Disease relevance of Mesothelioma

• Simian virus-40 large-T antigen binds p53 in human mesotheliomas [1].
• The mesotheliomas, irrespective of cell type or grade, showed lower gamma-glutamyl transpeptidase (GGT) concentration than 36 of the 38 pulmonary adenocarcinomas [2].
• The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas [2].
• METHODS: Retinoblastoma (Rb) and p16INK4 protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen [3].
• Influence of age at the start of treatment was minimal or not apparent for mesotheliomas, uterine adenocarcinomas, or pituitary adenomas; however, pituitary cystoid degeneration and hyperplasia and cervical adenosis occurred in higher frequency and/or with shorter duration of DES exposure the earlier that treatment was started [4].

Psychiatry related information on Mesothelioma

• The observed co-expression of HGF/SF and c-Met in malignant pleural mesotheliomas suggests a possible self-stimulation (autocrine loop) of tumour cells [5].

High impact information on Mesothelioma

• Absence of BCL10 mutations in human malignant mesothelioma [6].
• The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma [7].
• We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas [1].
• We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins [8].
• Chrysotile, tremolite, and mesothelioma [9].

Chemical compound and disease context of Mesothelioma

• Membranoproliferative glomerulonephritis following gemcitabine and vinorelbine chemotherapy for peritoneal mesothelioma [10].
• Early diagnosis and monitoring of transplanted human malignant mesothelioma by serum hyaluronic acid [11].
• Mesothelioma in child with prenatal exposure to isoniazid [12].
• Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the surface of mesothelial cells, mesotheliomas, and ovarian cancers [13].
• Treatment of human pleural mesothelioma (MS-1) cells with phorbol myristate acetate (PMA) and cycloheximide results in 17- and 10-fold, respectively, increases in steady-state expression of urokinase-type plasminogen activator receptor (uPAR) mRNA [14].
• ERK5 silencing increased doxorubicin-induced cell death and doxorubicin retention in malignant mesothelioma cells [15].

Biological context of Mesothelioma

• Secreted frizzled-related protein 4 is silenced by hypermethylation and induces apoptosis in beta-catenin-deficient human mesothelioma cells [16].
• Dose-dependent inhibition (IC50 < 2.5 micromol/L) of cell growth in mesothelioma cell lines, but not in H2052, H2452, and nonmalignant MeT-5A (IC50 > 10 micromol/L), was observed with the small-molecule c-Met inhibitor SU11274 [17].
• Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27Kip1 has been mapped to the short arm of chromosome 12 at the 12p12-12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas [18].
• Inhibition of ERK phosphorylation or transfection with dominant-negative fra-1 constructs reversed the transformed phenotype of mesothelioma cells and anchorage-independent growth in soft agar [19].
• Cytogenetic analysis was conducted on cells of 15 rat mesotheliomas induced in rats by the i.p. inoculation of crocidolite or chrysotile asbestos [20].

Anatomical context of Mesothelioma

• RESULTS: We demonstrated abnormal p16INK4 expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines [3].
• Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers [13].
• Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma [17].
• Results show that the EGFR mediates both asbestos-induced proto-oncogene expression and epithelial cell proliferation, providing a rationale for modification of its phosphorylation in preventive and therapeutic approaches to lung cancers and mesothelioma [21].
• The ligand, [3H] (+)-4-[alpha-R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide ([3H](+)BW373U86), bound with high-affinity [Kd (dissociation constant) = 0.066 +/- 0.012 nM] to membranes prepared from six different SCLC cell lines but not to those from seven NSCLC cell lines, including one mesothelioma [22].

Gene context of Mesothelioma

• Homozygous deletion of the INK4a/ARF locus is common in human mesothelioma and may result in the loss of p14(ARF) and the inactivation of p53 [23].
• All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts [24].
• Intrapleural injections of recombinant human IFN-gamma have shown some efficacy in reducing tumor growth in early stages of diffuse malignant mesothelioma (DMM) [25].
• This finding indicates that these nonmalignant isolates may retain properties of reactive mesothelial cells and suggests that targets in addition to COX2 may be involved in the antiproliferative response of mesothelioma cell lines [26].
• Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma [27].
• Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations [28].
• Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially [29].

Analytical, diagnostic and therapeutic context of Mesothelioma

• These data show that intracavitary IFN-beta gene therapy using an adenoviral vector provides strong CD8(+) T-cell-mediated antitumor effects in murine models of mesothelioma and suggest that this may be a promising strategy for the treatment of localized tumors such as mesothelioma or ovarian cancer in humans [30].
• To further analyze the efficacy of hsp-65 immunotherapy in clinically relevant models of localized cancer, immunocompetent mice bearing i.p. murine mesothelioma were treated with four i.p. doses of a cationic lipid complexed with plasmid DNA (pDNA) containing hsp65, LacZ, or a null plasmid [31].
• On Western blot analysis, antibodies raised against the anionic GST purified from mesothelioma detect protein of Mr approximately 25,000 in extracts of both normal kidney and tumors containing anionic GST activity but not in extracts of human liver that did not contain detectable anionic activity [32].
• We report the results of this investigation: (a) DNA and protein analyses revealed SV40 sequences and SV40 large T antigen expression in 10 of 12 mesotheliomas tested (83%); and (b) electron microscopy demonstrated variable amounts of asbestos fibers in 5 (71%) of 7 corresponding lung tissues available for analysis [33].
• For investigation of early mesothelial reactions associated with the development of mesotheliomas, C57BL/6 mice were given intraperitoneal injections of 200 micrograms of short or long crocidolite asbestos fibers, toxic silica particles, or nontoxic titanium dioxide particles [34].

References