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Biologische, genethische en moleculaire kenmerken van het mesothelioomgezwel

12-07-2006 00:00

In twee artikelen wordt de huidige kennis over het mesothelioomgezwel beschreven met betrekking tot de rol van genen en chromosomen, de invloed van het sv-40 virus en de mate waarin bepaalde merkers ter identificatie kunnen worden. Bronnen: Hicks J., (2006). Biologic, cytogenetic, and molecular factors in mesothelial proliferations. Ultrastructural Pathology Jan-Feb.30(1):19-30. Ramos-Nino, M.E., et al. (2006). Cellular and molecular parameters of mesothelioma. Journal of Cellular Biochemistry, Jul 1.98(4):723-34.

Hicks J., (2006). Biologic, cytogenetic, and molecular factors in mesothelial proliferations. Ultrastructural Pathology Jan-Feb.30(1):19-30.

Abstract


Although mesothelioma cases may have peaked in the 1990s in developed countries, it is expected that there will be over 70,000 cases diagnosed in the United States over the next 5 decades. With the industrial expansion in Southeast Asia and China and the continued use of asbestos, an epidemic of mesothelioma cases is anticipated over the next several decades. A considerable amount has been learned about the cytogenetic and molecular genetics of mesotheliomas. However, in-depth studies are needed to further define specific factors that may provide for early diagnosis, surgical treatment, oncologic management, and gene therapy. Serologic markers for surveillance of those with asbestos exposure and at risk for mesothelioma are needed. Targeted therapy using molecular markers and gene therapy may provide a means to reverse mesothelial proliferations or stabilize tumor growth and allow for surgical resection. The future holds great promise in identifying mesothelioma gene expression profiles (genomics, gene microarrays) and proteins (proteomics) that may produce the key to dealing with this dismal and devastating neoplasm.



Ramos-Nino ME, Testa JR, Altomare DA, Pass HI, Carbone M, Bocchetta M, Mossman BT (2006). Cellular and molecular parameters of mesothelioma. Journal of Cellular Biochemistry, Jul 1.98(4):723-34.

Abstract


Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors.