[Inhibin B level helps evaluate the testicular function of prepubertal patients with varicocele].

OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

Insulin-like growth factor-I induces chemoresistence to docetaxel by inhibiting miR-143 in human prostate cancer.

Elevated levels of insulin-like growth factor-I (IGF-I) are associated with carcinogenesis and cancer progression. However, the molecular mechanisms by which IGF-I promotes prostate cancer development remain to be elucidated. Docetaxel chemotherapy is an important therapeutic strategy in many types of human cancers including prostate cancer. In this study, we showed that IGF-I rendered PC-3 and DU145 cells more resistant to docetaxel treatment. IGF-I treatment decreased miR-143 expression, but increased the expression levels of IGF-I receptor (IGF-IR) and insulin receptor substrate 1 (IRS1), direct targets of miR-143. Overexpression of miR-143 abolished IGF-I-induced chemoresistance to docetaxel treatment, decreased expression levels of IGF-I, IRS1, and vascular endothelial growth factor (VEGF) in prostate cancer cell lines. Furthermore, docetaxel treatment significantly inhibited VEGF transcriptional activation, whereas IGF-I treatment induced VEGF transcriptional activation in a dose-dependent manner. Forced expression of IGF-IR and IRS1 cDNAs without the 3' UTR regions restored miR-143-inhibited VEGF transcriptional activation. Finally, miR-143 inhibited tumor growth and made cells more sensitive to docetaxel treatment for decreasing tumor growth in vivo. Taken together, our data demonstrates that IGF-I induces docetaxel resistance and upregulates IGF-IR and IRS1 expression through miR-143 downregulation, whereas miR-143 acts as a tumor suppressor by targeting its targets IGF-IR and IRS1.

[Impact of preoperative nutritional risk on complications after radical cystectomy].

OBJECTIVE: To evaluate whether urological patients at nutritional risk are at higher risk for complications after radical cystectomy than those not at nutritional risk. METHODS: We performed a retrospective observational study in the consecutive patients undergoing radical cystectomy between 2010 and 2013. A total of 147 patients were enrolled in this study. The nutritional risk score was assessed preoperatively by a specialized study nurse. The patients with NRS (nutritional risk screening, NRS2002)scores≥3 were considered to have nutritional deficiency. Postoperative complications were defined using the standardized Clavien-Dindo classification. Univariate and multivariate analyses were performed to identify the predictors of complications. RESULTS: The patients aged ≥70 years(50.57%) were more prone to nutritional risk than those aged <70 years (31.67%, P=0.023). Of the 63 patients at nutritional risk, 39 (61.90%) presented with at least 1 complication compared with 29 of the 84 controls (34.52%, P=0.001). The patients at nutritional risk were at threefold risk for complications on binary Logistic analysis (OR=3.128,95%CI 1.538-6.361,P=0.002). The length of hospital stay of the patients at higher nutritional risk was longer than that of those without nutritional risk [(12.9±5.7) d vs. (10.4±4.3) d, P=0.003]. CONCLUSION: The patients aged ≥70 years are at higher nutritional risk than that of those aged <70 years. Patients at nutritional risk are more prone to complications after radical cystectomy.

MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1.

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin.

NADPH oxidase subunit p22(phox)-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer.

Excessive generation of reactive oxygen species (ROS) in cancer cells is associated with cancer development, but the underlying mechanisms and therapeutic significance remain elusive. In this study, we reported that levels of ROS and p22(phox) expression are greatly increased in human prostate cancer tissues, and knockdown of p22(phox) by specific small interfering RNA (siRNA) decreased ROS levels in prostate cancer cells. We also showed that stable downregulation of p22(phox) in prostate cancer cells inhibited cell proliferation and colony formation, which was mediated by AKT and extracellular signal-regulated kinase (ERK)1/2 signaling pathways and their downstream molecules hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). The NADPH oxidase subunit NOX1 was also elevated in prostate cancer cells, and was involved in activation of AKT/ERK/HIF-1/VEGF pathway and regulation of cell proliferation. Knockdown of p22(phox) resulted in inhibition of tumor angiogenesis and tumor growth in nude mice. These findings reveal a new function of p22(phox) in tumor angiogenesis and tumor growth, and suggest that p22(phox) is a potential novel target for prostate cancer treatment.

[Antisperm-antibodies induced by testicular torsion and its influence on testicular function].

OBJECTIVE: To investigate the changes of antisperm antibodies (AsAb), sexual hormones, and inhibin B (INH B) in patients before and after testicular torsion, as well as the effects of these factors on testicular function and reproduction. METHODS: Ten patients with single acute testicular torsion (left side 9 and right side 1), aged 16-45 years (19.6 on average), disease course of 3-6 days (averaging 4.7 days), underwent surgical removal of the damaged testis. Before and after the operation, serum AsAb (IgG, IgM, IgA) and INH B were measured by ELISA, and serum follicle-stimulating hormone (FSH), luteotropic hormone (LH), and testosterone (T) determined by chemoluminescence autoanalyzer. RESULTS: After the operation, the AsAb levels rose significantly and remained high for at least 26 weeks. The level of INH B was the lowest in the 3rd week and restored to normal in the 12th week, with significant difference between preoperation and the 3rd or the 6th week after the operation. The levels of LH and INH B in the 26th week were elevated significantly compared with the 6th. CONCLUSION: Testicular injury induced the elevation of AsAb, which would last a very long time. The change of INH B was closely related with the injury of the testis, which reflected the degree of testicular injury and functional restoration of the patients after the operation. Our study showed that AsAb and INH B can be used as useful tools for monitoring testicular function and reproduction.