title: Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model.
abstract: Recently, local chemotherapy proved its efficacy against malignant gliomas. Under the hypothesis that local delivery of chemotherapeutic agents into the brain parenchyma induce opening of the blood-brain barrier (BBB), we evaluated the opening of BBB after convection-enhanced delivery of nimustine hydrochloride into the brain parenchyma. Local convection-enhanced delivery of nimustine hydrochloride transiently opened the BBB from about 7-12 days after delivery in normal rodent brain. Systemic chemotherapy during this period of BBB disruption had synergistic effects resulting in prolonged survival of tumor-bearing rats. The present strategy may provide a new approach for glioma chemotherapy.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Taigen
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kumabe
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D018481:Convection; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems / Q000379:methods*; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D015376:Nimustine / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015376:Nimustine; D004317:Doxorubicin