title: Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most malignant histological type of glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma. Even after the application of surgery, radio and chemotherapy, the effect and survival for patients with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined.
  
  
  METHODS
  In this study, we have evaluated the therapeutic potential of the combination of two different drugs: intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and rodent orthotopic xenograft survival analysis.
  
  
  RESULTS
  The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold in xenotransplanted animals without rise in toxicity.
  
  
  CONCLUSIONS
  In summary, we propose a very powerful new combination therapy for glioma.
authors.forename: Marina
authors.initials: M
authors.lastname: Mendiburu-Eliçabe
authors.affiliation: Department of Neurosurgery, University of California San Francisco, 1855 Folsom Street, MCB 226, San Francisco, CA 94103, USA. btg@cbm.csic.es.
authors.forename: Jon
authors.initials: J
authors.lastname: Gil-Ranedo
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016903:Drug Monitoring; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007263:Infusions, Parenteral; D000077146:Irinotecan; D008081:Liposomes; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D002166:Camptothecin