Development of systemic antitumor effect against malignant glioma by local convection-enhanced delivery

2010 Fiscal Year Final Research Report

• Project/Area Number: 21791341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: SAITO Ryuta Tohoku University, 大学院・医学系研究科, 助教 (10400243)
• Project Period (FY): 2009 – 2010
• Keywords: 脳腫瘍 / 化学療法 / 免疫療法 / ドラッグデリバリー / 免疫遺伝子治療

Research Abstract

This study was started with the aim to develop systemic immunity by locally delivering agents with novel drug delivery system, i.e. convection-enhanced delivery. First, we analyzed the changes in brain tissue that received CED of chemotherapeutic agent ; ACNU. Transient opening of the Blood-brain barrier was noted with the delivery of ACNU at safety dose. With this finding, we tried to combine systemic chemotherapy using liposomal doxorubicin with CED of ACNU to treat rodent brain tumor model. Prolonged survival of the model was noted with this treatment. Consequently, we tested the ability of local CED delivery of adenovirus encoding OX-40 protein to induce systemic immunity. With this strategy antitumor efficacy was observed using rodent brain tumor model.

Research Products

• [Journal Article] Regression of recurrent glioblastoma infiltrating the brainstem after convection-enhanced delivery of nimustine hydrochloride. (2011)
  • Author(s): Saito R, Sonoda Y, Kumabe T, Nagamatsu K, Watanabe M, Tominaga T.
  • Journal Title: J Neurosurg Pediatr 7 Pages: 522-526
  • Peer Reviewed
• [Journal Article] Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors. (2011)
  • Author(s): Kawaguchi T, Kumabe T, Kanamori M, Saito R, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T.
  • Journal Title: J Neurooncol. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Infratentorial brain metastases of pediatric non-epithelial malignant tumors : three case reports. (2011)
  • Author(s): Osawa SI, Kumabe T, Saito R, Sonoda Y, Niizuma H, Watanabe M, Tominaga T.
  • Journal Title: Brain Tumor Pathol. 28 Pages: 167-174
  • Peer Reviewed
• [Journal Article] The safety of combination chemotherapy with ifosfamide, cisplatin, and etoposide (ICE) : single-institution retrospective review of 108 cases. (2010)
  • Author(s): Kanamori M, Kumabe T, Saito R, Yamashita Y, Sonoda Y, Tominaga T.
  • Journal Title: No Shinkei Geka 38 Pages: 997-1005
  • Peer Reviewed
• [Journal Article] Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts. (2010)
  • Author(s): Yokosawa M, Sonoda Y, Sugiyama S, Saito R, Yamashita Y, Nishihara M, Satoh T, Kumabe T, Yokoyama M, Tominaga T.
  • Journal Title: Tohoku J Exp Med 221 Pages: 257-264
  • Peer Reviewed
• [Journal Article] Early detection of venous thromboembolism in patients with neuroepithelial tumor : efficacy of screening with serum D-dimer measurements and Doppler ultrasonography. (2010)
  • Author(s): Kawaguchi T, Kumabe T, Kanamori M, Nakamura T, Saito R, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T.
  • Journal Title: J Neurooncol 101 Pages: 495-504
  • Peer Reviewed
• [Journal Article] Insulo-opercular gliomas : four different natural progression patterns and implications for surgical indications. (2010)
  • Author(s): Saito R, Kumabe T, Kanamori M, Sonoda Y, Tominaga T.
  • Journal Title: Neurol Med Chir (Tokyo) 50 Pages: 286-290
  • Peer Reviewed
• [Journal Article] Melanotic neuroectodermal tumor of the brain recurring 12 years after complete remission : case report. (2010)
  • Author(s): Omodaka S, Saito R, Kumabe T, Kawagishi J, Jokura H, Sonoda Y, Watanabe M, Kayama T, Tominaga T.
  • Journal Title: Brain Tumor Pathol 27 Pages: 51-57
  • Peer Reviewed
• [Journal Article] O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma. (2010)
  • Author(s): Sonoda Y, Yokosawa M, Saito R, Kanamori M, Yamashita Y, Kumabe T, Watanabe M, Tominaga T.
  • Journal Title: Int J Clin Oncol 15 Pages: 352-358
  • Peer Reviewed
• [Journal Article] Dissemination limits the survival of patients with anaplastic ependymoma after extensive surgical resection, meticulous follow up, and intensive treatment for recurrence. (2010)
  • Author(s): Saito R, Kumabe T, Kanamori M, Sonoda Y, Tominaga T.
  • Journal Title: Neurosurg Rev 33 Pages: 185-91
  • Peer Reviewed
• [Journal Article] Imaging of hypoxic lesions in patients with gliomas by using positron emission tomography with 1-(2-[18F] fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, a new 18F-labeled 2-nitroimidazole analog. (2010)
  • Author(s): Shibahara I, Kumabe T, Kanamori M, Saito R, Sonoda Y, Watanabe M, Iwata R, Higano S, Takanami K, Takai Y, Tominaga T.
  • Journal Title: J Neurosurg 113 Pages: 358-368
  • Peer Reviewed
• [Journal Article] 脳腫瘍の外科療法Convection-enhanced delivery-原理・現状・展望- (2010)
  • Author(s): 齋藤竜太、園田順彦、隈部俊宏、冨永悌二
  • Journal Title: 日本臨床 68 suppl 10 Pages: 388-391
• [Journal Article] Glioblastoma:臨床研究と新規治療 (2010)
  • Author(s): 齋藤竜太, 園田順彦, 隈部俊宏, 冨永悌二
  • Journal Title: 脳神経外科速報 20 Pages: 559-568
• [Journal Article] Intraoperative neuronavigation system without rigid pin fixation. (2009)
  • Author(s): Akamatsu Y, Kumabe T, Kanamori M, Nagamatsu K, Saito R, Sonoda Y, Sato K, Tominaga T.
  • Journal Title: No Shinkei Geka 37 Pages: 1193-1199
  • Peer Reviewed
• [Journal Article] Optimal treatment strategy for intracranial germ cell tumors : a single institution analysis. (2009)
  • Author(s): Kanamori M, Kumabe T, Saito R, Yamashita Y, Sonoda Y, Ariga H, Takai Y, Tominaga T.
  • Journal Title: J Neurosurg Pediatr 4 Pages: 506-514
  • Peer Reviewed
• [Presentation] Convection-enhanced delivery:現状と展望 (2011)
  • Author(s): 齋藤竜太, 園田順彦, 隈部俊宏, 冨永悌二
  • Organizer: 第31回日本脳神経外科コングレス総会
  • Place of Presentation: 横浜 パシフィコ横浜(ランチョンセミナー)
  • Year and Date: 20110506-20110508
• [Presentation] 脳腫瘍への有効な薬剤送達技術:コンベクション・エンハンスト・デリバリー (2010)
  • Author(s): 齋藤竜太, 園田順彦, 隈部俊宏, 冨永悌二
  • Organizer: 第28回日本脳腫瘍学会学術集会
  • Place of Presentation: 軽井沢 軽井沢プリンスホテル(指定口演)
  • Year and Date: 20101128-20101130
• [Presentation] Local Application of Chemotherapeutics Transiently Opens Blood-Brain Barrier and Improves Efficacy of Systemic Chemotherapy against Intracranial Xenograft Tumor Model. (2010)
  • Author(s): Ryuta Saito, Taigen Nakamura, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga.
  • Organizer: 2010 Society for Neurooncology Annual Meeting
  • Place of Presentation: カナダ・モントリオール
  • Year and Date: 20101118-20101121
• [Presentation] Convection-enhanced deliveryを用いた悪性神経膠腫新規治療法の開発:現状と展望 (2010)
  • Author(s): 齋藤竜太, 園田順彦, 山下洋二, 金森政之, 永松謙一, 隈部俊宏, 冨永悌二
  • Organizer: 第69回日本脳神経外科学術総会
  • Place of Presentation: 福岡 福岡国際会議場
  • Year and Date: 20101027-20101029
• [Presentation] 脳腫瘍に対する理想的な投薬を目指して:Convection-enhanced delivery (2010)
  • Author(s): 齋藤竜太, 山下洋二, 園田順彦, 隈部俊宏, 冨永悌二
  • Organizer: 第30回日本脳神経外科コングレス総会
  • Place of Presentation: 横浜 パシフィコ横浜(ランチョンセミナー)
  • Year and Date: 20100507-20100509
• [Presentation] Drug Delivery. (2010)
  • Author(s): 齋藤竜太
  • Organizer: 第43回東北脳腫瘍研究会
  • Place of Presentation: 仙台 東北大学艮陵会館
  • Year and Date: 2010-04-03
• [Presentation] テモゾロミド不応性再発神経膠腫に対するACNU局所投与 (2009)
  • Author(s): 齋藤竜太, 園田順彦, 山下洋二, 金森政之, 永松謙一, 隈部俊宏, 冨永悌二
  • Organizer: 第28回脳腫瘍学会学術集会
  • Place of Presentation: 大阪 全日空ゲートタワーホテル大阪
  • Year and Date: 20091108-20091110
• [Presentation] Convection-enhanced Delivery of ACNU Under MRI Monitoring Against Recurrent Gliomas- Development of Computational Simulation of Drug Distribution. (2009)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Ken-ichi Funamoto, Toshiyuki Hayase, Teiji Tominaga.
  • Organizer: The Ninth International Symposium on Advanced Fluid Information and Transdisciplinary Fluid Integration
  • Place of Presentation: 仙台 仙台メトロポリタンホテル
  • Year and Date: 20091104-20091105
• [Presentation] 再発神経膠腫に対するMRIモニタリングを併用したConvection-enhanced Delivery法によるACNUの投与 (2009)
  • Author(s): 齋藤竜太, 園田順彦, 山下洋二、金森政之, 永松謙一, 隈部俊宏, 冨永悌二
  • Organizer: 日本脳神経外科学会第68回学術総会
  • Place of Presentation: 東京
  • Year and Date: 20091014-20091016
• [Presentation] CED of ACNU. (2009)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga.
  • Organizer: First International Meeting of the Society for CNS Interstitial Deliveryof Therapeutics (SCIDOT)
  • Place of Presentation: リーブランド・米国
  • Year and Date: 20090911-20090912