Seminars in Oncology – Volume 29, Issue 1, Pages 62-69 (February 2002) by Paul Baas
Here is an excerpt: “Abstract – It has been a challenge to find effective chemotherapeutic treatments for malignant mesothelioma. Over the last several decades numerous single-drug and combination regimens have been examined, but no standard treatment with chemotherapy alone has emerged. Possible explanations for this lack of success are the heterogeneity between the different subclasses of mesothelioma and the difficulties experienced in determining responses on computed tomographic (CT) scan. This review will present the results of most chemotherapy trials. An attempt is also been made to overcome the problem of identifying the overall response rate by presenting the median survival time. Other types of response evaluation and guidelines for patient selection are warranted to properly compare chemotherapeutic treatments. Semin Oncol 29:62-69.
Another interesting study is called, “Intrapleural Production of Interleukin 6 during Mesothelioma and Its Modulation by ?-Interferon Treatment” by Gianpaola Monti, Marie-Claude Jaurand, Isabelle Monnet, Pascale Chretien, Laure Saint-Etienne, Lin Zeng, Alain Portier, Philippe Devillier, Pierre Galanaud, Jean Bignon, and Dominique Emilie – Cancer Res August 15, 1994 54; 4419. Here is an excerpt: “Abstract – In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected in pleural effusions, contrasting with low levels of IL-1? and tumor necrosis factor ?. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human ?-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and soluble CD8 concentrations. In vitro ?-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, cachexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local ?-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.”
Another interesting study is called, “Long-term survival in peritoneal mesothelioma the role of radiotherapy and combined modality treatment” by Gilbert S. Lederman MD, Abram Recht MD, Terence Herman MD, Robert Osteen MD, Joseph Corson MD, Karen H. Antman MD – Cancer Volume 59, Issue 11, pages 1882–1886, 1 June 1987. Here is an excerpt: “Abstract – Ten patients with peritoneal mesothelioma were treated at the Joint Center for Radiation Therapy between 1968 and 1985. Six of the ten patients remained free of disease at 19+ to 78+ months after diagnosis. The six patients received sequential surgical debulking, combination chemotherapy, and whole-abdomen irradiation. Four patients not treated with this multimodality approach died with disease. This approach may have an impact on the natural course of peritoneal mesothelioma, and warrants further study.”
Another interesting study is called, “Somatic genetic alterations in human malignant mesothelioma (review).” By Lee WC, Testa JR. – Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Int J Oncol. 1999 Jan;14(1):181-8. Here is an excerpt: “Abstract – A review of cytogenetic and molecular genetic findings in human malignant mesotheliomas (MMs) is presented. The complex profile of somatic genetic changes characteristic of MMs implicates a multistep process of tumorigenesis in this malignancy. In particular, the occurrence of multiple, recurrent cytogenetic deletions in MMs suggests that loss and/or inactivation of tumor suppressor genes (TSGs) are critical to the development and progression of such tumors. Karyotypic and comparative genomic hybridization analyses of MMs have demonstrated frequent deletions of specific regions within chromosome arms 1p, 3p, 6q, 9p, 15q and 22q, and subsequent loss of heterozygosity (LOH) studies have documented high frequencies of allelic loss from each of these chromosomal sites. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., p16/CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. Homozygous deletions appear to be the major mechanism affecting p16/CDKN2A, whereas inactivating mutations coupled with allelic loss occur at the NF2 locus. High density LOH analyses have pinpointed minimal regions of deletion in 1p, 3p, 6q, and 15q and are expected to facilitate efforts to identify putative TSGs at these locations which contribute to the pathogenesis of MMs.”
Tags: asbestos exposure, chemotherapy trials, combination regimens, interferon treatment, interleukin 6, malignant mesothelioma, philippe devillier, pleural effusions, tumor necrosis factor, vivo production