ABSTRACT
To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement.
Subject(s)
Prostate/pathology , Prostate/surgery , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Period , Prostatic Hyperplasia/physiopathology , Prostatic Hyperplasia/surgery , Quality of Life , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (pâ¯<â¯0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).
Subject(s)
Autophagy-Related Protein-1 Homolog/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Kidney Neoplasms/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Autophagy-Related Protein-1 Homolog/antagonists & inhibitors , Autophagy-Related Protein-1 Homolog/genetics , Benzamides/pharmacology , Benzamides/therapeutic use , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/drug therapy , Cell Line , Female , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/genetics , Kaplan-Meier Estimate , Kidney Neoplasms/drug therapy , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic useABSTRACT
The current study is a retrospective analysis of 49 patients with bone metastatic prostate cancer: 26 receiving androgen deprivation therapy (ADT) alone versus 23 receiving cytoreductive cryosurgery of the primary tumor plus ADT treatment. Progression-free survival (PFS) was the primary outcome variable, and Cox proportional hazards regression analysis was used to identify predictors for PFS. The baseline characteristics were generally comparable between the 2 groups. Median follow-up time was 41 months (range 24-56) and 37 months (range 19-53) in ADT alone group and cryosurgery groups, respectively. Patients receiving cryosurgery had significantly longer PFS (35 vs 25 months, P = 0.0027) and time to castration resistance (36 vs 25 months, P = 0.0011). Cox multivariate analysis associated longer PFS with the following factors: cryosurgery (HR0.207, 95% CI 0.094-0.456), lower prostate specific antigen at diagnosis (≤100 ng/ml, HR0.235, 95% CI 0.072-0.763) and lower Gleason score (≤7, HR0.195, 95% CI 0.077-0.496). Cryosurgery reduced the risk of progression by 79.3%. In conclusion, cytoreductive cryosurgery of the primary tumor in patients with bone metastatic prostate cancer could reduce the risk of progression and delay time to castration-resistant prostate cancer.
