Prostate cancer is the second cause of cancer death in Brazilian men. One of the relevant phenomena to the inherited susceptibility is the presence of allelic variants in genes involved with the DNA repair pathway. The aim of this study was to analyze the frequencies of prevalent, heterozygous and rare genotypes of the base excision repair genes APEX1 and XRCC1 in a case-control study and relate the genotypes with tumoral aggressiveness. DNA from peripheral blood of 172 patients and 172 controls were analyzed by RFLP-PCR method. The polymorphisms were also evaluated in relation to clinical and pathological parameters. The OR (Odds Ratio) and confidence interval (CI = 95%) were used in the association study and the Chi-square and ANOVA tests for the evaluation of histopathological parameters. The rare genotypes frequencies of the gene APEX1 increased the risk for the development of prostate cancer (OR = 1.68 95% CI 1.10-2.58). No association was found for the gene XRCC1 (OR = 0.82 95% CI 0.53-1.27). The combined analysis for both genes did not show association with this neoplasia (OR = 1.27 95% CI 0.79-20.5). The relationship of XRCC1 and APEX1 genotypes with cancer aggressiveness through the correlation with histopathological parameters, did not find any association. Our results suggest that the polymorphism in the gene APEX1 may be indicated as a potential marker for prostate cancer risk.
Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy.
carboxymethyl-glucan (cm-G) is a water-soluble derivative of β(1-3)(1-6) glucan that is well known for its immunostimulant and hematopoiesis-enhancing activities. in this clinical trial, we assessed the effects of oral cm-G administration on the peripheral blood cells of patients with advanced prostate cancer, and examined its ability to alter hepatic and renal function. after cm-G administration, the total leukocyte count increased significantly (p≤0.02), with no associated changes in the lifestyle habits of the patients. A significant increase (p≤0.001) was also observed for red blood cell, hematocrit, hemoglobin and platelet counts. no changes were observed in hepatic or renal function after cm-G administration, and no side effects associated with its use were recorded. these results suggest that using cm-G as an adjuvant to cancer treatment may improve the health parameters of prostate cancer patients.
The determination of %FPSA and PSAD can allow a better discrimination between PCa and benign disease that the isolated use of PSA. The combination of PSADTZ, %FPSA, TZV and age promote a high accuracy for PCa detection.
Aim:Compare inflammation and collagen production induced by four sling materials in female rats. Methods: Adult female rats (n=144) were submitted to a urinary incontinence model and neutering. After four weeks they were randomized in 5 groups: Sham; autologous sling; Marlex; swine intestinal submucosa (SIS), and polypropylene mesh (TVT). Animals were killed at 7, 30 and 90 days. The inflammatory infiltrated area was rated from 0 to 3 (0=area smaller than 25%, 1=between 25% and 50%, 2 between 50% and 75%, and 3 for areas greater than 75%). The presence of granuloma and necrosis was noted. Penetration in the vesical wall was evaluated employing a system of scores from 0 to 3. The amount of collagen I and III, and the total was assessed using the Picro-Sirius staining technique. Results: The Sham group presented lower inflammatory parameters at 7 days. On the 30th day, the autologous fascia presented inflammatory reactions similar to the Sham group, and lower than the remaining groups. The synthetic materials demonstrated greater inflammatory reactions at 60 days. No differences between groups were observed other than those concerning collagen production, except at 60 days, when TVT and SIS differed from Fascia and Sham in the production of collagen III. Conclusion: Autologous fascia produced less inflammatory reaction and collagen. TVT and Marlex caused more intense and longer-lasting inflammatory reaction with greater visceral penetration. When TVT was used , this process resulted in a higher quantity of collagen III. The presence of SIS, although presenting a less intense inflammatory reaction than the synthetics, also caused greater collagen III production at 60 days.
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