Browsing by Author "Plješa-Ercegovac, Marija (16644038900)"

Ovarian cancer is regarded as the most lethal gynecological cancer with a five-year survival below 45%. It represents the seventh most common cancer among women. Due to the limited availability of biomarkers and reliable screening methods for early diagnosis of ovarian cancer, much research is being conducted to explore and understand the factors that may increase the risk of developing this kind of cancer. When surgery and chemotherapy treatments have been fully utilized, the development of chemoresistance becomes a critical factor in the progression of the disease. Glutathione transferases (GSTs) are a group of enzymes that play a role in the process of detoxification. Genes that code for GSTs proteins exhibit polymorphism, which can lead to either total or partial loss of enzymatic function. Cytosolic GST activity is composed of many different isoenzymes that facilitate interactions between glutathione and hazardous chemicals, including cancerogenes, anticancer drugs, and byproducts of oxidative stress. The scope of this review is to clarify the association of common GST polymorphisms with ovarian cancer risk and chemoresistance. © 2024, Serbia Medical Society. All rights reserved.

Introduction: It has been supposed that endocrine disturbances might be responsible for PCOS-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinaemic adolescent girls newly diagnosed with polycystic ovary syndrome (PCOS). Materials and methods: Nitrotyrosin, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, IGI, Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosin concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS. © 2018 Via Medica.All right reserved.

Introduction: It has been supposed that endocrine disturbances might be responsible for PCOS-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinaemic adolescent girls newly diagnosed with polycystic ovary syndrome (PCOS). Materials and methods: Nitrotyrosin, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, IGI, Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosin concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS. © 2018 Via Medica.All right reserved.

The aim of the study was to evaluate high-sensitivity C-reactive protein (hs-CRP) and fibrinogen in non-obese normoinsulinemic adolescent girls with polycystic ovary syndrome (PCOS) and their relationship with anthropometric and lipid parameters. The study comprised a total of 26 adolescent girls newly diagnosed with PCOS and 12 healthy controls with regular ovulatory menstrual cycles. The concentration of hs-CRP, fibrinogen, anthropometric measurements, and biochemical and hormonal testing were assessed. PCOS adolescent girls had significantly higher levels of hs-CRP and fibrinogen compared to healthy controls. In univariate regression analysis, statistically significant associations of hs-CRP and fibrinogen levels of PCOS patients have been shown with body mass index (BMI), waist circumference (WC), hip circumference (HC) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio, while hs-CRP levels were also associated with cholesterol and LDL. In the multivariate regression model, we found that hs-CRP levels were predicted by BMI (β=0.541, p<0.001) and LDL (β=0.507, p=0.014), while fibrinogen levels were predicted by BMI (β=0.449, p=0.004). We have shown an association of proinflammatory indices hs-CRP and fibrinogen with anthropometric and lipid parameters of adolescent women with PCOS. The inflammatory markers might be useful in monitoring normal-weight adolescent women with PCOS in an effort to timely prevent unfavorable changes in body mass and lipid profile. © 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.

The aim of the study was to evaluate high-sensitivity C-reactive protein (hs-CRP) and fibrinogen in non-obese normoinsulinemic adolescent girls with polycystic ovary syndrome (PCOS) and their relationship with anthropometric and lipid parameters. The study comprised a total of 26 adolescent girls newly diagnosed with PCOS and 12 healthy controls with regular ovulatory menstrual cycles. The concentration of hs-CRP, fibrinogen, anthropometric measurements, and biochemical and hormonal testing were assessed. PCOS adolescent girls had significantly higher levels of hs-CRP and fibrinogen compared to healthy controls. In univariate regression analysis, statistically significant associations of hs-CRP and fibrinogen levels of PCOS patients have been shown with body mass index (BMI), waist circumference (WC), hip circumference (HC) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio, while hs-CRP levels were also associated with cholesterol and LDL. In the multivariate regression model, we found that hs-CRP levels were predicted by BMI (β=0.541, p<0.001) and LDL (β=0.507, p=0.014), while fibrinogen levels were predicted by BMI (β=0.449, p=0.004). We have shown an association of proinflammatory indices hs-CRP and fibrinogen with anthropometric and lipid parameters of adolescent women with PCOS. The inflammatory markers might be useful in monitoring normal-weight adolescent women with PCOS in an effort to timely prevent unfavorable changes in body mass and lipid profile. © 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.

Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.

Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.

Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.

Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.