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<node id="C0007131" name="Carcinoma, Non-Small-Cell Lung" semtype="neop" visible="true" color="#EEC8DE" x="110" y = "-29" umlsks_url="http://mor.nlm.nih.gov/perl/semnav.pl?DB_CODE=UMLS_2006AA&amp;HREL=ALL&amp;REM_TRANS=1&amp;CUI=C0007131" omim_url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=omim&amp;cmd=Retrieve&amp;list_uids=211980,188890"/>
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<node id="C0079427" name="Tumor Suppressor Genes" semtype="gngm" visible="true" color="#D2A2A2" x="178" y = "-40" umlsks_url="http://mor.nlm.nih.gov/perl/semnav.pl?DB_CODE=UMLS_2006AA&amp;HREL=ALL&amp;REM_TRANS=1&amp;CUI=C0079427"/>
<edge source="C0020196" target="C0812413" label="TREATS" color="#0000FF" ><sentence id = "23790737.ab.n" text = "METHODS: Pleural fluid HA concentrations were measured in 334 patients, including 50, 48, 85, 18, 86, 6, and 41 patients with MPM, benign asbestos pleurisy (BAP), lung cancer (LC), other malignant conditions (OMCs), infectious pleuritis (IP), collagen disease (CD), and other conditions, respectively."/></edge>
<edge source="C0812413" target="C0027651" label="COEXISTS_WITH" color="#2F4F4F" ><sentence id = "23975423.ab.n" text = "Evaluation of TERT mRNA expression by quantitative RT-PCR showed overexpression in MPM in culture compared with normal mesothelial cells, and in MPM tumor samples compared with normal pleura."/><sentence id = "23975423.ab.n" text = "We identified a 'hot spot' of mutations in the TERT gene core promoter in both MPM in culture and in MPM tumor samples with an overall frequency of 15%."/></edge>
<edge source="C0007634" target="C0008838" label="LOCATION_OF" color="#008000" ><sentence id = "23977343.ab.n" text = "Interferon-beta produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells."/><sentence id = "23624653.ab.n" text = "Furthermore, we overexpressed Numb in NCI-H2452, an epithelioid human MPM cell line, and investigated the effect of Numb overexpression on the proliferation, apoptosis and sensitivity to cisplatin in cells."/></edge>
<edge source="C0008838" target="C0027651" label="AFFECTS" color="#32CD32" ><sentence id = "23977343.ab.n" text = "These data demonstrated firstly to our knowledge that IFN-beta produced synergistic anti-tumor effects with cisplatin or pemetrexed on mesothelioma through up-regulated p53 expression."/><sentence id = "23977343.ab.n" text = "Interferon-beta produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells."/><sentence id = "23977343.ab.n" text = "A combinatory use of IFN-beta and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions."/></edge>
<edge source="C0210657" target="C0027651" label="AFFECTS" color="#32CD32" ><sentence id = "23977343.ab.n" text = "These data demonstrated firstly to our knowledge that IFN-beta produced synergistic anti-tumor effects with cisplatin or pemetrexed on mesothelioma through up-regulated p53 expression."/><sentence id = "23977343.ab.n" text = "Interferon-beta produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells."/><sentence id = "23977343.ab.n" text = "A combinatory use of IFN-beta and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions."/></edge>
<edge source="C1176309" target="C0812413" label="TREATS" color="#0000FF" ><sentence id = "23791541.ab.n" text = "BACKGROUND: This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)(1) as primary end-point."/><sentence id = "23762382.ab.n" text = "Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM), two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05-10)."/></edge>
<edge source="C0020196" target="C0812413" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "24161718.ab.n" text = "Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma."/><sentence id = "23790737.ab.n" text = "CONCLUSIONS: A diagnosis of MPM should be strongly considered in patients with pleural fluid HA concentrations exceeding 100,000ng/ml."/></edge>
<edge source="C0210657" target="C0007131" label="TREATS" color="#0000FF" ><sentence id = "23522487.ab.n" text = "Two cases of NE have been reported after the appliance of pemetrexed for treatment of non-small cell lung cancers."/><sentence id = "23851735.ab.n" text = "Pemetrexed is a novel, multitargeted antifolate approved for the treatment of malignant pleural mesothelioma and non-small cell lung cancer."/></edge>
<edge source="C0008838" target="C0812413" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "23624653.ab.n" text = "Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma."/><sentence id = "23791541.ab.n" text = "Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052)."/><sentence id = "24023280.ab.n" text = "Cisplatin in combination with pemetrexed or raltitrexed increased survival in MPM, whereas vinorelbine and gemcitabine have led to good response rates."/></edge>
<edge source="C0796392" target="C0812413" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "23860535.ab.n" text = "Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma."/><sentence id = "23860535.ab.n" text = "However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM."/></edge>
<edge source="C0007131" target="C0812413" label="COEXISTS_WITH" color="#2F4F4F" ><sentence id = "24028146.ab.n" text = "Five-year local relapse-free survival (RFS) rates were 55.2% in NSCLC, 24.4% in MPM, 64.8% in thymoma, and 27.2% in tumours metastatic to the lung and pleura."/><sentence id = "24028146.ab.n" text = "Five-year overall survival rates were 37.4% in NSCLC, 15.9% in MPM, 91.7% in thymoma, and 25.8% in metastatic lung tumour."/></edge>
<edge source="C0210657" target="C0025500" label="TREATS" color="#0000FF" ><sentence id = "24225007.ab.n" text = "Pemetrexed and cisplatin-based chemotherapy remains the reference treatment, which has proved in mesothelioma some efficacy on overall survival in randomized trials, with a 13-15 months median-overall survival."/><sentence id = "23977343.ab.n" text = "A combinatory use of IFN-beta and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions."/><sentence id = "23687910.ab.n" text = "Case studies examined reporting for infliximab for Crohn's Disease, pemetrexed for mesothelioma, and ADHD (Attention Deficit Hyperactivity Disorder) medicines atomoxetine and methylphenidate."/><sentence id = "23857408.ab.n" text = "&amp;amp;quot;One marker does not fit all&amp;amp;quot;: additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma."/></edge>
<edge source="C0042172" target="C0027651" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "23453740.ab.n" text = "The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126)."/><sentence id = "23453740.ab.n" text = "Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423)."/></edge>
<edge source="C0380162" target="C0032227" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "24167356.ab.n" text = "In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin."/><sentence id = "24167356.ab.n" text = "Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum."/><sentence id = "23873013.ab.n" text = "Clinical value of mesothelin in pleural effusions versus histology by medical thoracoscopy: brief report."/></edge>
<edge source="C0008838" target="C0812413" label="TREATS" color="#0000FF" ><sentence id = "24158772.ab.n" text = "Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined."/><sentence id = "23624653.ab.n" text = "These results suggest that Numb may be involved in epithelioid MPM development, and its upregulation may confer sensitivity to cisplatin, suggesting potential therapeutic options for MPM."/></edge>
<edge source="C0079427" target="C0812413" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "23963927.ab.n" text = "BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM."/><sentence id = "24148817.ab.n" text = "CONCLUSIONS: The miR-15/16 family is downregulated and has tumour suppressor function in MPM."/></edge>
<edge source="C0210657" target="C0812413" label="TREATS" color="#0000FF" ><sentence id = "24023280.ab.n" text = "The value of pemetrexed for the treatment of malignant pleural mesothelioma: a comprehensive review."/><sentence id = "23486267.ab.n" text = "CONCLUSIONS: Although previous retrospective data suggest that TS and FPGS expression might be potential markers of Pem efficacy in MPM, our data indicate these markers lack sufficient predictive value in individual patients and should not be used to guide therapeutic decisions in the absence of prospective studies."/><sentence id = "23486267.ab.n" text = "PURPOSE: Thymidylate synthase (TS) is a potential predictor of outcome after pemetrexed (Pem) in patients with malignant pleural mesothelioma (MPM), and assays measuring TS levels are commercially marketed."/><sentence id = "23851735.ab.n" text = "Pemetrexed is a novel, multitargeted antifolate approved for the treatment of malignant pleural mesothelioma and non-small cell lung cancer."/><sentence id = "23486267.ab.n" text = "Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma."/><sentence id = "23522487.ab.n" text = "To our knowledge, NE has never been reported due to treatment with pemetrexed for malignant pleural mesothelioma (MPM)."/><sentence id = "23810210.ab.n" text = "INTRODUCTION: Platinum-based chemotherapy is besides the standard antifolate therapy with pemetrexed, the cornerstone for treatment of patients with malignant pleural mesothelioma (MPM), and its efficacy depends on several DNA repair enzymes."/><sentence id = "24023280.ab.n" text = "This review aims to provide insight into treatment of malignant pleural mesothelioma (MPM) considering effects on survival, quality of life (QoL) and costs, in order to determine the value of pemetrexed in MPM treatment."/></edge>
<edge source="C0007634" target="C0380162" label="LOCATION_OF" color="#008000" ><sentence id = "24260587.ab.n" text = "The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells."/></edge>
<edge source="8650" target="C0812413" label="ASSOCIATED_WITH" color="#D19275" ><sentence id = "23624653.ab.n" text = "The present study was designed to analyze the role of Numb in epithelioid MPM."/><sentence id = "23624653.ab.n" text = "Loss of Numb expression was associated with poor prognosis in epithelioid MPM."/><sentence id = "23624653.ab.n" text = "These results suggest that Numb may be involved in epithelioid MPM development, and its upregulation may confer sensitivity to cisplatin, suggesting potential therapeutic options for MPM."/><sentence id = "23624653.ab.n" text = "The expression of Numb was significantly lower in MPM compared to the control group and Numb had an inverse correlation with the ki-67 labeling index."/></edge>

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