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Optimisation of surgical strategy using syngenic mouse model of of metastatic neuroblastoma

Research Project

Project/Area Number 20K08988
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Sakai kohei  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (30515292)

Co-Investigator(Kenkyū-buntansha) 文野 誠久  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40405254)
田尻 達郎  九州大学, 医学研究院, 教授 (80304806)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords神経芽腫 / 転移マウスモデル / 外科切除 / 全身侵襲 / 転移 / マウスモデル / 外科治療
Outline of Research at the Start

本研究の目的は,活動性転移を有する神経芽腫において局所腫瘍切除が転移巣に及ぼす影響を明らかにすることである.申請者らの開発した転移性神経芽腫シンジェニックマウスモデルは,局所腫瘍切除後に遠隔転移を有した状態で一定期間観察が可能であり,さらに自然免疫・獲得免疫を完全に保持しており,手術に対する生体反応などの観点からより臨床に近い変化が観察可能である.腫瘍原発巣切除の転移巣に与える現象として,Concomitant tumorresistance現象との関連に着目し,局所腫瘍切除に伴う個体への免疫学的影響,転移巣の組織学的変化,化学療法と腫瘍切除のタイミングによる転移巣への影響について解析を行う.

Outline of Final Research Achievements

The aim of this study was to elucidate the effect of local tumor resection of neuroblastoma on metastases.
Tumor cells from a spontaneous mouse model of neuroblastoma were cultured in passaging and subcutaneously transplanted into allogeneic mice to generate syngeneic mice with a high rate of distant metastasis.
Comparison of the complete tumor resection group and the tumor-free group showed that complete tumor resection promoted metastasis development. A sham-operated model in which a vinyl chloride acetate sponge was implanted subcutaneously and the tumor was not resected was also compared with a partial tumor resection model, and the vinyl chloride acetate sponge group showed significantly accelerated metastatic growth. The systemic invasion itself may contribute to the metastasis-promoting effect.

Academic Significance and Societal Importance of the Research Achievements

以上の所見から,神経芽腫において,術後の慢性炎症を防ぐ(術後合併症の予防,抗炎症薬の使用)ことで転移を抑制できる可能性が示唆された.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (40 results)

All 2022 2021 2020

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (22 results) (of which Int'l Joint Research: 4 results) Book (3 results)

  • [Journal Article] Outcome of children with relapsed high-risk neuroblastoma in Japan and analysis of the role of allogeneic hematopoietic stem cell transplantation2022

    • Author(s)
      Hara Junichi、Nitani Chika、Shichino Hiroyuki、Kuroda Tatsuo、Hishiki Tomoro、Soejima Toshinori、Mori Tetsuya、Matsumoto Kimikazu、Sasahara Yoji、Iehara Tomoko、Miyamura Takako、Kosaka Yoshiyuki、Takimoto Tetsuya、Nakagawara Akira、Tajiri Tatsuro、Japan Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG)
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 52 Issue: 5 Pages: 486-492

    • DOI

      10.1093/jjco/hyac007

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model2022

    • Author(s)
      Kambe Kosuke、Iguchi Masafumi、Higashi Mayumi、Yagyu Shigeki、Fumino Shigehisa、Kishida Tsunao、Mazda Osam、Tajiri Tatsuro
    • Journal Title

      Pediatric Surgery International

      Volume: 39 Issue: 1 Pages: 43-43

    • DOI

      10.1007/s00383-022-05310-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ileocecal-Valve-Preserving Operation for the Cystic Intestinal Duplications of the Terminal Ileum: Report of Two Cases2021

    • Author(s)
      小西 快、青井 重善、山師 幸大、長野 心太、坂井 宏平、東 真弓、文野 誠久、古川 泰三、田尻 達郎
    • Journal Title

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 57 Issue: 7 Pages: 1066-1070

    • DOI

      10.11164/jjsps.57.7_1066

    • NAID

      130008131301

    • ISSN
      0288-609X, 2187-4247
    • Year and Date
      2021-12-20
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Chronic Idiopathic Constipation in Which Emergency Surgery Was Required Owing to Defecation Difficulty2021

    • Author(s)
      山師 幸大、古川 泰三、竹内 雄毅、坂井 宏平、東 真弓、文野 誠久、青井 重善、田尻 達郎
    • Journal Title

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 57 Issue: 3 Pages: 656-662

    • DOI

      10.11164/jjsps.57.3_656

    • NAID

      130008027792

    • ISSN
      0288-609X, 2187-4247
    • Year and Date
      2021-04-20
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Pediatric Case of Intestinal Obstruction Due to Stent–Stone Complex After Undergoing Cyst Incision to Treat Duodenal Duplication2021

    • Author(s)
      長野 心太、田尻 達郎、古川 泰三、竹本 正和、竹内 雄毅、坂井 宏平、東 真弓、文野 誠久、青井 重善、小西 英幸
    • Journal Title

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 57 Issue: 3 Pages: 645-651

    • DOI

      10.11164/jjsps.57.3_645

    • NAID

      130008027794

    • ISSN
      0288-609X, 2187-4247
    • Year and Date
      2021-04-20
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laparoscopic approach for abdominal neuroblastoma in Japan: results from nationwide multicenter survey2021

    • Author(s)
      Kawano Takafumi、Souzaki Ryota、Sumida Wataru、Ishimaru Tetsuya、Fujishiro Jun、Hishiki Tomoro、Kinoshita Yoshiaki、Kawashima Hiroshi、Uchida Hiroo、Tajiri Tatsuro、Yoneda Akihiro、Oue Takaharu、Kuroda Tatsuo、Koshinaga Tsugumichi、Hiyama Eiso、Nio Masaki、Inomata Yukihiro、Taguchi Tomoaki、Ieiri Satoshi
    • Journal Title

      Surgical Endoscopy

      Volume: 36 Issue: 5 Pages: 3028-3038

    • DOI

      10.1007/s00464-021-08599-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-relapse effect of trametinib on a local minimal residual disease neuroblastoma mouse model2021

    • Author(s)
      Togashi Yuichi、Tanaka Tomoko、Takemoto Masakazu、Takeuchi Yuki、Higashi Mayumi、Fumino Shigehisa、Tajiri Tatsuro
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 56 Issue: 7 Pages: 1233-1239

    • DOI

      10.1016/j.jpedsurg.2021.03.031

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The synergistic antitumor effect of combination therapy with a MEK inhibitor and YAP inhibitor on pERK-positive neuroblastoma2021

    • Author(s)
      Takemoto Masakazu、Tanaka Tomoko、Tsuji Ryota、Togashi Yuichi、Higashi Mayumi、Fumino Shigehisa、Tajiri Tatsuro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 570 Pages: 41-46

    • DOI

      10.1016/j.bbrc.2021.07.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical staining of phosphorylated-ERK in post-chemotherapeutic samples is a potential predictor of the prognosis of neuroblastoma2021

    • Author(s)
      Tanaka Tomoko、Togashi Yuichi、Takeuchi Yuki、Higashi Mayumi、Fumino Shigehisa、Tajiri Tatsuro
    • Journal Title

      Pediatric Surgery International

      Volume: 37 Issue: 2 Pages: 287-291

    • DOI

      10.1007/s00383-020-04806-w

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 局所進行性小児固形がんに対する集学的治療2021

    • Author(s)
      文野誠久,田尻達郎
    • Journal Title

      京都府立医科大学雑誌

      Volume: 130 Pages: 375-382

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【これでわかる 婦人科稀少腫瘍】卵巣腫瘍 卵黄嚢腫瘍.2021

    • Author(s)
      文野誠久,永藪和也,田尻達郎
    • Journal Title

      産科と婦人科

      Volume: 88 Pages: 212-216

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【小児外科疾患における公費負担医療の種類と申請方法】仙尾部奇形腫.2021

    • Author(s)
      文野誠久,田尻達郎
    • Journal Title

      小児外科

      Volume: 53 Pages: 286-289

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【周産期の周辺を強化する プレコンセプションケアと産後ケアの充実に向けて】他科と連携したプレコ ンセプションケアと産後ケア 内科医/小児科医との連携 移行期医療への対応 小児外科疾患.2021

    • Author(s)
      文野誠久
    • Journal Title

      周産期医学

      Volume: 51 Pages: 611-614

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【シミュレーションとナビゲーション】小児がん(リンパ管奇形を含む).2021

    • Author(s)
      文野誠久,髙山勝平,田尻達郎
    • Journal Title

      小児外科

      Volume: 53 Pages: 554-558

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maldevelopment of intrapulmonary bronchial cartilage in congenital diaphragmatic hernia2020

    • Author(s)
      Tando So、Sakai Kohei、Takayama Shohei、Fukunaga Kenji、Higashi Mayumi、Fumino Shigehisa、Aoi Shigeyoshi、Furukawa Taizo、Tajiri Tatsuro、Ogi Hiroshi、Itoh Kyoko
    • Journal Title

      Pediatric Pulmonology

      Volume: 55 Issue: 7 Pages: 1771-1780

    • DOI

      10.1002/ppul.24799

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for neuroblastoma mouse model2022

    • Author(s)
      Kambe K, Iguchi M, Higashi M, Yagyu S, Fumino S, Kishida T, Mazda O, Tajiri T
    • Organizer
      35th International Symposium on Paediatric Surgical Research (ISPSR)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Systemic inflammation on a local tumor-bearing host enhances metastatic growth in a mouse syngenic metastatic neuroblastoma model2022

    • Author(s)
      Fumino S, Yamashi K, Inoue M, Higashi M, Tajiri T
    • Organizer
      35th International Symposium on Paediatric Surgical Research (ISPSR)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小児固形悪性腫瘍に対する集学的治療における小児外科医の役割【シンポジウム;小児がん集学的治療における外科系診療科の果たす役割】2022

    • Author(s)
      文野誠久,髙山勝平,金 聖和,青井重善,古川泰三,家原知子,内藤泰行,山岸正明,井上匡美,相部則博,田尻達郎
    • Organizer
      第47回日本外科系連合学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経芽腫群腫瘍における原発巣切除に対する至適アプローチ:Open?鏡視下手術?【パネルディスカッション;小児腫瘍に対する至適アプローチ:Open vs 内視鏡外科手術】2022

    • Author(s)
      文野誠久,瀧本篤朗,三村和哉,髙山勝平
    • Organizer
      第35回日本内視鏡外科学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗GD2抗体発現遺伝子を導入した間葉系幹細胞による神経芽腫新規細胞免疫療法の開発in vitro結果2021

    • Author(s)
      Iguchi M, Maniwa J, Kambe K, Higashi M, Fumino S, Aoi S, Furukawa T, Yagyu S, Mazda O, Tajiri T
    • Organizer
      第63回日本小児血液・がん学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] L-MRDマウスモデルを用いたMEK阻害剤による神経芽腫局所微小残存病変に対する新たな治療戦略の検討2021

    • Author(s)
      富樫佑一,竹本正和,竹内雄毅,田中智子,東 真弓,文野誠久,田尻達郎
    • Organizer
      第121回日本外科学会定期学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経芽腫に対するマウス由来抗GD2抗体遺伝子導入間葉系幹細胞の開発2021

    • Author(s)
      井口雅史,馬庭淳之介,神部浩輔,東 真弓,文野誠久,青井重善,古川泰三,柳生茂希,岸田綱郎,松田 修,田尻達郎
    • Organizer
      第58回日本小児外科学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] The synergistic anti-tumor effect of combination therapy with a MEK inhibitor and YAP inhibitor on pERK-positive neuroblastoma.2021

    • Author(s)
      Takemoto M, Tanaka M, Tsuji R, Togashi Y, Higashi M, Fumino S, Tajiri T
    • Organizer
      54th Pacific Association of Pediatric Surgeons (PAPS)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗GD2抗体免疫療法と今後の展開.2021

    • Author(s)
      田尻達郎
    • Organizer
      第63回日本小児血液・がん学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Usefulness of navigation surgery for pediatric neoplastic diseases.2021

    • Author(s)
      Fumino S, Furukawa T, Aoi S, Higashi M, Kim K, Takayma S, Tajiri T
    • Organizer
      The 53rd Annual Congress of the International Society of Paediatric Oncology (SIOP)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 巨大後腹膜奇形腫の手術戦略【特別講演】2021

    • Author(s)
      田尻達郎
    • Organizer
      第121回日本外科学会定期学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 日本小児外科学会の現況と課題【理事長講演】.2021

    • Author(s)
      田尻達郎
    • Organizer
      第58回日本小児外科学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 仙尾部奇形腫の治療戦略【教育講演】.2021

    • Author(s)
      田尻達郎
    • Organizer
      第57回日本周産期・新生児医学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 胚細胞腫瘍【教育講演】2021

    • Author(s)
      文野誠久
    • Organizer
      小児外科第36回卒後教育セミナー
    • Related Report
      2021 Research-status Report
  • [Presentation] 小児期に診断された多発性内分泌腺腫症MEN2Bにおける小児外科医の包括的役割と領域横断的治療戦略【外科学再興シンポジウム;遺伝性腫瘍に対する包括的な取り組みと問題点】2021

    • Author(s)
      文野誠久,古川泰三,青井重善,坂井宏平,富樫佑一,坂野慎哉,浅野麻衣,本郷文弥,田尻達郎
    • Organizer
      第121回日本外科学会定期学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 小児領域における術中イメージングとナビゲーション【シンポジウム;小児領域における術中イメージングとナビゲーション】.2021

    • Author(s)
      髙山勝平,文野誠久,坂井宏平,東 真弓,青井重善,古川泰三,田尻達郎
    • Organizer
      第121回日本外科学会定期学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 頸部リンパ管奇形に対する積極的外科切除と集学的治療による新たな治療戦略【シンポジウム;頭頚部リンパ管腫の診断と治療】.2021

    • Author(s)
      文野誠久,古川泰三,青井重善,金 聖和,髙山勝平,杉山庸一郎,平野 滋,打谷円香,田尻達郎
    • Organizer
      第16回日本小児耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] 小児におけるネスキープを用いた被ばく低減外科治療の提案【シンポジウム;体内空間可変治療(スペーサー留置治療)の現状】.2021

    • Author(s)
      文野誠久,高木大輔,髙山勝平,金 聖和,青井重善,古川泰三,宮地 充,家原知子,相部則博,田尻達郎
    • Organizer
      日本放射線腫瘍学会第34回学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] biosheetとdirect reprogrammingによる誘導筋芽細胞による骨格筋シートの開発~腹壁欠損モデルマウスを用いて~【シンポジウム;泌尿 器・多能性幹細胞】.2021

    • Author(s)
      長野心太,文野誠久,廣畑吉昭,高山勝平,金 聖和,東 真弓,青井重善,古川泰三,岸田綱郎,松田 修,田尻達郎
    • Organizer
      第37回日本小児外科学会秋季シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 胆道閉鎖症におけるIL-13およびPeriostinの肝門部線維化への関与2021

    • Author(s)
      仙石由貴,東 真弓,永藪和也,古川泰三,髙山勝平,金 聖和,文野誠久,青井重善,田尻達郎
    • Organizer
      第48回日本胆道閉鎖症研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経芽腫転移マウスモデルにおける原発巣局所切除による微小遠隔転移巣への影響.2020

    • Author(s)
      井上真帆,富樫佑一,馬庭淳之介,文野誠久,東 真弓,土谷佳樹,小池宣也,梅村康浩,井之川仁,八木田和弘,田尻達郎
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 転移性神経芽腫syngeneic modelを用いた高リスク神経芽腫の転移巣進行要因の解析.2020

    • Author(s)
      Yamashi K, Inoue M, Higashi M, Fumino S, Furukawa T, Tajiri T
    • Organizer
      第62回日本小児血液・がん学会学術集会
    • Related Report
      2020 Research-status Report
  • [Book] Pediatric Surgical Oncology2022

    • Author(s)
      Tajiri T, Higashi M
    • Total Pages
      455
    • Publisher
      CRC Press
    • Related Report
      2022 Annual Research Report
  • [Book] 小児がん治療後の長期フォローアップガイド2021

    • Author(s)
      前田尚子、石田也寸志、文野誠久、他
    • Total Pages
      416
    • Publisher
      クリニコ出版
    • Related Report
      2021 Research-status Report
  • [Book] Introduction to Biliary Atresia2021

    • Author(s)
      Tajiri T, Furukawa T, Nio M.
    • Total Pages
      361
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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