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Inhibition of P-glycoprotein-mediated transport by S-adenosylmethionine and cynarin in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells.

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Multidrug resistance (MDR) to anticancer chemotherapy is often mediated by the overexpression of the plasma membrane drug transporter P-glycoprotein (Pgp) encoded by multidrug resistance gene (MDR1). Various chemosensitizing agents are able to inhibit Pgp activity but their clinical application is

DNA methyltransferases in normal and avian sarcoma virus-transformed rat cells. Quantitation of 5-methyldeoxycytidine in DNA and enzyme kinetics study.

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In rat kidney cells transformed by avian sarcoma virus (B77 strain) DNA is hypomethylated (2.61 +/- 0.07%) when compared to DNA extracted from normal cells (3.33 +/- 0.11%) as revealed by high-performance liquid chromatography analysis. Kinetics studies showed that no significant differences could

Amelioration of thrombocytopenia with concomitant ornithine in sarcoma-bearing rats receiving high dose difluoromethylornithine.

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The dose limiting toxicity of difluoromethylornithine (DFMO), when administered by continuous infusion, is thrombocytopenia. DFMO-induced antitumor activity and thrombocytopenia were time- and dose-dependent up to 1700 mg/kg/d when administered continuously for 12 days. Concomitant ornithine

Demonstration of an altered S-adenosylmethionine synthetase in human malignant tumors xenografted into athymic nude mice.

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S-Adenosylmethionine synthetase isoenzymes (EC 2.5.1.6) were studied in human malignant tumors xenografted into athymic nude mice and were studied in normal human and rat tissues. The tumors included 7 melanomas; 4 colon carcinomas; 3 each of mammary, cervical, and ovary carcinomas; 2 each of lung

Accumulation of spliced avian retrovirus mRNA is inhibited in S-adenosylmethionine-depleted chicken embryo fibroblasts.

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The synthesis and processing of B77 avian sarcoma virus RNA in infected chicken embryo fibroblasts was followed in the presence and absence of cycloleucine, a competitive inhibitor of the synthesis of S-adenosylmethionine and thus an inhibitor of RNA methylations. An increase in the steady-state

Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA.

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Cycloleucine, a competitive inhibitor of ATP: L-methionine S-adenosyltransferase in vitro, has been used to reduce intracellular concentrations of S-adenosylmethionine and by this means to inhibit virion RNA methylation in chicken embryo cells that are infected with B77 avian sarcoma virus. Under

Role of methionine adenosyltransferase α2 and β phosphorylation and stabilization in human hepatic stellate cell trans-differentiation.

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Myofibroblastic trans-differentiation of hepatic stellate cells (HSCs) is an essential event in the development of liver fibrogenesis. These changes involve modulation of key regulators of the genome and the proteome. Methionine adenosyltransferases (MAT) catalyze the biosynthesis of the methyl

Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs.

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BACKGROUND Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases. OBJECTIVE Dogs

Reduction of N-nitrosodiethylamine carcinogenesis in rats by lipotrope or amino acid supplementation of a marginally deficient diet.

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In studies in this and other laboratories, induction of hepatocardinoma by several different chemical carcinogens was enhanced in rats fed diets deficient in lipotropes (choline, methionine, folic acid), amino acids, and niacin, and high in fat. In some cases, specific supplementation with

Deregulation of methionine metabolism as determinant of progression and prognosis of hepatocellular carcinoma.

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The under-regulation of liver-specific MAT1A gene codifying for S-adenosylmethionine (SAM) synthesizing isozymes MATI/III, and the up-regulation of widely expressed MAT2A, MATII isozyme occurs in hepatocellular carcinoma (HCC). MATα1:MATα2 switch strongly contributes to the fall in SAM liver content

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