Causes of Mesothelioma - Asbestos Lawyer
A median survival time of 12 months was observed in 23 patients with pleural mesothelioma treated with surgery and intracavitary photodynamic therapy.263 Attempts at inhibiting the effects of growth factors, such as PDGF, are being explored with the use of antisense oligonucleotides.105 Gene therapy has been successful against human mesothelioma cell lines by transfer of the herpes simplex virus thymidine kinase (hsvtk) with an adenovirus vector, followed by treatment with ganciclovir (GCV).244 Initial clinical trials with such intrapleural gene therapy in 26 patients at the University of Pennsylvania showed dosedependent detectable gene transfer in 17 patients, and the maximum tolerated dose was not reached.252a One patient with early disease remained without evidence of recurrence in a period of 31 months.
One partial response and 3 disease stabilizations were observed.252a The median survival was 11 months among the 18 patients who died. A similar approach is under investigation at Louisiana State University In in vitro mixing experiments, gene-modified ovarian tumor cells killed both mouse and human mesothelioma cells in a dosedependent manner. Use of the ovarian HSV-TK ovarian cells also prolonged survival of mice with DMM in a dose-dependent fashion.
These data have served as the basis for an ongoing phase I clinical gene therapy trial to determine the maximal tolerated dose of an HSVTK-transduced ovarian cancer cells infused into the pleural cavities of mesothelioma patients followed by systemic administration of GCV.235a Another trial of gene therapy in Perth, Australia, has used a vaccinia virus producing Il-2, with no response among the first six patients treated.252a
Prospectus and Prevention
Much research remains to be conducted on mesotheliomas to achieve earlier diagnosis and better treatment of these increasingly frequent neoplasms. The use of a consistent staging system would allow a better evaluation of therapeutic results, particularly for surgery. Further research into the chemotherapy of mesothelioma is warranted, since tumor responses and even complete remissions have already been obtained. Transplanting a rare tumor, such as malignant mesothelioma, into nude mice provides a useful model to evaluate many agents of as yet unknown clinical activity.56
Correlation between results in that model and clinical experience appears quite good, as shown for agents such as mitomycin, cisplatin, carboplatin, and IFN-‡, alone and in various combinations.61,242 Such correlation has also been shown by direct patient-xenograft comparisons.60,61 The effects of biologic agents (i.e., IFN, IL-2), alone or with chemotherapy, and of combined modalities, including cytoreductive surgery followed by radiotherapy and/or chemotherapy, deserve further trials.
Meanwhile, preventive measures that attempt to eliminate or at least reduce asbestos pollution are mandatory, with the use of safer and alternative materials for construction, insulation, and other consumer and industrial applications, and by dust control and personal protection.
The spraying of asbestos fireproofing was banned in New York in 1972. Dust control has been enforced in the United States by the Occupational Health and Safety Administration.238 The efficacy of these safety standards has been subject to criticism, since the dose-response relationships of the oncogenic effects of asbestos are not fully established, at least for mesothelioma, for which there appears to be no safe threshold of exposure. Tight encapsulation of friable asbestos in buildings is a necessary measure and often more feasible than costly alternatives, such as total removal.
For individuals who have already been exposed, prophylactic measures could be considered. A synthetic vitamin A analogue, retinyl methyl ether, has been shown to prevent asbestos-induced hyperplasia and squamous metaplasia of hamster tracheal cells in organ culture.184 Retinoids can reverse these cytologic changes even when administered after their occurrence.41 Alpha-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has a similar effect, suggesting that this effect is mediated by depletion of polyamines.41 The role of antioxidant enzymes, such as catalase, has been evaluated for their potential in reducing pulmonary asbestosis or asbestos-stimulated induction of ODC.169
The prophylactic potential of such compounds may be most useful in asbestos-induced lung cancer rather than in mesothelioma, but clinical trials are necessary to clarify their potential. The increasing knowledge of gene products and growth factors implicated in the genesis of mesothelioma may lead to novel therapeutic and preventive measures, and the study of serum tumor markers such as hyaluronic acid may provide useful tools for screening and early detection in populations at risk.
Mesothelioma Information
Causes of mesothelioma have been limited to prolonged asbestos exposure. The harmful mineral is responsible for a variety of diseases, including asbestos lung cancer, asbestosis, diffuse pleural thickening and fibrosis.
If you or a loved one has been diagnosed with malignant mesothelioma, contact a mesothelioma lawyer or asbestos lawyer to get information about your right to compensation.