Combination of navitoclax (Bcl-2 and Bcl-xL inhibitor) and Debio-0932 (Hsp90 inhibitor) suppresses the viability of prostate cancer cells via induction of apoptotic signaling pathway.

Prostate cancer is one of the most common cancers in men. Given the diverse nature of prostate cancer and its tendency to respond differently to various treatments, combination therapies are often employed to enhance outcomes. In this study, the synergetic efficiency of chemotherapeutic drug Navitoclax and heat shock protein 90 (Hsp90) inhibitor Debio-0932 was evaluated in human prostate cancer cell line (PC3). Our results indicated that Navitoclax-Debio-0932 combination exhibited synergistic activity in PC3 cells at concentrations lower than IC50 values. The combination of Navitoclax and Debio-0932 decreased PC3 cell viability in a dose dependent manner at 48 h. To investigate the apoptotic potential of the Navitoclax-Debio-0932 combination against prostate cancer cells, the mRNA and protein expression levels of apoptotic and antiapoptotic markers (Bax, Bcl-2, Bcl-xL, Cyt-c, Apaf-1, Casp-3, Casp-7, and Casp-9) were measured using RT-PCR and ELISA assay. Furthermore, the cleavage activity of Casp-3 was determined by colorimetric assay. The results revealed that Navitoclax-Debio-0932 combination potently induced intrinsic apoptotic pathway in PC3 cells rather than using drugs alone. The combined treatment of Navitoclax and Debio-0932 displayed synergistic cytotoxic and apoptotic effects on prostate cancer cells, presenting a promising approach for combination therapy in prostate cancer.

Molecular mechanism of anticancer effect of heat shock protein 90 inhibitor BIIB021 in human bladder cancer cell line.

Bladder cancer is a type of urologic malignancy that exhibits significant morbidity, mortality, and treatment costs. Inhibition of heat shock protein 90 (HSP90) activity has been a promising pharmacological strategy for blocking of bladder cancer pathogenesis. BIIB021 is a next-generation HSP90 inhibitor which interrupts ATP hydrolysis process of HSP90 and inhibits the stabilization and correct folding of client proteins. In current study, we aimed to investigate the molecular mechanism of the anticancer activity of BIIB021 in human bladder cancer T24 cells. Our results revealed that nanomolar concentration of BIIB021 decreased viability of T24 cell. BIIB021 downregulated HSP90 expression in T24 cells and inhibited the refolding activity of luciferase in the presence of T24 cell lysate. PCR array data indicated a significant alteration in transcript levels of cancer-related genes involved in metastases, apoptotic cell death, cell cycle, cellular senescence, DNA damage and repair mechanisms, epithelial-to-mesenchymal transition, hypoxia, telomeres and telomerase, and cancer metabolism pathways in T24 cells. All findings hypothesize that BIIB021 could exhibit as effective HSP90 inhibitor in the future for treatment of bladder cancer patients.

Microperc Versus Miniperc for Treatment of Renal Stones Smaller Than 2 cm in Pediatric Patients.

PURPOSE: Pediatric stone disease is an important clinical problem in pediatric urology practice. We aimed to compare mini-percutaneous nephrolithotomy (miniperc) and micro-percutaneous nephrolithotomy (microperc) in pediatric patients who underwent unsuccesful SWL procedure. MATERIALS AND METHODS: A number of 43 pediatric patients, aged 17 years or younger, were treated with miniperc or microperc procedures due to renal calculi by a single surgeon. In group 1, there were 27 patients who underwent miniperc procedure. In group 2, 16 patients were treated by microperc. RESULTS: Mean age of the patients were 9.5 (3-17) years in group 1 and 7.9 (2-16) years in group 2 (P = .25). Stone burden was similar between the two groups. Mean operation duration was 74.1 (40-110) minutes in miniperc group and 37.2 (20-55) minutes in microperc group (P < .01). Patients who underwent microperc were discharged from clinic earlier. Hyperthermia without bacteraemia was observed in 2 children in the miniperc group and was treated by using a single dose of paracetamol and also 2 children in the same group needed blood transfusion. There was a tendency for low haemoglobin decrease in microperc group compared to miniperc (P > .05). CONCLUSION: The management of pediatric stone disease has evolved with improvements in techniques and minimalisation of surgical instruments and thus, it can be effectively and safely used in children by experienced surgeons. .