The efficacy and safety of dutasteride and finasteride in patients with benign prostatic hyperplasia: a systematic review and meta-analysis.

Background: Although the efficacy and safety of monotherapy in the treatment of benign prostatic hyperplasia (BPH) have been established clinically, the efficacy and safety of dutasteride and finasteride have not been compared. The aim was to systematically evaluate the efficacy and safety of the two drugs in the treatment of BPH to provide medical evidence for clinical treatment. Methods: A search of relevant articles was conducted using the electronic databases PubMed, Embase, Medline, Cochrane Library, China Academic Journals Full-text Database (CJFD), Chinese Science and Technology Journal Database (VIP) and Wanfang Database. Randomized controlled trials (RCTs) comparing the efficacy of finasteride (control group) with that of dutasteride (experimental group) in the treatment of BPH with respect to the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), prostate volume (PV), quality of life (QOL), serum prostate-specific antigen (PSA) level and adverse drug reactions (ADRs) after medication were strictly evaluated and considered for inclusion. Rev Man 5.4 software was used for the meta-analysis. Results: A total of 8 RCTs were included, with a total of 2,116, patients. The meta-analysis showed that compared with finasteride, dutasteride can effectively improve the Qmax of patients with BPH [mean difference (MD) =0.32; 95% confidence interval (CI): (0.01, 0.63); P=0.04]. There was no significant difference in reducing IPSS [MD =0.13; 95% CI: (-0.55, 0.82); P=0.70], improving PV [MD =-1.25; 95% CI: (-3.30, 0.79); P=0.23], reducing QOL [MD =-0.44; 95% CI: (-0.93, 0.05); P=0.08] and serum PSA level [MD =-0.04; 95% CI: (-0.15, 0.07); P=0.50], and the occurrence of ADRs [relative risk (RR) =-0.01; 95% CI: (-0.05, 0.04); P=0.72], there was no significant difference. Discussion: Dutasteride is better than finasteride in improving the Qmax of patients with BPH. There was no statistically significant difference in symptoms, PV, PSA, QOL, or adverse reactions. Dutasteride is an effective and safe treatment for BPH. Due to the limitations of the methodological quality and sample size of the included studies, this conclusion needs to be verified by stratified RCTS with high volumes and long follow-up times.

Long non-coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer.

BACKGROUND: Bone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa. METHODS: NORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD. RESULTS: PCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells. CONCLUSIONS: NORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.

Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinoma.

BACKGROUND: In the clinic, how to stratify renal cell carcinoma (RCC) patients with different risks and to accurately predict their prognostic outcome remains a crucial issue. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients. METHODS: The expression of gankyrin was examined in public databases and validated in specimens from two independent centers. The clinical practice and disease correlation of gankyrin in RCC were evaluated in RCC patients, various cell lines and an orthotopic RCC model. FINDINGS: Upregulation of gankyrin expression in RCC was corroborated in two independent cohorts. High gankyrin expression positively associated with disease progression and metastasis of RCC patients. A positive correlation between gankyrin and sunitinib-resistance was also observed in RCC cell lines and in an orthotopic RCC model. Kaplan-Meier analysis revealed that patients with higher gankyrin expression presented worse prognosis of RCC patients in the two cohorts. Gankyrin served as an independent prognostic factor for RCC patients even after multivariable adjustment by clinical variables. Time-dependent AUC and Harrell's c-index analysis presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Fuhrman nuclear grade or SSIGN score achieved a greater accuracy than without it in predicting prognosis of RCC patients. All results were confirmed in randomized training and validation sets from the two patient cohorts. INTERPRETATION: Gankyrin can serve as a reliable biomarker for disease progression and for prognosis of RCC patients. Combining gankyrin with the current clinical parameters may help patient management. FUND: National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Medical Discipline Construction Project of Pudong New Area Commission of Health and Family Planning (PWYgf2018-03), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No. PWR12016-05).

[Expression and significance of GFR alpha 1 gene in the recovery spermatogenesis of mice].

OBJECTIVE: To discuss the expression and significance of glial cell-derived neurotrophic factor (GDFN) receptor alpha 1 gene (GFR alpha 1) in the recovery spermatogenesis of mice. METHODS: Adult Kunming mice were injected intraperitoneally with 2 doses of busulfan (10 mg/kg) 24 days apart so as to establish the recovery spermatogenesis model. Testes were harvested 1 w, 2 w, 3 w, 4 w, 6 w, 8 w and 10 w after the second injection, and normal testes were used as control. The recovery spermatogenesis was observed by light and electron microscopy, and the GFR alpha 1 mRNA was measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization. RESULTS: The expression of GFR alpha 1 mRNA increased significantly at 1 w and reached its peak at 2 w after the second injection [(104.72 +/- 24.4)% vs normal control, P < 0.01]; its expression reduced significantly at 3 w and reached its valley at 4 w [(20.77 +/- 4.25)% vs normal control, P < 0.01], and then increased gradually and restored to the normal level at 10 w. GFR alpha 1 mRNA was mainly expressed by undifferentiated spermatogonia. CONCLUSIONS: In the course of recovery spermatogenesis, the expression of GFR alpha 1 plays a key role in turning the spermatogonial stem cell reactivity to GDNF, which promotes self-renewal at a high level, or results in differentiation at a low level.