Expression of prothrombin fragment 1+2 in cancer tissue as an indicator of local activation of blood coagulation.

Immunohistochemistry was applied to AMeX-fixed tissue sections of 12 adenocarcinomas of the stomach (seven intestinal adenocarcinomas and five diffuse carcinomas), 12 adenocarcinomas of the pancreas (nine ductal adenocarcinomas and three signet ring carcinomas), and 12 squamous cell carcinomas of the larynx obtained at surgical resection to examine the possibility of extravascular activation of blood coagulation in cancer tissues by exploring the in loco patterns of distribution of fibrinogen, a final product of blood coagulation, fibrin, and a by-product of coagulation reactions (prothrombin fragment 1+2). Gastric, pancreatic, and laryngeal cancers exhibited fibrinogen antigen in abundance throughout the tumor stroma. Fibrin was detected along the edges of nests of carcinoma cells and at the host-tumor interface. Prothrombin fragment 1+2 was present in the blood vessels in areas of neoangiogenesis at the host-tumor interface (gastric and pancreatic cancer tissues) and on the tumor cell bodies (pancreatic and laryngeal cancer tissues). The presence of prothrombin fragment 1+2 in cancer tissues appears to be a good indicator of coagulation activation and thrombin generation at the tumor burden.

Expression of tissue factor and tissue factor pathway inhibitor in situ in laryngeal carcinoma.

The blood coagulation mechanism may support tumor progression by several mechanisms including promotion of cell proliferation and angiogenesis. Immunohistochemical procedures were applied to AMeX-fixed sections of twelve cases of squamous cell carcinoma of the larynx obtained at surgical resection to determine the presence and distribution of tissue factor (TF), tissue factor pathway inhibitor (TFPI), other coagulation factors, fibrinogen, and fibrin in situ. TF antigen was present in normal squamous epithelial cells and tumor cells, predominantly in immature tumor cells in the vicinity of the host-tumor interface. Tumor cells stained also for factors VII and X. Staining for TFPI antigen was demonstrated in the connective tissue stroma adjacent to the tumor, in microvascular endothelial cells, and in normal squamous epithelial cells. Fibrinogen and factor XIIIa were distributed throughout the tumor connective tissue stroma. Fibrin (thrombin-cleaved fibrinogen) was detected at the host-tumor interface and along the margins of tumor nodules. Tumor cells in carcinoma of the larynx express a functional, TF-initiated pathway of blood coagulation. Interpretation of these findings together with the results of clinical trials of inhibitors of TF-induced coagulation activation versus effects of inhibitors of TF expression suggest novel approaches to the experimental therapy of laryngeal carcinoma.

Prothrombin activation fragment 1 + 2 and thrombin-antithrombin-III complexes in plasma of patients with essential arterial hypertension.

Prothrombin activation fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III complexes (TAT) were measured in plasma of 34 patients with newly diagnosed essential hypertension. The patients with hypertension showed an increase in both F1 + 2 and TAT concentrations. The obtained results point to the intravascular thrombin generation in very early stages of essential hypertension.

Immunohistochemical demonstration of fibrin II in gastric cancer tissue.

Immunohistochemistry was applied to AMeX-fixed sections of twelve cases of gastric carcinoma obtained at surgical resection to explore the occurrence and distribution of fibrin deposits in situ. Fibrinogen was distributed in abundance throughout perivascular zones and in the connective tissue of the tumor stroma. Fibrin II (des-fibrinopeptide B-type fibrin) was easily identified in a direct apposition to the surface membranes of viable carcinoma cells, predominantly at the host-tumor interface and in the regions immediately adjacent to the zones of angiogenesis. Further studies are required to identify the triggers of the coagulation reactions as well as fibrinolytic system components in the gastric cancer tissue.

Effects of combinations of a molsidomin with different antithrombotic drugs in laser-induced thrombosis.

Molsidomin is a vasodilating drug and a specific activator of the endothelium-derived relaxing factor (EDRF). Molsidomin has been found to prevent thrombus formation in various animal thrombosis models. To obtain more information about a possible interaction of Molsidomin with other vasoactive agents, Molsidomin, Iloprost, HN-11500, Fraxiparin and Aspisol have been investigated alone and in combinations. The antithrombotic effect of these agents was studied in a thrombosis model in rats, in which mesenteric venules, with a diameter of 20-30 microns, were injured by Argon laser produced lesions. In this animal microcirculatory thrombosis model all agents showed a significant dose dependent antithrombotic effect. A strong additive effect was observed when Molsidomin was infused together with Iloprost. An additive effect was also observed when Molsidomin was administered with Fraxiparin. There was a slight but non significant effect between Molsidomin and the thromboxane receptor antagonist. No additive effect was shown when a minimal effective dose of Molsidomin was infused together with a minimal effective dose of Aspisol.