Sule Seckin

Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer.

The aim of our study was to determine the effect of monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and CC chemokine receptor 5 (CCR5) gene polymorphisms on the susceptibility and clinicopathological characteristics of prostate cancer. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 156 histopathologically confirmed prostate cancer patients and 152 healthy subjects. Individuals with AA genotype or at least one A allele of CCR2 V64I gene polymorphism had a higher risk for prostate cancer as compared with those with GG genotype (p=0.010 and p=0.028, respectively). CCR5 Δ32/wt genotype and CCR5 Δ32 allele were also found to be involved in the susceptibility to prostate cancer (p=0.028 and p=0.030, respectively). However, there was no significant association between MCP-1-2518 A/G gene polymorphism and prostate cancer risk. Prostate cancer patients carrying AA genotype or at least one A allele of CCR2 V64I had significantly increased risk for high stage disease (p=0.002 and p=0.039, respectively) and metastasis (p=0.004 and p=0.022, respectively). The CCR2 A allele (64I allele) was significantly associated with high T stage (p=0.001) and metastasis (p=0.005) as compared with CCR2 G allele (64V allele). Our data indicate that gene polymorphism of CCR2 V64I may influence the susceptibility and clinicopathological characteristics of prostate cancer and CCR5 Δ32 allele may also be an important risk factor for prostate cancer in Turkish men population.

Manganese superoxide dismutase Ile58Thr, catalase C-262T and myeloperoxidase G-463A gene polymorphisms in patients with prostate cancer: relation to advanced and metastatic disease

To evaluate the relationship between manganese superoxide dismutase (MnSOD) Ile58Thr, catalase (CAT) C‐262T and myeloperoxidase (MPO) G‐463A gene polymorphisms and the susceptibility and clinicopathological characteristics of prostate cancer.

Despite the lack of association between different genotypes and the presence of prostate cancer, endothelial nitric oxide Synthase a/b (eNOS4a/b) polymorphism may be associated with advanced clinical stage and bone metastasis

OBJECTIVES To investigate the relationship between the distribution of endothelial NO synthase (eNOS4a/b) gene polymorphism and clinical features of prostate cancer (PCa). METHODS AND MATERIALS One hundred thirty-two patients with PCa (mean age 64.10 ± 7.23 years) and 158 healthy controls (mean age 62.50 ± 7.53 years) with normal serum total prostate specific antigen (PSA) levels (<4 ng/ml) and digital rectal examinations (DRE) were enrolled in this prospectively designed study. PCa patients were classified as clinical T1 and T2 stages (Group 1), clinical T3 and T4 stages without bone metastasis (Group 2), and patients with bone metastasis (Group 3). Genotypes (aa, bb, ab) for eNOS4a/b gene polymorphisms were identified by polymerase chain reaction analysis. Meanwhile, plasma nitrate and nitrite levels (NO(x)) were used to estimate the amounts of endogenous NO formation for both groups of patients. RESULTS Despite lack of statistically significant differences between PCa patients and the control group in terms of distribution of genotypes and frequency of alleles, plasma NO(x) levels were found to be significantly increased in PCa patients compared with controls. Meanwhile, there was no significant difference between the group of PCa patients with high and low grade tumors (Gleason score ≥ 7 vs. < 7) in terms of genotype (aa + ab genotypes or a-allele vs. bb genotype) distribution. However, bb genotype was observed to be present at a higher frequency (85.1% vs. 60%) in Group 1; whereas a-allele was more frequent in Group 2 (13.3% vs. 5.7%) and Group 3 (26.7 vs. 9.2). In addition, patients with a-allele had a 3.79-fold risk of having advanced disease and bone metastasis in comparison with bb genotype. Moreover, multivariable logistic regression analysis revealed that eNOS4a/b polymorphism and plasma NOx levels were predictive factors for developing bone metastasis and high stage disease after adjustment for age and BMI. CONCLUSIONS Our data did not reveal any relationship between any of these genotypes and the presence of PCa. However, the finding that PCa patients with bb genotype generally manifest localized disease and develop bone metastasis less frequently in comparison patients with a-allele may indicate an important role for this polymorphism in the molecular pathophysiology of PCa.

Nitric oxide synthase (eNOS4a/b) gene polymorphism is associated with tumor recurrence and progression in superficial bladder cancer cases.

PURPOSE We investigated the relationship between the distribution of the eNOS4a/b polymorphism and the clinical features of superficial bladder cancer. MATERIALS AND METHODS This study included 201 healthy controls with a mean ± SD age of 62.35 ± 7.96 years and 123 patients with a mean age of 64.03 ± 11.00 years diagnosed with histopathologically confirmed superficial bladder cancer. The eNOS4a/b polymorphism genotype (aa, bb or ab) was identified by polymerase chain reaction. Blood glutathione and plasma malondialdehyde levels were measured by spectrophotometry as an indicator of oxidative stress. We estimated total plasma levels of nitric oxide metabolites using a colorimetric assay kit. RESULTS There were no significant differences in age or body mass index between patients and controls. Malondialdehyde and nitric oxide metabolite levels were statistically significantly increased (p = 0.000 and 0.024, respectively) and glutathione levels were decreased (p = 0.000) in patients with superficial bladder cancer. The bb genotype of the eNOS4a/b polymorphism is the most frequent one in the Turkish population and the aa genotype was significantly more common in patients with superficial bladder cancer (p = 0.000). Also, the aa plus ab genotype was significantly more common in patients with high grade tumors (p = 0.013) and in those with more progression to muscle invasive disease (p = 0.000). This genotype was also a significant independent risk factor for recurrence after adjusting for smoking status, stage, grade and the presence of carcinoma in situ on logistic regression analyses (OR 3.095, 95% CI 1.21-7.86, p = 0.018). CONCLUSIONS The current study suggests that a genotype containing the a allele of the eNOS4a/b polymorphism may be a risk factor for bladder cancer. Additionally, patients harboring the aa plus ab genotype are more likely to experience tumor recurrence and progression.

Urinary IP-10, MCP-1, NGAL, Cystatin-C, and KIM-1 Levels in Prenatally Diagnosed Unilateral Hydronephrosis: The Search for an Ideal Biomarker

OBJECTIVE To investigate the urinary interferon gamma-induced protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, and kidney injury molecule-1 (KIM-1) levels in the management of children with prenatally diagnosed unilateral hydronephrosis. MATERIALS AND METHODS Twenty-seven children with antenatally diagnosed hydronephrosis were enrolled into the study. The controls consisted of 9 healthy children (6 boys, 3 girls; mean age: 41.77 ± 5.30 months). Thirteen children (9 boys, 4 girls; mean age: 48.46 ± 21.11 months) underwent pyeloplasty on follow-up; the remaining 14 (13 boys, 1 girl; mean age: 36.57 ± 14.02 months) were followed up after being diagnosed as having nonobstructive dilatation (NOD). The urinary marker levels were measured in the pyeloplasty, the NOD, and the control groups. RESULTS The preoperative concentrations of IP-10, MCP-1, NGAL, and KIM-1 were significantly higher in the pyeloplasty group than in the control group (P = .024, P = .002, P = .032, P = .001, respectively). The urinary IP-10 and MCP-1 levels were also significantly higher in the pyeloplasty group than in the NOD group (P = .038, P = .037, respectively). There was no significant difference between the pyeloplasty group and the NOD group regarding urinary NGAL and KIM-1. In the pyeloplasty group, urinary marker levels except cystatin-C were significantly decreased in the postoperative period. CONCLUSION A decrease in levels of IP-10, MCP-1, NGAL, and KIM-1 after pyeloplasty may be used as a predictor of surgical outcome. Additionally, IP-10 and MCP-1 were superior to NGAL and KIM-1 in predicting who required surgery.

Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model.

Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T‐shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty‐four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia.

Effect of low-energy shockwave therapy on angiogenic factors in the penile tissue of diabetic rats

OBJECTIVE The aim of this study is to investigate the effect of low-energy shock wave therapy (LESWT) on angiogenesis factors at penile tissue in a diabetic rat model. MATERIAL AND METHODS A total of 30 male Sprague-Dawley rats which were allocated into three equal groups were included study. Group 1 (control group) included 10 male rats which did not receive any treatment were randomly chosen to serve as normal control. The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce diabetes. Diabetic rats were divided into two equal group which constituted diabetic control, and LESWT treatment (DM+LESWT) group. Each rat in the DM+LESWT group received L-ESWT therapy. Endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) mRNA expression levels of penile tissue were evaluated. RESULTS Following STZ dosing eNOS level dropped in the diabetic control group relative to the control group. Statistically significant increase in eNOS levels were seen in the LESWT+DM group. Similarly, in the diabetic control group STZ treatment decreased VEGF levels, while in the LESWT+DM group VEGF nearly approached to baseline levels. However variations in VEGF levels were not statistically significant. CONCLUSION Mechanism action of ESWT in the penile tissue seems to involve angiogenic factors.