519-520 20/7/06 11:00 Page 1 INTERNATIONAL JOURNAL OF ONCOLOGY 29: 519-520, 2006 1 Cover legend: Michihiko Kuwano; a member of The Editorial Academy of The International Journal of Oncology merase II·, thioredoxin, glutathione S-transferase and some transcriptional factors with acquired drug-resistance in cancer cells. In particular, they found that transcriptional activation of human MDR1 gene by anticancer agents, radiation and other environmental stimuli is specifically mediated through Y-box binding protein-1 (YB-1) in human cancer cells, suggesting that MDR1 gene is an SOS gene that is highly susceptible to anticancer treatments. Moreover, he developed various angiogenesis model systems in vivo as well as in vitro to study how tumor angiogenesis is induced in collaboration with Dr Mayumi Ono (Kyushu University) and Dr Yasufumi Sato (Tohoku University). Dr Kuwano then moved to Graduate School of Medical Sciences Kyushu University (1993-2003) as professor and Dr Michihiko Kuwano is professor and director at Research chairman. He continued to look for molecular targets that Center for Innovative Cancer Therapy at Kurume University, could be useful in development of potent therapeutic Kurume, Fukuoka, Japan. At present, his focus is on the strategies against human cancer. Dr Kuwano and his establishment of molecular targets that could be closely colleagues first succeeded in isolating a human multidrug associated with drug resistance and other malignant resistance-related protein 2 (MRP2)/ABCC2 and MRP3/ characteristics in cancer cells and their micro-environments ABCC3, and identified ABCC2 gene as responsible for a in tumor stroma. These molecular targets will be intrinsically hereditary familiar hepatic jaundice, Dubin-Johnson important to development of novel and useful therapeutic syndrome. Moreover, they presented paracrine and autocrine strategies that could be great help for cancer patients. control of angiogenesis in response to inflammatory Dr Kuwano graduated from Kyushu University School cytokines at molecular basis, indicating a model that of Medicine (M.D.) in 1964. He had already started his infiltration of activated macrophages plays a critical role in research career in molecular biology of bacteria and bacterio- the inflammatory angiogenesis in cancer. phage when he was a medical student. He received his Ph.D. Currently, Dr Kuwano continues his translational on genetics on ribosomes by analysis of bacterial antibiotics- research on the molecular targets discovered to apply this resistant mutants at Medical Institute of Bioregulation, Kyushu knowledge to novel and potent therapeutic strategies for University (Professor Hideya Endo). Based on this molecular cancer patients, at Kurume University as Professor (2003- biology study with bacterial mutants, he further continued present). Dr Kuwano has published almost 400 peer-viewed bacterial molecular biology research on protein synthesis and original research articles, and is now focused on two unique mRNA degradation during postdoctoral fellowship at anticancer research fields of intrinsic importance. 1) How to Department of Microbiology and Immunology, Washington develop scientific evidence-based therapeutic strategy by University School of Medicine (St. Louis) (Professor David YB-1 in various human malignancies. He has recently Schlessinger) (1969-1971), and at the Medical Institute of repoted a novel finding that nuclear translocation of YB-1 Bioregulation, Kyushu University (1971-1978). confers acquired multiple drug-resistance. This suggests that An important discovery was the determination of a gene YB-1 is a global drug resistance-related molecular target. Dr named ams (altered mRNA stability)/RNaseE which plays a Kuwano is now eager to establish YB-1 related gene key role in turnover of messenger RNA. In the middle of networks as plausible targets to limit global drug resistance 1970, Dr Kuwano started his research on cancer with and other malignant characteristics. 2) Dr Kuwano together mammalian cells. He established mutants from cancer cells with Dr Mayumi Ono has presented that infiltration of with altered sensitivity to various anticancer drugs in Japan, macrophages and/or tumor-associated macrophages play key and examined how drug-resistance is acquired at molecular roles in acquiring various malignant characteristics including basis. Dr Kuwano moved to Oita University School of tumor angiogenesis and invasion, possibly through activation Medicine as professor and chairman of Biochemistry (1978- of inflammatory signals by NF-κB, cyclooxygenases, 1993). Together with Dr Shin-ichi Akiyama (Kagoshima inflammatory cytokine, and chemokines. His final goals are University) and Dr Kimitoshi Kohno (University of to find molecules in cancer cells and their environment, and Occupational and Environmental Health), he discovered the to develop a therapeutic strategy by targeting these molecules close association of P-glycoprotein/MDR1, DNA topoiso- for cancer patients. 519-520 20/7/06 11:00 Page 2 INTERNATIONAL JOURNAL OF ONCOLOGY 29: 519-520, 2006 Besides his scientific devotion to cancer research, Dr Dr Kuwano's career has been dedicated to development Kuwano was also the Dean of Graduate School of Medical of somatic cell genetics on anticancer drug resistance, and Sciences, Kyushu University (1999-2003). He organized the molecular biology of growth, motility/invasion and 1st Annual Meeting of Japanese Society of Medical Oncology angiogenesis by cancer cells. Based on these basic studies on (JSMO) (2003), and also the 63rd Annual Meeting of the cancer progression and acquirement of malignant Japanese Cancer Association (JCA) (2004) as a president. He characteristics, Dr Kuwano will further contribute to the has also been working as an editorial member of International development of translational research to the bed-side. These Journal of Oncology, Molecular Cancer Therapeutics, Cancer research activities currently continue in good harmony with Science, Angiogenesis, and other international journals. He both young and senior scientists, presenting a novel and received the Yamagiwa-Yoshida International Medical Fund useful knowledge to ‘the concept of proof of principle’ in (UICC, 1974) and the Japanese Biochemical Society Prize clinical oncology as well as cancer biology. (1978). He now energetically continues his cancer research at Kurume University..