Ameliorating Treatment for Mesothelioma Disease

Ameliorating Treatment for Mesothelioma Disease

Another interesting study is called, “Epirubicin in the treatment of malignant mesothelioma: a phase II cooperative study. The North-Eastern Italian Oncology Group (GOCCNE) – Mesothelioma Committee.” By Magri MD, Veronesi A, Foladore S, De Giovanni D, Serra C, Crismancich F, Tuveri G, Nicotra M, Tommasi M, Morassut S, et al. – Tumori. 1991 Feb 28;77(1):49-51.  Division of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy.  Here is an excerpt: “Abstract – From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.”

Another interesting study is called, “Interleukin-12 induces an effective antitumor response in malignant mesothelioma.” By Caminschi I, Venetsanakos E, Leong CC, Garlepp MJ, Scott B, Robinson BW.  University Department of Medicine, University of Western Australia, and Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre, Nedlands, Australia.  Am J Respir Cell Mol Biol. 1998 Nov;19(5):738-46.  Here is an excerpt: “Abstract – Malignant mesothelioma (MM) is a fatal solid tumor of the mesothelium for which there is currently no ameliorating treatment. Using our murine model of this malignancy, which closely resembles the human disease, we have shown that immunotherapy may be of value in the treatment of MM. Because recombinant interleukin-12 (rIL-12) has strong immunomodulatory effects in vivo, we studied the effects of rIL-12 on murine antitumor immune responses, using a nonimmunogenic murine MM tumor cell line (AB1) in vivo. Systemic administration of rIL-12 at the time of tumor inoculation prevented AB1 tumor growth in up to 70% of treated mice, 50% of which were still resistant to AB1 upon rechallenge, indicating that long-term immunologic antitumor effects had been established. This rIL-12-induced effect was dependent on the involvement of both CD4(+) and CD8(+) but not natural killer (NK) cells. Importantly, treatment of established tumors with intralesional injections of rIL-12 resulted in temporary tumor regression or growth inhibition. This effect was dependent on the continuous presence of rIL-12 and correlated with increased numbers of CD4(+) and CD8(+) cells infiltrating the remaining tumor mass. Effective inhibition of tumor growth also occurred when IL-12 was released within MM tumors by coadministration of MM cells that had been stably transfected with the gene for IL-12. These data indicate that IL-12 has potential in the immunotherapy of MM, through gene transfer or local cytokine administration, provided that significant intratumor levels of IL-12 can be achieved for prolonged periods.”

Another interesting study is called, “Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology” by Patricia A. Fetsch M.T. (A.S.C.P.), Andrea Abati M.D., Yasmine M. Hijazi M.D. Cancer Cytopathology Volume 84, Issue 2, pages 101–108, 25 April 1998.  Here is an excerpt: “Abstract – The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM.  METHODS – In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM.

RESULTS – Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%).  CONCLUSIONS – CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens.Cancer (Cancer Cytopathol) 1998;84:101-8. © 1998 American Cancer Society.

Pleural effusions may be the first manifestation of both mesotheliomas and metastatic adenocarcinomas. In these circumstances, cytology can play a pivotal role in the initial diagnosis. The differential diagnosis of malignant mesothelioma (MM) from adenocarcinoma (ACA) in cytologic specimens is aided greatly by immunocytochemistry. Because no specific antigen has been shown to be diagnostic for distinguishing MM from ACA, the use of a panel of antibodies provides the highest degree of accuracy. This panel most often includes antibodies to carcinoembryonic antigen (CEA), LeuM1, B72.3, BerEP4, and epithelial membrane antigen (EMA), with markers for keratin and vimentin also included in some laboratories.1-8 Positivity for CEA, BerEP4, B72.3, or LeuM1 favors the diagnosis of ACA over MM.5, 6, 8, 9 This study examined three additional markers (CA 19-9, HBME-1, and thrombomodulin [TM]), which are believed by some authors to be of clinical utility in surgical pathology specimens, and their diagnostic utility in 87 cytologic specimens with a confirmed diagnosis of either MM or ACA.10-16 The diagnostic applications of these antibodies in cytopathology specimens are as yet untested in the medical literature.

Anti-CA 19-9 is a monoclonal antibody directed against alpha (2,3)-sialylated Lewis-a (Le-a), a blood group antigen.10 Immunoreactivity for CA 19-9 has been observed in many gastrointestinal (GI) primary ACAs, but has been reported to be absent in MM.11

HBME-1 is an antibody raised against cultured mesothelioma cells and recognizes an antigen on the microvillus surface.12, 13 It has been reported to be present in both MM and ACA, but with a different staining pattern; MMs are said to have a “thick (bushy) membrane” pattern, whereas ACAs are found to have a “thin membrane” or a cytoplasmic staining pattern.12

TM is a transmembrane glycoprotein receptor, located on the vascular endothelial cell surface. The distribution of TM in normal tissue includes endothelial and mesothelial cells. It has been reported to stain a majority of MMs and only a rare number of ACAs.14-16″

Monty Wrobleski is the author of this article.  For more information please click on the following links

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