Convection-enhanced delivery of micellar retinoic acid as a new treatment strategy for malignant glioma

• Project/Area Number: 21390401
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: KUMABE Toshihiro 東北大学, 大学院・医学系研究科, 准教授 (10250747)
• Co-Investigator(Kenkyū-buntansha): SONODA Yukihiko 東北大学, 病院, 講師 (90302140) ; SAITO Ryuta 東北大学, 大学院・医学系研究科, 助教 (10400243)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 脳腫瘍 / 分化誘導療法 / ドラッグデリバリー / 薬剤担体 / レチノイン酸 / グリオーマ / Convection-enhanced delivery / テモゾロミド / ミセル化抗癌剤 / 薬物送達 / 膠芽腫 / ミセル / CED法

Research Abstract

We evaluated the efficacy of intracerebral administration of polymeric micellar synthetic retinoid(Am80)by convection-enhanced delivery(CED)combined with systemic admin istration of temozolomide in a U87MG intracranial xenograft model. As a result, CED of micellar Am80 provided significantly longer survival(P<0. 05). Combination of CED of micellar Am80 and systemic treatment of temozolomide provided significantly longer s urvival than the single treatment(P<0. 005, P<0. 005). Consequently, Temozolomide combined with CED administration of Am80 may be a promising strategy for the treatment of malignant gliomas.

Research Products

• [Journal Article] Clinicopathological analysis of nine consecutive central nervous system primitive neuroectodermal tumors in a single institute (2012)
  • Author(s): Aizawa-Kohama M, Kumabe T, Saito R, Kanamori M, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T.
  • Journal Title: Brain Tumor Pathol Volume: 21
  • Peer Reviewed
• [Journal Article] IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas (2011)
  • Author(s): Shibahara I, Sonoda Y, Kanamori M, Saito R, Yamashita Y, Kumabe T, Watanabe M, Suzuki H, Kato S, Ishioka C, Tominaga T.
  • Journal Title: Int J Clin Oncol Volume: 6
  • NAID: 10031155913
  • Peer Reviewed
• [Journal Article] Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic resonance imaging (2011)
  • Author(s): Saito R, Kumabe T, Kanamori M, Yamashita Y, Sonoda Y, Higano S, Takahashi S, Tominaga T.
  • Journal Title: Minim Invasive Neurosurg Volume: 54(3) Pages: 105-9
  • Peer Reviewed
• [Journal Article] Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model (2011)
  • Author(s): Nakamura T, Saito R, Sugiyama S, Sonoda Y, Kumabe T, Tominaga T.
  • Journal Title: Cancer Lett Volume: 310(1) Pages: 77-83
  • Peer Reviewed
• [Journal Article] New insights into glioma classification based on isocitrate dehydrogenase 1 and 2 gene status (2011)
  • Author(s): Shibahara I, Sonoda Y, Kanamori M, Saito R, Kumabe T, Tominaga T.
  • Journal Title: Brain Tumor Pathol Volume: 28(3) Pages: 203-8
  • Peer Reviewed
• [Journal Article] Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma : single-institute experience and differences in efficacy for subgroups of medulloblastoma (2011)
  • Author(s): Saito R, Kumabe T, Sonoda Y, Kanamori M, Yamashita Y, Watanabe M, Tominaga T.
  • Journal Title: Childs Nerv Syst Volume: 27(9) Pages: 1399-406
  • Peer Reviewed
• [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 Volume: 7(5) Pages: 522-6
  • 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 Volume: 104(3) Pages: 779-87
  • Peer Reviewed
• [Journal Article] Infratentorial brain metastases of pediatric non-epithelial malignant tumors : three case reports (2011)
  • Author(s): Osawa S, Kumabe T, Saito R, Sonoda Y, Niizuma H, Watanabe M, Tominaga T.
  • Journal Title: Brain Tumor Pathol Volume: 28(2) Pages: 167-74
  • 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 (2011)
  • Author(s): Kawaguchi T, Kumabe T, Kanamori M, Nakamura T, Saito R, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T.
  • Journal Title: J Neurooncol Volume: 101(3) Pages: 495-504
  • Peer Reviewed
• [Journal Article] Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model (2011)
  • Author(s): Nakamura T, Saito R, Sugiyama S, Sonoda Y, Kumabe T, Tominaga T
  • Journal Title: Cancer Letter Volume: 310 Issue: 1 Pages: 77-83
  • DOI: 10.1016/j.canlet.2011.06.018
  • Peer Reviewed
• [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 Volume: 7 Issue: 5 Pages: 522-526
  • DOI: 10.3171/2011.2.peds10407
  • Peer Reviewed
• [Journal Article] Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic resonance imaging (2011)
  • Author(s): Saito R, Kumabe T, Kanamori M, Yamashita Y, Sonoda Y, Higano S, Takahashi S, Tominaga T
  • Journal Title: Minim Invasive Neurosurg Volume: 54 Issue: 03 Pages: 105-109
  • DOI: 10.1055/s-0031-1279715
  • Peer Reviewed
• [Journal Article] New insights into glioma classification based on isocitrate dehydrogenase 1 and 2 gene status (2011)
  • Author(s): Shibahara I, Sonoda Y, Kanamori M, Saito R, Kumabe T, Tominaga T
  • Journal Title: Brain Tumor Pathol Volume: 28 Issue: 3 Pages: 203-208
  • DOI: 10.1007/s10014-011-0050-4
  • Peer Reviewed
• [Journal Article] Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma : single-institute experience and differences in efficacy for subgroups of medulloblastoma (2011)
  • Author(s): Saito R, Kumabe T, Sonoda Y, Kanamori M, Yamashita Y, Watanabe M, Tominaga T
  • Journal Title: Childs Nerv Syst Volume: 27 Issue: 9 Pages: 1399-1406
  • DOI: 10.1007/s00381-011-1485-y
  • 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 Volume: 104 Pages: 779-787
  • Peer Reviewed
• [Journal Article] he 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: Shinkei Geka Volume: 38(11) 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 Volume: 221(4) Pages: 257-64
  • NAID: 10027085245
  • 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) Volume: 50(4) Pages: 286-290
  • NAID: 10026192192
  • 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 Volume: 50(4) Pages: 286-90
  • Peer Reviewed
• [Journal Article] 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 Volume: 15(4) Pages: 352-8
  • 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 Volume: 33(2) 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 Volume: 113(2) Pages: 358-68
  • Peer Reviewed
• [Journal Article] Tohoku Brain Tumor Study Group : Association of stem cell marker CD133 expression with dissemination of glioblastomas (2010)
  • Author(s): Sato A, Sakurada K, Kumabe T, Sasajima T, Beppu T, Asano K, Ohkuma H, Ogawa A, Mizoi K, Tominaga T, Kitanaka C, Kayama T
  • Journal Title: Neurosurg Rev Volume: 33 Pages: 175-183
  • Peer Reviewed
• [Journal Article] Development of the Japanese version of the Pediatric Quality of Life Inventory Brain Tumor Module (2010)
  • Author(s): Sato I, Higuchi A, Yanagisawa T, Mukasa A, Ida K, Sawamura Y, Sugiyama K, Saito N, Kumabe T, Terasaki M, Nishikawa R, Ishida Y, Kamibeppu K
  • Journal Title: Health Qual Life Outcomes Volume: 8 Pages: 38-38
  • 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, Tommaga T.
  • Journal Title: Thhoku J Exp Med. Volume: 221 Pages: 257-264
  • NAID: 10027085245
  • Peer Reviewed
• [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 Volume: 37(12) Pages: 1193-9
  • 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 Volume: 4(6) Pages: 506-14
  • Peer Reviewed
• [Journal Article] Predictive factors for overall and progression-free survival, and dissemination in oligodendroglial tumors (2009)
  • Author(s): Kanamori M, Kumabe T, Sonoda Y, Nishio Y, Watanabe M, Tominaga T
  • Journal Title: J Neurooncol Volume: 93 Pages: 219-228
  • Peer Reviewed
• [Journal Article] Collision tumor of anaplastic oligodendroglioma and gangliocytoma : a case report. (2009)
  • Author(s): Takeuchi Y, Kanamori M, Kumabe T, Saito R, Sonoda Y, Watanabe M, Tominaga T.
  • Journal Title: Brain Tumor Pathol Volume: 26(2) Pages: 89-93
  • Peer Reviewed
• [Journal Article] Differential diagnosis between radiation necrosis and glioma progression using sequential proton magnetic resonance spectroscopy and methionine positron emission tomography (2009)
  • Author(s): Nakajima T, Kumabe T, Kanamori M, Saito R, Tashiro M, Watanabe M, Tominaga T.
  • Journal Title: Neurol Med Chir(Tokyo) Volume: 49(9) Pages: 394-401
  • NAID: 10025948513
  • Peer Reviewed
• [Journal Article] Analysis of IDH1 and IDH2 mutations in Japanese glioma patients (2009)
  • Author(s): Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H, Tominaga T.
  • Journal Title: Cancer Sci Volume: 100(10) Pages: 1996-8
  • NAID: 10027196311
  • Peer Reviewed
• [Journal Article] Magnetic resonance imaging for preoperative identification of the lenticulostriate arteries in insular glioma surgery. Technical note (2009)
  • Author(s): Saito R, Kumabe T, Inoue T, Takada S, Yamashita Y, Kanamori M, Sonoda Y, Tominaga T.
  • Journal Title: J Neurosurg Volume: 111(2) Pages: 278-81
  • Peer Reviewed
• [Presentation] Safety and Feasibility of MRI guided convection-enhanced delivery of nimustine hydrochloride against recurrent glioma affecting brainstem (2011)
  • Author(s): Saito R, Sonoda Y, Yamashita Y, Kanamori M, Kumabe T, Tominaga T.
  • Organizer: 2011Society for Neurooncology Annual Meeting
  • Place of Presentation: Orange County, USA
  • Year and Date: 2011-11-20
• [Presentation] 悪性神経膠腫に対するConvection-enhanced delivery:現状と展望 (2011)
  • Author(s): 齋藤竜太、園田順彦、山下洋二、金森政之、隈部俊宏、冨永悌二
  • Organizer: 第70回日本脳神経外科学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-13
• [Presentation] 悪性神経膠腫に対するConvection-enhanced delivery :現状と展望 (2011)
  • Author(s): 齋藤竜太、園田順彦、山下洋二、金森政之、隈部俊宏、冨永悌二
  • Organizer: 第70回日本脳神経外科学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-12
• [Presentation] MRI Guided Convection-Enhanced Delivery of Nimustine Hydrochloride Against Recurrent Glioma Affecting Brain Stem (2011)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Yoji Yamashita, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga
  • Organizer: 8th Annual World Congress of IBMISPS on Brain, Spinal Cord Mapping and Image Guided Therapy
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2011-06-10
• [Presentation] MRI Gmded Convection-Enhanced Delivery of Nimustine Hydrochloride Against Recurrent Glioma Affecting Brain Stem (2011)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Yoji Yamashita, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga
  • Organizer: 8th Annual World Congress of IBMISPS on Brain, Spinal Cord Mapping and Image Guided Therapy
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2011-06-10
• [Presentation] MRI Guided Convection-Enhanced Delivery of Nimustine Hydrochloride Against Recurrent Glioma Affecting Brain Stem (2011)
  • Author(s): Saito R, Sonoda Y, Yamashita Y, Kanamori M, Kumabe T, Tominaga T.
  • Organizer: 8th Annual World Congress of IBMISPS on Brain, Spinal Cord Mapping and Image Guided Therapy
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-06-09
• [Presentation] Convection-enhanced Delivery:現状と展望 (2011)
  • Author(s): 斎藤竜太・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
  • Year and Date: 2011-05-07
• [Presentation] Local Application of Chemotherapeutics Transiently Opens Blood-Brain Barrier and Improves Efficacy of Systemic Chemotherapy against Intracranial Xenograft Tumor Model (2010)
  • Author(s): Saito R, Nakamura T, Sonoda Y, Kumabe T, Tominaga T.
  • Organizer: 2010Society for Neurooncology Annual Meeting
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2010-11-19
• [Presentation] 神経膠腫における基本手技(シンポジウム:こだわりの手術) (2010)
  • Author(s): 隈部俊宏、冨永悌二
  • Organizer: 第15回日本脳腫瘍の外科学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-10-01
• [Presentation] What does awake surgery bring into the glioma surgery (2010)
  • Author(s): Kumabe T
  • Organizer: 2010 Current Trends in the Management of Malignant Gliomas
  • Place of Presentation: Tokyo
  • Year and Date: 2010-07-31
• [Presentation] Logarithmic Decrease of Serum Alpha-Fetoprotein Level in Response to Chemotherapy can Distinguish the Subgroup with better Prognosis Among Highly Malignant Intracranial Non-Germinomatous Germ Cell Tumors (2010)
  • Author(s): Kumabe T, Kawaguchi T, Saito R, Kanamori M, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T
  • Organizer: ASNO2010 The 7th Meeting of Asian Society for Neuro
  • Place of Presentation: Oncology, Seoul
  • Year and Date: 2010-06-11
• [Presentation] Imaging of hypoxic lesion in glioma patients by PET with [18F]FRP-170, a new 18F-labeled 2-nitroimidazole analog (2010)
  • Author(s): Kumabe T, Shibahara I, Kanamori M, Saito R, Sonoda Y, Watanabe M, Iwata R, Higano S, Takanami K, Takai Y, Tominaga T
  • Organizer: 18th International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Travemunde, Germany
  • Year and Date: 2010-05-19
• [Presentation] 覚醒下手術の準備と実際(ランチョンセミナー:覚醒下手術) (2009)
  • Author(s): 隈部俊宏、冨永悌二
  • Organizer: 社団法人日本脳神経外科学会第68回学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-15
• [Presentation] モニタリングは神経膠腫の長期生存を向上させたか?(シンポジウム) (2009)
  • Author(s): 隈部俊宏、齋藤竜太、金森政之、山下洋二、園田順彦、冨永悌二
  • Organizer: 社団法人日本脳神経外科学会第68回学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-15
• [Presentation] ラット脳腫瘍モデルに対するConvection enhanced delivery法を用いたミセル内包合成レチノイン酸とテモゾロミド併用療法の抗腫瘍効果の検討 (2009)
  • Author(s): 横沢路子
  • Organizer: (社)日本脳神経外科学会第68回学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-14
• [Book] 脳腫瘍の外科-社会が望む脳腫瘍外科 (2011)
  • Author(s): 隈部俊宏、冨永悌二
  • Publisher: メディカ出版
• [Book] 松果体部腫瘍-Occipital transtentorial approach. ビジュアル脳神経外科 Anatomy & Surgical Approach 4 (2011)
  • Author(s): 隈部俊宏、冨永悌二
  • Publisher: 株式会社メジカルビュー社
• [Book] 1. 低悪性度グリオーマ. イラストレイテッド脳腫瘍外科学. C-TV各種脳腫瘍の手術 (2011)
  • Author(s): 隈部俊宏
  • Publisher: 株式会社医学書院
• [Book] Visualization of lateral lenticulostriate arteries using 3-tesla magnetic resonance imaging (2010)
  • Author(s): Kumabe T, Saito R, Kanamori M, Sonoda Y, Higano S, Takahashi S, Tominaga T
  • Publisher: Springer-Verlag
• [Book] Ischemic complication associated with resection of opercular gliomas (2010)
  • Author(s): Kumabe T, Kanamori M, Saito R, Nagamatsu K, Sonoda Y, Higano S, Takahashi S, Tominaga T
  • Publisher: Springer-Verlag
• [Book] 神経膠腫治療成績の変化. 新時代の脳腫瘍学-診断・治療の最前線-V. 脳腫瘍の治療. 概論. 日本臨床68巻 (2010)
  • Author(s): 隈部俊宏、冨永悌二
  • Publisher: 株式会社日本臨床社
• [Book] 脳腫瘍-手術療法-I. 臓器部位別の治療戦略. がん治療最前線-米国癌学会(ASCO)のトピックスを中心に- (2010)
  • Author(s): 隈部俊宏、冨永悌二
  • Publisher: 総合医学社発行
• [Book] 2. 星細胞腫に放射線治療は必要か (2010)
  • Author(s): 隈部俊宏、冨永悌二
  • Publisher: 中外医学社発行
• [Book] Ependymoblastoma上衣芽腫 (2009)
  • Author(s): 隈部俊宏、渡辺みか
  • Total Pages: 95