Variants on 8q24 and prostate cancer risk in Chinese population: a meta-analysis.

Previous studies have identified 8q24 as an important region to prostate cancer (PCa) susceptibility. The aim of this study was to investigate the role of six genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T; rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online electronic databases were searched to retrieve related articles concerning the association between 8q24 variants and PCa risk in men of Chinese population published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence interval (CI) were employed to assess the strength of association. Total eleven case-control studies were screened out, including 2624 PCa patients and 2438 healthy controls. Our results showed that three risk alleles of rs1447295 A (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95% CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80, P<0.00001) on8q24 were significantly associated with PCa risk in Chinese population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC; rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01). No association was found between rs6983267, rs7837688 and PCa risk. In conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979 on 8q24 might be associated with PCa risk in Chinese population, indicating these four variations may contribute risk to this disease. This meta-analysis was the first study to assess the role of 8q24 variants on PCa risk in Chinese population.

Downregulation of rho-associated protein kinase 1 by miR-124 in colorectal cancer.

AIM: To investigate the roles and interactions of rho-associated protein kinase (ROCK)1 and miR-124 in human colorectal cancer (CRC). METHODS: Expression of ROCK1 protein was examined by Western blotting, and quantitative reverse transcriptase PCR was performed to measure expression of ROCK1 mRNA and miR-124. Two cancer cell lines were transfected with pre-miR-124 (mimic) and anti-miR-124 (inhibitor) and the effects on ROCK1 protein and mRNA expression were observed. In addition, cell proliferation was assessed via a 5-ethynyl-2' deoxyuridine assay. Soft agar formation assay, and cell migration and invasion assays were used to determine the effect of survivin on the transformation and invasion activity of CRC cells. RESULTS: miR-124 was significantly downregulated in CRC compared to normal specimens (0.603 ± 0.092 vs 1.147 ± 0.286, P = 0.016) and in metastatic compared to nonmetastatic CRC specimens (0.416 ± 0.047 vs 0.696 ± 0.089, P = 0.020). Expression of miR-124 was significantly associated with CRC metastasis, tumor T and N stages, and tumor grade (all P < 0.05). ROCK1 protein was significantly increased in CRC compared to normal tissues (1.896 ± 0.258 vs 0.866 ± 0.136, P = 0.026), whereas ROCK1 mRNA expression was unaltered (2.613 ± 0.251 vs 2.325 ± 0.246). miR-124 and ROCK1 were inversely expressed in CRC tissues and cell lines. ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (Ps < 0.05). Transformation and invasion of cells transfected with miR-124 inhibitor were significantly increased compared to those in normal controls (P < 0.05). Cells transfected with miR-124 inhibitor showed increased cell proliferation. CONCLUSION: miR-124 promotes hyperplasia and contributes to invasion of CRC cells, but downregulates ROCK1. ROCK1 and miR-124 may play important roles in CRC.

Beneficial effect of splanchnic nerve transection and harmful effect of vagotomy on acute necrotizing pancreatitis in the dog.

BACKGROUND: The nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. However, the influence of visceral nerve (VN) on acute necrotizing pancreatitis (ANP) has drawn little attention. AIM: To investigate the influence of VN on the pathophysiological process of ANP in dogs. METHODS: The dogs were divided into a sham operation (SO) group, ANP group, ANP + vagal nerve trunk transection (VNTT) group, and ANP + greater splanchnic nerve transection (GSNT) group. The VNTT and GSNT groups underwent VNTT and GSNT respectively immediately after ANP induction. The levels of serum pancreatic amylase (AMY), calcium, high-sensitivity C-reactive protein (HCRP), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-10 (IL-10) were monitored dynamically and the pathological examinations of the pancreas was performed at postoperative day 7. RESULTS: All serum parameters among the four groups showed no differences before the experiment (p > 0.05). At different postoperative times, the serum TNF-α, IL-1ß, HCRP, and AMY were significantly increased, however, the serum calcium and IL-10 had dropped in the ANP group versus SO group (p < 0.05); an alike variation trend occurred between the VNTT group and ANP group (p < 0.05); an opposite variation trend occurred between the GSNT group and the ANP group (p < 0.05). The pancreas pathological scoring of VNTT group was highest in the four groups (p < 0.05) and GSNT group was lower versus ANP group (p < 0.05). CONCLUSIONS: The GSNT has been shown to alleviate development of ANP, however, VNTT may exacerbate the ANP.

Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis.

AIM: To investigate the expression of microRNA-218 (miR-218) in serum from gastric cancer patients and its relationship with clinicopathological characteristics. METHODS: A total of 68 patients with pathologically diagnosed gastric cancer and 56 healthy individuals were recruited to this study. The expression of miR-218 was detected in the serum of gastric cancer patients and healthy individuals by quantitative real-time polymerase chain reaction. The clinical data were collected and analyzed by statistical software. RESULTS: miR-218 was reduced significantly in the serum of gastric cancer patients compared to healthy individuals (1.15 ± 0.08 vs 0.37 ± 0.023; P = 0.026). In the gastric cancer group, serum expression of miR-218 was lower in patients with metastasis and poorly differentiated cancer compared with non-metastatic and well-differentiated cancer (0.19 ± 0.011 vs 0.45 ± 0.021, P = 0.031 and 0.21 ± 0.019 vs 0.49 ± 0.021, P = 0.025). Serum miR-218 was found to be significantly associated with gastric cancer metastasis (P = 0.003), tumor T stage (P = 0.018) and tumor grade (P = 0.012). Low serum expression of miR-218 was related to an increase in the stage of gastric cancer. The expression level of miR-218 in the serum was correlated with the 3-year survival. Ninety-seven percent of patients with a high level of miR-218 expression survived for 3 years, while only 54% of those with low miR-218 expression survived. CONCLUSION: miR-218 is deregulated in gastric cancer patients and is strongly correlated with tumor stage, grade and metastasis. Serum expression of miR-218 may be a prognostic marker.

[Efficacy of combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia with overactive bladder].

OBJECTIVE: To evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB). METHODS: We randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different RESULTS: Among the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse CONCLUSION: Combination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

[Effects of neoadjuvant chemotherapy on the prognostic mortality risk of invasive transitional bladder cancer: a meta-analysis].

OBJECTIVE: To systematically assess the effects of neoadjuvant chemotherapy on the prognostic risk of invasive transitional bladder cancer. METHODS: All known randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment of invasive transitional bladder cancer, published from the date of database building to September 2012, were retrieved from such databanks as Pubmed, CBMdisc, Embase and Cochrane. The data on 5-year survival rate of included studies were extracted for further heterogeneity exploration, subgroup analysis and statistical pooling with the RevMan 5.10 software. RESULTS: Fourteen subjects involving 2072 cases and 2086 controls were published from 1991 to 2012. The overall odds ratio of survival suggested a 21% relative reduction in mortality risk for neoadjuvant chemotherapy compared to that on control (OR = 0.79, 95%CI:0.70-0.90). In subgroup analysis according to different neoadjuvant chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed significant benefit to overall survival with 28% and 25% reduction in risk of death respectively (OR = 0.72,95%CI:0.60-0.86, OR = 0.75,95%CI:0.59-0.96) . However, no significant difference existed in effects between C (cisplatin) chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and docetaxel) chemotherapy and controls. In subgroup analysis according to local treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the patients with cystectomy showed significant benefits in overall survival with 25% reduction in risk of death (OR = 0.75, 95%CI:0.65-0.87). However, the patients with radiotherapy or radiotherapy plus cystectomy showed no significant benefits in overall survival. CONCLUSIONS: MCV and MVAC neoadjuvant chemotherapies improve survival among patients with bladder cancer. And neoadjuvant chemotherapy has better long-term survival after cystectomy.