We conduct clinical and basic research with the aim of elucidating the mechanisms related to carcinogenesis and resistance acquisition of urological malignancies and development of novel therapeutic strategies. In clear-cell type renal cell carcinoma, a molecular targeted drug targeting the VEGF-VEGFR signaling pathway downstream of VHL is the key of drug therapy for advanced renal cell carcinoma. We are interested in VBC-Cul2 complex acting as a ubiquitin ligase in its signaling pathway. We are aiming to elucidate the molecules involved in the proliferative and invasive potential of renal cancer cells themselves by identifying new target
molecules via VBC-Cul2 complex under three-dimensional culture using Matrigel or
inducible expression system of VHL gene product pVHL. In urological cancer as well, immuno - checkpoint inhibitor has shown excellent therapeutic effect. Using CyTOF
2 as new cell protein expression analysis tool, we are trying to identify unknown cell populations which leads to prediction of treatment effect or drug resistance in human. Using urine samples from a model mouse, a search for diagnostic biomarkers for human Xp11.2 translocation type renal carcinoma, which is a rare subtype of renal cancer and detailed molecular mechanisms of carcinogenesis and progression have not yet been clarified, is on-going. We focus on the angiopoietin-like factor (ANGPTL Angiopoietin-like protein) family as a protein that promotes angiogenesis and lymphangiogenesis, especially ANGPTL2 which is said to act on vascular cells and monocyte cells. We are investigating the effects of ANGPTL2 on cancer development using mice to elucidate the mechanism of carcinogenesis of renal cell carcinoma. Recently, it has been reported that C5a receptor (C5aR) is expressed in many cancer tissues such as breast cancer and gastric cancer and involved in promoting infiltration ability of cancer cells. We are aiming for novel drug development by elucidating the biological significance of C5a expression in prostate cancer progression. Our department aims to acquire knowledge as a physician and skills as a surgeon through daily clinical practice, and at the same time, we value the viewpoint as a scientist. We believe that such research minds will be of great help to resolve many clinical questions which we encounter in daily practice.