title: Combined therapy of temozolomide and ZD6474 (vandetanib) effectively             reduces glioblastoma tumor volume through anti-angiogenic and anti-proliferative             mechanisms.
abstract: Currently, clinically available options for treating glioblastoma (GBM) are quite limited, and there is a clear need to develop novel treatment strategies that can more effectively manage tumors. Here, we present a combination treatment of temozolomide (TMZ), a blood-brain barrier penetrating DNA alkylating agent, and ZD6474 (vandetanib), a VEGFR2 and EGFR dual-targeting anti-angiogenic agent, as a novel treatment strategy for GBM. In a U-87MG orthotopic xenograft model, the combination treatment provided a marked 94% tumor volume reduction. This reduction was greater than that achieved by monotherapy of either agent, and was correlated with a statistically significant reduction in microvessel density (CD31+ cells) and proliferation (PCNA+ cells). These results confirm the necessity to target angiogenesis in addition to utilizing cytotoxic approaches, and provide the rationale for application of TMZ + ZD6474 combination therapy for treating GBM patients in the clinical setting.
authors.affiliation: Department of Neurosurgery, Samsung Medical Center and Sungkyunkwan                     University School of Medicine, Seoul, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Jo
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Kim
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Kim
authors.forename: Se Jeong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.forename: Hyeon Ho
authors.initials: HH
authors.lastname: Kim
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D000077204:Temozolomide; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; D003606:Dacarbazine; D000077204:Temozolomide; C452423:vandetanib