ESTABLISHMENT OF TUMOR SPECIFIC MOLECULER TARGETTING THERAPY AGAINST HYPDXIA INDUCIBLE FACTOR

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18592201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Showa University
• Principal Investigator: HATORI Masashi Showa University, Dept Oral Maxillofac Surg., Associate Professor (20245814)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Takahiko Showa Univ., Dept Oral Maxillofac Surg., Assistant Professor (90338533) ; ITO Hidetoshi Showa Univ., Dept Oral Maxillofac Surg., Assistant Professor (80384303)
• Project Period (FY): 2006 – 2007
• Keywords: HYPOXIA / OSCC / CELL CYCLE / MMP / INVASIVENESS

Research Abstract

1.Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G1 phase cell cycle wrest
1) Hypoxia did not affect cell viability of OSCC cells up to 8 hour incubation
2) Hypoxia did not affect cell proliferation of NA and SAS, whereas the proliferation ofHSC-3, CA9-22 was down-regulated.
3) Hypoxia sensitive cells (HS) display enhanced expression of HIF-1 α within 24 h incubation in hypoxia chamber.
4) Hypoxia resistant cells (HR) display constitutive expression of HIF-1α.
5) HS showed G1 arrest under the hypoxic condition.
6) Enhanced cyto-toxicity of 5-FU was observed in HS.
2, Effects of hypoxia on cell invasiveness of OSCC cells
1) Hypoxia enhances invasiveness of OSCC cells in Matrigel invasion assay.
2) Hypoxia induces expression of MMP-2, MMP-9 of OSCC cells.
3) Hypoxia ski induces secretion of MMPs in culture supernatant.
4) Activated MMP-2 in OSCC cells was up-regulated by hypoxia
5) Fibroblast conditioned medium cultured in hypoxia chamber enhanced MMP-2 expression.

Research Products

• [Journal Article] Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors (2007)
  • Author(s): Iwase, M, Yoshiba, S, Uchida, M, Takaoka, S, Kurihara, Y, Ito, D, Hatori, M, Shintani, S
  • Journal Title: Int J Oncol 31 Pages: 1141-1147
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thalidomide suppresses melanoma growth by activating natural killer cells in mice (2006)
  • Author(s): Kawamata A, Hatori M, et. al.
  • Journal Title: Oncology Report 16 Pages: 1231-1236
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Thalidomide suppresses melanoma growth by activatiing natural killer cells in mice (2006)
  • Author(s): Kawamata, A, Ito, D, Odani, T, Isobe, T, Iwase, M, Hatori, M, Nagumo, M
  • Journal Title: Oncology Report 16 Pages: 1231-1236
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors
  • Author(s): Iwase M, Hatori M, et. al.
  • Journal Title: Int J Oncology (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 頬脂肪体有茎弁移植による口蓋腫瘍切除後の再建:症例報告と文献的考察
  • Author(s): 伊東 大典, 羽鳥 仁志, 他
  • Journal Title: Dental Medicine Research (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Presentation] 低酸素環壌における口腔扁平上皮癌のHIF-1αの発現及び浸潤能の解析 (2006)
  • Author(s): 栗原 祐史, 羽鳥 仁志, 他
  • Organizer: 第51回日本口腔外科学会総会
  • Place of Presentation: 小倉
  • Year and Date: 2006-10-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Effects of hypoxia on cell invasiveness of OSCC cells
  • Author(s): Yuji, Kuria, Masashi, Hatori, Yuriko, Kinygasa, Masako, Saito, Hidetoshi, Ito, Masaru, Ohaghi, Masao, Nagumo
  • Organizer: The 30th Annual meeting of Japan society for Head andNeck Cancer
  • Description: 「研究成果報告書概要(欧文)」より