Search

Renal cell carcinoma (RCC) is the predominant type of kidney cancer. Mammalian target of rapamycin (mTOR) inhibitor everolimus is currently used as a second-line therapy for sorafenib or sunitinib-refractory metastatic RCC patients. The clinical limitation confronted during everolimus therapy is the onset of drug resistance that decreases the efficacy of the drug. Elevated level of anti-apoptotic Bcl-2 protein is proposed to be an emerging feedback loop for the acquired drug-resistance in various cancer types. In this study, the Bcl-2 inhibitor ABT-737 was used in combination with everolimus to enhance its anti-tumor effectiveness in everolimus-resistant RCC cell lines. Everolimus and ABT-737 combination synergistically led to a decrease in the proliferation of primary site A-498 and metastatic site Caki-1 RCC cell lines, which was accompanied by a reduction in protein levels of cell cycle and mTOR pathway proteins. In both RCC cell lines, everolimus-ABT-737 combination not only induced apoptosis, caspase and PARP-1 cleavage but also a decrease in Bcl-2 protein levels in parallel with a concomitant increase in Bim and Noxa levels. In order to confirm our in vitro findings, we have generated everolimus-resistant RenCa cell line (RenCares) to establish a RCC mouse xenograft model. Animals co-treated with everolimus and ABT-737 exhibited a complete suppression of tumor growth without any notable toxicity. This study thus proposes the everolimus-ABT-737 combination as a novel therapeutic strategy for the treatment of RCC to overcome the current clinical problem of everolimus resistance. © Ivyspring International Publisher. Türkiye Bilimsel ve Teknolojik AraÅ?tirma Kurumu: 114S332 This work was partly supported by The Scientific and Technological Research Council of Turkey (Grant number 114S332) and Yeditepe University Hospital. A. H. Nayman is a recipient of doctoral fellowships from the Yeditepe University. H. Siginc is a recipient of doctoral fellowship from The Scientific and Technological Research Council of Turkey. We thank Emrah Nikerel (Yeditepe University, Turkey) for advices concerning the statistical analysis. We would also like to acknowledge Burcin Asutay and Engin Sumer (Yeditepe University, Turkey) for their technical support.

Background: Prostate cancer is one of the most common solid tumors and the second leading cause of the death due to malignancy in men. Caspase 9 (CASP9) is a member of the intrinsic pathway and plays a central role in the apoptosis. Patients and Methods: Genotyping of the CASP9 (rs1052576) polymorphism were performed using real-time polymerase chain reaction for blood samples of prostate cancer patients (n=69) and controls (n=76). Results: There were no significant differences between the groups in the frequency of CASP9 genotypes (chi 2 = 1.363; p=0.506). Patients with CASP9 (rs1052576) CT genotype were 12.8 fold higher in pathological stage of pT2a compared to any other stages of cancer (OR=0.078, 95% CI= 0.009-0.062; p=0.004). Also TT genotype carriers were 11.3 times lower in pathological stage of pT2a (OR=11.33, 95% CI= 2.39-53.748; p=0.000). C allele carriers were 11.36 fold higher in pathological stage of pT2a compared to any other stages of cancer (OR=0.088, 95% CI= 0.019-0.418; p=0.002). Conclusion: CASP9 (rs1052576) C allele was decreasing the risk for pathological stage of patients with prostate cancer and also CT genotype had positive impact on pathological stage of patients with prostate cancer. CASP9 (rs1052576) TT genotype was seemed to be associated with higher risk of pathological stage. Those results implicated that CASP9 variations could be associated with severity of prostate cancer.

BACKGROUND: Apolipoprotein E (ApoE) is a potential inhibitor of cell proliferation, immune regulation and modulation of cell growth and differentiation; it also has a substantial role in antioxidant activity. ApoE has a potential role in prostate cancer progression.MATERIALS AND METHODS: ApoE genotyping was performed using real-time polymerase chain reaction (RT-PCR) for blood samples from a group of patients with prostate cancer (n=68) and a control group (n=78).RESULTS: The frequency of the E3/E3 genotype was significantly higher in patients compared to controls (p=0.004). E3/E3 genotype carriers were 3.6-fold more likely to be patients than controls (odds ratio=3.67, 95% confidence interval=1.451-9.155; p=0.004). Additionally, the patients with E3/E3 genotype had significantly higher Gleason score (p=0.017), and more patients with this genotype had a Gleason score higher than 7 (p=0.007). Individuals carrying the E4 allele were significantly more common in the control group (p=0.006). The frequency of the E3/E4 genotype was found to be significantly higher in controls compared to patients (p=0.007), and patients were significantly less likely to have this genotype than controls (odds ratio=0.89, 95% confidence interval=0.833-0.967, p=0.007). Individuals carrying the E2/E3 genotype had a significantly lower Gleason score (p=0.049)-all of the patients with this genotype had a Gleason score lower than 7 (p=0.024).CONCLUSION: E3/E3 genotype may be a potential risk factor for prostate cancer and high Gleason scoring. The E4 allele maybe a risk-reducing factor for prostate cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

… FEBS

Background: Cytokine-mediated immune and inflammatory responses are considered to play an important role in the pathogenesis of prostate cancer. The present study investigated certain interleukin-1 beta (IL1 beta) polymorphisms and their association with prostate cancer. Materials and Methods: Genotyping of the IL1B-31(rs 1143627 G>A) and IL1B-511(rs 16944 A

…

…

… World Federat Soc Anaesthesiol (WFSA)

Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis. © 2010 Elsevier Ireland Ltd.

…

[No abstract available]

Objectives: There is a small risk of ureteral injury during laparoscopic radical prostatectomy (LRP). It is important to recognise and repair such ureteral injuries immediately. Laparoscopic reconstructive surgery has proven to be feasible for the treatment of ureteral injury. We report our experience of ureteral injuries during LRP including the incidence, mechanism of injury, management, prevention and outcome. Materials and methods: During a 9-year period, 2,164 LRP's were performed at our clinic. Three cases were complicated by lower ureteral injuries including two complete and one partial transection. The complete transections occurred during posterior dissection of the bladder neck and seminal vesicles, and the partial transection during an extended lymph node dissection. All were recognised and managed intraoperatively. We performed Lich-Gregoir (LG) extravesical ureteral reimplantation for complete transections, and primary repair for the partial ureteral transection. Results: Overall, the incidence of ureteral injuries was 0.13%. Laparoscopic reconstructive surgery was performed successfully in all cases without complication. This added 71, 46 and 59 min, respectively, to LRP operative time. The postoperative course was uneventful in all patients. Hospital stay was 8 days. After 30, 17 and 14 months of follow-up, intravenous urography (IVU) demonstrated good drainage. Conclusion: Recognition and repair of ureteral injuries during LRP requires a high index of suspicion, and expertise in laparoscopic technique. Laparoscopic reimplantation or primary repair of these injuries during LRP is, in experienced hands, a safe, feasible and minimally invasive procedure with the benefits of laparoscopic surgery maintained for the patient. © Springer-Verlag 2009.

Background: Use of an augmented reality (AR)-based soft tissue navigation system in urologic laparoscopic surgery is an evolving technique. Objective: To evaluate a novel soft tissue navigation system developed to enhance the surgeon's perception and to provide decision-making guidance directly before initiation of kidney resection for laparoscopic partial nephrectomy (LPN). Design, setting, and participants: Custom-designed navigation aids, a mobile C-arm capable of cone-beam imaging, and a standard personal computer were used. The feasibility and reproducibility of inside-out tracking principles were evaluated in a porcine model with an artificially created intraparenchymal tumor in vitro. The same algorithm was then incorporated into clinical practice during LPN. Interventions: Evaluation of a fully automated inside-out tracking system was repeated in exactly the same way for 10 different porcine renal units. Additionally, 10 patients underwent retroperitoneal LPNs under manual AR guidance by one surgeon. Measurements: The navigation errors and image-acquisition times were determined in vitro. The mean operative time, time to locate the tumor, and positive surgical margin were assessed in vivo. Results and limitations: The system was able to navigate and superpose the virtually created images and real-time images with an error margin of only 0.5 mm, and fully automated initial image acquisition took 40 ms. The mean operative time was 165 min (range: 135-195 min), and mean time to locate the tumor was 20 min (range: 13-27 min). None of the cases required conversion to open surgery. Definitive histology revealed tumor-free margins in all 10 cases. Conclusions: This novel AR tracking system proved to be functional with a reasonable margin of error and image-to-image registration time. Mounting the pre- or intraoperative imaging properties on real-time videoendoscopic images in a real-time manner will simplify and increase the precision of laparoscopic procedures. © 2009 European Association of Urology.

…

BACKGROUND: Data on utilizing complexed prostate specific antigen (cPSA) offering increased diagnostic performance over other available clinical parameters in diagnosis of prostate cancer is still controversial. Our objective was to determine diagnostic performance of cPSA compared to total prostate specific antigen (tPSA) and corresponding ratios for possible routine application. METHODS: In a prospective study including overall 315 consecutive men, 177 patients with suspicious digital rectal examination, and/or tPSA value > 2.5 ng/ml underwent prostate biopsy. Serum samples for tPSA, cPSA and free PSA were analyzed using automated chemiluminometric technology. RESULTS: Area under the curve (AUC) for cPSA, although greater, was not statistically different compared to that of tPSA (p = 0.253). AUCs of f/c, f/t and c/t ratios were all found significantly inferior. At clinically relevant 2.37 ng/ml threshold, cPSA performed with 85% sensitivity and significantly higher specificity of 63.1%, compared to same sensitivity and specificity of 57.2% at a 3.00 ng/ml cut off for tPSA. CONCLUSIONS: Utilizing automated assay systems at predetermined cut off value for cPSA we would be able to save 27.1% of the biopsies while missing 13.4% of the cancers. Therefore, results of this study indicate higher discriminatory power of cPSA in diagnosis of prostate cancer for clinically relevant 2.5-4 ng/ml tPSA range.

Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia /reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these unestimated adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

Splenosis is a well-known entity, caused by autotransplantation of splenic tissue as a result of trauma or splenectomy. Patients are generally asymptomatic, and this entity is diagnosed during routine diagnostic imaging. Cystic changes in splenic implants have been defined before but, as to our knowledge, radiological demonstration of cystic components has not been published in the literature. It is well-known that unusual locations of the splenic implants create diagnostic problems, sometimes leading to unnecessary surgical interventions. In this report splenosis, mimicking a renal tumour, with cystic changes in the biggest splenule, and diagnosis with ferrumoxide-enhanced MRI is presented. © 2007 The Authors.

…

Introduction: 46 XX male syndrome (de la Chapelle syndrome) is a rarely seen genetic disorder causing male infertility. It is generally a result of unequal crossing over between X and Y chromosomes. Case report: A 26-year-old infertile male was referred to the Urology Department. He had normal external male genital phenotype and secondary sex characters. No gynecomastia was noted. At physical examination soft and atrophic testes were palpated. Laboratory analysis and testis biopsies indicated nonobstructive azospermia. Chromosomal analysis showed 46 XX karyotype. Conclusion: In the literature, there are various phenotypic properties of 46 XX male patients. Thus, translocation of the sex determining region (SRY) the gene probably cannot be the only reason for XX male syndrome. There might be some other abnormalities leading to de la Chapelle syndrome.

Introduction: Glycosaminogylicans (GAG) play as a promotor and inhibitor in some phases of stone formation. Sialic acid (SA) is a low-molecular weight aminosaccaride and found in the molecular structure of GAG and on the surface of many cells. Plasma SA level increases in inflamatory diseases, glomerulonephritis and metabolic abnormalities. Unfortunately, there are only a few studies investigating the relationship between SA level in urine and urological diseases. In this study, the relationship between calcium oxalate crystalization and free, total and complex sialic acid levels in urine and plasma has been investigated. Additionally, possible effect of potassium citrate on this relationship was also studied. Material and Methods: Thirty wistar female rats were included in this study. They were randomly divided in three groups. 0.12 ml of %5 ethylene glycole was dissolved in water and given to the rats in group 1 by feeding tube two times a day and every other day 0.5 microgram vitamin D3 was added to their drinking water to expose them hyperoxlacuric and hypercalciuric, respectively. Rats in group 2 were exposed to the same procedure as group1. Additionally, 5 mg/day K-Citrat was added to their diet. No special diet program was applied in group 3 (control group). At the end of 30 days, 24 hours urine samples were collected by using metabolic cages and blood samples were taken from each rat. Free and total SA levels were calculated by the technique of measuring thiobarbituric acid as mmol/liter (Warren's method). One way ANOVA test was applied for statistical analysis. Result: Calcium levels measured in plasma and urine were higher in group 1 and 2 than the control group. Similarly, oxalate levels in urine were also higher in group 1 and group 2., The differences were statistically significant when compared with the control group (p

Glikozaminoglikanlar taş oluşumunun bazı aşamalarında promoter, bazı aşamalarında ise inhibitor gibi davranmaktadır. Düşük molekül ağırlıklı bir aminosakkarid olan sialik asit (SA) glikozaminoglikanlanın yapısında bulunur. Kontrollü deney grupları oluşturarak kalsiyum-okzalat kristalizasyonu ile idrarda serbest ve bağlı SA ilişkisini ve potasyum sitratm bu ilişki üzerine etkisini araştırdık. Çalışmamızda Wistar cinsi dişi sıçanlardan 10'arlı 3 ayrı grup oluşturuldu. Grup l 'e 0.12 mi %5 etilen glikol l mi normal çeşme suyunda çözündürülerek 2x1 feeding tüple verilip hiperoksalürik ve günaşırı 0.5 mikrogram vitamin ds sularına karıştırılıp hiperkalsiürik hale getirildi. Grup 2, Grup l'den farklı olarak sularına 5mg/gün K-Sitrat eklendi. Grup 3'e normal beslemne yapıldı. Bütün sıçanlardan 30. günde metabolik kafesler kullanılarak 24 saatlik idrar ve kan örnekleri alındı. İdrarda serbest ve total SA düzeyleri Warren'in tarif ettiği tiobarbüritik asit tekniği ile standart eğrilere göre mmol/litre cinsinden hesaplandı. İstatistiksel analizde One way ANOVA test'i kullanıldı.Seram ve idrar kalsiyum, idrar okzalat düzeyleri grup l ve 2'de grup 3'e göre artmış olup istatistiksel anlamlı bulundu. Serum total ve bağlı SA düzeyi üç grupta normal sınırlar içerisinde fakat serbest SA grup l ve 2'de kontrol grubuna göre düşük bulundu ve bu istatistiksel anlamlı idi. İdrar total ve bağlı SA düzeyleri grup l ve 2'de grup 3'e göre azalmış bulundu ve bu istatistiksel anlamlı iken kendi aralarında istatistiksel anlamlılık yoktu. Her üç grup idrar serbest SA düzeyi arasında istatistiksel anlamlılık bulunmadı. Kristalüri ile idrar ve serum SA düzeyleri arasında anlamlı ilişki vardır. Potasyum sitrat'ın seram ve idrar SA üzerine anlamlı bir etkisi yoktur. Introduction: Glycosaminogylicans (GAG) play as a promoter and inhibitor in some phases of stone formation. Sialic acid (SA) is a low-molecular weight aminosaccaride and found in the molecular, structure of GAG and on the surface of many cells. Plasma SA level increases in inflammatory diseases, glomerulonephritis and metabolic abnormalities. Unfortunately, there are only a few studies investigating the relationship between SA level in urine and urological diseases. In this study, the relationship between calcium oxalate crystalization and free, total and complex sialic acid levels in urine and plasma has been investigated. Additionally, possible effect of potassium citrate on this relationship was also studied. Material and Methods: Thirty Wistar female rats were included in this study. They were randomly divided in three groups. 0.12 ml of %5 ethylene glycole was dissolved in water and given to the rats in group 1 by feeding tube two times a day and every other day 0.5 microgram vitamin D3 was added to their drinking water to expose them hypcroxlacuric and hypercalciuric, respectively. Rats in group 2 were exposed to the same procedure as group l Additionally, 5 mg/day K-Citrat was added to their diet. No special diet program was applied in group 3 (control group). At the end of 30 days, 24 hours urine samples were collected by using metabolic cages and blood samples were taken from each rat. Free and total SA levels were calculated by the technique of measuring thiobarbituric acid as mmol/liter (Warren's method). One way ANOVA test was applied for statistical analysis. Result: Calcium levels measured in plasma and urine were higher in group 1 and 2 than the control group. Similarly, oxalate levels in urine were also higher in group 1 and group 2., The differences were statistically significant when compared with the control group (p

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

Background: Cytokine-mediated immune and inflammatory responses are considered to play an important role in the pathogenesis of prostate cancer. The present study investigated certain interleukin-1? (IL1?) polymorphisms and their association with prostate cancer. Materials and Methods: Genotyping of the IL1B-31(rs 1143627 G>A) and IL1B-511(rs 16944 A

To assess the impact of a diagnosis of bladder cancer on smoking behavior and to analyze the role of the physician in smoking cessation. Nonmuscle-invasive bladder cancer patients completed a phone survey of their smoking habits. They were asked about smoking behavior before and after the diagnosis of cancer and whether they had been informed by their physician about the relation between smoking and bladder cancer. Two hundred-twelve patients responded to the survey. The mean age was 60.03±6.36 years. Ninety-three of the 135 current smokers (68.9%) were advised to quit smoking, whereas nine of 20 nonsmokers (45%) were not commented about the future risks of smoking. The results showed that 13% of the current smokers and 35% of the current nonsmokers were not warned about the relation of bladder cancer with smoking. Statistical significance was not seen in terms of sex, disease stage, and tumor grade at diagnosis. The relation between smoking and bladder cancer has been well established. However, some patients are not informed to quit smoking by their physicians. © 2015, TIP ARASTIRMALARI DERNEGI. All rights reserved.

Purpose: To compare the efficacy of RIRS and PNL in lower pole stones ?2 cm. Materials and and Methods: A total of 109 patients who underwent PNL or RIRS for solitary lower pole stone between April 2009 and December 2012, were retrospectively analyzed. Lower pole stone was diagnosed with CT scan. Stone size was assessed as the longest axis of the stone. All patients were informed about the advantages, disadvantages and probable complications of both PNL and RIRS before the selection of the procedure. Patients decided the surgery type by themselves without being under any influences and written informed consent was obtained from all patients prior to the surgery. Patients were divided into two groups according to the patients' preference of surgery type. Group 1 consisted of 77 patients who underwent PNL and Group 2 consisted of 32 patients treated with RIRS. Stone free statuses, postoperative complications, operative time and hospitalization time were compared in both groups. Results: There was no statistical significance between the two groups in mean age, stone size, stone laterality, mean follow-up periods and mean operative times. In PNL group, stone-free rate was 96.1% at first session and 100% after the additional procedure. In Group 2, stone-free rate was 90.6% at the first procedure and 100% after the additional procedure. The final stone-free rates and operative times were similar in both groups. Conclusions: RIRS should be an effective treatment alternative to PNL in lower pole stones larger than 2 cm, especially in selected patients.