[Modification of metastasis formation by inhibition of platelet aggregation. Experimental and clinical results].
Our clinical study to prevent relapse and metastases in several sarcomas and malignant lymphomas of the head and neck region with a long-term treatment with mopidamole was initiated in 1972 because the pyrimido-pyrimidine derivative was shown to inhibit platelet aggregation in vivo and to increase significantly the circulation time of intravenously injected, 32P-labelled Ehrlich ascites tumour cells in mouse blood. The aggregation of platelets to circulating tumour cells and their subsequent adhesion to vascular endothelium in turn appeared to be part of the early stages of the metastatic process. It seems, however, that other related mechanisms are also involved in the clinical results obtained. Mopidamole, as other related derivatives, probably inhibits platelet aggregation by inhibition of PDE-induced decomposition of cAMP and may stimulate the synthesis and/or release of prostacyclin from the vessel wall which in turn activates adenylate cyclase involved in cAMP synthesis. The latter mechanism was definitely shown only for the related pyrimido-pyrimidine derivative dipyridamole, the methyl-xanthine derivative pentoxifylline and the methyl-pyrazoline derivative nafazatrom. The increase of cAMP levels by mopidamole results in an inhibition of 3H-thymidine incorporation into human neoplastic cells and a direct inhibition of its mitotic rate. The adding of mopidamole to a culture of a human promyelocytic leukemic cell line promotes a reverse transformation of the malignant cells to normal which appears to be a permanent phenotypic change. Furthermore, mopidamole was shown to diminish significantly spontaneous lung metastases in syngenic Wilms' tumor (nephroblastoma) of the rat, the C1300-neuroblastoma of the mouse and the HM-Kim mammary carcinoma of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001537:Bencyclane / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D009012:Mopidamol / Q000494:pharmacology* / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010431:Pentoxifylline / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D010974:Platelet Aggregation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats
D010761:Phosphorus Radioisotopes; D011720:Pyrazoles; D047069:Pyrazolones; D011743:Pyrimidines; D009012:Mopidamol; D004176:Dipyridamole; D001537:Bencyclane; C018845:nafazatrom; D010431:Pentoxifylline
Beeinflussung der Metastasierung durch Hemmung der Thrombozytenaggregation. Experimentelle und klinische Ergebnisse.