Mutaion analysis for desmoid type fibromatosis and research for the establishment of a novel treatment algorithm

• Project/Area Number: 26293334
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Nishida Yoshihiro 名古屋大学, 医学系研究科, 准教授 (50332698)
• Co-Investigator(Kenkyū-buntansha): 莚田 泰誠 国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (40392146) ; 生田 国大 名古屋大学, 医学部附属病院, 医員 (40732657) ; 浦川 浩 名古屋大学, 医学部附属病院, 病院講師 (60584753) ; 小澤 英史 名古屋大学, 医学部附属病院, 病院助教 (60635572) ; 新井 英介 名古屋大学, 医学部附属病院, 病院助教 (40612841) ; 濱田 俊介 名古屋大学, 医学部附属病院, 医員 (90747289)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000); Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: デスモイド / CTNNB1 / 変異 / アルゴリズム / デスモイド型線維腫症 / 臨床成績 / 遺伝子変異 / 動物モデル / オフラベル薬剤 / 医療・福祉 / 臨床 / トランスレーショナルリサーチ

Outline of Final Research Achievements

CTNNB1 analyses were achieved in over 70 cases with pathologically diagnosed as desmoid-type fibromatosis (DF). Mutational status was 41A, 45F and 45P in order of descending prevalence. Relationship between CTNNB1 mutation analysis and clinical outcome of meloxicam or simple resection was determined. Based on the results of these studies, three English papers were accepted. According to the evidence of these study, treatment algorithm was established and approved by Japanese Orthopaedic Association. This algorithm is used for establishment of clinical care guideline for DF. Genome wide association study revealed that gene X is related to the clinical outcome of low dose chemotherapy for DF. APC deficient mice is obtained and subjected to the experiment for DF-development model.

Research Products

• [Journal Article] Simple resection of truncal desmoid tumors: A case series. (2016)
  • Author(s): Nishida Y, Tsukushi S, Urakawa H, Hamada S, Kozawa E, Ikuta K, Ishiguro N.
  • Journal Title: Oncol Lett Volume: 12 Pages: 1564-1568
  • DOI: 10.3892/ol.2016.4792
  • NAID: 120005868225
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characteristics of cultured desmoid cells with different CTNNB1 mutation status. (2016)
  • Author(s): Hamada S, Urakawa H, Kozawa E, Arai E, Ikuta K, Sakai T, Ishiguro N, Nishida Y.
  • Journal Title: Cancer Med. Volume: 5(2): Pages: 352-60
  • DOI: 10.1002/cam4.582
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Low-dose chemotherapy with methotrexate and vinblastine for patients with demoid tumors: relationship to CTNNB1 mutational status. (2015)
  • Author(s): Nishida Y, Tsukushi S, Urakawa H, Hamada S, Kozawa E, Ikuta K, Ando Y, Ishiguro N.
  • Journal Title: Int J Clin Oncol Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: a pilot study. (2014)
  • Author(s): Hamada S, Futamura N, Ikuta K, Urakawa H, Kozawa E, Ishiguro N, Nishida Y.
  • Journal Title: PLoS One. Volume: 9(5):
  • DOI: 10.1371/journal.pone.0096391
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nuclear expression of β-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors. (2014)
  • Author(s): Hamada S, Urakawa H, Kozawa E, Futamura N, Ikuta K, Shimoyama Y, Nakamura S, Ishiguro N, Nishida Y.
  • Journal Title: Tumour Biol. Volume: 35(5): Pages: 4561-6
  • DOI: 10.1007/s13277-013-1600-7
  • Peer Reviewed
• [Presentation] Clinical features and treatment outcome of desmoid-type fibromatosis based on data of the bone and soft tissue tumor registry in japan (2016)
  • Author(s): Nishida Y, Akira Kawai A, Toguchida J, Ogose A, Ae K, Kunisada T, Matsunobu T, Hamada S, Sakai T
  • Organizer: 21st Annual Meeting Connective Tissue Oncology Society
  • Place of Presentation: Lisbon (Portugal)
  • Year and Date: 2016-11-09
  • Int'l Joint Research
• [Presentation] デスモイド型線維腫症における非リン酸化β-catenin免疫染色の有用性 (2016)
  • Author(s): 酒井 智久, 濱田 俊介, 生田 国大, 大田 剛広, 浦川 浩, 小澤 英史, 石黒 直樹, 西田 佳弘
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-10-13
• [Presentation] 術後再発を来した腹腔外発生デスモイド線維腫症に対する治療成績 (2016)
  • Author(s): 酒井 智久, 濱田 俊介, 浦川 浩, 小澤 英史, 生田 国大, 石黒 直樹, 西田 佳弘
  • Organizer: 第49回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 東京ドームホテル（東京都文京区）
  • Year and Date: 2016-07-14
• [Presentation] R1 resection for selected patients with extra-peritoneal desmoid-type fibromatosis (2016)
  • Author(s): Yoshihiro Nishida, Hiroshi Urakawa, Shunsuke Hamada, Eiji Kozawa, Kunihiro Ikuta, Tomohisa Sakai, Naoki Ishiguro
  • Organizer: The 29th annual meeting of the European Musculo Skeletal Oncology Society (EMSOS)
  • Place of Presentation: La Baule (France)
  • Year and Date: 2016-05-25
  • Int'l Joint Research
• [Presentation] 日整会骨・軟部腫瘍登録データに基づいたデスモイド型線維腫症の診療実態・治療成績調査 (2016)
  • Author(s): 西田 佳弘, 戸口田 淳也, 生越 章, 阿江 啓介, 国定 俊之, 松延 知哉, 濱田 俊介, 酒井 智久, 川井 章
  • Organizer: 第89回日本整形外科学会学術総会
  • Place of Presentation: パシフィコ横浜、他（神奈川県横浜市）
  • Year and Date: 2016-05-12
• [Presentation] Planned Simple Resection for Selected Patients with Desmoid-Type Fibromatosis in the Conservative Treatment Algorithm (2016)
  • Author(s): Nishida Y, Urakawa H, Hamada S, Kozawa E, Ikuta K, Sakai T, Ishiguro N
  • Organizer: The 11th Meeting of The Asia Pacific Musculoskeletal Tumour Society
  • Place of Presentation: Singapore
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] メロキシカム治療抵抗性デスモイド腫瘍患者に対するメソトレキセートとビンブラスチンによる低用量化学療法 (2015)
  • Author(s): 西田佳弘, 筑紫聡, 浦川浩, 濱田俊介, 小澤英史, 生田国大, 石黒直樹
  • Organizer: 第48回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: かがわ国際会議場、サンポートホール高松、JRホテルクレメント高松（香川県高松市）
  • Year and Date: 2015-07-09
• [Presentation] デスモイド腫瘍におけるMRIの信号強度とメロキシカム治療反応性の相関 (2015)
  • Author(s): 濱田俊介, 筑紫聡, 浦川浩, 小澤英史, 生田国大, 石黒直樹, 西田佳弘
  • Organizer: 第48回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: かがわ国際会議場、サンポートホール高松、JRホテルクレメント高松（香川県高松市）
  • Year and Date: 2015-07-09
• [Presentation] Low-dose chemotherapy with methotrexate and vinblastine for Japanese patients with desmoid tumors: Relationship to CTNNB1 mutational status. (2015)
  • Author(s): Nishida Y, Tsukushi S, Urakawa H, Hamada S, Kozawa E, Ikuta K, Ando Y, Ishiguro N.
  • Organizer: 51st Annual Meeting of the American Society of Clinical Oncology
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-05-29
  • Int'l Joint Research
• [Presentation] 孤発性デスモイド腫瘍の運動力学的環境とメロキシカムの治療効果との相関性 (2015)
  • Author(s): 濱田俊介, 西田佳弘, 筑紫聡, 浦川浩, 小澤英史, 生田国大, 石黒直樹
  • Organizer: 第88回日本整形外科学会学術総会
  • Place of Presentation: 神戸国際会議場、神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2015-05-21
• [Presentation] Treatment algorithm for sporadic desmoid tumors based on CTNNB1 mutational status. (2015)
  • Author(s): Nishida Y, Tsukushi S, Hamada S, Urakawa H, Kozawa E, Ikuta K, Ishiguro N.
  • Organizer: 2015 Annual Meeting of American Academy of Orthopaedic surgeons
  • Place of Presentation: Venetian/Sands EXPO （米国ラスベガス）
  • Year and Date: 2015-03-24 – 2015-03-28
• [Presentation] CTNNB1 mutational status directed treatment modality for patients with extra-peritoneal desmoids tumors. (2014)
  • Author(s): Nishida Y, Hamada S, Urakawa H, Ikuta K, Tsukushi S, Kozawa E, Ota T, Ishiguro N.
  • Organizer: 19th Annual meeting Connective Tissue Oncology Society
  • Place of Presentation: InterContinental Berlin Hotel（ドイツ・ベルリン）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] CTNNB1(β-catenin)遺伝子変異によるデスモイド腫瘍に対するメロキシカム治療の効果予測 (2014)
  • Author(s): 濵田俊介, 浦川浩, 小澤英史, 筑紫聡, 石黒直樹, 西田佳弘
  • Organizer: 第123回中部日本整形外科災害外科学会・学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 腫瘍径の大きなデスモイド腫瘍に対する治療アルゴリズム (2014)
  • Author(s): 西田佳弘, 筑紫聡, 浦川浩, 小澤英史, 新井英介, 二村尚久, 濵田俊介, 生田国大, 石黒直樹
  • Organizer: 第47回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] デスモイド腫瘍に対するメロキシカム治療の効果予測 CTNNB1(β-catenin)遺伝子変異による (2014)
  • Author(s): 濵田俊介, 浦川浩, 新井英介, 小澤英史, 二村尚久, 生田国大, 筑紫聡, 石黒直樹, 西田佳弘
  • Organizer: 第47回日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] Treatment algorithm for patients with desmoid tumors: Key to an “enigma” tumor (2014)
  • Author(s): Nishida Y.
  • Organizer: 2014 Catholic University International Symposium of Musculoskeletal Oncology and Case Conference of KBJTS
  • Place of Presentation: The Catholic University of Korea（韓国ソウル）
  • Year and Date: 2014-06-13
  • Invited
• [Presentation] MTX and VBL treatment for patients with desmoid tumors resistant to meloxicam treatment: Relationship between efficacy and CTNNB1 mutation status. (2014)
  • Author(s): Nishida Y, Hamada S, Tsukushi S, Urakawa H, Ishiguro N, Ando Y.
  • Organizer: American Society of Clinical Oncology Annual ’14 Meeting
  • Place of Presentation: McCormick Place（米国シカゴ）
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] デスモイド治療のアルゴリズム：メロキシカム抵抗性デスモイド腫瘍 (2014)
  • Author(s): 西田佳弘, 筑紫聡, 浦川浩, 小澤英史, 新井英介, 二村尚久, 濵田俊介, 生田国大, 石黒直樹
  • Organizer: 第87回日本整形外科学会学術総会
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場、神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-05-22 – 2014-05-25
• [Book] 肉腫化学療法マスタークラス (2015)
  • Author(s): 西田佳弘、川井章、遠藤誠、岩本幸英、尾崎敏文、細井創、宮地充、田仲和宏、安藤正志、石井猛、中馬広一、杉原進介、小林英介、下井辰徳、米盛勧、髙橋俊二、久保寿夫、田端雅弘、松田正典、他
  • Total Pages: 366
  • Publisher: 南山堂