One interesting study is called, Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structurefunction relationship by Christopher Potten, Zbigniew Darzynkiewicz, Kohsuke Sasaki, A. Syrokou, G. Tzanakakis, T. Tsegenidis, A. Hjerpe, N. K. Karamanos - Cell Proliferation Volume 32, Issue 2-3, pages 8599, April 1999. Here is an excerpt: Abstract. Proteoglycans interact with other effective macromolecules regulating a variety of cellular events via their glycosaminoglycan (GAG) chains. The effects of all known glycosaminoglycans (GAGs) produced by normal cells and tissues on the proliferation of two human malignant mesothelioma cell lines, one with fibroblast-like morphology and the other with epithelial differentiation both able to produce hyaluronan (HA), galactosaminoglycans (GalAGs) and heparan sulphate (HS) containing proteoglycans have been studied. Cell proliferation was assessed by measuring [3H]thymidine incorporation and cell number. GalAGs, i.e. chondroitin sulphates (CSs) and dermatan sulphate (DS), strongly stimulate the proliferation of fibroblast-like cells in a dose-dependent manner (170250% at 100 g/ml), independently of their sulphation pattern. In epithelial cells, however, only DS stimulates cell proliferation. The effects of CSs on proliferation of epithelial cells are not depended on their sulphation pattern. Thus, CSs either with -[GlcA-GalNAc-(-6-O-SO3)]- or -[GlcA-GalNAc-(-4-O-SO3]- as the commonest unit, had no significant effect. l-Iduronic acid (IdoA)-rich heparin and fast-moving HS (fm-HS), a HS fraction with a heparin-like structure, had significant antiproliferative effects on mesothelioma cells of both types (3070% at 1.0 g/ml and 8590% at 100 g/ml, respectively). GlcA-rich HS, however, had no significant effects. HA inhibits only the proliferation of fibroblast-like cells by 25% at 50 and 100 g/ml. Keratan sulphate suppresses cell proliferation (1030%) in both cell lines. In the view of these findings, a structurefunction relationship of GAGs on cell proliferation of the two human malignant mesothelioma cell lines is discussed. Other factors, such as chain conformation and geometry, as well as interactions of growth factors with GAGs, possibly involved in the regulation of cell proliferation, are also discussed.

Another study is called, Inhibition of mesothelioma cell growth in vitro by doxycycline Presented at a symposium at the national meeting of the American College of Chest Physicians, Chicago, IL, November 1999. Volume 138, Issue 2, Pages 101-106 (August 2001). Here is an excerpt: Abstract - Malignant mesothelioma causes profound morbidity and nearly universal mortality that is often refractory to conventional treatment modalities of aggressive surgery, radiotherapy, or chemotherapy. Doxycycline, a commonly used antibiotic, has anti-tumor activity against several malignancies, but its anti-tumor effects on malignant mesothelioma have not been evaluated. We report here that concentrations of doxycycline achievable in serum with typical oral doses had cytostatic effects to varying extent on all eight of the mesothelioma cell lines studied but did not affect normal lung fibroblasts. Doxycycline inhibited the production of mitochondrial cytochrome c oxidase, especially in mesothelioma cells more sensitive to its cytostatic effects, and directly inhibited gelatinase A activity; both of these activities are putative mechanisms for the cytostatic activity of doxycycline in other tumor cells. Thus doxycycline may have a role as adjuvant therapy for malignant mesothelioma. (J Lab Clin Med 2001;138:101-6)

Another study is called, The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant Mesothelioma by E. Andreopoulou, P. J. Ross, M. E. R. O'Brien*, H. E. R. Ford, K. Priest, T. Eisen, A. Norton, S. Ashley and I. E. Smith - Oxford Journals Medicine Annals of OncologyVolume15, Issue9Pp. 1406-1412. Here is an excerpt: Abstract - Background: With the rising incidence of malignant mesothelioma (MM), it is important to optimise treatment to control symptoms, maintain quality of life and, if possible, prolong life. We have analysed prospectively collected data to evaluate a frequently used palliative chemotherapy regimen. Patients and methods: Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP (mitomycin C 8mg/m2 every 6 weeks, vinblastine 6mg/m2 every 3 weeks and cisplatin 50mg/m2 every 3 weeks) chemotherapy. Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy.

Results: One hundred and fifty patients were treated with MVP for mesothelioma. Forty-three per cent had a performance status (PS) 2 or worse. The response rate was 15.3%, with 68.6% having stable disease. Sixty-nine per cent reported an improvement in symptoms; in particular there were good responses for pain (71%), cough (62%) and dyspnoea (50%). The most common grade 3/4 toxicity was neutropenia (22%). Median overall survival was 7 months, with 1-year survival 31% and 2-year survival 11%. Median survival for patients with PS 0/1 was 10 months, and was 6 months for patients with PS 2/3. Poor prognostic factors in univariate analysis included poor PS, weight loss, mixed or sarcomatoid histology, low haemoglobin and high white blood cell count. Excluding pathological subtype, the prognostic significance of poor PS and weight loss were retained in multivariate analysis. Conclusions: Palliation of symptoms in MM is achievable with current cisplatin-based treatments.

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