Fundamental research for new molecular mechanism of anticancer resistance in urogenital cancer

• Project/Area Number: 18390437
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Okayama University
• Principal Investigator: NASU Yasutomo Okayama University, 大学院・医歯薬学総合研究科, 准教授 (20237572)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Masakiyo 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70379840) ; SAIKA Takashi 岡山大学, 医学部・歯学部付属病院, 講師 (10314676) ; EBARA Shin 岡山大学, 医学部・歯学部附属病院, 助手 (70379741)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥14,120,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥2,520,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
• Keywords: 腫瘍学 / 遺伝子治療学 / 薬剤耐性 / ストレス応答分子 / JNK / REIC / DKK3 / P-glycoprotein / Dkk3 / Dkk-3 / HSP70

Research Abstract

抗がん剤による治療を行った場合に、徐々にその効果が低下することは臨床上しばしば認めることであり、そのメカニズムを解明しその結果に基づき新たな治療法を開発することは極めて重要なことである.がん細胞に対してアポトーシス(細胞死)誘導するREIC/Dkk-3が耐性獲得抑制、耐性克服もしくは感受性増強のための標的となることを明らかにした.特に、REIC/Dkk-3により抗がん剤耐性獲得におけるkey moleculeであるP-glycoproteinの発現が低下することを突き止めた.

Research Products

• [Journal Article] REIC/Dkk-3overexpression downregulates P-glycoprotein in multidrug-resistant MCF7 /ADR cells and induces apoptosis in breast cancer (2008)
  • Author(s): Kawasaki K., Watanabe M., Sakaguchi M., Ogasawara Y., Ochiai K., Nasu Y., Doihara H., Kashiwakura Y., Huh N-h., Kumon H., Date H.
  • Journal Title: Cancer Gene Therapy 16 Pages: 65-75
  • Peer Reviewed
• [Journal Article] An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis (2008)
  • Author(s): Abarzua F., Kashiwakura Y., Takaoka M., Watanabe M., Ochiai K., Sakaguchi M., Iwawaki T., Tanimoto R., Nasu Y., Huh NH., Kumon H.
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 614-618
  • Peer Reviewed
• [Journal Article] N-h.Mechanistic Analysis of Resistance to REIC/Dkk-3-induced Apoptosis in Human Bladder Cancer Cells (2008)
  • Author(s): Kobayashi, T., Sakaguchi M., Tanimoto R., Abarzua, F., Takaishi M., Kaku, H. Kataoka, , K., Saika T.,Nasu Y., Miyazaki M., Kumon H., Huh
  • Journal Title: Acta Med Okayama 62 Pages: 379-384
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer (2008)
  • Author(s): Kawasaki K., Nasu Y
  • Journal Title: Cancer Gene Therapy 16 Pages: 65-75
  • Peer Reviewed
• [Journal Article] An N-terninal 78 amino acid truncation of REIC/Dkk-3 effect ively induces apoptosis (2008)
  • Author(s): Abarzua F., Nasu Y
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 614-618
  • Peer Reviewed
• [Journal Article] Mechanistic Analysis of Resistance to REIC/Dkk-3-induced Apoptosis in Human Bladder Cancer Cells (2008)
  • Author(s): Kobayashi T., Nasu Y
  • Journal Title: Ada Med Okayama 62 Pages: 379-384
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer (2007)
  • Author(s): Tanimoto R, Abarzua F, Sakaguchi M, Takaishi M, Nasu Y, Kumon H, Huh NH
  • Journal Title: Int J Mol Med. 19 Pages: 363-368
  • NAID: 10019918537
  • Peer Reviewed
• [Journal Article] Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3 (2007)
  • Author(s): Abarzua F, Sakaguchi M, Tanimoto R, Sonegawa H, Li DW, Edamura K, Kobayashi T, Watanabe M, Kashiwakura Y, Kaku H, Saika T, Nakamura K, Nasu Y, Kumon H, Huh NH
  • Journal Title: Int J Mol Med. 20 Pages: 37-43
  • Peer Reviewed
• [Journal Article] Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumo growth and metastasis in an orthotopic prostate cancer model (2007)
  • Author(s): Edamura K, Nasu Y, Takaishi M, Kobayashi T, Abarzua F, Sakaguchi M, Kashiwakura Y, Ebara S, Saika T, Watanabe M, Huh NH, Kumon H
  • Journal Title: Cancer Gene Ther. 14 Pages: 765-772
  • Peer Reviewed
• [Journal Article] Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients withlocal recurrence of prostate cancer after hormonal therapy (2007)
  • Author(s): Nasu Y, Saika T, Ebara S, Kusaka N, Kaku H, Abarzua F, Manabe D, Thompson T.C, Kumon H
  • Journal Title: Mol Ther. 15 Pages: 834-840
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer (2007)
  • Author(s): Tanimoto R. Abarzua F, Sakaguchi M, Takaishi M, Nasu Y, Kumon H, Huh NH
  • Journal Title: Int J Mol Med 19 Pages: 363-368
  • NAID: 10019918537
  • Peer Reviewed
• [Journal Article] Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients with local recurrence of prostate cancer after hormonal therapy (2007)
  • Author(s): Nasu Y, Saika T, Ebara S, Kusaka N, Kaku H, Abarzua F, Manabe D, Thompson T.C, Kumon H
  • Journal Title: Mol Ther 15 Pages: 834-840
  • Peer Reviewed
• [Journal Article] Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model (2007)
  • Author(s): Edamura K, Nasu Y, Takaishi M, Kobayashi T, Abarzua F, Sakaguchi M, Kashiwakura Y, Ebara S, Saika T, Watanabe M, Huh N.H. Kumon H
  • Journal Title: Cancer Gene Ther 14 Pages: 765-772
  • Peer Reviewed
• [Journal Article] 前立腺癌-基礎・臨床研究のアップデート-II.臨床研究 治療 遺伝子治療自殺遺伝子・サイトカイン遺伝子を用いた遺伝子治療 (2007)
  • Author(s): 賀来春紀, 那須保友, 雑賀隆史, 公文裕巳
  • Journal Title: 日本臨牀 65 Pages: 522-527
• [Journal Article] REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer (2007)
  • Author(s): Tanimoto R, Nasu Y et al.
  • Journal Title: Int J Mol Med 19 Pages: 363-8
  • NAID: 10019918537
• [Journal Article] Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3 (2007)
  • Author(s): Abarzua F, Nasu Y et al.
  • Journal Title: Int J Mol Med (In press)
• [Journal Article] Suicide gene therapy with adenoviral vector delivery of HSV-tk gene and the intravnous administration of ganciclovir for patients with local recurrence of prostate cancer after hormonal therapy (2007)
  • Author(s): Nasu Y, Saika T et al.
  • Journal Title: Molecular Therapy (In press)
• [Patent(Industrial Property Rights)] 抗癌剤耐性癌において抗癌剤増強作用を有する癌細胞死誘導剤 (2007)
  • Inventor(s): 公文裕巳、那須保友、渡部昌実、柏倉祐司、川崎賢祐
  • Industrial Property Rights Holder: 国立大学法人岡山大学、桃太郎源株式会社産業財産権の種類
  • Industrial Property Number: 2007-287373
  • Filing Date: 2007-11-05
• [Patent(Industrial Property Rights)] 抗癌剤耐性癌において抗癌剤増強作用を有する癌細胞死誘導剤。 (2007)
  • Inventor(s): 公文 裕巳
  • Industrial Property Rights Holder: 国立大学法人岡山大学
  • Industrial Property Number: 2007-287373
  • Filing Date: 2007-11-05