Gene therapy for refractory laryngeal diseases.

• Project/Area Number: 23592545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: National Defense Medical College
• Principal Investigator: ARAKI Koji 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 病院, 講師 (70317220)
• Co-Investigator(Kenkyū-buntansha): SHIOTANI Akihiro 防衛医科大学校, 病院, 教授 (80215946)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 遺伝子治療 / 反回神経麻痺 / 喉頭気管狭窄 / 神経再生チューブ / センダイウイルスベクター / c-myc / FIR / laser-induced shock wave / センダイウイルス / 筋電図 / 神経トレーサー / 免疫抑制剤 / 気管狭窄動物モデル / LISW法

Research Abstract

We performed basic research to develop novel treatment for refractory laryngeal diseases such as (1) Recurrent laryngeal nerve (RLN) palsy and (2) Laryngotracheal stenosis (LTS).
(1) Animal model to evaluate the misdirection of nerve regeneration was established. The utility of novel nerve regeneration tube was also assessed. The basic model and techniques were established to evaluate RLN regeneration after the gene therapy for RLN palsy. (2) The rat LTS Model was established. The novel treatment for LTS using Sendai virus mediated FIR gene therapy was assessed and demonstrated preventive effect for LTS. (3) Additionally, novel gene transduction technique using LISW was also assessed and proved to be useful.

Research Products

• [Journal Article] Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in Head and Neck : Mouse Study (2014)
  • Author(s): Araki K, Mizokami D, Tomifuji M, Yamashita T, Ohnuki K, Umeda IO, Fujii H, Kosuda S, Shiotani A
  • Journal Title: Otolaryngol Head Neck Surg Volume: (Epub ahead of print)
• [Journal Article] Targeted Gene Transfer into Head and Neck Squamous Cell Carcinoma by Nanosecond Pulsed Laser-induced Stress Waves. (2014)
  • Author(s): Araki K, Mizokami D, Tanaka N, Suzuki H, Sato S, Shiotani A.
  • Journal Title: Lasers Med Sci. Volume: 29 Issue: 1 Pages: 231-238
  • DOI: 10.1007/s10103-013-1324-3
  • Peer Reviewed
• [Journal Article] Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in Head and Neck: Mouse Study. (2014)
  • Author(s): Araki K, Mizokami D, Tomifuji M, Yamashita T, Ohnuki K, Umeda IO, Fujii H, Kosuda S, Shiotani A.
  • Journal Title: Otolaryngol Head Neck Surg. Volume: Epub ahead of print Issue: 3 Pages: 589-597
  • DOI: 10.1007/s00405-013-2575-0
  • Peer Reviewed
• [Journal Article] Sendai Virus Transgene in a Novel Gene Therapy for Laryngotracheal Disease. (2013)
  • Author(s): Mizokami D, Araki K, Tanaka N, Suzuki H, Tomifuji M, Yamashita T, Inoue M, Hasegawa M, Shiotani A.
  • Journal Title: Laryngoscope Volume: 29 Issue: 7 Pages: 1717-1724
  • DOI: 10.1002/lary.23917
  • Peer Reviewed
• [Journal Article] Comparison of voice quality after laser cordectomy with that after radiotherapy or chemoradiotherapy for early glottic carcinoma. (2013)
  • Author(s): Tomifuji M, Araki K, Niwa K, Miyagawa Y, Mizokami D, Kitagawa Y, Yamashita T, Matsunobu T, Shiotani A.
  • Journal Title: ORL J Otorhinolaryngol Relat Spec Volume: 75 Issue: 1 Pages: 18-26
  • DOI: 10.1159/000346934
  • Peer Reviewed
• [Journal Article] 【甲状腺・副甲状腺診療Update】 術中反回神経モニタリング (2013)
  • Author(s): 荒木 幸仁, 塩谷 彰浩
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Volume: 85 Pages: 562-567
• [Journal Article] 嚥下手術（私の術式）「反回神経麻痺における誤嚥の外科的対応」 BIOPEX声帯内注入術 (2013)
  • Author(s): 荒木 幸仁、塩谷 彰浩、大久保 啓介
  • Journal Title: 嚥下医学 Volume: 2 Pages: 191-193
• [Journal Article] 咽喉頭・頭頸部領域の腫瘍性疾患とのどの異常感（悪性腫瘍を含む） (2013)
  • Author(s): 荒木幸仁、塩谷彰浩
  • Journal Title: ENTONI Volume: 160 Pages: 23-31
• [Journal Article] Sendai Virus Transgene in a Novel Gene Therapy for Laryngotracheal Disease (2013)
  • Author(s): Mizokami D, Araki K, Tanaka N, Suzuki H, Tomifuji M, Yamashita T, Inoue M, Hasegawa M, Shiotani A.
  • Journal Title: Laryngoscope Volume: 000
  • Peer Reviewed
• [Journal Article] Targeted gene transfer into rat facial muscles by nanosecond pulsed laser-induced stress waves. (2011)
  • Author(s): Kurita A, Matsunobu T, Satoh Y, Ando T, Sato S, Obara M, Shiotani A
  • Journal Title: J Biomed Opt. Volume: 16 Pages: 98002-98002
  • Peer Reviewed
• [Journal Article] Two Cases Involving the Use of Composite Hyoid Interposition Grafts for Laryngotracheal Stenosis
  • Author(s): Mizokami D, Araki K, Tomifuji M, Mori Y, Shiotani A
  • Journal Title: ORL J Otorhinolaryngol Relat Spec Volume: (In press)
• [Presentation] 非伝播型c―myc 転写抑制因子FIR 搭載組換えセンダイウイルスベクターによる気管狭窄の遺伝子治療 (2014)
  • Author(s): 溝上大輔、荒木幸仁、田中伸明、鈴木洋、山下拓、冨藤雅之、上田泰次、島田英昭、松下一之、塩谷彰浩
  • Organizer: 第115回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: 福岡
• [Presentation] Tacrolimus Prevent the Development of Laryngo-tracheal stenosis in the Novel Rat model (2013)
  • Author(s): Araki K, Mizokami D, Yamashita T, Tanaka N, Tomifuji M, Shiotani A
  • Organizer: 2013 AAO-HNSF Annual Meeting & OTO EXPO
  • Place of Presentation: Vancouver, Canada
• [Presentation] Feasibility Animal Study of Novel ICG Sentinel Node Detection Technique in Head and Neck Region (2013)
  • Author(s): Araki K, Mizokami D, Tomifuji M, Yamashita T, Kosuda S, and Shiotani A
  • Organizer: 2013 AAO-HNSF Annual Meeting & OTO EXPO
  • Place of Presentation: Vancouver, Canada
• [Presentation] 頭頸部癌におけるICG法によるセンチネルリンパ節生検の工夫.ICG-コロイド化法の基礎的検討 (2013)
  • Author(s): 荒木幸仁、溝上大輔、冨藤雅之、山下拓、藤井博史、小須田茂、塩谷彰浩
  • Organizer: 第15回SNNS研究会学術集会
  • Place of Presentation: 釧路
• [Presentation] Tacrolimus Prevent the Development of Laryngo-tracheal stenosis in the Novel Rat model. (2013)
  • Author(s): Araki K, Mizokami D, Yamashita T, Tanaka N, Tomifuji M, Shiotani A
  • Organizer: 2013 AAO-HNSF Annual Meeting & OTO EXPO
  • Place of Presentation: Vancouver, Canada
• [Presentation] Feasibility Animal Study of Novel ICG Sentinel Node Detection Technique in Head and Neck Region. (2013)
  • Author(s): Araki K, Mizokami D, Tomifuji M, Yamashita T, Kosuda S, and Shiotani A
  • Organizer: 2013 AAO-HNSF Annual Meeting & OTO EXPO
  • Place of Presentation: Vancouver, Canada
• [Presentation] Feasibility of novel ICG-radiocolloid sentinel node detection technique in head and neck region using animal model. (2013)
  • Author(s): S. Kosuda, K. Araki, D. Mizokami, M. Tomifuji, T. Yamashita, A. Shiotani
  • Organizer: EANM'13 - Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Lyon/FRANCE
• [Presentation] 有茎舌骨弁による喉頭気管狭窄治療 (2012)
  • Author(s): 溝上大輔,冨藤雅之,荒木幸仁,森有子,塩谷彰浩
  • Organizer: 第64回日本気管食道科学会
  • Place of Presentation: 東京
• [Presentation] Sendai Virus-Mediated Transgene Expression in the Novel Laryngo-tracheal Stenosis Model (2012)
  • Author(s): Daisuke Mizokami, Koji Araki, Nobuaki Tanaka, Hiroshi Suzuki, Tomifuji M, Makoto Inoue, Mamoru Hasegawa, Shiotani A
  • Organizer: The 92nd Annual meeting of American Laryngological Association at COSM
  • Place of Presentation: SanDiego, USA
• [Presentation] Novel gene therapy for Head&Neck Squamous cell carcinoma-Sendai Virus mediated FUSE binding protein interacting repressor (FIR) Therapy (2012)
  • Author(s): Nobuaki Tanaka, KOJI Araki, et al.
  • Organizer: 8th International Conference on Head&Neck Cancer
  • Place of Presentation: Toronto, Canada
• [Presentation] Recent Advances in Laryngology 'Gene Therapy for Laryngeal Diseases'. Symposium 3 (2012)
  • Author(s): KOJI Araki, Mizokami D, Tanaka Nobuaki, Yamashita T, Shiotani A
  • Organizer: 14th Korea Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
  • Place of Presentation: 京都
  • Invited
• [Presentation] Sendai Virus-Mediated Transgene Expression in the Novel Laryngo-tracheal Stenosis Model. (2012)
  • Author(s): Daisuke Mizokami, KOJI Araki, Nobuaki Tanaka, Hiroshi Suzuki, Tomifuji M, Makoto Inoue, Mamoru Hasegawa, Shiotani A
  • Organizer: The 92nd Annual meeting of American Laryngological Association
  • Place of Presentation: Chicago, USA
• [Presentation] Sendai Virus Vector Mediated Transgene Expression in the Larynx (2011)
  • Author(s): Daisuke Mizokami, Koji Araki, Nobuaki Tanaka, Hiroshi Suzuki, Shiotani Akihiro
  • Organizer: The 91st Annual meeting of American Laryngological Association at COSM
  • Place of Presentation: Boston, USA
• [Presentation] Sendai virus vector-mediated transgene expression in the larynx (2011)
  • Author(s): Mizokami D, Araki K, Tanaka N, Suzuki H, Tomifuji M, Inoue M, Hasegawa M, Shiotani A
  • Organizer: The 91st Annual meeting of American Laryngological Association
  • Place of Presentation: Chicago, USA
• [Presentation] センダイウイルスベクターを用いた喉頭への遺伝子導入 (2011)
  • Author(s): 溝上大輔, 荒木幸仁, 田中伸明, 鈴木洋, 井上誠, 長谷川護, 塩谷彰浩
  • Organizer: 第112回日本耳鼻咽喉科学会
  • Place of Presentation: 京都
• [Presentation] センダイウイルスベクターを用いたラット気管狭窄モデルへの遺伝子導入 (2011)
  • Author(s): 溝上大輔, 荒木幸仁, 田中伸明, 鈴木洋, 井上誠, 長谷川護, 塩谷彰浩
  • Organizer: 第63回日本気管食道科学会
  • Place of Presentation: 名古屋