Project description:We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morpho-logical evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler and Cancer Transcriptome Atlas to compare epithelioid and sarcomatoid components transcriptional profile and reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions.
Project description:RATIONALE: Using BG00001 to insert the gene for interferon-beta into a person’s pleural cavity may improve the body’s ability to fight cancer.
PURPOSE: Phase I trial to study the effectiveness of intrapleural BG00001 in treating patients who have malignant pleural mesothelioma or malignant pleural effusions.
Project description:To identify regions that display DNA copy number alterations in malignant pleural mesothelioma (MPM), we carried out array comparative genomic hybridization (CGH) analysis with 14 MPM cell lines. Regions of genomic aberrations observed in >20% of individuals were 9p21.3, 13q12.11, 16p13, and 22q12.2 of losses. The most frequent alteration was 9p21.3, which include the p16INK4/p14ARF. The loss of 22q12.2 regions include the NF2 was observed in 3 out of 14 cell lines. In 3 cell lines, loss of 13q12.11 region which contains Large Tumor Suppressor, homolog 2 (LATS2) was detected. Human malignant pleural mesothelioma cell lines were profiled on Agilent 244K aCGH arrays according to manufacturer’s instructions. Pooled normal human genomic DNA was used as the reference.
Project description:Diagnosis of malignant pleural mesothelioma (MPM) is difficult, the most common differential diagnosis being benign pleural diseases and metastatic adenocarcinomas. In order to identify novel markers able to improve diagnostic accuracy, we performed a genome-wide gene expression analysis on tumor cells lines established from pleural effusions (13 MPM and 4 lung adenocarcinoma). Our microarray analysis led to the identification of genes encoding novel cellular and soluble markers whose expression was validated by RT-qPCR. Immunohistochemical staining of tumor biopsies with anti-type-III collagen antibodies were positive in mesothelioma cells but not in adenocarcinoma cells. Using ELISA, we showed that the C-C motif chemokine 2 (CCL2) concentration was significantly higher in pleural effusions from patients with mesothelioma (n = 61) than in subjects with adenocarcinoma (n = 25) or with benign pleural effusions (n = 15): median (interquartile range) = 2.99 ng/mL (1.76-6.01) versus 0.99 ng/mL (0.51-1.83) and 1.47 ng/mL (0.80-1.56), respectively, P < 0.0001. Conversely, the galectin-3 concentration was lower in mesothelioma: 11.50 ng/mL (6.73-23.53) versus 24.74 ng/mL (20.42-70.35) and 17.64 ng/mL (14.81-24.68), respectively, P < 0.0001. The AUC for CCL2 were 0.8030 and 0.7716 for differentiating mesothelioma from adenocarcinoma or benign effusions, respectively. Similarly, the AUC obtained for galectin-3 were 0.7980 and 0.6923, respectively. In conclusion, type-III collagen, CCL2 and galectin-3 are promising new diagnostic markers for mesothelioma.
Project description:For establishing a live-cell biobank of Malignant Pleural Mesothelioma (MPM) samples, cultures of two MPM patients were compared to the original tumor tissue using Affymetrix OncoScan Microarrays for genome-wide CNV and LOH detection.
Project description:SNP array data from 45 cell lines of Malignant Pleural Mesothelioma were used to explore recurrent copy number alterations. This study was part of Cartes d'Identité des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer.
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.
Project description:MiRNA screening was performed to identify differentially expressed miRNAs in a series of 14 formalin fixed paraffin-embedded (FFPE) malignant pleural mesothelioma (MPM) samples representative of the epithelioid, biphasic and sarcomatoid histotypes in comparison with normal mesothelium. MiRNA expression in FFPE MPM and normal mesothelial specimens was analyzed through the miRCURY™ LNA™ Array microRNA Profiling Service (Exiqon). RNA samples were subjected to quality control and, subsequently, 450 ng were labelled with the Hy3™ fluorescent label with the miRCURY™ LNA™ Array power labelling kit. A common reference, against which each individual sample could be tested to assay biological variations among the specimens, was constituted by pooling equal amounts of RNA from each tumor and control and labelled with Hy5™. The Hy3™-labelled samples and the Hy5™-labelled reference RNA sample were mixed pair-wise and hybridized to the miRCURY™ LNA™ array version 11.0 (208200-A Exiqon) according to the manufacturer instructions.
Project description:Diagnosis of malignant pleural mesothelioma (MPM) is a challenging task because of its overlap with other neoplasms or even reactive conditions. Recently, DNA methylation analysis proved to be an effective tool for tumor diagnosis. We thus set out to test this approach for MPM diagnosis. A discovery (n=33) and an independent validation cohort (n=46) of MPM samples were subjected to array-based DNA methylation analyses and their DNA methylation patterns were compared to a representative set of both malignant and benign diagnostic mimics. By both unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analysis, MPM samples of the discovery cohort exhibited a distinct DNA methylation profile, different from that of other neoplastic and reactive mimics.