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先端医療開発センター

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主な研究内容

新規口内炎鎮痛薬Compound Xの創薬に向けた橋渡し研究

Compound Xの非臨床試験、Proof of Concept確立、特許化、企業への導出。 中央病院支持療法開発部門との共同でPhase1(First in Human) 試験実施へ。 — 上市を見据えた臨床研究。
(日本医療研究開発機構(AMED)創薬支援推進事業による支援)

  1. Uezono Y, Miyano K, Sudo Y, Suzuki M, Shiraishi S, Terawaki K. A review of traditional Japanese medicines and their potential mechanism of action. Curr Pharm Des, 18:4839-4853, 2012. [PubMed]
  2. Hitomi S, Ono K, Miyano K, Ota Y, Uezono Y, Matoba M, Kuramitsu S, Yamaguchi K, Matsuo K, Seta Y, Harano N, Inenaga K. Novel methods of applying direct chemical and mechanical stimulation to the oral mucosa for traditional behavioral pain assays in conscious rats. J Neurosci Methods, 239:162-169, 2015. [PubMed]
  3. Miyano K, Ueno T, Yatsuoka W, Uezono Y. Treatment for cancer patients with oral mucositis: assessment based on the Mucositis study group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and proposal of possible novel treatment with a Japanese herbal medicine. Curr Pharm Des, 22:2270-2278, 2016. [PubMed]
  4. Yamaguchi K, Ono K, Hitomi S, Ito M, Nodai T, Goto T, Harano N, Watanabe S, Inoue H, Miyano K, Uezono Y, Matoba M, Inenaga K. Distinct TRPV1- and TRPA1-based mechanisms underlying enhancement of oral ulcerative mucositis-induced pain by 5-fluorouracil. Pain, 157:1004-1020, 2016. [PubMed]

難治性疼痛克服に向けた脂質シグナル修飾による新規鎮痛薬の開発

難治性疼痛を継続する脂質シグナルループを阻害することによる難治性疼痛改善薬の創製。 — シーズ開発
(AMED次世代がん医療創生研究事業による研究)
(国立国際医療研究センター研究所脂質シグナリングプロジェクトとの共同研究)

  1. Motoyama N, Morita K, Kitayama T, Shiraishi S, Uezono Y, Nishimura F, Kanematsu T, Dohi T. Pain-releasing action of platelet-activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action. Eur J Pain, 17:1156-1167, 2013. [PubMed]
  2. Shindou H, Shiraishi S, Tokuoka SM, Takahashi Y, Harayama T, Abe T, Bando K, Miyano K, Kita Y, Uezono Y, Shimizu T. Relief from neuropathic pain by blocking of platelet-activating factor-pain loop. FASEB J, Epub ahead of print, 2017. [PubMed]

新規オピオイド製剤の創製と臨床開発

新規μ/δオピオイド二量体化受容体特異的アゴニストの開発。
薬剤耐性を起こさないオピオイド製剤の独自手法による新薬開発およびシーズ展開。
(国立がん研究センター研究開発費シーズ選定による研究)
(北里大学薬学部生命薬化学研究室との共同研究)

  1. Imai S, Sudo Y, Nakamura A, Ozeki A, Asato M, Hojo M, Devi LA, Kuzumaki N, Suzuki T, Uezono Y, Narita M. Possible involvement of β-endorphin in a loss of the coordinated balance of μ-opioid receptors trafficking processes by fentanyl. Synapse, 65:962-966, 2011. [PubMed]
  2. Narita M, Imai S, Nakamura A, Ozeki A, Asato M, Rahmadi M, Sudo Y, Hojo M, Uezono Y, Devi LA, Kuzumaki N, Suzuki T. Possible involvement of prolonging spinal µ-opioid receptor desensitization in the development of antihyperalgesic tolerance to µ-opioids under a neuropathic pain-like state. Addict Biol, 18:614-622, 2013. [PubMed]
  3. Miyano K, Sudo Y, Yokoyama A, Hisaoka-Nakashima K, Morioka N, Takebayashi M, Nakata Y, Higami Y, Uezono Y. History of the G protein-coupled receptor (GPCR) assays from traditional to a state-of-the-art biosensor assay. J Pharmacol Sci, 126:302-309, 2014. [PubMed]
  4. Ohbuchi K, Miyagi C, Suzuki Y, Mizuhara Y, Mizuno K, Omiya Y, Yamamoto M, Warabi E, Sudo Y, Yokoyama A, Miyano K, Hirokawa T, Uezono Y. Ignavine: orthosteric enhancer of the μ opioid receptor. Sci Rep, 6:31748, 2016. [PubMed]

がん悪液質改善薬の開発 — グレリンおよびデスアシルグレリンの、分子メカニズム解明に基づく悪液質改善薬としての臨床応用

グレリン・デスアシルグレリン製剤によるがん悪液質症状の改善。 — 上市を見据えた臨床研究。
(デスアシルグレリン受容体の同定:国立循環器病研究センターおよび鹿児島大学との共同研究)

  1. Terawaki K, Sawada Y, Kashiwase Y, Hashimoto H, Yoshimura M, Suzuki M, Miyano K, Sudo Y, Shiraishi S, Higami Y, Yanagihara K, Kase Y, Ueta Y, Uezono Y. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line. Am J Physiol Endocrinol Metab, 306:E373-387, 2014. [PubMed]
  2. Fujitsuka N, Asakawa A, Morinaga A, Amitani MS, Amitani H, Katsuura G, Sawada Y, Sudo Y, Uezono Y, Mochiki E, Sakata I, Sakai T, Hanazaki K, Yada T, Yakabi K, Sakuma E, Ueki T, Niijima A, Nakagawa K, Okubo N, Takeda H, Asaka M, Inui A. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1. Mol Psychiatry, 21:1613-1623, 2016. [PubMed]
  3. Tagami K, Kashiwase Y, Yokoyama A, Nishimura H, Miyano K, Suzuki M, Shiraishi S, Matoba M, Ohe Y, Uezono Y. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: an in vitro study with cells expressing cloned human growth hormone secretagogue receptor. Neuropeptides, 58:93-101, 2016. [PubMed]
  4. Terawaki K, Kashiwase Y, Sawada Y, Hashimoto H, Yoshimura M, Ohbuchi K, Sudo Y, Suzuki M, Miyano K, Shiraishi S, Higami Y, Yanagihara K, Hattori T, Kase Y, Ueta Y, Uezono Y. Development of ghrelin resistance in a cancer cachexia rat model using human gastric cancer-derived 85As2 cells and the palliative effects of the kampo medicine rikkunshito on the model. PLoS One, 12:e0173113, 2017. [PubMed]
  5. Ohnishi S, Watari H, Kanno M, Ohba Y, Takeuchi S, Miyaji T, Oyamada S, Nomura E, Kato H, Sugiyama T, Asaka M, Sakuragi N, Yamaguchi T, Iwase S, Uezono Y. Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02). J Gynecol Oncol, 28:e44, Epub ahead of print, 2017.