EVALUATION OF GRANDE OF MALLIGNANCY ON THE BASIS OF CELL CYCLE ADHESION MOLECULESIN ORAL SQUAMOUS CELL CARCUNOMA

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18592222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Sapporo Medical University
• Principal Investigator: YAMAGUCHI Akira Sapporo Medical University, DPT OF ORAL SURG, SCHOOL OF MEDICINE, Associate Professor (10210353)
• Co-Investigator(Kenkyū-buntansha): NAKAMORI Kenji SAPPORO MEDICAL UNIVERSITY, DPT OF ORAL SURG, SCHOOL OF MEDICINE, Instructor (60295334) ; MIYAZAKI Akihiro SAPPORO MEDICAL UNIVERSITY, DPT OF ORAL SURG, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR (10305237) ; OGI Kazuhiro SAPPORO MEDICAL UNIVERSITY, DPT OF ORAL SURG, SCHOOL OF MEDICINE, Instructor (40433114)
• Project Period (FY): 2006 – 2007
• Keywords: oral cancer / cell cycle / p53 / genomics / RAS signaling

Research Abstract

Dysregulation of tumor suppressor gene p53 has been shown to play a significant role in development of a wide variety of human malignancies. Some investigators have suggested that accumulated expression of p53 gene protein is useful as a prognostic indicator in oral squamous cell carcinoma (OSCC), although others have reported conflicting result. The aim of this study is to determine the correlation between the expression of p53 gene protein and the clinicopathological features of 140 OSCC. Tumor biopsies obtained from patients with OSCC were examined for the immunohistochemical detection of p53 gene product with special reference to expression pattern correlated with clinicopathological findings and overall survival. Nuclear accumulation of p53 was visualized as marginal pattern, dispersed pattern, or mixed pattern. Simple evaluation of p53 expression (negative and positive) defined with value of 10% did not provide useful information as to the assessment of oral.cancer However, dispe rsed type p53 protein expression significantly correlated with nodal metastasis, differentiation of tumor cell, overall survival and mutation. These finding suggest that p53 expression may, but not p53 positivity, be one of biological makers for the degree of malignancy in OSCC.
Genetic and epigenetic alterations in tumor-suppressor genes play important roles in human neoplasia. Ras signaling is often activated in OSCC, although RAS mutations are rarely detected in OSCC patients. In present study, we examined the expression and and methylation statuses of RAS association family (RASSF) genes in OSCC. We frequently detected methlaion of RASSF1 (7/17:41.2%) RASSF2 (12/17:70.6%), RASSF5 (4/17:23.5%) in a panel of OSCC cell lines, as well as in specimens collected from 46 OSCC patient (RASSF1, 6/46, 13.0%; RAsSF2,12/46, 26.1%; RASSF5,5/46,10.9%). Our findings indicate that epigenetic inactivation of RASSF plays a key role in OSCC tumorigenesis, and that RASSF may be an important molecular target for the diagnosis and treatment of OSCC.

Research Products

• [Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma (2008)
  • Author(s): Imai T
  • Journal Title: Cancer Sci. (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A single-institute phase I/II trial combining Nedaplatin doss escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma (2008)
  • Author(s): Miyazaki A
  • Journal Title: Oral Oncol (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Bisphosphonate製剤投与を受ける乳癌多発骨転移患者にみられた顎骨骨髄炎 (2008)
  • Author(s): 冨原 圭
  • Journal Title: 癌と化学療法 35 Pages: 113-116
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. (2008)
  • Author(s): Imai, T., Toyota, M., Suzuki, H., Akino, K., Sogabe, Y., kasima, R., Nojima, M., MIta, H., Sasaki, Y., Itoh, F., Imai, K., Shinomura, Y., Hiratsuka, H., Tokino, T
  • Journal Title: Cancer Sci (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma (2008)
  • Author(s): Miyazaki, A., Kobayashi, J., Yamamoto, T., Kido, Y., Takemura, K., Abe, M., Dehari, H., Nakamori, K., Nagai, I., Hiratsuka, H
  • Journal Title: Oral Oncol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Current progress and perspective for human tumor immunotherapy (2006)
  • Author(s): Sato N
  • Journal Title: Tumor Res 41 Pages: 1-13
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 舌癌の郭清範囲に関する検討 (2006)
  • Author(s): 仲盛 健治
  • Journal Title: 頭頚部癌 32 Pages: 429-433
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Current progress and perspectives for human tumor immunotherapy (2006)
  • Author(s): Sato, N., Hirohashi, Y., Tukahara, T., Kamiguchi, K., Ichimiya, S., Sahara, H., Takahashi, N., Turuma, T., Hirata, K., Miyazaki, A., Yamaguchi, A., Hiratsuka, H., Tsukamoto, T., Kawaguchi, S., Wada, T., Yamashita, T., Takahashi, H., Shijyubo, N., Ogasawara, M., Tamura, Y., Torigoe, T
  • Journal Title: Tumor Res 41(1) Pages: 1-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 口腔力がん者におけるHLA class Iとsurvivinの発現に関する組織学的検討 (2008)
  • Author(s): 小林 淳一
  • Organizer: 第26回日本口腔腫瘍学会
  • Place of Presentation: 別府市
  • Year and Date: 2008-01-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 癌抗原STEAPを標的とする口腔腫瘍免疫治療法開発 (2008)
  • Author(s): 山本 崇
  • Organizer: 第26回日本口腔腫瘍学会
  • Place of Presentation: 別府市
  • Year and Date: 2008-01-24
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Dispersed type expression of p53 tumor suppressor gene protein isassociate with a poor prognosis in patients oral cancer (2007)
  • Author(s): Yamaguchi A
  • Organizer: 18th International Conference on Oral and Maxillo-facial Surgery
  • Place of Presentation: Bangalore India
  • Year and Date: 2007-11-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] IFN-γ induces Q2 NK-mediated antitumor effects against oral aquamous cell carcinoma cells (2007)
  • Author(s): Tomihara K
  • Organizer: 18th International Conference on Oral and Maxillo-facial Surgery
  • Place of Presentation: Bangalore India
  • Year and Date: 2007-11-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] IFN-γ induces Q2 NK-mediated antitumor effects against oral squamous cell carcinoma cells (2007)
  • Author(s): Tomihara, K
  • Organizer: 18th International Conference on Oral and Maxillo-facial Surgery
  • Place of Presentation: Bangalore India
  • Year and Date: 2007-11-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Dispersed type expression of p53 tumor suppressor gene protein is associate with a poor prognosis in patients oral cancer (2007)
  • Author(s): Yamaguchi, A
  • Organizer: 18th International Conference on Oral and Maxillo-facial Surgery
  • Place of Presentation: Bangalore India
  • Year and Date: 2007-11-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 口腔癌に対するIFAとIFN-αを併用したsurvivinペプチドワクチン療法の第1相臨床試験 (2007)
  • Author(s): 宮崎 晃亘
  • Organizer: 第45回日本癌治療学会
  • Place of Presentation: 京都市
  • Year and Date: 2007-10-26
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Stage II舌扁平上皮癌の頸部廓清の適応基準-標準的治療の確率を目指して (2007)
  • Author(s): 仲盛 健治
  • Organizer: 第45回日本癌治療学会
  • Place of Presentation: 京都市
  • Year and Date: 2007-10-25
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] A phase I clinical trial of surviving-2B peptide vaccine therapy for patient with advanced recurrent oral cancer (2007)
  • Author(s): Miyazaki A
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Alteration of RAS signaling pathway in oral squamous cell carcinoma (2007)
  • Author(s): Imai T
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] STEAP,a potent tumor specific antigen,in oral cancer (2007)
  • Author(s): Yamamoto T
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] STEAP, a potent tumor specific antigen in oral cancer (2007)
  • Author(s): Yamamoto, T
  • Organizer: 65th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A phase I clinical trial trial of surviving-2B peptide vaccine therapy for patient with advanced recurrent oral cancer (2007)
  • Author(s): Miyazaki, A
  • Organizer: 65th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 口腔扁平上皮癌におけるRAS関連遺伝子の異常の解析 (2007)
  • Author(s): 今井 崇
  • Organizer: 第52回日本口腔外科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2007-09-29
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Excisional biopsyを行った舌扁平上皮癌の発育様式、腫瘍の厚みと頸部リンパ節転移との関連性の検討 (2007)
  • Author(s): 仲盛 健治
  • Organizer: 第31回日本頭頸部癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-06-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] RAS関連遺伝子のジェネティックおよびエピジェネティックな異常の解析 (2007)
  • Author(s): 今井 崇
  • Organizer: 第61回日本口腔科学会
  • Place of Presentation: 神戸市
  • Year and Date: 2007-04-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] survivin癌ペプチドワクチンが奏功した切除不能再発頬粘膜癌の一例 (2007)
  • Author(s): 宮崎 晃亘
  • Organizer: 第25回日本口腔腫瘍学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2007-02-02
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Interferon-gamma enhances the anti-cancer effect of TRAIL in human oral squamous cell carcinoma (2006)
  • Author(s): Dehari, H
  • Organizer: 7th Asian Congress on Oral and Maxillofacial Surgery
  • Place of Presentation: Hong Kong
  • Year and Date: 2006-11-07
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 口腔癌に対する癌ペプチドワクチン療法の第一相臨床試験 (2006)
  • Author(s): 宮崎 晃亘
  • Organizer: 第44回日本癌治療学会
  • Place of Presentation: 東京都
  • Year and Date: 2006-10-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Stage II舌扁平上皮癌の頸部廓清に関する検討 (2006)
  • Author(s): 仲盛 健治
  • Organizer: 第44回日本癌治療学会
  • Place of Presentation: 東京市
  • Year and Date: 2006-10-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 口腔扁平上皮癌患者におけるHLA class I発現と臨床病理学的所見の検討 (2006)
  • Author(s): 宮崎 晃亘
  • Organizer: 第51回日本口腔外科学会
  • Place of Presentation: 北九州市
  • Year and Date: 2006-10-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 癌抗原STEAPを標的とする口腔腫瘍免疫療法開発 (2006)
  • Author(s): 山本 崇
  • Organizer: 第65回日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2006-09-29
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 口腔扁平上皮癌におけるRAS関連遺伝子のエピジェニックな異常の解析 (2006)
  • Author(s): 今井 崇
  • Organizer: 第65回日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2006-09-29
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 舌癌の頸部廓清に関する検討 (2006)
  • Author(s): 仲盛 健治
  • Organizer: 第30回日本頭頸部癌学会
  • Place of Presentation: 大阪市
  • Year and Date: 2006-06-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 口腔癌免疫療法に向けての基礎的研究-口腔扁平上皮癌細胞株及び癌組織におけるSTEAPの発現 (2006)
  • Author(s): 山本 崇
  • Organizer: 第60回日本口腔科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2006-05-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HLA-A24拘束性自家口腔扁平上皮癌障害性T細胞の解析 (2006)
  • Author(s): 小林 淳一
  • Organizer: 第60回日本口腔科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2006-05-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 口腔扁平上皮癌におけるRASSFファミリー遺伝子のエピジェニックな異常の解析 (2006)
  • Author(s): 今井 崇
  • Organizer: 第60回日本口腔科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2006-05-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 口腔癌免疫療法に向けての基礎的研究-口腔扁平上皮癌細胞株及び癌組織におけるSTEAPの発現- (2006)
  • Author(s): 今井 崇
  • Organizer: 第60回日本口腔科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2006-05-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HLA-A24拘束性自家口腔扁平上癌障害性T細胞の解析 (2006)
  • Author(s): 小林 淳一
  • Organizer: 第60回日本口腔科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2006-05-12
  • Description: 「研究成果報告書概要(和文)」より