Ann Thorac Surg 1995;60:598
© 1995 The Society of Thoracic Surgeons
Invited Commentary
Invited Commentary
Scott M. Freeman, MD
Department of Pathology, SL 79, Tulane University Medical Center, 1432 Tulane Ave, New Orleans, LA 70112-2699
See also page 593.
Although many patients with cancer can achieve long-term survival with standard therapy, some patients who have either tumor relapse or primary tumors do not respond to treatment. Malignant mesothelioma is an example of a carcinoma for which there is no effective treatment. Kucharczuk and colleagues have described an important animal model that can be used to test new forms of therapy for pleural mesothelioma. This animal model is appropriate for analyzing new treatment modalities because of the following features: (1) reproducibility, (2) a syngeneic tumor, and (3) a close resemblance to human disease. Kucharczuk and colleagues have developed an important new model for investigating malignant mesothelioma, because only intraperitoneal models for mesothelioma have been studied to date.
This model will allow testing of novel therapies such as those developed in the area of gene therapy. To determine whether gene therapy may be useful in this disease, Kucharczuk and colleagues inoculated an adenoviral vector containing the Escherichia coli lacZ gene into the pleural cavity of tumor-bearing rats. They report the important finding that the normal mesothelial cell lining of the pleural cavity prevents the adenoviral vector from entering the underlying tissues (ie, lung and muscle). Thus gene transfer technology into the pleural cavity of a tumor-bearing animal using an adenoviral vector will confine gene delivery to tumor cells and mesothelial cells.
This model is ideally suited for testing a number of gene therapy strategies for pleural-based mesothelioma. Our results and those of others demonstrate that transfer of the herpes simplex virus thymidine kinase gene (HSV-TK) into tumors confined to an organ cavity (eg, ovarian cancer, mesothelioma, glioblastoma) can be killed by exposure to ganciclovir. In the case of HSV-TK gene transfer, only a fraction of the tumor mass needs to express the gene to obtain an antitumor response because the ganciclovir-treated HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor cells in what has been termed the ``bystander effect.'' The delivery of immunopotentiating genes (eg, GM-CSF, IL-2) to a tumor could also be tested in this model. A number of investigators have demonstrated the importance of this gene therapy approach, and Kucharczuk and colleagues have provided the animal model to test it for pleural mesothelioma.
In summary, the development of a good animal model for pleural mesothelioma is long overdue. The model described in this report will allow the testing of current novel technologies and the development of new therapies unique to mesothelioma.
Related Article
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Pleural-Based Mesothelioma in Immune Competent Rats: A Model to Study Adenoviral Gene Transfer
- John C. Kucharczuk, Ashraf A. Elshami, Hong Bing Zhang, W. Roy Smythe, Harry C. Hwang, James S. Tomlinson, Kunjlata M. Amin, Leslie A. Litzky, Steven M. Albelda, and Larry R. Kaiser
Ann. Thorac. Surg. 1995 60: 593-597.
[Abstract]
[Full Text]
