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Effect of systemic celecoxib on human meningioma after intracranial transplantation into nude mice.
MedLine Citation:
PMID:  23143216     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Meningiomas are mostly benign, but they may have a notorious tendency to recur when total resection is not possible. Systemic chemotherapeutical treatment has been largely disappointing. The treatment of meningiomas with the cyclooxygenase-2 (COX-2) inhibitor celecoxib showed inhibitory-growth effects in vitro and in vivo after subcutaneous transplantation into mouse. So far, celecoxib has never been tested in an orthotopic model of meningioma. In this work, we tested the effects of celecoxib on the growth of human benign meningiomas after transplantation into the prefrontal cortex of nude mice after confirming the inhibitory in vitro effect on these cells. METHODS: Primary cell cultures were stereotactically implanted into mice and were treated with 0, 750, or 1,500 ppm celecoxib for 3 months. The mice were then killed and blood was analyzed for celecoxib concentration. The mice brains were histologically processed for measurement of tumor volume, COX-2 expression, proliferation index (PI), intratumoral microvessel density (iMVD), and vascular endothelial growth factor (VEGF) expression. RESULTS: Treatment with celecoxib had no effect on tumor volume, despite the fact that we found a dose-dependent inhibitory effect on cell cultures and there was a sufficiently high celecoxib concentration in blood plasma and brain tissue. Additionally, celecoxib had neither an effect on COX-2 and VEGF expression nor on the PI and iMVD. CONCLUSIONS: Our findings suggest that celecoxib may not be effective on meningioma growth in clinical settings. In general, these results may indicate that the effect of treatment on brain tumors should not only be tested in a heterotopic environment but also in the orthotopic location of these tumors.
Authors:
Sabrina Friedrich; Kerstin Schwabe; Michaela Grote; Joachim K Krauss; Makoto Nakamura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-11
Journal Detail:
Title:  Acta neurochirurgica     Volume:  -     ISSN:  0942-0940     ISO Abbreviation:  Acta Neurochir (Wien)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0151000     Medline TA:  Acta Neurochir (Wien)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurosurgery, Hannover Medical School , Carl-Neuberg-Str. 1, 30625, Hannover, Germany, friedrich.sabrina@kabelmail.de.
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