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Annual Report 2018

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 specific 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 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 2018, our division undertook and conducted four major projects regarding the development of novel pain-killers and drugs to improve symptoms of cancer cachexia 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, intellectually and financially supported 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) Screening out novel drugs for "Relief from neuropathic pain by blocking the plateletactivating factor (PAF)-pain loop", which is supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the AMED.

3) Identification of novel receptors specific for des-acylghrelin, and its application as a drug for improvement of cardio-toxicity induced by anti-cancer drugs in cancer patients. This project is supported by the National Cancer Center Research and Development Fund.

4) Development of novel biomarkers that predict dexmedetomidine-refactory delirium in cancer patients after and during surgical operation. This project is supported by the Practical Research for Innovative Cancer Control of the AMED.

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 2018

Journal

 1. Meguro Y, Miyano K, Hirayama S, Yoshida Y, Ishibashi N, Ogino T, Fujii Y, Manabe S, Eto M, Nonaka M, Fujii H, Ueta Y, Narita M, Sata N, Yada T, Uezono Y. Neuropeptide oxytocin enhances mu opioid receptor signaling as a positive allosteric modulator. J Pharmacol Sci, 137:67-75, 2018

 2. Miyano K, Nonaka M, Uzu M, Ohshima K, Uezono Y. Multifunctional Actions of Ninjinyoeito, a Japanese Kampo Medicine: Accumulated Scientific Evidence Based on Experiments With Cells and Animal Models, and Clinical Studies. Front Nutr, 5:93, 2018

 3. Sudo Y, Otsuka H, Miyakawa R, Goto A, Kashiwase Y, Terawaki K, Miyano K, Hirao Y, Taki K, Tagawa R, Kobayashi M, Okita N, Uezono Y, Higami Y. Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia. Int J Mol Sci, 19:2018

 4. Terawaki K, Kashiwase Y, Uzu M, Nonaka M, Sawada Y, Miyano K, Higami Y, Yanagihara K, Yamamoto M, Uezono Y. Leukemia inhibitory factor via the Toll-like receptor 5 signaling pathway involves aggravation of cachexia induced by human gastric cancer- derived 85As2 cells in rats. Oncotarget, 9:34748-34764, 2018

Book

 1. Uezono Y, Miyano K. Visceral hypersensitivity in functional dyspepsia (FD) - Therapeutic approaches to FD based on suppression of visceral hypersensitivity. In: Tominaga T, Kusunoki H (ed), Functional Dyspepsia: Evidences in Pathophysiology and Treatment, Singapore, Springer Singapore, pp 167-178, 2018