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Gene therapy for oral cancer by cell cycle regulators and tumor vaccine genetically mokified to secrete cytokines.

Research Project

Project/Area Number 13557174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YAMAGUCHI Satoshi  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 大学院・医歯学総合研究科, 助手 (00280628)

Co-Investigator(Kenkyū-buntansha) YAMADA Schumpei  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 大学院・医歯学総合研究科, 助手 (60302890)
ARAI Naoya  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 大学院・医歯学総合研究科, 助手 (80323723)
NIINAKA Yasufumi  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 大学院・医歯学総合研究科, 助手 (80361715)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywordsoral cancer / cell cycle / cytokine / vaccine / gene therapy / cyclin / AMF / 免疫
Research Abstract

1)The effect of p53, p33 or p27 gene transfer by adenoviral vector were investigated in oral squamous cell carcinoma cell lines, HSC3,4. Overexpression of p53 induced apoptosis in both of cell lines, and overexpression of p27 suppressed cell growth in both cell lines. But, overexpression of p33 did not affect cell growth Furthermore, direct injection of p53 into established s.c. xenogiaft of HSC3 in nude mice inhibited tumor growth.
2)The V-ATPase inhibitors concanamycin A induced apoptosis in human oral squamous cell carcinoma cell lines, HSC2,3,4. Furthermore, direct injection of concanamycin A into established s.c. xenograft of HSC3 in nude mice inhibited tumor growth. These-results showed the potential of concanamycin A as anticancer drug on oral squamous cell carcinoma
3)Vaccination with irradiated tumor cells genetically modified to secrete cytokines were studied using murine oral squamous cell line, sq1979. The murine cDNA of II2, IL4, IL10, GM-CSF, TNF-α, IFN-γ were tmafered into … More sq1970 by retrovairal vector. We found that irradiated tumor cells expressing GM-CSF or IFN-γ suppressed the growth of parental sg1979 cells in vivo.
4)We examined the expression profile of cyclin E1 and E2 in human oral squamous cell carcinoma cell lines, and found that the expression of cyclin E1 protein were hardly detected in HSC2. Although cyclin E2 was abundantly expressed, histone H1 kinase activities of both type of cyclin were undetectable in HSC2. Inhibition of cyclin E1 nor E2 suppressed the growth of HSC2. In contrast, HSC2 expressed cyclin D1 and hyperphosphorelated form of Rb protein family, and were arrested in G1 by overexpression of p16. These results indicate hat HSC2 lost proper growth control specifically mediated by cyclin E and suggest that deregulation of its downstream pathway contribute to tumorigenesis of SCC.
5)We investigated the characterization of a high-metastatic cell line LMF4 and a low-metastatic cell line HSC3 in comparison with non-metatic cell line HSC2 and HSC4. Morphological and motility analyses revealed LMF4 to have the highest motility, but LMF4 shared the similar features with HSC3, high level secretion Autocrone Motility Factor (AMF), enhancement of gp78 expression, co-expression of vimentin and cytokeratin. AMF-transfected HSC3 augmented the AMF-R and vimentin expression, but abrogated cytokeratin expression.
6)The correlation between expression of pRb2/p130 and clinicopathologic factors in oral squamous cell carcinoma was studied. Expression of pRb2/p130 may be a good prognostic indicator in patients with oral squamous cell carcinoma and also may be utilized for the subclassification of tumors with Grade 3 mode of invasion.
7)The clinicopathological studies on sarcomas of oral and maxillofacial region and late metastasis in patients with Stage I〜II tongue squamous cell carcinoma was performed Adequate excision with safety surgical margin as the initial therapy is important for better survival in treatment of sarcoma. The pattern of invasion at the invasive font and invasive front grading score had predictive values for late nodal metastasis. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All 2004 2003 2002 2001 Other

All Journal Article (15 results) Publications (2 results)

  • [Journal Article] Sarcomas of the oral and maxillofacial region, a review of 32 cases in 25 years2004

    • Author(s)
      Yamaguchi S, Nagasawa H et al.
    • Journal Title

      Clinical Oral Investigation 8

      Pages: 52-55

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Loss of cyclin E requirement in cell growth of an oral squamous cell line Implies deregulation of its downstream pathway2004

    • Author(s)
      Yamada S, Sumrejkanchankij P et al.
    • Journal Title

      International Journal of Cancer 111

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Sarsomas of the oral and maxillofacial region, a review of 32 cases in 25 years.2004

    • Author(s)
      Yamaguchi S, Nagasawa H, Suzuki T, Fujii E, Iwaki H, Takage M, Amagasa T
    • Journal Title

      Clin Oral Invest. 8

      Pages: 52-55

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Loss of cyclin E requirement in cell growth of an oral squamous cell carcinoma cell line implies deregulation of its downstream pathway.2004

    • Author(s)
      Yamada S, Sumrejkanchankij P, Amagasa T, Ikeda M
    • Journal Title

      Int J Cancer. 111

      Pages: 17-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Axillary nodal metastasis from oral and maxilofacial cancer, A report of 3 cases.2004

    • Author(s)
      Aung Lwin Oo, Yamaguchi S, Iwaki H, Amagasa T
    • Journal Title

      J oral Maxillofac Surg. 62

      Pages: 1019-1024

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Pattern of invasion and invasive front grading score as predictive factors of late cervical lymph node metastasis in surgically treated stage I〜II tongue carcinoma.2003

    • Author(s)
      Aung Lwin Oo, Yamaguchi S, et al.
    • Journal Title

      Oral Medicine and Pathology 8

      Pages: 117-124

    • NAID

      110006792257

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Autocrine motility factor signaling induces tumor apoptotic resistance by regulations Apaf-1 and caspase-9 apoptosome expression.2003

    • Author(s)
      Haga A, Funasaka T, Niinaka Y, Raz A, Nagase H.
    • Journal Title

      Int J Cancer. 107

      Pages: 707-714

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Pattern of invasion and invasive front grading score as predictive factors of late cervical lymph node metastasis in surgically treated stage I〜II tongue carcinomas.2003

    • Author(s)
      Aung Lwin Oo, Yamaguchi S, Yamada T, Iwaki H, Amagasa T
    • Journal Title

      Oral Med Pathol. 8

      Pages: 117-124

    • NAID

      110006792257

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 口腔扁平上皮癌細胞の遊走様式についての研究2002

    • Author(s)
      新中康史, 新井直也, 山口聰 他
    • Journal Title

      口腔組織培養学会誌 11(1)

      Pages: 19-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Regulation of cell motility via high and low affinity autocrine motility factor(AMF) receptor in human oral squamous carsinoma.2002

    • Author(s)
      Niinaka Y, Haga A, et al.
    • Journal Title

      Oral Oncology 38

      Pages: 49-55

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Cell motility of oral squamous cell carcinoma.2002

    • Author(s)
      Niinaka F, Arai N, Yamaguchi S, Raz A, Amagasa T.
    • Journal Title

      Jpn.J.Tissue Cult.Dent.Res. 11(1)

      Pages: 19-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Regulation of cell motility via high and low affinity autocrine motility factor (AMF) receptor in human oral squamous carcinoma.2002

    • Author(s)
      Niinaka Y, Haga A, Negishi A, Yoshimasu H, Raz A, Amagawa T
    • Journal Title

      Oral Oncology 38

      Pages: 49-55

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 口腔扁平上皮癌細胞におけるAutocrine motility factor(AMF)によるVimentin 発現誘導2001

    • Author(s)
      新中康史, 新井直也, 山口聰, 他
    • Journal Title

      口腔組織培養学会誌 10(2)

      Pages: 35-43

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] pRb2/p130 Protein expression is correlated with clinicopathologic findings in patients with oral squamous cell carcinoma.2001

    • Author(s)
      Tanaka N, Ogi K, Odajima T, Dehari H, Yamada S, Sonoda T, Kohama G
    • Journal Title

      CANCER 92(8)

      Pages: 2117-2125

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Vimentin expression in oral squamous carcinoma cells induced by Autocrine Motility Factor (AMF).2001

    • Author(s)
      Niinaka F, Arai N, Yamaguchi S, Amagasa T.
    • Journal Title

      Jpn.J.Tissue Cult.Dent.Res. 10(2)

      Pages: 35-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shumpei Yamada: "E-type cyclin-independent growth of oral squamous cell carcinoma HSC-2 cells"International Journal of Cancer. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 新中康史: "口腔扁平上皮癌細胞の遊走様式についての研究"口腔組織培養学会誌. 11・1. 19-20 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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