細胞生理学

  1. Okinami T, Imamura M, Nishikawa N, Negoro H, Sugino Y, Yoshimura K, Kanematsu A, Hashitani H, Ogawa O. Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis. PLoS One 2014; 9(8):e104216. PMID: 25099633
  2. Mitsui R, Hashitani H. Functional properties of submucosal venules in the rat stomach. Pflugers Arch.2014; 467:1327-42. PMID: 25066613
  3. Shigemasa Y, Lam M, Mitsui R, Hashitani H. Voltage dependence of slow wave frequency in the guinea pig prostate. J Urol. 2014; 92:1286-92. PMID: 24641914
  4. Lang RJ, Tonta MA, Takano H, Hashitani H. Voltage - operated Ca2+ currents and Ca2+ - activated Cl- currents in single interstitial cells of the guinea - pig prostate. BJU Int. 2014; 114:436-46. PMID: 24467706

脳神経生理学

  1. Jung CG, Uhm KO, Horike H, Kim MJ, Misumi S, Ishida A, Ued Y, Choi EK, Kim YS, Michikawa M, Hida H. Auraptene increases the production of amyloid-beta via c-Jun N-terminal kinase-dependent activation of γ-secretase. J Alzheimers Dis, 43: 1215-28, 2015.
  2. Uhm KO, Kim MJ, Kawaguchi M, Akatsu H, Miura Y, Misumi S, Hida H, Choi EK, Kim YS, Michikawa M, Jung CG. ATBF1 is a novel amyloid-β protein precursor protein (AβPP) binding protein that affects AβPP expression. J Alzheimers Dis, 43: 243-257, 2015.
  3. Nagaya Y, Aoyama M, Tamura T, Kakita H, Kato S, Hida H, Saito S, Asai K. Inflammatory cytokine tumor necrosis factor (TNF) suppresses neuroprotective erythropoietin (EPO) expression in astrocytes. Eur J Neurosci. 40(11): 3620-6, 2014.
  4. Ueda Y, Masuda T, Ishida A, Misumi S, Shimizu Y, Jung CG, Hida H. Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration.  J Neurosci. Res., 92(11): 1499-1508, 2014.

実験病態病理学

実験病態病理学では、主に前立腺癌・肝癌・膵癌・大腸癌を中心に発がん過程から転移に至る多段階発がんメカニズムの解析および多種多様な因子の発がん修飾作用を追究している。また環境中の化学物質などのヒトへの健康に対する影響を評価するリスクアセスメントや食品中に含まれる成分のがん予防効果の検討に関する研究を実施している。

  1. Sato, S., Suzuki, S., Naiki-Ito, A., Komiya, M., Long, N., Kato, H., Sagawa, H., Yamashita, Y., Shirai, T., Takahashi, S.: Establishment of an invasive prostate cancer model in transgenic rats by intermittent testosterone administration. J Toxicol Pathol, 27: 43-49, 2014.
  2. Naiki, T., Naiki-Ito, A., Asamoto, M., Kawai, N., Tozawa, K., Etani, T., Sato, S., Suzuki, S., Shirai, T., Kohri, K., Takahashi, S.: GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer. Carcinogenesis, 35: 1962-1967, 2014.
  3. Punfa, W., Suzuki, S., Pitchakarn, P., Yodkeeree, S., Naiki, T., Takahashi, S., Limtrakul, P.: Curcumin-loaded PLGA nanoparticles conjugated with anti-P-glycoprotein antibody to overcome multidrug resistance. Asian Pac J Cancer Prev, 15: 9249-9258, 2014.
  4. 内木綾、内木拓、高橋智:前立腺癌の発生. 臨床泌尿器科, 68: 27-31, 2014.
  5. 佐藤慎哉、鈴木周五、内木綾、白井智之、高橋智:前立腺癌に対するHDAC阻害剤の予防および治療効果の検討. 泌尿器外科, 27: 1217-1219, 2014.
  6. 白井智之:職業発がんの歴史. 日本の現状. 病理と臨床, 32: 606-613, 2014.
  7. Naiki-Ito, A., Chewonarin, T., Tang, M., Pitchakarn, P., Kuno, T., Ogawa, K., Asamoto, M., Shirai, T., Takahashi, S.: Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis. Prostate, 75: 151-160, 2015.
  8. Hayashi, N., Kataoka, H., Yano, S., Tanaka, M., Moriwaki, K., Akashi, H., Suzuki, S., Mori, Y., Kubota, E., Tanida, S., Takahashi, S., Joh, T.: A novel photodynamic therapy targeting cancer cells and tumor-associated macrophages. Mol Cancer Ther, 14: 452-460, 2015.
  9. Suzuki, S., Naiki-Ito, A., Kuno, T., Punfa, W., Long, N., Kato, H., Inaguma, S., Komiya, M., Shirai, T., Takahashi, S.: Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats. J Toxicol Pathol, 28: 21-26, 2015.
  10. Etani, T., Suzuki, T., Naiki, T., Naiki-Ito, A., Ando, R., Iida, K., Kawai, N., Tozawa, K., Miyata, N., Kohri, K., Takahashi, S.: NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect. Oncotarget, 6: 2865-2878, 2015.

免疫学

癌や免疫疾患の分子機構の解明と新しい治療法への貢献を目指し、樹状細胞と制御性T細胞の相互関係の研究及び補体の制御機構の研究を行っている。

2014年度業績
Yamazaki S, Nishioka A, Kasuya S, Ohkura N, Hemmi H, Kaisho T, Taguchi O, Sakaguchi S, Morita A. Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin. J Immunol. 193:5488-97. 2014


細菌学

  1. Analysis of the roles of NrdR and DnaB from Streptococcus pyogenes in response to host defense. Zhang Y, Okada R, Isaka M, Tatsuno I, Isobe K, Hasegawa T. APMIS. 2015 Mar;123(3):252-9. doi: 10.1111/apm.12340. Epub 2014 Dec 3.
  2. Emergence of type I restriction modification system-negative emm1 type Streptococcus pyogenes clinical isolates in Japan. Okada R, Matsumoto M, Zhang Y, Isaka M, Tatsuno I, Hasegawa T. APMIS. 2014 Oct;122(10):914-21.
  3. Relevance of the two-component sensor protein CiaH to acid and oxidative stress responses in Streptococcus pyogenes. Tatsuno I, Isaka M, Okada R, Zhang Y, Hasegawa T. BMC Res Notes. 2014 Mar 28;7:189. doi: 10.1186/1756-0500-7-189.
  4. Simultaneous isolation of emm89-type Streptococcus pyogenes strains with a wild-type or mutated covS gene from a single streptococcal toxic shock syndrome patient. Masuno K, Okada R, Zhang Y, Isaka M, Tatsuno I, Shibata S, Hasegawa T. J Med Microbiol. 2014 Apr;63(Pt 4):504-7. doi: 10.1099/jmm.0.070300-0. Epub 2014 Jan 25.

分子毒性学

ナノ材料等の新規物質の発がん性評価法の開発および評価を行っています。また、発がんモデル動物の開発、発がん性を評価できる腫瘍マーカーの探索も行なっています。

  1. Numano T, Xu J, Futakuchi M, Fukamachi K, Alexander DB, Furukawa F, Kanno J, Hirose A, Tsuda H, Suzui M. Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro. Asian Pac J Cancer Prev. 2014;15(2):929-935.
  2. Sakai Y, Fukamachi K, Futakuchi M, Miyoshi I, Tsuda H, Suzui M, Hayashi H. A novel transgenic mouse model carrying human Tribbles related protein 3 (TRB3) gene and its site specific phenotype. Biol Pharm Bull. 2014;37(6):1068-1074.
  3. Xu J, Alexander DB, Futakuchi M, Numano T, Fukamachi K, Suzui M, Omori T, Kanno J, Hirose A, Tsuda H. Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes. Cancer Sci. 2014;105(7):763-769.
  4. Fukamachi K, Iigo M, Hagiwara Y, Shibata K, Futakuchi M, Alexander DB, Hino O, Suzui M, Tsuda H. Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer. PLoS One. 2014;9(10):e111481.

腎・泌尿器科学

腎・泌尿器科学講座では、以下の各分野においてラット・マウスを用い研究を行っている。
@ 尿路結石研究グループ:尿路結石をメタボリックシンドロームの一病態と捉え、遺伝因子と環境因子の両面から研究を推し進め、尿路結石形成過程における分子機構の解明と治療への応用をめざしている。
A 小児先天異常研究グループ:尿道下裂、停留精巣、逆流性腎症などの疾患の病態解明を通じ、生殖細胞の発生・分化、性分化機構、尿路の発生過程を明らかにすべく研究を行っている。
B 不妊研究グループ:遺伝子導入法を用いた精子形成関連遺伝子の機能解析などの動物実験および臨床研究から、造精機能障害の病態解明をめざして研究を進めている。
C 腫瘍研究グループ:分子生物学的手法を用いた、泌尿器癌の制圧を目標としている。膀胱癌の早期診断や分子標的治療、前立腺癌の転移機構の解明、温熱治療をめざして研究を行っている。
D 排尿研究グループ:前立腺肥大症の細胞増殖機構や過活動膀胱における膀胱興奮性発生機序の解明と効果的かつ効率的な治療をめざして研究を進めている。

【2014年度業績】
  1. 1. Moritoki Y, Hayashi Y, Mizuno K, Kamisawa H, Nishio H, Kurokawa S, Ugawa S, Kojima Y, Kohri K. Expression profiling of microRNA in cryptorchid testes: miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1. J Urol., 191: 1174-1180, 2014. (doi: 10.1016/j.juro.2013.10.137)
  2. Ichikawa J, Okada A, Taguchi K, Fujii Y, Zuo L, Niimi K, Hamamoto S, Kubota Y, Umemoto Y, Itoh Y, Yasui T, Kawai N, Tozawa K, Kohri K. Increased crystal-cell interaction in vitro under co-culture of renal tubular cells and adipocytes by in vitro co-culture paracrine systems simulating metabolic syndrome. Urolithiasis, 42: 17-28, 2014. (doi: 10.1007/s00240-013-0612-5)
  3. Yasui T, Kobayashi T, Okada A, Hamamoto S, Hirose M, Mizuno K, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Gao B, Kohri K. Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid. BMC Res Notes, 7:87, 2014. (doi: 10.1186/1756-0500-7-87)
  4. Zuo L, Okada A, Yasui T, Taguchi K, Ito Y, Hirose Y, Fujii Y, Niimi K, Hamamoto S, Ando R, Itoh Y, Zuo J, Tozawa K, Kohri K. A paracrine mechanism involving renal tubular cells, adipocytes, and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment. J Urol. 191: 1906-1912, 2014. (doi: 10.1016/j.juro.2014.01.013)
  5. Nishio H, Hayashi Y, Moritoki Y, Kamisawa H, Mizuno K, Kojima Y, Kohri K. Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes. J Urol. 191: 1564-1572, 2014. (doi: 10.1016/j.juro.2013.10.071)
  6. Hamakawa T, Sasaki S, Shibata Y, Imura M, Kubota Y, Kojima Y, Kohri K. Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells. Prostate, 74: 590-601, 2014. (doi: 10.1002/pros.22773)
  7. Niimi K, Yasui T, Okada A, Hirose Y, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Kohri K. Novel effect of the inhibitor of mitochondrial cyclophilinD activation, N-methyl-4-isoleucine cyclosporine, on renal calcium crystallization. Int J Urol. 21: 707-713, 2014. (doi: 10.1111/iju.12425)
  8. Naiki T, Naiki-Ito A, Asamoto M, Kawai N, Tozawa K, Etani T, Sato S, Suzuki S, Shirai T, Kohri K. Takahashi S. GPX2 overexpression is involved in cellproliferation and prognosis of castration-resistant prostate cancer. Carcinogenesis. 35: 1962-1967, 2014. (doi: 10.1093/carcin/bgu048)
  9. Taguchi K, Okada A, Kitamura H, Yasui T, Naiki T, Hamamoto S, Ando R, Mizuno K, Kawai N, Tozawa K, Asano K, Tanaka M, Miyoshi I, Kohri K. Colony-stimulating factor-1 signaling suppresses renal crystal formation. J Am Soc Nephrol, 25: 1680-1697, 2014. (doi: 10.1681/ASN.2013060675)
  10. Iwatsuki S. Influence of siRNA-expressing vector transfection on adult rat testis in vivo. Nagoya Medical Journal. 54: 9-21, 2014.
  11. Yamada K. UQCRAB is involved in bladder carcinogenesis in mouse and human. Nagoya Medical Journal. 54: 23-32, 2014.
  12. 梅本 幸裕:精子形成障害への遺伝子治療。医学のあゆみ、249: 44-48、2014
  13. 河合 憲康:前立腺がん骨転移巣に対する抗RANKL抗体結合型マグネタイトを用いた選択的磁場誘導加温法の開発。がん治療のあゆみ、1-6、2014

病態モデル医学

  1. Sherman-Baust CA, Kuhn E, Valle BL, Shih IM, Kurman RJ, Wang TL, Amano T, Ko MS, Miyoshi I, Araki Y, Lehrmann E, Zhang Y, Becker KG, Morin PJ. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol., 10.1002/path.4353. 2014