Ahmet Sahin

Amaç: ERK 1/2 (ekstraselüler sinyalle düzenlenen kinaz 1, 2) ve p38α’nın, FGFR1 Ser 777’yi fosforile etmek yoluyla anti-tümörojenik etki göstermesi muhtemeldir. Ser777 fosforilasyonunun ise FGFR1 aktivasyonunu inhibe ettiği bilinmektedir. Dolayısıyla Ser777’nin mutasyona uğramasının FGFR1’i aktive ederek; karsinogenez ile bunu devam ettirebilecek mekanizmaları harekete geçirebileceği düşünülmüştür. Bu kapsamda gerçekleştiren çalışmada; mesane kanseri ile FGFR1 Ser777 mutasyonu arasındaki ilişkinin tespiti amaçlanmıştır. Yöntem: Çalışmada; mesane kanseri tümör dokusu (n=62) ve kontrol grubu örneklerinde (n=30) DNA izolasyonunun ardından, FGFR1 Ser777 mutasyon analizi, DNA dizi analizi yöntemi ile gerçekleştirilmiştir. Bulgular: Bildiğimiz kadarıyla ilk defa çalışılan söz konusu mutasyon, incelenen hasta ve kontrol grubu örneklerinde tespit edilememiştir. Sonuç: Elde edilen bulgular, Ser777’nin mesane kanserinde mutasyona uğramadığını düşündürmüştür. Literatürde konuyla ilgili başka çalışma bulunmadığı göz önüne alındığında, çalışma sonuçlarının literatüre önemli katkı sağlayabileceği düşünülmektedir. Dahası, diğer kanser türlerinde de FGRF1 Ser777 mutasyonunun çalışılmasının farklı bakış açıları ortaya koyabileceğini düşünmekteyiz.

Purpose To investigate the expression profiles of 86 miRNAs in paclitaxel-resistant prostate cancer cell lines and to identify the genes that have a role in the development of drug resistance. Methods Three prostate cancer cell lines, androgen-dependent VCaP, androgen-independent PC-3 and DU-145, were used to obtain paclitaxel-resistant cells by progressively increasing the concentration of paclitaxel in the culture medium. Viability assays with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and sulforhodamine B were used to assess the cell resistance level and cytotoxic effects of paclitaxel treatment. Total RNA was isolated from both prostate cancer cell lines and their resistant versions, and cDNA samples were reverse transcribed from total RNA. Selected target genes of miRNAs that showed differences in expression and were estimated to be effective on drug resistance mechanism were analyzed with western blot analysis. Results Expression study of 86 miRNAs by RT-PCR demonstrated that several of the miRNAs were expressed at different levels in paclitaxel-resistant cells compared to wild-type cells. Moreover, the expression profiles of these miRNAs varied among different prostate cancer cell line types, with 13 miRNAs being up-regulated in the resistant cells. Among these, miR-200b-3p, miR-34b-3p and miR-375 exhibited a marked up-regulation. Further, miR-100-5p showed a prominent increase in paclitaxel-resistant VCaP-R and DU145-R cells. Western blot and RT-PCR studies showed that only the LARP1 and CCND1 genes were over-expressed up to 2–5 times in all paclitaxel-resistant cell lines compared to the other investigated genes. Conclusions In this study, the three paclitaxel-resistant prostate cancer cell lines examined showed remarkably different miRNA expression profiles.

Objectives: To assess treatment effectiveness and safety of bilateral same-session ureterorenoscopy (BSSU) for the management of stone disease involving the entire urinary system. Patients and methods We reviewed the records of 64 patients who underwent BSSU for the treatment of bilateral ureteric and/or kidney stones. Size, number, location per side, and the total burden of stones were recorded. Data on stenting, lithotripsy, and stone retrieval, and details of hospital stay and operation times were investigated. Treatment results were assessed using intraoperative findings and postoperative imaging. The outcome was considered successful in patients who were completely stone-free or who had only residual fragments of ≤2 mm. Results: The outcome was successful in 82.8% of the patients who received BSSU (54.7% stone-free and 28.1% insignificant residual fragments). The success rate per renal unit was 89.8%. There were no adverse events in 73.4% of the patients. The most common intraoperative complication was mucosal injury (36%). The complications were Clavien–Dindo Grade I in 9.4% and Grade II in 7.8%. Grade IIIa and IIIb (9.4%) complications required re-treatments. Statistical evaluation showed no association between complication grades and stone, patient, or operation features. Stone burden had no negative impact on BSSU results. The presence of impacted proximal ureteric stones was significantly related to unsuccessful outcomes. Conclusion: BSSU is safe and effective for the management of bilateral urolithiasis. BSSU can prevent recurrent surgeries, reduce overall hospital stay, and achieve a stone-free status and complication rates that are comparable to those of unilateral or staged bilateral procedures.

Background/aim: We aimed to study polymorphisms of the B7-H4 gene in order to evaluate a possible association in urothelial carcinoma, as it is highly expressed in cancer tissues. Materials and methods: In this study B7-H4 gene rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a control group including 30 patients without bladder cancer. Results: We detected that the rs10754339 polymorphism was more frequent in the cancer patients when compared with the control group (P < 0.05). Only the rs3738414 polymorphism showed a statistically significant difference in frequency between pathologic diagnostic groups. Conclusion: The rs10754339 AA genotype distribution was found to have a higher frequency whereas the rs3738414 AG genotype distribution was lower in the bladder cancer group (P < 0.05). None of the genotype distributions showed a significant difference from the control group for the rs10801935 polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic marker in urothelial carcinoma.

We analyzed factors that might affect outcome in terms of success and incidence of complications in children up to 17 years after undergoing percutaneous nephrolithotomy. The data of 346 renal units (294 patients) were analyzed in terms of postoperative outcome. Factors investigated that might affect outcome were patient gender, age, stone laterality, largest stone size, stone burden, number of stones, location of a single stone, previous intervention and instrument size. Mean ± SD patient age was 8.51 ± 4.91 years, and male-to-female ratio was 209:137. Mean ± SD stone burden was 3.49 ± 3.3 cm(2). Stone-free rates after a single procedure were 84.4% and 73.1% in patients with and without clinically insignificant residual stones, respectively. On univariate and multivariate analyses stone burden and number of stones affected the stone-free rate. Complications consisted of bleeding in 41 patients (11.8%), postoperative urinary tract infection in 21 (6%), urosepsis in 4 (0.1%) and hydrothorax in 4 (0.1%). One patient died of multiple organ failure. Through the years blood transfusion and complication rates decreased, and the use of smaller instruments increased significantly. Although bleeding occurred less often in cases where a 14Fr sheath was used rather than a larger sheath (5% vs 12%, p = 0.142), the difference was not significant. No significant factor affecting complication rates was detected. As in adults, percutaneous nephrolithotomy can be used in children with acceptable complication rates and good success rates for surgical treatment of complex renal stones. Number of stones and stone burden are predictive of postoperative stone-free rate.