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BASIC RESEARCH OF ORAL CANCER THERAPY TARGETING TO THE EGF RECEPTOR AND ITS SIGNAL TRANSDUCTIONAL MOLECULES.

Research Project

Project/Area Number 15390610
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionGIFU UNIVERSITY

Principal Investigator

SHIBATA Toshiyuki  GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFFESOR, 大学院・医学系研究科, 教授 (50226172)

Co-Investigator(Kenkyū-buntansha) HAMADA Junichi  HOKKAIDO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATED PROFFESOR, 大学院・医学研究科, 助教授 (50192703)
TOIDA Makoto  GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATED PROFFESOR, 大学院・医学系研究科, 助教授 (90313890)
YAMASHITA Tomomi  GIFU UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT PROFFESOR, 医学部附属病院, 講師 (80345793)
MAKITA Hiroki  GIFU UNIVERSITY, UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (50345790)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsSCC / HUMAN / EGF / INVASION / EGF RECEPTOR / PKC
Research Abstract

Our previous studies revealed that EGF enhanced the random motility of oral squamous cell carcinoma cell lines in a dose-dependent fashion and exposure to EGF let to an increased production of urokinase type plasminogen activator and matrix metalloproteniase-9 by the same cells. These results strongly suggest the EGF may promote the invasion and metastasis of human oral squamous cell carcinomas. In this project, to reveal the signal pathway concerning the cell motility and inhibiting effects of signal pathway, we established s-1 clone cells from Ca9-22 cell line, which was most sensitive clone against the EGF stimulation and also we established i-1 clone cells, which was most insensitive clone. Further studies were done using s-1 clone cells. When EGF bind to the EGF receptor, tyrosine phosphorelation is firstly occurred and subsequently PKC is activated through the activation of PLCr arising from erbB homodimer and/or activation of PI3-kinase arising from erbB3 heterodimer. Furthermore, erbB homodimer activates the nPKCd through the activation of PLC and also erbB/erbB-3 heterodimer activates aPKCe through the activation of PI3K. These results suggest that inhibition of aPKCe or nPKCd can reduce the invasion and metastasis of human oral cancer cells and that the useful model in the investigations of molecular target medicines is possibly established. Furthermore, as an auspicious candidate of new target molecules, aPKCe and nPKCd were closed up. Especially, these molecles were more specific than EGF receptor, PI3K, and so on, which recently developed molecular target medicines.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005 2004 Other

All Journal Article (27 results) Publications (6 results)

  • [Journal Article] siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells.2006

    • Author(s)
      Tanaka H, Shirkoohi R, Nakagawa K, Oiao H, Fujita H, Okada F, Hamada J, et al-3
    • Journal Title

      Int J Cancer. 118

      Pages: 1680-1691

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibitory effects of fermented brown rice and rice bran on the development of acute hepatitis in Long-Evans Cinnamon rats.2006

    • Author(s)
      Shibata T, et al.-7
    • Journal Title

      Oncol Rep. 15(4)

      Pages: 869-867

    • NAID

      120006340757

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Preoperative radiotherapy contributes to induction of proliferative activity of CD8+ tumor-infiltrating T-cells in oral squamous cell carcinoma.2006

    • Author(s)
      Suwa T, Saio M, Umemura N, Yamashita T, Toida M, Shibata T, Takami T.
    • Journal Title

      Oncol Rep. 15(4)

      Pages: 757-763

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Disordered expression of HOX genes in human non-small cell lung cancer.2006

    • Author(s)
      Abe M, Hamada J, Takahashi O, Takahashi Y, Tada M, Miyamoto M, Morikawa T, Kondo S, Moriuchi T.
    • Journal Title

      Oncol Rep. 15(4)

      Pages: 797-802

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] siRNA gelsolin knockdown induces epithelial-mesenchymal transition with cadherin switch in human mammary epithelial cells.2006

    • Author(s)
      Tanaka H, Shirkoohi R, Nakagawa K, Oiao H, Fujita H, Okada F, Hamada J, et al.-3
    • Journal Title

      Int J Cancer. 118

      Pages: 1680-1691

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of ameloblastomas by comparative genomic hybridization and fluorescence in situ hybridization2005

    • Author(s)
      Toida M, Balazs M, et al-7, Shibata T, Adany R.
    • Journal Title

      Cancer Genet Cytogenet. 159

      Pages: 99-104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats2005

    • Author(s)
      Yoshida K, Tanaka T, et al--6, Shibata T, Mori H.
    • Journal Title

      Cancer Lett 221

      Pages: 29-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte-derived dendritic cells2005

    • Author(s)
      Zhao W, Darmanin S, Fu O, Okada F, Hamada J, et al. 3.
    • Journal Title

      Eur J Immunol. 35

      Pages: 3468-3477

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aberrant expression of HOX genes in human invasive breast carcinoma2005

    • Author(s)
      Makiyama K, Hamada J, et al-12
    • Journal Title

      Oncol Rep. 13

      Pages: 673-679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered expressions of HOX genes in human cutaneous malignant melanoma2005

    • Author(s)
      Maeda K, Hamada J, et al-5
    • Journal Title

      Int J Cancer. 114

      Pages: 436-441

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of ameloblastomas by comparative genomic hybridization and fluorescence in situ hybridization.2005

    • Author(s)
      Toida M, Shimokawa K, Makita H, Kato K, Kobayashi A, Kusunoki Y, Hatakeyama D, Fujitsuka H, Yamashita T, Shibata T.
    • Journal Title

      Cancer Genet Cytogenet. 159(2)

      Pages: 99-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats.2005

    • Author(s)
      Yoshida K, Tanaka T, Hirose Y, Yamaguchi F, Kohno H, Toida M, Hara A, Sugie S, Shibata T, Mori H.
    • Journal Title

      Cancer Lett. 221(1)

      Pages: 29-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas : manifestation and localization of their activity.2005

    • Author(s)
      Kato K, Hara A, Kuno T, Kitaori N, Huilan Z, Mori H, Toida M, Shibata T.
    • Journal Title

      J Cancer Res Clin Oncol. 131(6)

      Pages: 340-346

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte-derived dendritic cells.2005

    • Author(s)
      Zhao W, Darmanin S, Fu Q, Chen J, Cui H, Wang J, Okada F, Hamada J, Hattori Y, Kondo T, Hamuro J, Asaka M, Kobayashi M.
    • Journal Title

      Eur J Immunol. 35(12)

      Pages: 3468-3477

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered expressions of HOX genes in human cutaneous malignant melanoma.2005

    • Author(s)
      Maeda K, Hamada J, Takahashi Y, Tada M, Yamamoto Y, Sugihara T, Moriuchi T.
    • Journal Title

      Int J Cancer. 114(3)

      Pages: 436-441

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of ameloblastomas by comparative genomic hybridization and fluorescence in situ hybridization2005

    • Author(s)
      Toida M, Balazs M, et al.-7, Shibata T, Adany R.
    • Journal Title

      Cancer Genet Cytogenet. 159

      Pages: 99-104

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats.2005

    • Author(s)
      Yoshida K, Tanaka T, et al.-6, Shibata T, Mori H.
    • Journal Title

      Cancer Lett. 221

      Pages: 29-39

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte-derived dendritic cells2005

    • Author(s)
      Zhao W, Darmanin S, Fu O, Okada F Hamada J, et al.3.
    • Journal Title

      Eur J Immunol. 35

      Pages: 3468-3477

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression of HOX genes in human invasive breast carcinoma.2005

    • Author(s)
      Makiyama K, Hamada J, et al.-12
    • Journal Title

      Oncol Rep. 13

      Pages: 673-679

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Altered expressions of HOX genes in human cutaneous malignant melanoma2005

    • Author(s)
      Maeda K, Hamada J, et al.-5
    • Journal Title

      Int J Cancer. 114

      Pages: 436-441

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of Ameloblastomas by comparative genomic hybridization and fluore scence in situ hybridyzation2005

    • Author(s)
      M.Toida, M.Balazs, A.Treszl, T.Shibata R.Adany
    • Journal Title

      Cancer Genetics and Cytogenetics (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Matrix matalloproteinase 2 and 9 in oral squamous cell carcinomas : manifestation and localization of their activity2005

    • Author(s)
      K.Kato, T.Shibata, et al.
    • Journal Title

      Journal of cancer research and clinical oncology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of SAPK/JNK in prostaglandin E(1)-induced VEGF synthesis in osteoblast-like cells.2004

    • Author(s)
      Kanno Y, Tokuda H, Nakajima K, Ishisaki A, Shibata T, Numata O, Kozawa O.
    • Journal Title

      Mol Cell Endocrinol. 220(1-2)

      Pages: 89-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of p38 mitogen-activated protein kinase mediates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.2004

    • Author(s)
      Ishisaki A, Tokuda H, Yoshida M, Hirade K, Kunieda K, Hatakeyama D, Shibata T, Kozawa O.
    • Journal Title

      Mol Cell Endocrinol. 214(1-2)

      Pages: 189-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of SAPK/JNK in prostaglandin E1-induced VEGF synthesis in osteoblast-like cells2004

    • Author(s)
      Y.Kanno, H.Tukuda, K.Nakajima, A.Ishisaki, T.Shibata, O.Mumata
    • Journal Title

      Molecular and Cellular Endocrinology 220

      Pages: 89-95

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint2004

    • Author(s)
      M.Tomida, J.-I.Ishimaru, M.Kurachi S.Era, T.Shibata
    • Journal Title

      British J Oral and Maxillofacial Surgery 42

      Pages: 405-409

    • Related Report
      2004 Annual Research Report
  • [Journal Article] がんの化学予防:口腔がん2004

    • Author(s)
      柴田敏之
    • Journal Title

      最新医学 59巻11号

      Pages: 2447-2453

    • Related Report
      2004 Annual Research Report
  • [Publications] J.ISHIMARU, N.OGI, T.MIZUI, K.MIYAMOTO, T.SHIBATA, K.KURITA: "Effect of a single arthrocentesis and a COX-2 inhibitor on disorders of temporomandibular joints. A preliminary clinical study"British Journal of Oral and Maxillofacial Surgery. 41. 323-328 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.KITAJO, T.SHIBATA, H.NAGAYASU, T.KAWANO, J.HAMADA, T.YAMASHITA: "Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells"Oncology Reports. 10. 1351-1356 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.TOIDA, T.HASEGAWA, F.WATANABE, K.KATO, H.MAKITA, T.SHIBATA: "Lobular capillary hemangioma of the oral mucosa : clinicopathological study of 43 cases-"Pathology International. 53. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.TOKUDA, D.HATAKEYAMA, M.YOSHIDA, T.SHIBATA, O.KOZAWA: "Involvement of MAP kinases in TGF-beta-stimulated vascular endothelial growth factor synthesis in osteoblasts"Arch.Biochem.Biophys.. 415. 117-125 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.TOKUDA, D.HATAKEYAMA, T.SHIBATA, O.KOZAWA: "p38 MAP kinases regulates BMP-4-stimulated VEGF synthesis via p70 S6 kinase in osteoblasts"Am.J.Physiol.Endocrynol.Metab.. 284. 1202-1209 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K YOSHIDA, Y HIROSE, T TANAKA, K SAKATA, S SUGIE, T SHIBATA, H MORI: "Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-NQO"Cancer Science. 94. 365-371 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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