Division of Clinical Pharmacology and Translational Research

Akinobu Hamada, Mitsuhiro Hayashi, Hiroaki Aikawa, Makiko Yamashita, Shoraku Ryu, Mayu Ohuchi, Tomomi Nishijo, Mariko Mizui, Yuki Murai, Rina Baba, Ryosuke Matsukane, Miyuki Momma

Introduction

The Division of Clinical Pharmacology and Translational Research is focused on the development of pharmacokinetics/pharmacodynamics/Pharmacogenetics (PK/PD/PGx) analyzing systems to evaluate efficacy and toxicity in patients and animal models treated with chemotherapy. The system provides drug exposure in blood and tissues by using high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS), a spatial drug distribution on tissue by using mass spectrometry imaging without labeling reagents, and next generation sequencer systems. Recently, we are also focused on the development of an immunomonitoring system detecting patient's ADCC activity.

Our team and what we do

We develop new anticancer agents using unique assay systems.

Research activities

1)There only exist limited evaluation systems for large molecular pharmacokinetics such as antibody drugs that contribute to the obstacle of drug development and translation research. We are trying to evaluate the tissue distribution of antibody drug using a new method in collaboration with an analytical company. We detected the distribution of one approved antibody drug on preclinical tumor tissues using this method. In addition, we have been trying to detect that using a different method such as mass spectrometer.

2)Nanoscale drug delivery system is very useful as it can specifically transmit anti-cancer drugs to tumor sites. The specific accumulation of nanoparticles in tumor was visualized using mass spectrometry imaging. In combination with histological estimation, the factors which influence the delivery of nanoparticles in tumor tissues were also investigated.

Education

Dr. Hamada is Visiting Professor, Department of Medical Oncology and Translational Research, Graduate School of Medical Sciences, Kumamoto University.

Future prospects

The combination of PK/PD/PGx analysis, mass spectrometry imaging, measurement of ADCC activity, and establishment of PDX model can provide us more accurate information about patients. These systems will help develop new anticancer agents and establish personalized medicine in the future.

List of papers published in 2016

Journal

1.Iwamoto N, Shimada T, Terakado H, Hamada A. Validated LC-MS/MS analysis of immune checkpoint inhibitor Nivolumab in human plasma using a Fab peptide-selective quantitation method: nano-surface and molecular-orientation limited (nSMOL) proteolysis. J Chromatogr B Analyt Technol Biomed Life Sci, 1023-1024:9-16, 2016

2.Kurihara H, Shimizu C, Miyakita Y, Yoshida M, Hamada A, Kanayama Y, Yonemori K, Hashimoto J, Tani H, Kodaira M, Yunokawa M, Yamamoto H, Watanabe Y, Fujiwara Y, Tamura K. Molecular imaging using PET for breast cancer. Breast Cancer, 23:24-32, 2016

3.Yamashita M, Kitano S, Aikawa H, Kuchiba A, Hayashi M, Yamamoto N, Tamura K, Hamada A. A novel method for evaluating antibody-dependent cell-mediated cytotoxicity by flowcytometry using cryopreserved human peripheral blood mononuclear cells. Sci Rep, 6:19772, 2016

4.Aikawa H, Hayashi M, Ryu S, Yamashita M, Ohtsuka N, Nishidate M, Fujiwara Y, Hamada A. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging. Sci Rep, 6:23749, 2016

5.Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Goto-Yamaguchi L, Fujiki Y, Fujiwara S, Sueta A, Hayashi M, Takeshita T, Inao T, Iwase H. Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer. Cancer Sci, 107:491-498, 2016

6.Ryu S, Furihata K, Koda M, Wei F, Miyakawa T, Tanokura M. NMR-based analysis of the chemical composition of Japanese persimmon aqueous extracts. Magn Reson Chem, 54:213-221, 2016

7.Tamura T, Hirata T, Tabata M, Hinotsu S, Hamada A, Motoki T, Iwamoto T, Mizoo T, Nogami T, Shien T, Taira N, Matsuoka J, Doihara H. A Phase I Trial of 100 mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer. Acta Med Okayama, 70:425-427, 2016

8.Hirayama M, Tomita Y, Yuno A, Tsukamoto H, Senju S, Imamura Y, Sayem MA, Irie A, Yoshitake Y, Fukuma D, Shinohara M, Hamada A, Jono H, Yuba E, Kono K, Yoshida K, Tsunoda T, Nakayama H, Nishimura Y. An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs. Oncoimmunology, 5:e1123368, 2016

9.Yamagishi M, Tsuta K, Shimoi T, Tanabe Y, Hirai M, Kohno T, Shiraishi K, Nakaoku T, Sunami K, Shimada Y, Tamura K, Hamada A. Automated and rapid system for detection of ALK rearrangement genes in non-small cell lung cancer based on a Quenching Probe method. Biomed Res Clin Prac, 1:36-41, 2016

10.Iwamoto N, Takanashi M, Hamada A, Shimada T. Validated LC/MS Bioanalysis of Rituximab CDR Peptides Using Nano-surface and Molecular-Orientation Limited (nSMOL) Proteolysis. Biol Pharm Bull, 39:1187-1194, 2016

11.Tsuchiya K, Hayashida T, Hamada A, Oka S, Gatanaga H. Brief Report: High Peak Level of Plasma Raltegravir Concentration in Patients With ABCB1 and ABCG2 Genetic Variants. J Acquir Immune Defic Syndr, 72:11-14, 2016

12.Iwamoto N, Takanashi M, Umino Y, Aoki C, Hamada A, Shimada T. Application of nano-surface and molecular-orientation limited proteolysis to LC-MS bioanalysis of cetuximab. Bioanalysis, 8:1009-1020, 2016

13.Iwamoto N, Umino Y, Aoki C, Yamane N, Hamada A, Shimada T. Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano-surface and molecular-orientation limited (nSMOL) proteolysis. Drug Metab Pharmacokinet, 31:46-50, 2016

14.Fujiwara Y, Hamada A, Mizugaki H, Aikawa H, Hata T, Horinouchi H, Kanda S, Goto Y, Itahashi K, Nokihara H, Yamamoto N, Ohe Y. Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism. Cancer Sci, 107:1117-1123, 2016