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Biomedical subjects

Kutsal Yorukoglu

Publications and source records attributed to Kutsal Yorukoglu.

At least 19 recordsLinked to original sources

Analysis of NKX3.1 expression in prostate cancer tissues and correlation with clinicopathologic features.

This study aimed to analyze NKX3.1 expression in tissue samples of benign prostate hyperplasia (BPH) and in three different prostate cancer categories. The correlation of NKX3.1 expression with clinical and pathologic features of patients having undergone radical prostatectomy also was investigated. NKX3.1 expression was determined in tissue samples obtained from four different histopathological categories: (1) from patients treated with transurethral prostatectomy for BPH (n = 26), (2) localized prostate cancer patients subjected to radical prostatectomy (n = 38), (3) biopsy samples from prostate cancer patients who were metastatic at the initial admission (n = 10), and (4) tissue samples of prostate cancer patients administered antiandrogens, but who had undergone transurethral prostatectomy for infravesical obstruction (n = 11). Standard immunohistochemical staining was performed using an antiserum raised against recombinant human NKX3.1. Staining was seen in all categories of prostatic tissues. Immunohistochemistry staining scores were lower in prostate cancer patients. The staining scores were significantly higher in patients with BPH compared to metastatic or localized prostate cancer patients. Staining scores of patients with BPH and of those under antiandrogen therapy were similar. No significant correlation was found between NKX3.1 expression and tumor volume, Gleason sum scores, the presence of extraprostatic extension, tumor stage, or serum PSA. NKX3.1 expression is significantly decreased in prostate cancer patients when compared to BPH. However, the decline of NKX3.1 expression was not correlated with prostate cancer progression and was not associated with advanced stage. Thus, NKX3.1 expression is not a clinically valuable prognostic factor.

Aged↗

Expression of COX-2 in normal and pyelonephritic kidney, renal intraepithelial neoplasia, and renal cell carcinoma.

OBJECTIVES: The role of inflammation in carcinogenesis is unknown. To determine the relationship between cyclooxygenase 2 (COX-2) expression, inflammation, and carcinogenesis in human renal cell carcinoma (RCC), we looked for COX-2 expression in normal and pyelonephritic kidney, renal intratubular neoplasia (RIN), and RCC tissues. METHODS: COX-2 expression was assessed immunohistochemically in tissues obtained from 20 pyelonephritic kidneys, 16 normal kidneys, 19 RIN, and 75 RCC cases. RESULTS: COX-2 expression was found to be positive in 64% of RCCs. It was positive in 13 chronic pyelonephritic (65%), 9 normal (56%), and 15 RIN (79%) cases. COX-2 expression was significantly higher in RCC and RIN than the normal and pyelonephritic cases (p<0.001 and p<0.001, respectively). No statistically significant difference was noted between RCC and RIN cases. CONCLUSIONS: Although the function of COX-2 in tumor development has not been exactly elucidated, the increased expression of COX-2 in RIN and RCC might be a factor that may play a role in the development of RIN or progression to RCC, which warrants further research.

Carcinoma in Situ↗

Association of mast cells with microvessel density in renal cell carcinomas.

BACKGROUND: Growth of solid tumors requires angiogenesis. Evidence indicates that mast cells (MCs) play an important role in tumor angiogenesis. The aim of this study was to investigate the possible effects of angiogenesis and the presence of MCs on the prognosis of renal cell carcinoma (RCC). METHODS: Seventy-one patients who underwent radical nephrectomy for RCC were included in this study. Paraffin sections from tumor and nonneoplastic kidney were stained with CD31 antibody with the standard streptavidin-biotin immunperoxidase method. Microvessels were quantified by a stereologic method. Tumors and the surrounding area were also stained with toludine blue stain to show MCs in tumor and surrounding tissue. The correlation between microvessels and MC counts was evaluated and compared with tumor stage, grade, and other clinicopathologic parameters. RESULTS: MCs in RCC and peritumoral areas were observed to be greater than nonneoplastic kidney tissue. No correlation was found between MC number and various clinicopathologic features such as tumor size, stage, grade, and patient survival. No association was noted between angiogenesis and clinicopathologic features. On the other hand, significant correlation was found between the number of MCs and microvessel density (p=0.034, r=0.295). CONCLUSION: Our results suggest that MC infiltration may contribute to tumor angiogenesis and acceleration of tumor growth, whereas stereologic assessment of angiogenesis does not help to predict biologic behavior in RCC. Further research is required to confirm these observations.

Adult↗

Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate.

INTRODUCTION: Finasteride is a 5-alpha-reductase inhibitor used in the medical treatment of benign prostatic hyperplasia (BPH) and appears to be effective in treating prostatic bleeding secondary to BPH. The exact mechanism of this effect is not known. The aim of this study was to evaluate the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate. MATERIALS AND METHODS: Nineteen adult male rats were used. Finasteride was given to 14, and there were 5 in the control group. Finasteride 80 mg/kg was administered daily via orogastric tube as a suspension for three months. Rats were sacrificed and vascular structures of the prostates were labelled immunohistochemically using CD31 antibodies. VSD and NVES of the prostates were assessed by means of a peroxidase labeled streptavidin-biotin method. VEGF expression was examined by immunohistochemistry using VEGF monoclonal antibody. RESULTS: Mean prostatic weights were decreased significantly in rats given finasteride (p=0.0001). Although an increase in VSD was detected in the finasteride group it was not significant (p=0.26). NVES was significantly increased in the finasteride group (p=0.033). No significant difference was detected between the two groups in terms of VEGF expression (p=0.48). CONCLUSION: Finasteride does not seem to decrease VSD, NVES and VEGF expression at the level of the rat prostate. The effect of reduction of bleeding in BPH is likely to be due to its effect on shrinking glandular hyperplasia which might enhance vessel wall stability rather than decreasing overall vascularity.

Animals↗

Relation between acute urinary retention, chronic prostatic inflammation and accompanying elevated prostate-specific antigen.

OBJECTIVE: To determine if there is a relationship between acute urinary retention (AUR), the prostate-specific antigen (PSA) level and chronic inflammation of the prostate. We therefore studied patients with benign prostatic obstruction (BPO) with (n = 64) or without (n = 168) acute urinary retention (AUR) who underwent transurethral resection of the prostate (TURP) in a retrospective case control study. MATERIAL AND METHODS: Between 2001 and 2004, a total of 232 patients underwent TURP due to BPO with or without AUR. The mean values of age, prostate volume, weight of resected prostate and PSA level and the histopathologic results of patients with and without AUR were compared. Chi(2) analysis was used to examine the relationship between prostatic inflammation and AUR. The contribution of each variable to AUR was assessed by means of multiple linear regression. RESULTS: A total of 64 patients (28%) were operated on for AUR due to BPO. There were no statistical differences between patients with or without AUR with respect to the mean values of PSA, percent free PSA, prostate size or weight of the resected prostate tissue. Elevated PSA values (>or=4.0 ng/ml) were detected in 64% and 38% of the patients in the AUR and non-AUR groups, respectively (p = 0.01). Histopathological re-evaluation demonstrated that chronic prostatic inflammation was present in 56% and 37% of the specimens in the AUR and non-AUR groups, respectively (p = 0.014). In the AUR group, the mean PSA level was significantly higher in patients with than without prostatic inflammation (7.75+/-5.26 vs 5.07+/-3.21 ng/ml; p = 0.022). The odds ratio of AUR for patients with chronic prostatic inflammation and elevated PSA was determined as 4.14 (95% CI 1.65-10.41). Multiple linear regression revealed that prostatic inflammation made a significant contribution to AUR. CONCLUSIONS: Chronic prostatic inflammation may be histopathological evidence of both elevated PSA level and AUR; hence it may play a role in the pathophysiology of AUR.

Aged↗

The effects of non-selective and cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs on heterotopic ossification in rats.

BACKGROUND: Review of the literature revealed several experimental studies on the effects of selective COX-2 inhibitors on fracture healing, but no reports were encountered regarding the effects of these compounds on experimental heterotopic bone formation, so the present study was conducted. MATERIAL/METHODS: Thirty adult male Wistar rats were divided into three groups of ten animals each. Tibial and femoral bones were collected from the rats, cleaned and demineralized, and diaphyseal parts were implanted in muscle pouches created in the right gluteal region, one into each rat. Group 1 received DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), a highly selective COX-2 inhibitor, at a dose of 1.1 mg/kg/day. Group 2 received 2 mg/kg/day of indomethacin. The drugs were administered by oral gavage with 0.5% methyl cellulose as a delivery vehicle for eleven days, beginning on the first postoperative day. Group 3 received only methyl cellulose. RESULTS: Thirty days after the implantation of the demineralized bone matrix, 6/10 of DFU-treated, 9/9 of the indomethacin-treated, and 8/9 of the control rats displayed new bone formation. CONCLUSIONS: The results of this study suggest that no form of non-steroidal anti-inflammatory drug has inhibitory effects on heterotopic bone formation in rats. In our opinion, bone formation is a quite complex process that requires several events and is regulated by several factors, so further investigations other than those using non-steroidal anti-inflammatory drugs are required.

Animals↗

Risk factors for mucosal prostatic urethral involvement in superficial transitional cell carcinoma of the bladder.

OBJECTIVE: Prostatic transitional cell carcinoma (TCC) may involve urethral mucosa, ducts, acini and stroma of the gland. In this study, we evaluated the risk factors for mucosal prostatic urethral (PU) involvement in superficial TCC of the bladder. METHODS: The data of 340 consecutive male patients with the diagnosis of primary superficial TCC of the bladder who were treated at our institution were reviewed. Median age of the patients was 64 years and median follow-up was 66 months. The impact of pathological stage, grade, tumour multiplicity and presence of carcinoma in situ (CIS) on mucosal PU involvement were evaluated. RESULTS: Twenty one patients (6.2%) had mucosal involvement of the PU and concomitant multifocal TCC of the bladder. Of those, 12 patients (3.5%) had macroscopic mucosal involvement of the PU while the other 9 patients (2.7%) had microscopic tumour. Increased pathological stage, grade and tumour multiplicity were found to be risk factors for mucosal PU involvement in patients with superficial bladder cancer. Multivariate analysis showed that only the tumour multiplicity was found to be an independent risk factor for mucosal PU involvement by TCC (p=0.001). CONCLUSIONS: The incidence of mucosal PU involvement increases as the stage, grade and number of tumours increase in patients with superficial TCC of the bladder. We recommend PU sampling particularly in patients with multiple bladder tumours which may have an impact on further management of these patients.

Adult↗

1,25 Dihydroxyvitamin D(3) receptor expression in superficial transitional cell carcinoma of the bladder: a possible prognostic factor?

OBJECTIVE: Vitamin D receptors (VDR) have been detected in normal tissues and in a number of cancer types. This study was undertaken to determine the VDR expression status and to elucidate the prognostic significance of VDRs in superficial transitional cell carcinoma (TCC) of the human bladder. METHODS: VDR expression was investigated in the tumour tissue blocks which were obtained by transurethral resection from 105 patients with superficial TCC without concomitant carcinoma in situ and in 30 control subjects. Median follow-up of the patients was 40 months. The expression of nuclear VDR was evaluated immunohistochemically using avidin-biotin-peroxidase method and a monoclonal VDR antibody. VDR staining intensity in samples were assessed semi-quantitatively and graded as [-] if VDR was lacking, [+] if <33% of cells were stained, [++] if 33-66% of cells and [+++] if >66% were stained. Staining characteristics were compared with the clinico-pathologic results. RESULTS: VDRs were detected in 85.7% of the patients with superficial TCC and in 66.6% of the controls (p = 0.02). No correlation was found between VDR expression and pathological stage and grade (p = 0.05 and p = 0.09, respectively). Progression in pathologic stage was significantly higher in VDR[+++] tumours (p = 0.001). Also, disease-free survival was significantly lower and tumour size was significantly greater in VDR [+++] tumours than [-], [+] and [++] ones (p = 0.02, p = 0.008 and 0.007, respectively). No significant difference was found between patient age, sex, tumour multiplicity in terms of VDR expression. Survival was not affected by VDR expression. In multivariate analysis VDR expression was not found to be an independent prognostic factor. CONCLUSION: Superficial TCC of the bladder express VDRs. The association of increased VDR expression and higher disease progression may be useful in discriminating less differentiated superficial TCCs with poor outcome.

Adult↗

Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer.

The aim of the study was to investigate immunohistochemically the expression of vascular endothelial growth factor (VEGF) in untreated and androgen-deprived patients with prostate cancer. The study included 20 patients with prostate cancer who had undergone transurethral prostatectomy due to infravesical obstruction. All patients had been receiving androgen deprivation therapy for at least 3 months. Transurethral prostatectomy specimens were examined for VEGF expression after androgen deprivation, and the biopsy samples of the same patients were used for the evaluation of VEGF expression before androgen deprivation. VEGF expression was analyzed using immunohistochemistry. Staining patterns determined by the staining scores were compared before and after treatment. The correlation of VEGF expression with PSA, Gleason score, and the percent change in PSA after treatment was also investigated. Eligible biopsy specimens were available in 15 of the 20 patients, allowing for the evaluation of VEGF expression before treatment. All prostate cancer specimens were positive. VEGF was localized mainly in the cytoplasm or on the membrane of carcinoma cells. Staining was strong in 86.7% of patients before androgen deprivation. Heterogeneous staining (strong in 25%, moderate in 35%, and weak in 40%) was observed after treatment. Staining scores were significantly higher in patients before androgen deprivation and showed a significant decrease after androgen deprivation (p = 0.007). Tumor staining correlated with Gleason score. No significant correlation was determined between VEGF expression and pre-treatment PSA and percent change of PSA after treatment. Immunohistochemical results indicate that VEGF expression is downregulated by androgen deprivation therapy. VEGF may be a potential target for therapeutic intervention in prostate cancer.

Adenocarcinoma↗

Echo contrast-enhanced power Doppler ultrasonography for assessment of angiogenesis in renal cell carcinoma.

OBJECTIVE: Tumoral growth is an angiogenesis-dependent event. Although there are studies about the importance of histopathologic angiogenesis in various malignancies, the assessment of the angiogenesis by radiologic techniques is not well established. The aim of this study was to investigate the efficacy of echo contrast-enhanced power Doppler ultrasonography (PDUS) in determining the angiogenic status of renal cell carcinoma (RCC). METHODS: Power Doppler ultrasonography was performed before and after intravenous administration of an echo contrast agent in 42 patients with renal masses. Twenty-one of these renal masses were diagnosed as RCC histopathologically, and these 21 patients were reevaluated retrospectively. The color pixel ratios of selected images were calculated as the ratio of the number of pixels showing power Doppler signals to the total number of pixels within the lesion. The results were compared with the histopathologic microvessel density (MVD). RESULTS: A significant correlation was found between color pixel ratio and MVD values in both PDUS techniques. The use of the echo contrast agent improved this correlation and P values (Spearman rho from 0.436 to 0.551; P from .048 to .01). CONCLUSIONS: Color pixel ratio values reflect the MVD in RCC. Therefore, these results suggest that preoperative quantification of angiogenesis can be possible with the help of PDUS in RCC.

Adult↗

Conservative management of mucosal prostatic urethral involvement in patients with superficial transitional cell carcinoma of the bladder.

OBJECTIVE: Treatment of patients with mucosal prostatic urethral transitional cell carcinoma (TCC) is controversial. In this study, we evaluated the outcome of patients with mucosal prostatic urethral TCC who were managed conservatively. METHODS: The data of 290 consecutive male patients with superficial TCC of the bladder who were treated at our institution were reviewed. Median age was 63 years and median follow-up was 63 months. Initially, all patients with mucosal PU involvement without evidence of ductal and/or stromal involvement underwent intravesical BCG or Epirubicin therapy. RESULTS: Nineteen patients (6.6%) had mucosal involvement of the prostatic urethra (PU) and concomitant multifocal TCC of the bladder. Of those, 12 patients (12/19, 4.2%) had macroscopic mucosal involvement of the PU, while the other 7 patients (7/19, 2.4%) had microscopic PU tumor. Seven of 12 patients who were treated with BCG and 2 of 7 patients who were treated with Epirubicin achieved complete response. Progression occurred in 3 patients who received BCG and no patients progressed in the Epirubicin group. CONCLUSIONS: Prostatic urethral sampling should be considered necessary in intermediate and high risk patients with superficial TCC of the bladder. Intravesical therapy, especially with BCG seems to be an effective treatment alternative in the management of mucosal PU involvement.

Adjuvants, Immunologic↗

Significance of COX-2 expression in human renal cell carcinoma.

OBJECTIVES: To evaluate the expression of cyclooxygenase-2 (COX-2) and its association with clinicopathologic parameters, and to investigate the relationships between COX-2 expression and inflammation and carcinogenesis in human renal cell carcinoma. COX-2 expression is associated with aggressive clinicopathologic parameters and an unfavorable prognosis in several human malignancies. METHODS: COX-2 expression was examined immunohistochemically in tumor tissues obtained from 71 patients who underwent radical nephrectomy for renal cell carcinoma. The correlation between COX-2 expression and clinicopathologic findings and patient survival was determined. RESULTS: Of 71 tumors, 63.4% were positive for COX-2 expression. Correlation was found between COX-2 expression and various clinicopathologic features, including tumor size, tumor stage, and tumor grade (P = 0.038, P = 0.004, and P = 0.004, respectively). We found no relationship between COX-2 expression and patient survival. However, the immunoreactivity of COX-2 in renal cell carcinoma and peritumoral areas with inflammation was greater than in areas without inflammation. A statistically significant correlation was found between COX-2 expression and the tubules associated with inflammation (P = 0.038). CONCLUSIONS: COX-2 expression in patients with renal cell carcinoma is associated with several clinicopathologic features. COX-2 expression seems to play a role in the inflammation-carcinoma sequence in renal cell carcinoma. Additional research is required to determine the link between carcinogenesis and inflammation in renal cell carcinoma.

Adult↗

Tenascin C and cathepsin d expression in adipocytic tumors: an immunohistochemical investigation of 43 cases.

Cathepsin D (CatD) and tenascin C (Tn-C) have been implicated in invasion and metastasis of carcinomas. However, little is known about CatD and Tn-C distribution in mesenchymal tumors. Therefore, we aimed to investigate the expression of Tn-C and CatD in adipocytic tumors. Tn-C and CatD expressions in 27 lipomas, 5 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLS) and 11 liposarcomas (LS) were evaluated by immunohistochemistry and scored semiquantitatively. CatD expression was higher in ALT/WDLS than in lipomas (p<0.001), and higher in LS than in ALT/WDLS (p=0.009). Stromal Tn-C expression was higher in ALT/WDLS than in lipomas (p=0.02), but no difference was observed between ALT/WDLS and LS (p>0.05). These results indicate that Tn-C and CatD may be markers of locally aggressive or malignant behavior in adipocytic tumors.

Adolescent↗

Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder.

OBJECTIVES: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. METHODS: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). RESULTS: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically ( P>0.05). Reproducibility was lower in low-grade tumors for both classifications. CONCLUSIONS: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.

Carcinoma, Papillary↗

Primary renal lymphoma of mucosa-associated lymphoid tissue.

Mucosa-associated lymphoid tissue-type lymphomas have recently been recognized as a distinctive form of B-cell malignant lymphoma. In contrast to other types of low-grade lymphomas, these tumors have a tendency to be localized at diagnosis and to be curable with local therapy. We report an unusual case of primary localized low-grade lymphoma of mucosa-associated lymphoid tissue arising in the kidney. The patient underwent radical nephrectomy and was free of disease at 28 months of follow-up without additional treatment. Once properly staged and classified, lymphoma of mucosa-associated lymphoid tissue involving the kidney can be managed by radical nephrectomy and follow-up.

Adult↗

Erythropoietin exerts neuroprotective effect in neonatal rat model of hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy seen in survivors of perinatal asphyxia is a frequently encountered and a major clinical problem for which there is currently no effective treatment. Hematopoietic neuroprotective agents, such as erythropoietin (EPO) may rescue neurons from cell death in this setting. EPO is a cytokine hormone that has neuroprotective effect in vitro and in vivo. In this study, we evaluated the effect of posthypoxic EPO administration in an animal model of neonatal hypoxic-ischemic injury. Our results show that a single intracerebroventricular injection of EPO immediately after hypoxic-ischemic insult in neonatal rat model of hypoxic-ischemia reduced the extent of hypoxic-ischemic brain damage. The mean infarct volume assessed 7 days after hypoxia was significantly smaller in EPO-treated group than in the control group. These findings suggest that EPO may provide benefit after hypoxic-ischemic events in the developing brain, a major contributor to static encephalopathy and cerebral palsy.

Animals↗