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Ren Y.,Urologic | Zheng J.,Wenzhou Medical College | Yao X.,Urologic | Weng G.,Urologic | Wu L.,Ningbo Women and Childrens Hospital
International Journal of Molecular Medicine | Year: 2014

Phosphodiesterase type 5 (PDE5) plays a key role in regulating the intracellular cyclic GMP (cGMP) concentration, which influences anti-proliferative and pro-apoptotic mechanisms in multiple carcinomas. PDE5 inhibitors, such as exisulind and its analogs have anticancer activities. In this study, we found that suppressing PDE5 gene expression by PDE5 siRNA inhibited cell proliferation and induced apoptosis in OS-RC-2 human renal cell carcinoma cells. These effects were enhanced by 8-Br-cGMP, a cell membrane permeable cGMP derivative, and were inhibited by KT5823, a protein kinase G (PKG) inhibitor, indicating that PKG was activated by intracellular cyclic GMP. In addition, there was a reduction in both the mRNA and protein expression of cyclin D1, while p21 protein expression was increased; the reduction in cyclin D1 expression was blocked by the proteasome inhibitor, MG132, or c-Jun N-terminal kinase (JNK) inhibitor; both β-catenin and JNK were phosphorylated by activated PKG. Furthermore, p21 protein expression was decreased in Sp1 siRNA transfected-cells treated with 8-Br-cGMP, indicating that p21 may be partly controlled by the PKG activation through Sp1. Furthermore, we found that PKG Iβ was responsible for the anticancer activities. Our findings indicate that the downregulation of PKG-activated genes, such as cyclin D1 partly accounts for the pro-apoptotic effects in PDE5 siRNA-transfected OS-RC-2 cells.

Zhu W.-F.,Zhejiang University | Wang C.-L.,Zhejiang University | Liang L.,Zhejiang University | Shen Z.,Zhejiang University | And 4 more authors.
Lipids in Health and Disease | Year: 2014

Background: Although the association between the apolipoprotein A5 (APOA5) genetic variants and hypertriglyceridemia has been extensively studied, there have been few studies, particularly in children and adolescents, on the association between APOA5 genetic variants and obesity or non-high-density lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma non-HDL-C levels in Chinese child population. Methods. This was a case-control study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an association study in 569 obese or overweight and 194 healthy Chinese children and adolescents. Results: Genotype distributions for all polymorphisms in both cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all increased in obese or overweight patients compared to the controls. After adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence interval (CI): 1.074-2.084, P = 0.017] higher risk for developing obesity or overweight than subjects with TT genotype, while C carriers in rs651821 had a 1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P = 0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly different among rs662799 variants and both were higher in carriers of minor allele than in noncarriers for TG (1.64 ± 0.96 vs. 1.33 ± 0.67 mmol/L) (P < 0.001), and for non-HDL-C (3.23 ± 0.92 vs. 3.02 ± 0.80 mmol/L) (P = 0.005), respectively. There was also a trend towards increased TG and non-high-density lipoprotein cholesterol levels for rs651821 C carriers (P < 0.001 and P = 0.002, respectively). Furthermore, to confirm the independence of the associations between APOA5 gene and TG or non-HDL-C levels, multiple linear regression analysis was performed and the relationships were not eliminated by adjustment for age, sex and BMI. Conclusions: These findings suggest the TG-raising genetic variants in the APOA5 gene may influence the susceptibility of the individual to obesity, which may also contribute to an increased risk of high non-HDL-C levels in Chinese obese children and adolescents. © 2014 Zhu et al.; licensee BioMed Central Ltd.

Zhong H.,Ningbo Women and Childrens Hospital | Wang F.,Ningbo Women and Childrens Hospital
Journal of Laparoendoscopic and Advanced Surgical Techniques | Year: 2014

Objective: To conduct a meta-analysis of contralateral metachronous inguinal hernia (CMIH) that originated from negative laparoscopic evaluation for contralateral patent processus vaginalis (CPPV) in children who presented with a unilateral inguinal hernia and to determine the incidence of and factors associated with such a CMIH. Materials and Methods: A PubMed search was performed for all studies concerning laparoscopic repair or evaluation of inguinal hernia in children. The search strategy was as follows: (laparoscop* OR coelioscop* OR peritoneoscop* OR laparoendoscop* OR minilaparoscop*) AND ("inguinal hernia" OR "metachronous hernia") AND child*. Inclusion criteria included unilateral inguinal hernia in children, negative laparoscopic evaluation of CPPV, without history of contralateral inguinal surgery previously, and clearly reporting CMIH development or not. Editorials, letters, review articles, case reports, animal studies, and duplicate patient series were excluded. Results: Twenty-three studies comprising 6091 children with negative CPPV fulfilled the inclusion criteria and were included in the final analysis, of whom 80 (1.31%) subsequently presented with a CMIH. Subgroup analysis showed that CMIH incidence was lower through an umbilical approach than via an inguinal one (0.85% versus 1.78%, P=.009). As for the transinguinal approach, there was a CMIH incidence of 0.78% and 2.05%, respectively, for laparoscopy with a small angle (30 and 70), whereas there was no CMIH development for that with a large angle (110, 120, and flexible). A high pneumoperitoneum pressure (>10 mm Hg, >12 mm Hg, and >14 mm Hg) was usually associated with a slightly higher CMIH incidence than a low one (≤10 mm Hg, ≤12 mm Hg, and ≤14 mm Hg), all without significant difference. CMIH incidence was slightly lower for using a broad CPPV definition than for using a narrow one (0.64% versus 1.35%, P=.183). Conclusions: CMIH following negative laparoscopic evaluation for CPPV was a rare but possible phenomenon. Choosing the transumbilical approach, transinguinal laparoscopy with a large angle, low-pressure pneumoperitoneum, and broad CPPV definition would probably reduce the occurrence of such CMIHs. © 2014, Mary Ann Liebert, Inc.

Wang Y.,Ningbo Women and Childrens Hospital | Jiang B.,Ningbo Women and Childrens Hospital
Medical Journal of Wuhan University | Year: 2014

Objective: To compare the effects of different therapies for earlier stage bulky cervical cancer.Methods: We retrospectively analyzed the efficiency of 103 patients with stage Ib2- IIa2 bulky cervical cancer in our department from January 2005 to September 2008. The patients were divided into three groups. Group A were treated with neoadjuvant intra-arterial chemotherapy (NAIC) and then underwent radical surgery. Group B were treated with neoadjuvant chemotherapy (NACT) and then underwent radical surgery. Group C were given an extensive hysterectomy and pelvic lymphnode operation.Results: The primary tumor size was significantly decreased after chemotherapy in group A and group B. The short-term effect was satisfactory. The volumes of blood loss in group A and group B were less than that in group C, and pathological diagnosis after surgery revealed that positive nodes in group A and group B were less than in group C. But there were no significant difference in the five year survival rate between the three groups.Conclusion: Cervical cancer patients in Ib2- IIa2 stage have good response rate to neoadjuvant chemotherapy. The downstaging effect and benefit on surgery quality of neoadjuvant chemotherapy were confirmed. It can effectively eliminate the pathological risk factors, but can not raise the five year survival rate.

Wang F.,Ningbo Women and Childrens Hospital | Xu Y.,Ningbo Women and Childrens Hospital
International Journal of Cancer | Year: 2014

Obesity is accepted as one of the major risk factors for renal cell cancer (RCC). However, conflicting results persist for the pooled risks based on the results from case-control and cohort studies combined, and the exact shape of the dose-response relationship has not been clearly defined yet. To help elucidate the role of obesity, PubMed and Embase databases were searched for published cohort studies on associations between body mass index (BMI) and risk of RCC. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by the available characteristics of studies and participants. Cohort studies (21) with 15,144 cases and 9,080,052 participants were identified. Compared to normal weight, the pooled relative risks and the corresponding 95% confidence intervals of RCC were 1.28(1.24-1.33) for preobesity and 1.77(1.68-1.87) for obesity, respectively. A nonlinear dose-response relationship was also found for RCC risk with BMI (p = 0.000), and the risk increased by 4% for each 1 kg/m2 increment in BMI. There was no significant between-study heterogeneity among studies (I 2 = 35.6% for preobesity and I2 = 44.2% for obesity, respectively). Subgroup analysis showed a basically consistent result with the overall analysis. These results suggest that increased BMI are associated with increased risk of RCC both for men and women. What's new? Obesity is known to be a major risk factor for renal-cell cancer (RCC). However, various studies have yielded conflicting results regarding the exact impact of increasing body mass index (BMI) on RCC risk. In this study, the authors conducted a dose-response meta-analysis of all published cohort studies involving BMI and risk of RCC. They found that, compared to normal weight, obesity conferred a relative risk of 1.77 for RCC, and that risk increased by 4% for each 1kg/m2 increment in BMI. © 2014 UICC.

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