Kutsal Yorukoglu

Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinsons Disease via increasing nitric oxide production.

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.

Prognostic Significance of Microvascular Invasion in Localized Renal Cell Carcinoma

Objectives: The treatment of localized and even advanced renal cell carcinoma (RCC) is radical nephrectomy. However, 30% of these patients progress after radical nephrectomy. Prognostic factors are needed in order to determine the course of disease in patients undergoing radical nephrectomy. The aim of this study is to study the prognostic significance of microvascular invasion (MVI) in patients who had undergone radical nephrectomy for localized RCC.Methods: Between June 1989 and February 1999, pathologic sections of the specimens from 41 patients without metastases, nodal involvement or macroscopic venous involvement were investigated for MVI.Results: MVI was observed in 17% of the patients. MVI was related to the grade of the tumor and tumor size (p = 0.032, p = 0.017). In sarcomatoid–type RCC, MVI was more common than in other histologic types (p = 0.003). After a median follow–up of 48 months, the progression rate was 29% in patients with MVI and 17% without MVI (p = 0.001). Median progression time was 3 months in those with MVI and 41 months with no MVI (p = 0.01). The survival rate decreased from 85 to 70% in patients with MVI during a median follow–up of 48 months (p = 0.031). In multivariate analysis, MVI was not found to be an independent prognostic factor.Conclusion: Although MVI is closely related to progression and prognosis, in multivariate analysis it was not found to be an independent prognostic factor in localized RCC. We conclude that MVI should also be evaluated together with tumor grade in predicting the prognosis of patients with localized RCC.

Bellini duct (collecting duct) carcinoma of the kidney.

Bellini duct (collecting duct) carcinoma of the kidney is a rare entity often misinterpreted as renal or transitional cell carcinoma on histologic examination. Immunohistochemical identification of specific antigens is needed for the differential diagnoses. We describe a case of Bellini duct carcinoma that arose from the collecting ducts of Bellini and was treated with aggressive surgery and interferon-based immunochemotherapy.

Prognostic significance of angiogenesis and immunoreactivity of cathepsin d and type IV collagen in high-grade stage T1 primary bladder cancer

OBJECTIVES To assess the prognostic significance of biologic parameters such as angiogenesis, expression of cathepsin D (a lysosomal protease), and degradation of type IV collagen (a basement membrane protein), we studied 20 patients with primary grade III Stage T1 transitional cell carcinoma of the bladder. METHODS Endothelial cells were labeled immunohistochemically using factor VIII-related antigen. The vascular surface density (VSD) and the microvessel number (NVES) were assessed by means of stereology. The tumor tissues were also analyzed by immunohistochemical methods for the expression of cathepsin D and the staining pattern of type IV collagen. RESULTS Eight patients (40%) having either recurrence or progressive disease showed greater NVES and VSD values (P = 0.002 and P = 0.01, respectively) than patients without. The significance of vascular parameters was found to be statistically independent from coexisting carcinoma in situ, bacille Calmette-Guerin (BCG) treatment, tumor size, and number. Additionally, these parameters did not show statistical significance between progressive and recurrent tumors. However, tumors with solid morphologic features had higher VSD values and a significantly greater rate of recurrence or progression (P = 0.01 and P = 0.07, respectively). Tissue from 17 (85%) of 20 tumors showed absent or patchy basement membrane staining for type IV collagen, and 12 (60%) showed strong immunoreactivity for cathepsin D antibody. There were no differences for either molecule with either BCG treatment or other parameters related to prognosis. CONCLUSIONS Angiogenesis may have an independent role in predicting prognosis in grade III Stage T1 bladder carcinoma. Grade III Stage pT1 tumors with solid morphologic features have higher angiogenetic activity and a worse prognosis. Cathepsin D and type IV collagen do not seem to play a role in predicting biologic behavior.

99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation of the relationship between99mTc-MIBI uptake and P-alvcoprotein expression in tumour tissue

Technetium-99m hexakis-2-methoxyisobutyl-isonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression. Two scintigraphic patterns - TI(+)/MIBI(−) in primary tumour and TI(+)/MIBI(+) in metastatic tumour — were observed, suggesting high- and low-level PGP expression, respectively. Immunochemical study for PGP revealed strong staining of the primary tumour cells. This case clinically validates the previously suggested relationship between99mTc-MIBI uptake and PGP expression.

Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor size and volume.

Objectives: There is no established tumor marker for renal cell carcinoma (RCC). Ferritin is shown to be expressed by the tumor, and proposed as a tumor marker. The aim of this study is to assess the relation between ferritin levels and tumor volume, size and prognosis in RCC. Methods: We studied ferritin levels in serum from peripheral and renal veins of 52 patients with RCC who underwent surgery. Ferritin levels were measured by an enzyme immunoassay method. Tumor volume and the largest tumor diameter were calculated from the pathologic specimens. Results: The mean serum ferritin level from the renal vein (RVF) was statistically higher than the ferritin level from the peripheral vein (PVF) (p = 0.028). Although mean RVF level increased with increasing stage, it was not significant. While there was a correlation with tumor size, volume and RVF, PVF was in correlation with disease status. PVF in patients with metastatic and/or locally advanced disease was significantly higher than the patients with localized disease (p = 0.023). The initial RVF and PVF levels were predictive of survival (p = 0.028 and p = 0.034, respectively). Conclusions: Higher levels in the renal vein, its positive correlation with tumor size and volume suggest that ferritin is expressed by RCC. Initial peripheral serum values of ferritin can be indicative of disease status and also be a prognosticator of survival.

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. χ2 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 (≥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.

Significance of P-glycoprotein, p53, and survivin expression in renal cell carcinoma.

OBJECTIVES This study addresses the relationship between cell cycle control protein p53, apoptosis inhibitor gene survivin, and chemotherapy resistance protein P-glycoprotein (P-gp) expression, and their prognostic impact in renal cell carcinoma (RCC). METHODS A group consisting of 104 patients with RCC was included from a predefined period of time. The median follow-up was 46 months. Tumor stage was defined according to the 2002 Tumor-Node-Metastasis staging system, and Fuhrman nuclear grading was used. Expression of p53, survivin, and P-gp was assessed on immunohistochemically stained slides of the representative blocks of the tumors. RESULTS A significant relationship was found between survival and histologic subtype (P = 0.001), tumor stage (P = 0.011), and tumor grade (P < 0.001). Although there was inverse correlation between p53 expression and stage (P = 0.014) and grade (P = 0.04), no correlation was observed with the histopathologic type or survival. There was no correlation between survivin expression and histologic subtype, stage, or survival, but there was a significant inverse correlation between survivin expression and tumor grade (P = 0.018). No significant correlation was found between any parameters tested, and P-gp expression. CONCLUSIONS Survivin, P-gp, and p53 expression do not play a role in prognosis of RCC. Our results suggest that survivin expression may be positively regulated by mutant p53 in RCC, and this expression may have an impact on resistance to chemotherapy in RCC.

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.