Browsing by Author "Radojevic-Skodric, Sanja (15726145200)"

Purpose: Indications of kidney cancer outcome in lower-income countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). Methods: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. Results: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. Conclusion: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC. © 2017 Zerbinis Publications. All rights reserved.

Purpose: Indications of kidney cancer outcome in lower-income countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). Methods: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. Results: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. Conclusion: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC. © 2017 Zerbinis Publications. All rights reserved.

Purpose: There is a need for identifying molecular prognostic biomarkers to better predict clinical outcomes in patients with renal cell carcinoma (RCC). This study investigated the pattern of cyclin D1 and p57 expression in RCC patients and evaluated their relation with clinicopathological characteristics and overall survival (OS). Methods: Immunohistochemistry was applied to paraffin-embedded tissue sections of 74 RCC patients. Two cut-off groups were defined by the fraction of positive cells as fol-lows: ≤10% and >10% positive cells for cyclin D1, and ≤5% and >5% positive cells for p57. Results: Cyclin D1 expression in >10% of positive cells was observed mostly in the clear cell RCC, while p57 expression in ≤5% of positive cells was found in 86% of chromophobe RCC specimens. The higher expression of cyclin D1 and lower expression of p57 were more frequent in grade I-II tumors. OS was associated with unfavorable clinicopathological characteristics. However, cyclin D1/p57 expression did not influence the survival rates. Conclusion: Although cyclin D1 and p57 expression did not affect survival rates in RCC patients, proper validation and establishment of the qualitative cut-off point are needed for these tumors. © 2019 Zerbinis Publications. All Rights Reserved.

Purpose: There is a need for identifying molecular prognostic biomarkers to better predict clinical outcomes in patients with renal cell carcinoma (RCC). This study investigated the pattern of cyclin D1 and p57 expression in RCC patients and evaluated their relation with clinicopathological characteristics and overall survival (OS). Methods: Immunohistochemistry was applied to paraffin-embedded tissue sections of 74 RCC patients. Two cut-off groups were defined by the fraction of positive cells as fol-lows: ≤10% and >10% positive cells for cyclin D1, and ≤5% and >5% positive cells for p57. Results: Cyclin D1 expression in >10% of positive cells was observed mostly in the clear cell RCC, while p57 expression in ≤5% of positive cells was found in 86% of chromophobe RCC specimens. The higher expression of cyclin D1 and lower expression of p57 were more frequent in grade I-II tumors. OS was associated with unfavorable clinicopathological characteristics. However, cyclin D1/p57 expression did not influence the survival rates. Conclusion: Although cyclin D1 and p57 expression did not affect survival rates in RCC patients, proper validation and establishment of the qualitative cut-off point are needed for these tumors. © 2019 Zerbinis Publications. All Rights Reserved.

Purpose: The purpose of this study was to examine wheth er cytomegalovirus (CMV) is present in different histologi cal types of salivary gland cancer (SGC) by detecting CMV immediate-early (IE) and early gene products, and to deter mine the presence of its association with the overexpression of interleukin (IL)-6. Methods: Immunohistochemical analysis of 92 cases of dif ferent histological types of SGC was performed to determine the presence of IL-6 and CMV antigen and its intensity in tumor tissue. Twenty samples of normal salivary gland tis sue obtained during autopsy served as healthy controls. Results: CMV antigens were not found in healthy acinar tissue of salivary glands, but were expressed in epithelium of salivary gland ducts. Negative expression of CMV an tigens was also found in salivary gland tissue surround ing tumors. On the other hand, CMV was detected in 65/92 SGC cases (70.6%). Higher expression of IL-6 was found in SGC (70.7%) than in normal tissue (20%). There was a high association of CMV antigen presence with the presence of IL-6, and with the IL-6 expression intensity. Conclusions: Positive expression of CMV antigens in a high percentage of SGC cells suggests that it might play an important role in carcinogenesis by increasing IL-6 pro duction and leading to inhibition of apoptosis and tumor development.

Purpose: The purpose of this study was to examine wheth er cytomegalovirus (CMV) is present in different histologi cal types of salivary gland cancer (SGC) by detecting CMV immediate-early (IE) and early gene products, and to deter mine the presence of its association with the overexpression of interleukin (IL)-6. Methods: Immunohistochemical analysis of 92 cases of dif ferent histological types of SGC was performed to determine the presence of IL-6 and CMV antigen and its intensity in tumor tissue. Twenty samples of normal salivary gland tis sue obtained during autopsy served as healthy controls. Results: CMV antigens were not found in healthy acinar tissue of salivary glands, but were expressed in epithelium of salivary gland ducts. Negative expression of CMV an tigens was also found in salivary gland tissue surround ing tumors. On the other hand, CMV was detected in 65/92 SGC cases (70.6%). Higher expression of IL-6 was found in SGC (70.7%) than in normal tissue (20%). There was a high association of CMV antigen presence with the presence of IL-6, and with the IL-6 expression intensity. Conclusions: Positive expression of CMV antigens in a high percentage of SGC cells suggests that it might play an important role in carcinogenesis by increasing IL-6 pro duction and leading to inhibition of apoptosis and tumor development.

The physiologic stress induced by physical activity is reflected in immune system perturbations, oxidative stress, muscle injury, and inflammation. We investigated the effect of astaxanthin (Asx) supplementation on salivary IgA (sIgA) and oxidative stress status in plasma, along with changes in biochemical parameters and total/differential white cell counts. Forty trained male soccer players were randomly assigned to Asx and placebo groups. Asx group was supplemented with 4 mg of Asx. Saliva and blood samples were collected at the baseline and after 90 days of supplementation in preexercise conditions. We observed a rise of sIgA levels at rest after 90 days of Asx supplementation, which was accompanied with a decrease in prooxidant-antioxidant balance. The plasma muscle enzymes levels were reduced significantly by Asx supplementation and by regular training. The increase in neutrophil count and hs-CRP level was found only in placebo group, indicating a significant blunting of the systemic inflammatory response in the subjects taking Asx. This study indicates that Asx supplementation improves sIgA response and attenuates muscle damage, thus preventing inflammation induced by rigorous physical training. Our findings also point that Asx could show significant physiologic modulation in individuals with mucosal immunity impairment or under conditions of increased oxidative stress and inflammation. © 2015 Ivana Baralic et al.

[No abstract available]

Purpose: Renal cell carcinoma (RCC) is the most common renal cancer in adults and includes several subtypes that may be distinguished by their histology, genetic background, clinical course and responses to treatment. Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been linked to RCC development. The purpose of this study was to search for genetic and epigenetic alterations in hTERT (promoter mutations and methylation and gene amplification), and to establish a possible association between molecular and clinico-pathological characteristics of RCC. Methods: DNA was extracted from 31 formalin-fixed, paraffin-embedded tumor samples and 23 blood samples from 54 patients with RCC. Polymerase chain reaction (PCR) products were sequenced and analyzed using the Sequencher software. HTERT amplification was determined by quantitative PCR, while the promoter methylation status was assessed by methylation specific PCR. Statistical analysis was performed using SPSS. Results: No mutations could be detected in the hTERT promoter but only a single nucleotide polymorphism (SNP) (-245 T>C). In 54 analyzed RCC cases, the variant allele C was present in homozygous or heterozygous form in 48% of the patients. The C allele was significantly more frequent in low grade tumors (p=0.046). Gene amplification was detected in 19.4% of the 31 RCCs and hTERT methylation in 54.8% of the 31 samples. An association was established between methylation and histological type of RCC (p=0.047). Conclusions: HTERT seems to be implicated in RCC pathogenesis since the promoter polymorphism exerts a modulation effect on tumor behavior. In addition, hTERT promoter methylation status is related to RCC histology. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: Renal cell carcinoma (RCC) is the most common renal cancer in adults and includes several subtypes that may be distinguished by their histology, genetic background, clinical course and responses to treatment. Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been linked to RCC development. The purpose of this study was to search for genetic and epigenetic alterations in hTERT (promoter mutations and methylation and gene amplification), and to establish a possible association between molecular and clinico-pathological characteristics of RCC. Methods: DNA was extracted from 31 formalin-fixed, paraffin-embedded tumor samples and 23 blood samples from 54 patients with RCC. Polymerase chain reaction (PCR) products were sequenced and analyzed using the Sequencher software. HTERT amplification was determined by quantitative PCR, while the promoter methylation status was assessed by methylation specific PCR. Statistical analysis was performed using SPSS. Results: No mutations could be detected in the hTERT promoter but only a single nucleotide polymorphism (SNP) (-245 T>C). In 54 analyzed RCC cases, the variant allele C was present in homozygous or heterozygous form in 48% of the patients. The C allele was significantly more frequent in low grade tumors (p=0.046). Gene amplification was detected in 19.4% of the 31 RCCs and hTERT methylation in 54.8% of the 31 samples. An association was established between methylation and histological type of RCC (p=0.047). Conclusions: HTERT seems to be implicated in RCC pathogenesis since the promoter polymorphism exerts a modulation effect on tumor behavior. In addition, hTERT promoter methylation status is related to RCC histology. © 2018 Zerbinis Publications. All Rights Reserved.

The aim of our study was to investigate the expression of γ-catenin in normal kidney and in Wilms' tumor by immunohistochemistry and to correlate the results with tumor stage, histological type, and prognostic group. We investigated 28 cases of Wilms' tumor, 2 Wilms' tumor metastases in lungs, and 1 specimen of normal renal tissue. Expression of γ-catenin was detected in 14 cases. There was a weak inverse relationship between γ-catenin expression and tumor stage. Expression of γ-catenin was detected in various histologic types of Wilms' tumor, but there was no statistically significant correlation, except in cases with diffuse anaplasia that were negative. In 2 metastatic cases and in the case of bilateral Wilms' tumor γ-catenin immunostaining was not observed Our findings suggest an absence of strong correlation between the loss of γ-catenin and unfavorable outcome. Copyright © Informa Healthcare USA, Inc.

Purpose: The purpose of this study was to investigate into the expression of cyclin A and telomerase in renal cell carcinoma (RCC) and to analyze the relationship between expression and the clinicopathological characteristics of the tumor and their impact on survival. Methods: The overall material included 74 samples of RCC and 4 of normal renal tissue. Primary cyclin A antibody from Santa Cruz Biotechnology and TERT MA5-16034 antibody from Thermo Fisher Scientific Inc were used. Staining was performed by streptavidin-biotin technique using DAKO LSAB+ kit. Statistical analyses were performed using of SPSS 23 Statistics software from IBM. Results: No differences in cyclin A and telomerase expression among gender and age groups were found, nor did the tumor dimensions have any significant impact on expression. Also, tumor grades and stages did not differ. However, histological types differed in favor of the papillary type. A significant positive correlation between both markers, as well as between the expression and tumor stage and grade was noticed. Only the tumor stage had negative impact on survival. Conclusions: Although not affecting survival, the expression of cyclin A and telomerase increased with tumor stage and grade, suggesting that cyclin A and telomerase could be potential proliferative immunohistochemical markers of RCC. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: The purpose of this study was to investigate into the expression of cyclin A and telomerase in renal cell carcinoma (RCC) and to analyze the relationship between expression and the clinicopathological characteristics of the tumor and their impact on survival. Methods: The overall material included 74 samples of RCC and 4 of normal renal tissue. Primary cyclin A antibody from Santa Cruz Biotechnology and TERT MA5-16034 antibody from Thermo Fisher Scientific Inc were used. Staining was performed by streptavidin-biotin technique using DAKO LSAB+ kit. Statistical analyses were performed using of SPSS 23 Statistics software from IBM. Results: No differences in cyclin A and telomerase expression among gender and age groups were found, nor did the tumor dimensions have any significant impact on expression. Also, tumor grades and stages did not differ. However, histological types differed in favor of the papillary type. A significant positive correlation between both markers, as well as between the expression and tumor stage and grade was noticed. Only the tumor stage had negative impact on survival. Conclusions: Although not affecting survival, the expression of cyclin A and telomerase increased with tumor stage and grade, suggesting that cyclin A and telomerase could be potential proliferative immunohistochemical markers of RCC. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults. Dysregulation of the cell cycle can lead to cancer development. In this study, the mitosis-associated cyclin A and p16, a negative controller, were investigated as potential key points in the RCC development. Methods: This retrospective study included 74 patients with RCC. The expression of cyclin A and p16 and their correlation to histopathological parameters (TNM stage, histological subtype, nuclear grade, tumor size), gender, age, and clinical outcome were studied and analyzed. Results: The highest median value for cyclin A (40%; range 0-70)) and for p16 (57.5%; range 35-80) were found in the papillary histological subtype. Survival analysis showed that in the group of patients that had died before September 2015, the median value for cyclin A was 20% (range 0-60), which was significantly higher than 5% (range 0-70), found in the group of patients that survived (p=0.019). Conclusions: In relation to the histological subtype, the papillary type of RCC was associated with a significantly higher expression of cyclin A and p16 compared to other subtypes of RCC. High expression of cyclin A indicated worse prognosis, therefore cyclin A could be considered to be a significant prognostic marker. © 2017 Zerbinis Publications. All rights reserved.

Purpose: Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults. Dysregulation of the cell cycle can lead to cancer development. In this study, the mitosis-associated cyclin A and p16, a negative controller, were investigated as potential key points in the RCC development. Methods: This retrospective study included 74 patients with RCC. The expression of cyclin A and p16 and their correlation to histopathological parameters (TNM stage, histological subtype, nuclear grade, tumor size), gender, age, and clinical outcome were studied and analyzed. Results: The highest median value for cyclin A (40%; range 0-70)) and for p16 (57.5%; range 35-80) were found in the papillary histological subtype. Survival analysis showed that in the group of patients that had died before September 2015, the median value for cyclin A was 20% (range 0-60), which was significantly higher than 5% (range 0-70), found in the group of patients that survived (p=0.019). Conclusions: In relation to the histological subtype, the papillary type of RCC was associated with a significantly higher expression of cyclin A and p16 compared to other subtypes of RCC. High expression of cyclin A indicated worse prognosis, therefore cyclin A could be considered to be a significant prognostic marker. © 2017 Zerbinis Publications. All rights reserved.

Purpose: Survivin is thought to play an important role in carcinogenesis and is found to be associated with poor clinical outcome in various malignancies. Gene -31 G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The purpose of this study was to investigate the association between survivin gene promoter -31C/G polymorphism and urothelial carcinoma (UC) risk in Serbian population and to compare the different expressions of survivin in UC of different disease stages, histological grades and tumor location in the upper or lower urinary tract. Methods: DNA from 94 patients with primary UC and from 82 healthy subjects was subjected to PCR restriction fragment length polymorphism analysis (PCR-RFLP) to identify individual genotypes. UC samples were subjected to immunohistochemical analysis to assess survivin expression in these lesions. Results: It was observed that the frequency of G/G genotype was greater in patients with UC (58.7%) than in controls (32%). Compared with study subjects carrying the C/G or C/C genotypes, significantly increased UC risk was found for individuals carrying the GIG genotype. Those carrying the G/G genotype had a significantly increased UC risk compared with those with C/G or C/C genotypes. Patients with UC carrying the G/G genotype had a greater prevalence of muscle-invading (stage T2-T4), high-grade (G2) tumor and immunohistochemicaly overexpressed survivin compared with those carrying the C/G or C/C genotypes. Conclusions: G/G genotype of the -31C/G polymorphism might be a risk factor for UC development.

Purpose: Survivin is thought to play an important role in carcinogenesis and is found to be associated with poor clinical outcome in various malignancies. Gene -31 G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The purpose of this study was to investigate the association between survivin gene promoter -31C/G polymorphism and urothelial carcinoma (UC) risk in Serbian population and to compare the different expressions of survivin in UC of different disease stages, histological grades and tumor location in the upper or lower urinary tract. Methods: DNA from 94 patients with primary UC and from 82 healthy subjects was subjected to PCR restriction fragment length polymorphism analysis (PCR-RFLP) to identify individual genotypes. UC samples were subjected to immunohistochemical analysis to assess survivin expression in these lesions. Results: It was observed that the frequency of G/G genotype was greater in patients with UC (58.7%) than in controls (32%). Compared with study subjects carrying the C/G or C/C genotypes, significantly increased UC risk was found for individuals carrying the GIG genotype. Those carrying the G/G genotype had a significantly increased UC risk compared with those with C/G or C/C genotypes. Patients with UC carrying the G/G genotype had a greater prevalence of muscle-invading (stage T2-T4), high-grade (G2) tumor and immunohistochemicaly overexpressed survivin compared with those carrying the C/G or C/C genotypes. Conclusions: G/G genotype of the -31C/G polymorphism might be a risk factor for UC development.

Purpose: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. Methods: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. Results: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). Conclusion: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT. © 2012 Zerbinis Medical Publications.

Purpose: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. Methods: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. Results: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). Conclusion: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT. © 2012 Zerbinis Medical Publications.

The rate of apoptosis varies in malignant tumors, and it can be involved in diminishing tumor size. Different protein-regulators of apoptosis, such as Bcl-2, BclX, and Bax have an influence on the rate of apoptosis in various tumors. In human renal diseases, such as the experimental model of acute renal failure, and many tumors, including Wilms' tumor, the expression of antiapoptotic members of Bcl-2 family is increased, while the expression of proapoptotic members is low. Aim: The aim of our study was to investigate Bcl-X S/L protein expression in Wilms' tumor, to compare it with the expression in normal renal tissue, as well as to see if there is a correlation between Bcl-X S/L expression in Wilms' tumor with tumor stage, histological type, prognostic group, or response to preoperative chemotherapy. Materials and Methods: Twenty-eight cases of Wilms' tumor (two cases with metastasis) and two samples of normal kidney tissue were studied using streptavidin-biotin-complex technique. Bcl-X S/L expression levels were semiquantitatively scored. Results: The expression of Bcl-X S/L was observed in the majority of cases (60.7%), more often in the blastemal than in the epithelial component of Wilms' tumor: 60.7% and 28.6%, respectively (p=0.02). There was a statistically significant inverse relationship between Bcl-X S/L expression and tumor stage (p=0.015). Bcl-X S/L was found less frequently in high-risk tumors then in tumors with good prognosis (p=0.02). Treated Wilms' tumors showed Bcl-X S/L expression more often than nontreated tumors, but the relationship was not statistically significant (p=0.08). Expression of Bcl-X S/L was detected in various histological types of Wilms' tumor, but there was no statistically significant association (p=0.82) except in cases with diffuse anaplasia (p=0.012), which were always negative. No Bcl-X S/L immunostaining was observed in two cases of metastasis or in one case of bilateral Wilms' tumor. Conclusion: Our results suggest that the expression of Bcl-X S/L protein is associated with prognostic group, tumor stage, and presence of anaplasia.