疼痛治療用ヘルペスウイルスの作製

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24592421
• Research Institution: The University of Tokyo
• Principal Investigator: 福原 浩 東京大学, 医学部附属病院, 准教授 (20292948)
• Co-Investigator(Kenkyū-buntansha): 伊藤 伸子 東京大学, 医学部附属病院, 講師 (80332609)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 疼痛

Outline of Annual Research Achievements

本研究の趣旨は、ヘルペスウイルス(HSV-1)を用いて、間質性膀胱炎や癌性疼痛など難治性疼痛の治療を行うことである。神経節に潜伏感染するという、HSV-1が本来有する特徴に着目し、潜伏感染時もモルヒネ様分子を持続的に発現させて難治性疼痛を緩和させるウイルスを作製することを研究目的としている。治療のイメージとしては、疼痛部位にウイルスを注射すると、ウイルス自身が軸索を逆行性に後根神経節まで伝達していき、そこで潜伏感染してLATプロモータ下にモルヒネ様物質が持続的に発現し、疼痛の緩和を図る、というものである。
平成24年度には、既存のT-BACシステムを改変して、潜伏感染LATプロモータ下にモルヒネ様物質を発現するウイルスT3-Xを作製した。平成25年度には、新たに作製されたT3-Xの動物実験における疼痛の評価を様々な方法で行った。
最終年度である平成26年度には、これまでの実験結果から適切なモデルを選択し、行動実験を進めた。具体的には、マウス足底にウイルスを注射して、右足底皮下に30G 針を用いて5％ホルマリン溶液を投与し、右後肢へのlicking time の持続時間を測定するホルマリンテストを行った。その行動実験では、モルヒネ様物質の発現群が対照群と比較して有意に疼痛を減弱させていた。さらに、その神経後根でRT-PCRにてモルヒネ様物質の発現の有無を確認した。
これは、神経後根でのモルヒネ様物質の発現が疼痛を減弱させることを証明し、さらに、モルヒネ様物質を発現する疼痛ウイルスの作製に成功したことを示している。

Research Products

• [Journal Article] A pilot study of autologous tumor lysate-loaded dendritic cell vaccination combined with sunitinib for metastatic renal cell carcinoma. (2015)
  • Author(s): Matsushita H, Enomoto Y, Kume H, Nakagawa T, Fukuhara H, Suzuki M, Fujimura T, Homma Y, Kakimi K.
  • Journal Title: J Immunother Cancer Volume: in press Pages: in press
  • DOI: 10.1186/s40425-014-0030-4. eCollection 2014.
  • Peer Reviewed / Open Access
• [Journal Article] Intermittent docetaxel chemotherapy is feasible for castration-resistant prostate cancer. (2015)
  • Author(s): Kume H, Kawai T, Nagata M, Azuma T, Miyazaki H, Suzuki M, Fujimura T, Nakagawa T, Fukuhara H, Homma Y
  • Journal Title: Molecular and Clinical Oncology Volume: 3 Pages: 303-307
  • Peer Reviewed / Open Access
• [Journal Article] Nocturia in men is a chaotic condition dominated by nocturnal polyuria. (2015)
  • Author(s): Fujimura T, Yamada Y, Sugihara T, Azuma T, Suzuki M, Fukuhara H, Nakagawa T, Kume H, Igawa Y, Homma Y
  • Journal Title: Int J Urol. Volume: 22 Pages: 496-501
  • DOI: 10.1111/iju.12710
  • Peer Reviewed
• [Journal Article] Adjuvant Chemotherapy Is Possibly Beneficial for Locally Advanced or Node-Positive Bladder Cancer. (2015)
  • Author(s): Kanatani A, Nakagawa T, Kawai T, Naito A, Sato Y, Yoshida K, Nozaki K, Nagata M, Yamada Y, Azuma T, Suzuki M, Fujimura T, Fukuhara H, Nishimatsu H, Kume H, Igawa Y, Homma Y
  • Journal Title: Clin Genitourin Cancer Volume: 13 Pages: e107-112
  • DOI: 10.1016/j.clgc.2014.09.007. Epub 2014 Nov 6.
  • Peer Reviewed
• [Journal Article] Long-term caloric restriction in rats may prevent age-related impairment of in vitro bladder function. (2015)
  • Author(s): Ito H, Aizawa N, Fujita Y, Suzuki M, Fukuhara H, Homma Y, Kubota Y, Ito M, Andersson KE, Igawa Y
  • Journal Title: J Urol. Volume: 193 Pages: 2123-2130
  • DOI: 10.1016/j.juro.2014.11.005.
  • Peer Reviewed
• [Journal Article] Combination of docetaxel, ifosfamide and cisplatin (DIP) as a potential salvage chemotherapy for metastatic urothelial carcinoma. (2015)
  • Author(s): Kakutani S, Fukuhara H, Taguchi S, Nagata M, Niimi A, Hattori M, Miyazaki H, Fujimura T, Nakagawa T, Kume H, Igawa Y, Homma Y
  • Journal Title: Jpn J Clin Oncol. Volume: 45 Pages: 281-285
  • DOI: 10.1093/jjco/hyu201.
  • Peer Reviewed
• [Journal Article] Selective inhibitory effect of imidafenacin and 5-hydroxymethyl tolterodine on capsaicin-sensitive C-fibers of the primary bladder mechanosensitive afferent nerves in the rat. (2015)
  • Author(s): Aizawa N, Ito H, Sugiyama R, Fujimura T, Suzuki M, Fukuhara H, Homma Y, Igawa Y
  • Journal Title: J Urol. Volume: 193 Pages: 1423-1432
  • DOI: 10.1016/j.juro.2014.09.005.
  • Peer Reviewed
• [Journal Article] Risk factors for clinical metastasis in men undergoing radical prostatectomy and immediate adjuvant androgen deprivation therapy. (2014)
  • Author(s): Taguchi S, Fukuhara H, Kakutani S, Takeshima Y, Miyazaki H, Suzuki M, Fujimura T, Nakagawa T, Igawa Y, Kume H, Homma Y
  • Journal Title: Asian Pac J Cancer Prev. Volume: 15 Pages: 10729-10733
  • Peer Reviewed / Open Access
• [Journal Article] Ultra-early versus early salvage androgen deprivation therapy for post-prostatectomy biochemical recurrence in pT2-4N0M0 prostate cancer. (2014)
  • Author(s): Taguchi S, Fukuhara H, Azuma T, Suzuki M, Fujimura T, Nakagawa T, Ishikawa A, Kume H, Igawa Y, Homma Y
  • Journal Title: BMC Urol. Volume: 14 Pages: 81-86
  • DOI: 10.1186/1471-2490-14-81.
  • Peer Reviewed / Open Access
• [Journal Article] Granulocyte macrophage colony-stimulating factor as a predictor of the response of metastatic renal cell carcinoma to tyrosine kinase inhibitor therapy. (2014)
  • Author(s): Yamada D, Matsushita H, Azuma T, Nakagawa T, Nagata M, Yamada Y, Suzuki M, Fujimura T, Fukuhara H, Kume H, Homma Y, Kakimi K
  • Journal Title: Mol Clin Oncol. Volume: 2 Pages: 1023-1027
  • Peer Reviewed / Open Access
• [Journal Article] Robot-assisted versus other types of radical prostatectomy: population-based safety and cost comparison in Japan, 2012-2013. (2014)
  • Author(s): Sugihara T, Yasunaga H, Horiguchi H, Matsui H, Fujimura T, Nishimatsu H, Fukuhara H, Kume H, Yu C, Kattan MW, Kiyohide F, Homma Y.
  • Journal Title: Cancer Sci. Volume: 105 Pages: 1421-1426
  • DOI: 10.1111/cas.12523.
  • Peer Reviewed
• [Journal Article] Improvement of symptoms of aging in males by a preparation LEOPIN ROYAL containing aged garlic extract and other five of natural medicines - comparison with traditional herbal medicines (Kampo). (2014)
  • Author(s): Nishimatsu H, Kitamura Y, Yamada D, Nomiya A, Niimi A, Suzuki M, Fujimura T, Fukuhara H, Nakagawa T, Enomoto Y, Kume H, Igawa Y, Homma Y.
  • Journal Title: Aging Male Volume: 17 Pages: 112-116
  • DOI: 10.3109/13685538.2013.771328.
  • Peer Reviewed
• [Journal Article] Long-term results of radical prostatectomy with immediate adjuvant androgen deprivation therapy for pT3N0 prostate cancer. (2014)
  • Author(s): Sato YT, Fukuhara H, Suzuki M, Fujimura T, Nakagawa T, Nishimatsu H, Kume H, Morikawa T, Fukayama M, Homma Y.
  • Journal Title: BMC Urol. Volume: 14 Pages: 13-18
  • DOI: 10.1186/1471-2490-14-13.
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors for septic shock in acute obstructive pyelonephritis requiring emergency drainage of the upper urinary tract. (2014)
  • Author(s): Kamei J, Nishimatsu H, Nakagawa T, Suzuki M, Fujimura T, Fukuhara H, Igawa Y, Kume H, Homma Y
  • Journal Title: Int Urol Nephrol. Volume: 46 Pages: 493-497
  • DOI: 10.1007/s11255-013-0545-5.
  • Peer Reviewed
• [Journal Article] Multiple primary malignant neoplasms of the glottis, renal pelvis, urinary bladder, oral floor, prostate, and esophagus in a Japanese male patient: a case report. (2014)
  • Author(s): 2. Mukaiyama Y, Suzuki M, Morikawa T, Mori Y, Takeshima Y, Fujimura T, Fukuhara H, Nakagawa T, Nishimatsu H, Kume H, Homma Y.
  • Journal Title: World J Surg Oncol. Volume: 12 Pages: 294
  • DOI: 10.1186/1477-7819-12-294.
  • Peer Reviewed / Open Access
• [Journal Article] Intrascrotal dedifferentiated leiomyosarcoma originating from dartos muscle. (2014)
  • Author(s): Teshima T, Takahashi S, Nagamoto S, Miyazaki H, Nakagawa T, Fujimura T, Fukuhara H, Kume H, Homma Y.
  • Journal Title: Case Rep Urol. Volume: 84 Pages: 1929
  • DOI: 10.1155/2014/841929.
  • Peer Reviewed / Open Access