title: Suppression of tumor-associated hyperfibrinogenemia and free fatty acidemia with p-phenoxybenzalbutyrate (clofibrate).
abstract: Previous work in our laboratory has indicated that free fatty acids stimulate synthesis of fibrinogen by the liver. The effect of the hypolipidemic agent clofibrate on hyperfibrinogenemia associated with tumors was evaluated by monitoring clofibrate-induced changes in plasma fibrinogen concentration and biosynthesis of the protein in Buffalo rats implanted with a localized, nonmetastasizing neoplasm derived from a tumorigenic hepatoma cell line (HTC4). In tumor-bearing animals not treated with clofibrate, cancer growth was associated with elevated rates of fibrinogen synthesis and a doubling of plasma fibrinogen concentrations. Plasma free fatty acid concentrations and serum free fatty acid/albumin molar ratios were also increased in tumor-bearing rats. Treatment with clofibrate in doses which normalized the plasma free fatty acid/albumin ratio also prevented the tumor-associated rise in plasma fibrinogen. Rates of fibrinogen synthesis were lowered significantly in clofibrate-treated animals. Tumor growth was not affected by clofibrate. These results indicate that hyperfibrinogenemia associated with nonmetastasizing tumors may reflect changes in lipid metabolism which are neutralized by clofibrate. Thus, treatment with clofibrate or other hypolipidemic agents should be evaluated in cancer patients with elevated plasma fibrinogen levels and their attendant complications.
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005340:Fibrinogen / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000097:blood* / Q000188:drug therapy; D008297:Male; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D012709:Serum Albumin; D005340:Fibrinogen; D002994:Clofibrate