Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors.

The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations.

Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer.

Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.

Expression of miRNA-21 and miRNA-221 in clear cell renal cell carcinoma (ccRCC) and their possible role in the development of ccRCC.

AIM: Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer after prostate and bladder cancer but has the highest rate of mortality affecting over 40% of patients. microRNAs (miRNAs) are small noncoding RNAs that have become potential biomarkers and molecular targets for cancer treatment. Molecular markers such as miRNAs may have a role in the diagnosis of ccRCC. In this study, we examined the expressions of miRNA-21 and miRNA-221 in renal cancer patients׳ tumor and adjacent paired normal tissues investigating the possible role of these miRNAs in the development of ccRCC. MATERIALS AND METHODS: Renal tumors (n = 24) and paired normal renal tissue (n = 24) samples, obtained from the Department of Urology, University of Debrecen, were analyzed for miRNA-21 and miRNA-221 expressions with quantitative real-time polymerase chain reaction. RESULTS: miRNA-21 and miRNA-221 expressions were significantly up-regulated in tumor specimens compared to normal tissue (P<0.05). miRNA-21 and miRNA-221 showed coexpression pattern in 19 (79.2%) cases of tumor samples and 8 (33.3%) cases of paired normal renal tissues. Increased miRNA pattern showed a positive correlation with pathological status of the patients. CONCLUSIONS: Expression of oncogenic miRNA-21 and miRNA-221 in human ccRCC tumor tissue samples compared to adjacent nontumorous tissues might suggest that these miRNAs are involved in the development of ccRCC.

Competitive mobilization of phosphate and arsenate associated with goethite by root activity.

Arsenate (As V) is the predominant form of arsenic in soils under aerobic conditions and competes with the major plant nutrient phosphorus (P) in the form of phosphate (PV) not only for sorption sites on mineral surfaces in soil but also for root membrane transporters. Plants have evolved several mechanisms for the mobilization of PV in soils in response to P deficiency, such as the release of organic anions and protons. The aim of the present study was to test whether these mechanisms result in a simultaneous mobilization of arsenate and what would be the consequences for As transfer from soil to plant. The compartment system approach with Zea mays as model crop was chosen as an experimental setup. The system is equipped with micro suction cups and allowed us to investigate processes occurring in the vicinity of roots. As a case study, an artificial quartz substrate with well defined soil physical properties was fertilized, spiked with As V, and amended with increasing amounts of goethite (0, 1, and 4 g kg(-1) in treatments G-0, G-1, and G-4, respectively). The addition of goethite alleviated the As V-induced growth reduction and reduced As V transfer from the substrate to the plant but induced P deficiency at the same time. When low amounts of goethite (1 g kg(-1)) were added, plants mobilized PV but not As V, which might be related to differences in surface complexation reported for PV and As V. No mobilization of PV or As V was observed with the addition of higher amounts of goethite, probably because of decreasing competition between organic anions, PV, and As V for binding sites.

Effect of 2,4-dichlorophenol on DPPC/water liposomes studied by X-ray and freeze-fracture electron microscopy.

The effect of 2,4-dichlorophenol (DCP) was studied on the fully hydrated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)--water liposomes. The structure and the thermotropic phase behaviour of the liposomes was examined in the presence of DCP (DCP/DPPC molar ratio, varied from 2x10(-2) up to 1) using small- and wide-angle X-ray scattering (SAXS, WAXS) and freeze-fracture electron microscopy. The structural behaviour of the DPPC/DCP/water system was strongly dependent on the concentration of the DCP. In the pretransition range the DCP molecules (at 2x10(-2) DCP/DPPC molar ratio) induced the interdigitated phase beside the parent (gel and rippled gel) phases, locally which can be form at higher DCP concentration. When the DCP/DPPC molar ratio was increased the pretransition disappeared and the main transition was shifted to lower temperatures. In the molar ratio range from 2x10(-1) up to 5x10(-1), a coexistence of different phases was observed in the wide temperature range from 20 up to 40 degrees C. With a further increase of the DCP/DPPC molar ratio (6x10(-1) to 1) only the interdigitated gel phase occurred below 25 degrees C. A schematic phase diagram of DPPC/DCP/water system was constructed to summarise the results.