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Common経路とspecific経路による食道癌化学療法感受性の解析

Research Project

Project/Area Number 21659302
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

土岐 祐一郎  大阪大学, 医学系研究科, 教授 (20291445)

Co-Investigator(Kenkyū-buntansha) 瀧口 修司  大阪大学, 医学系研究科, 助教 (00301268)
藤原 義之  大阪大学, 医学系研究科, 講師 (40314330)
宮田 博志  大阪大学, 医学系研究科, 助教 (80362713)
山崎 誠  大阪大学, 医学系研究科, 助教 (50444518)
黒川 幸典  大阪大学, 医学系研究科, 助教 (10470197)
牧野 知紀  大阪大学, 医学部附属病院, 医員 (80528620)
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2009: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsDNAマイクロアレイ / 化学療法感受性 / 放射線感受性 / 食道癌 / P53
Research Abstract

昨年までの段階:食道癌化学療法感受性因子をDNAマイクロアレイによる網羅的遺伝子発現解析を用いて、発現変化の頻度は低いが、その変動(増加もしくは減少)の幅が大きく、細胞機能に強く影響すると思われる遺伝子(specific gene)を同定しようと試みた。化学療法前の生検標本を用い、12遺伝子(CD63,KRT18,FCGBP,DKKI,LRRC,BYSL,TNFSF10,ABCC2,SLC25A6,CHKB,KRT8,FN1)を感受性候補遺伝子として同定した。これらについてRT-PCRや免疫組織染色にて検証を行った。そしてこれまでにKRT18,KRT8,DKK1が新たなる感受性因子、予後因子であることを見いだしたので論文報告した。今年は新たにABCC2(=MRP2)について、免疫組織染色と細胞実験を行なった、siRNAを用いてMRP2の発現を抑制したところ、シスアラテンに対する感受性の回復を認めた。臨床研料においてもMRP2免疫染色と感受性の間に関連を認めた。これを論文報告した。(Br J Cancer, in press, 2010)。また、本研究の基本となる生検サンプルを用いてDNAチップにて感受性を予測するという研究についても報告した(Int J Oncol.37:1113-1120,2010)。また、本研究を推進するにあたり、癌間質細胞と癌細胞の遺伝子発現の違いが解析を困難にしているという事実を確認したので、マイクロダイセクションを行い、腫瘍部分の間質部分を分けて評価し、感受性因子を検索するというプロジェクトを開始した。この手法を用いてまず、FOXC2が予後因子であることを報告した。引き続いて間質部分に注目し間質にて強発現するテネイシンが新しい予後因子であること、感受性と関連することを見いだした。これについても論文投稿中である。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (19 results)

All 2010 2009

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (2 results)

  • [Journal Article] Pre- and post-therapy nodal status equally affects survival of patients with oesophageal squamous cell carcinoma receiving preoperative chemoradiation2010

    • Author(s)
      Miyata H., Yamasaki M., Takiguchi S., Nakajima K., Fujiwara Y., Mori M., Doki Y
    • Journal Title

      Oncol Rep

      Volume: 23(5) Pages: 1331-1337

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] :p53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer2010

    • Author(s)
      Makino T., Yamasaki M., Miyata H., Yoshioka S., Takiguchi S., Fujiwara Y., Nakajima K., Nishida T., Mori M., Doki Y
    • Journal Title

      Ann Surg Oncol

      Volume: 17(3) Pages: 804-811

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus.2010

    • Author(s)
      Yamasaki M., Miyata H., Fujiwara Y., Takiguchi S., Nakajima K., Nishida T., Yasuda T., Matsumiya J., Mori M., Doki Y
    • Journal Title

      Ann Surg Oncol

      Volume: 17(3) Pages: 634-642

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of the response to chemotherapy in advanced esophageal cancer by gene expression profiling of biopsy samples2010

    • Author(s)
      Motoori M., Takemasa I., Yamasaki M., Komori Y., Takeno A., Miyata H., Takiguchi S., Fujiwara Y., Yasuda T., Yano M., Matuura M., Matsubara K., Monden M., Mori M., Doki Y
    • Journal Title

      Int J Oncol

      Volume: 37 Pages: 1113-1120

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CEA-Antigen and SCC-Antigen mRNA Expression in Peripheral Blood Predict Hematogenous Recurrence After Resection in Patients with Esophageal Cancer2010

    • Author(s)
      Tanaka K., Yano M., Motoori M., KIshi K., Miyashiro I., Shingai T., Gotoh K., Nomura S., Takahashi H., Ohue M., Yamada T., Ohigashi H., Yamamoto T., Yamasaki T., Doki Y., Ishikawa O
    • Journal Title

      Ann Surg Oncol

      Volume: 17 Pages: 2779-2786

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FOXC2 is a Novel Prognostic Factor in Human Esophageal Squamous Cell Carcinoma2010

    • Author(s)
      Nishida N., Mimori K., Yokobori T., Sudo T., Tanaka F., Shibata K., Ishii H., Doki Y., Mori M.
    • Journal Title

      Ann Surg Oncol

      Volume: (in Press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer.2010

    • Author(s)
      Miyata H., Yamasaki M., Takiguchi S., Nakajima K., Fujiwara Y., Konishi K., Morii E., Mori M., Doki Y
    • Journal Title

      Ann Surg Oncol

      Volume: (in Press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Survival factors in patients with recurrence after curative resection of esophageal squamous cell carcinomas2010

    • Author(s)
      Miyata H., Yamasaki M., Kurokawa Y., Takiguchi S., Nakajima K., Fujiwara Y., Konishi K., Mori M., Doki Y
    • Journal Title

      Ann Surg Oncol

      Volume: (in Press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Utility of response evaluation to neo-adjuvant chemotherapy by (18)F-fluorodeoxyglucose-positron emission tomography in locally advanced esophageal squamous cell carcinoma2010

    • Author(s)
      Makino T., Miyata H., Yamasaki M., Fujiwara Y., Takiguchi S., Nakajima K., Higuchi I., Hatazawa J., Mori M., Doki Y
    • Journal Title

      Surgery

      Volume: 148(5) Pages: 908-918

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in esophageal squamous cell carcinoma2010

    • Author(s)
      Yamasaki M., Makino T., Masuzawa T., Kurokawa Y., Miyata H., Takiguchi S., Nakajima K., Fujiwara Y., Matsuura N., Mori M., Doki Y
    • Journal Title

      Br J Cancer

      Volume: (in Press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer.2010

    • Author(s)
      Takeno A., et. al
    • Journal Title

      Ann Surg Oncol 17(4)

      Pages: 1033-42

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 genotype predicts tesponse to chemotherapy in patients with squamous cell carcinoma of the esophagus.2009

    • Author(s)
      Yamasaki M., et. al
    • Journal Title

      Ann Surg Oncol 17(2)

      Pages: 634-42

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer.2009

    • Author(s)
      Makino T., et. al
    • Journal Title

      Ann Surg Oncol 17(3)

      Pages: 804-11

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling.2009

    • Author(s)
      Motoori M., et. al
    • Journal Title

      Int J Oncol 35(2)

      Pages: 265-71

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy.2009

    • Author(s)
      Miyata H., et. al
    • Journal Title

      Cancer 115(14)

      Pages: 3324-34

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus2009

    • Author(s)
      Makino T., et. al
    • Journal Title

      Br J Cancer 101(8)

      Pages: 1298-306

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dickkopf-1 expression as a marker for predicting clinical outcome in esophageal squamous cell carcinoma.2009

    • Author(s)
      Makino T., et. al
    • Journal Title

      Ann Surg Oncol. 16(17)

      Pages: 2058-64

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] The feasibility and effectiveness of a hand-assisted laparoscopic surgery in radical esophagectomy for patients with thoracic esophageal cancer.2010

    • Author(s)
      Yamasaki M., Miyata H., Takiguchi S., Nakajima K., Fujiwara Y., Mori M., Doki Y
    • Organizer
      12th World Congress of the International Society for Diseases of the Esophagus
    • Place of Presentation
      鹿児島
    • Related Report
      2010 Annual Research Report
  • [Presentation] Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer.2010

    • Author(s)
      Miyata H., Yamasaki M., Takiguchi S., Nakajima K., Fujiwara Y., Konishi K., Morii E., Mori M., Doki Y
    • Organizer
      12th World Congress of the International Society for Diseases of the Esophagus
    • Place of Presentation
      鹿児島
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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