Wednesday, January 26th, 2005.

Respirology 10, no. 1 (2005): 2-8. [Link]

Marie-Claude Jaurand¹ and Jocelyne Fleury-Feith^1,2

1. INSERM E0337, Faculty of Medicine, University Paris XII, Creteil Cedex
2. Histology and Biology of Tumours Tenon Hospital, University Paris VI, Paris, France

Abstract

Malignant pleural mesothelioma (MPM) results from neoplastic transformation of mesothelial cells. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos fibres and MPM has been largely proved by epidemiological and experimental studies. Asbestos fibres induce DNA and chromosome damage linked to oxidative stress following phagocytosis. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The origin of human infection has been associated with SV40-contaminated polio vaccines, although to date, no epidemiological data supports this hypothesis. SV40 may act as a coactivator of asbestos in mesothelial oncogenesis. The transforming potency of SV40 results from the activity of two viral proteins, large T and small t antigens. SV40 infection stimulates production of growth factors elsewhere implicated in autocrine growth of mesothelioma cells and inactivates RASSF1, a gene silenced in MPM. Roles for ionising radiation, chemicals or genetic factors have also been suggested from the observation of sporadic MPM cases or animal studies. Genetic alterations in the tumour suppressor genes, P16/CDKN2A and neurofibromatosis 2 (NF2), are found both in human MPM and in asbestos-exposed Nf2-deficient mice. MPM is still of great international concern. Despite a ban on asbestos use in Western countries, the incidence of MPM is increasing, due to the long delay between asbestos exposure and diagnosis. Moreover, asbestos is still used in developing countries. The implication of other risk factors, especially SV40, supports a need for further research into MPM.

Glossary

risk factor

anything that increases a person's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposure to sunlight is a risk factor for skin cancer, smoking is a risk factor for lung and other cancers, and a high-fat, low-fiber diet is a risk factor for colorectal cancer. Some risk factors, such as smoking, can be controlled. Others, like a person's age, can't be changed

growth factors

a naturally occurring protein that causes cells to grow and divide. Too much growth factor production by some cancer cells helps them grow quickly, and new treatments to block these growth factors are being tested in clinical trials. Other growth factors help normal cells recover from side effects of chemotherapy.

gene

a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

DNA

(dee-ok-see-ri-bo-new-CLAY-ic) abbreviation for deoxyribonucleic acid. DNA holds genetic information on cell growth, division, and function.

virus

very small organisms that cause infections. Viruses are too small to be seen with a regular microscope. They reproduce only in living cells.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

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