoma multiforme is the most aggressive type of primary brain tumors in humans . In this study , we introduce oxidative stress-energy depletion ( OSED ) therapy as a new suggested treatment for glioblastoma . OSED utilizes D-amino acid oxidase ( DAO ) , which is a promising therapeutic protein that induces oxidative stress and apoptosis through generating hydrogen peroxide ( H2O2 ) . OSED combines DAO with 3-bromopyruvate ( 3BP ) , a hexokinase II ( HK II ) inhibitor that interferes with Warburg effect , a metabolic alteration of most tumor cells that is characterized by enhanced aerobic glycolysis . Our data revealed that 3BP induced depletion of energetic capabilities of glioma cells. 3BP induced H2O2 production as a novel mechanism of its action . C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation , clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes . DAO gene therapy using atelocollagen as an in vivo transfection agent proved effective in a glioma tumor model in Sprague-Dawley ( SD ) rats , especially after combination with 3BP . OSED treatment was safe and tolerable in SD rats . OSED therapy may be a promising therapeutic modality for glioma .\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: Senescence limits the proliferative capacity of primary cells in culture . We describe here a genetic screen to identify genes that allow bypass of this checkpoint . Using retroviral cDNA expression libraries , we identify BCL6 as a potent inhibitor of senescence . BCL6 is frequently activated in non-Hodgkin's lymphoma , but its mechanism of action has remained unclear . BCL6 efficiently immortalizes primary mouse embryonic fibroblasts and cooperates with RAS in oncogenic transformation . BCL6 overrides the senescence response downstream of p53 through a process that requires induction of cyclin D1 expression , as cyclin D1 knockout fibroblasts are specifically resistant to BCL6 immortalization . We show that BCL6 expression also dramatically extends the replicative lifespan of primary human B cells in culture and induces cyclin D1 expression , indicating that BCL6 has a similar activity in lymphoid cells . Our results suggest that BCL6 contributes to oncogenesis by rendering cells unresponsive to antiproliferative signals from 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: Background . An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients . However , whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites . Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors , but their presence in breast cancer bone metastases has not been assessed previously . Results . Fourteen patients with breast cancer bone metastases were biopsied by three methods : CT-guided bone biopsies ; bone marrow trephine biopsies ; and bone marrow aspiration . Samples that were positive for cancer cells were obtained from six patients . Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells . Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases . For each of these , the PIK3CA mutation status was the same in the primary and metastatic sites . Conclusions . PIK3CA mutations occur frequently in breast cancer bone metastases . The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour . Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The relevance of many BRCA2 variants of uncertain significance ( VUS ) to breast cancer has not been determined due to limited genetic information from families carrying these alterations . Here , we classified six new variants as pathogenic or nonpathogenic by analysis of genetic information from families carrying 64 individual BRCA2 DNA binding domain ( DBD ) missense mutations using a multifactorial likelihood model of cancer causality . Next , we evaluated the use of a homology-directed DNA break repair ( HDR ) functional assay as a method for inferring the clinical relevance of VUS in the DBD of BRCA2 using 18 established nonpathogenic missense variants and all 13 established pathogenic missense mutations from the BRCA2 DBD . Compared with the known status of these variants based on the multifactorial likelihood model , the sensitivity of the HDR assay for pathogenic mutations was estimated at 100% [ 95% confidence interval ( CI ) : 75.3%-100% ] and specificity was estimated at 100% ( 95% CI : 81.5%-100% ) . A statistical classifier for predicting the probability of pathogenicity of BRCA2 DBD variants was developed using these functional results . When applied to 33 additional VUS , the classifier identified eight with 99% or more probability of nonpathogenicity and 18 with 99% or more probability of pathogenicity . Thus , in the absence of genetic evidence , a cell-based HDR assay can provide a probability of pathogenicity for all VUS in the BRCA2 DBD , suggesting that the assay can be used in combination with other information to determine the cancer relevance of BRCA2 VUS .\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 examined how well the human papillomavirus ( HPV ) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer : the Asian-American E6 variant ( AAE6 ) . This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant , as evidenced by independent epidemiological data . Using cell culture and cell-based functional assays , we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant . The ability to immortalize and transform primary human foreskin keratinocytes ( PHFKs ) to acquire resilient phenotypes and the ability to promote cell migration were evaluated . The immortalization capability was assayed based on population doublings , number of passages , surpassing mortality stages 1 and 2 , human telomerase reverse transcriptase ( hTERT ) expression , and the ability to overcome G(1) arrest via p53 degradation . Transformation and migration efficiency were analyzed using a combination of functional cell-based assays . We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs , although AAE6 was more potent in doing so . The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype . Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer , as evidenced by a superior immortalization , transformation , and metastatic potential .\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: Oncostatin M ( OSM ) , an interleukin-6 type cytokine , acts via the gp130 signaling receptor to inhibit proliferation and induce differentiation of breast cancer cells . EGF , a mitogen for breast cells , signals via EGFR/ErbB tyrosine kinase receptors which are implicated in breast cancer pathogenesis . Here we show paradoxically that EGF enhanced the OSM-induced inhibition of proliferation and induction of cellular differentiation in both estrogen receptor positive and negative breast cancer cells . This functional synergism was also seen with heregulin but not SCF , PDGF or IGF-1 , indicating that it was specific to EGF-related growth factors . Immunoprecipitation experiments revealed that gp130 was constitutively associated with ErbB-2 and ErbB-3 . There was a similar association between the OSMRbeta and ErbB-2 . Furthermore , EGF unexpectedly induced tyrosine phosphorylation of gp130 . We show that OSM induced phosphorylation of STAT3 . Both OSM and EGF activated the p42/44 MAP kinases , but while the MEK inhibitor , PD98059 , ablated the OSM-induced inhibition , it only partially ablated the inhibitory effects of OSM plus EGF . Thus , we have demonstrated that the receptors and signalling pathways of two apparently unrelated growth factors were intimately linked , resulting in an unexpected biological effect . This provides a new mechanism for generating signalling diversity and has potential clinical implications in breast cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Mutations in the tumor suppressor tuberin ( TSC2 ) are a common factor in the development of lymphangioleiomyomatosis ( LAM ) . LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma . The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated , although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells . Here we show that tuberin-null cells become nonadherent and invasive . These nonadherent cells express cleaved forms of β-catenin . In reporter assays , the β-catenin products are transcriptionally active and promote MMP7 expression . Invasion by the tuberin-null cells is mediated by MMP7 . Examination of LAM tissues shows the expression of cleaved β-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a β-catenin-dependent mechanism , which may underlie the development of LAM .\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 mechanisms of formation of sister chromatid exchanges ( SCEs ) and chromosome aberrations following inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide were studied in Chinese hamster ovary cell lines deficient in different repair pathways . The results confirm earlier findings that ( a ) the ' spontaneous ' SCEs are formed due to the incorporated BrdU in the DNA , ( b ) ' spontaneous ' and induced SCEs originate from different mechanisms , and ( c ) SCEs and chromatid exchanges are formed by different pathways .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Purpose . The purpose of this paper is to evaluate a new PET tracer ( 64)Cu-NODAGA-c(RGDyK ) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans . Procedures . Nude mice with human neuroendocrine tumor xenografts ( H727 ) were administered ( 64)Cu-NODAGA-c(RGDyK ) i.v. for study of biodistribution as well as for dynamic PET . Gene expression of angiogenesis markers integrin α(V) , integrin β(3) , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors ( %ID/g ) . From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM . Results . Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake , for integrin α(V) R = 0.76 , integrin β(3) R = 0.75 and VEGF-A R = 0.81 ( all P &lt ; 0.05 ) . The whole body effective dose for humans was estimated to be 0.038 and 0.029 mSv/MBq for females and males , respectively , with highest absorbed dose in bladder wall . Conclusion . ( 64)Cu-NODAGA-c(RGDyK ) is a promising new angiogenesis PET tracer with potential for human use .\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: AIM To investigate whether luteolin , a highly prevalent flavonoid , reverses the effects of epithelial-mesenchymal transition ( EMT ) in vitro and in vivo and to determine the mechanisms underlying this reversal . METHODS Murine malignant melanoma B16F10 cells were exposed to 1% O(2) for 24 h . Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay , respectively . EMT-related proteins , such as E-cadherin and N-cadherin , were examined using Western blotting . Female C57BL/6 mice ( 6 to 8 weeks old ) were injected with B16F10 cells ( 1�10(6) cells in 0.2 mL per mouse ) via the lateral tail vein . The mice were treated with luteolin ( 10 or 20 mg/kg , ip ) daily for 23 d . On the 23rd day after tumor injection , the mice were sacrificed , and the lungs were collected , and metastatic foci in the lung surfaces were photographed . Tissue sections were analyzed with immunohistochemistry and HE staining . RESULTS Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips , which was accompanied by increased cellular adhesion and invasion . Luteolin ( 5-50 μmol/L ) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner . Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells ( indicating the occurrence of EMT-like transformation ) , which was reversed by luteolin ( 5 μmol/L ) . In B16F10 cells , luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway . In experimental metastasis model mice , treatment with luteolin ( 10 or 20 mg/kg ) reduced metastatic colonization in the lungs by 50% . Furthermore , the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues . CONCLUSION Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin , suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent .\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 ASPP2 ( also known as 53BP2L ) tumor suppressor is a proapoptotic member of a family of p53 binding proteins that functions in part by enhancing p53-dependent apoptosis via its C-terminal p53-binding domain . Mounting evidence also suggests that ASPP2 harbors important nonapoptotic p53-independent functions . Structural studies identify a small G protein Ras-association domain in the ASPP2 N terminus . Because Ras-induced senescence is a barrier to tumor formation in normal cells , we investigated whether ASPP2 could bind Ras and stimulate the protein kinase Raf/MEK/ERK signaling cascade . We now show that ASPP2 binds to Ras-GTP at the plasma membrane and stimulates Ras-induced signaling and pERK1/2 levels via promoting Ras-GTP loading , B-Raf/C-Raf dimerization , and C-Raf phosphorylation . These functions require the ASPP2 N terminus because BBP ( also known as 53BP2S ) , an alternatively spliced ASPP2 isoform lacking the N terminus , was defective in binding Ras-GTP and stimulating Raf/MEK/ERK signaling . Decreased ASPP2 levels attenuated H-RasV12-induced senescence in normal human fibroblasts and neonatal human epidermal keratinocytes . Together , our results reveal a mechanism for ASPP2 tumor suppressor function via direct interaction with Ras-GTP to stimulate Ras-induced senescence in nontransformed human cells .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Peroxisome proliferator-activated receptor-γ ( PPARγ ) is an anti-inflammatory molecule . To study its biologic function in myeloid cells , dominant-negative PPARγ ( dnPPARγ ) was overexpressed in a myeloid-specific bitransgenic mouse model . In this bitransgenic system , overexpression of the dnPPARγ-Flag fusion protein in myeloid-lineage cells abnormally elevated frequencies and total numbers of IL-7Rα(-)Lin(-)c-Kit(+)Sca-1(-) , Lin(-)/Scal(+)/c-Kit(+) , common myeloid , and granulocyte-monocyte progenitor populations in the BM. dnPPARγ overexpression led to up-regulation of IL-1β , IL-6 , and TNFα in the blood plasma . As a result , CD11b(+)Ly6G(+) cells were systemically increased in association with activation of Stat3 , NF-κB , Erk1/2 , and p38 molecules . Myeloid-derived suppressor cells ( MDSCs ) inhibited the proliferation and lymphokine production of wild-type CD4+ T cells in vitro . CD4+ T cells from doxycycline-treated bitransgenic mice displayed reduced proliferation and lymphokine release . Both CD4+ and CD8+ T-cell populations were decreased in doxycycline-treated bitransgenic mice . Multiple forms of carcinoma and sarcoma in the lung , liver , spleen , and lymph nodes were observed in doxycycline-treated bitransgenic mice . BM transplantation revealed that a myeloid-autonomous defect was responsible for MDSC expansion , immunosuppression , and tumorigenesis in these mice . These studies suggest that anti-inflammatory PPARγ in myeloid-lineage cells plays a key role in controlling pro-inflammatory cytokine synthesis , MDSC expansion , immunosuppression , and the development of cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In this study , laboratory experiments were carried out in order to come to a better understanding of the fate of polycyclic aromatic hydrocarbons ( PAHs ) in the marine environment and especially on their bioaccumulation , biotransformation and genotoxic effects in fish . Juveniles of turbot ( Scophthalmus maximus ) were exposed to PAHs through different routes via ( 1 ) a mixture of dissolved PAHs , ( 2 ) a PAH-polluted sediment and ( 3 ) an oil fuel elutriate . Fish were exposed 4 days followed by a 6-day depuration period . In each experiment , PAH concentrations in the seawater of the tanks were analysed regularly by gas chromatography coupled with mass spectrometry . Muscle and liver samples were also analysed for parent PAH levels and PAH bioconcentration factors were calculated . Biotransformation was evaluated by measuring the levels of PAH metabolites in fish bile . Genotoxicity was assessed by the alkaline comet assay . Regardless of exposure route , the parent PAH concentrations in the liver and muscle showed a peak level 1 day after the beginning of the exposure , followed by a decrease up to the background level towards the end of the experiment , except for the exposure to dissolved PAHs for which levels were relatively low throughout the study . As a consequence , no bioaccumulation was observed in fish tissues at the end of the experiment . In contrast , regardless of exposure routes , a rapid production of biliary metabolites was observed throughout the whole exposure experiment . This was especially true for 1-hydroxypyrene , the major metabolite of pyrene . After 6 days of recovery in clean water , a significant decrease in the total metabolite concentrations occurred in bile . Fish exposed through either route displayed a significant increase in DNA strand breaks after 4 days of exposure , and significant correlations were observed between the level of biliary PAH metabolites and the level of DNA lesions in fish erythrocytes . Overall results indicate that exposure to either a mixture of dissolved PAHs , a PAH-contaminated sediment or a dispersed oil fuel elutriate leads to biotransformation and increase in DNA damage in fish . The quantification of PAH metabolites in bile and DNA damage in erythrocytes appear to be suitable for environmental monitoring of marine pollution either in the case of accidental oil spills or sediment contamination .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Astrocytoma arises in the central nervous system as a tumor of great lethality , in part because of the invasive potential of the neoplastic cells that are able to release extracellular matrix-degrading enzymes . Furin convertase activates several precursor matrix metalloproteases involved in the breakdown of the extracellular matrix . In the present study inhibition of furin was achieved by gene transfer of alpha(1)-antitrypsin Portland ( PDX ) cDNA . EXPERIMENTAL DESIGN This furin inhibitor was transfected into two tumorigenic astrocytoma cell lines . The inhibitory effect was evaluated using in vivo tumorigenicity , invasion , and proliferation assays , as well as by investigating impairment of furin substrate processing . RESULTS Expression of PDX prevented the s.c. growth of the transfected cells . Invasion assays demonstrated that PDX-transfected cells exhibited a reduced invasive ability in vitro and in vivo . Furthermore , s.c. growth of PDX transfectant xenotransplants showed a significant reduction in size that coincided with a significant decrease of the in vitro doubling time and of the in vivo cell proliferation ability . Additional studies showed that the furin substrates insulin-like growth factor IR , transforming growth factor beta and membrane type 1-matrix metalloprotease were not activated in PDX-expressing astrocytoma cells . CONCLUSIONS PDX expression in astrocytoma cells demonstrated a direct mechanistic link between furin inhibition , and decreased astrocytoma proliferation and invasive ability . Because furin inhibition inhibits both invasiveness and cell growth in astrocytoma , furin should be considered a promising target for glioblastoma therapy .\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: Manipulating acetylation status of key gene targets is likely to be crucial for effective cancer therapy . In this study , we utilized green tea catechins , epicatechin ( EC ) , epigallocatechin ( EGC ) and epigallocatechin-3-gallate ( EGCG ) to examine the regulation of androgen receptor acetylation in androgen-dependent prostate cancer cells by histone acetyl-transferase ( HAT ) activity . EC , EGC and EGCG induced prostate cancer cell death , suppressed agonist-dependent androgen receptor ( AR ) activation and AR-regulated gene transcription . These results demonstrated a similar tendency to HAT inhibitory activities ; EGCG>EGC>EC . The strongest HAT inhibitor among them , EGCG ( 50 �M ) , downregulated AR acetylation and finally , AR protein translocation to nucleus from the cytoplasmic compartment was effectively inhibited in the presence of the agonist . These results suggest another mechanism to develop effective therapeutics based on green tea catechins .\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: Insulin-like growth factor ( IGF)-I receptor ( IGF-IR ) signaling is required for carcinogenicity and progression of several cancers but the function of this pathway and its utility as a therapeutic target have not been studied comprehensively in biliary tract carcinomas ( BTC ) . We investigated the immunohistochemical expression of elements of the IGF axis , matrilysin , overexpression of p53 and the methylation status of the IGFBP-3 promoter in 80 surgically resected BTC . We also assessed the effect of IGF-IR blockade on signal transduction , proliferation and survival in three BTC cell lines using a new tyrosine kinase inhibitor , BMS-536924 , and dominant negative IGF-IR ( IGF-IR/dn ) . The effects of IGF-IR blockade was also studied in nude mouse xenograft models . IGF-I was expressed in 60% and IGF-II in 50% of tumors . High expression was associated with tumor size . IGF-IR was expressed in 69% of the cases and was associated with advanced stage and matrilysin expression . Hypermethylation of the IGFBP-3 promoter was detected in 41% of BTC and was inversely correlated with p53 expression . BMS-536924 blocked autophosphorylation of IGF-IR and both Akt and ERK activation by both IGF-I and insulin . BMS-536924 suppressed proliferation and tumorigenicity in vitro in a dose-dependent fashion . This inhibitor upregulated chemotherapy-induced apoptosis in a dose-dependent fashion . Moreover , IGF-IR blockade was effective against tumors in mice . IGF-IR might identify a subset of BTC with a particularly aggressive phenotype and is a candidate therapeutic target in this disease . BMS-536924 might have significant therapeutic utility .\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: There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo . In this study , we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo . The human pancreatic cancer cell line Hs-776T ( HS-W ) produces slow-growing tumors in SCID mice . Cells of a variant form ( HS-R ) of Hs-776T produced faster-growing tumors compared to HS-W . Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) . Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2 , but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R . Cell proliferation was similar in both tumor types in vivo , whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells ( EC ) . Subsequently , VEGF was over-expressed in Hs-776T cells ( HS-VF ) , resulting in rapidly growing tumors and lowering tumor and EC apoptosis . Collectively , our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Bulky DNA adducts are considered a potential biomarker of cancer risk . In this study , the association between various lifestyle , environmental , and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort . At enrollment , blood samples were collected and information on lifestyle , including dietary and smoking habits , obtained . Previously , bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort . Of these 500 individuals , data on 375 individuals were included in this study , excluding 125 cases , which developed lung cancer within the first 3 yr after blood sampling . Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined . Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses . Women tended to have higher adduct levels than men . Living in central Copenhagen and surface darkness of fried meat and fish were associated with quantitative higher adduct levels . No significant associations were found between dietary factors or smoking and DNA adduct levels . Further , the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels . Overall , our study showed only few associations between dietary , environmental , and genetic factors and levels of bulky DNA adducts measured in peripheral leukocytes in a general Danish population .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Melanoma progression is associated with the expression of different growth factors , cytokines , and chemokines . Because TGFβ1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development , we analyzed in A375 human melanoma cells , the effect of TGFβ1 on monocyte chemoattractant protein-1 ( MCP-1 ) and interleukin-10 ( IL-10 ) expression , two known factors responsible for melanoma progression . TGFβ1 increased the expression of MCP-1 and IL-10 in A375 cells , an effect mediated by the cross-talk between Smad , PI3K ( phosphoinositide 3-kinase)/AKT , and BRAF-MAPK ( mitogen activated protein kinase ) signaling pathways . Supernatants from TGFβ1-treated A375 cells enhanced MCP-1-dependent migration of monocytes , which , in turn , expressed high levels of TGF,β1 , bFGF , and VEGF mRNA . Moreover , these supernatants also inhibited functional properties of dendritic cells through IL-10-dependent mechanisms . When using in vitro , the TGFβ1-blocking peptide P144 , TGFβ1-dependent Smad3 phosphorylation , and expression of MCP-1 and IL-10 were inhibited . In vivo , treatment of A375 tumor-bearing athymic mice with P144 significantly reduced tumor growth , associated with a lower macrophage infiltrate and decreased intratumor MCP-1 and VEGF levels , as well as angiogenesis . Finally , in C57BL/6 mice with B16-OVA melanoma tumors , when administered with immunotherapy , P144 decreased tumor growth and intratumor IL-10 levels , linked to enhanced activation of dendritic cells and natural killer cells , as well as anti-OVA T-cell responses . These results show new effects of TGFβ1 on melanoma cells , which promote tumor progression and immunosuppression , strongly reinforcing the relevance of this cytokine as a molecular target in melanoma .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: 4-Hydroxy-2-nonenal ( HNE ) , a major racemic product of lipid peroxidation , reacts with histidine to form a stable HNE-histidine Michael addition-type adduct possessing three chiral centers in the cyclic hemiacetal structure . In the present study , we characterized configurational isomers of a HNE-N(alpha)-acetylhistidine adduct by NMR spectroscopy and by molecular orbital calculations . In addition , we raised monoclonal antibodies against ( R)-HNE-histidine and ( S)-HNE-histidine adducts , characterized their specificities , and examined in vivo localizations of each adduct under oxidative stress . To facilitate structural characterization of the configurational isomers of an HNE-histidine adduct , we prepared the ( R)-HNE-histidine and ( S)-HNE-histidine adducts by incubating N(alpha)-acetylhistidine with each HNE enantiomer , both of which provided two peaks ( Ra and Rb from ( R)-HNE-histidine and Sa and Sb from ( S)-HNE-histidine adducts ) in reversed-phase high-performance liquid chromatography . The NMR analysis showed that each peak was a mixture of two diastereomers . In addition , the analysis of the nuclear Overhauser effect enabled the determination of configurations of the eight isomers . The relative amounts of these isomers in the NMR analysis correlated with the relative energies calculated by molecular orbital methods . On the other hand , using ( R)-HNE-modified and ( S)-HNE-modified keyhole limpet hemocyanins as the antigens , we raised the monoclonal antibodies , mAbR310 and mAbS412 , which enantioselectively recognized the ( R)-HNE-histidine and ( S)-HNE-histidine adducts , respectively . Among the mixtures ( Ra , Rb , Sa , and Sb ) of diastereomers , mAbR310 showed the highest immunoreactivity to Rb ( the mixture of 2R,4S,5R and 2S,4S,5R isomers ) , whereas mAbS412 preferentially recognized Sa ( the mixture of 2R,4S,5S and 2S,4S,5S isomers ) . The presence of ( R)-HNE and ( S)-HNE epitopes in vivo was immunohistochemically examined in the kidney of rats exposed to the renal carcinogen , ferric nitrilotriacetate , by which nuclear and cytosolic stainings with mAbR310 and mAbS412 , respectively , were detected .\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: Most hepatocellular carcinomas ( HCC ) develop in the context of severe liver fibrosis and cirrhosis caused by chronic liver inflammation , which also results in accumulation of reactive oxygen species ( ROS ) . In this study , we examined whether the stress-activated protein kinase p38α ( Mapk14 ) controls ROS metabolism and development of fibrosis and cancer in mice given thioacetamide to induce chronic liver injury . Liver-specific p38α ablation was found to enhance ROS accumulation , which appears to be exerted through the reduced expression of antioxidant protein HSP25 ( Hspb1 ) , a mouse homolog of HSP27 . Its reexpression in p38α-deficient liver prevents ROS accumulation and thioacetamide-induced fibrosis. p38α deficiency increased expression of SOX2 , a marker for cancer stem cells and the liver oncoproteins c-Jun ( Jun ) and Gankyrin ( Psmd10 ) and led to enhanced thioacetamide-induced hepatocarcinogenesis . The upregulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole . Intriguingly , the risk of human HCC recurrence is positively correlated with ROS accumulation in liver . Thus , p38α and its target HSP25/HSP27 appear to play a conserved and critical hepatoprotective function by curtailing ROS accumulation in liver parenchymal cells engaged in oxidative metabolism of exogenous chemicals . Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The association between acute myeloid leukaemia ( AML ) and the aberrant expression of Hoxa9 is evidenced by ( 1 ) proviral activation of Hoxa9 and Meis1 in BXH-2 murine AML , ( 2 ) formation of the chimeric Nup98-HoxA9 transactivator protein as a consequence of the t(7;11) translocation in human AML , and ( 3 ) the strong expression of HoxA9 and Meis1 in human AML . In mouse models , enforced retroviral expression of Hoxa9 alone in marrow is not sufficient to cause rapid AML , while co-expression of Meis1 and Hoxa9 induces rapid AML . In contrast , retroviral expression of Nup98-HoxA9 is sufficient to cause rapid AML in the absence of enforced Meis1 expression . Previously , we demonstrated that Hoxa9 could block the differentiation of murine marrow progenitors cultured in granulocyte-macrophage colony-simulating factor ( GM-CSF ) . These progenitors lacked Meis1 expression , could not proliferate in stem cell factor ( SCF ) , but could differentiate into neutrophils when switched into granulocyte colony-simulating factor ( G-CSF ) . Ectopic expression of Meis1 in these Hoxa9 cells suppressed their G-CSF-induced differentiation , permitted proliferation in SCF , and therein offered a potential explanation of cooperative function . Because Meis1 binds N-terminal Hoxa9 sequences that are replaced by Nup98 , we hypothesized that Nup98-HoxA9 might consolidate the biochemical functions of both Hoxa9 and Meis1 on target gene promoters and might evoke their same lymphokine-responsive profile in immortalized progenitors . Here we report that Nup98-HoxA9 , indeed mimicks Hoxa9 plus Meis1 coexpression - it immortalizes myeloid progenitors , prevents differentiation in response to GM-CSF , IL-3 , G-CSF , and permits proliferation in SCF . Unexpectedly , however , Nup98-Hoxa9 also enforced strong transcription of the cellular Hoxa9 , Hoxa7 and Meis1 genes at levels similar to those found in mouse AML's generated by proviral activation of Hoxa9 and Meis1 . Using Hoxa9(-/-) marrow , we demonstrate that expression of Hoxa9 is not required for myeloid immortalization by Nup98-HoxA9 . Rapid leukaemogenesis by Nup98-HoxA9 may therefore result from both the intrinsic functions of Nup98-HoxA9 , as well as of those of coexpressed HOX and MEIS1 genes .\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: Osteoblastic bone metastases are the most common metastases produced by human prostate cancers ( PCa ) . Deregulated activity of Wnt growth factors resulting from overexpression of the Wnt inhibitor Dickkopf-1 ( DKK-1 ) is known to contribute to formation of the osteoblastic component of PCa skeletal bone metastases . In this study , we report that DKK-1 knockdown in osteolytic human PCa cells unexpectedly delays the development of both soft tissue and osseous lesions . PCa cells deficient in DKK-1 expression did not increase canonical Wnt signaling in target osteoblast cell lines ; however , DKK-1 knockdown PCa cells exhibited increased expression of the CDK inhibitor p21(CIP1/WAF1) and a 32% increase in G(1) arrest compared with control cells . Ablating p21(CIP1/WAF1) in PCa cells deficient in DKK-1 was sufficient to rescue tumor growth . Collectively , our findings demonstrate that DKK-1 overexpression supports tumor growth in part by restricting expression of p21(CIP1/WAF1) through a mechanism independent of canonical Wnt signaling .\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: The effects of genomic changes in hepatitis B virus ( HBV ) on the occurrence of hepatocellular carcinoma ( HCC ) are still unclear , especially in relation to the genotype of HBV . In this study , we examined the effects of genomic changes in HBV of genotype C2 on the development of HCC . A total of 318 patients with HBV-associated HCC and 234 patients with chronic hepatitis B ( CHB ) were studied . All of HCC cases were diagnosed histologically and treated with surgical resection . The whole of the X , S , basal core promoter ( BCP ) and precore regions of the viral genome from sera or liver tissues were sequenced . All subjects had HBV of genotype C2 . The prevalence of the T1653 mutation in the X region and the A1896 mutation in the precore region of HBV was significantly higher in the HCC group than in the control CHB group ( 22% vs 11% , P = 0.003 ; 50% vs 23% , P &lt ; 0.001 , respectively ) . Moreover , the T1762/A1764 mutations in the BCP region in combination with either T1653 or A1896 were more common in the HCC compared with the CHB group ( BCP+X1653 : 18% vs 11% , P = 0.05 ; BCP+PC , 40% vs 15% , P &lt ; 0.001 , respectively ) . In multivariate analysis , T1653 and A1896 were revealed to be independent risk factors for HCC development . G1896A in the precore region and C1653T mutation in the X region of genotype C2 HBV are important risk factors for HCC development . Also , the A1762T/G1764A double mutation may act in synergy with C1653T to increase the risk of HCC in patients chronically infected with HBV genotype C2 .\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: Vascular endothelial growth factor A ( VEGF-A ) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis . SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase . We have developed a reproducible murine model for neuroblastoma , a childhood cancer , based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells . We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels , that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume &gt ; 1.4 ml , and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals . Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity . SU5416 treatment also suppressed tumor angiogenesis , despite an increase in plasma VEGF-A levels per ml tumor volume during therapy . Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE We did this retrospective study to explore the association between epidermal growth factor receptor ( EGFR ) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer ( NSCLC ) . MATERIALS AND METHODS We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007 . The start of tyrosine kinase inhibitor therapy was treated as a censoring event . Corresponding surgical specimens of primary tumors were used to test for EGFR mutations . RESULTS Thirty patients presented with local recurrence and distant recurrence was identified in 56 . Thirty-four of the 86 patients ( 40% ) harbored EGFR mutations . Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence ( 48% versus 23% ; P = 0.024 ) . On multivariate analysis , distant recurrence was associated with a high frequency of EGFR mutations ( OR , 3.3 ; P = 0.028 ) . Survival analysis showed poor survival of patients with mutated EGFR ( HR , 2.3 ; P = 0.017 ) or with non-adenocarcinoma histology ( HR , 3.3 ; P = 0.001 ) . CONCLUSION The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients . In addition , our data indicate unfavorable disease process of EGFR mutated tumors . Further studies need to be conducted to validate these findings .\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: Palmitoylation is required for the activities of several cancer-associated proteins , making the palmitoyl acyltransferase ( PAT ) enzymes that catalyze these reactions potential targets for anticancer therapeutics . In this study , we sought to identify and characterize a human PAT with activity toward N-terminally myristoylated and palmitoylated proteins . NIH/3t3 cells were stably transfected with vectors containing no insert , wild type human DHHC20 , or a serine-substituted DHHS20 mutant . Compared with control cells , cells overexpressing wild-type DHHC20 displayed an increase in palmitoylation activity toward a peptide that mimics the N-terminus of myristoylated and palmitoylated proteins , but had no change in activity toward a peptide that mimics the C-terminus of farnesylated and palmitoylated proteins . Cells expressing DHHS20 had no significant change in activity toward either peptide . Overexpression of DHHC20 also caused phenotypic changes consistent with cellular transformation , including colony formation in soft agar , decreased contact inhibition of growth , and increased proliferation under low-serum conditions . Quantitative polymerase chain reaction analyses of human tissues demonstrated that DHHC20 is expressed in a tissue-specific manner , and is overexpressed in several types of human tumors , including ovarian , breast and prostate . Overall , these results demonstrate that DHHC20 is a human N-terminal-myristoyl-directed PAT involved in cellular transformation , that may play a role in cancer .\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: Exposure to benzo[a]pyrene ( BaP ) can induce inflammatory skin diseases and skin cancer , which are both associated to oxidative stress . BaP is known to bind with high specificity to the aryl hydrocarbon receptor ( AhR ) , modifying the expression of CYP1A1 , involved both in cancer and inflammation . While the current knowledge is based on murine skin and cell culture data , in this study human healthy skin has been treated with 5muM BaP in conditions simulating occupational and environmental exposure . AhR and CYP1A1 expression was evaluated by Western blotting , which revealed their presence even in control untreated skin ; both enzyme and receptor increased more than twofold after exposure to BaP . AhR expression level was lower than CYP1A1 in basal conditions and following induction . Oxidative stress was evaluated in terms of MTT reduction , protein peroxidation and reactive oxygen species ( ROS ) formation . A significant increase in ROS and carbonyl compound production , as well as reduced tissue viability have been determined by BaP . The results of this experiment indicate that BaP , an AhR agonist , can significantly increase receptor and CYP1A1 expression and induce oxidative stress in human skin , confirming the involvement of this pathway in the pathogenesis of tissue damage due to polycyclic aromatic hydrocarbons .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Though an increased efficacy of carmustine and temozolomide ( TMZ ) has been demonstrated by inactivation of O(6)-methylguanine-DNA methyltransferase ( MGMT ) with O(6)-benzyl-guanine ( BG ) in human pancreatic tumors refractive to alkylating agents , the regulatory mechanisms have not been explored . METHODS The effects of TMZ and BG on apoptosis , cell growth , the mitotic index , cell cycle distribution , and protein expression were studied by TUNEL , cell counting , flow cytometry , and Western blot analysis , respectively . RESULTS The wt-p53 human pancreatic tumor cell line Capan-2 and p53-efficient mouse embryonic fibroblasts ( MEFs ) were more responsive to treatment with TMZ + BG than mutant p53 Capan-1 and p53-null MEFs . S phase delay with a subsequent G2/M arrest was observed in Capans in response to BG + TMZ . The G1-to-S transition delay in Capan-2 was associated with p53-dependent apoptosis and was distinctly different from the presumed mismatch repair ( MMR ) killing operative during the G2/M arrest . The effect of p53 on BG + TMZ toxicity was supported by a marked change in apoptosis when p53 function was restored/inactivated . There was an early induction of MMR proteins in p53-efficient lines . CONCLUSION p53 provokes a classic proapoptotic response by delaying G1-to-S progression , but it may also facilitate cell killing by enhancing MMR-related cell cycle arrest and cell death .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;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: In the present study , the question was addressed whether anthocyanins interfere with the topoisomerase I poison irinotecan in vivo . In vivo complexes of enzyme to DNA bioassay was used to detect irinotecan-induced stabilization of topoisomerase I/DNA complexes and single cell gel electrophoresis to determine DNA-strand-break induction in the colon of male Wistar rats . Furthermore , analysis of anthocyanin concentrations in rat plasma and rat colon was included in the testing , demonstrating that anthocyanins reach the colon and the concentrations do not differ between rats that only received anthocyanins and the anthocyanin/irinotecan group . Blackberry extract was found to significantly reduce irinotecan-mediated topoisomerase I/DNA cleavable complex formation . Overall , anthocyanins did not notably increase cleavable complex formation . However , a significant increase of DNA damage was shown after a single dose of irinotecan as well as the single compounds cyanidin ( cy ) and cyanidin-3-glucoside ( cy-3-g ) . Furthermore , a significant reduction of irinotecan-induced DNA-strand breaks after a pretreatment with cy , cy-3-g and blackberry extract was observed . Thus , the question arises whether anthocyanin-rich preparations might interfere with chemotherapy or whether , due to low systemic bioavailability , the preparations might provide protective potential in the gastrointestinal tract .\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 wanted to investigate the effects of gamma radiation on DNA single-strand breaks ( SSB ) and glutathione ( GSH ) levels in mononuclear blood cells ( MNC ) of radiotherapy technicians . DNA SSB in MNC of radiotherapy technicians who use ( 60)Co-gamma source in their works were detected by alkaline filter elution and compared to control subjects . In addition , GSH levels were measured using the enzymatic method in MNC . Blood samples were collected from radiotherapy technicians on Monday and Friday . DNA SSB levels were found to be significantly higher in smoking controls compared to non-smoking controls . Significant increases of 36% and 49% in DNA SSB were detected from Monday to Friday for non-smoking and smoking radiotherapy technicians , respectively . GSH levels were found to be decreased significantly from Monday to Friday . Gamma-radiation resulted in increased DNA SSB levels of MNC in radiotherapy technicians throughout the working week and these breaks have been observed to be repaired at the weekend . Smoking habit caused an additional increase in the SSBs observed in radiotherapy technicians .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE Osteosarcoma is an aggressive primary bone cancer characterized by expression of platelet-derived growth factor ( PDGF ) and its cognate receptor . Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms . It has been reported previously that STI571 has specific activity in inhibiting select tyrosine kinase receptors , including PDGF and c-Kit . Osteosarcomas express low levels of c-Kit but abundant levels of PDGF receptor ( PDGFR ) . EXPERIMENTAL DESIGN To investigate the potential of STI571 as therapy for osteosarcoma , we studied its effects on PDGF-mediated cell growth in vitro and in an in vivo mouse model . RESULTS PDGF acted as a potent mitogen in a dose-dependent manner in two osteosarcoma cell lines . STI571 ( 1.0 micro M ) inhibited both PDGFR-alpha and PDGFR-beta phosphorylation and the downstream phosphorylation targets extracellular signal-regulated kinase and Akt . STI571 also inhibited PDGF-mediated growth and induced apoptosis in vitro as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining . To study the effect of STI571 alone or in combination with Taxol in an in vivo model , an osteosarcoma cell line ( KRIB ) was transplanted into the tibia of athymic nude mice . Mice were treated with STI571 ( 50 mg/kg p.o. q M-F ) , Taxol ( 8 mg/kg i.p. weekly ) , or STI571 plus Taxol for 6 weeks . There was no significant difference in tumor size between treatment and control mice . Aberrant signaling pathways downstream of the PDGFR in the v-Ki-ras oncogene-transformed KRIB cell line may in part explain this finding . CONCLUSIONS Our data demonstrate that STI571 inhibits PDGF-mediated growth and leads to apoptosis of osteosarcoma cells in vitro by selective inhibition of the PDGFR tyrosine kinase . The effectiveness of STI571 in our studies suggests targeting of PDGFRs as a novel treatment for osteosarcoma .\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: A tumor growth-dependent elevation in the hepatic levels of Zn and metallothionein ( MT ) , without a change in the level of Cu , was found in mice and rats bearing solid tumors in the inguinal region . The levels of Zn and MT thus elevated gave a significant correlation ( r = 0.95 ) between them . Nevertheless , when tumor-bearing mice and rats were fed a Zn-deficient diet , the hepatic levels of Zn and MT did not increase . In mice in which inflammation was induced at the same region , on the other hand , hepatic levels of Zn and MT increased transiently after the injection of turpentine or carrageenan even when they were fed the Zn-deficient diet . These results suggest that the elevation of MT and Zn levels can be a helpful marker for detecting malignancy .\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: PURPOSE This study aims to investigate the role of the aberrant expression of Transkelolase-like 1 ( TKTL1 ) in head and neck squamous cell carcinoma ( HNSCC ) tumorigenesis and to characterize TKTL1 contribution to HNSCC tumorigenesis through aerobic glycolysis and HIF1alpha stabilization . EXPERIMENTAL DESIGN TKTL1 promoter hypomethylation and mRNA/protein aberrant expression were studied in human HNSCC tumor samples and normal mucosas . Oncogenic functions of TKTL1 were examined in HNSCC cell line panels and tumor xenograft models with TKTL1 expression construct . The metabolite levels of fructose-6-phosphate , glyceraldehydes-3-phosphate , pyruvate , lactate , and the levels of HIF1alpha protein and its downsteam glycolytic targets were compared between the TKTL1-expressing and vehicle-expressing HNSCC cells . Meanwhile , the effects of HIF1alpha/glycolytic inhibitors were evaluated on the TKTL1 transfectants . RESULTS TKTL1 exhibits high frequency of promoter hypomethylation in HNSCC tumors compared with the normal mucosas , correlating with its overexpression in HNSCC . Overexpression of TKTL1 in HNSCC cells promoted cellular proliferation and enhanced tumor growth in vitro and in vivo . Overexpression of TKTL1 increased the production of fructose-6-phosphate and glyceraldehyde-3-phosphate , in turn elevating the production of pyruvate and lactate , resulting in the normoxic stabilization of the malignancy-promoting transcription factor HIF1alpha and the upregulation of downstream glycolytic enzymes . Notably , the reduction of TKTL1 expression decreased HIF1alpha accumulation and inhibition with HIF1alpha and/or the glycolysis inhibitor could abrogate the growth effects mediated by TKTL1 overexpression . CONCLUSION TKTL1 is a novel candidate oncogene that is epigenetically activated by aberrant hypomethlation and contributes to a malignant phenotype through altered glycolytic metabolism and HIF1alpha accumulation .\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: Vaccination is , in theory , a safe and effective approach for controlling disseminated or metastatic cancer due to the specificity of the mammalian immune system , yet its success in the clinic has been hampered thus far by the problem of immune tolerance to tumor self-antigen . Here we describe a DNA vaccination strategy that is able to control cancer by overcoming immune tolerance to tumor self-antigen . We engineered a DNA construct encoding a dimeric form of a secreted single chain trimer of major histocompatibility complex class I heavy chain , β2-microglobulin , and peptide antigen linked to immunoglobulin G ( SCT-Ag/IgG ) . The chimeric protein was able to bind to antigen-specific CD8+ T cells with nearly 100% efficiency and strongly induce their activation and proliferation . In addition , the chimeric protein was able to coat professional antigen-presenting cells through the Fc receptor to activate antigen-specific CD8+ T cells . Furthermore , intradermal vaccination with DNA encoding SCT-Ag/IgG could generate significant numbers of cytotoxic effector T cells against tumor self-antigen and leads to successful therapeutic outcomes in a preclinical model of metastatic melanoma . Our data suggest that the DNA vaccine strategy described in the current study is able to break immune tolerance against endogenous antigen and result in potent therapeutic antitumor effects . Such strategy may be used in other antigenic systems for the control of infections and/or cancers .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;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: Gliomas display anoikis resistance , enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies . Our studies on increased anoikis sensitization in matrix metalloproteinase-2 ( MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 ( PAK4 ) inhibition , prompting us to further investigate the role of PAK4 in glioma . Here , we report the PAK4 upregulation in positive correlation with increasing glioma pathological grades . The siRNA-mediated PAK4 knockdown elevated anoikis , and inhibited invasion and migration by downregulating MMP-2 , αvβ3-integrin and phospho-epidermal growth factor receptor ( phospho-EGFR ) . The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation and adhesion in PAK4-knockdown cells . Most importantly , glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain . Individual EGFR/ErbB2 inhibitor and αvβ3 antibody treatments in PAK4si-treated cells indicated the regulation of αvβ3/EGFR survival signaling by PAK4 . Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines . Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death , and severely inhibited invasive and migratory properties in these cells . PAK4si inhibited in vivo tumor growth in nude mice by inhibiting MMP-2 , β3-integrin and phospho-EGFR levels in tumors . Our findings indicate a physical association between PAK4 and MMP-2 , and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment .\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 upregulate glycolysis , increasing glucose uptake to meet energy needs . A small fraction of a cell's glucose enters the hexosamine biosynthetic pathway ( HBP ) , which regulates levels of O-linked beta-N-acetylglucosamine ( O-GlcNAc ) , a carbohydrate posttranslational modification of diverse nuclear and cytosolic proteins . We discovered that breast cancer cells upregulate the HBP , including increased O-GlcNAcation and elevated expression of O-GlcNAc transferase ( OGT ) , which is the enzyme catalyzing the addition of O-GlcNAc to proteins . Reduction of O-GlcNAcation through RNA interference of OGT in breast cancer cells leads to inhibition of tumor growth both in vitro and in vivo and is associated with decreased cell-cycle progression and increased expression of the cell-cycle inhibitor p27(Kip1) . Elevation of p27(Kip1) was associated with decreased expression and activity of the oncogenic transcription factor FoxM1 , a known regulator of p27(Kip1) stability through transcriptional control of Skp2 . Reducing O-GlcNAc levels in breast cancer cells decreased levels of FoxM1 protein and caused a decrease in multiple FoxM1-specific targets , including Skp2 . Moreover , reducing O-GlcNAcation decreased cancer cell invasion and was associated with the downregulation of matrix metalloproteinase-2 , a known FoxM1 target . Finally , pharmacological inhibition of OGT in breast cancer cells had similar anti-growth and anti-invasion effects . These findings identify O-GlcNAc as a novel mechanism through which alterations in glucose metabolism regulate cancer growth and invasion and suggest that OGT may represent novel therapeutic targets for breast cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;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: Capsaicin , one of the major pungent ingredients found in red peppers , has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism . In this study , the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated . The results of a Cell Counting Kit-8 ( CCK-8 ) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner . Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment . Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment . Furthermore , we revealed that phospho-PI3 Kinase p85 ( Tyr458 ) and phospho-Akt ( Ser473 ) in PANC-1 cells were downregulated in response to capsaicin . Moreover , capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice . An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice . In vivo , capsaicin downregulated the expression of phospho-PI3 Kinase p85 ( Tyr458 ) and phospho-Akt ( Ser473 ) . In conclusion , we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells , and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo .\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: DNA polymerases beta ( pol beta ) and eta ( pol eta ) are the only two eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro . Frameshift errors are an important aspect of mutagenesis . We have compared the types of frameshifts that occur during translesion synthesis past cisplatin and oxaliplatin adducts in vitro by pol beta and pol eta on a template containing multiple runs of nucleotides flanking a single platinum-GG adduct . Translesion synthesis past platinum adducts by pol beta resulted in approximately 50% replication products containing single-base deletions . For both adducts the majority of -1 frameshifts occurred in a TTT sequence 3-5 bp upstream of the DNA lesion . For pol eta , all of the bypass products for both cisplatin and oxaliplatin adducts contained -1 frameshifts in the upstream TTT sequence and most of the products of replication on oxaliplatin-damaged templates had multiple replication errors , both frameshifts and misinsertions . In addition , on platinated templates both polymerases generated replication products 4-8 bp shorter than the full-length products . The majority of short cisplatin-induced products contained an internal deletion which included the adduct . In contrast , the majority of oxaliplatin-induced short products contained a 3 ' terminal deletion . The implications of these in vitro results for in vivo mutagenesis are discussed .\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: This study aimed to investigate the mechanism by which the human lung cancer drug resistance-related gene BC006151 regulates chemosensitivity by down-regulating BC006151 expression via antisense gene transfer in H446/(C)DDP cells . A retroviral vector containing the antisense BC006151 sequence was constructed and transfected into H446/(C)DDP cells . Transfection of the empty vector served as a negative control . The two groups of transfected cells were treated with various chemotherapeutic agents , after which morphological changes in cell ultrastructure were compared by transmission electron microscopy , cell proliferation and chemosensitivity to particular chemotherapeutic agents were compared by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method , the effects of chemotherapy on cell cycle and apoptosis were compared by flow cytometry , and Bcl-2 was evaluated by immunohistochemistry and Western blot analysis . Results showed that apoptotic body-like structures were identified by transmission electron microscopy in the antisense gene-transfected cells . MTT founded that these cells exhibited a significantly lower level of proliferation than the control cells ( p<0.01 ) , together with a markedly increased sensitivity to various chemotherapeutic agents ( p<0.01 ) . Flow cytometry analysis revealed that a G1 phase arrest accounted for the reduction in proliferation in the antisense gene-transfected cells ; increased apoptosis was also detected ( p<0.01 ) . Both immunohistochemistry and western blot analysis confirmed that Bcl-2 expression was significantly down-regulated in the antisense gene-transfected cells compared to controls . In a word , down-regulation of BC006151 can significantly inhibit proliferation and increase apoptosis of H446/(C)DDP cells after chemotherapy , and this gene may play an important role in the development of multidrug resistance in lung cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Recently , our group reported the discovery of three new withanolides , physangulidines A-C , from Physalis angulata . In this study , the biological effects of physangulidine A ( 1 ) , which was the most active and abundant of the three new constituents , are described . It was found that 1 significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines . Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1 induces cell cycle arrest in the G(2)/M phase and causes defective mitosis . It was determined also that 1 produces programed cell death by apoptosis , as evidenced by biochemical markers and distinct changes in cell morphology . These results imply that the antimitotic and proapoptotic effects of 1 may contribute significantly to the biological activities and potential medicinal properties of its plant of origin .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We studied whether feeding pregnant female rats different high fat diets affects structural zones in the spleen and lymph nodes , involved in production of T and B cells , as well as cell kinetics and apoptosis in some offspring with mammary glands tumors . Rat mothers were fed either a 7% or 15% corn-oil or a 7% or 15% olive-oil diet . At four weeks of age , female offspring ( n=10-15 per group ) were transferred to 7% corn oil diet . Five-week old offspring were exposed twice to the carcinogen , dimethylbenz(a)antracene ( 10 mg/rat/week ) . Three months later , tumors were counted and sized , and samples from the spleen , axillary lymph nodes and tumors collected for immunohistochemical analyses . Feeding the mothers with both the 7% and 15% olive-oil diets significantly increased the number of tumor-free rats in offspring . Tumors were characterized with active mitosis , intensive lymphoid infiltration inside a knot and high rates of apoptosis , particularly in tumors obtained from rats whose mothers were fed the 15% olive-oil diet . In the spleen , the 15% olive-oil diet significantly increased the areas of the follicles and germinal centers but only in tumor-free rats . In tumor-bearing rats , areas of germinal centers increased compared to the 7% olive-oil diet . The 15% olive-oil diet increased all areas of the lymph nodes in tumor-free rats , while in tumor-bearing rats , this diet increased the areas of the cortex and mantle layer . We conclude that exposure to various diets in utero and during lactation affects the immune system . In addition , the promotion of apoptosis may play a key role in the mechanisms involved in the transplacental effects on mammary tumor development as seen using a 15% olive-oil diet , similar to the high fat diets of Mediterranean countries .\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: p38 kinases activated by growth factors , hormones , and environmental stresses exert diverse functions in regulating normal and malignant cell pathophysiology . Enhanced levels of activated p38 isoforms have been linked with poor prognosis in breast cancer , although the mechanistic basis for this association is poorly understood . In this study , we report that p38 activation in cervical cancer cells is driven by osteopontin ( OPN ) , an extracellular matrix-associated cytokine that drives invasive progression . OPN regulates CD44-mediated p38 phosphorylation that induces NF-κB activation and NF-κB-dependent expression of furin , an extracellular protease implicated in human papilloma virus ( HPV ) processing that enhances cervical cancer cell motility . OPN induces CD44-mediated MKK3/6 phosphorylation which in turn phosphorylates p38 in these cells . OPN-induced furin expression and cell motility was impeded by blockades to MKK3/6 , p38α/β or NF-κB signaling . In a mouse xenograft model of human cervical cancer , tumor growth was enhanced by OPN overexpression and blocked by short hairpin RNA ( shRNA)-mediated OPN silencing . Furin overexpression similarly augmented tumor growth in the model , whereas blocking MKK3/6 , p38 , or furin reduced OPN-induced cervical tumor growth . Analysis of clinical specimens revealed that enhanced expression of OPN , phosphorylated NF-κB , p65 , and furin correlated with cervical cancer progression , further strengthening the in vitro and in vivo results . In summary , our findings offer a proof of concept for targeting OPN and its downstream p38 signaling as a novel therapeutic strategy to manage cervical 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: p53 is a tumor suppressor gene that is mutated in many human malignancies , including gastric cancer . It remains unclear why patients with germ-line p53 mutations ( i.e. , Li-Fraumeni syndrome ) are not at increased risk for gastric adenocarcinoma , despite the fact that they show a high rate of many other tumors . Furthermore , the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections ( such as Helicobacter spp. ) has not been investigated . To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer , p53(+/-) and wild-type ( WT ) C57BL/6 mice were infected with H. felis . The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection . The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation , parietal and chief cell loss , mucus metaplasia , and helicobacter colonization . Nonparametric statistical analysis was performed to determine the effects of p53(+/-) , infection status , and postinoculation ( p.i. ) time on inflammation , preneoplastic changes , invasive lesions , and helicobacter colonization. mRNA expression for gammaIFN , interleukin ( IL)-1 , IL-10 , and IL-4 was quantified by PCR . Sera were also evaluated for H. felis antibody by ELISA . Antral inflammation increased significantly with time in infected mice . There was a significant , protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele ( P &lt ; 0.05 ) . Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i. ; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice . None of these lesions were observed in 33 p53(+/-) mice , infected or not , at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response . In sera from WT mice , IgG2a , considered a proinflammatory Th1 response , continued to rise throughout the 15-month study ( P &lt ; 0.004 ) . In contrast , IgG2a levels of the p53(+/-) mice were 50-60% lower than those of the WT mice at each time point ( P range , <0.012 to 0.002 ) and did not progress in magnitude between 12 and 15 months of chronic H. felis infection ( P = 0.167). mRNA levels for gammaIFN and IL-1 were significantly up-regulated in WT mice infected with H. felis ( P &lt ; 0.05 ) but were slightly elevated or were at background levels in p53(+/-) mice . IL-10 and IL-4 mRNA expression was not significantly different from control samples . Our results support the hypothesis that germ-line deletion of one p53 allele results in a down-regulated Th1 response to gastric helicobacter infection , possibly because of T-cell senescence , which may indirectly protect against the development of gastric cancer and other epithelial-derived neoplasms associated with chronic inflammation .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;activating invasion and metastasis;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: DNA mismatch repair ( MMR ) of simple base mismatches and small insertion-deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 ( MSH2)-MSH6 heterodimer to mismatched DNA . Cadmium ( Cd ) is a genotoxic heavy metal that has been recognized as a human carcinogen . Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity . Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish ( Danio rerio ) embryos . This study was undertaken to explore if Cd-induced oxidative stress down-regulated MSH gene activities . Following the exposure of zebrafish embryos at 1 h post fertilization ( hpf ) to sublethal concentrations of Cd at 3-5 μM for 4 or 9 h , a parallel down-regulation of MSH2 , MSH6 and Cu/Zn superoxide dismutase ( Cu/Zn-SOD ) gene expression was detected by real-time RT-PCR and the expression levels were 40-50% of control after a 9-h exposure . Cd exposure also induced oxidative stress , yet no inhibition of catalase gene activity was observed . Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene ( BHT ) , d-mannitol or N-acetylcysteine ( NAC ) at 1-10 μM restored Cd-suppressed msh6 expression . QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6 mRNA production . Down-regulated MSH gene activities reaching about 50% of control were also induced in embryos exposed to paraquat , a reactive oxygen species ( ROS)-generating herbicide , or hydrogen peroxide at 200 μM . Hence , Cd at sublethal levels down-regulates msh2/msh6 expression primarily via ROS as signaling molecules . The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 ( Sp1 ) . Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay , therefore excluding the involvement of Sp1 inactivation in Cd-induced MSH gene inhibition in zebrafish embryos .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A 51-year-old previously healthy man , an ex-smoker , was admitted to the authors ' medical department with a 3-month history of dry cough ; intermittent fever ; painless , ulcerated cutaneous lesions over the trunk and limbs ( Figure 1 ) ; and progressive weight loss . He was of Greek descent . His medical history was remarkable for nasal polyps , which were surgically removed 15 years earlier . Initially , he had been treated with antibiotics , without improvement . Several days before admission , chest radiography revealed pulmonary infiltrates in the left lower lobe . On admission , physical examination revealed a well-orientated man in mild distress , with inspiratory rhonchi at the lower part of the left lung and scattered erythematous nodules of variable size , some of which were ulcerated . Laboratory values were notable for leukopenia , 3.3 x 10(9)/L ; total protein , 5.9 g/dL ; globulin , 2.2 g/dL ; serum glutamic oxaloacetic transaminase , 86 IU/L ; serum glutamic pyruvic transaminase , 71 IU/L ; and lactate dehydrogenase , 519 U/L . Computed tomograph ( CT ) of the chest showed multiple alveolar opacities bilaterally ( Figure 2 ) . Fiberoptic bronchoscopy did not reveal any important pathologic findings . Results of bronchial biopsy , cytology of bronchoalveolar lavage , washing , brushing , and sputum following bronchoscopy were negative . CT of the brai and sinonasal area revealed an abnormal low-density mass in the left nasal area . CT findings of the abdomen were negative , as were results of a bone marrow biopsy . There was no evidence of immunosuppression . The differential diagnosis , considering the evidence described , included granulomatous or infectious diseases , angiocentric lymphoproliferative lesions , and lymphomas . Biopsy of a skin lesion showed lymphoproliferative infiltration of the dermis with a follicular and angiocentric growth pattern and regional epidermal necrosis . Immunohistochemical stains showed that the tumor cell were positive for CD56 and CD3 ( cytoplasmic positivity ) and expressed the cytotoxic proteins T-cell intracellular antigen and granzyme B ( Figure 3 ) They lacked TdT , CD34 , CD7 , CD8 , TCL-1 , and CD123 . Findings from an in situ hybridization study for Epstein-Barr virus were negative . Give this result , molecular analysis ofT-cell receptor ( TCR ) gene rearrangements was performed using polymerase chain reaction-based TCR-gamma gene , wit negative results . The morphology and the immunophenotype were consistent with natural killer/T-cell lymphoma , nasal-type . Nasal involvement must be first excluded to proceed to the diagnosis of nasal-type natural killer-cell lymphoma . Indeed , histologic examination of the nasal mass revealed its polypoid nature . Thus , the authors were led to the diagnosis of extranodal extranasal natural killer/T-cell lymphoma , nasal-type , CD56-positive , Ep stein-Barr virus-negative , TCR-negative . The patient received combination chemotherapy and completed 4 cycles of cyclophosphamide , doxorubicin vincristine , and prednisone every 14 days for 2 months . Skin lesions improved , and there was no fever soon after the initiation of therapy . Reevaluatio after the fourth cycle , however , disclosed pulmonary infiltrations as well as leukemic infiltration of the central nervous system . The patient had receive systemic salvage chemotherapy and intrathecal infusions of methotrexate . Although the lung lesions had diminished at that time , the patient develope paraplegia , his clinical course rapidly deteriorated , and he eventually died .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aim of the present study was to evaluate immunomodulator ginsan , a polysaccharide extracted from Panax ginseng , on carbon tetrachloride ( CCl(4))-induced liver injury . BALB/c mice were injected i.p. with ginsan 24 h prior to CCl(4) administration . Serum liver enzyme levels , histology , expression of antioxidant enzymes , and several cytokines/chemokines were subsequently evaluated . Ginsan treatment markedly suppressed the serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels , and hepatic histological necrosis increased by CCl(4) treatment . Ginsan inhibited CCl(4) induced lipid peroxidation through the cytochrome P450 2E1 ( CYP2E1 ) downregulation . The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents , such as superoxide dismutase ( SOD ) , catalase , and glutathione peroxidase ( GPX ) as well as restoration of the hepatic glutathione ( GSH ) concentration . The marked increase of proinflammatory cytokines ( IL-1beta , IFN-gamma ) and chemokines ( MCP-1 , MIP-2beta , KC ) in CCl(4) treated mice was additionally attenuated by ginsan , thereby preventing leukocyte infiltration and local inflammation . Our results suggest that ginsan effectively prevent liver injury , mainly through downregulation of oxidative stress and inflammatory response .\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: Evaluation of immune dysfunction during the tumor-bearing state is a critical issue in combating cancer . In this study , we initially found that IL-6 , one of the cachectic factors , suppressed CD4(+) T cell-mediated immunity through downregulation of MHC class II by enhanced arginase activity of dendritic cells ( DC ) in tumor-bearing mice . We demonstrated that administration of Ab against IL-6R ( anti-IL-6R mAb ) greatly enhanced T cell responses and inhibited the growth of tumor in vivo . We also found that IL-6 upregulated the expression of arginase-1 and arginase activity of DC in vitro . Tumor-infiltrating CD11c(+) DC exhibited upregulated mRNA expression of arginase-1 but reduced expression of MHC class II in parallel with the increase in serum IL-6 levels at the late stage in tumor-bearing hosts . However , the administration of anti-IL-6R mAb into tumor-bearing mice inhibited both the downmodulation of MHC class II and the upregulation of arginase-1 mRNA levels in DC . Furthermore , we noted that N(ω)-hydroxy-L-arginine or L-arginine , an arginase-1 inhibitor , blocked the reduction in MHC class II levels on CD11c(+) DC during the tumor-bearing state . Finally , we demonstrated that the administration of N(ω)-hydroxy-L-arginine at the peritumor site significantly enhanced CD4(+) T cell responses and inhibited tumor growth . Thus , IL-6-mediated arginase activation and the subsequent reduction in MHC class II expression on DC appeared to be critical mechanisms for inducing dysfunction of the immune system in the tumor-bearing state . Blockade of the IL-6-arginase cascade is a promising tool to overcome the dysfunction of antitumor immunity in tumor-bearing hosts .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The knowledge of alterations in regulation of autophagy during tumorigenesis may also help our understanding of its normal control . We established an experimental system and reported recently that autophagic capacity , measured as the cell's capability of increasing segregation ( formation of autophagosomes ) and subsequent degradation of cytoplasmic quanta were highly increased in premalignant nodule cells 6 months after initiation by azaserine in the rat pancreas in vivo . In the present study , we followed changes of these autophagic functions throughout the tumour progression . We carried out electron-microscopic morphometrical analysis of the expansion of autophagic vacuole compartment and subcompartments induced by vinblastine ( an in vivo segregation enhancer ) , as well as their regression upon segregation-inhibitor cycloheximide post-treatment . Premalignant tumour samples were taken at month 5 , month 8 ( nodules ) , month 10 and month 15 ( adenomas ) after initiation . In all these stages , a highly increased and varying autophagic capacity was found compared with the host tissue . The basal ( non-stimulated ) autophagic compartment was measurable only at month 5 and month 15 , and its regression upon cycloheximide was consistent with increased basal autophagic activity . Compared with the host tissue , autophagic capacity profoundly decreased in the differentiated and anaplastic adenocarcinomas at month 20 , when , surprisingly , cycloheximide was unable to inhibit segregation . Our conclusion is that down-regulation of the cycloheximide sensitive segregation and a partly compensatory up-regulation of an alternative pathway of segregation might occur along with malignant transformation .\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 effects of tea polyphenols and tea pigments on cell cycle of hepatic cancer cells were studied . HepG2 cells were incubated with 50 and 100 mg/L tea polyphenols and tea pigments for 48 h respectively . Flow cytometry , Western blot and RT-PCR analysis were used . Flow cytometry analysis showed that tea polyphenols and tea pigments induced G1 arrest . Western blot analysis showed tea polyphenols and tea pigments significantly inhibited the expression of cyclin D1 protein and induced higher expression of P21WAFI/CIPI protein . The result of RT-PCR analysis demonstrated that Cdk4 was significantly inhibited by tea polyphenols and tea pigments . It is concluded that the induction of cell cycle arrest may be an important mechanism of tea on cancer prevention .\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: Immortalization ( senescence bypass ) is a critical rate-limiting step in the malignant transformation of mammalian somatic cells . Human cells must breach at least two distinct senescence barriers to permit unfettered clonal evolution during cancer development : ( 1 ) stress- or oncogene-induced premature senescence ( SIPS/OIS ) , mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive pathways , and ( 2 ) replicative senescence triggered by telomere shortening . In contrast , because their telomerase is constitutively active , cells from small rodents possess only the SIPS/OIS barrier , and are therefore useful for studying SIPS/OIS bypass in isolation . Dermal fibroblasts from the Syrian hamster ( SHD cells ) are exceptionally resistant to spontaneous SIPS bypass , but it can be readily induced following exposure to a wide range of chemical and physical carcinogens . Here we show that a spectrum of carcinogen-specific mutational and epigenetic alterations involving the INK4A ( p16 ) , p53 and INK4B ( p15 ) genes are associated with induced SIPS bypass . With ionizing radiation , immortalization is invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2 locus . In comparison , SHD cells immortalized by the powerful polycyclic hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the DNA-binding domain of p53 coupled with INK4 alterations such as loss of expression of p15 . Epimutational silencing of p16 is the primary event associated with immortalization by nickel , a human non-genotoxic carcinogen . As SIPS/OIS bypass is a prerequisite for the immortalization of normal diploid human epithelial cells , our results with the SHD model will provide a basis for delineating combinations of key molecular changes underpinning this important event in human carcinogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Retrovirally induced immunosuppression may elevate the incidence of chemically induced cancers . A proposed hypothesis to explain this relationship is the increased free radical activity observed during retroviral infection and carcinogen activation . We previously found that vitamin E retarded growth of esophageal tumors accompanied by reductions of free radical products . This study investigated the contribution that retroviral immunosuppression has on esophageal cancer induced by the carcinogen N-nitrosomethylbenzylamine ( NMBzA ) , and the response that increased levels of dietary vitamin E has on this induced carcinogenesis . Female C57BL/6 mice received NMBzA or vehicle ( corn oil ) i.p. weekly for 3 weeks . Then some of the mice were infected with LP-BM5 murine retrovirus and fed diets containing 30 IU vitamin E or 172 IU vitamin E/kg of diet . As an assessment of free radical activity , exhaled ethane was measured prior to killing the animals at 26 weeks . Esophagi from the various mice groups were assessed for size and frequency of tumors . Livers homogenates were analyzed for vitamins A and E , lipid fluorescence , conjugated dienes and malondialdehyde . Hepatic levels of vitamin A and E were decreased ( P &lt ; 0.05 ) and indices of lipid peroxidation were greater ( P &lt ; 0.05 ) in NMBzA-treated mice relative to controls . Lipid peroxidation and serum transaminases ( ALT and AST ) were greatest in mice given NMBzA and infected with the retroviruses . Incidence of esophageal tumors were also greatest in the NMBzA-treated , immunocompromised animals . Mice fed vitamin E-supplemented diets showed increased ( P &lt ; 0.05 ) hepatic concentrations of vitamin E and vitamin A , decreased activities of serum transaminases , decreased indices of lipid peroxidation , and decreased size and frequency of esophageal tumors in both the immunocompromised and non-immunocompromised mice . These results suggest that vitamin E plays an antioxidant function that retards the incidence of esophageal cancers in immunocompromised and non-immunocompromised animals .\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: Cellular senescence , an irreversible cell cycle arrest induced by a diversity of stimuli , has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy . Using a targeted proteomics approach , we show that fibroblasts induced into senescence by expression of oncogenic Ras exhibit a decrease of global acetylation on all core histones , consistent with formation of senescence-associated heterochromatic foci . We also detected clear increases in repressive markers ( e.g. >50% elevation of H3K27me2/3 ) along with decreases in histone marks associated with increased transcriptional expression/elongation ( e.g . H3K36me2/3 ) . Despite the increases in repressive marks of chromatin , 179 loci ( of 2206 total ) were found to be upregulated by global quantitative proteomics . The changes in the cytosolic proteome indicated an upregulation of mitochondrial proteins and downregulation of proteins involved in glycolysis . These alterations in primary metabolism are opposite to the well-known Warburg effect observed in cancer cells . This study significantly improves our understanding of stress-induced senescence and provides a potential application for triggering it in antiproliferative strategies that target the primary metabolism in cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;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: Adenoid cystic carcinoma ( ACC ) of the salivary glands is a highly infiltrative malignant tumour with a tendency for lung metastasis . Gene therapy could be a potentially effective therapy for ACC and its metastasis . The aims of the study were : To transduce interleukin-2 ( IL-2 ) gene into an ACC cell line with predisposition for lung metastasis ( ACC-M ) ; to compare the bioactivity of the gene-transduced cells and the parent cell line in vitro and in vivo . The IL-2 gene was transduced via a bicistronic retroviral vector into the ACC-M cells . The growth rate and DNA cell cycles of the parent ACC-M , the control viral vector AmGCEN , and the gene transduced AmIL-2 cell cultures were compared quantitatively and by flow cytometry , respectively . The tumourigenic ability of the three cell lines was verified by inoculation in athymic nude mice . The tumours developed were extracted and compared quantitatively and histologically . There was no difference in the growth rate and the DNA count between the ACC-M , AmGCEN , and AmIL-2 cell cultures . In the animal experiment , both the ACC-M and AmGCEN cells stimulated lung metastasis in all the mice , whereas there was no tumour found in the 1 x 10(6) AmIL-2 cells inoculation . On 3 x 10(6) AmIL-2 cells stimulation , three out of six mice developed tumours but the mass and volume of the tumours were smaller than the other two groups . Under light microscopy , the ACC-M tumours were mainly poorly differentiated with minimal cellular matrix , whereas the AmIL-2 tumours were well differentiated with ample matrix . The transduction of IL-2 gene can reduce the tumourigenicity of ACC-M cells and induces tumour cell differentiation in mice . The IL-2 gene can be a potential effective gene for the treatment of adenoid cystic carcinoma of salivary glands and its lung 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: The retinoic acid receptor beta2 ( RARbeta2 ) protein is a putative tumor suppressor that inhibits proliferation and can induce apoptosis when introduced into breast , cervical , lung , and pancreatic cancer cell lines . To determine if RARbeta2 suppresses proliferation of mammary-derived cancer cells in vivo , we transduced MDA-MB-435 breast cancer cells with the LXSN retroviral vector containing RARbeta2 and implanted LXSN vector- or RARbeta2-transduced cells into the mammary fat pads of nude and severe combined immune deficiency ( SCID ) mice . We analyzed the xenografts for several tumor parameters , including tumor size , inflammation , vascularity , mitoses , tumor recurrence at the primary site following resection , and metastases . We found that 19 of 52 mice inoculated with vector-transduced cells developed metastases in multiple organs while only one of 55 mice receiving RARbeta2-transduced cells displayed evidence of metastases ( p &lt ; 0.000001 , combined experiments , two-tailed Fisher's exact test ) . Moreover , RARbeta2-tumor cell recipient mice had a lower incidence of post-resection tumor recurrence ( 8/55 vs. 25/52 , p = 0.0004 ) , 34% less necrosis ( in three of four experiments , p = 0.001 ) , and 39% fewer mitoses in tumor tissue ( p &lt ; 0.000001 ) . Our findings suggest that RARbeta2 may play a role in inhibiting the metastatic cascade in a mouse mammary gland xenograft tumor model and is a potential candidate for therapeutic intervention in human breast 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: BACKGROUND Hepatocellular carcinoma ( HCC ) is a leading cause of death worldwide . Frequent cytogenetic abnormalities that occur in HCC suggest that tumor-modifying genes ( oncogenes or tumor suppressors ) may be driving selection for amplification or deletion of these particular genetic regions . In many cases , however , the gene(s) that drive the selection are unknown . Although techniques such as comparative genomic hybridization ( CGH ) have traditionally been used to identify cytogenetic aberrations , it might also be possible to identify them indirectly from gene-expression studies . A technique we have called comparative genomic microarray analysis ( CGMA ) predicts regions of cytogenetic change by searching for regional gene-expression biases . CGMA was applied to HCC gene-expression profiles to identify regions of frequent cytogenetic change and to identify genes whose expression is misregulated within these regions . RESULTS Using CGMA , 104 HCC gene-expression microarray profiles were analyzed . CGMA identified 13 regions of frequent cytogenetic change in the HCC samples . Ten of these regions have been detected in previous CGH studies ( +lq , -4q , +6p , -8p , +8q , -13q , -16q , -17p , +17q , +20q ) . CGMA identified three additional regions that have not been previously identified by CGH ( +5q , +12q , +19p ) . Genes located in regions of frequent cytogenetic change were examined for changed expression in the HCC samples . CONCLUSIONS Our results suggest that CGMA predictions using gene-expression microarray datasets are a practical alternative to CGH profiling . In addition , CGMA might be useful for identifying candidate genes within cytogenetically abnormal regions .\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: Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone . The use of a tissue-selective estrogen complex ( TSEC ) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen . Combination of bazedoxifene ( BZA ) with conjugated estrogens ( CEs ) , the first TSEC , has shown beneficial effects . Whether it would exert antiestrogenic effects on breast cancer is not clear . To address this issue , we compared estradiol ( E(2) ) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells . CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E(2) . Both CE and E(2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK , Akt , and p70S6K and up-regulation of antiapoptotic factors survivin , Bcl-2 , and X-linked inhibitor of apoptosis protein , These effects could be completely blocked by BZA . Gene expression studies demonstrated that CE and E(2) were equally potent on expression of cMyc , pS2 , and WNT1 inducible signaling pathway protein 2 , whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E(2) . BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone . Our results indicate that the stimulatory effects of E(2) or CE on breast cancer cells could be completely abrogated by BZA . These studies imply that the CE/BZA , TSEC , exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women , resulting in an overall reduction in tumor incidence .\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: AIMS To screen the genes and possible signal transduction pathways with which nucleostemin ( NS ) interacts and explore the mechanism of NS in prostate cancer . METHODS NS-specific short-hairpin RNA expression plasmid was used to downregulate the NS level in PC-3 cells and the changes of cell cycle were studied . After that , oligonucleotide DNA microarray was used to screen the genome changes in PC-3 cells and quantitative real-time PCR was used to further confirm the differentially expressed genes . RESULTS Detection of cell cycle showed a decrease of S stage and an increase of G1 stage after downregulation of NS. 219 differentially expressed genes were found and these genes were involved in cell cycle , cell proliferation , signal transduction , cell apoptosis and cell differentiation , and so on . Genes related to cell cycle were discussed emphatically . INK4 family genes ( P15 , P16 , P18 ) were upregulated while cyclin D1 HDAC1 were downregulated . These genes were tightly related to CDK4/6-cyclin D and pRb-E2F1 complexes . CONCLUSION NS is an important G1/S checkpoint regulator and it could regulate cell cycles via a p53-independent pathway in prostate cancer .\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: To evaluate the effects of adenovirus ( Ad)-mediated transfer of p53 and p16 on human bladder cancer cells EJ , EJ were transfected with Ad-p53 and Ad-p16 . Cell growth , morphological change , cell cycle , apoptosis were measured using MTT assay , flow cytometry , cloning formation , immunocytochemical assays . Ad-p16 or Ad-p53 alone could inhibit the proliferating activity of EJ cells in vitro . Ad-p53 could induce apoptosis of partial EJ cells . G1 arrest was observed 72 h after infection with Ad-p16 , but apoptosis was not obvious . The transfer of Ad-p16 and Ad-p53 could significantly inhibit the growth of EJ cells , decrease the cloning formation rate and induce apoptosis of large number of EJ cells . The occurrence time of subcutaneous tumor was delayed and the tumor volume in 4 weeks was diminished by using Ad-p53 combined with Ad-p16 and the difference was significant compared with using Ad-p53 or Ad-p16 alone . It was suggested that the transfer of wild-type p53 and p16 could significantly inhibit the growth of human bladder cancer in vitro and in vivo .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The purpose of this study was to combine a three-dimensional NMR-compatible bioreactor with hyperpolarized ( 13)C NMR spectroscopy in order to probe cellular metabolism in real time . JM1 ( immortalized rat hepatoma ) cells were cultured in a three-dimensional NMR-compatible fluidized bioreactor . ( 31)P spectra were acquired before and after each injection of hyperpolarized [ 1-(13)C ] pyruvate and subsequent ( 13)C spectroscopy at 11.7 T . ( 1)H and two-dimensional ( 1)H-(1)H-total correlation spectroscopy spectra were acquired from extracts of cells grown in uniformly labeled ( 13)C-glucose , on a 16.4 T , to determine ( 13)C fractional enrichment and distribution of ( 13)C label . JM1 cells were found to have a high rate of aerobic glycolysis in both two-dimensional culture and in the bioreactor , with 85% of the ( 13)C label from uniformly labeled ( 13)C-glucose being present as either lactate or alanine after 23 h . Flux measurements of pyruvate through lactate dehydrogenase and alanine aminotransferase in the bioreactor system were 12.18 +/- 0.49 nmols/sec/10(8) cells and 2.39 +/- 0.30 nmols/sec/10(8) cells , respectively , were reproducible in the same bioreactor , and were not significantly different over the course of 2 days . Although this preliminary study involved immortalized cells , this combination of technologies can be extended to the real-time metabolic exploration of primary benign and cancerous cells and tissues prior to and after therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cellular senescence , initially observed during subculturing of normal diploid fibroblasts , can also be induced by chronic exposure to cellular stress , such as UV light , oxidative stress , or DNA damaging agents . Here we demonstrate that stable expression of an activated form of MKK6 ( MKK6EE ) , a direct activator of the stress-induced p38(HOG) mitogen-activated protein kinase pathway , is sufficient for inducing features of senescence including a flattened , vacuolated , and irregular morphology , staining for acidic beta-galactosidase , and accumulation of age-associated pigments . Consistent with the senescent phenotype , p38(HOG) activation induces a G(1) cell cycle arrest , which is permanent and irreversible after 4 days . MKK6EE also induces biochemical features of senescence in a p38-dependent manner , including enhanced expression of p21(CIP) , a cyclin-dependent kinase inhibitor . Microarray analysis of MKK6EE cells showed a pattern of gene expression noted previously in Werner Syndrome and senescent fibroblasts . These results define p38(HOG) as an intracellular pathway that activates a senescence checkpoint in tumor cells and may play a role in Ras- or stress-induced senescence .\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: Targeting cancer cell metabolism is a new promising strategy to fight cancer . Metformin , a widely used antidiabetic agent , exerts antitumoral and antiproliferative action . In this study , the addition of metformin to 2-deoxyglucose ( 2DG ) inhibited mitochondrial respiration and glycolysis in prostate cancer cells leading to a severe depletion in ATP . The combination of the two drugs was much more harmful for cancer cells than the treatment with metformin or 2DG alone , leading to 96% inhibition of cell viability in LNCaP prostate cancer cells . In contrast , a moderate effect on cell viability was observed in normal prostate epithelial cells . At the cellular level , the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase , and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity . In addition to apoptosis , the combination of metformin and 2DG arrested prostate cancer cells in G(2)-M . This G(2)-M arrest was independent of p53 and correlated with a stronger decrease in cell viability than obtained with either drug . Finally , metformin inhibited 2DG-induced autophagy , decreased beclin 1 expression , and triggered a switch from a survival process to cell death . Our study reinforces the growing interest of metabolic perturbators in cancer therapy and highlights the potential use of the combination of metformin and 2DG as an anticancerous treatment .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: OBJECTIVE To study the effects of angiostatin(AS) gene mediated by liposome on human pancreatic cancer cell line SW1990 . METHODS Angiostatin gene was cloned into the eukaryotic expression vector pRC/CMV . The recombinant of pRC/CMV-AS was introduced into the pancreatic cancer cell line , SW1990 . The mechanism of anti-tumor was studied and tested . RESULTS The eukaryotic expression vector pRC/CMV-AS was identified by the restriction digest. pRC/CMV-AS was stably integrated into the target cells and expressed by Western blot and drug-sensitivity tests , and inhibited the vascular endothelial cells proliferation in vitro . In addition , the effects of the angiostatin vector on reducing the volume of tumors implanted in nude mouse models were also noted . CONCLUSION This study demonstrated that the recombinant pRC/CMV-AS mediated by liposome may play a potential role in the treatment of pancreatic cancer in the future .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response . In the present study , we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma . METHODS Ninety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined . All patients underwent radical thoracic surgery of primary tumor ( lobectomy or pneumonectomy ) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry . Follow-up was available for all patients ; mean duration of follow-up was 27.50 ± 14.07 months ( range 0.2-57 months , median 24 months ) . RESULTS Sixty-three patients ( 65.2% ) died during the follow-up period . The mean survival time was 32.2 ± 1.9 months ( 95% confidence interval [ CI ] : 28.5-35.8 months ; median 30.0 months ) ; 1- , 2- and 3-year survival rates were 86.5% ± 3.5% , 57.3% ± 5.1% , and 37.1% ± 5.4% , respectively . Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression ( 35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression , P = 0.009 ; hazard ratio [ HR ] 1.95 , 95% CI : 1.15-3.30 ) . Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival ( HR 2.15 , 95% CI : 1.22-3.79 , P = 0.026 ) . A combined p53/γ-H2AX analysis was performed , and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes . CONCLUSION Our study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer . Further studies are needed to confirm our results .\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: Progression to malignancy requires that cells overcome senescence and switch to an immortal phenotype . Thus , exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation . In the present study , we have globally profiled DNA methylation in relation to gene expression in primary , senescent and immortalized mouse embryonic fibroblasts . Using a high-resolution genome-wide mapping technique , followed by extensive locus-specific validation assays , we have identified 24 CpG islands that display significantly higher levels of CpG methylation in immortalized cell lines as compared to primary murine fibroblasts . Several of these hypermethylated CpG islands are associated with genes involved in the MEK-ERK pathway , one of the most frequently disrupted pathways in cancer . Approximately half of the hypermethylated targets are developmental regulators , and bind to the repressive Polycomb group ( PcG ) proteins , often in the context of bivalent chromatin in mouse embryonic stem cells . Because PcG-associated aberrant DNA methylation is a hallmark of several human malignancies , our methylation data suggest that epigenetic reprogramming of pluripotency genes may initiate cell immortalization . Consistent with methylome alterations , global gene expression analysis reveals that the vast majority of genes dysregulated during cell immortalization belongs to gene families that converge into the MEK-ERK pathway . Additionally , several dysregulated members of the MAP kinase network show concomitant hypermethylation of CpG islands . Unlocking alternative epigenetic routes for cell immortalization will be paramount for understanding crucial events leading to cell transformation . Unlike genetic alterations , epigenetic changes are reversible events , and as such , can be amenable to pharmacological interventions , which makes them appealing targets for cancer therapy when genetic approaches prove inadequate .\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: PURPOSE : Acid ceramidase ( AC ) occupies an important place in the control of cancer cell proliferation . We tested the influence of AC inhibition on the effects of PSC 833 , a P-glycoprotein antagonist with potent ceramide-generating capacity , to determine whether AC could be a therapeutic target in pancreatic cancer . METHODS : Ceramide metabolism was followed using ( 3)H-palmitate , and molecular species were determined by mass spectroscopy . Apoptosis was measured by DNA fragmentation , autophagy by acridine orange staining , and cell cycle was assessed by flow cytometry and RB phosphorylation . AC was measured in intact cells using fluorescent substrate . RESULTS : Exposure of human PANC-1 or MIA-PaCa-2 cells to PSC 833 promoted increases in de novo ( dihydro)ceramides , ( dihydro)glucosylceramides , and ( dihydro)sphingomyelins , demarking ceramide generation and robust metabolism . Despite the multifold increases in ( dihydro)ceramide levels , cells were refractory to PSC 833 . However , PSC 833 produced a dose-dependent decrease in DNA synthesis and dose- and time-dependent decreases in RB phosphorylation , consistent with cell cycle arrest as demonstrated at G1 . Cytostatic effects of PSC 833 were converted to cytotoxic end-point by acid ceramidase inhibition . Cytotoxicity was accompanied by formation of acridine orange-stained acidic vesicles and an increase in LC3 expression , indicative of autophagic response . Cell death was not reversed by preexposure to myriocin , which blocks PSC 833-induced ceramide generation . CONCLUSION : Although the role of ceramide in end-point cytotoxicity is unclear , our results suggest that acid ceramidase is a viable target in pancreatic cancer . We propose that AC inhibition will be effective in concert with other anticancer therapies .\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: Optimal lymphocyte activation requires the simultaneous engagement of stimulatory and costimulatory receptors . Stimulatory immunoreceptors are usually composed of a ligand-binding transmembrane protein and noncovalently associated signal-transducing subunits . Here , we report that alternative splicing leads to two distinct NKG2D polypeptides that associate differentially with the DAP10 and KARAP ( also known as DAP12 ) signaling subunits . We found that differential expression of these isoforms and of signaling proteins determined whether NKG2D functioned as a costimulatory receptor in the adaptive immune system ( CD8+ T cells ) or as both a primary recognition structure and a costimulatory receptor in the innate immune system ( natural killer cells and macrophages ) . This strategy suggests a rationale for the multisubunit structure of stimulatory immunoreceptors .\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: OBJECTIVE : Emerging evidences implicate long noncoding RNAs ( lncRNAs ) are deregulated in cancer development . The purpose of the current study is to investigate the role of new lncRNA , named PlncRNA-1 , in prostate cancer ( CaP ) pathogenesis . MATERIALS AND METHODS : In this study , real-time q-PCR was used to demonstrate the expression of PlncRNA-1 in 16 pairs CaP tissues and matched normal tissues , 14 pairs CaP tissues and BPH tissues , 4 CaP cell lines , including LNCaP , LNCaP-AI , PC3 , and C4-2 , and 2 normal prostate epithelial cell lines RWPE-1 and PWR-1E . After PlncRNA-1 was suppressed by siRNA in LNCaP and LNCaP-AI cell lines , cell proliferation and apoptosis were assessed using CCK-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) . After PlncRNA-1 and AR was suppressed by siRNA in LNCaP and LNCaP-AI cell lines , real-time q-PCR and Western blotting were used to measure reciprocal regulation of PlncRNA-1 and AR . RESULTS : We showed that expression PlncRNA-1 , was significantly higher in CaP cells relative to normal prostate epithelial cells , as well as higher in human CaPs compared with normal tissues and benign prostatic hyperplasia ( BPH ) . Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI . Mechanistically , PlncRNA-1 suppression by siRNA resulted in a decrease of androgen receptor ( AR ) mRNA , protein and AR downstream target . Of note , blockade of AR signaling with siRNA also resulted in a suppression of PlncRNA-1 expression in CaP cell lines . CONCLUSIONS : Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target .\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: The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects . Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk . All mice developed tumors by 13 wk of promotion . However , in mice pretreated with 30 microL eugenol , no tumors were detected until 8 wk ( following anti-initiation protocol ) and until 14 wk ( following antipromotion protocol ) of tumor promotion . PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively . The effect of eugenol was assessed on specific stages of carcinogenesis . Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA . However , pretreatment with eugenol led to overexpression of these genes , which probably helped stimulate apoptosis of the initiated cells . To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol , its effect was investigated on markers of tumor promotion and inflammation : ODC activity and iNOS and COX-2 expression , and on levels of proinflammatory cytokines ( IL-6 , TNF-alpha , and PGE(2) ) . Eugenol markedly inhibited all . Eugenol also inhibited the upstream signaling molecule : NF-kappaB , which regulates the expression of these genes . TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol . From these results , it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative , anti-inflammatory , and antioxidant activities .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;sustaining proliferative signaling;evading growth suppressors;genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The aberrant activation of sonic hedgehog ( SHH ) pathway contributes to initiation and progression of various malignancies . However , the roles and underlying mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer have not been well understood . In this study , we found that SHH signaling was activated and correlated with invasion and metastasis in hepatocellular carcinoma ( HCC ) . Enhanced SHH signaling by recombinant human SHH N-terminal peptide ( rSHH-N ) promoted hepatoma cell adhesion , migration and invasion , whereas blockade of SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma cell adhesion , migration and invasion . Furthermore , matrix metalloproteinase ( MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated by rSHH-N and SHH signaling inhibitor , respectively . The rSHH-N-mediated hepatoma cell migration and invasion was blocked by MMP-specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9 . In addition , phosphorylations of AKT and focal adhesion kinase ( FAK ) were increased and decreased by rSHH-N and SHH signaling inhibitor , respectively . Further investigations showed that activation of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9 , cell migration and invasion . Finally , we found that SHH protein expression was positively correlated with phosphorylatd FAK Tyr397 , phosphorylatd AKT Ser473 , MMP-2 and MMP-9 protein expressions in HCC samples . Taken together , our findings suggest that SHH pathway induces cell migration and invasion through FAK/AKT signaling-mediated MMP-2 and MMP-9 production and activation in liver 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: ABSTRACT : BACKGROUND : The ubiquitin-proteasome system and macroautophagy ( hereafter referred to autophagy ) are two complementary pathways for protein degradation . Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy . Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired . METHOD : Autophagy activation was measured using acridine orange staining and LC3 transition . Cell viability and apoptosis were measured using MTT assay and flow cytometry , respectively . Beclin 1 expression vectors or shRNA against Beclin 1 ( shBeclin 1 ) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors . RESULTS : Proteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells . Neither phosphoinositide 3-kinase ( PI3K ) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors . Moreover , Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells . CONCLUSIONS : For the first time , the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells . In addition , this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The increasing evidence supported the role of Enhancer of Zeste Homolog 2 ( EZH2 ) in the cancer development and progression . However , its precise role in the tumorigenesis of Nasopharyngeal Carcinoma ( NPC ) remains to be elucidated . EZH2 was depleted by retroviral infection in the NPC cells ( HK-1 , CNE-2 , CNE-1 and C666-1 ) . The degree of EZH2 knockdown was then assessed by real-time quantitative PCR and Western Blot analysis . Cell proliferation was assessed using the soluble tetrazolium salt ( MTS ) cell proliferation assay , and cell cycle was measured by FACS test . The methylation status of p16(INK4a )was determined by bisulphate treatment of the DNA , followed by MSP . EZH2 was over-expressed in NPC cells , and the expression in undifferentiated-derived NPC cells ( CNE-1 , C666-1 ) was more significant than differentiated-derived NPC cells ( HK-1 , CNE-2 ) . EZH2 was successfully depleted after retroviral infection in C666-1 cells , and the EZH2 depletion could inhibit the proliferation and arrested G1/S phase of NPC cells . In addition , both mRNA and protein levels of p16(INK4a) increased significantly in presence of EZH2 depletion . The further Methylation-Specific Polymerase Chain Reaction ( MSP ) assay suggested that over-expressed EZH2 may contribute to the reduction of p16(INK4a) expression by hyper methylating its promoter . EZH2 is overexpressed in NPC and reduces expression of p16(INK4a) by influencing methylation , opening therapeutic options .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer ( NSCLC ) patients was studied . Furthermore , transferrin receptors 1 ( TfR1 ) and ferritin expression in tumor tissue , tumor stroma , and normal lung tissue were analyzed . Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis . TfR1 and ferritin expression were determined by immuno-histochemical methods . About 50% of patients survived 12 months only . At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin . Iron content of serum ferritin ( ICF ) was below the reference values in 90% of patients . Furthermore , ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR . The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients , respectively . Tumor stroma was TfR1 negative and sporadically ferritin positive . Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit ( Ht ) , and positive correlation with ferritin , erythrocyte sedimentation rate ( ESR ) , alpha-1 globulin , and alpha-2 globulin . Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin . The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed . Therefore , we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload . Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The G protein-coupled human gastrin-releasing peptide receptor ( hGRP-R ) is frequently found aberrantly expressed in human cancers of the colon , stomach , and lung , and its ligand-specific activation has been implicated in cell proliferation and differentiation . Here , we demonstrated hGRP-R activation stimulated sustained cyclic AMP response element binding protein ( CREB ) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway . In contrast , intracellular calcium , ERK1/2 , protein kinase A , and PI3 kinase were not involved . This novel signaling mechanism might be of importance for regulation of CREB-dependent gene expression in human cancer expressing functional hGRP-R .\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: Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy . Therefore , there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response . Recently , several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer . In order to explore the predictive value of inflammation in breast cancer patients , we measured the inflammatory biomarkers serum ferritin and C-reactive protein ( CRP ) in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival . The elevation in pre-treatment serum ferritin ( >250 ng/ml ) or CRP ( >7.25 mg/l ) was a significant predictor of reduced progression-free survival and shorter overall survival . When patients were stratified based on their serum ferritin and CRP levels , patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy . Therefore , the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy . Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics .\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: Adhesion to the extracellular matrix ( ECM ) is critical for epithelial tissue homeostasis and function . ECM detachment induces metabolic stress and programmed cell death via anoikis . ECM-detached mammary epithelial cells are able to rapidly activate autophagy allowing for survival and an opportunity for re-attachment . However , the mechanisms controlling detachment-induced autophagy remain unclear . Here we uncover that the kinase PERK rapidly promotes autophagy in ECM-detached cells by activating AMP-activated protein kinase ( AMPK ) , resulting in downstream inhibition of mTORC1-p70(S6K) signaling . LKB1 and TSC2 , but not TSC1 , are required for PERK-mediated inhibition of mammalian target of rapamycinin MCF10A cells and mouse embryo fibroblast cells . Importantly , this pathway shows fast kinetics , is transcription-independent and is exclusively activated during ECM detachment , but not by canonical endoplasmic reticulum stressors . Moreover , enforced PERK or AMPK activation upregulates autophagy and causes luminal filling during acinar morphogenesis by perpetuating a population of surviving autophagic luminal cells that resist anoikis . Hence , we identify a novel pathway in which suspension-activated PERK promotes the activation of LKB1 , AMPK and TSC2 , leading to the rapid induction of detachment-induced autophagy . We propose that increased autophagy , secondary to persistent PERK and LKB1-AMPK signaling , can robustly protect cells from anoikis and promote luminal filling during early carcinoma progression.Oncogene advance online publication , 19 November 2012 ; doi:10.1038/onc.2012.512 .\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: Although regulatory T cells ( T(regs) ) are known to suppress self-reactive autoimmune responses , their role during T cell responses to nonself antigens is not well understood . We show that T(regs) play a critical role during the priming of immune responses in mice . T(reg) depletion induced the activation and expansion of a population of low-avidity CD8(+) T cells because of overproduction of CCL-3/4/5 chemokines , which stabilized the interactions between antigen-presenting dendritic cells and low-avidity T cells . In the absence of T(regs) , the avidity of the primary immune response was impaired , which resulted in reduced memory to Listeria monocytogenes . These results suggest that T(regs) are important regulators of the homeostasis of CD8(+) T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: This study aimed to analyze the role of endothelial progenitor cell ( EPC)-derived angiogenic factors and chemokines in the multistep process driving angiogenesis with a focus on the recently discovered macrophage migration inhibitory factor ( MIF)/chemokine receptor axis . Primary murine and murine embryonic EPCs ( eEPCs ) were analyzed for the expression of angiogenic/chemokines and components of the MIF/CXC chemokine receptor axis , focusing on the influence of hypoxic versus normoxic stimulation . Hypoxia induced an upregulation of CXCR2 and CXCR4 but not CD74 on EPCs and triggered the secretion of CXCL12 , CXCL1 , MIF , and vascular endothelial growth factor ( VEGF ) . These factors stimulated the transmigration activity and adhesive capacity of EPCs , with MIF and VEGF exhibiting the strongest effects under hypoxia . MIF- , VEGF- , CXCL12- , and CXCL1-stimulated EPCs enhanced tube formation , with MIF and VEGF exhibiting again the strongest effect following hypoxia . Tube formation following in vivo implantation utilizing angiogenic factor-loaded Matrigel plugs was only promoted by VEGF . Coloading of plugs with eEPCs led to enhanced tube formation only by CXCL12 , whereas MIF was the only factor which induced differentiation towards an endothelial and smooth muscle cell ( SMC ) phenotype , indicating an angiogenic and differentiation capacity in vivo . Surprisingly , CXCL12 , a chemoattractant for smooth muscle progenitor cells , inhibited SMC differentiation . We have identified a role for EPC-derived proangiogenic MIF , VEGF and MIF receptors in EPC recruitment following hypoxia , EPC differentiation and subsequent tube and vessel formation , whereas CXCL12 , a mediator of early EPC recruitment , does not contribute to the remodeling process . By discerning the contributions of key angiogenic chemokines and EPCs , these findings offer valuable mechanistic insight into mouse models of angiogenesis and help to define the intricate interplay between EPC-derived angiogenic cargo factors , EPCs , and the angiogenic target tissue .\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: Recent studies indicate that cyclooxygenase-2 ( COX-2 ) is overexpressed in pancreatic adenocarcinoma and may play a critical role in this rapidly progressing form of cancer . A human pancreatic adenocarcinoma cell line , Mia PaCa-2 , was incubated for 18 hours with 5 micromol/L of rofecoxib ( Vioxx ) , a selective COX-2 inhibitor . Total RNA was isolated and gene expression analyzed by DNA microarray chips . In a separate experiment , athymic mice were orthotopically injected with 7.5 x 10(5) Mia PaCa-2 cells through a minilaparotomy . After 1 month , laparotomy was repeated to measure tumor size , and mice were randomized to receive reformulated rodent chow containing either 12.5 mg/kg/day of rofecoxib or no drug for 21 days . Tumor growth was assessed by comparing volume before and after treatment . In vitro , rofecoxib decreased gene expression of cyclin D1/PRAD1 , a key component of cell cycle progression , while increasing expression of several cell cycle arrest genes , including p21/WAF1 , p33/ING , GADD34 , and GADD45 ( P &lt ; 0.05 ) . In vivo , tumor growth was significantly reduced in treated vs. control mice ( P &lt ; 0.05 ) . No systemic toxicity was observed in mice receiving rofecoxib . These data suggest that rofecoxib slows the growth of human pancreatic cancer through changes in gene expression that favor 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: Retinoblastoma ( Rb ) is the most common intraocular tumor of childhood . In this study we examined primary Rb specimens and Rb cell lines for the expression of immunoglobulin superfamily ( IgSF ) antigens : MHC class I and II ( MHC-I and MHC-II ) , neural cell adhesion molecule ( NCAM ) , intercellular adhesion molecule-1 ( ICAM-1 ) , and Thy-1 , which play an important role in immune system and tumor cell interactions . MHC-I and-II , ICAM-1 ( CD54 ) , NCAM ( CD56 ) , and Thy-1 ( CDw90 ) immunoreactivity was studied in eight primary Rb biopsy specimens using immunohistochemistry , three using immunoelectron microscopy , and six Rb cell lines using flow cytometry ( FCM ) . Parenchymal and vascular-associated cells , phenotypically similar to retinal microglia , strongly expressed MHC-II immunoreactivity and were distributed throughout primary Rb specimens . However , MHC-II expression on Rb cell lines was similar to nonspecific control levels . Tumor cells in primary Rb specimens displayed high NCAM , moderate Thy-1 , and low MHC-I and ICAM-1 immunolabeling . Tumor vasculature expressed low to moderate MHC-I and ICAM-1 immunoreactivity and moderate Thy-1 immunoreactivity . NCAM was not detected on the vasculature of primary Rb specimens . Rb cell lines displayed variable expression of Thy-1 , ICAM-1 , and MHC-I . NCAM was highly expressed on five of six Rb cell lines . The high levels of constitutive NCAM immunoreactivity on Rb tumor cells confirm the neuroectodermal origins of this tumor . Additionally , the variable expression of Thy-1 may suggest separate neural lineages or differences in the maturational status ofsome Rb tumors . The presence of a population of infiltrating MHC-II-positive cells in primary Rb tumors has implications for immunomodulation of Rb growth .\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: Maintenance of genomic integrity is essential for adult tissue homeostasis and defects in the DNA-damage response ( DDR ) machinery are linked to numerous pathologies including cancer . Here , we present evidence that the DDR exerts tumor suppressor activity in gliomas . We show that genes encoding components of the DDR pathway are frequently altered in human gliomas and that loss of elements of the ATM/Chk2/p53 cascade accelerates tumor formation in a glioma mouse model . We demonstrate that Chk2 is required for glioma response to ionizing radiation in vivo and is necessary for DNA-damage checkpoints in the neuronal stem cell compartment . Finally , we observed that the DDR is constitutively activated in a subset of human GBMs , and such activation correlates with regions of hypoxia .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Thymidine phosphorylase ( TYMP ) is an angiogenic factor that has potent chemotactic activity for endothelial cells and is involved in 5-fluorouracil ( 5-FU ) metabolism . In colorectal cancer ( CRC ) , previous studies evaluating the relationship between TYMP expression and clinicopathological features have yielded inconsistent results . The aim of this study was to investigate the prognostic value of TYMP , its association with other angiogenic factors , proliferation markers and , to our knowledge , for the first time its relationship with extracellular matrix components . MATERIALS AND METHODS Formalin-fixed , paraffin-embedded specimens from 97 patients with CRC were immunostained for TYMP , vascular endothelial growth factor ( VEGF ) , microvascular density ( CD34 ) , proliferation marker ( Ki-67 ) , proliferating cell nuclear antigen ( PCNA ) , p53 oncoprotein and extracellular matrix components ( collagen type IV , fibronectin , tenascin and laminin ) . Survival curves were calculated with the Kaplan-Meier method . RESULTS Immunoreactivity was observed in the cytoplasm ( cyt ) and nucleus ( n ) of the tumor cells , as well in the stroma ( st ) , endothelium and tumor-associated macrophages . High TYMPcyt expression was observed in 7.2% of the cases , moderate in 22.7% and weak in 59.9% , while 10.3% were negative . High TYMPst expression was observed in 58.8% of the cases . TYMPcyt expression was correlated with the VEGF expression of tumor cells and VEGF expression of vessels ( p=0.014 and p=0.022 , respectively ) . TYMPst expression was correlated with VEGF expression and tenascin ( p=0.014 and p=0.011 , respectively ) . Patients with higher TYMPcyt expression had a more favorable overall survival ( p=0.041 ) in univariate analysis compared to patients without TYMP expression . CONCLUSION These findings suggest that TYMP plays an important role in angiogenesis , extracellular matrix remodeling and in the prognosis of patients with CRC , but further studies are needed to clearly define its role in CRC .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Autotaxin ( ATX ) is an extracellular lysophospholipase D that generates lysophosphatidic acid ( LPA ) from lysophosphatidylcholine ( LPC ) . Both ATX and LPA have been shown to be involved in many cancers . However , the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma ( HCC ) remain elusive . RESULTS In this study , ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects . ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis . In addition , ATX expression was examined in normal human hepatocytes and liver cancer cell lines . Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did . Proinflammtory cytokine tumor necrosis factor alpha ( TNF-alpha ) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells , which led to a corresponding increase in lysophospholipase-D activity . Moreover , we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B ( NF-kappaB ) in basal and TNF-alpha induced ATX expression . Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion . CONCLUSIONS This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC . Our observation that links the TNF-alpha/NF-kappaB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;activating invasion and metastasis" } ]