The role of Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD)expression in 5-FU based chemoradiation for head and neck cancer

• Project/Area Number: 20592021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kyushu University
• Principal Investigator: NAKASHIMA Torahiko Kyushu University, 大学病院, 講師 (00284505)
• Co-Investigator(Kenkyū-buntansha): YASUMATSU Ryuji 九州大学, 医学研究院, 研究員 (00444787)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 頭頸部癌 / 放射線化学療法 / 核酸代謝酵素 / フッ化ピリミジン / TS / DPD

Research Abstract

Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD) are key enzymes for 5-FU metabolism. The relationship between the expression of TS/DPD and 5-FU sensitivity in head and neck squamous carcinoma (HNSCC) cells was analyzed in vitro.
Increasing the expression of TS or DPD decreased the cytotoxicity of 5-FU against HNSCC cells.
Clinico-pathological analysis was also performed utilizing specimens from oral cancer and maxillary sinus cancer. There was a correlation between high TS expression and poor prognosis of the patients. Assessment of TS/DPD activity may be useful in predicting the effect and prognosis of HNSCC patients who are receiving 5-FU based chemo(radio)therapy.

Research Products

• [Journal Article] Relative level of thymidylate synthase mRNA expression in primary tumors and normal tissues predicts survival of patients with oral tongue squamous cell carcinoma. (2010)
  • Author(s): 安松隆治, 中島寅彦, et al.
  • Journal Title: Eur Arch Otolaryngol 267 Pages: 581-586
• [Journal Article] 早期舌癌に対する手術療法の治療成績一放射線治療との比較- (2010)
  • Author(s): 中島寅彦、中村和正、白土秀樹、安松隆治, 他
  • Journal Title: 日耳鼻 113 Pages: 456-462
• [Journal Article] Thymidylate synthase expression as a predictor of clinical response to 5-fluorouracil-based chemoradiotherapy in patients with maxillary sinus squamous cell carcinoma. (2010)
  • Author(s): 安松隆治,中島寅彦, et al.
  • Journal Title: Auris Nasus Larynx in press
• [Journal Article] Thymidylate synthase expression as a predictor of clinical response to 5-fluorouracil-based chemoradiotherapy in patients with maxillary sinus squamous cell carcinoma. (2010)
  • Author(s): Yasumatsu R, Nakashima T, et al.
  • Journal Title: Auris Nasus Larynx Volume: (Epub)
  • Peer Reviewed
• [Journal Article] 早期舌癌に対する手術療法の治療成績-放射線治療との比較- (2010)
  • Author(s): 中島寅彦、中村和正、白土秀樹、安松隆治, ほか
  • Journal Title: 日本耳鼻咽喉科学会会報 Volume: 113 Pages: 456-462
  • NAID: 10026518472
  • Peer Reviewed
• [Journal Article] Relative level of thymidylate synthase mRNA expression in primary tumors and normal tissues predicts survival of patients with oral tongue squamous cell carcinoma (2010)
  • Author(s): Yasumatsu R, Nakashima T, et al.
  • Journal Title: Eur Arch Otorhinolaryngol 267 Pages: 581-586
  • Peer Reviewed
• [Journal Article] The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells. (2009)
  • Author(s): 安松隆治, 中島寅彦, et al.
  • Journal Title: Oral Oncology 45 Pages: 141-147
• [Journal Article] Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma. (2009)
  • Author(s): 安松隆治, 中島寅彦, et al.
  • Journal Title: Chemotherapy 55 Pages: 36-41
• [Journal Article] 頭頸部癌放射線化学療法 (2009)
  • Author(s): 中島寅彦
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Pages: 81441-81447
• [Journal Article] 頭頸部癌放射線化学療法 (2009)
  • Author(s): 中島寅彦
  • Journal Title: 耳鼻咽喉科・頭頸部外科 81 Pages: 441-447
• [Journal Article] The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells. (2009)
  • Author(s): Yasumatsu R, Nakashima T, et al.
  • Journal Title: Oral Oncology 45 Pages: 141-147
  • Peer Reviewed
• [Journal Article] Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma. (2009)
  • Author(s): Yasumatsu R, Nakashima T, et al.
  • Journal Title: Chemotherapy 55 Pages: 36-41
  • Peer Reviewed
• [Presentation] 下咽頭癌治療のピットフォールー化学放射線療法のピットフォールー (2011)
  • Author(s): 中島寅彦
  • Organizer: 第21回日本気管食道科学会認定気管食道科専門医大会
  • Place of Presentation: 大阪市
  • Year and Date: 2011-02-26
• [Presentation] 頭頸部癌に対する化学放射線療法の現状と将来展望 (2010)
  • Author(s): 中島寅彦
  • Organizer: 第62回日本気管食道科学会 ランチョンセミナー
  • Place of Presentation: 別府市
  • Year and Date: 2010-11-05
• [Presentation] Thymidylate synthase expression as a predictor of clinical response to 5-fluorouracil-based chemoradiotherapy in patients with maxillary sinus squamous cell carcinoma. (2010)
  • Author(s): Ryuji Yasumatsu, Torahiko Nakashima, Shizuo Komune
  • Organizer: 4^<th> World congress of International Federation of Head and Neck Oncologic Societies
  • Place of Presentation: Seoul Korea
• [Presentation] Treatment Outcome of Concurrent Chemoradiotherapy with Intraarterial CDDP/DOC and Oral S-1 for Advanced Head and Neck Cancer (2010)
  • Author(s): Torahiko Nakashima, Ryuji Yasumatsu, Yoshiyuki Shioyama, Takeshi Kamitani, Shizuo Komune
  • Organizer: AAO-HNSF 2010 Research Workshop
  • Place of Presentation: Arlington USA
• [Presentation] Thymidylate synthase expression as a predictor of clinical response to 5-FU-based chemotherapy in patients with maxillary sinus (2010)
  • Author(s): Ryuji Yasumatsu, Torahiko Nakashima, Shizuo Komune.
  • Organizer: SCC AAO-HNSF 2010 Research Workshop
  • Place of Presentation: Arlington USA
• [Presentation] Thymidylate synthase expression as a predictor of clinical response to 5-FU-based chemotherapy in patients with maxillary sinus SCC (2010)
  • Author(s): Ryuji Yasumatsu, Torahiko Nakashima, et al
  • Organizer: 4^<th> world congress of international federation of head and neck oncologic societies
  • Place of Presentation: ソウル、韓国
• [Presentation] Treatment Outcome of Concurrent Chemoradiotherapy with Intraarterial CDDP/DOC and Oval S-1 for Advanced Head and Neck Cancer (2010)
  • Author(s): Torahiko Nakashima, Ryuji Yasumatsu, et al
  • Organizer: AHNS 2010 Research Workshop
  • Place of Presentation: アーリントン、USA
• [Presentation] Thymidylate synthase expression as a predictor of clinical response to 5-FU-based chemotherapy in patients with maxillary sinus SCC (2010)
  • Author(s): Ryuji Yasumatsu, Torahiko Nakashima, et al
  • Organizer: AHNS 2010 Research Workshop
  • Place of Presentation: アーリントン、USA
• [Presentation] ピリミジン系代謝酵素をターゲットとした頭頸部癌治療に関する基礎的臨床的検討 (2009)
  • Author(s): 安松隆治、中島寅彦, 他
  • Organizer: 日本耳鼻咽喉科学会総会
  • Place of Presentation: 東京
• [Presentation] Concurrent chemoradiotherapy with intraarterial CDDP/DOC and S-1 American Academy of Otolaryngology (2009)
  • Author(s): Torahiko Nakashima, Hideki Shiratsuchi, Ryuji Yasumatsu, Shizuo Komune
  • Organizer: HNS 2009
  • Place of Presentation: SanDiego
• [Presentation] 頭頚部扁平上皮癌におけるThymidilate synthase発現とその役割について (2008)
  • Author(s): 安松隆治, 中島寅彦, 他
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-30
• [Presentation] 頭頚部扁平上皮癌におけるTS発現とその役割 (2008)
  • Author(s): 安松隆治, 中島寅彦, 他
  • Organizer: 第32回日本頭頚部癌学会
  • Place of Presentation: 東京都
  • Year and Date: 2008-06-12
• [Presentation] 頭頸部扁平上皮癌におけるThymidilate synthase発現とその役割について (2008)
  • Author(s): 安松隆治、中島寅彦, 他
  • Organizer: 第46回日本癌治療学会総会
• [Remarks] ホームページ等
  • URL: http://www.c-shop.net/kyudai_jibi/index.htm1