losartan-potassium and Carcinoma-256--Walker

In patients with advanced cancer, anemia is a common complication indicative of a poor prognosis. Attempts to alleviate this have met with mixed success and interventions including erythropoietin often fail to elicit an appropriate response. We have used rats implanted with the Walker 256 carcinosarcoma as a model of non-responsive anemia. This study demonstrates that the provision of recombinant erythropoietin in the presence of clenbuterol, a beta2 agonist, attenuates both the cancer induced anemia and the growth of the tumor in this model. We hypothesize that this treatment relieves the tumor induced inhibition of hematopoiesis, which allows for not only an increase in hematocrit but an increased immunosurveillance resulting in tumor suppression.

Topics: Adrenergic beta-Agonists; Anemia; Animals; Carcinoma 256, Walker; Cell Division; Clenbuterol; Erythropoietin; Hematocrit; Pentoxifylline; Rats; Rats, Sprague-Dawley; Recombinant Proteins

Topics: Anemia; Animals; Carcinoma 256, Walker; Chronic Disease; Erythrocyte Aging; Erythropoietin; Inflammation; Iron; Liver; Male; Mononuclear Phagocyte System; Rats; Spleen; Turpentine

The purpose of this study was to further clarify the pathophysiology of anemia in malignancy. To accomplish this end a total of 210 normal or splenectomized rats with or without the solid form of Walker 256 carcinosarcoma was studied. In vivo studies demonstrated that in stage I cancer (tumor weight less than 10% of body weight) a slightly shortened red cell survival resulted in a mild degree of anemia. With increasing tumor size, 51Cr red cells mass decreased further, in spite of extramedullary erythropoiesis and a slightly increased incorporation transferrin-bound iron into red cells. Splenectomized rats with stage II cancer developed a more profound degree of anemia associated with a significantly decreased incorporation of 59Fe into red cells. Marrow cell culture studies demonstrated that heme synthesis in response to erythropoietin in stage I cancer was not significantly different from normal, but in rats with stage II cancer (tumor weight greater than 10% of body weight) heme synthesis in response to erythropoietin was markedly decreased. In vitro studies demonstrated that plasma erythropoietin levels were appropriately increased in most rats with transplanted malignancy. These studies indicate that bone marrow heme synthesis in response to erythropoietin is impaired in rats with the anemia of advanced malignancy.

Topics: Anemia; Animals; Bone Marrow; Bone Marrow Cells; Carcinoma 256, Walker; Cells, Cultured; Erythropoietin; Heme; Male; Rats; Splenectomy

Assay of the enzyme ferrochelatase in marrow, liver, spleen, and red cells has been employed to assess the extent of erythropoietic stimulation in animals bearing the Walker 256 carcinosarcoma and in rats treated by administration of phenylhydrazine, cobalt chloride, human urinary erythropoietin, or chronic blood loss. In all instances, the spleen sustains the most marked increase of ferrochelatase activity, per gram of tissue. Spleen erythropoietic activity stimulation was confirmed by quantitative measurements in respiring slices of (59)Fe and (14)C incorporation into hemoglobin and ferritin. Increased spleen ferrochelatase activity in cobalt chloride-treated rats is prevented by actinomycin D, indicating that stimulated synthesis of the enzyme is associated with the metabolism of RNA.

Topics: Animals; Bone Marrow; Carbon Isotopes; Carcinoma 256, Walker; Chlorides; Cobalt; Dactinomycin; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Ferritins; Glycine; Hemoglobins; Iron Isotopes; Liver; Lyases; Phenylhydrazines; Rats; RNA; Spleen; Stimulation, Chemical