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Research Projects

First-in-human, second and third clinical trials to develop a novel analgesic for oral mucositis in cancer patients

First-in-human trial and II/III clinical trials

(Supported by the Drug Discovery Support Promotion Project, Japan Agency for Medical Research and Development (AMED))

  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]

Development of novel compounds for the inhibition of platelet-activating factor (PAF) signaling loops, the pathway causing progression of severe chronic pain

Innovation of novel PAF-loop inhibiting compounds – seeds innovation

(Collaboration research with the Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, and supported by the Japan Agency for Medical Research and Development (AMED))

  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]

Development of novel and specific agonists for m/g opioid heterodimerized receptors

Innovation of opioid analgesics that cause fewer side effects – seeds innovation

(Collaboration research with Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, and supported by National Cancer Center Research and Development Fund)

  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]

Development of compounds for the improvement of cancer cachexic symptoms: clinical application of ghrelin and des-acyl ghrelin for the inhibition of cardiac intoxication from chemotherapy and/or improvement of symptoms of cancer cachexia

  •  Development of ghrelin and des-acyl ghrelin as novel compounds for improvement of symptoms of cancer cachexia – I, II, III clinical trial
  • Identification of a novel des-acyl ghrelin receptor yet cloned with collaboration with National Cerebral and Cardiovascular Center and Kagoshima University)
  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.