Genetherapy for Head and Neck Cancer using carrier cell-based delivery of replication-selective adenoviral vector

• Project/Area Number: 21390462
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kobe University
• Principal Investigator: NIBU Ken-ichi 神戸大学, 医学研究科, 教授 (20251283)
• Co-Investigator(Kenkyū-buntansha): OTSUKI Naoki 神戸大学, 医学研究科, 准教授 (40343264) ; SHIRAKAWA Toshiro 神戸大学, 医学研究科, 准教授 (70335446)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 頭頸部癌 / 遺伝子治療 / アデノウイルス / ミドカイン / siRNA / Gene therapy / midkine / gene therapy / EGFR / VEGF / 制限増殖型 / アデノウイルスベクター / シスプラチン / Endostatin

Research Abstract

While multimodal treatments have been performed for the treatment of head and neck cancers, the prognoses of the patients with advanced head and neck cancer are still poor. The estimated survival rates of those patients are around 30%. New strategies for the treatment for head and neck cancer are desirable. To address this issue, we developed the midkine promoter-driven replication-selective adenoviral vector containing siRNA for EGFR or VEGF. With this adenoviral vector, synergistic effect of oncolytic adenovirus and inhibition of oncogene via RNA interference is effect.

Research Products

• [Journal Article] E10A, an adenovirus-carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma (2012)
  • Author(s): Adhim Z, Lin X, Huang W, Morishita N, Nakamura T, Yasui H, Otsuki N, Shigemura K, Fujisawa M, Nibu K, Shirakawa T
  • Journal Title: Cancer Gene Ther Volume: 19 Pages: 144-152
• [Journal Article] Multi-institutional analysis of solitary extramedullary plasmacytoma of the head and neck treated with curative radiotherapy (2012)
  • Author(s): Sasaki R, Yasuda K, Abe E, Uchida N, Kawashima M, Uno T, Fujiwara M, Shioyama Y, Kagam i Y, Shibamoto Y, Nakata K, Takada Y, Kawabe T, Uehara K, Nibu K, Yamada S
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: 82 Pages: 626-34
• [Journal Article] Blowing ratio as an evaluation tool for velopharyngeal function after oral and oropharyngeal cancer resection (2012)
  • Author(s): Katoh C, Saitoh M, Tsuneyuki M, Tanimoto H, Hashikawa K, Tahara S, Otsuki N, Nibu K
  • Journal Title: Head Neck Volume: 32 Pages: 1012-8
• [Journal Article] Multi-institutional analysis of solitary extramedullary plasmacytoma of the head and neck treated with curative radiotherapy. (2012)
  • Author(s): Sasaki R
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 82(2) Issue: 2 Pages: 626-634
  • DOI: 10.1016/j.ijrobp.2010.11.037
  • Peer Reviewed
• [Journal Article] Four cases of spinal accessory nerve passing through the fenestrated internal jugular vein (2012)
  • Author(s): Hashimoto Y, Otsuki N, Morimoto K, Saito M, Nibu KI
  • Journal Title: Surg Radiol Anat Volume: (in press) Issue: 4 Pages: 373-375
  • DOI: 10.1007/s00276-011-0875-x
  • Peer Reviewed
• [Journal Article] In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines (2011)
  • Author(s): Adhim Z, Matsuoka T, Bito T, Shigemura K, Lee KM, Kawabata M, Fujisawa M, Nibu K, Shirakawa T
  • Journal Title: B r J Cancer Volume: 102 Pages: 393-402
• [Journal Article] Weekly paclitaxel in patients with recurrent or metastatic head a nd neck cancer (2011)
  • Author(s): T ahara M, Minami H, Hasegawa Y, Tomita K, Watanabe A, Nibu K, Fujii M, Onozawa Y, Kurono Y, Sagae D, Seriu T, Tsukuda M
  • Journal Title: Cancer Chemother Pharmacol Volume: 68 Pages: 769-76
• [Journal Article] In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines (2011)
  • Author(s): Adhim Z, Matsuoka T, Bito T, Shigemura K, Lee KM, Kawabata M, Fujisawa M, Nibu K, Shirakawa T
  • Journal Title: Br J Cancer Volume: 102 Issue: 3 Pages: 393-402
  • DOI: 10.1038/bjc.2011.262
  • Peer Reviewed
• [Journal Article] Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer (2011)
  • Author(s): Tahara M, Minami H, Hasegawa Y, Tomita K, Watanabe A, Nibu K, Fujii M, Onozawa Y, Kurono Y, Sagae D, Seriu T, Tsukuda M
  • Journal Title: Cancer Chemother Pharmacol Volume: 68 Issue: 3 Pages: 69-76
  • DOI: 10.1007/s00280-010-1550-3
  • Peer Reviewed
• [Journal Article] Swallowing rehabilitation before and during concurrent chemoradiotherapy for oropharyngeal cancer (2011)
  • Author(s): 常行美貴、米澤宏一郎、森本浩一、谷本均、齋藤幹、大月直樹、丹生健一
  • Journal Title: Toukeibu Gan Volume: 37 Issue: 1 Pages: 116-120
  • DOI: 10.5981/jjhnc.37.116
  • NAID: 10030815016
  • ISSN: 1349-5747, 1881-8382
  • Peer Reviewed
• [Journal Article] Indications of elective neck dissection and postoperative radiotherapy for parotid cancers (2011)
  • Author(s): 柴田智久、米澤宏一郎、森本浩一、山下大介、大月直樹、西村英輝、佐々木良平,丹生健一
  • Journal Title: Toukeibu Gan Volume: 37 Issue: 1 Pages: 78-82
  • DOI: 10.5981/jjhnc.37.78
  • NAID: 10030814927
  • ISSN: 1349-5747, 1881-8382
  • Peer Reviewed
• [Journal Article] Post-operative radiation therapy for locally advanced hypopharyngeal carcinoma (2011)
  • Author(s): 西村英輝、佐々木良平, 吉田賢史, 宮脇大輔, 大月直樹, 斉藤幹, 清田尚臣, 副島俊典, 杉村和朗, 丹生健一
  • Journal Title: Toukeibu Gan Volume: 37 Issue: 1 Pages: 62-66
  • DOI: 10.5981/jjhnc.37.62
  • NAID: 10030814868
  • ISSN: 1349-5747, 1881-8382
  • Peer Reviewed
• [Journal Article] 頭頸部癌における集学的治療頸部郭清術後の肩・上肢運動機能のリハビリテーション (2011)
  • Author(s): 大月直樹、丹生健一
  • Journal Title: JOHNS27 Volume: 4 Pages: 630-633
  • Peer Reviewed
• [Journal Article] 耳鼻咽喉科・頭頸部外科の看護技術2011癌治療に対する看護口腔・中咽頭癌 (2011)
  • Author(s): 常行美貴、米澤宏一郎、齋藤幹、大月直樹、丹生健一
  • Journal Title: JOHNS27 Volume: 3 Pages: 407-411
  • Peer Reviewed
• [Journal Article] Quality of life after neck dissection : a multicenter longitudinal study by the Japanese Clinical Study Group on Standardization of Treatment for Lymph Node Metastasis of Head and Neck Cancer (2010)
  • Author(s): Nibu K, Ebihara Y, Ebihara M, Kawabata K, Onitsuka T, Fujii T, Saikawa M
  • Journal Title: Int J Clin Oncol Volume: 15 Pages: 33-8
• [Journal Article] Depressed expression of Klotho and FGF receptor1in hyperplastic parathyroid glands from uremic patients (2010)
  • Author(s): Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, Tominaga Y, Otsuki N, Nibu K, Nakagawa K, Tsugawa N, Okano T, Kitazawa R, Fukagawa M, Kita T
  • Journal Title: Kidney Int Volume: 77 Pages: 232-8
• [Journal Article] Nuclear factor-kappaB expression as a novel marker of radioresistance in early-stage laryngeal cancer (2010)
  • Author(s): Yoshida K, Sasaki R, Nishimura H, Okamoto Y, Suzuki Y, Kawabe T, Saito M, Otsuki N, Hayashi Y, Soejima T, Nibu K, Sugimura K
  • Journal Title: Head Neck Volume: 32 Pages: 646-55
• [Journal Article] Quality of life after neck dissection-a multicenter longitudinal study by the Japanese study group on standardization of treatment for lymph node metastasis of head and neck cancer. (2010)
  • Author(s): Nibu K, et al.
  • Journal Title: Int J Clin Oncol Volume: 15 Pages: 33-38
  • Peer Reviewed
• [Journal Article] Nuclear factor-kb expression as a novel marker of radioresistance in early-stage laryngeal cancer. (2010)
  • Author(s): Yoshida K, et al
  • Journal Title: Head Neck Volume: 32 Pages: 646-655
  • Peer Reviewed
• [Journal Article] Outpatient administration of radioactive iodine after total thyroidectomy for pediatric thyroid cancer : a report of three cases (2009)
  • Author(s): T akano T, Yane K, Oue T, Otsuki N, Nibu K, Hidaka Y
  • Journal Title: Int J Pediatr Otorhinolaryngol Volume: 73 Pages: 1810-3
• [Journal Article] Cyclooxygenase2promoter-based replication-selective adenoviral vector for hypopharyngeal cancer (2009)
  • Author(s): Nakagawa T, Tanaka H, Shirakawa T, Gotoh A, Hayashi Y, Hamada K, Tsukuda M, Nibu K
  • Journal Title: Arch Otolaryngol Head Neck Surg Volume: 135 Pages: 282-6
• [Journal Article] Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer.
  • Author(s): Tahara M, et al.
  • Journal Title: Cancer Chemother Pharmacol Volume: (in press)
  • Peer Reviewed
• [Presentation] Serum and tissue metabolomics of head and neck cancer (2011)
  • Author(s): Yonezawa K, Otsuki N, Nibu K
  • Organizer: 11^<th> Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2011-12-08
• [Presentation] E10A, an adenovirus carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low dose cisplatin in a xenograft mouse model for head and neck squamous cell carcinoma (2011)
  • Author(s): Zainal Adhimi, Xubin Lin, Wenlin Huang, Tsutomu Nakamura, Hiroyuki Yasui, Naoki Otsuki, Masato Fujisawa, Ken-ichi Nibu, Toshiro Shirakawa
  • Organizer: The 11th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: 神戸日本
  • Year and Date: 2011-12-08
• [Presentation] Morishita N, Kawabata M, Nibu K. Gene silencing with siRNA targeting E6/E7 as a therapeutic intervention against Head and Neck Cancer containing HPV16 cell lines (2011)
  • Author(s): A dhim Z, Otsuki N, Shirakawa T
  • Organizer: San Francisco2011Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery
  • Place of Presentation: SanFrancisco
  • Year and Date: 2011-11-11
• [Presentation] Gene silencing with siRNA targeting E6/E7 as a therapeutic intervention against Head and Neck Cancer containing HPV16 cell lines (2011)
  • Author(s): Zainal Adhim, Naoki Otsuki, Toshiro Shirakawa, Naoya Morishita, Masato Kawabata, Ken-ichi Nibu
  • Organizer: Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery 2011
  • Place of Presentation: サンフランシスコ、アメリカ
  • Year and Date: 2011-09-11
• [Presentation] E10A, an adenovirus carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low dose cisplatin in a xenograft mouse model for head and neck squamous cell carcinoma (2011)
  • Author(s): Zainal Adhimi Xubin Lin, Wenlin Huang, Tsutomu Nakamura, Hiroyuki Yasui, Naoki Otsuki Masato Fujisawa, Ken-ichi Nibu, Toshiro Shirakawa
  • Organizer: Annual Meeting of Japan Society of Gene Therapy 2011
  • Place of Presentation: 福岡日本
  • Year and Date: 2011-07-16
• [Presentation] E10A, an adenovirus carrying endostatin gene, enhanced anti-tumor effect of metronomic chemotherapy with low dose cisplatin in a xenograft mouse model for head and neck squamous cell carcinoma (2011)
  • Author(s): Zainal Adhimi, Xubin Lin, Wenlin Huang, Tsutomu Nakamura, Hiroyuki Yasui, Naoki Otsuki, Ken-ichi Nibu, Masato Fujisawa, Toshiro Shirakawa
  • Organizer: Annual Meeting of American Society of Gene Therapy and Cellular Therapy 2011
  • Place of Presentation: シアトル、アメリカ
  • Year and Date: 2011-05-21
• [Presentation] E10A, an adenovirus carrying endostatin gene, enhanced anti-tumor effect of metronomic chemotherapy with low dose cisplatin in a xenograft mouse model for head and neck squamous cell carcinoma (2011)
  • Author(s): Adhim Z, Lin X, H uang W, Nakamura T, Yasui H, Otsuki N, Nibu K^1, Fujisawa M, Shirakawa T
  • Organizer: 14^<th> Annual Meeting of American Society of Gene Therapy and Cellular Therapy
  • Place of Presentation: Seattle
  • Year and Date: 2011-05-18
• [Presentation] Combination therapy of Ad-Endostatin and Cisplatium for head and neck cancer (2009)
  • Author(s): Zainal Adhim
  • Organizer: International Symposium at Korea University Combined tumor immunotherapy using oncolytic virus and innate immunity
  • Place of Presentation: Soul, Korea
  • Year and Date: 2009-08-18
• [Book] 耳下腺腫脹今日の治療指針2011 (2011)
  • Author(s): 大月直樹
  • Publisher: 医学書院
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/jibi/1.ht