Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis.

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer.

High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Estrogen inhibition of Mullerian inhibiting substance in the chick embryo.

Diethylstilbestrol (DES) feminizes the embryonic chick testes and causes retention of the Mullerian duct, an observation made by Etienne Wolff in 1939. The present study was designed to determine if the feminized testis could produce Mullerian Inhibiting Substance (MIS). DES in various doses was injected into the air sac or yolk of 5-day chick embryos, with removal of the gonads at 13-16 days of incubation. That the DES-treated testis was feminized was documented by the development of a left "ovarian" cortex, yet this gonad continued to produce MIS as estimated by a graded organ-culture assay. The male chick Mullerian ducts, exposed to both endogenous MIS and exogenous estrogen (DES), however, were preserved, indicating that the Mullerian duct retention seen in DES-treated embryos was not caused by suppression of MIS secretion. These data support the hypothesis that MIS and estrogens interact at the target-organ (i.e., Mullerian duct), resulting in Mullerian duct retention. The implications of this hypothesis for mammalian sexual development especially in regard to the effect of DES-treatment on male fetuses, and the possible role of MIS and estrogens in testicular descent are considered.

[Influence of puromycin on the regression of Mullerian ducts in chick embryos submitted to a testicular graft]. / Influence de la puromycine sur la régression des canaux de Müller de l'embryon femelle de Poulet, soumis à la greffe testiculaire

Puromycin, an inhibitor of protein synthesis, strongly reduces the incidence of retrogression of the mullerian ducts provoked by testicular graft in the female chick embryo.