Mesothelioma Cells And Resistance To Propylthiouracil

Another interesting study is called, The Human Type 2 Iodothyronine Deiodinase Is a Selenoprotein Highly Expressed in a Mesothelioma Cell Line by Cyntia Curcio, Munira M. A. Baqui, Domenico Salvatore, Bertrand H. Rihn, Steve Mohr, John W. Harney, P. Reed Larsen and Antonio C. Bianco - August 10, 2001 The Journal of Biological Chemistry, 276, 30183-30187 Here is an excerpt: Abstract - Types 1 and 3 iodothyronine deiodinases are known to be selenocysteine-containing enzymes. Although a putative human type 2 iodothyronine deiodinase (D2) gene (hDio2) encoding a similar selenoprotein has been identified, basal D2 activity is not selenium (Se)-dependent nor has D2 been labeled with75Se. A human mesothelioma cell line (MSTO-211H) has recently been shown to have 40-fold higher levels ofhDio2 mRNA than mesothelial cells. Mesothelioma cell lysates activate thyroxine (T4) to 3,5,3-triiodothyronine with typical characteristics of D2 such as low K m (T4), 1.3 nm, resistance to propylthiouracil, and a short half-life (30 min). D2 activity is 30-fold higher in Se-supplemented than in Se-depleted medium. An antiserum prepared against a peptide deduced from theDio2 mRNA sequence precipitates a 75Se protein of the predicted 31-kDa size from 75Se-labeled mesothelioma cells. Bromoadenosine 35 cyclic monophosphate increases D2 activity and 75Se-p31 2.5-fold whereas substrate (T4) reduces both D2 activity and 75Se-p31 23-fold. MG132 or lactacystin (10 m), inhibitors of the proteasome pathway by which D2 is degraded, increase both D2 activity and 75Se-p31 34-fold and prevent the loss of D2 activity during cycloheximide or substrate (T4) exposure. Immunocytochemical studies with affinity-purified anti-hD2 antibody show a Se-dependent increase in immunofluorescence. Thus, human D2 is encoded by hDio2 and is a member of the selenodeiodinase family accounting for its highly catalytic efficiency in T4 activation.

Another interesting study is called, Concentration of hyaluronic acid in pleural fluid as a diagnostic aid for malignant mesothelioma. By T Pettersson, B Frseth, H Riska, and M Klockars - CHEST November 1988 vol. 94 no. 5 1037-1039. Here is an excerpt: Abstract - Hyaluronic acid (HA) was determined with a radiometric assay in the serum and pleural fluid of 85 patients with pleural effusions, including 15 with malignant mesothelioma, 32 with other cancer, 31 with nonmalignant inflammatory diseases, and seven with congestive heart failure. With a cutoff level at 100 mg/L, the pleural fluid concentration of HA was raised in 73 percent of patients (11 of 15) with malignant mesothelioma and in 23 percent with nonmalignant inflammatory diseases, but in none with other cancer and in none with congestive heart failure. The median concentration of pleural fluid HA was significantly higher in patients with mesothelioma than in those with other cancer (p less than 0.005). Determination of carcinoembryonic antigen (CEA) in pleural fluid further helped to differentiate between mesothelioma and other types of cancer; concentrations of CEA above 10 micrograms/L were found in four of 15 (27 percent) patients with mesothelioma, but in 38 percent of the patients with other cancer. We concluded that in the differential diagnosis of pleural effusions associated with malignant tumors a high concentration of HA in pleural fluid combined with a low concentration of CEA suggests malignant mesothelioma as opposed to other types of cancer.

We all owe a debt of gratitude to these fine researchers for their work. If you found any of these excerpts helpful, please read the studies in their entirety.

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