Expression of TopBP1 in hereditary breast cancer

TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p < 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (p < 0.05 and p < 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (p < 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer

Relationship of urinary isoprostanes to prostate cancer occurence

To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation–isoprostanes (8-isoPGF2) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer’s instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2–2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.This study was supported by the Grant 506/810(KBO) from University of Lodz, Polan