Project description:With the goal of designing a universal vaccine that can be used to target MM in mice, we analyzed expression of all the mRNA produced by different MM tumors and normal tissues. Our hypothesis was that antigens highly expressed in MM tumors can be used as target for vaccination, as long the expression of those antigens is extremely low in all normal mouse tissues.
Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy and largely unresponsive to conventional chemotherapy or radiotherapy. Novel, more effective therapeutic strategies are needed for this fatal disease. We performed microarray analysis of MM using Affymetrix Human U133 Plus 2.0 array. Aberrant expression of the genes participating in semaphorin signaling were detected in malignant mesothelioma cells. All MM cells downregulated the expression of more than one gene for SEMA3B, 3F, and 3G when compared with Met5a, a normal pleura-derived cell line. In 12 of 14 epithelioid MM cells, the expression level of SEMA3A was lower than that in Met5a. An augmented expression of VEGFA was detected in half of the MM cells. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a and the non-epithelioid MMs. Next, gene expression profiling for the polycomb and trithorax group genes revealed that expression of BAP1, the catalytic subunit of the polycomb repressive deubiquitinase complex, and many trithorax group genes was downregulated in MMs compared with the expression of the same genes in Met5a cells. Perturbation of the polycomb–trithorax balance plays a significant role in the pathogenesis of malignant mesothelioma.
Project description:Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naïve PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.
Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy. Discrimination between MM and reactive mesothelial hyperplasia (RM) is often difficult. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor, but better prognosis has been reported with the epithelioid type of MM than the non-epithelioid type. We applied a genome-wide analysis to the identification of new markers that may aid in differentiating the epithelioid type of MM from other histological types and from RM cells. Array-based comparative genomic hybridization analysis was performed on malignant mesothelioma (MM) primary cell cultures, reactive mesothelial hyperplasia (RM) primary cell cultures; early passage of in vitro primary cell cultures to minimize acquisition of additional genomic changes. If available, matched peripheral blood was applied to analysis.
Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy. Discrimination between MM and reactive mesothelial hyperplasia (RM) is often difficult. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor, but better prognosis has been reported with the epithelioid type of MM than the non-epithelioid type. We applied a genome-wide analysis to the identification of new markers that may aid in differentiating the epithelioid type of MM from other histological types and from RM cells.
Project description:Desmoplastic malignant mesothelioma is a rare tumor. Due to the rarity, genomic profile of desmoplastic malignant mesothelioma is not unveiled. To elucidate genomic profile of desmoplastic malignant mesothelioma, we used illumina infinium omini exomeexpress in an established patient-derived cell line of desmoplastic malignant mesothelioma.
Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor. We applied a copy-number analysis to the identification of new fragile genes in regions 3p21 and 16p13.3 in MM.
Project description:Malignant Mesothelioma (MM) is one of the most lethal human malignancies of the thoracic cavity. We have determined the cell of origin of these tumors by inactivating Nf2 and Trp53 in Cdkn2a-deficient mesothelial cells both in vitro and in vivo. Cloned, in vitro switched cell lines showed distinct protein marker profiles that upon grafting in recipient mice, gave rise to epithelial, sarcomatoid or biphasic MM. We show that corresponding cell types are present in the mesothelial lining, each capable to serve as a cell of origin of one of the distinct MM subtypes of which the RNA expression profile aligns with corresponding human samples. Therefore, the specific target cell is a critical factor in dictating the tumor subtype of MM.
Project description:Desmoplastic malignant mesothelioma is a rare tumor. Due to the rarity, development of new treatment for desmoplastic malignant mesothelioma is difficult. To develop new treatment strategy using existing anti-cancer drugs, kinase activity profiling has not been thoroughly studied. We used PamChip array to identify the peptide profiles of desmoplastic malignant mesothelioma between the patient-derived cell line and the tumor tissue.
Project description:In order to discover critical pathways /networks or therapeutic targets in pleural mesothelioma we profiled 55 tumors along with paired normal tissue (for 41 tumors) using Affymetrix U133 plus 2.0 chips