Background: The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance.Methods: Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay.Results: Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin,comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel.Conclusion: The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance

Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.

Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS), and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT) is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.
Aged ; Deamino Arginine Vasopressin ; Drinking ; Efficiency ; Humans ; Hypogonadism ; Lower Urinary Tract Symptoms ; Male ; Mental Health ; Nocturia* ; Quality of Life ; Sleep Wake Disorders ; Testosterone*

AIMTo examine the physiological role of the androgen receptor (AR) in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter.

METHODSWe generated an AR-expressing PC-3(AR)9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3(AR)2 (stable clone that expresses AR under the control of the cytomegalovirus (CMV) promoter, established by Heisler et al.) after androgen treatment.

RESULTSWe found that dihydrotestosterone (DHT) from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3(AR)2 compared with its vector control, PC-3(pIRES). In contrast, PC-3(AR)9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT.

CONCLUSIONThese data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer (AIPC) PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3(AR)9 prostate cancer cells.

Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; DNA, Complementary ; biosynthesis ; Dihydrotestosterone ; pharmacology ; Humans ; Male ; Promoter Regions, Genetic ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Androgen ; biosynthesis ; genetics ; Transfection

Aging ; Biochemistry ; Brachytherapy ; Humans ; Hypogonadism ; Injections, Intramuscular ; Male ; Polycythemia ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Recurrence ; Reference Values ; Testosterone

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of≥7 and 273 had a GS of <7 or no malignancy. In this study, patients aged 75 years or older were classified as elderly patients. GS ≥ 7 was characterized by a prostate-specific antigen (PSA) of the maximum area under the curve of 12 ng ml