Thymoma

Studies from University of Texas describe new findings in DNA research

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"Thirty-one patients with refractory malignancies received decitabine 2.5 to 10 mg/m(2) on days 1 to 5, and 8 to 12 or 15 to 20 mg/m(2) on days 1 to 5. Tumor was assessed for DNA methylation (by LINE assays), apoptosis, necrosis, mitoses, Ki67, DNA methyltransferase (DNMT1), CTR1, and p16. Febrile neutropenia was dose limiting. One thymoma patient responded. Decitabine decreased tumor DNA methylation (from median 51.2% predecitabine to 43.7% postdecitabine; P=0.01, with effects at all doses) and in peripheral blood mononuclear cells (from 65.3-56.0%). There was no correlation between tumor and peripheral blood mononuclear cells. starting clecitabine <= 2 versus >3 months after last prior cytotoxic or targeted therapy had lower predecitabine tumor CTR1 scores (P=0.02), higher p16 (P=0.04), and trends (P=0.07) toward higher tumor methylation and apoptosis. Decitabine decreased tumor DNMT1 for scores initially >0 (P = 0.04). Decitabine increased tumor apoptosis (P < 0.05), mitoses (if initially low, P = 0.02), and CTR1 (if initially low, P = 0.025, or if <= 3 months from last prior therapy, P = 0.04). Tumor CTR1 scores correlated inversely with methylation (r = -0.41, P = 0.005), but CTR1 promoter was not hypermethylated. Only three patients had tumor p16 promoter hypermethylation. P16 scores did not increase. Higher blood pressure correlated with lower tumor necrosis (P = 0.03) and a trend toward greater DNA demethylation (P = 0.10). Exposure to various cytotoxic and targeted agents might generate broad pleiotropic resistance by reducing CTR1 and other transporters," wrote D.J. Stewart and colleagues, University of Texas.

The researchers concluded: "Decitabine decreases DNA methylation and augments CTR1 expression through methylation-independent mechanisms.."

Stewart and colleagues published their study in Clinical Cancer Research (Decitabine Effect on Tumor Global DNA Methylation and Other Parameters in a Phase I Trial in Refractory Solid Tumors and Lymphomas. Clinical Cancer Research, 2009;15(11):3881-3888).

Additional information can be obtained by contacting D.J. Stewart, University of Texas MD Anderson Cancer Center, Dept. of Thorac Head & Neck Med Oncology, Houston, TX 77030, USA.

The publisher of the journal Clinical Cancer Research can be contacted at: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: United States, Houston, DNA Research, Apoptosis, Cancer Research, Clinical Trial Research, Copper, DNA, Dacogen, Decitabine, Drug Resistance, Drugs, Enzyme Research, Experimental Design, Hematology, Lymphoma, Methyltransferase, Necrosis, Neutropenia, Oncology, Pharmaceuticals, Solid Cancers, Solid Carcinomas, Therapy, Thymoma, Treatment, University of Texas.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.