EBV gene expression profile which is affected by virus reactivation and oncogenesis of nasopharyngeal carcinoma.

• Project/Area Number: 18390456
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kanazawa University
• Principal Investigator: TOMOKAZU Yoshizaki (YOSHIZAKI Tomokazu) Kanazawa University, 医学系, 教授 (70262582)
• Co-Investigator(Kenkyū-buntansha): 室野 重之 金沢大学, 医学系研究科, 助教 (20345622) ; 脇坂 尚宏 金沢大学, 医学部附属病院, 助教 (70377414) ; 近藤 悟 金沢大学, 医学部附属病院, 助教 (70436822)
• Co-Investigator(Renkei-kenkyūsha): MURONO Shigeyuki 金沢大学, 附属病院, 講師 (20345622) ; WAKISAKA Naohiro 金沢大学, 附属病院, 講師 (70377414) ; KONDO Satoru 金沢大学, 附属病院, 助教 (70436822)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥17,990,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 癌 / 上咽頭癌 / Epstein-Barrウイルス / LMP1 / ウイルス複製 / メチル化 / Epstein-Barr / ウイルス / エピジェネティクス / がん化 / 上咽頭がん

Research Abstract

ウイルス増殖活性化と癌化の関連について検討した。
1)EBERsはプロテインキナーゼRを阻害して細胞増殖能を促進する
2)ウイルス複製サイクル誘導により、細胞死に至る
3)脱メチル化およびアセチル化、いずれの処理によってもLMP1、EBV複製は誘導されない
4)ウイルス複製により脱メチルかがおこり、複製直後のEBV感染細胞内のLMP1発現は複製誘導前よりも増加する
以上より、EBVLMP1発現は上咽頭がん発癌過程に密接に関与する。しかし、一度がん化した後はがん細胞に影響を及ぼさないことが示唆された。

Research Products

• [Journal Article] Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration. (2009)
  • Author(s): Endo K, Yoshizaki T.
  • Journal Title: Oncogene 8 Pages: 1725-35
  • 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, Yoshizaki T.
  • Journal Title: Blood 11;113 Pages: 6148-52
  • Peer Reviewed
• [Journal Article] Concurrent intra-arterial chemotherapy and radiotherapy for advanced laryngeal cancer. (2009)
  • Author(s): Yoshizaki T.
  • Journal Title: Ann Otol Rhinol Laryngol 118 Pages: 172-8
  • Peer Reviewed
• [Journal Article] Concurrent Intra-arterial Chemotherapy and Radiotherapy for Advanced Laryngeal Cancer (2009)
  • Author(s): Yoshizaki T, Kondo S, Wakisaka N, Murono S, Kitagawa N, Tsuji A, Nakashima M, Sanada J, Matsui O.
  • Journal Title: Ann Otol Rhinol Laryngol 118 Pages: 172-178
  • Peer Reviewed
• [Journal Article] 再発性喉頭乳頭腫に対するシドフォビル治療 (2009)
  • Author(s): 吉崎智一, 辻亮, 室野重之
  • Journal Title: 日本気管食道学会会報 60 Pages: 344-347
  • NAID: 10026104938
  • Peer Reviewed
• [Journal Article] 思春期の頭頸部ウイルス感染症と頭頸部癌 -2種類のがんウイルスEBVとHPVについて- (2009)
  • Author(s): 吉崎智一
  • Journal Title: 耳鼻免疫アレルギー (JJIAO) 27 Pages: 285-289
  • NAID: 10026518265
  • Peer Reviewed
• [Journal Article] Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue. (2008)
  • Author(s): Uramoto N, Furukawa M, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx 36 Pages: 104-5
  • NAID: 120001008422
  • Peer Reviewed
• [Journal Article] Induction of receptor for advanced glycation end products by EBV latent membrane protein 1 and its correlation with angiogenesis and cervical lymph node metastasis in nasopharyngeal carcinoma. (2008)
  • Author(s): Tsuji A, Yoshizaki T.
  • Journal Title: Clin Cancer Res. 14 Pages: 5368-75
  • NAID: 120001130604
  • Peer Reviewed
• [Journal Article] Impact of MDM2 Single Nucleotide Polymorphism on Tumor Onset in Head and Neck Squamous Cell Carcinoma. (2008)
  • Author(s): Nakashima M, Yoshizaki T.
  • Journal Title: Acta Otolaryngologica 128 Pages: 808-13
  • NAID: 120001130200
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer. (2008)
  • Author(s): Shimizu Y, Kondo S, Shirai A, Furukawa M, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx 35 Pages: 381-9
  • Peer Reviewed
• [Journal Article] Treatment of locally recurrent Epstein-Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir. (2008)
  • Author(s): Yoshizaki T, Furukawa M.
  • Journal Title: J Med Virol. 80 Pages: 879-82
  • NAID: 120001135568
  • Peer Reviewed
• [Journal Article] Post-operative pharyngocutaneous fistula after laryngectomy. (2008)
  • Author(s): Wakisaka N, Murono S, Kondo S, Furukawa M, Yoshizaki T.
  • Journal Title: Nasus Larynx 35 Pages: 203-8
  • NAID: 120001135567
  • Peer Reviewed
• [Journal Article] Treatment of locally recurrent Epstein-Barrvirus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir (2008)
  • Author(s): Yoshizaki T(他7名,1番目)
  • Journal Title: J Med Virol 80 Pages: 879-882
  • NAID: 120001135568
• [Journal Article] 悪性疾患をうたがう顔面および頚部所見 上深頚部腫脹 (2008)
  • Author(s): 吉崎智一
  • Journal Title: ENTONI 85 Pages: 41-47
  • Peer Reviewed
• [Journal Article] Treatment of locally recurrent Epstein-Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir. (2008)
  • Author(s): Yoshizaki T, Wakisaka N, Kondo S, Murono S, Shimizu Y, Nakashima M, Tsuji A, Furukawa M.
  • Journal Title: J Med Virol 80 Pages: 879-882
  • NAID: 120001135568
  • Peer Reviewed
• [Journal Article] 動注化学療法の限界 (2008)
  • Author(s): 吉崎智一
  • Journal Title: 癌と化学療法 35 Pages: 1106-1109
  • Peer Reviewed
• [Journal Article] Intra-arterial chemotherapy less intensive than RADPLAT with concurrent radiotherapy for resectable advanced head and neck squamous cell carcinoma: a prospective study. (2007)
  • Author(s): Yoshizaki T, Furukawa M.
  • Journal Title: Ann Otol Rhinol Laryngol 116 Pages: 754-61
  • Peer Reviewed
• [Journal Article] Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. (2007)
  • Author(s): Horikawa T, Yoshizaki T.
  • Journal Title: Cancer Res 67 Pages: 1970-8
  • Peer Reviewed
• [Journal Article] MUC1 induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling. (2007)
  • Author(s): Kondo S, Yoshizaki T.
  • Journal Title: J Virol 81 Pages: 1554-62
  • Peer Reviewed
• [Journal Article] Oncogenic role of Epstein-Barr virus-encoded small RNAs (EBERs) in nasopharyngeal carcinoma. (2007)
  • Author(s): Yoshizaki T, Furukawa M.
  • Journal Title: Auris Nasus Larynx 34 Pages: 73-8
  • Peer Reviewed
• [Journal Article] Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma (2007)
  • Author(s): Horikawa T, Yoshizaki T(他5名, 4番目).
  • Journal Title: Cancer Res 67 Pages: 1970-1978
  • Peer Reviewed
• [Journal Article] MUC1 induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling (2007)
  • Author(s): Kondo S, Yoshizaki T(他7名, 2番目)
  • Journal Title: J Virol 81 Pages: 1554-1562
  • Peer Reviewed
• [Journal Article] Intra-arterial chemotherapy less intensive than RADPLAT with concurrent radiotherapy for resectable advanced head and neck squamous cell carcinoma: a prospective study (2007)
  • Author(s): Yoshizaki T(他9名,1番目)
  • Journal Title: Ann Otol Rhinol Laryngol 116 Pages: 754-761
• [Journal Article] Oncogenic role of Epstein-Barr virus-encoded small RNAs(EBERs)in nasopharyngeal carcinoma (2007)
  • Author(s): Yoshizaki T, Endo K, et. al.
  • Journal Title: Auris Nasus Larynx 34 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Intra-arterial Chemotherapy Less Intensive Than RADPLAT With Collcurrent Radiotherapy for Resectable Asvanced Head and NeckSquamous Cell Carcinoma:A Prospectiv (2007)
  • Author(s): T.Yoshizaki, N.Wakisaka, S.Murono, S.Kondo, Y.Shimizu, T.Takanaka, J.Sanada, N.Terayama, 0.Matsui, M.Furukawa
  • Journal Title: Ann Otol Rhinol Laryngol 116 Pages: 754-761
  • Peer Reviewed
• [Journal Article] 急速動注化学療法による上顎洞癌治療-CDDP投与量との関連について- (2007)
  • Author(s): 吉崎 智一、塚谷 才明、脇坂 尚宏、室野 重之、近藤 悟、高仲 強、古川 仭
  • Journal Title: 頭頸部癌 33 Pages: 434-438
  • NAID: 10020282497
  • Peer Reviewed
• [Journal Article] EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells. (2006)
  • Author(s): Kondo S, Yoshizaki T.
  • Journal Title: Cancer Res 66 Pages: 9870-7
  • Peer Reviewed
• [Journal Article] A case report: Epstein-Barr virus-associated undifferentiated carcinoma of the tongue base. (2006)
  • Author(s): Wakisaka N, Murono S, Minato H, Furukawa M, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx 33 Pages: 87-91
  • NAID: 120000809432
  • Peer Reviewed
• [Journal Article] Prognostic value of cell motility activation factors in patients with tongue squamous cell carcinoma. (2006)
  • Author(s): Endo K, Shirai A, Furukawa M, Yoshizaki T.
  • Journal Title: Hum Pathol 37 Pages: 1111-6
  • Peer Reviewed
• [Journal Article] Cricoid ossification mimicking an impacted foreign body. (2006)
  • Author(s): Wakisaka N, Miwa T, Yoshizaki T, Furukawa M.
  • Journal Title: J Laryngol Otol 120 Pages: 1-3
  • NAID: 120000806297
  • Peer Reviewed
• [Journal Article] Feeding Artery of Laryngeal and Hypopharyngeal Cancers: Role of the Superior Thyroid Artery in Superselective Intraarterial Chemotherapy. (2006)
  • Author(s): Terayama N, Yoshizaki T.
  • Journal Title: Cardiovasc Intervent Radiol 29 Pages: 536-43
  • Peer Reviewed
• [Journal Article] Cleavage of Amyloid-{beta} Precursor Protein (APP) by Membrane-Type Matrix Metalloproteinases. (2006)
  • Author(s): Ahmad M, Yoshizaki T.
  • Journal Title: J Biochem 139 Pages: 517-26
  • Peer Reviewed
• [Journal Article] EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolylydroxylases 1 and 3 in nasopharyngeal epithelial cells (2006)
  • Author(s): Kondo S, Yoshizaki T(他6名, 3番目)
  • Journal Title: Cancer Res 66 Pages: 9870-9877
• [Journal Article] Feeding artery of laryngeal and hypopharyngeal cancers : role of the superior thyroid artery in superselective intraarterial chemotherapy. (2006)
  • Author(s): Terayama N, Yoshizaki T, et al.
  • Journal Title: Cardiovasc Intervent Radiol. 29 Pages: 536-43
• [Journal Article] Cleavage of amyloid-beta precursor protein (APP) by membrane-type matrix metalloproteinases. (2006)
  • Author(s): Ahmad M, Yoshizaki T, et al.
  • Journal Title: J Biochem. 139 Pages: 517-26
• [Journal Article] Cricoid ossification mimicking an impacted foreign body. (2006)
  • Author(s): Wakisaka N, Yoshizaki T, et al.
  • Journal Title: J Laryngol Otol. 120
  • NAID: 120000806297
• [Journal Article] Prognostic value of cell motility activation factors in patients with tongue squamous cell carcinoma. (2006)
  • Author(s): Endo K, Yoshizaki T. et al.
  • Journal Title: Hum Pathol. 37 Pages: 1111-6
• [Journal Article] A case report : Epstein-Barr virus-associated undifferentiated carcinoma of the tongue base. (2006)
  • Author(s): Wakisaka N, Yoshizaki T. et al.
  • Journal Title: Auris Nasus Larynx. 33 Pages: 487-91
  • NAID: 120000809432
• [Journal Article] EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah 1-mediated down-regulation of prolyl hydoxylaser 1 and 3 in nasopharyngeal epithelial cells. (2006)
  • Author(s): Kondo S, Yoshizaki T, et al.
  • Journal Title: Cancer Res. 66 Pages: 9870-7
• [Journal Article] An extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer
  • Author(s): Murono S, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx (in press)
  • Peer Reviewed
• [Journal Article] Prognostic factors for squamous cell carcinoma of the temporal bone: extensive bone involvement or extensive soft tissue involvement?
  • Author(s): Ito M, Hatano M, Yoshizaki T.
  • Journal Title: Acta Otolaryngol (in press)
  • NAID: 120001728439
  • Peer Reviewed
• [Journal Article] A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG-PET findings.
  • Author(s): Wakisaka N, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx (in press)
  • NAID: 120001342300
  • Peer Reviewed
• [Journal Article] Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue.
  • Author(s): Uramoto N, Furukawa M, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx (in press)
  • NAID: 120001008422
  • Peer Reviewed
• [Journal Article] A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG-PET findings.
  • Author(s): Wakisaka N, Yoshizaki T.
  • Journal Title: Auris Nasus Larynx 36 Pages: 367-71
  • NAID: 120001342300
  • Peer Reviewed
• [Presentation] 抗ウイルス剤シドフォビルによる喉頭乳頭腫治療 (2010)
  • Author(s): 吉崎智一
  • Organizer: 第22回日本喉頭科学会総会・学術講演会
  • Place of Presentation: 海峡メッセ下関 (山口県)
  • Year and Date: 2010-03-04
• [Presentation] 喉頭乳頭腫に対するシドフォビル注入について (2008)
  • Author(s): 吉崎智一
  • Organizer: 第60回日本気管食道科学会
  • Place of Presentation: 熊本市
  • Year and Date: 2008-11-07
• [Presentation] 喉頭乳頭腫に対するシドフォビル注入について (2008)
  • Author(s): 吉崎智一
  • Organizer: 第60回日本気管食道科学会
  • Place of Presentation: 熊本県立劇場(熊本県)
  • Year and Date: 2008-11-06
• [Presentation] EB ウイルスRNA・EBERs 発現と感染細胞形質転換能 (2008)
  • Author(s): 吉崎智一
  • Organizer: 日本耳鼻咽喉科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-05-16
• [Presentation] Inter-arterial chemotherapy with concurrent radiotherapy for resectableadvanced head and neck squamous cell carcunoma (2007)
  • Author(s): T.Yoshizaki, T.Horikawa, M.Furukawa
  • Organizer: 第66回日本癌学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2007-10-04
• [Presentation] 遊離皮弁による再建部に再発した頭頸部癌に対する動注化学療法 (2007)
  • Author(s): 吉崎 智一、古川 仭
  • Organizer: 第69回耳鼻咽喉科臨床学会
  • Place of Presentation: 品川プリンスホテル(港区)
  • Year and Date: 2007-07-07
• [Presentation] 遊離皮弁による再建部に再発した頭頸部癌に対する動注化学療法 (2007)
  • Author(s): 吉崎智一, 古川仭
  • Organizer: 第69回耳鼻咽喉科臨床学会
  • Place of Presentation: 品川プリンスホテル, エグゼクティブタワー(東京都)
  • Year and Date: 2007-07-06
• [Presentation] 動注化学療法による上顎癌治療成績-CDDP投与量との関連について- (2007)
  • Author(s): 吉崎 智一、塚谷 才明, ら
  • Organizer: 第31回日本頭頸部癌学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2007-06-15
• [Presentation] 動注化学療法による上顎癌治療成績-CDDP投与量との関連について- (2007)
  • Author(s): 吉崎智一, 塚谷才明, 室野重之, 脇坂尚宏, 近藤悟, 三輪高喜, 古川仭
  • Organizer: 第31回日本頭頸部癌学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2007-06-13
• [Presentation] EBウイルスRNA・EBERs発現と感染細胞形質転換能 (2006)
  • Author(s): 吉崎智一, 清水良憲, 古川仭
  • Organizer: 第24回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 鳥羽国際ホテル(三重県)
  • Year and Date: 2006-03-02