A Novel Prediction Tool Based on Multiparametric Magnetic Resonance Imaging to Determine the Biopsy Strategy for Clinically Significant Prostate Cancer in Patients with PSA Levels Less than 50 ng/ml.

PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.

Replicate systematic review and meta-analyses on robotic surgery: a quality appraisal and overlap investigation.

BACKGROUND: The number of publications of systematic reviews and meta-analyses (MAs) on robotic surgery have been increasing, including many investigating the same topic. Their quality and extent of overlap remains unclear. We assessed the quality of the MAs in this area and investigated the extent of their overlap. METHODS: Relevant studies were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases up to August 1, 2017. Reporting and methodological quality levels were assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessment of Multiple Systematic Reviews (AMSTAR) checklists. A thorough investigation of the extent of overlap was performed. RESULTS: In total, 90 MAs in 5 surgical subspecialties were included after full-text review. The mean reporting and methodological quality scores were 22.5 (83.2%) and 7.6 (69.2%), respectively. Authors from university-affiliated institutions and the presence of statistician or epidemiologist coauthors were associated with better-reporting quality scores. The topics with the most overlapping MAs (all ≥ 6) were robot-assisted thyroidectomy, prostatectomy, gastrectomy, colectomy, and fundoplication. 36 (40%) of the included MAs cited previous MAs on the same topic. Among the 7 MAs comparing robot-assisted radical prostatectomy to the open procedure, most (6/7) drew the same conclusion. 50 to 86% of MAs on this topic included the same trials as primary studies. CONCLUSION: Conducting multiple overlapping MAs with identical conclusions on the same topic that are of suboptimal quality may be a waste of resource and effort. Authors from university-affiliated institutes and experts in epidemiology and statistics are more likely to conduct MAs that have better quality. More guidelines and registries are needed to avoid overlapping MAs.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma.

Renal cell carcinoma is among the leading causes of cancer-related death and was found to induce IL-10. We started by focusing on IL-10-secreting cells in tumor-infiltrating lymphocytes in renal cell carcinoma patients and observed that both CD3(+) T cells and CD19(+) B cells contributed to an elevated IL-10 expression. We then focused on IL-10-expressing B cells, and found that compared to non-IL-10-producing B cells, the IL-10-expressing B cells had significantly lower levels of CD19 and CD20 expression, a lack of IgM and IgD expression, while the level of CD27 was elevated. Moreover, culturing under unstimulated conditions resulted in higher antibody production by these IL-10-producing B cells than their peripheral blood counterparts, which strongly suggested that they are plasmablast-differentiating cells. Both IgA and IgG subtypes were found but IgA had a higher relative abundance in the tumor-infiltrating fraction. We then observed inverse correlations between the frequency of IL-10-producing B cells and pro-inflammatory cytokine-producing T cells and T cell proliferation. The expression of T cell exhaustion marker Tim-3, however, was upregulated in patients with high frequencies of IL-10-producing B cells. Moreover, supernatant from tumor B cells suppressed T cell inflammation. In addition, frequencies of IL-10-producing tumor-infiltrating B cells were inversely correlated with resected tumor size, and were higher in later stage tumors. Together, our data demonstrated that IL-10-producing B cells had plasmablast-differentiating phenotype, and could contribute to T cell immunosuppression in renal cell carcinoma.

[Surgical treatment of azoospermia caused by iatrogenic injury to bilateral vas deferens].

OBJECTIVE: To investigate the treatment of azoospermia induced by iatrogenic injury to the bilateral vas deferens. METHODS: We retrospectively analyzed 11 cases of azoospermia caused by iatrogenic injury to bilateral vas deferens. The patients were aged 20－33 years, all diagnosed with azoospermia preoperatively and none with a history of pelvic operation. Seven of them had received bilateral inguinal hernia repair and the other 4 undergone bilateral orchidopexy in the childhood. RESULTS: Intraoperative exploration of the bilateral inguinal region was performed in all the patients. Bilateral vas deference atresia was found in the inguinal canal in 6 cases, which was treated by microscopic vasovasostomy following removal of the atresic segment. Vas deferens residual was observed in or near the deep inguinal ring in the other 5 cases, with the distal vas deferens inaccessible, which was treated by bilateral vasovasostomy in 3 cases and unilateral vasovasostomy in 2 (for longer defect segment than could be anastomosed) following combined laparoscopic exploration of the abdominal cavity. The patients were followed up for 3－12 months postoperatively, during which sperm were detected in 7 cases, with sperm concentration ranging from 0.4×106/ml to 35×106/ml and grade a+b sperm from 15% to 46%. CONCLUSIONS: For the diagnosis of azoospermia, especially in patients with no history of pelvic operation, special attention should be paid to iatrogenic injury to the vas deferens. For the treatment of the disease, non-tension vasovasostomy is essential and, when necessary, the vas deferens can be reconstructed by changing its anatomical path and shortening its length.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.

Removal of numerous vesical magnetic beads with a self-made magnetic sheath.

INTRODUCTION: Sexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies. AIM: The aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made "magnetic sheath." METHODS: A 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way. MAIN OUTCOME MEASURE: The feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration. RESULTS: Under direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath. CONCLUSIONS: The self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation.

Phytochemical and Pharmacological Profile of Vitex negundo.

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti-nociceptive, antiinflammatory, anti-tumor, anti-oxidant, insecticidal, antimicrobial, anti-androgenic, anti-osteoporotic, anti-cataract, hepatoprotective and anti-hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure-activity relationship and their molecular mechanisms of action.

Calyceal diverticulum mimicking simple parapelvic cyst: a case report.

Calyceal diverticulum is a cystic intrarenal cavity lined by nonsecretory transitional epithelium that communicates with the collecting system via a narrow isthmus or infundibulum. It is a rare anatomic anomaly with an incidence of 0.2% to 0.6% in the patients undergoing renal imaging.1 Single imaging modality usually cannot differentiate calyceal diverticulum from other cystic renal diseases.2 Here, we report a 60-year-old male who was reliably diagnosed with calyceal diverticulum by retrograde urography combined with non-enhanced computed tomography (CT) and magnetic resonance urography (MRU).

Isolated upper pole access in percutaneous nephrolithotomy: a large-scale analysis from the CROES percutaneous nephrolithotomy global study.

PURPOSE: We analyzed the indications for and outcomes of percutaneous nephrolithotomy using upper pole access. MATERIALS AND METHODS: Between 2007 and 2009 prospective data were collected by the Clinical Research Office of the Endourological Society (CROES) from consecutive patients at 96 centers globally. Data on 4,494 patients were included in this analysis. Patients were divided into upper and lower pole access groups based on the location of percutaneous renal access. Preoperative characteristics and outcomes were compared between the 2 groups by univariate and multivariate tests. RESULTS: The upper pole access group had more staghorn stones (21.7% vs 15.5%, p <0.001) and a greater stone burden (mean ± SD 476 ± 390.5 vs 442 ± 344.9 mm(2), p = 0.091). Mean operative time was 92.4 ± 46.1 and 75.1 ± 41.3 minutes in the upper and lower pole groups, respectively (p <0.001). The stone-free rate was lower in the upper pole access group (77.1% vs 81.6%, p = 0.030). The overall complication rate was higher in the upper pole group with a higher incidence of hydrothorax (5.8% vs 1.5%) but a lower incidence of pelvic perforation (1.8% vs 3.2%). Mean hospital stay was longer in the upper pole group (p = 0.048). Success and complication rates were similar in upper pole access subgroups, defined as definitive (staghorn and isolated upper calyceal stones) and elective (pelvic, middle calyceal and lower pole stones) indications. CONCLUSIONS: Isolated upper pole access is indicated in a select group of patients with complex stones. Upper calyceal and staghorn stones are more commonly managed by upper pole access, which is associated with a higher complication rate and longer hospital stay as well as a lower stone-free rate due to procedure complexity.

Are the Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire suitable for the screening of late-onset hypogonadism in aging Chinese men?

The Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire have been widely used for screening men suspected of late-onset hypogonadism (LOH). We evaluated the consistency of the two questionnaires with sex hormone levels. A total of 985 men completed the two questionnaires, as well as an analysis of the serum levels of total testosterone (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone-binding globulin (SHBG). No correlation was observed between any hormone level and the psychological or somatic section of the AMS score, whereas the sexual section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant correlations were observed between the result of the two questionnaires and these hormone levels. When LOH was defined as TT < 300 ng/dl and FT < 5 ng/dl, the sensitivity and specificity of the AMS scale were 54.0% and 41.2% compared with 78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated with the two questionnaires, but neither of these questionnaires had sufficient sensitivity and specificity. It is necessary to provide a new questionnaire applicable to the Chinese population to screening LOH.

[Late-onset hypogonadism among old and middle-aged males in a rural community of Zhejiang Province].

OBJECTIVE: To investigate the epidemiology of late-onset hypogonadism (LOH) in old and middle-aged males in the rural area of Southern China. METHODS: Using the age-stratified sampling method, we conducted a questionnaire investigation on androgen deficiency in aging males (ADAM), aging male symptoms (AMS) and IIEF-5 among 996 males aged 40 -80 years in a rural community of Jiashan county, Zhejiang Province from April to October 2012. We also determined the concentrations of serum total testosterone (TT), serum sex hormone binding globulin (SHBG) and serum albumin (ALB), detected the levels of free testosterone (cFT) and bio-available testosterone (Bio-T) by Vermeulen formula, and measured the volumes of the prostate and testis by ultrasonography. RESULTS: The mean age of the males was 56.22 +/- 8.82 years. The positive rates of LOH were 62.86% and 23.05% based on ADAM and AMS, respectively, and the incidence of erectile dysfunction (ED) was 68.83%. There were significant differences among different age groups in the levels of luteinizing hormone (LH), SHBG, cFT and Bio-T, but not in TT concentration. CONCLUSION: Ours was the first survey on the epidemiology of LOH among old and middle-aged males in the rural area of China. The incidence of LOH in the rural community of Zhejiang Province was lower than that in the urban areas reported in other studies, but the positive rate of ED showed no significant difference.

[Transurethral seminal vesiculoscopy for refractory or recurrent hemospermia: clinical analysis of 162 cases].

OBJECTIVE: To investigate the feasibility and effect of transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory or recurrent hemospermia. METHODS: We retrospectively analyzed 162 cases of refractory or recurrent hemospermia examined and treated by transurethral seminal vesiculoscopy. The patients ranged in age from 19 to 76 years and had a hemospermia history of 3 months to 11 years, admitted due to poor therapeutic results or recurrence after 4 weeks of antibiotic medication. All the patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography and pelvis CT or MRI before surgery. RESULTS: Wine- or magenta-colored colloid and inflammation were found in one or both sides of the seminal vesicle in all the cases. Pathological biopsy revealed chronic inflammatory mucosa of the seminal vesicle in all the patients, and even calculi in the ejaculatory duct or seminal vesicle in 15 cases. Postoperative follow-up averaged 21.7 (12 -29) months. Hemospermia disappeared or was alleviated in 150 (92.64%) of the cases after 1-15 ejaculations, in which 7 experienced recurrence 3 months later. Four cases failed to respond, and 1 developed acute bilateral epididymitis after surgery. No such complications as retrograde ejaculation, urinary incontinence or rectal injury were observed postoperatively. CONCLUSION: Transurethral seminal vesiculoscopy is a safe, effective and feasible new method for the treatment of refractory or recrudescent hemospermia.

Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study.

PURPOSE: Current guidelines recommend prophylactic antibiotic therapy for all patients undergoing percutaneous nephrolithotomy. We examined the effects of antibiotic prophylaxis in patients undergoing percutaneous nephrolithotomy with negative preoperative urine cultures. MATERIALS AND METHODS: Of the 5,803 patients in the CROES (Clinical Research Office of the Endourological Society) Percutaneous Nephrolithotomy Global Study database, a group of 162 patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture who did not receive antibiotic prophylaxis were matched on preoperative nephrostomy, the presence of staghorn calculi and diabetes status with an equal number of patients who received antibiotic prophylaxis. Comparisons were made between the 2 groups in terms of operative and postoperative outcomes, including the incidence of fever and other complications. RESULTS: Patients who received antibiotic prophylaxis had a lower mean (SD) age at 44.9 (14.2) vs 50.1 (14.4) years (p = 0.001). They were also more likely to be in the prone position during the procedure (71.6% vs 39.5%, p <0.001) but less likely to receive postoperative stenting (17.3% vs 32.7%, p = 0.002) than those who did not receive prophylaxis. The 2 groups were comparable in terms of all other baseline characteristics and operative factors. Patients who received antibiotic prophylaxis were less likely to experience fever (2.5% vs 7.4%, p = 0.040) and other postoperative complications (1.9% vs 22.0%, p <0.0001), and had a higher stone-free rate after percutaneous nephrolithotomy (86.3% vs 74.4%, p = 0.006). CONCLUSIONS: Antibiotic prophylaxis of patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture is associated with a significant reduction in the rate of postoperative fever and other complications.

[Polymorphism of AR gene CAG copy number and late-onset hypogonadism in males].

OBJECTIVE: To analyze the association of the androgen receptor (AR) gene CAG-STR with late-onset hypogonadism (LOH), and explore the pathogenesis of LOH. METHODS: Our investigation involved 1 000 men aged 40-70 years. We randomly selected 127 normal old and middle-aged males and 19 cases of LOH. We detected their levels of Triglyceride (TG), fasting blood glucose (FBG), serum total testosterone (tT) and free testosterone (fT), measured their body mass index (BMI), height, waist circumference (WC) and blood pressure, and examined the length of CAG repeats of the AR gene in the peripheral blood by PCR. RESULTS: The numbers of CAG repeats ranged from 15 to 32, with a mean value 23.05 +/- 2.95. The mean BMI and FBG were significantly lower (P < 0.01), but TG, tT and fT remarkably higher in the normal than in the LOH men (P < 0.01), while the mean length of (CAG) n repeat polymorphism showed no statistically significant difference between the two groups (22.54 +/- 3.06 vs 23.23 +/- 2.24, P = 0.946). The frequencies of long alleles (n > or = 22) were significantly higher in the LOH than in the normal men (73.68% vs 48.82%, P < 0.05). The numbers of CAG repeats had no significant correlation with tT (r = 0.04, P > 0.05) and fT (r = 0.025, P > 0.05). CONCLUSION: The AR gene CAG length showed polymorphism in LOH men. The long alleles (CAG)n (n > or = 22) repeat polymorphism in the AR gene may be a genetic factor for LOH, but it has to be confirmed by further investigation.

[Lower urinary tract symptoms and prostatic growth pattern among old and middle-aged males in Shanghai community].

OBJECTIVE: To investigate the prevalence of lower urinary tract symptoms (LUTS) and the age-related growth pattern of the prostate among 40 -70 year-old males in Shanghai community. METHODS: Using cluster and stratified random sampling and IPSS, we investigated the prevalence of LUTS among 1000 males aged 40 -70 years in the general population of Shanghai from November 2009 to June 2010. We measured the transverse, anteroposterior and vertical diameters of the prostate and its transition zone in each volunteer by transrectal ultrasonography and established the equation for the age-related growth pattern of the prostate. RESULTS: In the 40 to 49-, 50 to 59- and 60 to 70-year groups, the incidence rates of moderate and severe LUTS (IPSS > or = 8) were 10.0%, 15.0% and 28.7%, respectively. The length, width, height and volume of the prostate and its transition zone were positively corrected with age (P < 0.05). The prostatic growth pattern equations based on the parameters of the transverse, anteroposterior and vertical diameters were Y = 1.6 x 10(-5)X3-0.002 1X2 + 0.074 6X + 0.677 2, Y = -2.4 x 10(-5)X3 + 0.003 3X2-0.1312X + 1.269, and Y = 1.6 x 10(-5)X3-0.001 8X2 + 0.073X- 0.690 9, respectively. The transverse and anteroposterior diameters of the prostate grew at a relatively similar rate, while the transverse diameter grew obviously faster than the vertical diameter before 60 years old, but the latter significantly increased and even exceeded the former after 60 years old. CONCLUSION: The prevalence of LUTS among old and middle-aged males in Shanghai community is similar to that recently reported at home and abroad. The transverse and anteroposterior diameters of the prostate grow at a relatively similar rate, but the vertical diameter increases faster after 60 years old.

[Prostate cancer cell line PC-3 conditioned medium promotes proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effects of prostate cancer cell line PC-3 conditioned medium (PC- 3-CM) on the proliferation and osteogenic differentiation of human bone marrow human basalis mesenchymal stem cells (hBMSCs). METHODS: hBMSCs were isolated and culture-expanded by density gradient centrifugation from normal volunteers. PC-3 cells were cultured till the time of logarithmic growth and then transferred to a fresh medium, which, after 24 hours of incubation, was collected as PC-3-CM. Passage 3 hBMSCs were cultured in the fresh medium alone (the control group) or that with 50% PC-3-CM (the experimental group), and the effect of PC-3-CM on the proliferation activity of the hBMSCs was detected by WST-8 assay. Based on the types of medium used, the hBMSCs were divided into Groups I (control), II (50% PC-3-CM), III (osteoblast inducer) and IV (osteoblast inducer containing 50% PC-3 CM). The effects of PC-3-CM on the osteoblastic differentiation of the hBMSCs were determined by ALP staining, ALP activity detection, Von Kossa staining, and calcium quantitation. RESULTS: At 1, 3, 5 and 7 days of incubation, the absorbance values of the cells in the experimental group were 0.4370 +/- 0.0285, 0.7980 +/- 0.0213, 1.9090 +/- 0.0612 and 2.3023 +/- 0.0610, and those in the control group were 0.4060 +/- 0.0223, 0.6643 +/- 0.0075, 1.3727 +/- 0.0176 and 1.7947 +/- 0.0115, respectively, with significant differences between the two groups (P < 0.01) except on day 1 (P > 0.05). The positive rate and intensity of ALP staining were gradually increased in the four groups, with the ALP activities of 0.29 +/- 0.03, 1.30 +/- 0.03, 2.13 +/- 0.08, and 3.80 +/- 0.03, respectively (P < 0.01), and so was the intensity of Von Kossa staining, with the calcium depositions of 0.04 +/- 0.01, 0.44 +/- 0.05, 0.98 +/- 0.03, and 1.27 +/- 0.04, respectively (P < 0.01). CONCLUSION: PC-3- CM can promote the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells.

Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.

Androgen-independent prostate cancers express high levels of Bcl-2, and this over-expression of Bcl-2 protects prostate cancer cells from undergoing apoptosis. Ursolic acid (UA) has demonstrated an anti-proliferative effect in various tumor types. The aim of this study is to evaluate the difference between UA-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP cells and androgen-independent prostate cancer cell line LNCaP-AI cells and to reveal the molecular mechanisms underlying the apoptosis. We found that UA treatment in vitro can effectively induce apoptosis in LNCaP and LNCaP-AI cells. UA can overcome Bcl-2-mediated resistance to apoptosis in LNCaP-AI cells. Intrinsic apoptotic pathways can be triggered by UA treatment because c-Jun N-terminal kinase (JNK) is activated and subsequently provokes Bcl-2 phosphorylation and degradation, inducing activation of caspase-9. Although further evaluation is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

Differential phosphoprotein levels and pathway analysis identify the transition mechanism of LNCaP cells into androgen-independent cells.

BACKGROUND: Androgen withdrawal can prolong life in men with advanced prostate cancer, but these remissions are temporary because the surviving cells progress as hormone-refractory cancer. The mechanisms that are involved in the transition of androgen-dependent prostate cancer into androgen-independent prostate cancer (AIPC) are not fully understood. OBJECTIVE: To identify globally differentially expressed phosphoproteins in the androgen-independent prostate, to elucidate the molecular mechanisms that underlie the formation of AIPC and to identify new molecular targets that can be used to develop treatments for the disease. METHODS: An androgen-independent LNCaP cell line, LNCaP-AI, was established using androgen ablation. Differentially expressed phosphoproteins in LNCaP cells and LNCaP-AI cells were enriched by immunoprecipitation, analyzed by 2D-PAGE and identified by MALDI-TOF MS. Total protein expression levels for two regulated proteins were confirmed by Western blot. Association network analysis was carried out using the STRING database. RESULTS: The phosphorylation statuses of 17 proteins were significantly (P < 0.05) different between LNCaP-AI cells and LNCaP cells. Most proteins that were identified are known to be involved in tumor progression, and several of these proteins could be constructed into an association network. A further analysis by bioinformatics indicated that P53, HSP27, and the MAPK pathway may contribute to the transition from androgen-dependence to androgen-independence. CONCLUSION: Blocking the MAPK signaling pathway may be useful in the treatment of AIPC.