The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.
Humans ; Male ; Carcinogenesis ; Circadian Clocks/physiology* ; Circadian Rhythm/physiology* ; Prostatic Neoplasms/physiopathology*

Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). However, whether the PFME guided by a therapist (G-PFME) can contribute to the recovery of urinary continence for patients after RP is still controversial. We performed this meta-analysis to investigate the effectiveness of G-PFME on UI after RP and to explore whether the additional preoperative G-PFME is superior to postoperative G-PFME alone. Literature search was conducted on Cochrane Library, Embase, Web of Science, and PubMed, to obtain all relevant randomized controlled trials published before March 1, 2018. Outcome data were pooled and analyzed with Review Manager 5.3 to compare the continence rates of G-PFME with control and to compare additional preoperative G-PFME with postoperative G-PFME. Twenty-two articles with 2647 patients were included. The continence rates of G-PFME were all superior to control at different follow-up time points, with the odds ratio (OR) (95% confidence interval [CI]) of 2.79 (1.53-5.07), 2.80 (1.87-4.19), 2.93 (1.19-7.22), 4.11 (2.24-7.55), and 2.41 (1.33-4.36) at 1 month, 3 months, 4 months, 6 months, and 12 months after surgery, respectively. However, there was no difference between additional preoperative G-PFME and postoperative G-PFME, with the OR (95% CI) of 1.70 (0.56-5.11) and 1.35 (0.41-4.40) at 1 month and 3 months after RP, respectively. G-PFME could improve the recovery of urinary continence at both early and long-term stages. Starting the PFME preoperatively might not produce extra benefits for patients at early stage, compared with postoperative PFME.
Humans ; Male ; Muscle, Skeletal/physiopathology* ; Pelvic Floor/physiopathology* ; Physical Therapy Modalities ; Prostatectomy/adverse effects* ; Prostatic Neoplasms/surgery* ; Treatment Outcome ; Urinary Incontinence/therapy*

Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy, specifically cancer-related fatigue (CRF) and quality of life (QoL).Methods Systematic searches for randomized clinical trials (RCTs) evaluating the effects of exercise on CRF and QoL of prostate cancer patients receiving androgen deprivation therapy were carried out to identify the eligible studies from EMBASE, PubMed and Cochrane library. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Standardized mean differences (SMD) and its 95% confidence interval (CI) were calculated.Results In all, 10 RCTs involving 841 prostate cancer patients (448 of whom exercised and 393 did not) were included in this study. With respect to CRF, there was good consistency among different studies, and it was remarkably reduced in the exercise group (SMD=-0.32, 95% CI: -0.45 to -0.18, P<0.00001, n=784). In regards to QoL, there was also good consistency among different studies, and it was also improved significantly in the exercise group (SMD=0.21, 95% CI: 0.08 to 0.34, P=0.002, n=841).Conclusion Exercise both reduced CRF and improved QoL in prostate cancer patients receiving androgen deprivation therapy.
Exercise Therapy ; methods ; Fatigue ; etiology ; physiopathology ; therapy ; Humans ; Male ; Prostatic Neoplasms ; physiopathology ; therapy ; Quality of Life ; Randomized Controlled Trials as Topic

ObjectiveTo investigate the relationship of the expression of vasodilator-stimulated phosphoprotein (VASP) with the metastasis and prognosis of prostate cancer.

METHODSProstate cancer PC3 cells were infected with VASP shRNA and control shRNA lentiviruses, respectively. The invasive ability of the PC3 cells was determined by transwell migration assay, the expression of VASP in the prostate cancer tissue from 56 patients was detected by immunohistochemistry, and the survival rate of the patients was analyzed according to the VASP expression levels and follow-up data after radical prostatectomy.

RESULTSVASP shRNA lentivirus significantly inhibited the expression of VASP and decreased the invasive ability of the PC3 cells as compared with the results obtained in the scramble shRNA and blank control groups (P<0.05). The survival analysis of the 56 prostate cancer patients showed that the time of biochemical recurrence was markedly shorter in the VASP positive and strongly positive groups than in the VASP-negative cases (P<0.05), but with no statistically significant difference between the former two groups (P>0.05).

CONCLUSIONSVASP is involved in the regulation of the invasive ability of prostate cancer PC3 cells, and the differences in the VASP expression are related to the prognosis of prostate cancer.

Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Humans ; Immunohistochemistry ; Lentivirus ; Male ; Microfilament Proteins ; metabolism ; Neoplasm Metastasis ; physiopathology ; Phosphoproteins ; metabolism ; Prognosis ; Prostatectomy ; Prostatic Neoplasms ; pathology ; surgery ; RNA, Small Interfering ; Survival Rate

OBJECTIVETo investigate the effects of the quinoline derivative PQ1 combined with cisplatin on the proliferation and gap junction communication of prostate cancer PC3 cells.

METHODSWe cultured in vitro prostate cancer PC3 cells and divided them into DMSO blank control, cisplatin control, and cisplatin (10 mg/ml) plus PQ1 (1, 2, 5, 10, and 15 μmol/L) groups. We measured the proliferation of the prostate cancer PC3 cells, determined the expressions of the connexin 43 (Cx43) mRNA and protein by RT-PCR and Western blot, and compared the indexes among different groups.

RESULTSCisplatin combined with PQl at 1 - 10 μmol/L significantly inhibited the proliferation of the PC3 cells and the inhibition rate rose in a concentration- and time-dependent manner, from (48.72 ± 0.98)% vs (50.33 ± 0.62)% at 0 μmol/L to (77.38 ± 1.12)% vs (83.50 ± 1.05)% at 15 μmol/L at 24 and 48 hours (P < 0.05). Compared with the cisplatin control, cisplatin combined with PQ1 at 1, 2, 5, 10, and 15 μmol/L increased the expression of Cx43 mRNA from 0.379 ± 0.113 to 0.669 ± 0.031, 0.831 ± 0. 127, 0.769 ± 0.100, 0.532 ± 0.086, and 0.475 ± 0.134, respectively (P < 0.05), and cisplatin combined with PQ1 at 1, 2, 5, and 10 μmol/L elevated that of Cx43 protein from 0.138 ± 0.146 to 0.263 ± 0.111, 0.306 ± 0.152, 0.415 ± 0.280, and 0.643 ± 0.310, respectively (P < 0.05).

CONCLUSIONThe quinoline derivative PQ1 can promote the gap junction communication of prostate cancer PC3 cells and enhance the killing effect of cisplatin on PC3 cells by upregulating the expressions of Cx43 mRNA and protein.

Aminoquinolines ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Connexin 43 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Gap Junctions ; drug effects ; physiology ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; physiopathology ; RNA, Messenger ; metabolism ; Time Factors

To investigate the effect of a novel EZH2 inhibitor GSK126 on cell growth, apoptosis and migration of prostate cancer cells.Prostate cancer PC-3 and DU145 cells were treated with GSK126 at different doses. Cell growth was detected by sulforhodamine assay. Cell apoptosis was assayed by Annexin V-/PI kit. Transwell chamber and wound healing assays were conducted to detect cell migration. The mRNA level was detected by quantitative PCR, and protein expression was detected by Western blot analysis.GSK126 showed significant effect on cell growth and apoptosis when the dose was higher than 50 μmol/L. Wound healing assay revealed that scratch space in PC-3 cells was significantly increased in a dose-dependent manner in GSK126-treated groups[(247.2±24.4),(347.2±19.2) and (410.5±18.1) μm in low, medium and high dose (5.0, 20.0, 50.0 μmol/L), respectively] as compared with the control group[(171.3±17.8) μm](all<0.05). Transwell assay showed that migrated PC-3 cells in control group was 322.0±17.9,while those in GSK126-treated groups were 198.3±15.4 (low),82.7±6.2 (medium) and 30.2±4.1 (high), and the differences between the control group and GSK126-treated groups were significant(all<0.05). In addition, GSK126 up-regulated E-cadherin mRNA expression and down-regulated N-cadherin and Vimentin mRNA expression, whereas had no significant effect on Snail, Fibronectin and VEGF-A mRNA expression. The protein expression of E-cadherin was elevated but VEGF-A protein did not change in GSK126-treated groups. Similar results were exhibited in DU145 cell.GSK126 can significantly inhibit cell migration and invasion in prostate cancer PC-3 and DU145 cells, which may be resulted from its effect on epithelial-mesenchymal transition. GSK126 may be used as a potential anti-prostate cancer dug in clinic.
Apoptosis ; drug effects ; Cadherins ; analysis ; drug effects ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Enhancer of Zeste Homolog 2 Protein ; analysis ; drug effects ; metabolism ; Fibronectins ; analysis ; drug effects ; metabolism ; Humans ; Indoles ; pharmacology ; Male ; Prostatic Neoplasms ; chemistry ; genetics ; physiopathology ; Pyridones ; pharmacology ; RNA, Messenger ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; analysis ; drug effects ; Vimentin ; analysis ; drug effects ; metabolism

To investigate the effect of compound Chinese traditional medicine PC-SPES II I in inhibiting proliferation of human prostate cancer cell LNCaP based on the androgen receptor (AR) signaling pathway. The effect of PC-SPES II on LNCaP cell proliferation was detected by MTT assay. According to the findings, at the mass concentration of 180-1 440 mg x L(-1), PC-SPES II significantly inhibited the proliferation of LNCaP cells; the IC50 of PC-SPES II at 24 h and 48 h were 311.48, 199.01 mg x L(-1), respectively. The flow Cytometry detection showed 240 mg x L(-1) PC-SPES II arrested cells in G2/M phase, and an obvious apoptotic peak appeared before G0/G1 peak and rose over time. Meanwhile, Hoechst 33258 staining revealed apoptotic cellular morphology. Annexin V-FITC/PI staining manifested an increase in apoptotic cell ratio at the PC-SPES II concentration of 480 mg x L(-1) in a dose dependent manner. The prostate specific antigen (PSA) secretion of LNCaP cells was tested by PSA ELISA kit. Besides, compared with 25 mg x L(-1) Bic, 480 mg x L(-1) PC-SPES II significantly reduced the cell secretion of PSA. The AR and PSA mRNA and protein expressions were detected by qRT-PCR and Western blot. According to the results, after the induction of LNCaP cells with synthetic androgen 25 μg x L(-1) R1881, 240-480 mg x L(-1) PC-SPES II notably down-regulated the AR and PSA mRNA and protein expressions and inhibited the translocation of AR from cytoplasm to nucleus. In summary, PC-SPES II significantly can inhibit the in vitro proliferation of LNCaP cells and arrest cell cycle arrest in G2/M phase. Its mechanism may be associated with the down-regulation of the AR and PSA expressions and the inhibition of AR nuclear translocation.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostate-Specific Antigen ; genetics ; metabolism ; Prostatic Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Receptors, Androgen ; genetics ; metabolism ; Signal Transduction ; drug effects

OBJECTIVETo compare the incidences of anemia, osteoporosis, and irritable bowel syndrome (IBS) after the application of different endocrine therapies in patients with prostate cancer.

METHODSTotally 125 patients aged 58 to 84 years with biopsy-confirmed local prostate cancer were recruited between September 2008 and September 2010. Of them 52 treated with orchiectomy (castration group) and 73 with luteinizing hormone-releasing hormone analogue (goserelin acetate 3.6mg/month) combined with androgen antagonist (bicalutamide 50mg/d) for at least 12 months (hormone group), but without blood transfusion or erythropoietin. Changes in total testosterone (TT), free testosterone (FT), prostate specific antigen (PSA), hemoglobin (Hb), red blood cell (RBC), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), bone mineral density (BMD) and gastrointestinal symptom rating scales (GSRS) were recorded and analyzed before treatment and 12 months after the initiation of treatment.

RESULTSIn the castration group, after 12 months, TT (P=0.0007), FT (P=0.0003), PSA (P=0.0006), Hb (P=0.0001), RBC (P=0.020), Hct (P=0.016), Z-score of lumbar spine (P=0.008), and femoral neck (P=0.004) decreased significantly, and GSRS (P=0.029) increased significantly. In hormone group, after 12 months, TT (P=0.0008), FT (P=0.0006), PSA (P=0.0006), Hb (P=0.0003), RBC (P=0.0001), Hct (P=0.0002), Z-score of lumbar spine (P=0.002), femoral neck (P=0.0002), and RDW (P=0.045) decreased significantly, and GSRS (P=0.010) increased significantly. After 12 months, TT (P=0.004), FT (P=0.012), PSA (P=0.007), Hb (P=0.016), Z-score of lumbar spine (P=0.033), and femoral neck (P=0.015) in hormone group were significantly lower than in the castration group, while GSRS (P=0.027) in hormone group was significantly higher than in the castration group. The incidences of anemia (P=0.006), osteoporosis (P=0.009), and IBS (P=0.022) were significantly different between these two groups. The serum level of testosterone was positively correlated with Hb, RBC, Hct, and BMD in both groups (P=0.039). Negative linear correlations could be seen between serum level of testosterone and GSRS in both groups (P=0.021), and between serum level of testosterone and RDW in medical group only (P=0.044).

CONCLUSIONThe endocrine therapies, particularly maximal androgen blockage, in patients with prostate cancer can be associated with anemia, osteoporosis, and IBS.

Aged ; Aged, 80 and over ; Anemia ; etiology ; Bone Density ; physiology ; Humans ; Incidence ; Irritable Bowel Syndrome ; etiology ; Male ; Middle Aged ; Osteoporosis ; etiology ; Prostatic Neoplasms ; complications ; physiopathology ; therapy ; Quality of Life

OBJECTIVETo study the effect of pseudolaric acid B (PLAB) on cell proliferation and cycle of human prostate carcinoma DU-145 cells. method: Its inhibitory effect on the cell growth was measured by MTT method. Characteristics of cell death were determined by Hoechest 33342 staining. The cell cycle was detected by flow cytometry. The expressions of cyclin B1, cyclin D1 and CDK1 were detected by Real time-PCR and Western blot, respectively.

RESULTPLAB notably inhibited DU-145 cell growth in a dose- and time dependent manner (P < 0.05). Its IC50 values of PLAB for DU-145 cells for 24, 48 and 72 h were 4.53, 2.39 and 2.08 micromol x L(-1), respectively. Having been treated with 5 micromol x L(-1) PLAB for 24 h, the cells showed such apoptosis characteristics as nuclei chromatin condensation and apoptotic body. With the increase in PLAB concentration, the proportion of G2/M phase cells strikingly increased in a dose- and time dependent manner (P < 0.05), meanwhile cyclin B1 and CDK1 showed over-expressions (P < 0.05), and the cyclin D1 showed under-expression (P < 0.05).

CONCLUSIONPLAB can inhibit the growth of DU-145 cells and induce the cell cycle G2/M arrest, accompanied with the over-expression of cyclin B1 and CDK1, which may be related with its regulation cycle-associated protein degradation.

Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; physiopathology

This article provides an overview of metastases to jaws (MJ), mainly concerning the differences between American and Chinese patients, and exploring the relationship between the primary tumors' prevalence (PTP) and constituent ratio of MJ. Information concerning of 399 MJ cases in 215 papers, including one new case in our hospital, was subjected to statistic analysis. The main clinical features of MJ, such as constituent ratio of PTP and that of MJ, metastatic sites, treatments, and prognosis were summarized. Breast, lung, kidney, prostate and thyroid (in descending order) were the leading primary sites of MJ. Furthermore, the constituent ratio of MJ was found to be correlated with that of PTP in all subjects including American and Chinese subjects in our study. As to metastatic sites in the mandible, a specific "M" shaped pattern appeared regardless of the tumor type or constituent ratios of MJ were in all subjects. Almost all subjects received traditionally palliative treatments, and the prognosis was quite poor. The PTP had a significant impact on the constituent ratio of MJ. However, it was the properties of the microenvironment rather than characteristics or constituent ratios of tumor cells, that decided the metastatic sites in various tumor subjects.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; Chi-Square Distribution ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Jaw Neoplasms ; mortality ; secondary ; therapy ; Kidney Neoplasms ; pathology ; Liver Neoplasms ; pathology ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; physiopathology ; Palliative Care ; Prognosis ; Prostatic Neoplasms ; pathology ; Statistics, Nonparametric ; Survival Analysis ; Thyroid Neoplasms ; pathology ; Young Adult