Combination of glucose uptake inhibition and radiation make synergistic inhibitory effect for head and neck squamous cell carcinoma

• Project/Area Number: 26861375
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: Hanamoto Atsushi 大阪大学, 医学系研究科, 助教 (20625917)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 頭頸部癌 / FDG-PET / 頭頸部扁平上皮癌 / グルコースの代謝

Outline of Final Research Achievements

We used human HNSCC cell lines. FaDu, Detroit562 and BICR6 had high expression of GLUT1, LDHA and MCT4. It revealed that anaerobic metabolism was high in these cell lines. Cell proliferation assay with or without glucose revealed that all of the cell lines without glucose grew slower than the cells with glucose. Glucose was essential for the growth of HNSCC cell lines. In hypoxia, FaDu, Detroit562 and BICR6 grew faster than those in normoxic condition. Western blot analyses revealed that the expressions of LDHA and MCT4 in hypoxia were higher than those in normoxia. In hypoxia, The knock down of GLUT1 or Ph-treatment inhibited the uptake of glucose. Cell proliferation assay revealed that HNSCC cell lines with Ph-treatment and radiation grew significantly slower than those with only radiation in hypoxia. Additionally, induction of apoptosis was detected in Ph-treated cell lines compared to cell lines treated with only radiation in hypoxia by TUNEL analysis.

Research Products

• [Journal Article] Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer. (2016)
  • Author(s): Takenaka Y, Takemoto N, Yasui T, Yamamoto Y, Uno A, Miyabe H, Ashida N, Shimizu K, Nakahara S, Hanamoto A, Fukusumi T, Michiba T, Cho H, Yamamoto M, Inohara H.
  • Journal Title: PLoS One. Volume: - Issue: 10 Pages: e0164057-e0164057
  • DOI: 10.1371/journal.pone.0164057
  • Peer Reviewed / Open Access
• [Journal Article] 甲状腺全摘直後の副甲状腺機能低下症に対するファレカルシトリオールの有効性及び安全性. (2016)
  • Author(s): 中原晋、花本敦、安井俊道、竹中幸則、山本佳史、福角隆仁、道場隆博、猪原秀典.
  • Journal Title: 頭頸部外科 Volume: 26 Pages: 197-201
  • Peer Reviewed
• [Journal Article] Chemoradiotherapy with weekly low-dose docetaxel and cisplatin concurrent with radiation for patients with locally advanced nasopharyngeal carcinoma, followed by adjuvant chemotherapy for selected patients. (2016)
  • Author(s): Nakahara S, Hanamoto A, Seo Y, Miyaguchi S, Yamamoto Y, Tomiyama Y, Yoshii T, Takenaka Y, Yoshioka Y, Isohashi F, Ogawa K, Inohara H.
  • Journal Title: Jpn J Clin Oncol. Volume: 46 Pages: 903-910
  • Peer Reviewed
• [Journal Article] A Case of Nasopharyngeal Cancer with Febrile Neutropenia Followed by Death during Adjuvant Chemotherapy (2015)
  • Author(s): Nakahara S, Kitamura K, Honma K, Yamamoto Y, Takenaka Y, Yasui T, Hanamoto A, Morii E, Inohara H.
  • Journal Title: Nihon Jibiinkoka Gakkai Kaiho Volume: 118 Pages: 763-9
  • NAID: 130005088299
  • Peer Reviewed
• [Journal Article] Factors predicting severe infections during chemotherapy in head and neck cancer patients. (2015)
  • Author(s): Sasaki T, Takenaka Y, Hayashi T, Yamamoto M, Cho H, Fukusumi T, Takemoto N, Hanamoto A, Yasui T, Nakahara S, Yamamoto Y, Mitani K, Inohara H
  • Journal Title: Acta Otolaryngol. Volume: 135 Issue: 10 Pages: 1086-91
  • DOI: 10.3109/00016489.2015.1060631
  • Peer Reviewed
• [Journal Article] Docetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma. (2015)
  • Author(s): Cho H, Nishiike S, Yamamoto Y, Takenaka Y, Nakahara S, Yasui T, Hanamoto A, Inohara H.
  • Journal Title: Auris Nasus Larynx Volume: 42 Issue: 5 Pages: 396-400
  • DOI: 10.1016/j.anl.2015.02.009
  • Peer Reviewed
• [Journal Article] Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer. (2015)
  • Author(s): Imai R, Takenaka Y, Yasui T, Nakahara S, Yamamoto Y, Hanamoto A, Takemoto N, Fukusumi T, Cho H, Yamamoto M, Inohara H.
  • Journal Title: Acta Otolaryngol. Volume: 135 Issue: 3 Pages: 295-301
  • DOI: 10.3109/00016489.2014.951454
  • Peer Reviewed
• [Journal Article] Prognostic significance of body mass index before treatment for head and neck cancer. (2015)
  • Author(s): Takenaka Y, Takemoto N, Nakahara S, Yamamoto Y, Yasui T, Hanamoto A, Fukusumi T, Michiba T, Cho H, Yamamoto M, Inohara H.
  • Journal Title: Head Neck. Volume: 37 Issue: 10 Pages: 295-301
  • DOI: 10.1002/hed.23785
  • Peer Reviewed
• [Journal Article] Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy. (2014)
  • Author(s): Hanamoto A, Tatsumi M, Takenaka Y, Hamasaki T, Yasui T, Nakahara S, Yamamoto Y, Seo Y, Isohashi F, Ogawa K, Hatazawa J, Inohara H.
  • Journal Title: Cancer Med. Volume: 3 Issue: 5 Pages: 1368-1376
  • DOI: 10.1002/cam4.295
  • Peer Reviewed / Open Access
• [Journal Article] 【咽頭癌・頸部食道癌の治療戦略Update】 個別化治療の現在 PETからみた咽頭癌の個別化治療(解説/特集) (2014)
  • Author(s): 花本敦
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Volume: 86 Pages: 812-818
• [Presentation] 甲状腺乳頭癌におけるFDGの集積による予後予測 (2016)
  • Author(s): 花本敦、鈴木基之、武本憲彦、道場隆博、平井崇、高野徹、猪原秀則
  • Organizer: 第49回甲状腺外科学会
  • Place of Presentation: 山梨
  • Year and Date: 2016-10-27
• [Presentation] SUVmax on FDG-PET Predicts Clinical Outcome in Papillary Thyroid Cancer (2016)
  • Author(s): Atsushi Hanamoto、Susumu Nakahara、Takahito Fukusumi、Takahiro Michiba、Hidenori Inohara
  • Organizer: AAO-HNSF annual meeting 2016
  • Place of Presentation: San Diego（アメリカ合衆国）
  • Year and Date: 2016-09-18
• [Presentation] 甲状腺癌におけるFDG-PETの検討 (2016)
  • Author(s): 花本敦、中原晋、福角隆仁、道場隆博、猪原秀則
  • Organizer: 第40回頭頸部癌学会
  • Place of Presentation: 埼玉
  • Year and Date: 2016-06-09
• [Presentation] 当科における甲状腺癌周囲臓器浸潤症例の検討 (2015)
  • Author(s): 花本 敦、中原 晋、福角隆仁、道場隆博、猪原秀典
  • Organizer: 第48回 甲状腺外科学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-28
• [Presentation] 当科における甲状腺癌周囲臓器浸潤症例の検討 (2015)
  • Author(s): 花本 敦、中原 晋、福角隆仁、道場隆博、猪原秀典
  • Organizer: 第334回 大阪地方連合会
  • Place of Presentation: 大阪
  • Year and Date: 2015-09-05
• [Presentation] CTとPETでの頭頸部癌の容積測定におけるInter-observer variationの検討 (2014)
  • Author(s): 花本敦
  • Organizer: 大阪地方連合会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-06
• [Presentation] グルコース取り込み抑制と放射線照射による頭頸部癌への相乗効果 (2014)
  • Author(s): 花本敦
  • Organizer: 頭頸部癌学会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-12 – 2014-06-13