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Homo sapiens

ABSTRACT: Upregulation of thymidylate synthase induces pemetrexed resistance in malignant pleural mesothelioma

PROVIDER: PRJDB11876 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR308055_1.fastq.gz	Fastqsanger.gz
	DRR308055_2.fastq.gz	Fastqsanger.gz
	DRR308056_1.fastq.gz	Fastqsanger.gz
	DRR308056_2.fastq.gz	Fastqsanger.gz
	DRR308057_1.fastq.gz	Fastqsanger.gz

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Transcription profiling by array of mesothelioma pre- and post-resistance biopsies in order to determine a resistance signature to pemetrexed/carboplatin treatment

Project description:Pemetrexed, a multi-folate inhibitor combined with a platinum compound is the first-line treatment of malignant mesothelioma, but median survival is still one year. Innate and acquired resistance to pemetrexed is common, but its biological basis is obscure. Here we report for the first time a genome-wide profile of acquired resistance in the tumour from an exceptional case with advanced pleural mesothelioma and almost six years survival after 39 cycles of second-line pemetrexed/carboplatin treatment.

2012-10-01 | E-MTAB-1109 | biostudies-arrayexpress

Pemetrexed and Erlotinib for Metastatic Colorectal Cancer

Project description:Pemetrexed is a multitargeted antifolate, which primarily inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase in the folate-dependent metabolic process. Nowadays, pemetrexed is used to treat malignant pleural mesothelioma and non-squamous non-small cell lung cancer. Preclinical and clinical studies showed that pemetrexed had cytotoxic activity in many kinds of cancers including colorectal cancer. Erlotinib is a tyrosine-kinase inhibitor of EGFR, which was approved for the treatment of non-small cell lung cancer. Erlotinib also showed activity to colorectal cancer cells. Recently, Zhang et al. demonstrated synergistic cytotoxicity of pemetrexed and gefitinib in preclinical study. In this multicenter, non randomized, open label phase II study, investigators aimed to evaluate the efficacy and safety of Pemetrexed and Erlotinib combination.

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Project description:Malignant pleural mesothelioma

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Discovery proteomics studies for the identification of a protein panel associated with the response to pemetrexed in platinum drug resistant cancer

Project description:Pemetrexed is a drug largely used in lung cancer, mesothelioma and proposed in some cases of ovarian cancers, a particularly severe cancer type. In this latest tumor type, therapy relies on debulking surgery and platinum-based chemotherapy. Despite the initial high response rates to platinum drugs, most patients relapse and die from the disease. Considering the high levels of thymidylate synthase, dhydrofolate reductase and other folate related proteins in platinum drug resistant patients, pemetrexed was proposed as a second line drugs due to its known mechanism of action that engage the mentioned proteins. However a successful outcome could only be expected on the basis of patients’ stratifications. In the present study, a discovery proteomics approach was applied to tissue samples collected beforepemetrexed treatment from platinum resistant patients who relapsed after the first-line carboplatin-based chemotherapy but responded differently to the pemetrexed treatment.

2018-06-06 | PXD007056 | Pride

Pemetrexed Alone as Salvage Treatment in Metastatic Colorectal Cancer Patients Who Were Failed After Standard Chemotherapy: A Phase II Single Arm Prospective Study

Project description:Pemetrexed is an anticancer agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed behaves as a multitargeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is used as a standard therapeutic agent for lung cancer, pleural mesothelioma, peritoneal mesothelioma.In addition to these effective anti-cancer effect, Pemetrexed is not severe side effects of the medicine. Pemetrexed has been research in colon cancer. Zhang, etc., demonstrated the anti-cancer effect of Pemetrexed in human colon cancer Cells. Although sometimes made also two or more clinical studies, Pemetrexed was reported 15-17% of the treatment response rate in these two studies.

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Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma

Project description:Regional delivery of oncolytic viruses has been shown to promote immune responses. Malignant pleural effusions comprise an immunosuppressive microenvironment, and the ability of oncolytic viruses to generate immune responses following regional delivery in patients with malignant pleural effusions is unknown. We conducted a phase I clinical trial that studied the intrapleural administration of oncolytic vaccinia virus to establish the safety and feasibility in patients with malignant pleural effusion due to malignant pleural mesothelioma or metastatic disease. In patients with malignant pleural mesothelioma, by correlative analysis of pre- and post-treatment tumor biopsies, we provide insight into tumor-specific viral uptake and associated immune responses.

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Project description:Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma

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Project description:Since loss of the NF2 tumor suppressor gene results in p21-activated kinase (Pak) activation, PAK inhibitors hold promise for the treatment of NF2-deficient tumors. To test this possibility, we asked if loss of Pak2, a highly expressed group I PAK member, affects the development of malignant mesothelioma in Nf2;Cdkn2a-deficient (NC) mice and the growth properties of NC mesothelioma cells in culture. In vivo, deletion of Pak2 resulted in a markedly decreased incidence and delayed onset of both pleural and peritoneal malignant mesotheliomas in NC mice. In vitro, Pak2 deletion decreased malignant mesothelioma cell viability, migration, clonogenicity, and spheroid formation. RNA-seq analysis demonstrated downregulated expression of Hedgehog and Wnt pathway genes in NC;Pak2-/- mesothelioma cells versus NC;Pak2+/+ mesothelioma cells. Targeting of the Hedgehog signaling component Gli1 or its target gene Myc inhibited cell viability and spheroid formation in NC;P+/+ mesothelioma cells. Kinome profiling uncovered kinase changes indicative of EMT in NC;Pak2-/- mesothelioma cells, suggesting that Pak2-deficient malignant mesotheliomas can adapt by reprogramming their kinome in the absence of Pak activity. The identification of such compensatory pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.

2023-03-10 | PXD030571 | Pride

Human pleural effusion LC-MSMS

Project description:We screened pleural effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass spectrometry-(MS-) based proteomics using isobaric tags for relative and absolute quantification (iTRAQ) and used narrow range immobilized pH gradient/high resolution isoelectric focusing (IPG/HiRIEF; pH 4 to 4.25) prior to analysis by nano liquid chromatography-coupled MS/MS. Pleural effusions from patients with malignant mesothelioma (n=6), lung adenocarcinoma (n=6), or benign mesotheliosis (n=7) were analyzed, and more than 1,300 proteins were identified.

2014-01-14 | PXD000531 | Pride

Homo sapiens

Project description:Chromosomal aberration of malignant pleural mesothelioma cell lines

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