Annual Report 2019
Division of Supportive Care Research
Yasuhito Uezono, Junko Ezuka
Introduction
In 2015, the Division of Supportive Care Research started its activities in the Exploratory Oncology Research & Clinical Trial Center (EPOC), aimed at innovative research specifically for supportive and palliative care. Supportive and palliative care research is important and indispensable for improving the quality of life (QOL) in patients suffering from cancer. Our division’s work is ongoing for this purpose, in particular, to innovate novel drugs for improving severe pain and symptoms of cancer cachexia that worsen the QOL in cancer patients.
Research activities
In 2019, our division undertook and conducted three major projects regarding the development of novel pain killers and drugs to improve symptoms of cancer cachexia and derilium after surgical operations as follows:
1) Development of "the new pain-killer compound X", which can remove oral pain without changing the texture and taste of food for cancer patients with severe painful stomatitis, supported intellectually and financially by the Project Promoting Support for Drug Discovery from the Japan Agency for Medical Research and Development (AMED). The compound was successfully licensed out to the pharmaceutical company Maruho Co. Ltd.
2) Identification of novel receptors specifically for des-acylghrelin, and its application as a novel drug for improvement of cardio-toxicity induced by anti-cancer drugs or in cachexia. This project is supported by the National Cancer Center Research and Development Fund.
3) Development of novel biomarkers that predict dexmedetomidine-refractory delirium in cancer patients after and during surgical operations. This project is supported by the Practical Research for Innovative Cancer Control of the AMED. We found several novel biomarkers that predict the onset of delirium itself, and patent applications are underway.
Future prospects
With novel seeds discovered by the Division of Cancer Pathophysiology of the National Cancer Center Research Institute (NCCRI) that we co-host in the National Cancer Center (NCC), we are going to propose and innovate novel therapeutics at the division to improve the QOL in patients suffering from cancer pain, cancer cachexia, and symptoms not relieved by drugs currently available.
List of papers published in 2019
Journal
1. Miyano K, Eto M, Hitomi S, Matsumoto T, Hasegawa S, Hirano A, Nagabuchi K, Asai N, Uzu M, Nonaka M, Omiya Y, Kaneko A, Ono K, Fujii H, Higami Y, Kono T, Uezono Y. The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis. Sci Rep, 10:625, 2020
2. Miyano K, Ohshima K, Suzuki N, Furuya S, Yoshida Y, Nonaka M, Higami Y, Yoshizawa K, Fujii H, Uezono Y. Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors. Front Nutr, 7:5, 2020
3. Miyano K, Ohbuchi K, Sudo Y, Minami K, Yokoyama T, Yamamoto M, Uzu M, Nonaka M, Shiraishi S, Murata H, Higami Y, Uezono Y. A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy. J Pharmacol Sci, 143:320-324, 2020
4. Yatsuoka W, Ueno T, Miyano K, Uezono Y, Enomoto A, Kaneko M, Ota S, Soga T, Sugimoto M, Ushijima T. Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw. PLoS One, 14:e0220712, 2019
5. Uzu M, Nonaka M, Miyano K, Sato H, Kurebayashi N, Yanagihara K, Sakurai T, Hisaka A, Uezono Y. A novel strategy for treatment of cancer cachexia targeting xanthine oxidase in the brain. J Pharmacol Sci, 140:109-112, 2019
6. Manabe S, Miyano K, Fujii Y, Ohshima K, Yoshida Y, Nonaka M, Uzu M, Matsuoka Y, Sato T, Uezono Y, Morimatsu H. Possible biased analgesic of hydromorphone through the G protein-over beta-arrestin-mediated pathway: cAMP, CellKey, and receptor internalization analyses. J Pharmacol Sci, 140:171-177, 2019
7. Miyano K, Shiraishi S, Minami K, Sudo Y, Suzuki M, Yokoyama T, Terawaki K, Nonaka M, Murata H, Higami Y. Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways. Int J Mol Sci, 20:E3271, 2019
8. Karaki F, Umemoto S, Ashizawa K, Oki T, Sato N, Ogino T, Ishibashi N, Someya R, Miyano K, Hirayama S, Uezono Y, Fujii H. A New Lead Identification Strategy: Screening an sp(3) -rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives. ChemMedChem, 14:1840-1848, 2019