Document Detail

Thrombin enhances glioma growth.
MedLine Citation:
PMID:  19388346     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Our previous studies have demonstrated that argatroban, a specific thrombin inhibitor, reduces brain edema and neurological deficits in rat glioma models. The present study investigated whether or not thrombin enhances glioma growth in vivo and in vitro. METHODS: There were two parts in this study. In the first part, rat C6 glioma cells were treated with or without thrombin. These cells were then injected into the right caudate of adult male Fischer 344 rats. Rats underwent behavioral testing prior to sacrifice 12 days later for tumor mass measurement. In the second part, C6 cells were incubated in serum-free medium for 24 hours and then treated with thrombin with or without argatroban, a thrombin inhibitor. DNA synthesis was examined using a 5-bromo-2'-deoxyuridine (BrdU) ELISA kit. Cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. FINDINGS: Treatment of C6 cells with thrombin prior to intracerebral implantation resulted in a larger tumor mass and worse neurological deficits at dayl2. In vitro, thrombin increased DNA synthesis in C6 glioma cells, and this effect was blocked by argatroban. MTT assay showed that thrombin significantly increased glioma cell proliferation in vitro. CONCLUSIONS: In summary, thrombin enhances C6 glioma growth in vivo and cell proliferation in vitro suggesting that thrombin may be a target of glioma therapy.
Ya Hua; Lingling Tang; Richard F Keep; Julian T Hoff; Jason Heth; Guohua Xi; Karin M Muraszko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Acta neurochirurgica. Supplement     Volume:  102     ISSN:  0065-1419     ISO Abbreviation:  Acta Neurochir. Suppl.     Publication Date:  2008  
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-06-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100962752     Medline TA:  Acta Neurochir Suppl     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  363-6     Citation Subset:  IM    
Department of Neurosurgery, University of Michigan, Room 5018, BSRB, Ann Arbor, MI 48109-2200, USA.
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MeSH Terms
Anticoagulants / pharmacology
Behavior, Animal
Brain Neoplasms / etiology*
Bromodeoxyuridine / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Enzyme-Linked Immunosorbent Assay / methods
Functional Laterality
Glioma / etiology*
Hemostatics / adverse effects*
Neoplasm Transplantation / methods
Pipecolic Acids / pharmacology
Rats, Inbred F344
Tetrazolium Salts / diagnostic use
Thiazoles / diagnostic use
Thrombin / adverse effects*
Time Factors
Grant Support
Reg. No./Substance:
0/Anticoagulants; 0/Hemostatics; 0/Pipecolic Acids; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 59-14-3/Bromodeoxyuridine; 74863-84-6/argatroban; EC

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