Reduced gene expression of bikunin as a prognostic marker for renal cell carcinoma

Aim: Experimental and clinical studies showed that bikunin, a Kunitz-type protease inhibitor, found in urine and amniotic fluid has a role in spread of tumor cells by providing a significant reduction in the levels of urokinase-type plasminogen activator (uPA) and its specific receptor urokinase-type plasminogen activator receptor (uPAR). The aim of this study was to investigate expression of bikunin at the mRNA level and screen for mutations in exon sequence in renal cell carcinoma (RCC) tissues. Materials and Methods: Total RNA and DNA were extracted from paired normal and tumor tissues of total 50 RCC (11 papillary, 8 chromophobe, 26 clear cell, and 5 other types) patients (23 females, mean age: 53.55 ± 14.17; 27 males mean age: 62.1 ± 7.92). Bikunin mRNA levels were detected using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Mutational screening was performed by using single strand conformation polymorphism (SSCP) method and nucleotide sequence analysis. Results: There was a statistically significant decrease in the 25 (50%) of tumor tissues comparing to normal tissues in terms of mRNA levels of bikunin (Wilcoxon signed rank test, p = 0.0337). According to the classification based on subtypes of RCC; clear cell RCC samples displayed a reduced gene expression (p = 0.0148). Additionally, the patients with the age above 50 had low bikunin expression. The SNP rs80057939 spanning 4th exon of bikunin was detected in 13 tumor tissues. However, it was not statistically significant (p > 0.05). Conclusion: Decreased bikunin mRNA level in renal cells might be associated with poor prognosis of renal carcinoma. Therefore, gene constructs or exogenous administration of bikunin might be a potential adjuvant therapy for RCC treatment. Key Words: Bikunin, nucleotide sequence analysis, prognostic marker, renal cell carcinoma, semi-quantitative RT-PCR

Intravesical device-assisted therapies for non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer (NMIBC), the most prevalent type of bladder cancer, accounts for ~75% of bladder cancer diagnoses. This disease has a 50% risk of recurrence and 20% risk of progression within 5 years, despite the use of intravesical adjuvant treatments (such as BCG or mitomycin C) that are recommended by clinical guidelines. Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect (RITE), conductive hyperthermic chemotherapy, and electromotive drug administration (EMDA), have shown promising efficacy. These device-assisted treatments are an attractive alternative to BCG, as issues with supply have been a problem in some countries. RITE might be an effective treatment option for some patients who have experienced BCG failure and are not candidates for radical cystectomy. Data from trials using EMDA suggest that it is effective in high-risk disease but requires further validation, and results of randomized trials are eagerly awaited for conductive hyperthermic chemotherapy. Considerable heterogeneity in patient cohorts, treatment sessions, use of maintenance regimens, and single-arm study design makes it difficult to draw solid conclusions, although randomized controlled trials have been reported for RITE and EMDA

Does tamsulosin change the management of proximally located ureteral stones?

The objective of this study is to assess the efficacy of an alpha-1 adrenergic receptor blocking agent on the spontaneous passage of proximal ureteral calculi ?10 mm. 92 patients having single radio-opaque proximal ureteral stone ?10 mm were randomized into two groups. Group 1 patients (n = 50) were followed with classical conservative approach and patients in Group 2 (n = 42) additionally received tamsulosin, 0.4 mg/day during 4 weeks follow-up. The stone passage rates, stone expulsion time, VAS score, change in colic episodes, and hospital re-admission rates for colicky pain were compared. The patients were furthermore stratified according to stone diameters <5 and 5-10 mm. The data of these subgroups were also compared. Stone expulsion rates showed statistically significant difference between tamsulosin receivers and non-receivers (35.7 vs 30%, p = 0.04). Time to stone expulsion period was also shortened in those receiving tamsulosin (8.4 ± 3.3 vs 11.6 ± 4.1 days, p = 0.015). Likewise, the mean VAS score and renal colic episodes during follow-up period were significantly diminished in Group 2 patients (4.5 ± 2.3 vs 8.8 ± 2.9, p < 0.01 and 66.6 vs 36%, p = 0.001, respectively). Among the stones <5 mm, tamsulosin receiving patients had higher spontaneous passage rate (71.4 vs 50%, p < 0.001). The prominent effect of tamsulosin on the 5-10 mm stones was the relocation of the stones to a more distal part of ureter (39.3 vs 18.7%, p = 0.001). Administration of tamsulosin in the medical management of proximal ureteral calculi can facilitate the spontaneous passage rate in the stone <5 mm and the relocation of the stones between 5 and 10 mm to more distal part of the ureter. © 2010 Springer-Verlag

The effect of indomethacin on hyperoxaluria-induced renal tubular epithelial injury [Hiperoksalürinin neden oldugu renal tübüler epiteliyal hasar üzerine indometazinin etkisi]

Objective: The aim of this study was to determine the effect of indomethacin, an anti-inflammatory agent, on apoptosis and crystal deposition developing as a consequence of tubular cell injury induced by hyperoxaluria in an animal model. Materials and methods: Fifty New Zealand rabbits were divided into 3 groups. The first 2 groups were fed with hyperoxaluric diet and Group 3 was the control group with no supplementary procedure or treatment. While the animals in Group 1 were given only hyperoxaluric diet, Group 2 animals was applied indomethacin in addition to the hyperoxaluric diet. Animals were sacrificed at the early (7th day) and late (28th day) periods and renal tis-sue specimens were sent for the pathological analysis of crystal deposition and apoptosis. Results: The presence and degree of crystal deposition were significantly less in the specimens obtained from indomethacin-treated group during both the early and late periods (p<0.001). Similarly, despite the evident tubular apoptosis in group receiving only hyperoxaluric diet; tubular apoptotic changes were limited in animals treated with additional indomethacin (p<0.001). Conclusion: As a result of cell injury developing due to hyperoxaluria, crystal deposition and apoptotic differences occur and the presence of ischemia increases both effects. At this point, in experimental model, indomethacin limits crystal deposition and apoptotic differences in the renal tissue