Development of mTOR-targeted novel therapy inducing autophagy for B-cell lymphoma

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: SATO Tsutomu 札幌医科大学, 医学部, 講師 (40404602)
• Co-Investigator(Kenkyū-buntansha): KOBUNE Masayoshi 札幌医科大学, 医学部, 准教授 (90336389)
• Co-Investigator(Renkei-kenkyūsha): KATO Junji 札幌医科大学, 医学部, 教授 (20244345)
• Project Period (FY): 2010 – 2012
• Keywords: リンパ腫 / オートファジー / mTOR / 治療

Research Abstract

Malignant lymphoma has been one of the hematological malignancies of which prognosis is still poor. The most possible reason of poor-prognosis is the resistance against conventional chemotherapeutic reagents, which are expected to induce apoptotic and/or necrotic death in lymphoma cells. Therefore, novel therapy with unique mechanism is required. Then, we have chosen the strategy inducing autolytic cell death, autophagy since the signaling of autophagic cell death does not depend on the apoptotic and necrotic signaling. For the induction of autophagy, we have used siRNA against mTOR. For the delivery of siRNA and the targeting of B-cell lymphoma, we have developed anti-CD19-targeted siRNA-PEG/KALA PECM system.

Research Products

• [Journal Article] Successful treatment by fibrin glue sealant for pneumothorax with chronic GVHD resistant to autologous blood patch pleurodesis (2012)
  • Author(s): Iyama S, Sato T, Murase K, Kikuchi S, Kamihara Y, Ono K, Takada K, Miyanishi K, Sato Y, Takimoto R, Kobune M, Obama T, Miyajima M, Watanabe A, Higami T, Hirayama Y, Kato J
  • Journal Title: Intern Med Volume: 51(15) Pages: 2011-4
  • Peer Reviewed
• [Journal Article] Intermittent administration of recombinant human soluble thrombomodulin successfully controlled chronic disseminated intravascular coagulation in a patient with dissecting aortic aneurysm on an outpatient basis (2012)
  • Author(s): Iyama S, Sato T, Murase K, Kamihara Y, Ono K, Kikuchi S, Takada K, Miyanishi K, Sato Y, Takimoto R, Kobune M, Kato J
  • Journal Title: Blood Coagul Fibrinolysis Volume: 23(6) Pages: 548-50
  • Peer Reviewed
• [Journal Article] Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis (2011)
  • Author(s): Sato T, Kobune M, Murase K, Kado Y, Okamoto T, Tanaka S, Kikuchi S, Nagashima H, Kawano Y, Takada K, Iyama S, Miyanishi K, Sato Y, Takimoto R, Kato J
  • Journal Title: Hepatol Res Volume: 41(7) Pages: 660-7
  • Peer Reviewed
• [Journal Article] Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia (2011)
  • Author(s): Sato T, Iyama S, Murase K, Kamihara Y, Ono K, Kikuchi S, Takada K, Miyanishi K, Sato Y, Takimoto R, Kobune M, Kato J
  • Journal Title: J Hematol Volume: 94(1) Pages: 101-3
  • Peer Reviewed
• [Presentation] et al. Intermittent administration of recombinant human soluble thrombomodulin for chronic DIC (2012)
  • Author(s): Iyama S, Sato T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2012-10-20
• [Presentation] et al. Novel missense mutation in the TMPRSS6 gene in a patient with iron-refractory iron deficiency anemia (2011)
  • Author(s): Kamihara Y, Sato T
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-15
• [Book] 血液症候群I「溶血性尿毒症症候群」 (2013)
  • Author(s): 佐藤 勉ら
  • Total Pages: 534
  • Publisher: 日本臨牀社
• [Book] 分子標的治療薬-最新の選び方・使い方- 「ゲムツズマブ オゾガマイシン」 (2011)
  • Author(s): 佐藤 勉ら
  • Total Pages: 450
  • Publisher: 総合医学社