title: Effect of systemic celecoxib on human meningioma after intracranial transplantation into nude mice.
abstract: 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.affiliation: Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. friedrich.sabrina@kabelmail.de
authors.forename: Sabrina
authors.initials: S
authors.lastname: Friedrich
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.forename: Michaela
authors.initials: M
authors.lastname: Grote
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D018929:Cell Culture Techniques; D002470:Cell Survival; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008579:Meningioma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib