Mechanism of cell death and development of a new therapy against noise-induced hearing loss

• Project/Area Number: 23592482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kobe University
• Principal Investigator: YAMASHITA Daisuke 神戸大学, 医学部附属病院, 准教授 (60306785)
• Co-Investigator(Kenkyū-buntansha): KANZAKI Sho 慶応義塾大学, 医学部付属病院, 講師 (50286556) ; FUJITA Takeshi 神戸大学, 医学部付属病院, 特定助教 (90533711)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 内耳 / 再生 / アポトーシス / 音響外傷 / 細胞死 / メタボローム解析

Research Abstract

We first manufactured the animal models that became hearing loss induced by intense noise. In the hearing loss animal model, we elucidated the mechanism which led to the cell death (apoptosis) of inner hair cells. Finally, based on these results, we examined the method that hearing loss was treated by various kinds of approaches, and the results that might cure hearing loss in the both sides where were in hearing function / inner ear morphology were obtained.

Research Products

• [Journal Article] Serum and tissue metabolomics of head and neck cancer (2013)
  • Author(s): Yonezawa K, Nishiumi S, Kitamoto-Matsuda J, Fujita T, Morimoto K, Yamashita D, Saito M, Otsuki N, Irino Y, Shinohara M, Yoshida M, Nimu KI
  • Journal Title: Cancer Genomics & Proteomics Volume: 10(5) Pages: 233-238
• [Journal Article] 耳下腺に発症したメトトレキサート関連リンパ増殖性疾患の2例 (2013)
  • Author(s): 四宮瞳、四宮弘隆、長谷川信吾、山下大介、大月直樹、丹生健一
  • Journal Title: 耳鼻咽喉科・頭頚部外科 Volume: 85(13) Pages: 1093-1097
• [Journal Article] 頸部リンパ節転移を認めた原発不明悪性黒色腫の2例米 (2013)
  • Author(s): 澤宏一郎、森本浩一、山下大介、谷本均、齋藤幹、大月直樹、清田尚臣、佐々木良一、丹生健一
  • Journal Title: 頭頸部癌 Volume: 39(1) Pages: 72-76
• [Journal Article] Serum and tissue metabolomics of head and neck cancer (2013)
  • Author(s): Yonezawa K, Nishiumi S, Kitamoto-Matsuda J, Fujita T, Morimoto K, Yamashita D, Saito M, Otsuki N, Irino Y, Shinohara M, Yoshida M, Niｂu KI.
  • Journal Title: Cancer Genomics & Proteomics. Volume: 10(5) Pages: 233-238
  • Peer Reviewed
• [Journal Article] Increased inner ear susceptibility to noise injury in mice with streptozosin-induced diabetes (2012)
  • Author(s): Fujita T, Yamashita D, Katsunuma S, Hasegawa S, Tanimoto H, Nibu KI.
  • Journal Title: Diabetes Volume: 61 Pages: 1-7
• [Journal Article] Increased inner ear susceptibility to noise injury in mice with streptozotocin-induced diabetes (2012)
  • Author(s): Fujita T, Yamashita D, Katsunuma S, Hasegawa S, Tanimoto H, Nibu K.
  • Journal Title: Diabetes Volume: 61 Issue: 11 Pages: 2980-2986
  • DOI: 10.2337/db11-1845
  • Peer Reviewed
• [Journal Article] Noise-induced apoptosis in fibrocytes of the cochlear spiral limbus of mice (2011)
  • Author(s): Cui Y, Sun G, Yamashita D, Kanzaki S, Matsunaga T, Fujii M, Kaga K, Ogawa K.
  • Journal Title: European Arch. Oto Volume: 268(7) Pages: 973-978
• [Journal Article] Oral candidiasis mimicking tongue cancer (2011)
  • Author(s): Shibata T, Yamashita D, Hasegawa S, Saito M, Otsuki N, Hashikawa K, Tahara S, Nibu K
  • Journal Title: Auris Nasus Larynx Volume: 38(3) Pages: 418-420
• [Journal Article] 耳下腺癌における予防的頸部郭清と術後放射線治療について (2011)
  • Author(s): 柴田智久、米澤宏一郎、森本浩一、山下大介、大月直樹、西村英輝、佐々木良平、丹生健一
  • Journal Title: 頭頸部癌 Volume: 37(1) Pages: 78-82
  • NAID: 10030814927
• [Journal Article] Noise-induced apoptosis in fibrocytes of the cochlear spiral limbus of mice. (2011)
  • Author(s): Cui Y, Sun G, Yamashita D, Kanzaki S, Matsunaga T, Fujii M, Kaga K, Ogawa K.
  • Journal Title: European Arch. Oto. Volume: 268(7) Pages: 973-978
  • Peer Reviewed
• [Presentation] Hearing loss in Xeroderma pigmentosum and mechanism of inner ear disorder (2014)
  • Author(s): Yamashita D, Fujita T, Otsuki N, Sakai Y, Kanda F, Nishigori C, Nibu KI
  • Organizer: International Symposium on Xeroderma pigmentosum and Related Disease
  • Place of Presentation: Kobe Japan
  • Year and Date: 2014-03-07
• [Presentation] Metabolome analysis of inner ear fluid in guinea pigs cochlea after intense noise. (2014)
  • Author(s): Yamashita D, Fikuda Y, Fujita T, Shinomiya H, Inokuchi G, Hasegawa S, Otsuki N, Nibu KI
  • Organizer: Association for Research in Otolaryngology meeting (37^<th> )
  • Place of Presentation: USA
  • Year and Date: 2014-02-24
• [Presentation] High-Fat Diets Delay the Progression of Age-Related Hearing Loss in C57BL/6J Mice (2014)
  • Author(s): Fujita T, Yamashita D, Hasegawa S, Nibu KI
  • Organizer: Association for Research in Otolaryngology meeting (37^<th>
  • Place of Presentation: USA
  • Year and Date: 2014-02-23
• [Presentation] Metabolome analysis of inner ear fluid in guinea pigs cochlea after intense noise (2014)
  • Author(s): Yamashita D, Fikuda Y, Fujita T, Shinomiya H, Inokuchi G, Hasegawa S, Otsuki N, Nibu KI.
  • Organizer: Association for Research in Otolaryngology meeting
  • Place of Presentation: USA
• [Presentation] High-Fat Diets Delay the Progression of Age-Related Hearing Loss in C57BL/6J Mice. (2014)
  • Author(s): Fujita T, Yamashita D, Hasegawa S, Nibu KI.
  • Organizer: Association for Research in Otolaryngology meeting
  • Place of Presentation: USA
• [Presentation] Hearing loss in Xeroderma pigmentosum and mechanism of inner ear disorder (2014)
  • Author(s): Yamashita D, Fujita T, Otsuki N, Sakai Y, Kanda F, Nishigori C, Nibu KI
  • Organizer: International Symposium on Xeroderma pigmentosum and Related Disease
  • Place of Presentation: Japan
• [Presentation] 5-year experience with primary major salivary gland carcinoma at a single institution in Japan (2013)
  • Author(s): Imamura Y, Kiyota N, Ohtsuki N, Hirai C, Funakoshi Y, Mukohara T, Yamashita D, Itoh T, Minami H, Nibu KI
  • Organizer: The European Cancer Congress Organization (8^<th> )
  • Place of Presentation: Belgium
  • Year and Date: 2013-10-01
• [Presentation] Metabolome analysis of inner ear fluid in guinea pigs cochlea (2013)
  • Author(s): Yamashita D, Fujita T, Hashimoto Y, Shinomiya H, Hasegawa S, Nibu KI.
  • Organizer: Association for Research in Otolaryngology meeting (36^<th> USA)
  • Place of Presentation: USA
  • Year and Date: 2013-02-18
• [Presentation] Clinical feature and prognosis of hearing impairment due to meningeal carcinomatosis (2013)
  • Author(s): Inokuchi G, Komatsu H, Sawada N, Yamashita D, Kumoi K
  • Organizer: Association for Research in Otolaryngology meeting (36^<th> USA)
  • Place of Presentation: USA
  • Year and Date: 2013-02-17
• [Presentation] Hearing impairments and cochlear changes in Type1 diabetes model mice and diet-induced obesity mice (2013)
  • Author(s): Fujita T, Yamashita D, Katsunuma S, Tanimoto H, Hasegawa S, Nibu KI.
  • Organizer: Association for Research in Otolaryngology meeting (36^<th> USA)
  • Place of Presentation: USA
  • Year and Date: 2013-02-16
• [Presentation] Managenet outcome following lateral temporal bone resection for cancer of external auditory canal (2012)
  • Author(s): Hasegawa S, Yamashita D, Fujita T, Nibu KI.
  • Organizer: International Conference on Cholesteatoma and Ear Surgery (9^<th> Nagasaki)
  • Place of Presentation: Nagasaki
  • Year and Date: 2012-06-03
• [Presentation] Congenital middle ear cholesteatoma in children; retrospective review (2012)
  • Author(s): Fujita T, Hasegawa S, Yamashita D, Nibu KI.
  • Organizer: International Conference on Cholesteatoma and Ear Surgery (9^<th> Nagasaki)
  • Place of Presentation: Nagasaki
  • Year and Date: 2012-06-03
• [Presentation] Hearing loss and mechanism in xeroderma pigmentosum (XP) (2012)
  • Author(s): Yamashita D, Fujita T, Hasegawa S, Otsuki N, Nibu KI
  • Organizer: East Asian Symposium on Otology (3th Nagasaki)
  • Place of Presentation: Nagasaki
  • Year and Date: 2012-06-01
• [Presentation] Subtotal temporal bone resection for the recurrent external auditory canal cancer after proton beam therapy : case report (2012)
  • Author(s): Sawada N, Hsegawa S, Morimoto K, Yamashita D, Tahara S, Nibu KI.
  • Organizer: East Asian Symposium on Otology (3th Nagasaki)
  • Place of Presentation: Nagasaki
  • Year and Date: 2012-06-01
• [Presentation] Mechanism and Protection Against Noise-Induced Hearing Loss (2012)
  • Author(s): Yamashita D, Kanzaki S, Ogawa K, Nibu K
  • Organizer: Japan-Korea Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2012-04-13
• [Presentation] Vulnerability for noise injury of inner era in diabetic model mice (2012)
  • Author(s): Fujita T, Yamashita D, Katsunuma S, Hasegawa S, Tanimoto H, Nibu K
  • Organizer: Japan-Korea Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2012-04-13
• [Presentation] Hearing impairments and cochlear changes in Type1 diabetes model mice (2012)
  • Author(s): Fujita T, Yamashita D, Katsunuma S, Tanimoto H, Hasegawa S, Nibu KI.
  • Organizer: Association for Research in Otolaryngology meeting (35^<th> USA)
  • Place of Presentation: USA
  • Year and Date: 2012-02-27
• [Presentation] Hearing loss in Xeroderma pigmentosum (XP) and mechanism of inner ear disorder (2012)
  • Author(s): Yamashita D, Fujita T, Hasegawa S, Otsuki N, Nibu KI
  • Organizer: Association for Research in Otolaryngology meeting (35^<th> USA)
  • Place of Presentation: USA
  • Year and Date: 2012-02-26
• [Presentation] Mechanism and Protection Against Noise-Induced Hearing Loss (2012)
  • Author(s): Yamashita D, Kanzaki S, Ogawa K, Nibu K
  • Organizer: Japan-Korea Joint Meeting of Otorihnolaryngology-Head and Neck Surgery
  • Place of Presentation: Kyoto
• [Presentation] Mechanism and Protection Against Noise-Induced Hearing Loss (2011)
  • Author(s): Yamashita D, Kanzaki S, Ogawa K, Nibu K.
  • Organizer: 11th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Kobe Japan
  • Year and Date: 2011-12-08
• [Presentation] Mechanism and Strategy to Prevent Noise-Induced Hearing Loss (2011)
  • Author(s): Yamashita D
  • Organizer: KANSAI RESEARCH SEMINAR for 80^<th> Anniversary of ENT
  • Place of Presentation: Osaka Japan
  • Year and Date: 2011-11-12
• [Presentation] Mechanism and Protection Against Noise-Induced Hearing Loss (2011)
  • Author(s): Yamashita D, Kanzaki S, Ogawa K, Nibu K
  • Organizer: 11th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery(招待講演)
  • Place of Presentation: Kobe-Hyogo, Japan（ANAクラウンプラザホテル神戸）
• [Book] 耳鼻咽喉科領域のジェネリック薬品特集・耳鼻咽喉科領域のジェネリック薬品とサプリメント (2013)
  • Author(s): 山下大介
  • Publisher: 山下大介耳鼻咽喉科・頭頸部外科
• [Book] 特集これだけは知っておきたい麻酔の知識局所麻酔手術の総論 (2012)
  • Author(s): 山下大介
  • Publisher: 東京医学社1
• [Book] 線維素性唾液管炎最新の診療NAVI(日常診療必携) (2012)
  • Author(s): 山下大介、小川郁
  • Publisher: 丹生健一耳鼻咽喉科・頭頸部外科84(5)
• [Book] 手足口病特集口腔内ウィルス感染の診断と治療 (2011)
  • Author(s): 山下大介、丹生健一
  • Publisher: ヘルパンギーナ