losartan-potassium and Bile-Duct-Neoplasms

Results of treatment of 39 patients, to whom pancreatoduodenal resection was performed for periampullar zone tumour, were analyzed. Anemia, revealed before the operation, had constituted the factor, which trustworthily increased the postoperative complications occurrence risk. Therapeutic course, using recombinant erythropoietins, was conducted for correction of anemia in 7 patients. This had promoted the hemoglobin level raising, the risk of postoperative complications occurrence lowering, but did not influence the intraoperative blood loss severity and perioperative hemotransfusion volume.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Bile Duct Neoplasms; Digestive System Neoplasms; Drug Administration Schedule; Duodenal Neoplasms; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Recombinant Proteins; Risk Factors; Treatment Outcome

It has been recently shown that the biological effects of erythropoietin (EPO) are not limited to the hematopoietic compartment but, as pleiotropic glycoprotein, this hormone can exert pro-angiogenic and tissue-protective functions also in a wide range of non-hematopoietic organs. The role of EPO and the effective functionality of its receptor in solid tumors are still a controversial point of debate. In the present work we analyzed the gene expression of EPO and its cognate receptor (EpoR) in a rat model of thioacetamide-induced damage and tumor. An analysis of the EPO/EpoR axis was also performed on human cholangiocarcinoma (CC) cell lines. A progressive increase of EPO and EpoR mRNA can already be observed during the fibrotic-cirrhotic development with a peak of expression rising at tumor formation (24.7 ± 9.9-fold increase and 15.5 ± 1.1-fold increase, respectively, for the two genes). Co-localization studies by immunofluorescence revealed hepatocytes in the regenerative cirrhotic nodules (Hep Par-1(+)) and in the dysplastic bile duct cells (CK19(+)) as the major EPO producers in this specific condition. The same cell populations, together with endothelial cells, exhibited an increased expression of EpoR, although all the non-parenchymal cell populations in the liver exhibited modest basal mRNA levels. Challenging human CC cells, Mz-Cha-2, with a combination of EPO and SCF resulted in a synergistic effect on the gene expression of EPO, CyclinD1 and PCNA. This study suggests that the autocrine and paracrine release of endogenous EPO in the microenvironment may contribute to the development and maintenance of the CC possibly in cooperation with other signaling pathways.

Topics: Animals; Bile Duct Neoplasms; Cholangiocarcinoma; Disease Models, Animal; Erythropoietin; Humans; Liver; Male; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; RNA, Messenger; Thioacetamide; Tumor Cells, Cultured