Studies of the biochemical properties of MAO-A (monoamine oxidase) are numerous, but the information about determination of MAO-A in human normal and tumour renal tissue is limited. Our objectives in the present study were to determine the localization of MAO-A in normal kidney and level of expression of this protein in tumour kidney. Enzyme immunohistochemical method was chosen for detection of MAO-A in 63 clinical samples of all histopathological types of RCC (renal cell carcinoma). Our results were compared to basic clinical and histopathological parameters such as histopathological type and tumour grade. We also compared MAO-A expression between normal and tumour tissue samples. We confirmed the elevated expression of MAO-A in high-grade tumours of renal cell carcinoma specimens. The percentage of MAO-positive samples progressively increased from 9% in grade 2 to 45% in grade 3. We also noted high levels of MAO-A immunoreactivity in epithelial cells of proximal tubules in normal renal tissue. MAO-A was absent or very low in epithelial cells of distal tubules and glomerular capsule, as well as in endothelial cells of renal vessels. Taken together, our results and findings of other studies show that MAO-A expression in high-grade tumours may have a direct role in maintaining a dedifferentiated phenotype and promoting aggressive behaviour. The ability of clorgyline (an MAO-A inhibitor) to counteract oncogenic pathways and promote differentiation suggests that MAO-A inhibitors, which have been used for many years in clinical practise for treating neurological disorders, could be therapeutic options for advanced stages of tumours.

Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin. [Mol Cancer Ther 2008;7(8):2263–71]

This study aimed to examine the relationship between XRCC1, p53 and MDR1 protein, along with polymorphisms of their genes and their prognostic values in breast cancer. The following clinical and pathological parameters were evaluated: histopathological type of tumor, grade, stage, Her2/neu expression, ER, PR positivity and involvement of regional lymph nodes. Expression of proteins was determined in 39 samples of breast cancer by immunohistochemistry. Nucleotide polymorphisms were analyzed by PCR-RFLP. For statistical analysis, chi-square test (Yates), Fisher’s exact test, and correlation test were used to analyze the data. The highest protein expression was immunohistochemically found in MDR1 protein, with 54% of samples testing positive. In addition, the evaluation of MDR1 expression revealed higher positive immunoreactivity in lobular (LIC) and other types of tumor in comparison to ductal (DIC) type. The expression of p53 and XRCC1 protein was equal, but lower compared to MDR1, both testing positive in 36% of all tissue samples. Comparison of XRCC1 protein and histopathological type of tumor revealed that DIC and LIC types were mostly XRCC1-negative, while other types, papillary and mucinous were more likely to be XRCC1-positive. Interestingly, when evaluating LIC samples separately, a negative correlation between the Her2/neu and expression of XRCC1 was detected. Apparently, all Her2/neu-positive samples were XRCC1-negative (6/86%). The correlation test indicated a negative correlation between Her2/neu-positive samples and XRCC1-negative specimens (r=1, p<0.05). Statistical analysis did not reveal a correlation of p53 expression with clinical and pathological parameters. Similarly, no statistically significant difference was found between the tested polymorphisms and protein expression. We did not find statistically significant correlation between tested polymorphisms and their protein expression.

A large number of renal cancer patients show poor or partial response to chemotherapy and the precise mechanism has not been understood yet. MDR is the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs and is associated with the elevated expression of MDR proteins. These are divided into two groups: ABC transporters and non-ABC transporters. The aim of our study was to determine the expression of MDR1/Pgp, MRP1 and LRP in 47 samples of renal cell carcinomas using immunohistochemical assay. Our results were analysed in relation to nuclear grade and other clinical and pathological parameters to see the possible correlation between the expression of MDR proteins and factors mentioned above. The majority of renal carcinoma specimens showed positivity for MDR proteins. In this regard, 21 % of samples revealed positive results for MDR1, 62 % for MRP1 and 76.6 % for LRP protein. Furthermore, our study displayed significant differences between MDR1, LRP and nuclear grade. On the other hand, no association was found between MRP1 and nuclear grade, as well as between the expression of three MDR proteins and other clinically relevant parameters.

This study aimed to describe glutathione peroxidase 4 (GPx4) in rat oocytes, preimplantation embryos, and female genital organs. After copulation, Sprague Dawley female rats were euthanized with anesthetic on the first (D1), third (D3), and fifth days of pregnancy (D5). Ovaries, oviducts, and uterine horns were removed, and oocytes and preimplantation embryos were obtained. Immunohistochemical, immunofluorescent, and Western blot methods were employed. Using immunofluorescence, we detected GPx4 in both the oocytes and preimplantation embryos. Whereas in the oocytes, GPx4 was homogeneously diffused, in the blastomeres, granules were formed, and in the blastocysts, even clusters were present mainly around the cell nuclei. Employing immunohistochemistry, we detected GPx4 inside the ovary in the corpus luteum, stroma, follicles, and blood vessels. In the oviduct, the enzyme was present in the epithelium, stroma, blood vessels, and smooth muscles. In the uterus, GPx4 was found in the endometrium, myometrium, blood vessels, and stroma. Moreover, we observed GPx4 positive granules in the uterine gland epithelium on D1 and D3 and cytoplasm of fibroblasts forming in the decidua on D5. Western blot showed the highest GPx4 levels in the uterus and the lowest levels in the ovary. Our results show that the GPx4 is necessary as early as in the preimplantation development of a new individual because we detected it in an unfertilized oocyte in a blastocyst and not only after implantation, as was previously thought.