subject: Autocrine Stimulation Of Growth And Mesothelioma Cells [print this page] Another interesting study is called, Human malignant mesothelioma cell lines express PDGF beta-receptors whereas cultured normal mesothelial cells express predominantly PDGF alpha-receptors. Oncogene. 1991 Nov;6(11):2005-11. Here is an excerpt: Abstract - In human malignant mesothelioma cell lines elevated expression of the platelet-derived growth factor (PDGF) beta-chain (c-sis) gene was previously reported, while normal mesothelial cells barely express this gene. Expression of the PDGF A-chain gene was only slightly elevated in these cell lines compared with normal mesothelial cells. For a putative autocrine function of the produced PDGF, in these cells expression of PDGF receptors is a prerequisite. In this paper we report on the expression of PDGF alpha- and beta-receptors in normal and malignant mesothelial cells. Cultured normal mesothelial cells expressed PDGF alpha-receptor mRNA and protein and had weak to undetectable levels of the PDGF beta-receptor mRNA and protein. In contrast, malignant mesothelioma cell lines were found to express PDGF beta-receptor mRNA and protein, while PDGF alpha-receptor expression was not detectable by Northern blotting and immunoprecipitation. Binding experiments with [125I]-PDGF-AA and [125I] PDGF-BB to normal and malignant mesothelial cell lines confirmed these observations. These results suggest that autocrine stimulation of growth may occur both in cultured normal mesothelial cells (PDGF-AA acting via the alpha-receptor) and in malignant mesothelioma cell lines (PDGF-BB acting via the beta-receptor).
Another interesting study is called, Fatal pneumonitis associated with intensity-modulated radiation therapy for Mesothelioma - Volume 65, Issue 3, Pages 640-645 (1 July 2006) International Journal of Radiation Oncology - Aaron M. Allen, M.D., Maria Czerminska, M.S., Pasi A. Jnne, M.D., Ph.D. David J. Sugarbaker, M.D. Raphael Bueno, M.D., Jay R. Harris, M.D., Laurence Court, Ph.D., Elizabeth H. Baldini, M.D., M.P.H. Here is an excerpt: Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Womens Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy.
Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m2). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test.
Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 557 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.322.3%), 15.2 Gy (range, 13.317 Gy), and 98.6% (range, 81100%), respectively, as compared with 10.9% (range, 5.524.7%) (p = 0.08), 12.9 Gy (range, 8.716.9 Gy) (p = 0.07), and 90% (range, 6698.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis.
Conclusions: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.
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.
by: Mont Wrobleski
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