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The role of thrombin in gliomas
Author(s) -
HUA Y.,
TANG L.,
KEEP R. F.,
SCHALLERT T.,
FEWEL M. E.,
MURASZKO K. M.,
HOFF J. T.,
XI G.
Publication year - 2005
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01446.x
Subject(s) - argatroban , glioma , thrombin , medicine , in vivo , pharmacology , discovery and development of direct thrombin inhibitors , cancer research , immunology , biology , platelet , microbiology and biotechnology
Summary. Background: In a previous study we found that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurologic deficits in a C6 glioma model. Objectives: To examine the role of thrombin in gliomas and whether systemic argatroban administration can reduce glioma mass and neurologic deficits and extend survival time in C6 and F98 gliomas. Methods: The presence of thrombin in human glioblastoma samples and rat C6 glioma cells ( in vitro and in vivo ) was assessed using immunohistochemistry. The effect of thrombin on C6 cell proliferation in vitro was assessed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide assay. The role of thrombin in vivo was assessed in rat C6 and F98 glioma cell models using argatroban, a thrombin inhibitor. The effects of argatroban on tumor mass, neurologic deficits and survival time were investigated. Results: Thrombin immunoreactivity was found in cultured rat C6 glioma cells and human glioblastomas. Thrombin induced C6 cell proliferation in vitro . In C6 glioma, argatroban reduced glioma mass ( P < 0.05) and neurologic deficits ( P < 0.05) at day 9. In F98 glioma, argatroban prolonged survival time ( P < 0.05). Conclusion: These results suggest that thrombin plays an important role in glioma growth. Thrombin may be a new therapeutic target for gliomas.