subject: Demonstrating the Feasibility of Intrapleural Cisplatin-Based Chemotherapy [print this page] Demonstrating the Feasibility of Intrapleural Cisplatin-Based Chemotherapy
Another study is called, "SV40 expression in human neoplastic and non-neoplastic tissues: perspectives on diagnosis, prognosis and therapy of human malignant mesothelioma." By Procopio A, Marinacci R, Marinetti MR, Strizzi L, Paludi D, Iezzi T, Tassi G, Casalini A, Modesti A. Dev Biol Stand. 1998;94:361-7. Department of Oncology and Neuroscience, Gabriele D'Annunzio University, Chieti, Italy. Here is an excerpt: "Abstract - We have recently demonstrated the association of SV40 and human pleural malignant mesothelioma. Here, we have investigated whether SV40 viral sequences may be associated with other human tumours or other non-neoplastic pathology and whether SV40 DNA or protein expression may be of diagnostic, prognostic or therapeutic relevance. DNA was extracted from paraffin embedded tissues. SV40, JC and BK viral sequences were detected by the polymerase chain reaction and molecular hybridization with specific probes. The screening with three different sets of SV40-related primers demonstrated that 7/18 (38.8%) mesothelioma specimens were SV40 positive as well as 5/18 (27.7%) tubercular pleural lesions. None of the 18 lung cancers, nor the 20 pleural non-specific inflammatory specimens tested were positive. Twenty-five blood samples and 18 urinary sediments from MM patients were also negative. We have also found that SV40 Tag proteins are present in mesothelioma cells and tumours. Tag proteins may interfere with tumour suppressor gene products, such as p53. Preliminary results suggest that wild type p53 transgene expression, obtained after infection with recombinant adenovirus (AdCMV.p53), inhibited in vitro and in vivo proliferation, inducing apoptosis of mesothelioma cells. Infections with control viruses were ineffective. Thus, SV40 DNA and Tag expression in mesothelioma tumour cells, though probably not relevant for diagnostic or prognostic purposes, may be crucial for innovative gene therapy strategies."
Another study is called, "Wnt2 as a new therapeutic target in malignant pleural Mesothelioma" by Julien Mazieres, Liang You, Biao He, Zhidong Xu, Sarah Twogood, Amie Y. Lee, Noemi Reguart, Sonny Batra, Iwao Mikami, David M. Jablons, - International Journal of Cancer - Volume 117, Issue 2, pages 326332, 1 November 2005. Here is an excerpt: "Malignant mesothelioma of the pleura (MPM) is a highly aggressive neoplasm with a poor prognosis and limited treatment options. A better understanding of its pathogenesis is essential to developing alternative therapeutic strategies. We previously demonstrated that the Wnt signaling pathway is activated in MPM through the overexpression of disheveled proteins. To extend our knowledge of Wnt signaling activation in MPM, we performed Wnt-specific microarrays in normal pleura and MPM. We found that the most common event in MPM was the upregulation of Wnt2. We inhibited Wnt2 by siRNA and a monoclonal anti-Wnt2 antibody and analyzed their effects on apoptosis and downstream signaling effectors. We then assessed the antiproliferative effects of the Wnt2 antibody and Alimta, one of the current standard treatments of MPM. We confirmed Wnt2 overexpression at the mRNA and protein level in MPM cell lines and tissues. We then demonstrated that inhibition of Wnt2 by siRNA or a monoclonal antibody induces programmed cell death in MPM cells. We next analyzed the effects of the anti-Wnt2 antibody and of Alimta on MPM cell proliferation. We found that although Wnt2 antibody by itself had less antiproliferative potency than Alimta, the two in combination had substantially more activity than Alimta alone. We thus propose that inhibition of Wnt2 is of therapeutic interest in the development of more effective treatments for MPM. 2005 Wiley-Liss, Inc.
Malignant pleural mesothelioma (MPM) is a highly aggressive and challenging cancer arising primarily from the pleural lining of the lung. Approximately 3,000 patients are diagnosed with MPM in the United States annually and the incidence of this tumor is predicted to increase dramatically over near term, peaking around 2020.1 Since MPM usually presents at an advanced stage, a curative resection is rarely possible. Radiotherapy has failed to show clinical benefit as a single treatment modality, and the administration of chemotherapy is mostly restricted to the advanced stage with limited efficiency.2 Alternative strategies based on pleural injections of recombinant cytokines have similarly proven unsatisfactory.3 Since current interventions offer only limited benefit and overall survival is low, there is an urgent need to develop new therapeutic agents based on a greater understanding of MPM's underlying molecular mechanisms.
Another interesting study is called, "Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in pleural Mesothelioma" - Oxford Journals Medicine Annals of Oncology Volume 6, Issue 6 Pp. 613-616 - A. S. T. Planting1, M. E. L. van der Burg, S. H. Goey, J. H. M. ScheUens, M. J. van den Bent, M. de Boer-Dennert, G. Stoter1 and J. Verweij. Here is an excerpt: "Abstract - Background In a previous phase II study with a dose-intensive weekly cisplatin schedule for six cycles, we observed a partial response in 5 of 14 patients with pleural mesothelioma. However, response duration was short (median 6 months). Since oral etoposide may theoretically be synergis-tic to cisplatin, we performed a phase II study with the combination of both drugs. Patients and methods Twenty-five chemo-naive patients with pleural mesothelioma were treated with cisplatin 70 mg/m2 days 1815 and days 293643 in combination with oral etoposide 50 mg days 115 and days 2943. Patients with stable disease, or better, continued treatment with oral etoposide 50 mg/m2/day days 121 every 28 days. Results All patients were evaluable for response and toxicity. Complete response was observed in one patient and partial responses in 5 patients (RR% 24%; 95% Cl: 10%45%) for a median duration of 30 weeks. Twelve patients had stable disease. The response status never improved during maintenance treatment with oral etoposide. Most patients tolerated the regimen very well. Toxicity was mainly haema-tologic with leukocytopenia causing treatment delays in 8 patients. Ototoxicity grade 1 or 2 was observed in 8 patients, neurotoxicity grade 1 in 9 patients and nephrotoxicity grade 1 in 1 patient. Conclusion Frequently administered cisplatin in combination with oral etoposide has a moderate but definite activity in pleural mesothelioma
We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.
