抗EGFR抗体-蛍光法による転移リンパ節に対するリンパ管化学療法の開発

2017 Fiscal Year Research-status Report

• Project/Area Number: 16K11247
• Research Institution: Teikyo University
• Principal Investigator: 横山 純吉 帝京大学, 医学部, 非常勤講師 (60312584)
• Co-Investigator(Kenkyū-buntansha): 長谷川 泰久 愛知県がんセンター(研究所), その他部局等, その他 (10261207) ; 大峡 慎一 順天堂大学, 医学部, 准教授 (20549274) ; 小島 雅貴 順天堂大学, 医学部, 助手 (30760003) ; 鈴木 雅明 帝京大学, 医学部, 教授(移行) (40261630) ; 杉本 晃 帝京大学, 医学部, 講師 (50436432) ; 石橋 謙一郎 愛知学院大学, 歯学部, 非常勤講師 (80714609) ; 福村 由紀 順天堂大学, 医学部, 准教授 (90407312)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: lymphatic chemotherapy / 抗EGFR抗体 / センチネルリンパ節理論 / Drud delivery system / Targeting chemotherapy / リンパ管の可視化 / ICG蛍光法 / アポトーシス

Outline of Annual Research Achievements

頭頸部扁平上皮癌の特性は95%以上にEGFR(epidermal growth factor receptor)を持つので抗EGFR抗体を利用したリンパ管化学療法は 効率的にリンパ管経由で転移リンパ節に移動し、転移リンパ節と強固に結合し抗癌作用を発揮するDrug Delivery System（DDS)を可視 化することで検証可能である。リンパ管を利用したDDSの確定のため抗EGFR抗体－IRDye800CW蛍光剤抱合の作成を試みた。抗EGFR抗体 とIRDye800CWに0.1 M Na2CO3.を加えてpH 8.5, 35°Cで2 時間 攪拌する。抗EGFR抗体とIRDye800CW比は1～10とし、未反応のIRDye800 CWを除去し、0.9%生食で溶出し調整した。しかし抗EGFR抗体とIRDye800CWの最適比が不安定で未だ確立できていません。この分野を担 当している共同研究者が教室の都合で海外出張があったためこの分野研究が少し遅れてしまいました。 同時に好転移性のVX2扁平上皮癌 を NZWに移植し、頭頸部癌の転移モデルを作成しているが、早期に転移し死亡するため実験可能な時 間が非常に限られる欠点があり治療のタイミングが確定されていません。予備実験として原発巣と転移リンパ節を採取し、免疫染色に て発現の有無は確認できています。EGFR発現を確認できているので最適比の抗EGFR抗体－IRDye800CW結合体をリンパ管経由で転移リン パ節投与する実験系を確立しつつあります。現在、共同研究者が帰国し、研究の遅れを取り戻すための綿密な連絡と打ち合わせを行っています。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

施設の移動があり研究体制の確立に時間がかかった。また、共同研究者が海外留学等重なり遅れました。共同研究者も帰国し今後研究体制ができてきました。

Strategy for Future Research Activity

移動先の施設を早急に整備し、研究体制を確立する。共同研究者も出張より帰り研究時間が確保できるため、遅れを取り戻せる予定です。研究時間を多く確保し集中的に実験を行う予定である。

Causes of Carryover

新規施設で研究体制が不十分であったので準備に時間がかかったことと、共同研究者が海外出張の為研究が中断するため、時間の確保できる次年度に研究費を使用するため。

Research Products

• [Journal Article] Total lesion glycolysis on FDG-PET/CT before salvage surgery predicts survival in laryngeal or pharyngeal cancer. (2018)
  • Author(s): Suzuki H, Tamaki T, Nishio M, Nakata Y, Hanai N, Nishikawa D, Koide Y, Hasegawa Y
  • Journal Title: Oncotarget Volume: 10 Pages: 19115-19122
  • DOI: 10.18632/oncotarget.24914.
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of decannulation, oral intake recovery, overall survival and lung metastasis following oral malignant tumor resection and reconstruction. (2018)
  • Author(s): Suzuki H, Hyodo I, Hasegawa Y
  • Journal Title: Oncol Lett. Volume: 15 Pages: 2686-2694
  • DOI: 10.3892/ol.2017.7585.
  • Peer Reviewed / Open Access
• [Journal Article] Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas. (2018)
  • Author(s): Hanai N, Terada H, Hirakawa H, Suzuki H, Nishikawa D, Beppu S, Hasegawa Y
  • Journal Title: Jpn J Clin Oncol. Volume: 48 Pages: 356-361
  • DOI: 10.1093/jjco/hyy008
  • Peer Reviewed / Open Access
• [Journal Article] Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). (2018)
  • Author(s): ahara M, Kiyota N, Yokota T, Hasegawa Y, Muro K, Takahashi S, Onoe T, Homma A, Taguchi J, Suzuki M, Minato K, Yane K, Ueda S, Hara H, Saijo K, Yamanaka T
  • Journal Title: Ann Oncol Volume: 29 Pages: 1004-1009
  • DOI: 10.1093/annonc/mdy040
  • Peer Reviewed / Open Access
• [Journal Article] The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma. (2018)
  • Author(s): Nishikawa D, Hanai N, Suzuki H, Koide Y, Beppu S, Hasegawa Y
  • Journal Title: ORL J Otorhinolaryngol Relat Spec Volume: 80 Pages: 1-9
  • DOI: 10.1159/000485515.
  • Peer Reviewed / Open Access
• [Journal Article] Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma. (2018)
  • Author(s): Saida K, Murase T, Ito M, Fujii K, Takino H, Masaki A, Kawakita D, Ijichi K, Tada Y, Kusafuka K,Iida Y, Onitsuka T, Yatabe Y, Hanai N, Hasegawa Y
  • Journal Title: Oncotarget Volume: 9 Pages: 17043-17055
  • DOI: 10.18632/oncotarget.24818.
  • Peer Reviewed / Open Access
• [Journal Article] Predictive biomarkers for combined chemotherapy with 5-fluorouracil and cisplatin in oro- and hypopharyngeal cancers. (2018)
  • Author(s): Hasegawa Y, Goto M, Hanai N, Ozawa T, Hirakawa H
  • Journal Title: Mol Clin Oncol. Volume: 8 Pages: 378-386.
  • DOI: 10.3892/mco.2017
  • Peer Reviewed
• [Journal Article] Renal protective effect of a hydration supplemented with magnesium in patients receiving cisplatin for head and neck cancer (2018)
  • Author(s): Kimura T, Ozawa T, Hanai N, Hirakawa H, Suzuki H, Hosoi H, Hasegawa Y
  • Journal Title: J Otolaryngol Head Neck Surg. 2018 Feb 2;47(1):10. Volume: 47 Pages: 10
  • DOI: 10.1186/s40463-018-0261-3
  • Peer Reviewed / Open Access
• [Journal Article] Pembrolizumab in Asia-Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE-012 (2018)
  • Author(s): Tahara M, Muro K, Hasegawa Y, Chung HC, Lin CC, Keam B, Takahashi K, Cheng JD,
  • Journal Title: Cancer Sci. 2018 ;109(3): Volume: 109 Pages: 771-776
  • DOI: 10.1111/cas.13480
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heterogeneous impact of smoking on major salivary gland cancer according to histopathological subtype: A case-control study. (2018)
  • Author(s): Sawabe M, Ito H, Takahara T, Oze I, Kawakita D, Yatabe Y, Hasegawa Y
  • Journal Title: Cancer. Volume: 124 Pages: 118-124.
  • DOI: 10.1002/cncr.30957.
  • Open Access
• [Journal Article] Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma. (2017)
  • Author(s): Makita C, Kodaira T, Daimon T, Tachibana H, Tomita N, Koide Y, Koide Y, Fukuda Y, NishikawaD, Suzuki H, Hanai N, Hasegawa Y
  • Journal Title: Jpn J Clin Oncol. Volume: 47 Pages: 1141-1150.
  • DOI: 10.1093/jjco/hyx137
  • Peer Reviewed
• [Journal Article] Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma. (2017)
  • Author(s): Hirakawa H, Hanai N, Suzuki H, Nishikawa D, Matayoshi S, Hasegawa Y
  • Journal Title: Jpn J Clin Oncol. Volume: 47 Pages: 1038-1046.
  • DOI: 10.1093/jjco/hyx097.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical results of definitive chemoradiotherapy for cervical esophageal cancer: Comparison of failure pattern and toxicities between intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy. (2017)
  • Author(s): Ito M, Kodaira T, Tachibana H, Tomita N, Makita C, Koide Y, Kato D, Abe T, Muro K, Tajika M, Niwa Y, Hasegawa Y.
  • Journal Title: Head Neck. Volume: 39 Pages: 2406-2415.
  • DOI: 10.1002/hed.24909.
  • Peer Reviewed
• [Journal Article] A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. (2017)
  • Author(s): Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen CJ, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH,
  • Journal Title: Oral Oncol. Volume: 73 Pages: 138-146.
  • DOI: 10.1016/j.oraloncology.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy. (2017)
  • Author(s): Iwae S, Fujii M, Hayashi R, Hasegawa Y, Fujii T, Okami K, Homma A, Onitsuka T,
  • Journal Title: Int J Clin Oncol. Volume: 22 Pages: :1001-1008.
  • DOI: 10.1007/s10147-017-1151-9
  • Peer Reviewed
• [Journal Article] Comparison between chemoselection and definitive radiotherapy in patients with cervical esophageal squamous cell carcinoma. (2017)
  • Author(s): Nakata Y, Hanai N, Nishikawa D, Suzuki H, Koide Y, Fukuda Y, Nomura M, Kodaira T, Shimizu T, Hasegawa Y
  • Journal Title: Int J Clin Oncol. Volume: 22 Pages: 1034-1041.
  • DOI: 10.1007/s10147-017-1149-3.
  • Peer Reviewed
• [Journal Article] MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma. (2017)
  • Author(s): Fujii K, Murase T, Beppu S, Saida K, Takino H, Masaki A, Ijichi K, Kusafuka K, Iida Y, Onitsuka T, Yatabe Y, Hanai N, Hasegawa Y
  • Journal Title: Histopathology Volume: 7 Pages: 823-834.
  • DOI: 10.1111/his.13281.
  • Peer Reviewed
• [Journal Article] FDG-PET/CT predicts survival and lung metastasis of hypopharyngeal cancer in a multi-institutional retrospective study. (2017)
  • Author(s): Suzuki H, Kato K, Nishio M, Tamaki T, Fujimoto Y, Hiramatsu M, Hanai N, Kodaira T, Itoh Y, Naganawa S, Sone M, Hasegawa Y
  • Journal Title: Ann Nucl Med Volume: 31 Pages: 514-520.
  • DOI: 10.1007/s12149-017-1176-1
  • Peer Reviewed / Open Access
• [Journal Article] Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE-A and NY-ESO-1 expression in adenoid cystic carcinoma. (2017)
  • Author(s): Beppu S, Ito Y, Fujii K, Saida K, Takino H, Masaki A, Murase T, Kusafuka K, Iida Y, Onitsuka T, Yatabe Y, Hanai N, Hasegawa Y,
  • Journal Title: Histopathology. Volume: 7 Pages: 305-315.
  • DOI: 10.1111/his.13226
  • Peer Reviewed
• [Journal Article] Complication and surgical site infection for salvage surgery in head and neck cancer after chemoradiotherapy and bioradiotherapy (2017)
  • Author(s): Suzuki H, Hanai N, Nishikawa D, Fukuda Y, Hasegawa Y
  • Journal Title: Auris Nasus Larynx. Volume: 44 Pages: :596-601.
  • DOI: 10.1016/j.anl.2016.11.009.
  • Peer Reviewed
• [Journal Article] Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study. (2017)
  • Author(s): Sawabe M, Ito H, Oze I, Hosono S, Kawakita D, Tanaka H, Hasegawa Y
  • Journal Title: Cancer Sci. Volume: 108 Pages: :91-100.
  • DOI: 10.1111/cas.13115.
  • Peer Reviewed / Open Access
• [Journal Article] Sentinel node biopsy for oral cancer: A prospective multicenter Phase II trial. (2017)
  • Author(s): Miura K, Hirakawa H, Uemura H, Yoshimoto S, Shiotani A, Sugasawa M, Homma A, Yokoyama J,
  • Journal Title: Auris Nasus Larynx. 2017 ;44(3):319-326 Volume: 44 Pages: 319-326
  • DOI: 10.1016/j.anl.2016.07.008.
  • Peer Reviewed
• [Presentation] 気管孔閉鎖の嚥下機能に関する検討 (2017)
  • Author(s): 横山純吉、大狭慎一
  • Organizer: 日本頭頸部癌学会
• [Presentation] エンドGIA自動吻合器を用いた誤嚥防止術の検討 (2017)
  • Author(s): 横山純吉
  • Organizer: 日本喉頭科学会
• [Presentation] 進行声門癌に対する超選択的動注療法後再発症例の検討 (2017)
  • Author(s): 大峡慎一、藤巻充寿、小島雅貴 横山純吉
  • Organizer: 日本頭頸部外科学会
• [Presentation] 頭頚部癌に対する集学的集学的治療とNivolumabの現在の位置付け (2017)
  • Author(s): 横山純吉
  • Organizer: 頭頚部癌東海Seminar in Tokai
  • Invited