A novel cancer therapy using type-I interferon, which is induced by siRNA or short single-stranded RNA in a nucleotide-specific manner

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: TAKEI Yoshifumi Nagoya University, 大学院・医学系研究科, 准教授 (70362233)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院・医学系研究科, 教授 (80204519)
• Project Period (FY): 2007 – 2008
• Keywords: siRNA / インターフェロン応答 / 抗腫瘍効果 / 治療 / 樹状細胞 / アポトーシス

Research Abstract

RNA干渉は標的遺伝子配列に相補的な短い2本鎖RNA(short interfering RNA, siRNA)による遺伝子発現抑制法である。近年、このsiRNA分子がある特別な塩基配列を持つときに限り、I型インターフェロン(=IFN)を誘導する能力があることが論文発表されている。本研究課題では、siRNA分子のIFN誘導能力に着目し、誘導したIFNを利用して癌細胞を殺す所(細胞、及び動物実験)までの成果を得た。
【語句説明】RNA干渉 : 短い2本鎖RNAが伝令RNAに結合することを介して標的遺伝子が蛋白質に翻訳されることを抑える手法。発見者は2006年のノーベル生理学・医学賞を受賞している。インターフェロン:動物体内で病原体(特にウイルス)や腫瘍細胞などの異物の侵入に反応して細胞が分泌するタンパク質である。癌細胞を殺す作用がある。

Research Products

• [Journal Article] Systemic delivery of siRNA specific to tumor mediated by atelocollagen : Combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer (2009)
  • Author(s): Mu P, Nagahara S, Makita N, Tarumi S, Kadomatsu K, Takei Y
  • Journal Title: Int J Cancer (in press)
  • Peer Reviewed
• [Journal Article] Lymphatic vessels develop in tubulo-interstitial fibrosis (2009)
  • Author(s): Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, anaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S
  • Journal Title: Kidney Int. (in press)
  • Peer Reviewed
• [Journal Article] Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction (2009)
  • Author(s): Takenaka H, Horiba M, Ishiguro H, Sumida A, Hojo M, Usui A, Akita T, Sakuma S, Ueda Y, Kodama I, Kadomatsu K
  • Journal Title: Am J Physiol Heart Circ Physiol Vol.296(No.2) Pages: H462-9
  • Peer Reviewed
• [Journal Article] In vivo silencing of a molecular target by short interfering RNA electroporation : tumor vascularization correlates to delivery efficiency (2008)
  • Author(s): Takei Y*, Nemoto T, Mu P, Fujishima T, Ishimoto T, Hayakawa Y, Yuzawa Y, MatsuoS, Muramatsu T, Kadomatsu K
  • Journal Title: Mol Cancer Ther. Vol.7(No.1) Pages: 211-21
  • Peer Reviewed
• [Journal Article] Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates hapten-induced contact hypersensitivity (2008)
  • Author(s): Ishimoto T, Takei Y*, Yuzawa Y, Hanai K, Nagahara S, Tarumi Y, Matsuo S, Kadomatsu K
  • Journal Title: Mol Ther Vol.16(No.2) Pages: 387-95
  • Peer Reviewed
• [Journal Article] 3' Poly(dA)-tailed thrombin DNA aptamer to increase DNase-resistance and clotting inhibitory activity (2008)
  • Author(s): Uehara S, Shimada N, Takeda Y, Koyama Y, Takei Y, Ando H, Satoh S, Uno A, Sakurai K
  • Journal Title: Bull Chem Soc Jpn. Vol.81(No.11) Pages: 1485-91
  • Peer Reviewed
• [Journal Article] Midkine is expressed by infiltrating macrophages in in-stent estenosis in hypercholesterolemic rabbits (2008)
  • Author(s): Narita H, Chen S, Komori K, Kadomatsu K.
  • Journal Title: J Vasc Surg Vol.47(No.6) Pages: 1322-9
  • Peer Reviewed
• [Journal Article] Plasma midkine level is a prognostic factor for human neuroblastoma (2008)
  • Author(s): Ikematsu S, Nakagawara A, Nakamura Y, Ohira M, Shinjo M, Kishida S, Kadomatsu K
  • Journal Title: Cancer Sci. Vol.99(No.10) Pages: 2070-4
  • Peer Reviewed
• [Journal Article] Basal and stimulated lactate fluxes in primary cultures of astrocytes are differentially controlled by distinct proteins (2008)
  • Author(s): Maekawa F, Minehira K, Kadomatsu K, Pellerin L
  • Journal Title: J Neurochem Vol.107(No.3) Pages: 789-98
  • Peer Reviewed
• [Journal Article] Midkine and its clinical significance in endometrial carcinoma (2008)
  • Author(s): Tanabe K, Matsumoto M, Ikematsu S Nagase S, Hatakeyama A, Takano T, Niikura H, Ito K, Kadomatsu K, Hayashi S, Yaegashi N
  • Journal Title: Cancer Sci Vol.99(No.6) Pages: 1125-30
  • Peer Reviewed
• [Journal Article] Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells (2007)
  • Author(s): Chen S, Bu G, Takei Y, Sakamoto K, Ikematsu S, Muramatsu T, Kadomatsu K
  • Journal Title: J Cell Sci. Vol.120(No.22) Pages: 4009-15
  • Peer Reviewed
• [Journal Article] Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms (2007)
  • Author(s): Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H
  • Journal Title: Biochem Biophys Res Commun Vol.362(No.1) Pages: 218-23
  • Peer Reviewed
• [Journal Article] Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy (2007)
  • Author(s): Kosugi T, Yuzawa Y, Sato W, Arata-Kawai H, Suzuki N, Kato N, Matsuo S, Kadomatsu K
  • Journal Title: Lab Invest Vol.87(No.9) Pages: 903-13
  • Peer Reviewed
• [Journal Article] Midkine as a novel target for antibody therapy in osteosarcoma (2007)
  • Author(s): Maehara H, Kaname T, Yanagi K, Hanzawa H, Owan I, Kinjou T, Kadomatsu K, Ikematsu S, Iwamasa T, Kanaya F, Naritomi K
  • Journal Title: Biochem Biophys Res Commun Vol.358(No.3) Pages: 757-62
  • Peer Reviewed
• [Journal Article] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia (2007)
  • Author(s): Hidaka H, Yagasaki H, Takahashi Y, Hama A, Nishio N, Tanaka M, Yoshida N, Villalobos IB, Wang Y, Xu Y, Horibe K, Chen S, Kadomatsu K, Kojima S
  • Journal Title: Leuk Res. Vol.31(No.8) Pages: 1045-51
  • Peer Reviewed
• [Presentation] The combinational therapy of Bcl-xL siRNA and cisplatin in prostate cancer. Biochemistry and Molecular Biology (2008)
  • Author(s): Mu P, Kadomatsu K, Takei Y
  • Organizer: BMB2008第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-12-12
• [Presentation] アテロコラーゲンを用いたsiRNAの腫瘍特異的デリバリー (2008)
  • Author(s): 武井佳史
  • Organizer: 第67回日本癌学会総会 Meet the Expert(Luncheon Seminar)共催株式会社高研
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-29
• [Presentation] 成長因子ミッドカインの癌進展への関与 (2008)
  • Author(s): 門松健治、武井佳史、岸田聡
  • Organizer: 第67回日本癌学会総会(International session Chemokine, cytokine, and Cancer)
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-28
• [Presentation] Paclitaxel fits nicely to combine with molecular targeting cancer therapy via RNA interference (2008)
  • Author(s): Takei Y
  • Organizer: Ehrlich II-2nd World Conference on Magic BulletsCelebrating the 100th Anniversary of the Nobel Prize Award to Paul Ehrlich(Invited Talk)
  • Place of Presentation: Nurnberg, Germany
  • Year and Date: 2008-10-05
• [Presentation] In vivo delivery of siRNA by electroporation (2007)
  • Author(s): Takei Y
  • Organizer: The 21st Century Center of Excellence(COE)Program 4th International Symposium on Functional Molecules Linked to Neurodegeneration and Oncogenesis-Towards Molecular Targeted Therapy
  • Place of Presentation: Nagoya, JAPAN.
  • Year and Date: 20071025-26
• [Presentation] Monocyte chemoattractant protein-1(MCP-1)発現を減少するsiRNAによる接触性過敏反応の抑制 (2007)
  • Author(s): 石本卓嗣、武井佳史、湯澤由起夫、松尾清一、門松健治
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-12-14
• [Presentation] Bcl-xL siRNAとシスプラチンの併用による前立腺癌治療 (2007)
  • Author(s): ムー・ピン、門松健治、武井佳史
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-12-14
• [Presentation] ヒトスキルス胃癌の腹膜播種性転移を制御するmicroRNA群の解析と治療への応用 (2007)
  • Author(s): 武井佳史、柳原五吉
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-05