The novel gene therapy using adeno-associated viral vector mediatedMDA7/IL-24 for human pancreatic cancer

• Project/Area Number: 22591444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Nippon Medical School
• Principal Investigator: AIMOTO Takayuki 日本医科大学, 医学部, 准教授 (10267122)
• Co-Investigator(Kenkyū-buntansha): MIYAKE Kouichi 日本医科大学, 医学部, 准教授 (90267211)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 膵癌 / 遺伝子治療 / MDA7/IL-24 / gemcitabine / MDA7/IL24

Research Abstract

We established a orthotropic pancreatic cancer model in hamsters using the pancreatic cancer cell line, PGHAM-1 and generated adeno-associated viral vector expressing MDA7/IL-24. The survival time both in the gene therapy alone and in the gene therapy plus gemcitabine group was longer than that in the control group. There were no detectable side effects. This novel gene therapy is a potentially effective treatment for pancreatic cancer although further studies are needed in the near future.

Research Products

• [Journal Article] Long-term Outcomes after Frey's Procedure for Chronic Pancreatitis with an Inflammatory Mass of the Pancreatic Head, with Special Reference to Locoregional Complications. (2013)
  • Author(s): Aimoto T, Uchida E, Matsushita A
  • Journal Title: J Nippon Med Sch Volume: 80 Pages: 148-154
  • NAID: 130004147216
  • Peer Reviewed
• [Journal Article] Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells. (2013)
  • Author(s): Komiyama H, Miyake K, Asai K, Mizuno K, Shimada T
  • Journal Title: Cell Biochemistry& Function Volume: (in press)
  • Peer Reviewed
• [Journal Article] DirectComparison of Administration Routes for AAV8-mediated Ocular Gene Therapy. (2013)
  • Author(s): Igarashi T, Miyake K, Asakawa N, MiyakeN, Shimada T, Takahashi H
  • Journal Title: Curr Eye Res Volume: in press.
  • Peer Reviewed
• [Journal Article] Time-dependent changes in endoscopic findings of intestine in patient with acute superior mesenteric arterial thrombosis after pancreaticoduodenectomy. (2012)
  • Author(s): Mizutani S, Suzuki H, Aimoto T
  • Journal Title: Dig Endosc. Volume: 24 Pages: 289-289
  • Peer Reviewed
• [Journal Article] Dedifferentiated liposarcoma arising from the mesocolon ascendens (2012)
  • Author(s): Takeda K, Aimoto T, Yoshioka M
  • Journal Title: report of a case J Nippon Med Sch Volume: 79 Pages: 385-390
  • Peer Reviewed
• [Journal Article] Serotype-independent Method of Recombinant Adeno-associated Virus (AAV) Vector Production and Purification. (2012)
  • Author(s): Miyake K, Miyake N, Yamazaki Y, Shimada T, Hirai Y
  • Journal Title: J Nippon Med Sch Volume: 79 Pages: 394-402
  • NAID: 130004057397
  • Peer Reviewed
• [Journal Article] Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. (2012)
  • Author(s): Inagawa K, Miyake K, Fukuda K
  • Journal Title: Cir Res Volume: 111 Pages: 1147-1156
  • Peer Reviewed
• [Journal Article] Successful gene therapy in utero for lethal murine hypophosphatasia. (2012)
  • Author(s): Sugano H, Matsumoto T, Miyake K
  • Journal Title: Hum Gene Ther. Volume: 23 Pages: 399-406
  • Peer Reviewed
• [Journal Article] AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice. (2012)
  • Author(s): Tamai H, Miyake K, Yamaguchi H, Takatori M, Dan K, Inokuchi K, Shimada T
  • Journal Title: Blood Volume: 119 Pages: 64-71
  • Peer Reviewed
• [Journal Article] Current Surgical Treatment forChronic Pancreatitis. (2011)
  • Author(s): Aimoto T, Uchida E, Nakamura Y
  • Journal Title: J Nippon Med Sch Volume: 78 Pages: 352-359
  • Peer Reviewed
• [Journal Article] The controlled release of basic fibroblast growth factorpromotes a rapid healing of pancreaticojejunal anastomosis with potent angiogenesis and accelerates apoptosis in granulation tissue. (2011)
  • Author(s): Katsuno A, Aimoto T, Uchida E, Tabata Y, Miyamoto M, Tajiri T
  • Journal Title: J Surg Res Volume: 167 Pages: 166-172
  • Peer Reviewed
• [Journal Article] Resistance of MLL-AFF1-positive acute lymphoblastic leukemia to tumor necrosis factor-alpha is mediated by S100A6 up-regulation. (2011)
  • Author(s): Tamai H, Miyake K, Yamaguchi H
  • Journal Title: Blood Cancer Journal Volume: 1
  • Peer Reviewed
• [Journal Article] Activated K-Ras protein accelerates humanMLL/AF4-inducedleukemo-lymphomogenicity in a transgenic mouse model. (2011)
  • Author(s): Tamai H, Miyake K, Takatori M(8 人、2 番 目)
  • Journal Title: Leukemia Volume: 25 Pages: 888-891
  • Peer Reviewed
• [Journal Article] Global gene transfer into the CNS across the BBB after neonatal systemic delivery of single-stranded AAV vectors. (2011)
  • Author(s): Miyake N, Miyake K, Yamamoto M, Hirai Y, Shimada T
  • Journal Title: Brain Res Volume: 10 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Direct comparison of four adeno-associated virus serotypes in mediating the production of antiangiogenic proteins in mouse muscle. (2011)
  • Author(s): Isotani M, Miyake K, Miyake N, Hirai Y, Shimada T
  • Journal Title: Cancer Invest Volume: 29 Pages: 353-359
  • Peer Reviewed
• [Journal Article] Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia. (2011)
  • Author(s): Wakita S, Yamaguchi H, Miyake K,Mitamura Y, Kosaka F, Dan K, Inokuchi K
  • Journal Title: Leukemia Volume: 25 Pages: 1423-1432
  • Peer Reviewed
• [Journal Article] Parkin-mediated protection of dopaminergic neurons in a chronic MPTP-minipump mouse model of Parkinson disease. (2011)
  • Author(s): Yasuda T, Miyake K, Takada M
  • Journal Title: J Neuropathol Exp Neurol Volume: 70 Pages: 686-697
  • Peer Reviewed
• [Journal Article] Laparoscopic distal pancreatectomy preserving spleen and splenic vessels for pancreatic insulinoma. (2010)
  • Author(s): Ueda J, Nakamura Y, Aimoto T
  • Journal Title: J Nippon Med Sch Volume: 77 Pages: 175-180
  • NAID: 130004147053
  • Peer Reviewed
• [Journal Article] Successful treatment of metachromatic leukodystrophy using bone marrow transplantation of HoxB4 overexpressing cells. (2010)
  • Author(s): Miyake N, Miyake K, Karlsson S, Shimada T
  • Journal Title: Mol Ther Volume: 18 Pages: 1373-1378
  • Peer Reviewed
• [Journal Article] Circadian disruption accelerates tumor growth andangio/stromagenesis through a Wntsignaling pathway. (2010)
  • Author(s): Yasuniwa Y, Miyake K, Kashiwagi E
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase. (2010)
  • Author(s): Matsumoto T, Miyake K, Yamamoto S
  • Journal Title: Hum Gene Ther Volume: 22 Pages: 1355-1364
  • Peer Reviewed
• [Journal Article] RPS19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model ofDiamond-Blackfan anemia. (2010)
  • Author(s): Miyake K, Utsugisawa T, Flygare J,Kiefer T, Hamaguchi I, Richter J, Karlsson S
  • Journal Title: Stem Cells Volume: 26 Pages: 323-329
  • Peer Reviewed
• [Presentation] 膵癌に対する左方アプローチ膵頭十二指腸切除術 (2012)
  • Author(s): 相本隆幸
  • Organizer: 日本臨床外科学会総会(第74回)
  • Place of Presentation: 東京
• [Presentation] 膵癌に対する左方アプローチ膵頭十二指腸切除術 (2012)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会大会(第10回)
  • Place of Presentation: 神戸
• [Presentation] 膵管内乳頭粘液性腫瘍(IPMN)由来浸潤癌に対する治療戦略 (2012)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会総会(第67回)
  • Place of Presentation: 富山
• [Presentation] Left posterior approach for pancreaticoduodenectomy for pancreatic head cancer (2012)
  • Author(s): Aimoto T
  • Organizer: 44th meeting of the EuropeanPancreatic Club
  • Place of Presentation: Prague, Czech
• [Presentation] 切除可能膵癌に対するGemcitabineを用いた術前化学療法 (2012)
  • Author(s): 相本隆幸
  • Organizer: 日本肝胆膵外科学会・学術集会(第24回)
  • Place of Presentation: 大阪
• [Presentation] 膵頭十二指腸切除術に対する行程別教育プログラムの実際と成果 (2012)
  • Author(s): 相本隆幸
  • Organizer: 日本外科学会(第112回)
  • Place of Presentation: 千葉
• [Presentation] Rescue of lethal hypophosphatasia mice by neonatal ex vivo gene therapy using lentivirally transduced bone marrow cells. (2012)
  • Author(s): Iijima O, Miyake K
  • Organizer: 54th American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: Atlanta,USA
• [Presentation] AAV9 mediated gene therapy of MLD model mice. (2012)
  • Author(s): Miyake N, Miyake K
  • Organizer: 20th Annual Meeting of the European Society of Gene & Cell Therapy
  • Place of Presentation: Versailles, France
• [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector. (2012)
  • Author(s): Miyake N, Miyake K
  • Organizer: 第4回国際ライソゾーム病フォーラム・第17回 日本ライソゾーム病研究会
  • Place of Presentation: 東京
• [Presentation] Successful treatment of adult MLD model mice by intrathecal administration of type 9 AAV vector. (2012)
  • Author(s): Miyake N, Miyake K
  • Organizer: The 18th Annual Meeting of Japan Society ofGene Therapy
  • Place of Presentation: 熊本
• [Presentation] Successful gene therapy in utero for lethal murine hypophosphatasia. (2012)
  • Author(s): Sugano H, Miyake K
  • Organizer: 6th Alkaline Phosphatasie and Hypophosphatasia International Symposium
  • Place of Presentation: Huningue,France
• [Presentation] Gene therapy of adult MLD model mice by intrathecal administration of type 9 AAV vector. (2012)
  • Author(s): Miyake N, Miyake K
  • Organizer: 15th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Philadelphia, USA
• [Presentation] 当科における膵頭十二指腸切除 術に対する教育プログラム (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会大会(第9回)
  • Place of Presentation: 福岡
• [Presentation] グルーブ膵癌 (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本癌学会学術総会(第70回)
  • Place of Presentation: 名古屋
• [Presentation] 切除可能膵癌に対する術前化学療法 (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本癌治療学会学術集会(第49回)
  • Place of Presentation: 名古屋
• [Presentation] 膵頭十二指腸切除術後の膵液瘻に対するドレーン管理 (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会総会(第66回)
  • Place of Presentation: 名古屋
• [Presentation] 切除可能膵癌に対するgemcitabineを用いた術前化学療法 (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本膵臓学会大会(第42回)
  • Place of Presentation: 青森
• [Presentation] Efficacy of a fluted drain withcontinuous suction on pancreatic fistula after pancreaticoduodenectomy. (2011)
  • Author(s): Aimoto T
  • Organizer: 43rd meeting of the European Pancreatic Club
  • Place of Presentation: Magdeburg, Germany
• [Presentation] PD術後膵液瘻に対するドレーン管理:基礎的実験と臨床例の検討 (2011)
  • Author(s): 相本隆幸
  • Organizer: 日本肝胆膵外科学会・学術集会(第23回)
  • Place of Presentation: 東京
• [Presentation] The effect and specific mechanisms of systemic gene therapy using AAV8-IL24 in MLL/AF4 Tg mice. (2011)
  • Author(s): 玉井 勇人, 三宅弘一
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Gene Therapy for MLD by Intrathecal Administration of Type 9AAV Vector Expressing ASA. (2011)
  • Author(s): Miyake N, Miyake K
  • Organizer: The 17th Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: 福岡
• [Presentation] AAV Type 8 Mediated Bone-Targeted and Muscle Directed Neonatal Gene Therapy for Hypophosphatasia. (2011)
  • Author(s): Miyake K
  • Organizer: The17th Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: 福岡
• [Presentation] Development of cell targeting strategy using HIV vector pseudtyped with HIV envelope. (2011)
  • Author(s): Miyake K
  • Organizer: The17th Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: 福岡
• [Presentation] Successful Treatment of Hypophosphatasia Model Mice by a Single Intramuscular Injection of AAV Type 8 Vector Expressing Tissue-Nonspecific Alkaline Phosphatase. (2011)
  • Author(s): Matsumoto T, Miyake K
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle, USA
• [Presentation] Intrathecal Administration of Type 9 AAV Vector Expressing Arylsulfatase A Is Effective for Reduction of Sulfatide Storage but Not for Correction of Neurological Deficits inAdult Metachromatic Leukodystrophy Model Mice with Overt Neurological Symptoms. (2011)
  • Author(s): Miyake N, Miyake K
  • Organizer: 14th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle, USA
• [Presentation] Development of adeno-associated viral (AAV) vector mediated muscle directed systemic anti-angiogenic cancer gene therapy (2010)
  • Author(s): 三宅弘一
  • Organizer: 日本癌学会学術総会(第69回)
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 膵液瘻なき膵消化管吻合術をめざして:bFGF 含浸ゼラチンハイドロゲル投与の意義 (2010)
  • Author(s): 相本隆幸
  • Organizer: 日本創傷治癒学会(第40回)
  • Place of Presentation: 東京
• [Presentation] IPMN 由来の浸潤癌における外科治療成績 (2010)
  • Author(s): 相本隆幸
  • Organizer: 日本臨床外科学会総会(第72回)
  • Place of Presentation: 横浜
• [Presentation] IPMN由来の浸潤癌症例の臨床病理学的検討 (2010)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会大会(第8回)
  • Place of Presentation: 横浜
• [Presentation] バイオマテリアルを用いた膵空腸吻合部の創傷治癒促進の試み-術後膵液瘻克服をめざして (2010)
  • Author(s): 相本隆幸
  • Organizer: 日本消化器外科学会総会(第65回)
  • Place of Presentation: 下関
• [Presentation] 肝胆膵外科領域における術後合併症対策 (2010)
  • Author(s): 相本隆幸
  • Organizer: 胆汁漏及び膵液漏対策を中心に、日本消化器外科学会総会(第65回)
  • Place of Presentation: 下関
• [Presentation] Controlled release of basicn fibroblast growth factor causes rapid healing of pancreaticojejunostomy (2010)
  • Author(s): Aimoto T
  • Organizer: 42th meeting of the European Pancreatic Club
  • Place of Presentation: Stockholm, Sweden
• [Presentation] 膵腸吻合部の創傷治療に対するbFGF含浸ゼラチンハイドロゲル投与の意義 (2010)
  • Author(s): 相本隆幸
  • Organizer: 日本外科学会定期学術集会(第110回)
  • Place of Presentation: 名古屋
• [Presentation] The Activated K-RAS Protein Accelerates Human Derived-MLL/AF4 Induced Leukemo- Lymphomogenicity In Transgenic Mice Model. (2010)
  • Author(s): Tamai H, Miyake K
  • Organizer: 18th European Society of Gene and Cell Therapy Annual Congress
  • Place of Presentation: Prague, Czech
• [Presentation] MLL/AF4 Positive Acute Lymphoblastic Leukemia Has Resistance to Tumor Necrosis Factor-Alpha Caused by up-Regration of S100A6. (2010)
  • Author(s): Tamai H, Miyake K
  • Organizer: 18th European Society of Gene and Cell Therapy Annual Congress
  • Place of Presentation: Prague, Czech
• [Presentation] Wang Nanya: Development of adeno-associated viral (AAV) vector mediated muscle directed systemic anti-angiogenic cancer gene therapy. (2010)
  • Author(s): 三宅弘一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Gene Therapy of Acute Lymphoblastic Leukemia with MLL/AF4 Using AAV8-IL24. (2010)
  • Author(s): 玉井勇人, 三宅弘一
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
• [Presentation] Establishment and Characterization of A New Lymphoid Malignancy Mouse Model Induced by thecombination of MLL/AF4 and K-RAS. (2010)
  • Author(s): 玉井勇人, 三宅弘一
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
• [Book] Novel Gene Therapy Approaches (2013)
  • Author(s): Miyake K,Shimada T
  • Total Pages: 396
  • Publisher: InTech
• [Book] InTech, Viral Gene Therapy (2011)
  • Author(s): Miyake K
  • Total Pages: 450
  • Publisher: Shimada T