Research of the mechanism of lymph node metastasis in nasopharyngeal carcinoma with bio-assay model

• Project/Area Number: 21592189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kanazawa University
• Principal Investigator: WAKISAKA Naohiro 金沢大学, 大学病院, 講師 (70377414)
• Co-Investigator(Renkei-kenkyūsha): YOSHIZAKI Tomokazu 金沢大学, 医学系, 教授 (70262582) ; MURONO Shigeyuki 金沢大学, 大学病院, 講師 (20345622) ; KONDO Satoru 金沢大学, 附属病院, 助教 (70436822)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: EBV / LMP1 / VEGF-C / リンパ管新生 / リンパ節転移 / 上咽頭癌 / 動物モデル / 胸管 / 舌癌 / センチネル・リンパ節

Research Abstract

The involvement of vascular endothelial growth factor (VEGF)-C/VEGF receptor-3 axis in the induction of lymphangiogenesis results in lymphatic spread of nasopharyngeal carcinoma. However, Epstein-Barr virus-associated latent membrane protein-1 was not associated with the mechanism.Knowing the status of lymphangiogenesis in the regional lymph nodes in tongue cancer would help in predicting which patients will develop nodal recurrence. Thus, therapeutic approach which blocks lymphangiogenic factors may be beneficial in suppressing the lymphatic spread of tongue cancer with intense intranodal lymphangiogenesis.

Research Products

• [Journal Article] Warthin's tumor associated with IgG4-related disease. (2012)
  • Author(s): Aga M, Kondo S, Yamada K, Sawada-Kitamura S, Yagi-Nakanishi S, Endo K,Wakisaka N, Murono S, Kawano M, Yoshizaki T
  • Journal Title: Auris NasusLarynx Volume: (In press) Issue: 5 Pages: 514-517
  • DOI: 10.1016/j.anl.2012.11.005
  • Peer Reviewed
• [Journal Article] Expression of seven-in-absentia homologue 1 and hypoxia-inducible factor 1 alpha: Novel prognostic factors of nasopharyngeal carcinoma (2012)
  • Author(s): Kitagawa N, Kondo S, Wakisaka N, Zen Y, Nakanishi Y, Tsuji A, Endo K, Murono S, Yoshizaki T
  • Journal Title: Cancer Lett. Epub Volume: 331(1) Issue: 1 Pages: 52-7
  • DOI: 10.1016/j.canlet.2012.12.002
  • NAID: 120005253837
  • Peer Reviewed
• [Journal Article] Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma. (2012)
  • Author(s): Endo K, Ueno T, Kondo S, Wakisaka N, Murono S, Ito M, Kataoka K, Kato Y,Yoshizaki T
  • Journal Title: Cancer Sci. Epub Volume: 104 Issue: 3 Pages: 369-74
  • DOI: 10.1111/cas.12079
  • NAID: 120005830602
  • Peer Reviewed
• [Journal Article] Oncological and functional outcome after transoral 532-nm pulsed potassium-titanyl-phosphate laser surgery for T1a glottic carcinoma (2012)
  • Author(s): Murono S, Endo K, Kondo S, Wakisaka N, Yoshizaki T
  • Journal Title: Lasers Med Sci. Epub Volume: 28 Issue: 2 Pages: 615-619
  • DOI: 10.1007/s10103-012-1121-4
  • Peer Reviewed
• [Journal Article] Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in pathological N0 squamous cell carcinoma of the tongue. (2012)
  • Author(s): Hirota K, Wakisaka N, Sawada-Kitamura S, Kondo S, Endo K, Tsuji A, Murono S,Yoshizaki T
  • Journal Title: Histopathology Volume: 61(6) Issue: 6 Pages: 1065-71
  • DOI: 10.1111/j.1365-2559.2012.04341.x
  • NAID: 120004754705
  • Peer Reviewed
• [Journal Article] Adjuvant chemotherapy withan oral fluoropyrimidine, S-1, following reduced RADPLAT in advanced laryngeal cancer (2012)
  • Author(s): Wakisaka N, Kondo S, Endo K, Murono S, Yoshizaki T
  • Journal Title: Ann Otol Rhinol Laryngol Volume: 121(8) Pages: 555-62
  • Peer Reviewed
• [Journal Article] Induction of lymphangiogenesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma (2012)
  • Author(s): Wakisaka N, Hirota K, Kondo S, Sawada-Kitamura S, Endo K, Murono S, Yoshizaki T
  • Journal Title: Oral Oncol Volume: 48(8) Issue: 8 Pages: 703-8
  • DOI: 10.1016/j.oraloncology.2012.02.003
  • NAID: 120003959476
  • Peer Reviewed
• [Journal Article] Efficacy and safety of garenoxacin in the treatment of upperrespiratory tract infections. (2012)
  • Author(s): Ito M, Maruyama Y, Murono S, Wakisaka N, Kondo S, Hatano M, Nakanishi S, MiwaT, Yoshizaki T
  • Journal Title: Auris Nasus Larynx Volume: 39(5) Issue: 5 Pages: 512-8
  • DOI: 10.1016/j.anl.2011.09.004
  • Peer Reviewed
• [Journal Article] Current understanding and management of nasopharyngeal carcinoma (2012)
  • Author(s): Yoshizaki T, Ito M, Murono S, Wakisaka N, Kondo S, Endo K
  • Journal Title: Auris Nasus Larynx Volume: 39(2) Issue: 2 Pages: 137-44
  • DOI: 10.1016/j.anl.2011.02.012
  • NAID: 120003959461
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus latent membrane protein 1 inducescancer stem/progenitor-like cells in nasopharyngeal epithelial cell lines (2011)
  • Author(s): Kondo S, Wakisaka N, Muramatsu M, Zen Y, Endo K, Murono S, Sugimoto H, YamaokaS, Pagano JS, Yoshizaki T
  • Journal Title: Jvirol Volume: 85(21) Issue: 21 Pages: 11255-64
  • DOI: 10.1128/jvi.00188-11
  • Peer Reviewed
• [Journal Article] Epidemiological analysis ofnasopharyngeal carcinoma in the central region of Japan during the period from 1996 to 2005. (2011)
  • Author(s): Kimura Y, Suzuki D, Tokunaga T, Takabayashi T, Yamada T, Wakisaka N, Yoshizaki T, Murata H, Miwa K, Shoujaku H, Watanabe Y, Yamada N, Ito Y, Yuta A, Takeuchi K,Hosokawa S, Mineta H, Hasegawa Y, Fujimoto Y, Nakashima T, Fujieda S
  • Journal Title: Auris Nasus Larynx Volume: 38(2) Issue: 2 Pages: 244-9
  • DOI: 10.1016/j.anl.2010.07.006
  • Peer Reviewed
• [Journal Article] Pseudoaneurysm of the lingual artery after concurrent intra-arterial chemotherapy with radiotherapy for advanced tongue cancer. (2011)
  • Author(s): Murono S, Nakanishi Y, Inoue D, Ozaki K, Kondo S, Wakisaka N, Matsui O,Yoshizaki T
  • Journal Title: Head Neck Volume: 33(8) Issue: 8 Pages: 1230-2
  • DOI: 10.1002/hed.21372
  • Peer Reviewed
• [Journal Article] Epidemiological analysis of nasopharyngeal carcinoma in the central region Japan during the period from 1996 to 2005 (2011)
  • Author(s): Kimura Y, et al
  • Journal Title: Auris Nasus Larynx Volume: 38 Pages: 244-9
  • Peer Reviewed
• [Journal Article] Epidemiological analysis of nasopharyngeal carcinoma in the central ragion of Japan during the period from 1996 to 2005. (2010)
  • Author(s): Kimura Y, et al
  • Journal Title: Auris Nasus Larynx Volume: 38 Pages: 244-249
  • Peer Reviewed
• [Journal Article] Pseudoaneurysm of the lingual artery after concurrent intra-arterial chemotherapy with radiotherapy for advanced tongue cancer (2010)
  • Author(s): Murono S, et al
  • Journal Title: Head Neck Volume: In press
  • Peer Reviewed
• [Journal Article] Discerning regulation of cis- and trans-presentation of CD8+ T-cell epitopes by EBV-encoded oncogene LMP-1 through self-aggregation. (2009)
  • Author(s): Smith C, Wakisaka N, Crough T, Peet J, Yoshizaki T, Beagley L, Khanna R
  • Journal Title: Blood Volume: 113(24) Issue: 24 Pages: 6148-52
  • DOI: 10.1182/blood-2009-02-203687
  • Peer Reviewed
• [Journal Article] An extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer. (2009)
  • Author(s): Murono S, Hirota K, Kondo S, Wakisaka N, Furukawa M, Yoshizaki T
  • Journal Title: Auris Nasus Larynx Volume: 36(5) Issue: 5 Pages: 614-7
  • DOI: 10.1016/j.anl.2009.01.010
  • Peer Reviewed
• [Journal Article] A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG-PET findings. (2009)
  • Author(s): Wakisaka N, Kondo S, Murono S, Minato H, Furukawa M, Yoshizaki T
  • Journal Title: Auris Nasus Larynx Volume: 36(3) Issue: 3 Pages: 367-71
  • DOI: 10.1016/j.anl.2008.05.010
  • NAID: 120001342300
  • Peer Reviewed
• [Journal Article] Discerning regulation of cis- and trans-presentation of CD8+ T-cell epitopes by EBV-encoded oncogene LMP-1 through self-aggregation. (2009)
  • Author(s): Wakisaka N, et al.
  • Journal Title: Blood 113 Pages: 6148-6152
  • Peer Reviewed
• [Journal Article] An extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer. (2009)
  • Author(s): Murono S, Wakisaka N, et al.
  • Journal Title: Auris Nasus Larynx 36 Pages: 614-617
  • Peer Reviewed
• [Journal Article] A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG-PET findings. (2009)
  • Author(s): Wakisaka N, et al.
  • Journal Title: Auris Nasus Larynx 36 Pages: 367-371
  • NAID: 120001130408
  • Peer Reviewed
• [Presentation] 上咽頭癌におけるEBV-LMP1抗原提示能に関する基礎的研究 (2012)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 第30回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 琵琶湖ホテル(大津)
  • Year and Date: 2012-02-16
• [Presentation] Adjuvant chemotherapy with an oral fluoropyrimidine, S-1, following reduced-RADPLAT in advanced laryngeal cancer (2012)
  • Author(s): Naohiro Wakisaka
  • Organizer: The14th Japan-Korea
  • Place of Presentation: 京都ホテル（京都）
• [Presentation] 進行喉頭癌における動注化学放射線療法後のS-1補助化学療法の有用性に関する検討 (2012)
  • Author(s): 脇坂 尚宏
  • Organizer: 第113回日本耳鼻咽喉科学会
  • Place of Presentation: 朱鷺メッセ（新潟）
• [Presentation] 上咽頭癌におけるリンパ管新生とリンパ節転移に関する免疫組織化学的検討 (2012)
  • Author(s): 脇坂 尚宏
  • Organizer: 第36回日本頭頸部癌学会
  • Place of Presentation: 島根県民会館（松江）
• [Presentation] 16 Concurrent intra-arterial chemotherapy and radiotherapy for advanced laryngeal cancer (2012)
  • Author(s): Shigeyuki Murono
  • Organizer: 9th ELS Congress 2012
  • Place of Presentation: Marina Congress Centre (Finland)
• [Presentation] 頭頸部癌CDDP化学療法における悪心・嘔吐に対する5-HT３受容体拮抗薬の有効性に関する検討 (2012)
  • Author(s): 脇坂 尚宏
  • Organizer: 第74回耳鼻咽喉科臨床学会
  • Place of Presentation: 東京ドームホテル（東京）
• [Presentation] 進行喉頭癌における動注化学放射線療法後のS-1補助化学療法の有用性に関する検討 (2012)
  • Author(s): 脇坂 尚宏
  • Organizer: 第64回日本気管食道科学会
  • Place of Presentation: ホテル日航東京（東京）
• [Presentation] 当科における進行喉頭癌に対する動注化学療法と放射線同時併用療法に関する検討 (2011)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 第63回日本気管食道科学会
  • Place of Presentation: 名古屋東急ホテル(名古屋)
  • Year and Date: 2011-11-10
• [Presentation] 頭頸部癌のリンパ節転移が疑われた神経鞘腫の2症例 (2011)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 第73回耳鼻咽頭科臨床学会
  • Place of Presentation: 長野県松本文化会館(松本)
  • Year and Date: 2011-06-23
• [Presentation] 当科における進行喉頭癌に対する動注化学療法と放射線同時併用療法に関する臨床的検討 (2011)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 第35回日本頭頸部癌学会
  • Place of Presentation: ウインクあいち(名古屋)
  • Year and Date: 2011-06-09
• [Presentation] 金沢大学における進行喉頭癌に対する動注化学療法と放射線同時併用療法に関する臨床的検討 (2011)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 第23回喉頭科学会
  • Place of Presentation: 旭川グランドホテル(旭川)
  • Year and Date: 2011-04-21
• [Presentation] 上咽頭癌におけるEBV-LMP1抗原提示能に関する基礎的研究 (2011)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大分県(全日空ホテルオアシスタワー)
  • Year and Date: 2011-02-12
• [Presentation] Regulation of cis-presentation of CD8+T-cell epitopes by EBV-encoded LMP1 through self-aggregation (2010)
  • Author(s): Naohiro Wakisaka, et al
  • Organizer: EBV Meeting
  • Place of Presentation: University of Birmingham 英国
  • Year and Date: 2010-09-06
• [Presentation] 頭頸部癌における動注化学療法と放射線療法の同時併用療法後のTS-1補助化学療法の有効性に関する検討 (2009)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 日本頭頸部癌学会
  • Place of Presentation: ロイトン札幌(札幌)
  • Year and Date: 2009-10-03
• [Presentation] Regulation of presentation of CD8+ T-cell epitopes specific for EBV-encoded oncogene LMP1 in nasopharyngeal carcinoma (2009)
  • Author(s): 脇坂尚宏, et al
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜国際会議場(横浜)
  • Year and Date: 2009-06-11
• [Presentation] 上咽頭癌におけるEBV-LMP1特異的な細胞障害性T細胞(CTL)活性化機構に関する基礎的研究 (2009)
  • Author(s): 脇坂尚宏, ら
  • Organizer: 日本耳鼻咽喉科学会
  • Place of Presentation: プリンスタワー東京(東京)
  • Year and Date: 2009-05-15
• [Book] 上咽頭癌 (2012)
  • Author(s): 脇坂尚宏, 吉崎智一
  • Publisher: 中山書店
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med31/