subject: Three Peritoneal and Three Pleural Mesotheliomas [print this page] Another interesting study is called, "Codeletion of p15 and p16 in primary malignant mesothelioma." By Xio S, Li D, Vijg J, Sugarbaker DJ, Corson JM, Fletcher JA. - Oncogene. 1995 Aug 3;11(3):511-5. Department of Pathology, Children's Hospital, Boston, Massachusetts. Here is an excerpt: "Abstract - The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in malignant mesothelioma and other cancers. p16 has been implicated recently as a potential target of 9p21 deletions in mesothelioma, but the role of this gene is uncertain because deletions have been detected more often in established cell lines than in primary tumor specimens. We determined p15 and p16 copy number by fluorescence in situ hybridization with a P1 contig in 50 primary mesotheliomas. Codeletion of p15 and p16 was found in 72% of mesotheliomas, including all cases with spindle-cell components (n = 21) and total deletion of p15 and p16 was found in several mesotheliomas that lacked cytogenetic deletion of the chromosome 9 short arm. Point mutations were not found, however, in exon 2 of retained p15 and p16 alleles from seven mesotheliomas. These findings demonstrate that p15, p16 and/or a closely neighboring gene, are the targets of frequent chromosome 9p deletion in primary malignant mesothelioma."
Another interesting study is called, "Coexpression of Simple Epithelial Keratins and Vimentin by Human Mesothelium and Mesothelioma in Vivo and in Culture" by
Paul J. LaRocca, and James G. Rheinwald Here is an excerpt: "Abstract - We have determined the intermediate filament proteins present in normal and malignant mesothelium in vivo. Pure sheets of normal lung mesothelium were obtained by transfer to agarcoated slides or by gentle scraping and cytocentrifugation. Cytoplasmic filament networks in the mesothelium were labeled via indirect immunofluorescence both by anti-Mr 40,000 keratin and anti-vimentin antisera. Two-dimensional gel electrophoresis of the Triton:high-salt-insoluble proteins of normal lung mesothelium disclosed the presence of vimentin and all but the largest (Mr 55,000) of the four simple epithelial keratins synthesized by mesothelial cells in culture. Samples of three peritoneal and three pleural mesotheliomas were found to contain either all four simple epithelial keratins or all but the Mr 55,000 keratin. Notably, none of the keratins characteristic of stratified and many glandular epithelia and their malignant forms was present in these mesotheliomas. Two mesothelioma samples from which the tumor cells could be obtained free of other cell types were found to contain vimentin as well as simple epithelial keratins and to synthesize these same proteins during short-term culture. None of the mesotheliomas placed in culture grew progressively in medium optimal for the growth of normal mesothelial cells. These data demonstrate that malignant mesothelial cells preserve the normal pattern of intermediate filament protein synthesis, including coexpression of simple epithelial keratins and vimentin, and suggest the use of this characteristic as an aid in the identification of cells of mesothelial origin."
Another interesting study is called, "Tumor necrosis factor-related apoptosis-inducing ligand and chemotherapy cooperate to induce apoptosis in mesothelioma cell lines." By Liu W, Bodle E, Chen JY, Gao M, Rosen GD, Broaddus VC. - Lung Biology Center, San Francisco General Hospital, University of California-San Francisco, San Francisco, CA 94143 Am J Respir Cell Mol Biol. 2001 Jul;25(1):111-8. Here is an excerpt: "Abstract - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in certain tumor cells. In addition, TRAIL and chemotherapy can act cooperatively, possibly as a result of chemotherapy-induced increases in expression of a TRAIL receptor, DR5. We used cell lines derived from a highly chemoresistant tumor, malignant mesothelioma, to learn whether TRAIL was effective alone or together with chemotherapy and whether cooperativity depended on increases in DR5 expression. TRAIL (codons 95-285) was expressed in a bacterial expression vector and purified by nickel affinity chromatography. TRAIL alone (25 to 500 ng/ml) had little effect on mesothelioma cells. TRAIL plus chemotherapy (doxorubicin, cis-platinum, etoposide, or gemcitabine) acted cooperatively to induce apoptosis in mesothelioma cells (M28, REN, VAMT, and MS-1). For example, in M28 cells treated for 18 h, apoptosis from TRAIL (100 ng/ml) plus doxorubicin (0.6 microg/ml; 71 +/- 11%) greatly exceeded that from TRAIL alone (21 +/- 8%) or from doxorubicin alone (6 +/- 2%) (means +/- standard deviation; P < 0.03). Mesothelioma cells treated with chemotherapy showed no change in DR5 protein by Western analysis or by immunocytochemistry. TRAIL plus chemotherapy was associated with an increase in mitochondrial cytochrome c release and mitochondrial depolarization. We conclude that TRAIL and chemotherapy act cooperatively to kill mesothelioma cell lines, not by increases in DR5 receptor but in association with mitochondrial amplification of apoptotic signals.
We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.
Three Peritoneal and Three Pleural Mesotheliomas
By: Montwrobleski77
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