Treatment strategies of urological cancers through the regulation of inflammatory immune response by novel NFkappaB inhibitors

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Tokyo Medical University
• Principal Investigator: NAKASHIMA Jun 東京医科大学, 医学部, 教授 (10167546)
• Co-Investigator(Kenkyū-buntansha): TACHIBANA Masaaki 東京医科大学, 医学部, 教授 (70129526) ; OHNO Yoshio 東京医科大学, 医学部, 准教授 (40266482) ; HORIGUCHI Yutaka 東京医科大学, 医学部, 准教授 (60229234) ; HASHIMOTO TAKESHI 東京医科大学, 医学部, 助教 (10421033) ; GONDO Tatsuo 東京医科大学, 医学部, 講師 (90408097) ; HIRASAWA Yosuke 東京医科大学, 医学部, 助教 (10725310)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: urological cancers / NFkappaB / cytotoxicity / inflammation / prognosis

Outline of Final Research Achievements

Novel NFκB inhibitors showed significant cytotoxicity on our cell lines derived from bladder cancer (BC), renal cell cancer (RCC) and prostate cancer (PC). Although some compounds failed to show a significant induction of apoptosis in PC cells, newly developed compounds showed significant cytotoxic effects on DU145 and PC3 cells. The expression of legumain was confirmed at the mRNA and protein levels in our PC cell lines. The immunochemical-staining patterns of legumain in prostatectomy specimens were significantly associated with unfavorable pathology and prognosis. However, hypoxia and so on did not regulate the expression of legumain. Sarcopenia, NLR and CRP were significantly associated with prognosis in patients with invasive BC, CRPC and advanced RCC and pyuria was an independent prognostic factor for intravesical recurrence in patients with superficial BC, which suggest that inflammatory immune response may play a key role in the disease progression in urological malignancies.

Free Research Field

医学、泌尿器科学