Overview of the biochemical and genetic processes in malignant mesothelioma / Panorama dos processos bioquímicos e genéticos presentes no mesotelioma maligno

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

O mesotelioma maligno (MM) é um câncer extremamente agressivo, com elevado período de latência e resistente aos protocolos de quimioterapia, além de ser extremamente fatal, com taxa de sobrevivência média inferior a um ano. O desenvolvimento do MM é fortemente correlacionado com a exposição ao amianto e erionita, assim como ao vírus símio 40. Apesar de vários países terem banido o uso de amianto, o MM tem se mostrado de difícil controle e sua incidência tende a aumentar nos próximos anos. No Brasil, o MM não é amplamente estudado do ponto de vista genético e bioquímico. Além disso, poucos estudos epidemiológicos foram realizados até o momento, e o perfil de incidência do MM não está bem estabelecido na população brasileira. O objetivo deste estudo foi revisar a literatura em relação ao processo de transformação maligna e seus respectivos mecanismos de tumorigênese no MM.

Knockdown of Bcl-xL Enhances Growth-Inhibiting and Apoptosis-Inducing Effects of Resveratrol and Clofarabine in Malignant Mesothelioma H-2452 Cells

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.

Malignant peritoneal mesothelioma deciduoid or anaplastic variant? Point to ponder.

A case of peritoneal mesothelioma displaying unusual morphology, occurring in a 53 year old woman is described. The role of immunohistochemistry and electron microscopy in the evaluation of this tumor is stressed. The appropriate terminology to be used and possible etiologic factor are also discussed.