Prostate cancers generally become androgen-independent and resistant to hormone therapy with progression. To understand the underlying mechanisms and facilitate the development of novel treatments for androgen-independent prostate cancer, we have investigated plasma membrane-associated sialidase (NEU3), the key enzyme for ganglioside hydrolysis participating in transmembrane signaling. We have discovered NEU3 to be upregulated in human prostate cancer compared with non-cancerous tissue, correlating with the Gleason score. NEU3 silencing with siRNA in prostate cancer PC-3 and LNCaP cells resulted in increased expression of differentiation markers and in cell apoptosis, but decrease in Bcl-2 as well as a progression-related transcription factor, early growth response gene (EGR-1). In androgen-sensitive LNCaP cells, forced overexpression of NEU3 significantly induced expression of EGR-1, androgen receptor (AR) and PSA both with and without androgen, the cells becoming sensitive to androgen. The NEU3-mediated induction was abrogated by inhibitors for PI-3 kinase and MAP kinase and more specifically by their silencing in the absence of androgen, being confirmed by increased phosphorylation of AKT and ERK1/2 in NEU3 overexpressing cells. NEU3 siRNA introduction caused reduction of cell growth of an androgen-independent PC-3 cells in culture and of transplanted tumors in nude mice. These data suggest that NEU3 regulates tumor progression through AR signaling, and thus be a potential tool for diagnosis and therapy of androgen-independent prostate cancer.

It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms.

7,543 double-contrast barium enema studied for the presence of diverticula which were classified into right-sided, left-sided and bilateral types, and the relationship of the frequency (detection rate) and numbers of diverticula to age were examined for the earlier (1982-87) and later (1988-92) periods. Diverticular disease was found in 22.2% of male and 15.5% of female examinees. The right-sided type predominated among the subjects. Frequency distribution by age of the bilateral type was similar to that of the left-sided type. Bilateral diverticular disease increased in frequency with advancing years in the sixth and seventh decade, the right-sided type increased in middle-aged subjects, and the left-sided type did not. The bilateral type was composed of diverticula in the right colon, where numbers were greater than in the pure right-sided type, but remained unchanged with increasing age, and diverticula in the left colon, where numbers were similar to the pure left-sided type, but did not increase with age. Increase in the prevalence of bilateral and not pure left-sided form has contributed to the recent increase in diverticula in the left colon among the Japanese, and might have been preceded by an increase in the right-sided type.

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