Datasets:

clinicalnlplab

/

HoC_train

like 0

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: AIMS Treatment decisions are difficult in clinically localised prostate cancer and further biomarkers of aggressive behaviour are required . We investigated the hypothesis that the tissue expression of three cell cycle markers , Rb , p21 and p16 , would provide helpful prognostic information in a well characterised series of prostate cancers which were clinically localised and treated conservatively . METHODS The immunohistochemical staining expression of these markers was assessed in tissue microarrays and correlated with 10 year prostate cancer survival and overall survival and then compared with pathological data including contemporary Gleason score , age , measures of tumour extent and initial serum prostate specific antigen ( PSA ) level . RESULTS Rb overexpression did not show any significant association with Gleason score or prostate cancer survival. p21 protein expression showed a significant association with prostate cancer survival ( p = 0.02 ) and overall survival ( p = 0.01 ) in a univariate model but not in a multivariate model with pathological and serum PSA data . There was a significant association between p16 cytoplasmic expression and prostate cancer survival ( HR = 2.52 , 95%CI = 1.79-3.55 , p < 0.001 ) and overall survival ( HR = 1.54 , 95% CI = 1.20-1.98 , p = 0.001 ) in a univariate model. p16 expression remained an independent prognostic factor for prostate cancer survival ( HR = 1.50 , 95%CI = 1.05-2.14 , p = 0.03 ) . CONCLUSION We conclude that p16 cytoplasmic expression can be used as a predictor of outcome in conservatively treated prostate cancer . Rb and p21 show no independent association with outcome and therefore further research is not warranted .\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: Peroxisome proliferator activated receptor γ ( PPARγ ) , a subgroup of ligand-activated nuclear receptors , plays critical roles in cell cycle regulation , differentiation , apoptosis and invasion . PPARγ is involved in tumorigenesis and is a potent target for cancer therapy . PPARγ transactivation of KLF4 has been demonstrated in various studies ; however , how PPARγ regulates KLF4 expression is not clear . In this study , we revealed that PPARγ regulates the expression of KLF4 by binding directly to the PPAR response element ( PPRE ) within the KLF4 promoter . The PPRE resided at -1657bp to -1669bp upstream of the KLF4 ATG codon , which is essential for the transactivation of TGZ-induced KLF4 expression . Furthermore , we found that stable silencing of KLF4 obviously suppressed the G1/S arrest and anti-proliferation effects induced by PPARγ ligands . Taken together , our data indicated that upregulating KLF4 upon PPARγ activation is mediated through PPRE in KLF4 promoter , thus providing further insights into PPARγ signal transduction pathway as well as a novel cancer therapeutic strategy .\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: Considerable debate centers on the optimal treatment for vulvar melanoma , as well as those clinicopathological factors influencing prognosis . We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990 . Primary tumors were assessed according to Chung ( 47 patients ) and Breslow ( 65 patients ) microstaging systems . Fifty-nine patients ( 76% ) underwent radical vulvectomy , ten patients ( 13% ) had a partial vulvectomy , and nine patients ( 12% ) had a wide local excision . Fifty-six also underwent inguinal node dissection . Median follow-up was 193 months . Median survival was 63 months . Ten-year survival by Chung level was as follows : I 100% ; II , 81% ; III , 87% ; IV , 11% ; V , 33% . Ten-year survival by tumor thickness was as follows : 0.75 mm , 48% ; 0.75-1.5 mm , 68% ; 1.51-3.0 mm , 44% ; greater than 3.0 mm , 22% . Increased depth of invasion was associated with increased incidence of inguinal node metastasis . Cox regression analysis demonstrated prognostic significance for tumor thickness ( P less than 0.001 ) , inguinal node metastasis ( P less than 0.001 ) , and older age at diagnosis ( P less than 0.001 ) . Radical vulvectomy did not seem to improve survival over less radical procedures . Based on this experience , we recommend radical local excision for patients with malignant melanoma of the vulva . Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection .\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 CD4+CD25+ regulatory T cell ( Treg ) is a special kind of T cell subset . Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases , transplantation tolerance and cancer . Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance . The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma ( HCC ) . A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods . Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status . The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ( 18.8% � 1.26% ) was found to be significantly higher than that in normal mice ( 9.99% � 1.90% ) ( P<0.01 ) . Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice , while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed . Anti-tumour immunity was suppressed , and this might be associated with the increase of Tregs . Our observations suggest that the CD4+CD25+Treg/ CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer .\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: Blockage of the metastasis process remains a significant clinical challenge , requiring innovative therapeutic approaches . For this purpose , molecules that inhibit matrix metalloproteinases activity or induce the expression of their natural inhibitor , the tissue inhibitor of metalloproteinases ( TIMPs ) , are potentially interesting . In a previous study , we have shown that synthetic ligands binding to cell surface nucleolin/nucleophosmin and known as HB 19 for the lead compound and NucAnt 6L ( N6L ) for the most potent analog , inhibit both tumor growth and angiogenesis . Furthermore , they prevent metastasis in a RET transgenic mice model which develops melanoma . Here , we investigated the effect of N6L on the invasion capacity of MDA-MB-435 melanoma cells . Our results show that the multivalent pseudopeptide N6L inhibited Matrigel invasion of MDA-MB-435 cells in a modified Boyden chamber model . This was associated with an increase in TIMP-3 in the cell culture medium without a change in TIMP-3 mRNA expression suggesting its release from cell surface and/or extracellular matrix . This may be explained by our demonstrated N6L interaction with sulfated glycosaminoglycans and consequently the controlled bioavailability of glycosaminoglycan-bound TIMP-3 . The implication of TIMP-3 in N6L-induced inhibition of cell invasion was evidenced by siRNA silencing experiments showing that the loss of TIMP-3 expression abrogated the effect of N6L . The inhibition of tumor cell invasion by N6L demonstrated in this study , in addition to its previously established inhibitory effect on tumor growth and angiogenesis , suggests that N6L represents a promising anticancer drug candidate warranting further investigation .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle , which then stops when confluence is reached again . Although the events involved in cell cycle entry have been widely documented , those managing cell cycle exit have remained so far ill defined . We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p , which acts as a mandatory signal triggering cell cycle arrest when confluence is reached . Blocking miR-483-3p accumulation strongly delays cell cycle exit , maintains cells into a proliferative state and retards their differentiation program . Using two models of cell cycle synchronization ( i.e. mechanical injury and serum addition ) , we show that an ectopic upregulation of miR-483-3p blocks cell cycle progression in early G1 phase . This arrest results from a direct targeting of the CDC25A phosphatase by miR-483-3p , which can be impeded using an anti-miRNA against miR-483-3p or a protector that blocks the complex formation between miR-483-3p and the 3'-untranslated region ( UTR ) of CDC25A transcript . We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which , in turn , abolishes CDK4/6 capacity to associate with D-type cyclins . This prevents CDK4/6 kinases ' activation , impairs downstream events such as cyclin E stimulation and sequesters cells in early G1 . We propose this new regulatory process of cyclin-CDK association as a general mechanism coupling miRNA-mediated CDC25A invalidation to CDK post-transcriptional modifications and cell cycle control .\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: Twelve postmenopausal women ( 54-93 years ) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery . Seven premenopausal patients ( 32-50 years ) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma . Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis , hormone receptor determination and analysis of proliferation fraction . Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy . Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells . A decreased proliferation fraction was observed in two tumors responding to tamoxifen . Eight patients , all with estrogen receptor positive tumors , had stable disease . Progressive disease was observed in two patients with less than 25% receptor positive cells . In these tumors the percentage of proliferating cells remained high during therapy . Objective response was recorded for six patients treated with chemotherapy . The clinical response was reflected in a decreased proliferation fraction . No correlation was observed between response and percentage of proliferating cells in the untreated tumor . The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas .\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: Colorectal tumors are continuously exposed to an inflammatory environment , which together with mitogenic signals sustain several cancer hallmarks . Nuclear factor-kappa B ( NFκB ) is a major regulator of inflammation and variation in NFκB-associated genes could potentially be used as biomarkers to identify patients with increased risk of colorectal cancer ( CRC ) development , and/or a rapidly progressing disease . In this study , 348 CRC cases and 806 randomly selected healthy individuals from southeastern Sweden were examined with regard to seven polymorphisms in NFκB pathway-associated genes . Log-rank-tests and Cox proportional hazard regression analysis examined the association between the polymorphisms and CRC-specific survival , whereas chi-square tests and logistic regression analysis were used to test for associations between the polymorphisms and CRC susceptibility . Gene expression and loss of heterozygosity analyses of TNFAIP3 were carried out in a subset of tumors to assess its role as a tumor suppressor in CRC . Heterozygous and polymorphic TNFAIP3 ( rs6920220 ) , heterozygous NLRP3 ( Q705K ) and polymorphic NFκB -94 ATTG ins/del genotypes were found to be associated with poorer survival in patients diagnosed with invasive CRC ( aHR = 5.2 , 95% CI : 2.5-10.9 , P &lt ; 0.001 ) . TNFAIP3 mRNA levels were significantly decreased in tumors compared with adjacent non-neoplastic mucosa ( P &lt ; 0.0001 ) and loss of heterozygosity of 6q23.3 ( TNFAIP3 ) was detected in 17% of cases , whereas only 2.5% of the investigated specimens displayed TNFAIP3 gene mutations . We propose that TNFAIP3 ( rs6920220 ) , NLRP3 ( Q705K ) and NFκB -94 ATTG ins/del polymorphisms are associated with poor survival in patients with advanced CRC and may be used as prognostic markers . Experimental results indicate that TNFAIP3 may act as a tumor suppressor in CRC .\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 research aims to give a new insight to the relationship between host local immune response and the biological behaviour of the tumor by evaluating of intratumoral natural killer ( NK ) cells and tumor necrosis factor-alpha ( TNFalpha ) expressions in oral squamous cell carcinomas . New paraffin sections of the deepest parts of the 46 cases of oral squamous cell carcinomas were immunohistochemically treated by CD57 , selected as NK cell indicator , and TNFalpha monoclonal antibodies . The tumors were graded according to histopathologic grading scores of invasive margins and categorized into 2 groups as \" good \" and \" poor \" prognostic groups . Fifteen cases , from which could be obtained full clinical data , were clinically staged and because of the scarcity of the cases in each group were divided , again , two groups as group 1 : stage I+stage II and group 2 : stage III+stage IV . The expression levels of CD57 and TNFalpha were evaluated according to histopathologic grading groups and clinical staging groups . The results showed that the density of CD57+cells ( NK cells ) was statistically lower in tumors graded as poor prognostic group compared to the cases in good prognostic group . On the contrary , expression level of TNFalpha was statistically higher in poor prognostic group . These findings suggested that increased secretion of TNFalpha in the tumors , which show high invasive potential , may be one of the facilitating factors for tumor invasion and be responsible from suppression of NK cells . Withdrawal of NK cells in the high invasive tumor areas also reminds the necessity of certain shared genetic rearrangements in tumor cells for getting protected from NK cell attacks and moving ahead within the extracellular matrix .\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: Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression . Using genome-wide chromatin-binding profiles , we describe binding of p53 also to regions located distantly from any known p53 target gene . Interestingly , many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions . We demonstrate that these p53-bound enhancer regions ( p53BERs ) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation . Furthermore , p53BERs produce , ina p53-dependent manner , enhancer RNAs ( eRNAs ) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest . Thus , our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site . Moreover , eRNA production from p53BERs is required for efficient p53 transcription enhancement .\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 DNA mismatch repair ( MMR ) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity . The genes of the MMR pathway are highly conserved across different organisms . Likewise , defective MMR function universally results in microsatellite instability ( MSI ) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer . ( Lynch syndrome ) . To identify previously unrecognized deleted genes or loci that can lead to MSI , we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae . This pool represents a collection of non-essential homozygous yeast diploid ( 2N ) mutants in which there are deletions for over four thousand yeast open reading frames ( ORFs ) . From our screen , we identified a deletion mutant strain of the PAU24 gene that leads to MSI . In a series of validation experiments , we determined that this PAU24 mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain , other deletion mutants and comparable to a MMR mutant involving the MLH1 gene . Likewise , in yeast strains with a deletion of PAU24 , we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen .\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: Bisphenol A ( BPA ) is one of the most prevalent chemicals in daily-use materials , therefore , human exposure to BPA is ubiquitous . We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 ( GPR30)-mediated epidermal growth factor receptor ( EGFR)-extracellular regulated kinase ( ERK)-c-Fos pathway . However , through the same pathway GPR30 expression has been shown to be induced by EGF , an EGFR ligand . Thus , we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells . By transient transfection with expression plasmids , 10(-9)M BPA significantly transactivates the Gpr30-5'-flanking region through activating the GPR30 , cGMP-dependent protein kinase ( PKG ) , estrogen receptor-α ( ER-α ) , and EFGR-ERK pathways . Furthermore , an activator protein-1 ( AP-1 ) site located within this region is found to be responsible for the transactivation of BPA . Expectedly , through the same pathways , BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30 , p-ERK1/2 , p-Ser118-ER-α and cell proliferation by BPA . Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos , ER-α , and PKG pathways , presumably boosting the cells proliferation via a regulatory loop . The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Intracystic papillary carcinoma ( IPC ) of the breast is a rare form of noninvasive breast cancer . An appreciation of associated pathology with IPC may be critical in surgical decision-making . METHODS The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed . Three patient groups were identified according to the pathologic features of the primary tumor : IPC alone , IPC with associated ductal carcinoma in situ ( DCIS ) , and IPC with associated invasion with or without DCIS . Types of treatment and outcomes were compared between groups . RESULTS Forty patients were treated for IPC during the study period . Fourteen had pure IPC , 13 had IPC with DCIS , and 13 had IPC with invasion . The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery ( mastectomy or segmental mastectomy ) performed and whether radiation therapy was administered . The disease-specific survival rate was 100% . CONCLUSIONS When IPC is identified , it is frequently associated with DCIS and or invasion . Standard therapy should be based on associated pathology . The role of radiation therapy in pure IPC remains to be determined .\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: Curcumin ( CUR ; diferuloylmethane ) , a rhizome extract of Curcuma Longa L. is commonly used as a food coloring and flavoring agent . Although oriental and Ayurvedic medicines have traditionally used CUR in the treatment of diseases , conventional medicine has just begun to recognize its potential therapeutic value . Numerous recent studies have demonstrated the ability of CUR to halt or prevent certain types of cancer , decrease inflammation , and improve cardiovascular health . However , very few studies have examined its ability to protect against drug-induced organ injury . This study explored whether CUR pre-exposure has the potential to prevent acetaminophen ( APAP)-induced : ( i ) hepatotoxicity , ( ii ) genomic injury , ( iii ) oxidative stress in the liver , and ( iv ) apoptotic and necrotic cell deaths in the liver in vivo . Additional goals were to investigate the interplay of pro- and anti-apoptotic genes and their ultimate impact on various forms of cell death . In order to study the CUR-APAP interaction , male B6C3F1 mice were gavaged with CUR ( 17 mg/kg/day , p.o. ) for 12 days followed by a single APAP exposure ( 400 mg/kg , ip ) . Four groups of animals ( control , CUR , APAP , CUR+APAP ) were sacrificed 24 h after APAP exposure . The results indicated that APAP-induced liver injury associated events as serum ALT ( 80-fold ) , lipid peroxidation ( 357% ) and DNA fragmentation ( 469% ) were markedly reduced to 3-fold , 134% and 162% , respectively , in the CUR+APAP group . The APAP-induced increase in expression of pro-apoptotic genes ( Bax , caspase-3 ) decreased while expression of anti-apoptotic genes ( Bcl-XL ) increased in CUR preexposed mouse livers , and these changes were mirrored in the pattern of apoptotic and necrotic cell deaths . Levels of DNA damage sensor P⁵³ and its counterpart Mdm2 were also analyzed during this interaction . Based on the available literature , and these results , it seems likely that CUR may impart global protection in vivo against drug-induced liver injury by opposing several crucial events instrumental to both apoptosis and necrosis .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo . Although it is generally accepted that contact inhibition plays a pivotal role in maintaining tissue homeostasis , the molecular mechanisms of contact inhibition are still not fully understood . FoxM1 is known as a proliferation-associated transcription factor and is upregulated in many cancer types . Vice versa , anti-proliferative signals , such as TGF-β and differentiation signals decrease FoxM1 expression . Here we investigated the role of FoxM1 in contact inhibition in fibroblasts . We show that protein expression of FoxM1 is severely and rapidly downregulated upon contact inhibition , probably by inhibition of ERK activity , which then leads to decreased expression of cyclin A and polo-like kinase 1 . Vice versa , ectopic expression of FoxM1 prevents the decrease in cyclin A and polo-like kinase 1 and causes a two-fold increase in saturation density indicating loss of contact inhibition . Hence , we show that downregulation of FoxM1 is required for contact inhibition by regulating expression of cyclin A and polo-like kinase 1 .\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: Immunosenescence , the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections , cancer and autoimmune conditions in the elderly . Senescence-accelerated mouse ( SAM ) was used to study the protective effects of Pu-erh tea in the elderly . The senile-prone sub-strain , SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125 , 250 or 500mg/kg . The results showed that Pu-erh tea significantly increased the fractions of na�ve T lymphocytes , CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood , but decreased the levels of IL-6 in aged mice . These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine . Thus , long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer .\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: Perlecan Domain V ( DV ) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells ( BECs ) following stroke . In this study , we define the specific mechanism of DV interaction with the α(5)β(1) integrin , identify the downstream signal transduction pathway , and further investigate the functional significance of resultant VEGF release . Interestingly , we found that the LG3 portion of DV , which has been suggested to possess most of DV's angio-modulatory activity outside of the brain , binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV . Additionally , we implicate DV's DGR sequence as an important element for the interaction of DV with α(5)β(1) . Furthermore , we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion . We show that DV increases the phosphorylation of ERK , which leads to subsequent activation and stabilization of eIF4E and HIF-1α . Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs . While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors , LY294002 and Akt IV . Lastly , we demonstrate that VEGF activity is critical for DV increases in BEC proliferation , as well as angiogenesis in a BEC-neuronal co-culture system . Collectively , our findings expand our understanding of DV's mechanism of action on BECs , and further support its potential as a novel stroke therapy .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2 , but clinical trials with Src inhibitors have shown little activity . The present study evaluated preclinical efficacy of a novel peptidomimetic compound , KX-01 ( KX2-391 ) , that exhibits dual action as an Src and pretubulin inhibitor . KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231 , MDA-MB-157 , and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells . Treatments were evaluated by growth/apoptosis , isobologram analysis , migration/invasion assays , tumor xenograft volume , metastasis , and measurement of Src , focal adhesion kinase ( FAK ) , microtubules , Ki67 , and microvessel density . KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition . KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts ( 1 and 5 mg/kg , twice daily ) . KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis . KX01 also resulted in microtubule disruption in tumors . Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver . KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis . As ER/PR/HER2-negative patients are candidates for paclitaxel therapy , combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death;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: Most ovarian cancers are estrogen-positive and hormonal treatments using anti-estrogens or aromatase inhibitors are under investigation for treating the tumors that are resistant to conventional therapies . In this study , the long-term effects of two anti-estrogens , namely 4-hydroxytamoxifen and fulvestrant ( or ICI182,780 ) , were investigated in ERα-positive BG1 epithelial ovarian cancer cells . To this aim , cells were grown in the presence of anti-estrogen concentrations that were sufficient to saturate the estrogen receptors , but were neither cytotoxic nor cytostatic as indicated by the absence of inhibition of cell proliferation . In these conditions and despite the lack of cytostatic effect of the drugs , long-term treatment ( 3 months ) with the pure anti-estrogen fulvestrant induced a specific , reproducible and irreversible inhibition of ERα expression . This inhibition was accompanied by loss of estrogen-induced cell proliferation and gene expression as indicated by the analysis of several estrogen-responsive genes . ERα down-regulation was not linked to deregulated expression of transcription factors which drive ERα transcription and did not involve DNA methylation or histone deacetylation . Altogether , these results demonstrate that non-cytotoxic concentrations of pure anti-estrogens affect estrogen signaling and might be relevant for the treatment for ovarian cancers .\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: Inhibition of Notch signaling is effective in inhibiting colon tumorigenesis , but targeting specific components of the pathway may provide more effective strategies . Here we show that the expression of Jagged1 , a ligand for canonical Notch signaling , was restricted to enteroendocrine cells or undetectable in the mucosa of the human small and large intestine , respectively . In contrast , increased expression characterized half of human colon tumors , although not all tumors with elevated Wnt signaling displayed elevated Jagged1 . Increased Jagged1 was also present in intestinal tumors of Apc(1638N/+) and Apc(Min/+) mice , but to a higher level and more frequently in the former , and in 90% of mouse tumors Notch signaling was elevated when Jagged1 was elevated . In the human HT29Cl16E colonic carcinoma cell line , induction of goblet cell differentiation by contact inhibition of growth depended on the loss of Jagged1-mediated Notch activation , with signaling through Notch1 and Notch2 acting redundantly . Therefore , targeting of Jagged1 could be effective in downregulating Notch signaling in a subset of tumors , but may avoid the limiting gastrointestinal toxicity caused by pharmacological inhibition of Notch 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: BACKGROUND Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis . In this study , we report that the latest member of the C-X-C-type chemokines , CXCL17 ( DMC/VCC-1 ) , recruits immature myeloid-derived cells and enhances early tumor progression . METHODOLOGY/PRINCIPAL FINDINGS CXCL17 was preferentially expressed in some aggressive types of gastrointestinal , breast , and lung cancer cells . CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro , but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice . Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+)Gr1(+) myeloid-derived cells at tumor sites in mice and promoted CD31(+) tumor angiogenesis . Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+)Gr1(high)F4/80(-) cells ( ≈ 90% ) with a neutrophil-like morphology in vitro . Although CXCL17 expression could not increase the number of CD11b(+)Gr1(+) cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells , the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation . CONCLUSIONS/SIGNIFICANCE These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: It is thought that high linear energy transfer ( LET ) radiation induces more complex DNA damage than low-LET particles , specifically clustered DNA damage that causes cells to repair DNA double strand breaks ( DSB ) more slowly and leads to severe biological consequences . The present study aimed to investigate the role of exogenously added glutathione ( GSH ) on ( 12)C-beam ( 287keV/mum ) and ( 7)Li-beam ( 60keV/mum ) induced chromosome aberration ( CA ) formation , particularly on exchange aberration formation . In order to characterize the role of GSH in the joining of DNA DSBs , we induced DNA lesions with bleomycin ( Blem ) in conjunction with either high- or low-LET radiation ( X-rays ) since the chemistry of the free DNA ends created by Blem and X-rays is similar . CHO cells were exposed to reduced GSH at a concentration of 2mM for 3h before radiation . Treatment with Blem ( 20mug/ml ) was carried out for 2h before the cells were exposed to radiation . Our results show that the frequency of chromosomal aberration increases with increased LET . Heavy ion exposed cells show a higher frequency of CA over time than do X-irradiated cells . An analysis of the first post-irradiation mitosis of exposed CHO cells shows that high-LET radiation induces more breaks than exchange-type aberrations and exogenous GSH has no influence on high-LET radiation-induced DNA damage . The DNA lesions induced by low-LET radiation interact relatively strongly with Blem-induced lesions whereas interaction between Blem and high-LET radiations was poor . This could be attributed to differences in repair kinetics and qualitative differences in the DNA lesions induced by Blem and high-LET radiation .\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: Alteration of the oxidative stress of hepatocellular carcinoma ( HCC ) cells can influence the expressions of genes favored angiogenesis . Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3 . Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3 . This study was to investigate the influence of therapeutic concentrations of prazosin ( 0.01 and 0.1μM ) on cell proliferation and differential expressions of CCL2 , CCL20 , CXCL6 , CXCL10 , IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines . Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress ( cell line A ; HCC24/KMUH ) and one with this effect ( cell line B ; HCC38/KMUH ) were investigated by 0.01 and 0.1μM prazosin . The premixed WST-1 cell proliferation reagent was applied for proliferation assay . Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction . Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines . Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes . However , 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion , high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress . Clinical application of prazosin in patients with HCC should consider this possibility .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Cancer cells undergo multi-step processes in obtaining the ability to metastasize , and are constantly exposed to signals that induce apoptosis . Acquisition of anti-apoptotic properties by cancer cells is important for metastasis , and recent studies suggest that transforming growth factor ( TGF)-β promotes the survival of certain types of cancer cells . Here , we found that in highly metastatic breast cancer cells , JygMC(A) , JygMC(B) and 4T1 , TGF-β ligands were produced in autocrine fashion . Pharmacological inhibition of endogenous TGF-β signalling by a TGF-β type I receptor kinase inhibitor in serum-free conditions increased the expression of BH3-only protein , Bim ( also known as Bcl2-like 11 ) in JygMC(A) and JygMC(B) cells , and caused apoptotic cell death . We also found that induction of Bim by TGF-β was not observed in Foxc1 knocked-down cancer cells . These findings suggest that TGF-β plays a crucial role in the regulation of survival of certain types of cancer cells through the TGF-β-Foxc1-Bim pathway , and that specific inhibitors of TGF-β signalling might be useful as apoptosis inducers in breast cancer cells .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The xeroderma pigmentosum group C ( XPC ) protein specifically involved in genome-wide damage recognition for nucleotide excision repair ( NER ) was purified as a tight complex with HR23B , one of the two mammalian homologs of RAD23 in budding yeast . This XPC-HR23B complex exhibits strong binding affinity for single-stranded DNA , as well as preferential binding to various types of damaged DNA . To examine the structure-function relationship of XPC , a series of truncated mutant proteins were generated and assayed for various binding activities . The two domains participating in binding to HR23B and damaged DNA , respectively , were mapped within the carboxy-terminal half of XPC , which also contains an evolutionary conserved amino acid sequence homologous to the yeast RAD4 protein . We established that the carboxy-terminal 125 amino acids are dispensable for both HR23B and damaged DNA binding , while interactions with transcription factor IIH ( TFIIH ) are significantly impaired by truncation of this domain . Furthermore , deletion of the extreme carboxy-terminal domain totally abolished XPC activity in the cell-free NER reaction . These results suggest that following initial damage recognition , the carboxy terminus of XPC may be essential for the recruitment of TFIIH , and that most truncation mutations identified in XP-C patients result in non-functional proteins .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: UNLABELLED BACKGROUND Cell lines are very useful for clinical and basic research . Thus far , only 11 reports have documented the characteristics of ovarian endometrioid adenocarcinoma cell lines in the literature . Due to the scarcity of information , the establishment of an ovarian malignant tumor cell line with distinctive characteristics is particularly important to study this disease . Thus , this study was undertaken to establish and characterize a new human endometrioid adenocarcinoma cell line of the ovary . METHODS The cell line NOMH-1 was established from an ovarian tumor of a 44-year-old woman . Features of the cell line studied included morphology , chromosome analysis , heterotransplantation , tumor markers , and chemosensitivity . RESULTS This cell line has been growing well for 232 months and subcultured more than 50 times . Monolayer cultured cells were polygonal in shape , showing a pavement-like arrangement and a tendency to stack without contact inhibition . They exhibited a human karyotype with a modal chromosomal number in the hypertriploid range . The cells could be transplanted into the subcutis of nude mice and produced tumors resembling the original tumor . NOMH-1 cells expressed both CEA and CA19-9 which were identified immunohistochemically in the original tumor and the heterotransplanted tumor . The cells were sensitive to paclitaxel , an agent commonly used in the treatment of gynecological cancers . CONCLUSIONS NOMH-1 is the first ovarian endometrioid adenocarcinoma cell line in which CEA and CA19-9 expression have been defined . This newly established cell line should be useful for investigating the characteristics of ovarian endometrioid adenocarcinoma .\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 Glioblastoma is the most common and most aggressive form of malignant glioma and is very difficult to treat . Controlling tumour cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients . Since constitutive activation of nuclear factor-κB ( NF-κB ) is necessary for tumour progression , NF-κB may be an important pharmacological target for this disease . Our study aimed to evaluate the antitumour effects of parthenolide , a NF-κB inhibitor , in two human glioblastoma cell lines ( U87MG and U373 ) and in glioblastoma xenografts . Furthermore , we aimed to investigate the molecular mechanisms underlying these effects . METHODS The anti-invasive and anti-angiogenic effects of parthenolide were analysed using in vitro invasion and angiogenesis assays . Parthenolide-induced growth inhibition of glioblastoma cells in vitro was determined using the MTT ( methyl thiazolyl tetrazolium ) assay . In addition , the effect of parthenolide on orthotropic implantation in vivo was evaluated using an intracerebral human glioblastoma xenograft model . RESULTS We found that parthenolide suppresses proliferation , invasion , and tumour- induced angiogenesis of glioblastoma cells . Molecular studies demonstrated that parthenolide suppresses gene and protein expression of angiogenic factors . Furthermore , parthenolide reduced Akt phosphorylation and activated mitochondrial signalling , suggesting that the antitumour function of parthenolide may be mediated not only by the inhibition of NF-κB but also by the inhibition of Akt signalling and the activation of apoptotic proteins . Parthenolide suppressed neovascularity and tumour growth in glioblastoma xenografts . CONCLUSION The present study identified parthenolide as a new therapeutic agent for glioblastomas .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;inducing angiogenesis;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: Pegylated Interferon-α2b ( pIFN-α ) is an integral part of the drug regimen currently employed against melanoma . Interferon Regulatory Factor-1 ( IRF-1 ) plays an important role in the transcriptional regulation of the IFN response , cell cycle and apoptosis . We have studied pIFN-α induced responses when combined with the chemotherapy agent , vinblastine in tumor and endothelial cell lines and the connection to IRF-1 signaling . Levels of IRF-1/IRF-2 protein expression were found to be decreased in tumor versus normal tissues. pIFN-α induced IRF-1 signaling in human melanoma ( M14 ) and endothelial ( EA.hy926 ) cells and enhanced cell death when combined with vinblastine . Upon combined IFN-α and vinblastine treatment , p21 expression , PARP cleavage and activated Bak levels were increased in M14 cells . An increase in p21 and cyclin D1 expression occurred in EA.hy926 cells after 6 h of treatment with pIFN-α which dissipated by 24 h . This biphasic response , characteristic of cellular senescence , was more pronounced upon combined treatment . Exposure of the EA.hy926 cells to pIFN-α was associated with an enlarged , multinucleated , β-galactosidase-positive senescent phenotype . The overall therapeutic mechanism of IFN-α combined with chemotherapy may be due to both direct tumor cell death via IRF-1 signaling and by premature senescence of endothelial cells and subsequent effects on angiogenesis in the tumor microenvironment .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;enabling replicative immortality;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: OBJECTIVE The study was undertaken to document and highlight the shortcomings of histopathology reporting of breast carcinoma in Pakistan so that improvements can be recommended and a standardized protocol devised . METHODS This was a descriptive cross sectional study and was conducted at Histopathology Department , Armed Forces Institute of Pathology , Rawalpindi from 1st January 2008 to 31st October 2008 . Fifty consecutive breast carcinoma reports received for review from different laboratories were analyzed for documentation of patients age , sex , type of procedure/specimen , specimen size , tumour size , invasive tumour type , invasive tumour grade , comment on excision margins , extent of lymph node involvement , insitu component , lymphovascular invasion , necrosis , skin involvement and tabular format . Frequencies and percentages were calculated for presence of these above mentioned variables in different reports , keeping in mind the possible information that could be obtained from a particular sample . RESULTS It was found that the variable least mentioned in the reports was in situ component commented upon in only 23.2% of reports . Necrosis was mentioned in 35% of reports . Tabular format was found in 36% of reports only . CONCLUSION Marked deficiencies are seen in histopathology reports for breast carcinoma due to the lack of any standardized reporting system . Separate checklist formats for trucut biopsies , lumpectomies and mastectomies should be introduced to ensure uniform reporting .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 ( PRC17 ) . When overexpressed in 3T3 mouse fibroblast cells , PRC17 induced growth in low serum , loss of contact inhibition , and tumor formation in nude mice . The PRC17 gene product contains a GTPase-activating protein ( GAP ) catalytic core motif found in various Rab/Ypt GAPs , including RN-Tre . Similar to RN-Tre , we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis . Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities , suggesting that GAP activity is essential for its oncogenic function . Whereas PRC17 is amplified in 15% of prostate cancers , it is highly overexpressed in approximately one-half of metastatic prostate tumors . The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;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: Chronic inflammation , increased reactivity to self-antigens and incidences of cancer are hallmarks of aging . However , the underlying mechanisms are not well understood . Age-associated alterations in the DNA either due to oxidative damage , defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible . Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells . We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-alpha from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine . Investigations into the mechanisms revealed that DNA from aged subjects is not degraded , neither is it more damaged compared to DNA from young subjects . However , there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity . Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation , autoimmunity and cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "avoiding immune destruction;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects , including anti-inflammatory , cardio-protective , and cancer-protective activities . It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders . Ulcerative colitis is an idiopathic , chronic inflammatory disease of the colon associated with a high colon cancer risk . Here , we used a dextran sulfate sodium ( DSS ) mouse model of colitis , which resembles human ulcerative colitis pathology . Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner . Resveratrol significantly improves inflammation score , downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria , and modulates CD3(+) T cells that express tumor necrosis factor-alpha and IFN-gamma . Markers of inflammation and inflammatory stress ( p53 and p53-phospho-Ser(15) ) are also downregulated by resveratrol . Because chronic colitis drives colon cancer risk , we carried out experiments to determine the chemopreventive properties of resveratrol . Tumor incidence is reduced from 80% in mice treated with azoxymethane ( AOM ) + DSS to 20% in mice treated with AOM + DSS + resveratrol ( 300 ppm ) . Tumor multiplicity also decreased with resveratrol treatment . AOM + DSS-treated mice had 2.4 +/- 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol , which had 0.2 +/- 0.13 tumors per animal . The current study indicates that resveratrol is a useful , nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis .\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 Multiple myeloma ( MM ) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype ( i.e. , the Warburg effect ) . We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane ( PM ) localization of GLUT4 , consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates , proliferative capacity , and viability . The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells . FINDINGS We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect . AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation , known to be required for inactivation of AS160 Rab-GAP activity . Importantly , we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines . Furthermore , we demonstrate that ectopic expression of a full-length , phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence , which is characteristic of MM cells . CONCLUSIONS This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer . Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease .\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 In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis , whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells . We show that this may result in cancer via mitotic failure , recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer , to a biophysical defect that may contribute to cancer initiation . MODEL Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance , disrupted microtubule dynamics , and finally , genomic instability , from which cancers can arise . Specifically , we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer . CONCLUSIONS A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell . Contrary to current understanding , this effect may precipitate cancer development , rather than follow from it , providing new insights into carcinogenesis , cancer treatment , and prevention .\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: ATM(Tel1) and ATR(Rad3) checkpoint kinases phosphorylate the C-terminus of histone H2AX ( H2A in yeasts ) in chromatin flanking DNA damage , establishing a recruitment platform for checkpoint and repair proteins . Phospho-H2A/X ( gammaH2A/X)-binding proteins at double-strand breaks ( DSBs ) have been characterized , but those required for replication stress responses are unknown . Here , we present genetic , biochemical , small angle X-ray scattering ( SAXS ) , and X-ray structural studies of the Schizosaccharomyces pombe Brc1 , a 6-BRCT-domain protein that is structurally related to Saccharomyces cerevisiae Rtt107 and mammalian PTIP . Brc1 binds gammaH2A to form spontaneous and DNA damage-induced nuclear foci . Spontaneous Brc1 foci colocalize with ribosomal DNA repeats , a region prone to fork pausing and genomic instability , whereas DNA damage-induced Brc1 foci colocalize with DSB response factors. gammaH2A binding is critical for Brc1 function . The 1.45 A resolution crystal structure of Brc1-gammaH2A complex shows how variable BRCT insertion loops sculpt tandem-BRCT phosphoprotein-binding pockets to facilitate unique phosphoprotein-interaction specificities , and unveils an acidic DNA-mimicking Brc1 surface . From these results , Brc1 docking to gammaH2A emerges as a critical chromatin-specific response to replication-associated DNA damage .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The purpose of this investigation was to study the variation of p73 gene expression in the apoptotic process of acute myeloid leukemia ( AML ) cell line U937 induced by methotrexate ( MTX ) . Morphological changes of apoptotic cells were observed with microscopy and Wright's + Giemsa staining . DNA ladder and cell cycle were examined by agarose gel electrophoresis and flow cytometry respectively . Using semi-quantitive reverse transcription-polymerase chain reaction ( RT-PCR ) , the expression of p73 mRNA was examined . Results showed that MTX could induce U937 cell apoptosis effectively . Condensed nuclei , fragmentation of chromosome and DNA ladder were seen after 6 hour following treatment of MTX 5 micro mol/L . Sub-G(1) peak and S + G(2)/M arrest were also determined by FCM , but the quantity of p73 expression was generally constant . In conclusion , U937 cell apoptosis induced by MTX did not change p73 mRNA level .\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: Reciprocity of inflammation , oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression . Whereas the mechanism of hypoxia-driven angiogenesis is well understood , the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure . Here we show that the end products of lipid oxidation , ω-(2-carboxyethyl)pyrrole ( CEP ) and other related pyrroles , are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma . The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 ( TLR2 ) , but not TLR4 or scavenger receptors on endothelial cells , leading to an angiogenic response that is independent of vascular endothelial growth factor . CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling . Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis . Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration . Taken together , these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns , providing a key link connecting inflammation , oxidative stress , innate immunity and angiogenesis .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;inducing angiogenesis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Energy deregulation and abnormalities of tumor cell metabolism are critical issues in understanding cancer . Hereditary leiomyomatosis renal cell carcinoma ( HLRCC ) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme fumarate hydratase ( FH ) , and one known to be highly metastatic and unusually lethal . There is considerable utility in establishing preclinical cell and xenograft models for study of disorders of energy metabolism , as well as in development of new therapeutic approaches targeting of tricarboxylic acid ( TCA ) cycle enzyme-deficient human cancers . Here we describe a new immortalized cell line , UOK 262 , derived from a patient having aggressive HLRCC-associated recurring kidney cancer . We investigated gene expression , chromosome profiles , efflux bioenergetic analysis , mitochondrial ultrastructure , FH catabolic activity , invasiveness , and optimal glucose requirements for in vitro growth . UOK 262 cells have an isochromosome 1q recurring chromosome abnormality , i(1)(q10) , and exhibit compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC . The cells also display glucose-dependent growth , an elevated rate of lactate efflux , and overexpression of the glucose transporter GLUT1 and of lactate dehydrogenase A ( LDHA ) . Mutant FH protein was present primarily in edematous mitochondria , but with catalytic activity nearly undetectable . UOK 262 xenografts retain the characteristics of HLRCC histopathology . Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme-deficient form of kidney cancer . This tumor model is the embodiment of the Warburg effect . UOK 262 provides a unique in vitro and in vivo preclinical model for studying the bioenergetics of the Warburg effect in human 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: Aurora A kinase has drawn considerable attention as a therapeutic target for cancer therapy . However , the underlying molecular and cellular mechanisms of the anticancer effects of Aurora A kinase inhibition are still not fully understood . Herein , we show that depletion of Aurora A kinase by RNA interference ( RNAi ) in hepatocellular carcinoma ( HCC ) cells upregulated FoxO1 in a p53-dependent manner , which induces cell cycle arrest . Introduction of an RNAi-resistant Aurora A kinase into Aurora A-knockdown cells resulted in downregulation of FoxO1 expression and rescued proliferation . In addition , silencing of FoxO1 in Aurora A-knockdown cells allowed the cells to exit cytostatic arrest , which , in turn , led to massive cell death . Our results suggest that FoxO1 is responsible for growth arrest at the G 2/M phase that is induced by Aurora A kinase inhibition .\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: Colorectal cancer represents one of the most challenging diseases . Increasing evidence indicates that aberrant expression of microRNAs ( miRNAs ) is related to pathogenesis of colorectal cancer . Cancer cells reprogram metabolic pathways to sustain higher proliferation rates . Whether mechanisms underlying the role of miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms through which miRNAs alter cancer metabolism are as yet unknown . Herein , we show that miR-124 , miR-137 and miR-340 are associated with poor prognosis of colorectal cancer . Expression of these miRNAs inhibits the growth of colorectal cancer cells . PKM ( pyruvate kinase isozyme ) alternative splicing proteins ( PTB1/hnRNAPA1/hnRNAPA2 ) , which control the inclusion of exon 9 ( PKM1 ) or exon 10 ( PKM2 ) , are targeted by miR-124 , miR-137 and miR-340 . Consequently , miR-124 , miR-137 and miR-340 switch PKM gene expression from PKM2 to PKM1 . High ratios of PKM1/PKM2 inhibit the glycolysis rate , but elevate the glucose flux into oxidative phosphorylation . These results demonstrate that miRNAs ( miR-124 , miR-137 and miR-340 ) impair colorectal cancer growth by counteracting the Warburg effect due to regulating alternative splicing of the PKM gene .\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 Barrett's esophagus ( BE ) is caused by gastroesophageal reflux with consecutive mucosal inflammation , predisposing patients to the development of esophageal adenocarcinoma ( EAC ) . We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography , a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function . RESULTS Biopsies were taken during endoscopy from BE , EAC , and normal control tissue , and proteomic microscopy was performed on 32 different epitopes . When the significance level was set to p &lt ; 0.0005 and the search depth to five antibody combinations , controls and BE can be differentiated by 63 , controls and EAC by 3222 , and BE from EAC by 1521 distinct protein combinations.For example , the number of activated apoptotic naïve and memory T cells was significantly increased only in BE , whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC . In contrast , the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC . Confirming different pathways in BE and EAC , the number of T lymphocytes with p53 expression and downregulation of bcl2 expression ( CD3+p53+Bcl2-NfkB- ) was significantly increased in EAC compared to BE and controls . Interestingly , the number of precursor T cells ( CD7+ ) was significantly elevated only in EAC . These cells lack Bax and caspase-8 , suggesting impaired apoptosis in the early stages of T cell differentiation . CONCLUSION Proteomic analysis showed for the first time that proteins , which are critically involved in the mucosal immune system of the esophagus , are distinctly expressed in BE and EAC , whereas others are comparably altered in both diseases , suggesting that many pathogenic events might be shared by both diseases . Topological proteomic analysis , therefore , helps us to understand the different pathogenic events in the underlying disease pathways .\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: Pilocytic astrocytoma is commonly viewed as a benign lesion . However , disease onset is most prevalent in the first two decades of life , and children are often left with residual or recurrent disease and significant morbidity . The Hedgehog ( Hh ) pathway regulates the growth of higher WHO grade gliomas , and in this study , we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas . Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed ( ages 1-22 years ) and correlated inversely with patient age . Evaluation of a tissue array revealed oligodendroglioma-like features , pilomyxoid features , infiltration , and necrosis more commonly in specimens from younger patients ( below the median patient age of 10 years ) . Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10 . A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured , and 86% of Ki67-positive cells also expressed PTCH . The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism . Taken together , these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth .\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: Cigarette smoking is implicated in numerous diseases , including emphysema and lung cancer . The clinical expression of lung disease in smokers is not well explained by currently defined variations in gene expression or simple differences in smoking exposure . Alveolar macrophages play a critical role in the inflammation and remodeling of the lung parenchyma in smoking-related lung disease . Significant gene expression changes in alveolar macrophages from smokers have been identified . However , the mechanism for these changes remains unknown . One potential mechanism for smoking-altered gene expression is via changes in cytosine methylation in DNA regions proximal to gene-coding sequences . In this study , alveolar macrophage DNA from heavy smokers and never smokers was isolated and methylation status at 25,000 loci determined . We found differential methylation in genes from immune-system and inflammatory pathways . Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune-system and inflammatory pathways . A significant number of genes with smoking-altered mRNA expression had inverse changes in methylation status . One gene highlighted by this data was the FLT1 , and further studies found particular up-regulation of a splice variant encoding a soluble inhibitory form of the receptor . In conclusion , chronic cigarette smoke exposure altered DNA methylation in specific gene promoter regions in human alveolar macrophages .\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: Uncontrolled estrogen exposure can induce an imbalance in BCL2/BAX expression in endometrial cells , leading to precancerous lesions and type I endometrial adenocarcinoma . This study aimed to explore the mechanism underlying this phenomenon . We show that the activated estrogen receptor can suppress the expression of BAX by upregulating a group of microRNAs including hsa-let-7 family members and hsa-miR-27a , thereby promoting an increased BCL2/BAX ratio as well as enhanced survival and proliferation in the affected cells . These ER-regulated hsa-let-7 microRNAs can be detected in most hyperplastic endometria , suggesting their potential utility as indicators of estrogen over-exposure .\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 aim of this study was to determine whether caffeine enhanced radiosensitivity of normal liver tissue in a rat radiation-induced liver disease model . Buffalo rat McA-RH7777 hepatocellular cancer cells and BRL3A normal liver cells were irradiated , and cell cycle distribution and apoptosis rates were analyzed . A rat model of radiation-induced liver disease was established , rats were randomized into four groups : control ; caffeine alone ; irradiation ( IR ) alone ; and caffeine plus IR ( Caff + IR ) group . Apoptosis rates in normal rat liver tissue after IR were evaluated by TUNEL staining and caspase-3 Western blot . Transaminase activity was measured and histopathological examination was done after IR . Caffeine abrogated IR-induced G2 phase arrest ( Caff + IR vs. IR : 40.9 ± 4.0 vs. 60.7 ± 5.5% , at 12 h after IR ) and increased apoptosis rates ( Caff + IR vs. IR : 56.1 ± 6.8 vs. 35.5 ± 4.0% , at 72 h after IR ) in McA-RH7777 cells , but did not affect IR-induced G2 phase arrest and apoptosis rates at any time point after IR in BRL3A cells . Caffeine did not enhance apoptosis , transaminase activity , or histopathological injury of normal rat liver tissue at any time points after IR . This study suggests that caffeine might not enhance radiosensitivity of normal liver tissue in vivo . In an earlier study , we reported that caffeine enhanced radiosensitivity of human hepatocellular cancer in a nude mice model . Together , these results offer feasibility of clinical application .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;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: Direct experimental evidence implicates telomere erosion as a primary cause of cellular senescence . Using a well characterized model system for breast cancer , we define here the molecular and cellular consequences of adriamycin treatment in breast tumor cells . Cells acutely exposed to adriamycin exhibited an increase in p53 activity , a decline in telomerase activity , and a dramatic increase in beta-galactosidase , a marker of senescence . Inactivation of wild-type p53 resulted in a transition of the cellular response to adriamycin treatment from replicative senescence to delayed apoptosis , demonstrating that p53 plays an integral role in the fate of breast tumor cells treated with DNA-damaging agents . Stable introduction of hTERT , the catalytic protein component of telomerase , into MCF-7 cells caused an increase in telomerase activity and telomere length . Treatment of MCF-7-hTERT cells with adriamycin produced an identical senescence response as controls without signs of telomere shortening , indicating that the senescence after treatment is telomere length-independent . However , we found that exposure to adriamycin resulted in an overrepresentation of cytogenetic changes involving telomeres , showing an altered telomere state induced by adriamycin is probably a causal factor leading to the senescence phenotype . To our knowledge , these data are the first to demonstrate that the mechanism of adriamycin-induced senescence is dependent on both functional p53 and telomere dysfunction rather than overall shortening .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;genomic instability and mutation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Lipoprotein lipase ( LPL ) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins . LPL is a member of a family of hydrolytic enzymes that include hepatic lipase and pancreatic lipase . Based on primary sequence homology of LPL to pancreatic lipase , Ser-132 , Asp-156 , and His-241 have been proposed to be part of a domain required for normal enzymic activity . We have analyzed the role of these potential catalytic residues by site-directed mutagenesis and expression of the mutant LPL in human embryonic kidney-293 cells . Substitution of Ser-132 , Asp-156 , and His-241 by several different residues resulted in the expression of an enzyme that lacked both triolein and tributyrin esterase activities . Mutation of other conserved residues , including Ser-97 , Ser-307 , Asp-78 , Asp-371 , Asp-440 , His-93 , and His-439 resulted in the expression of active enzymes . Despite their effect on LPL activity , substitutions of Ser-132 , Asp-156 , and His-241 did not change either the heparin affinity or lipid binding properties of the mutant LPL . In summary , mutation of Ser-132 , Asp-156 , and His-241 specifically abolishes total hydrolytic activity without disrupting other important functional domains of LPL . These combined results strongly support the conclusion that Ser-132 , Asp-156 , and His-241 form the catalytic triad of LPL and are essential for LPL hydrolytic activity .\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: RAD51 is a key enzyme of homologous recombination and repair of DNA double-strand breaks . RAD51 mRNA expression levels are significantly increased in laser-microdissected mammary simple carcinomas and their lymph node metastases when compared to adenomas or nonneoplastic mammary gland of the same dog . Here , RAD51 protein expression was analyzed by immunohistochemistry in paraffin-embedded mammary carcinomas and their lymph node metastases of 40 dogs , adenomas of 48 dogs , and nonneoplastic mammary gland of 88 dogs . Number of cells with nuclear RAD51 expression was significantly ( P &lt ; or = .05 ) increased in carcinomas when compared to adenomas and metastases . In contrast , no significant differences in the number of RAD51-expressing cells were detected when metastases were compared with adenomas and nonneoplastic gland . RAD51 expression in carcinomas was correlated with expression in metastases but not with histologic grade . In conclusion , the increased number of RAD51-expressing cells in carcinomas might indicate genomic instability in these cells . Nevertheless , the increased RAD51 mRNA expression in metastases could not be confirmed by immunohistochemistry .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;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: HM781-36B is an orally administered pan-human epidermal growth factor receptor ( HER ) inhibitor . To explore the role of pan-HER inhibitor in breast cancer , we investigated the antitumor effect and mechanisms of HM781-36B in breast cancer cell lines . Six breast cancer cell lines ( BT474 , MDA-MB-453 , SK-BR-3 , T47D , MCF-7 , and MDA-MB-231 ) were tested . The growth inhibitory effect was assessed using the tetrazolium bromide [ 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide ] assay . The cell cycle at various concentrations of HM781-36B was analyzed by flow cytometry , and analysis of downstream molecules was performed by western blot analysis . Interaction of HM781-36B with cytotoxic chemotherapeutic agents was analyzed by combination index using CalcuSyn . The HER2-amplified cells ( SK-BR-3 , BT474 , and MDA-MB-453 ) were sensitive to HM781-36B ( IC50=0.001 μmol/l , 0.0012 μmol/l , and 0.0095 μmol/l , respectively ) . HM781-36B induced G1 arrest and resulted in apoptosis . It reduced the level of p-HER2 , p-AKT , p-ERK , and p-STAT3 . HM781-36B combined with 5-fluorouracil , cisplatin , paclitaxel , or gemcitabine showed a synergistic inhibitory effect on the HER2-amplified and on some of the HER2-nonamplified breast cancer cells . HM781-36B could be a promising treatment for HER2-amplified breast cancer as a single agent or in combination with cytotoxic agents and can be a candidate for treatment of HER2-nonamplified breast cancer in combination with cytotoxic agents .\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: Tumor development requires angiogenesis and anti-angiogenic therapies have been introduced in the treatment of cancer . In this context , heparan sulfate proteoglycans ( HSPGs ) emerge as interesting targets , owing to their function as co-receptors of major , pro-angiogenic factors . Accordingly , previous studies have suggested anti-tumor effects of heparin , i.e. over-sulfated HS , and various heparin mimetics ; however , a significant drawback is their unspecific mechanism of action and potentially serious side-effects related to their anticoagulant properties . Here , we have explored the use of human ScFv anti-HS antibodies ( αHS ) as a more rational approach to target HSPG function in endothelial cells ( ECs). αHS were initially selected for their recognition of HS epitopes localized preferentially to the vasculature of patient glioblastoma tumors , i.e. highly angiogenic brain tumors . Unexpectedly , we found that these αHS exhibited potent pro-angiogenic effects in primary human ECs. αHS were shown to stimulate EC differentiation , which was associated with increased EC tube formation and proliferation . Moreover , αHS supported EC survival under hypoxia and starvation , i.e. conditions typical of the tumor microenvironment . Importantly , αHS-mediated proliferation was efficiently counter-acted by heparin and was absent in HSPG-deficient mutant cells , confirming HS-specific effects . On a mechanistic level , binding of αHS to HSPGs of ECs as well as glioblastoma cells was found to trigger p38 MAPK-dependent signaling resulting in increased proliferation . We conclude that several αHS that recognize HS epitopes abundant in the tumor vasculature may elicit a pro-angiogenic response , which has implications for the development of antibody-based targeting of HSPGs in cancer .\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: Lewis y ( LeY ) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface . Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis . However , the effects of LeY on ovarian cancer are not yet clear . Previously , we transfected the ovarian cancer cell line RMG-I with the α1,2-fucosyltransferase gene to obtain stable transfectants , RMG-I-H , that highly express LeY . In the present study , we examined the proliferation , tumorigenesis , adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody ( mAb ) . Additionally , we examined the expression of TGF-β1 , VEGF and b-FGF in xenograft tumors . The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb . When subcutaneously inoculated in nude mice , RMG-I-H cells produced large tumors , while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors . Moreover , the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb . Notably , the expression of TGF-β1 , VEGF and b-FGF all increased in RMG-I-H cells . In conclusion , LeY plays an important role in promoting cell proliferation , tumorigenecity and adhesion , and these effects may be related to increased levels of growth factors . The LeY antibody shows potential application in the treatment of LeY-positive tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: BACKGROUND Brain-metastatic breast cancer ( BMBC ) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown . Recent work has demonstrated that deregulation of epidermal growth factor receptor ( EGFR ) may correlate with BMBC progression . However , the exact contribution that EGFR makes to BMBC remains unclear . METHODS The role of EGFR in BMBC was explored by serial analyses in a brain-trophic clone of human MDA-MB-231 breast carcinoma cells ( 231-BR cells ) . EGFR expression was inhibited by stable short-hairpin RNA transfection or by the kinase inhibitor erlotinib , and it was activated by heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) . Cell growth and invasion activities also were analyzed in vitro and in vivo . RESULTS EGFR inhibition or activation strongly affected 231-BR cell migration/invasion activities as assessed by an adhesion assay , a wound-healing assay , a Boyden chamber invasion assay , and cytoskeleton staining . Also , EGFR inhibition significantly decreased brain metastases of 231-BR cells in vivo . Surprisingly , changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay , an anchorage-independent growth assay , and cell cycle analysis . Immunoblot analysis suggested that EGFR drives cells ' invasiveness capability mainly through phosphoinositide 3-kinase/protein kinase B and phospholipase C γ downstream pathways . In addition , EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen-activated protein kinase pathway . CONCLUSIONS The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231-BR cells , providing new evidence of the potential value of EGFR inhibition in treating BMBC .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: DNA-protein cross-links ( DPCs ) are formed upon exposure to a variety of chemical and physical agents and pose a threat to genomic integrity . In particular , acrolein and related aldehydes produce DPCs , although the chemical linkages for such cross-links have not been identified . Here , we report that oligodeoxynucleotides containing 1,N(2)-deoxyguanosine adducts of acrolein , crotonaldehyde , and trans-4-hydroxynonenal can form cross-links with the tetrapeptide Lys-Trp-Lys-Lys . We concluded that complex formation is mediated by a Schiff base linkage because DNA-peptide complexes were covalently trapped following reduction with sodium cyanoborohydride , and pre-reduction of adducted DNAs inhibited complex formation . A previous NMR study demonstrated that duplex DNA catalyzes ring opening for the acrolein-derived gamma-hydroxy-1,N(2)-propanodeoxyguanosine adduct to yield an aldehydic function ( de los Santos , C. , Zaliznyak , T. , and Johnson , F . ( 2001 ) J. Biol . Chem. 276 , 9077-9082 ) . Consistent with this earlier observation , the adducts under investigation were more reactive in duplex DNA than in single-stranded DNA , and we concluded that the ring-open aldehydic moiety is the induced tautomer in duplex DNA for adducts exhibiting high relative reactivity . Adducted DNA cross-linked to Arg-Trp-Arg-Arg and Lys-Trp-Lys-Lys with comparable efficiency , and N(alpha)-acetylation of peptides dramatically inhibited trapping ; thus , the reactive nucleophile is located at the N-terminal alpha-amine of the peptide . These data suggest that Schiff base chemistry can mediate DPC formation in vivo following the formation of stable aldehyde-derived DNA adducts .\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 is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer . Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables . Nigella sativa has been shown to possess anti-carcinogenic activity , inhibiting growth of several cancer cell lines in vitro . However , the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood . Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL ( P<0.05 ) . Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h . Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Androgens regulate both the physiological development of the prostate and the pathology of prostatic diseases . However , the mechanisms by which androgens exert their regulatory activities on these processes are poorly understood . In this study , we have determined that androgens regulate overall cell metabolism and cell growth , in part , by increasing autophagy in prostate cancer cells . Importantly , inhibition of autophagy using either pharmacological or molecular inhibitors significantly abrogated androgen-induced prostate cancer cell growth . Mechanistically , androgen-mediated autophagy appears to promote cell growth by augmenting intracellular lipid accumulation , an effect previously demonstrated to be necessary for prostate cancer cell growth . Further , autophagy and subsequent cell growth is potentiated , in part , by androgen-mediated increases in reactive oxygen species . These findings demonstrate a role for increased fat metabolism and autophagy in prostatic neoplasias and highlight the potential of targeting underexplored metabolic pathways for the development of novel therapeutics .\n OUTPUT:\n" }, { "from": "agent", "value": "resisting cell death;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Tumor endothelial marker ( TEM ) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis . So far , the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified . Here , we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel , during capillary morphogenesis in a three-dimensional collagen I matrix , and upon confluence on a two-dimensional matrix . TEM5 expression was not induced by a variety of soluble angiogenic factors , including VEGF and bFGF , in subconfluent endothelial cells . TEM5 upregulation was blocked by toxin B from Clostridium difficile , an inhibitor of the small GTPases Rho , Rac , and Cdc42 . The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression , whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation . An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation . Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;evading growth suppressors" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The results of experimental studies have indicated the pleiotropic effects of statins in organism , e.g. the influence on cell cycle , apoptosis or angiogenesis . In this study , the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined . Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment ( 18 weeks ) . At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis . In treated animals ( simvastatin 180 mg/kg ) , significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation . Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells . In high grade control carcinoma cells , the expression of Ki67 increased by 37% ( non-significantly ) in comparison with control low grade carcinomas . A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment . The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment .\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: Geraniol ( GOH ) , a naturally occurring monoterpene , has been shown to have antiproliferative , cell cycle arrest and apoptosis-inducing effects , and represents a promising cancer chemopreventive agent . In the present study , we investigated the chemopreventive potential of GOH ( 50 and 100 mg kg(-1) body weight ) against 7,12-dimethylbenz[a]anthracene ( DMBA)/12-O-tetradecanoylphorbol 13-acetate ( TPA)-mediated skin tumorigenesis in Swiss albino mice . The topical treatment of GOH , 30 min prior to TPA ( 2 µg per 200 µl of acetone ) treatment significantly inhibited TPA-induced skin edema , hyperplasia , COX-2 induction and oxidative stress response . The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [ (3) H ] thymidine incorporation by 53% ( P < 0.001 ) and 41% ( P < 0.001 ) , respectively . We found that GOH treatment significantly inhibited the tumor incidence and number of tumors ( P < 0.001 ) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice . Furthermore , we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor . Consistently , GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions . Thus , it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Ultraviolet ( UV ) light induces DNA-damage checkpoints and mutagenesis , which are involved in cancer protection and tumorigenesis , respectively . How cells identify DNA lesions and convert them to checkpoint-activating structures is a major question . We show that during repair of UV lesions in noncycling cells , Exo1-mediated processing of nucleotide excision repair ( NER ) intermediates competes with repair DNA synthesis . Impediments of the refilling reaction allow Exo1 to generate extended ssDNA gaps , detectable by electron microscopy , which drive Mec1 kinase activation and will be refilled by long-patch repair synthesis , as shown by DNA combing . We provide evidence that this mechanism maybe stimulated by closely opposing UV lesions , represents a strategy to redirect problematic repair intermediates to alternative repair pathways , and may also be extended to physically different DNA damages . Our work has significant implications for understanding the coordination between repair of DNA lesions and checkpoint pathways to preserve genome stability .\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: Radiotherapy is commonly used for cancer treatment . However , it often results in side effects due to radiation damage in normal tissue , such as bone marrow ( BM ) failure . Adult hematopoietic stem and progenitor cells ( HSPC ) reside in BM next to the endosteal bone surface , which is lined primarily by hematopoietic niche osteoblastic cells . Osteoblasts are relatively more radiation-resistant than HSPCs , but the mechanisms are not well understood . In the present study , we demonstrated that the stress response gene REDD1 ( regulated in development and DNA damage responses 1 ) was highly expressed in human osteoblast cell line ( hFOB ) cells after γ irradiation . Knockdown of REDD1 with siRNA resulted in a decrease in hFOB cell numbers , whereas transfection of PCMV6-AC-GFP-REDD1 plasmid DNA into hFOB cells inhibited mammalian target of rapamycin ( mTOR ) and p21 expression and protected these cells from radiation-induced premature senescence ( PS ) . The PS in irradiated hFOB cells were characterized by significant inhibition of clonogenicity , activation of senescence biomarker SA-β-gal , and the senescence-associated cytokine secretory phenotype ( SASP ) after 4 or 8 Gy irradiation . Immunoprecipitation assays demonstrated that the stress response proteins p53 and nuclear factor κ B ( NFkB ) interacted with REDD1 in hFOB cells . Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein expression in these cells , indicating that REDD1 was regulated by both factors . Our data demonstrated that REDD1 is a protective factor in radiation-induced osteoblast cell premature senescence .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors , including cellular immunity . We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms . However , how metastasis susceptibility genes interact with the tumor stroma is incompletely understood . Here , we employ a complex genetic screen to identify Cadm1 as a novel modifier of metastasis . We demonstrate that Cadm1 can specifically suppress metastasis without affecting primary tumor growth . Unexpectedly , Cadm1 did not alter tumor-cell-autonomous properties such as proliferation or invasion , but required the host's adaptive immune system to affect metastasis . The metastasis-suppressing effect of Cadm1 was lost in mice lacking T cell-mediated immunity , which was partially phenocopied by depleting CD8(+) T cells in immune-competent mice . Our data show a novel function for Cadm1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms , and this is the first report of a heritable metastasis susceptibility gene engaging tumor non-autonomous factors .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: A large number of human cancers display alterations in the Ink4a/cyclin D/Cdk4 genetic pathway , suggesting that activation of Cdk4 plays an important role in oncogenesis . Here we report that Cdk4-null mouse embryonic fibroblasts are resistant to transformation in response to Ras activation with dominant-negative ( DN ) p53 expression or in the Ink4a/Arf-null background , judged by foci formation , anchorage-independent growth , and tumorigenesis in athymic mice . Cdk4-null fibroblasts proliferate at normal rates during early passages . Whereas Cdk4(+/+)Ink4a/Arf(-/-) cells are immortal in culture , Cdk4(-/-)Ink4a/Arf(-/-) cells undergo senescence during continuous culture , as do wild-type cells . Activated Ras also induces premature senescence in Cdk4(-/-)Ink4a/Arf(-/-) cells and Cdk4(-/-) cells with DNp53 expression . Thus , Cdk4 deficiency causes senescence in a unique Arf/p53-independent manner , which accounts for the loss of transformation potential . Cdk4-null cells express high levels of p21(Cip1/Waf1) with increased protein stability . Suppression of p21(Cip1/Waf1) by small interfering RNA ( siRNA ) , as well as expression of HPV-E7 oncoprotein , restores immortalization and Ras-mediated transformation in Cdk4(-/-)Ink4a/Arf(-/-) cells and Cdk4(-/-) cells with DNp53 expression . Therefore , Cdk4 is essential for immortalization , and suppression of Cdk4 could be a prospective strategy to recruit cells with inactive Arf/p53 pathway to senescence .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Past studies have shown that amplified insulin-like growth factor 1 ( IGF1)/IGF1 receptor ( IGF1-R ) signalling has an important role in colorectal cancer ( CRC ) development , progression and resistance to treatment . In this report , we demonstrate that downregulation of microRNA-497 ( miR-497 ) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells . MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3 ' untranslated region ( 3'UTR ) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa . However , only overexpression of miR-497 led to suppression of the IGF1-R 3'UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells . This was associated with inhibition of cell survival , proliferation and invasion , and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil , and the death ligand tumour necrosis factor-related apoptosis-inducing ligand . The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling , as overexpression of an active form of Akt reversed its impact on cell survival and proliferation , recapitulating the effect of overexpression of IGF1-R . Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1 , where these miRs are located at proximity . Similarly to miR-195 , the members of the same miR family , miR-424 that was upregulated , and miR-15a , miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa , did not appear to have a role in regulating the expression of IGF1-R . Taken together , these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.Oncogene advance online publication , 18 June 2012 ; doi:10.1038/onc.2012.214 .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;activating invasion and metastasis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Various endocrine disrupting chemicals ( EDCs ) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation . Among EDCs , bisphenolA ( BPA ) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [ methoxychlor ( MXC) ] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors ( ERs ) , causing human health problems such as abnormal reproduction and carcinogenesis . In this study , we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells . MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line ; these cells are , therefore , a useful invitro model for detecting estrogenic activity in response to EDCs . We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay . We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH . To determine whether BPA and MXC stimulate cancer cell growth though ER signaling , we co-treated the cells with agonists ( propyl pyrazoletriol , PPT ; and diarylpropionitrile , DPN ) or an antagonist ( ICI 182,780 ) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs . These studies confirmed the carcinogenicity of EDCs invitro . As a result , BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes , especially ones affecting the G1/S transition via ERα signaling . These collective results confirm the carcinogenicity of these EDCs invitro . Further studies are required to determine whether EDCs promote carcinogenesis invivo .\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: Hypoxia is one of the inevitable circumstances of various tumors . It controls various levels of regulation in tumor progression and results in tumor resistance to radiotherapy and chemotherapy . Here we investigated a synthetic TPZ derivative , N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide ( XQ2 ) , a novel compound that induced anti-cancer effects both in normoxia and in hypoxia , cell proliferation assay found that XQ2 exhibited a potent inhibitory effect on the tested cancer cell lines both in normoxia and in hypoxia . Flow cytometry and western blot studies indicated that XQ2 induces G2/M arrest and a caspase-dependent apoptosis in A549 cells . Additionally , intracellular reactive oxygen species ( ROS ) appear to play a key role in the anticancer effect of XQ2 in hypoxia . Taken together , our data suggest that XQ2 exerted anticancer action by suppressing the ROS level and triggering cell-cycle arrest and the caspase-dependent pathway , which is associated with apoptosis .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;resisting cell death;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: PURPOSE : Prostate cancer ( PCa ) development is often associated with deletion or silencing of tumor suppressor PTEN , a negative regulator of the PI3K-Akt pathway , leading to resistance to various therapies . Therefore , the PI3K/Akt pathway plays a central role in various cellular processes leading to malignant phenotype , and , consequently is an attractive target . However , the efficacy of AKT inhibitors is limited by resistance mechanisms that result in minimal tumor cell death . Methods:Effects of Akt inhibitor AZD5363 were investigated on cell proliferation , apoptosis , Akt pathway and survival mechanisms . We then examined the impacts of inhibition of autophagy combined with AZD5363 on cell proliferation and apoptosis . Furthermore , the anti-cancer activity of combination treatment of the lysosomotropic inhibitor of autophagy ( chloroquine ) with Akt inhibitor AZD5363 was evaluated in PC-3 prostate cancer xenografts . RESULTS : we show that AZD5363 affected Akt downstream pathway by reducing p-mTOR , p-P70S6K and p-S6K . While AZD5363 monotherapy induced G2 growth arrest and autophagy , it failed to induce significant apoptosis in PC-3 and DU145 PCa cells . Blocking autophagy using pharmacological inhibitors or genetic inhibitors enhanced cell death induced by AZD5363 in these PCa cells . Importantly , the combination of AZD5363 with chloroquine significantly reduced tumor volume by 84.9% compared with the control group and by 77.5% compared with either drug alone in PC3 xenografts . CONCLUSIONS : These data demonstrate that Akt inhibitor AZD5363 , synergizes with the lysosomotropic inhibitor of autophagy , chloroquine , to induce apoptosis and delay tumor progression in PCa models that are resistant to monotherapy AZD5363 , providing a new therapeutic approach potentially translatable to patients .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Acute leukemia is a disorder of the hematopoietic system characterized by the expansion of a clonal population of cells blocked from differentiating into mature cells . Recent studies have shown that chalcones and their derivatives induce apoptosis in different cell lines . Since new compounds with biological activity are needed , the aim of this study was to evaluate the cytotoxic effect of three synthetic chalcones , derived from 1-naphthaldehyde and 2-naphthaldehyde , on human acute myeloid leukemia K562 cells and on human acute lymphoblastic leukemia Jurkat cells . Based on the results , the most cytotoxic compound ( A1 ) was chosen for further analysis in six human acute leukemia cells and in a human colon adenocarcinoma cell line ( HT-29 ) . Chalcone A1 significantly reduced the cell viability of K562 , Jurkat , Kasumi , U937 , CEM and NB4 cells in a concentration and time-dependent manner when compared with the control group ( IC(50) values between ∼1.5μM and 40μM ) . It was also cytotoxic to HL-29 cells . To further examine its effect on normal cells , peripheral blood lymphocytes collected from healthy volunteers were incubated with the compound . It has also been incubated with human fibroblasts cultured from bone marrow ( JMA ) . Chalcone A1 is non-cytotoxic to PBL cells and to JMA cells . A1 caused significant cell cycle arrest in all phases according to the cell line , and increased the proportion of cells in the sub G0/G1 phase . To evaluate whether this chalcone induced cell death via an apoptotic or necrotic pathway , cell morphology was examined using fluorescence microscopy . Cells treated with A1 at IC(50) demonstrated the morphological characteristic of apoptosis , such as chromatin condensation and formation of apoptotic bodies . Apoptosis was confirmed by externalization of phosphatidylserine , which was detected by the Annexin V-FITC method , and by DNA fragmentation . The results suggest that chalcone A1 has potential as a new lead compound for cancer therapy .\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: Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance . Here we report the novel finding that Tph-1 ( tryptophan hydroxylase-1 ) , a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan , is a potent regulator of immunity . In models of skin allograft tolerance , tumor growth , and experimental autoimmune encephalomyelitis , Tph-1 deficiency breaks allograft tolerance , induces tumor remission , and intensifies neuroinflammation , respectively . All of these effects of Tph-1 deficiency are independent of its downstream product serotonin . Because mast cells ( MCs ) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect , these experiments introduce a fundamentally new mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity .\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: MicroRNAs ( miRNAs ) are considered to be regulators of various biological processes in cancers , including the epithelial to mesenchymal transition ( EMT ) , which is a key factor in cancer metastasis . In this study , we aimed to clarify the potential roles of miR-490-3p in hepatocellular carcinoma ( HCC ) cells . Using real-time quantitative RT-PCR , we discovered that miR-490-3p was up-regulated in HCC tissues and cells compared with the adjacent non-tumor tissues and normal cells . We also found that overexpression of miR-490-3p led to an increase in cell proliferation , migration , and invasion abilities and that it contributed to EMT . The inhibition of miR-490-3p had the opposite effect on the cells . We identified ERGIC3 ( endoplasmic reticulum-Golgi intermediate compartment protein 3 ) as a direct target gene for miR-490-3p . Unlike most miRNA-mRNA interactions , miR-490-3p increased ERGIC3 mRNA and protein levels as well as the intensity of expression of the EGFP reporter gene controlled by the 3'-UTR of ERGIC3 mRNA . The up-regulation by miR-490-3p also required the participation of Ago2 . The inhibition of miR-490-3p reduced the expression of ERGIC3 . Overexpression of ERGIC3 led to the same effect on HCC cells as miR-490-3p overexpression , including EMT . Importantly , silencing ERGIC3 reversed the cellular responses mediated by miR-490-3p overexpression . In conclusion , our study indicated for the first time that miR-490-3p functioned like an oncogenic miRNA in HCC cells and that the inhibition of miR-490-3p might provide an potential treatment approach for HCC 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: BACKGROUND : Previously , we have observed that highly unsaturated dietary ( n-3 ) fatty acids inhibit cell proliferation in conjunction with stimulation of insulin-like growth factor-binding protein ( IGFBP)-6 secretion in Caco-2 cells , a human colon carcinoma cell line . METHODS : To test the converse hypothesis that inhibition of endogenous IGFBP-6 secretion stimulates Caco-2 cell proliferation , cells were transfected with the antisense IGFBP-6 expression construct or pcDNA3 vector only , and single colonies resistant to G418 sulfate were isolated . RESULTS : Our initial studies indicated that three antisense clones grew faster and produced less IGFBP-6 than two pcDNA3 clones , so antisense IGFBP-6 #5 and pcDNA3 #8 were selected for further detailed analysis . Both the control and antisense clones grew in serum-free medium reaching a plateau density at day eight . However , the antisense clone grew at a rate faster than that of the control and reached a final density that was 31 +/- 3% higher than the control . Northern blot , ligand blot and immunoblot analyses revealed that accumulation of IGFBP-6 mRNA and concentrations of IGFBP-6 peptide produced by the antisense clone were decreased by 80-90% compared to the control . The doubling times of the antisense and control clones were 21.9 +/- 0.4 and 24.8 +/- 0.3 h ( P &lt ; 0.05 ) , respectively . Exogenous IGF-I and IGF-II ( 0.2-200 nmol/L ) stimulated proliferation of both the control and antisense clones in a dose-dependent manner , but the relative potency and efficacy of IGF-II was higher in the antisense clone compared to the control . These results indicate that suppression of IGFBP-6 secretion correlates with an increase in the basal rate of Caco-2 cell growth . CONCLUSIONS : Our findings are consistent with the hypothesis that IGFBP-6 inhibits cell growth by binding to endogenously produced IGF-II , thereby preventing IGF-II from interacting with the IGF-I receptor to stimulate cellular proliferation by an autocrine mechanism .\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 vascular endothelial growth factor ( VEGF ) receptor tyrosine kinase inhibitor sunitinib has been approved for first-line treatment of patients with metastatic renal cancer and is currently being trialled in other cancers . However , the effectiveness of this anti-angiogenic agent is limited by the presence of innate and acquired drug resistance . By screening a panel of candidate growth factors we identified fibroblast growth factor 2 ( FGF2 ) as a potent regulator of endothelial cell sensitivity to sunitinib . We show that FGF2 supports endothelial proliferation and de novo tubule formation in the presence of sunitinib and that FGF2 can suppress sunitinib-induced retraction of tubules . Importantly , these effects of FGF2 were ablated by PD173074 , a small molecule inhibitor of FGF receptor signalling . We also show that FGF2 can stimulate pro-angiogenic signalling pathways in endothelial cells despite the presence of sunitinib . Finally , analysis of clinical renal-cancer samples demonstrates that a large proportion of renal cancers strongly express FGF2 . We suggest that therapeutic strategies designed to simultaneously target both VEGF and FGF2 signalling may prove more efficacious than sunitinib in renal cancer patients whose tumours express FGF2 .\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: Chromosomal translocations typically impair cell differentiation and often require secondary mutations for malignant transformation . However , the role of a primary translocation in the development of collaborating mutations is debatable . To delineate the role of leukemic translocation NUP98-HOXD13 ( NHD13 ) in secondary mutagenesis , DNA break and repair mechanisms in stimulated mouse B lymphocytes expressing NHD13 were analyzed . Our results showed significantly reduced expression of non-homologous end joining ( NHEJ)-mediated DNA repair genes , DNA Pkcs , DNA ligase4 , and Xrcc4 leading to cell cycle arrest at G2/M phase . Our results showed that expression of NHD13 fusion gene resulted in impaired NHEJ-mediated DNA break repair .\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: Filamin-A cross-links actin filaments into dynamic orthogonal networks , and interacts with an array of proteins of diverse cellular functions . Because several filamin-A interaction partners are implicated in signaling of cell mobility regulation , we tested the hypothesis that filamin-A plays a role in cancer metastasis . Using four pairs of filamin-A proficient and deficient isogenic cell lines , we found that filamin-A deficiency in cancer cells significantly reduces their migration and invasion . Using a xenograft tumor model with subcutaneous and intracardiac injections of tumor cells , we found that the filamin-A deficiency causes significant reduction of lung , splenic and systemic metastasis in nude mice . We evaluated the expression of filamin-A in breast cancer tissues by immunohistochemical staining , and found that low levels of filamin-A expression in cancer cells of the tumor tissues are associated with a better distant metastasis-free survival than those with normal levels of filamin-A . These data not only validate filamin-A as a prognostic marker for cancer metastasis , but also suggest that inhibition of filamin-A in cancer cells may reduce metastasis and that filamin-A can be used as a therapeutic target for filamin-A positive 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 Young age is a favorable prognostic factor for patients with glioblastoma multiforme ( GBM ) . We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers . PATIENTS AND METHODS Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed . All patients were treated with standard first-line therapy . The primary end points were overall survival ( OS ) and time to progression ( TTP ) . IDH1-R132H mutation status was analyzed using immunohistochemistry , and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction . RESULTS We included 70 patients ( 36 men and 34 women ) with a median age of 33 years . IDH1-R132H mutations were detected in 22 ( 39.3% ) of 56 cases and MGMT promoter methylation in 33 ( 61.1% ) of 54 cases with available tissue samples . In patients with wild-type IDH , median TTP was 8.2 months and median OS was 24 months , compared with 18 months and 44 months , respectively , observed in patients with mutated IDH . Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS . Of note , the social and economical situation of the young patients with GBM was alarming , because only 17% succeeded in staying employed after receiving the diagnosis . CONCLUSIONS We found a high frequency of IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age . The social and economic coverage of patients with glioma remains an unsolved socio-ethical problem .\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: Bisphosphonates ( BPs ) are the current standard of care for bone lesions in patients with multiple myeloma ( MM ) but they are associated with a number of side effects such as osteonecrosis of the jaw . The exact mechanisms of osteonecrosis are not elucidated , and its physiopathology is based on several hypotheses such as a decrease in bone remodeling or an inhibitory effect on angiogenesis . The aim of our study was to investigate the mechanism involved in the pathogenesis of osteonecrosis . We examined the apoptosis of circulating endothelial progenitor cells in MM subjects before and after BP treatment and in osteonecrosis patients using a flow-cytometric analysis . Our data showed an increase in endothelial cell apoptosis in MM patients after BP administration and in osteonecrosis subjects . Our study seems in agreement with the hypothesis that BPs can inhibit angiogenesis interfering with endothelial cell proliferation and survival , leading to loss of blood vessels and avascular necrosis .\n OUTPUT:\n" }, { "from": "agent", "value": "inducing angiogenesis;resisting cell death" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Current palliative chemotherapy ( CT ) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers , and long-term survivals are anecdotical . Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism , DNA repair and drug resistance can explain the observed individual differences in response to drugs , in survival and in different susceptibility to the toxic effects of CT . The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen . We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer , treated with CT and alive , disease-free , at 66-82 months . Four patients with typical clinical outcome represented the control group . Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance , DNA repair , cell cycle regulation and growth factors signalling . Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response . Expression analysis in long-term survivors revealed a significant upregulation of PTEN , TP63 , GADD45a and MAPK1 genes . We found also an upregulation of CYP1A1 , CYP3A4 and ERBB4 genes . EGF was found to be down-regulated in long-term survivors . ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients . The present study shed light on a set of genes , which could have a predictive role in survival of patients with metastatic gastric tumors .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress , inflammation , and aberrant nucleotide biosynthesis . Human inosine triphosphate pyrophosphatase ( ITPA ) hydrolyzes triphosphates of noncanonical purine bases ( i.e. , ITP , dITP , XTP , dXTP , or their mimic : 6-hydroxyaminopurine ( HAP ) deoxynucleoside triphosphate ) and thus regulates nucleotide pools and protects cells from DNA damage . We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA . A human polymorphic allele of the ITPA , 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP . The polymorphism has been associated with adverse reaction to purine base-analog drugs . The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant . The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs .\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: Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth . We observed promoter methylation and loss of expression in neurofilament heavy polypeptide ( NEFH ) in a significant proportion of primary esophageal squamous cell carcinoma ( ESCC ) samples that were of a high tumor grade and advanced stage . RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo , whereas forced expression of NEFH significantly inhibited cell growth and colony formation . Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase , via activation of the Akt/beta-catenin pathway , resulting in enhanced aerobic glycolysis and mitochondrial dysfunction . The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of beta-catenin expression , and was decreased by the treatment of 2-Deoxyglucose , a glycolytic inhibitor , or API-2 , an Akt inhibitor . Loss of NEFH activates the Akt/beta-catenin pathway and increases glycolysis and mitochondrial dysfunction . Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We present a novel gain-of-function mutation of TGF-β receptor II ( TβRII ) found in human oral squamous cell carcinoma ( OSCC ) . Expression of E221V/N238I mutant TβRII enhanced TGF-β signaling . Mutation of TβRII conferred cells higher migratory and invasive capabilities and MMP-2 activity . In mouse tumor model , mutant tumors exhibited poor differentiation and E-cadherin relocalization to the cytosol . Lipid-raft-dependent endocytosis of TβRII was attenuated in mutant TβRII , suggesting that enhancement of TGF-β signaling by this mutation is due to delayed TβRII internalization . Taken together , our results show a novel gain-of-function TβRII mutation , which enhances TGF-β signaling leading to more invasive phenotypic changes in human OSCC .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;sustaining proliferative signaling;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues . This was done to mimic the clinical setting where in , normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation . The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretreatment with macerated extract of Nigella sativa seeds ( 100 mg/kg ) , using alkaline comet assay , and also estimating biochemical and blood parameters such as levels of antioxidant enzymes superoxide dismutase and catalase , thiobarbituric acid reactive substances and protein oxidation in organs such as spleen , liver , brain and intestine haemoglobin and total leucocyte count , respectively . The results showed that the macerated extract of Nigella sativa seeds protected the liver , spleen , brain and intestines both in normal as well as tumour bearing mice . This study concludes that macerated extract of Nigella sativa seeds has protective effects against radiation-induced damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties . Hence macerated extract of Nigella sativa seeds , could be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating unwanted side effects of radiation in normal tissues .\n OUTPUT:\n" }, { "from": "agent", "value": "genomic instability and mutation;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Human diploid fibroblasts have a limited life span in vitro , and spontaneous immortalization is an extremely rare event . We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization . Comparison of a preimmortal transformant ( SVtsA/HF-A ) with its uncloned and cloned immortalized derivatives ( AR5 and HAL ) has failed to reveal any major alteration involving the simian virus 40 genome . Karyotypic analysis , however , demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21 . The karyotypic analysis was corroborated by DNA analyses . Southern analysis demonstrated that only one copy of three proto-oncogene loci ( ros1 , c-myb , and mas1 ) on 6q was retained in immortal cells . Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 ( D6S87 ) showed loss of heterozygosity . In addition , elevated expression of c-myb ( 6q22-23 ) was observed . We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization , consistent with the presence of a growth suppressor gene .\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: Gastrin stimulates the growth of pancreatic cancer cells through the activation of the cholecystokinin-B receptor ( CCK-BR ) , which has been found to be overexpressed in pancreatic cancer . In this study , we proposed that the CCK-BR drives growth of pancreatic cancer ; hence , interruption of CCK-BR activity could potentially be an ideal target for cancer therapeutics . The effect of CCK-BR downregulation in the human pancreatic adenocarcinoma cells was examined by utilizing specific CCK-BR-targeted RNA interference reagents . The CCK-BR receptor expression was both transiently and stably downregulated by transfection with selective CCK-BR small-interfering RNA or short-hairpin RNA , respectively , and the effects on cell growth and apoptosis were assessed . CCK-BR downregulation resulted in reduced cancer cell proliferation , decreased DNA synthesis , and cell cycle arrest as demonstrated by an inhibition of G(1) to S phase progression . Furthermore , CCK-BR downregulation increased caspase-3 activity , TUNEL-positive cells , and decreased X-linked inhibitor of apoptosis protein expression , suggesting apoptotic activity . Pancreatic cancer cell mobility was decreased when the CCK-BR was downregulated , as assessed by a migration assay . These results show the importance of the CCK-BR in regulation of growth and apoptosis in pancreatic cancer . Strategies to decrease the CCK-BR expression and activity may be beneficial for the development of new methods to improve the treatment for patients with pancreatic cancer .\n OUTPUT:\n" }, { "from": "agent", "value": "evading growth suppressors;sustaining proliferative signaling;resisting cell death;activating invasion and metastasis" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: We previously demonstrated that downregulation of protein kinase CKII induces cellular senescence in human colon cancer HCT116 cells . To investigate the role of microRNAs ( miRNAs ) in CKII downregulation during senescence , we employed computational algorithms . Four miRNAs ( miR-186 , miR-216b , miR-337-3p , and miR-760 ) were predicted to be miRNAs against CKIIα mRNA . Mimics of all four miRNAs jointly downregulated CKIIα expression in HCT116 cells . Reporter analysis and RT-PCR have suggested that these four miRNAs may stimulate degradation of CKIIα mRNA by targeting its 3 ' untranslated regions ( UTRs ) . The four miRNA mimics increased senescent-associated β-galactosidase ( SA-β-gal ) staining , p53 and p21(Cip1/WAF1) expression , and reactive oxygen species ( ROS ) production . In contrast , concomitant knockdown of the four miRNAs by antisense inhibitors increased the CKIIα protein level and suppressed CKII inhibition-mediated senescence . Finally , CKIIα overexpression antagonized senescence induced by the four miRNA mimics . Therefore , the present results show that miR-186 , miR-216b , miR-337-3p , and miR-760 cooperatively promote cellular senescence through the p53-p21(Cip1/WAF1) pathway by CKII downregulation-mediated ROS production in HCT116 cells .\n OUTPUT:\n" }, { "from": "agent", "value": "enabling replicative immortality;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: IL-16 is a ligand and chemotactic factor for CD4+ T cells . IL-16 inhibits the CD3 mediated lymphocyte activation and proliferation . The effects of IL-16 on the target cells are dependent on the cell type , the presence of co-activators etc . To understand the regulation function and mechanism of IL-16 on target cells , we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro . We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose ( 10(-9)M ) , but inhibited the growth of the cells at higher concentration ( 10(-5)M ) . Results showed that 10(-5) M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells . The treatment blocked the expression of FasL , but up-regulated the c-myc and Bid expression in the cells . Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells , respectively . The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner . The growth-inhibiting effects of rIL-16 might be Fas/FasL independent , but , associated with the activation of PKC , up-regulated expression of c-Myc and Bid , and the participation of the ERK signal pathway in Jurkat 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: Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment . This study investigates the hypothesis that manganese superoxide dismutase ( MnSOD ) regulates cellular redox flux and glucose consumption during the cell cycle . A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts , which was absent in MnSOD homozygous knockout fibroblasts . Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells , which was associated with an increase in glucose and oxygen consumption , and a decrease in MnSOD activity . Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine ( 68 , 89 , 122 , and 202 ) and arginine ( 197 and 216 ) residues . MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD . Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site . Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide , a negatively charged substrate . These results support the hypothesis that MnSOD regulates a \" metabolic switch \" during progression from quiescent through the proliferative cycle . We propose MnSOD as a new molecular player contributing to the Warburg effect .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics;sustaining proliferative signaling;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In human epithelial cancers , the microRNA ( miRNA ) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis , apoptosis , proliferation , and differentiation . Autophagy , a degradation pathway for long-lived protein and organelles , regulates the survival and death of many cell types . Increasing evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression . Using a combined bioinformatics approach , gene set enrichment analysis and miRNA target prediction , we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1 , BNIP3L , ATG12 , ATG5 , ATG2 . Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells . Finally , we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II . Taken together , our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway . This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy .\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: Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer . Here , we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger ( SDGE ) are potent inhibitors of proliferation of endometrial cancer cells . SDGE , isolated from six different batches of ginger rhizomes , consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50) of 1.25 �g/ml . SDGE also enhanced the anti-proliferative effect of radiation and cisplatin . Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3 . GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE , with the isomers neral and geranial constituting 30-40% . Citral , a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50) 10 �M ( 2.3 �g/ml ) . Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells . SDGE was more effective in inducing cancer cell death than citral , suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death . SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential . Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE . This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax . Inhibitor of p53 , pifithrin-α , attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg) SKOV-3 cells . Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial 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: Hypoxia has long been linked to the Warburg effect , yet the underlying mechanism remains largely unclear . It is also not known if lncRNAs are involved in the contribution of hypoxia to the Warburg effect . Here we show that lincRNA-p21 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis . Hypoxia/HIF-1α-induced lincRNA-p21 is able to bind HIF-1α and VHL and thus disrupts the VHL-HIF-1α interaction . This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation . These data indicate the existence of a positive feedback loop between HIF-1α and lincRNA-p21 that promotes glycolysis under hypoxia . The ability of lincRNA-p21 to promote tumor growth is validated in mouse xenograft models . Together , these findings suggest that lincRNA-p21 is an important player in the regulation of the Warburg effect and also implicate lincRNA-p21 as a valuable therapeutic target for 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: Interferon-gamma ( IFN-gamma ) has pleiotropic activities other than its antivirus action , including cell growth inhibition , natural killer ( NK ) cell and cytotoxic T lymphocyte ( CTL ) activation , and angiogenesis inhibitory activity , and these activities are supposed to be involved in its antitumour activity . However , it has not been completely elucidated which activity is mainly involved in the tumour suppression in vivo . In this study , we analysed inhibitory mechanisms of endogenous IFN-gamma against B16 melanoma experimental metastasis . After intravenous injection of tumour cells , tumour deposits in the lungs and liver were increased and life span was shorter in IFN-gamma(-/-) mice , indicating important roles for IFN-gamma in antitumour mechanisms . Interestingly , tumour deposits were not increased in IFN-gamma receptor ( R)(-/- ) mice . Furthermore , only low levels of cell-mediated immunity against the tumour and activation of NK cells were observed , indicating that antimetastatic effects of IFN-gamma is not mediated by host cells . The survival period of B16 melanoma-bearing IFN-gamma R(-/-) mice was , however , shorter than wild-type mice . These observations suggest that IFN-gamma prevents B16 melanoma experimental metastasis by directly inhibiting the cell growth , although antitumour host functions may also be involved in a later phase .\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: OBJECTIVES The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters . METHODS The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically . Stereologic method was used for evaluation of the percentage of positively stained tumor cells . RESULTS Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 ( r = 0.74 , p &lt ; 0.001 ) . MCM-2 and Ki-67 expression was significantly associated with histologic grade ( p &lt ; 0.05 ) , and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status ( p &lt ; 0.05 ) . No significant association was observed between MCM-2 or Ki-67 expression and patient age , tumor size , lymph node status , clinical stage and menopausal status . CONCLUSION Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity ( Ki-67 labelling index ) . Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma ( Tab. 1 , Fig. 4 , Ref. 34 ) . Full Text ( Free , PDF ) www.bmj.sk .\n OUTPUT:\n" }, { "from": "agent", "value": "sustaining proliferative signaling" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: In cancer cells , the aberrant conversion of pyruvate into lactate instead of acetyl-CoA in the presence of oxygen is known as the Warburg effect . The consequences and mechanisms of this metabolic peculiarity are incompletely understood . Here we report that p53 status is a key determinant of the Warburg effect . Wild-type p53 expression decreased levels of pyruvate dehydrogenase kinase-2 ( Pdk2 ) and the product of its activity , the inactive form of the pyruvate dehydrogenase complex ( P-Pdc ) , both of which are key regulators of pyruvate metabolism . Decreased levels of Pdk2 and P-Pdc in turn promoted conversion of pyruvate into acetyl-CoA instead of lactate . Thus , wild-type p53 limited lactate production in cancer cells unless Pdk2 could be elevated . Together , our results established that wild-type p53 prevents manifestation of the Warburg effect by controlling Pdk2 . These findings elucidate a new mechanism by which p53 suppresses tumorigenesis acting at the level of cancer cell metabolism .\n OUTPUT:\n" }, { "from": "agent", "value": "cellular energetics" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: The androgen receptor ( AR ) plays a central role in prostate cancer progression to the castration-resistant ( CR ) lethal state . L-Dopa decarboxylase ( DDC ) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells , where it may enhance AR activity . Here , we hypothesize that the DDC enzymatic inhibitor , carbidopa , can suppress DDC-coactivation of AR and retard prostate tumor growth . Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen ( PSA ) mRNA levels . Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays . The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells ( stably expressing AR ) . In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts , inducibly overexpressing DDC , were reverted to control levels with carbidopa administration . In castrated mice , treating LNCaP tumors , expressing endogenous DDC , with carbidopa delayed progression to the CR state from 6 to 10 weeks , while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold , respectively . Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors , decrease serum PSA , reduce tumor growth and delay CR progression . Since carbidopa is clinically approved , it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression .\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: Imiquimod is a synthetic compound with antitumor properties ; a 5% cream formulation is successfully used to treat skin tumors . The antitumor effect of imiquimod is multifactorial , although its ability to modulate immune responses by triggering TLR7/8 is thought to be key . Among the immune cells suggested to be involved are plasmacytoid DCs ( pDCs ) . However , a direct contribution of pDCs to tumor killing in vivo and the mechanism of their recruitment to imiquimod-treated sites have never been demonstrated . Using a mouse model of melanoma , we have now demonstrated that pDCs can directly clear tumors without the need for the adaptive immune system . Topical imiquimod treatment led to TLR7-dependent and IFN-α/β receptor 1-dependent ( IFNAR1-dependent ) upregulation of expression of the chemokine CCL2 in mast cells . This was essential to induce skin inflammation and for the recruitment of pDCs to the skin . The recruited pDCs were CD8α+ and induced tumor regression in a TLR7/MyD88- and IFNAR1-dependent manner . Lack of TLR7 and IFNAR1 or depletion of pDCs or CD8α+ cells from tumor-bearing mice completely abolished the effect of imiquimod . TLR7 was essential for imiquimod-stimulated pDCs to produce IFN-α/β , which led to TRAIL and granzyme B secretion by pDCs via IFNAR1 signaling . Blocking these cytolytic molecules impaired pDC-mediated tumor killing . Our results demonstrate that imiquimod treatment leads to CCL2-dependent recruitment of pDCs and their transformation into a subset of killer DCs able to directly eliminate tumor cells .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: To determine the threshold dose of β-Naphthoflavone ( BNF ) that induces hepatocellular tumor promoting effects , reactive oxygen species ( ROS ) generation and thiobarbituric acid-reactive substance ( TBARS ) formation , and drug-metabolizing enzymes that protect against ROS generation , two-stage liver carcinogenesis model was used . Partial hepatectomized rats ( n = 11 to 12 ) were fed diets containing 0 , 0.03 , 0.06 , 0.125 or 0.25% BNF for 6 weeks after an intraperitoneal injection of N-diethylnitrosamine ( DEN ) to initiate hepatocarcinogenesis . Histopathologically , glutathione S-transferase placental form ( GST-P)-positive foci significantly increased in rats given 0.25% BNF . No marked changes in ROS production and TBARS contents were observed between the BNF treated and DEN alone groups . Real-time RT-PCR showed that the expression of Cyp1a1 , Cyp1a2 , Cyp1b1 and Nqo1 significantly increased in the groups given 0.03% BNF or more , but Ugt1a6 , Akr7a3 and Gstm1 significantly increased in the groups given 0.125% BNF or more . Gpx2 and Yc2 significantly increased in the groups given 0.06% BNF or more and 0.25% BNF , respectively . Inflammation-related genes such as Ccl2 , Mmp12 , Serpine1 and Cox-2 significantly increased in the 0.25% BNF group . In immunohistochemistry , the number of cyclooxygenase-2 ( COX-2)-positive cells increased in rats given 0.25% BNF . These results suggest that 0.25% BNF is the threshold dose for liver tumor promotion , and the fact that inflammation-related genes and COX-2 protein increased in the 0.25% BNF group strongly suggests that inflammation is involved in the liver tumor promoting effect of BNF in rats .\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: Ovarian cancer-related angiogenesis is a complex process orchestrated by many positive and negative regulators . Many growth factors are involved in the development of the tumor-associated vasculature , and from these , endocrine gland-derived vascular endothelial growth factor ( EG-VEGF ) seems to play a crucial role . EG-VEGF is the first organ-specific angiogenic factor and its effects are restricted to the endothelial cells of the endocrine glands . Although EG-VEGF was detected in both normal and neoplastic ovaries , its clinical significance remains controversial . In the present study , we analyzed 30 patients with epithelial ovarian cancer , and the immunohistochemical expression of EG-VEGF was compared with the conventional clinico-pathological parameters of prognosis . Neoplastic cells of the ovarian carcinoma expressed EG-VEGF in 73.33% of the cases , as a cytoplasmic granular product of reaction . We found a strong correlation between the expression of EG-VEGF at protein level and tumor stage , grade , and microscopic type . The expression of EG-VEGF was found in patients with stage III and IV , but not in stage II . The majority of serous adenocarcinoma , half of the cases with clear cell carcinoma and two cases with endometrioid carcinoma showed definite expression in tumor cells . No positive reaction was found in the cases with mucinous carcinoma . Our results showed that EG-VEGF expression is an indicator not only of the advanced stage , but also of ovarian cancer progression . Based on these data , we concluded that EG-VEGF expression in tumor cells of the epithelial ovarian cancer is a good marker of unfavorable prognosis and could be an attractive therapeutic target in patients with advanced-stage tumors , refractory conventional chemotherapy .\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: Polo-like kinase 3 ( Plk3 , alternatively termed Prk ) is involved in the regulation of DNA damage checkpoint as well as in M-phase function . Plk3 physically interacts with p53 and phosphorylates this tumor suppressor protein on serine-20 , suggesting that the role of Plk3 in cell cycle progression is mediated , at least in part , through direct regulation of p53 . Here we show that Plk3 is rapidly activated by reactive oxygen species in normal diploid fibroblast cells ( WI-38 ) , correlating with a subsequent increase in p53 protein level . Plk3 physically interacts with Chk2 and the interaction is enhanced upon DNA damage . In addition , Chk2 immunoprecipitated from cell lysates of Daudi ( which expressed little Plk3 ) is capable of stimulating the kinase activity of purified recombinant Plk3 in vitro , and this stimulation is more pronounced when Plk3 is supplemented with Chk2 immunoprecipitated from Daudi after DNA damage . Furthermore , ectopic expression Chk2 activates cellular Plk3 . Together , our studies suggest Chk2 may mediate direct activation of Plk3 in response to genotoxic stresses .\n OUTPUT:\n" }, { "from": "agent", "value": "tumor promoting inflammation;genomic instability and mutation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Previous reports showed that treatment with non-steroidal anti-inflammatory agents ( NSAIA ) can alter the growth profile of a variety of tumours . In this study , the effect of NSAIA treatment on the growth of the primary tumour and the appearance of spontaneous pulmonary metastases , was investigated . A mammary adenocarcinoma of non-detected immunogenicity , C7HI , was grafted subcutaneously in the lateral flank of Balb/c mice . Oral treatment with approximately 1 mg kg-1 day-1 piroxicam delayed both tumour growth and the growth of pulmonary metastases . Survival of mice bearing the primary tumour was significantly lengthened by anti-inflammatory treatment . Similarly , in separate experiments , after surgical removal of the primary tumour by day 34 after grafting , the group of mice treated orally with piroxicam also exhibited a higher survival rate than the control group . Upon surgical removal of the primary tumour 34 days after grafting , piroxicam treatment significantly decreased both the number and size of pulmonary metastases . The results of this study lends support to the hypothesis that inhibition or modulation of inflammation may delay tumour organisation and growth . It is suggested that piroxicam treatment may be an appropriate adjunct therapy to delay the appearance of pulmonary metastases and to increase life-expectancy in a host whose primary tumour has to be surgically removed .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;tumor promoting inflammation" } ]

[ { "from": "human", "value": "The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.\n ###\n INPUT: Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer . We examined peripheral blood lymphocyte ( PBL ) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma ( mRCC ) who received combined treatment with IL-2 , interferon-?-2a and dendritic cell vaccine . We examined gene expression , cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry ( FCM ) . Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors ( HD ) . PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways , which was also reflected in lymphocyte subset distribution . Overall , PBL gene expression post-treatment ( POST ) was not significantly different than pre-treatment ( PRE ) . Nevertheless , treatment related changes in gene expression ( post-treatment minus pre-treatment ) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding ( R ) patients compared to non-responding ( NR ) patients . In addition , we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients . While exploratory in nature , this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy . This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC .\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: INTRODUCTION Cell-cell interaction is an essential component of atherosclerotic plaque development . Activated monocytes appear to play a central role in the development of atherosclerosis , not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development . Using serum free co-culture method , we determined the effect of monocytes on endothelial cell proliferation . METHODS Endothelial cell proliferation is determined by the amount of [ 3H]thymidine incorporated in to the DNA . Basic fibroblast growth factor ( b-FGF ) , vascular endothelial growth factor ( VEGF ) and interleukin-8 ( IL-8 ) levels in the conditioned medium were determined by ELISA . RESULTS Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation , whereas conditioned medium from activated monocytes promoted endothelial cell proliferation . The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF , VEGF and IL-8 . Neutralizing antibodies against b-FGF , VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes . When b-FGF , VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes , it is less mitogenic to endothelial cells . CONCLUSION Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors .\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: Immunosuppression has been related to the incidence of tumor apparition , including endocrine tumors . The intrasplenic ovarian tumor ( luteoma ) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and , from the immunological perspective , is located in a critical organ involved in immune response . To establish if immunosuppression could alter the development of this experimental tumor , the effects of cyclosporin A ( CsA ) and dexamethasone ( Dex ) were evaluated . After surgery , tumor-bearing and sham animals were kept without treatment for 4 weeks ; thereafter , they were distributed into CsA ( 25 mg/kg ) , Dex ( 0.1 mg/kg ) , or vehicle ( 75:25 castor oil:ethanol ) groups and were injected on alternate days for 50 days . Body weight was evaluated weekly . Animals were sacrificed after a jugular vein blood sample was obtained . Thymi were weighed . Tumors were measured and placed in formaline for histological studies . Serum luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) , prolactin ( PRL ) , and estradiol were measured by radioimmunoassay . Hematological parameters were determined . CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals ( P &lt ; 0.01 ) . Dex significantly impaired weight increase in both groups of animals . CsA induced a significant weight loss in sham animals , not observed in tumor-bearing animals . Dex induced thymus weight loss in both groups , whereas CsA induced thymus weight loss only in sham animals . Only Dex induced a decrease in lymphocyte number in both groups . CsA induced an increase in monocyte number only in sham animals . Treatments did not alter LH , FSH , or estradiol , whereas PRL was increased by CsA only in sham rats . Neither Dex nor CsA induced any significant variations in tumor volume , nor did they alter tumor histology . In addition , no visible metastases or alterations in other organs were observed . We conclude that , though immunological parameters were altered by the treatments , immunosuppressor drugs did not condition tumor development . In addition , tumors secrete one or more factor/s that counteract CsA effect .\n OUTPUT:\n" }, { "from": "agent", "value": "activating invasion and metastasis;avoiding immune destruction" } ]