Papers by M. Sirotković-skerlev
Biomarkers, 2012
In this study we investigated the prognostic significance of serum matrix metalloproteinase (MMP)... more In this study we investigated the prognostic significance of serum matrix metalloproteinase (MMP)-1 levels in early-stage breast cancer patients and correlated these levels with various clinicopathologic parameters. MMP-1 levels were determined by enzyme-linked immunosorbent assay. MMP-1 serum levels in patients (n = 60) were significantly lower than in healthy subjects (n = 20, p < 0.0001). We found significant negative correlation between serum levels of MMP-1 and several negative prognostic factors of breast cancer. Kaplan-Meier analysis showed significantly shorter 5-year survival in patients with lower values of MMP-1 compared to those with high levels of MMP-1 (p = 0.0147). Our results suggest a negative prognostic role of low serum MMP-1.
Pathology & Oncology Research, 2014
HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. T... more HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. The aim of this study was to analyze the relationship between HER-2/neu extracellular domain in the serum and the prognosis in breast cancer patients. We also correlated HER-2/neu ECD with various clinicopathological factors including steroid receptor, HER-2/neu receptor coexpression. The serum from seventy nine patients with invasive breast cancer and twenty individuals without malignancy was analyzed using the enzymelinked immune adsorbent assay method. The cutoff value was estimated by the ROC curve analysis (15.86 μg/L). HER-2/neu ECD values in the serum of patients with breast cancer were significantly higher than in control subjects. Circulating HER-2/neu ECD was significantly associated with the histological grade of tumors and the status of axillary lymph nodes. Negative correlation was observed between HER-2/neu ECD in the serum and estrogen receptor positivity. When we analyzed HER-2/neu ECD in relation with coexpression of steroid receptor and HER-2/neu receptor in tissue, statistically higher values were found in the subgroup of patients with steroid receptor negative, HER-2/neu negative tumors than in the other subgroups. HER-2/neu ECD was not an independent factor in the univariate and multivariate analysis. However, elevated HER-2/neu ECD levels were found in patients with breast cancer possessing more aggressive phenotype.
Periodicum Biologorum
Sirtuins (SIRT) are group of enzymes that require nicotinamide adenine dinucleotide (NAD+) to cat... more Sirtuins (SIRT) are group of enzymes that require nicotinamide adenine dinucleotide (NAD+) to catalyze their reactions. These chemical compounds have mono (ADP-ribosyl) transferase or deacetylases activities, and they can be found in nearly all species. The mammalian sirtuin family is described by seven proteins, namely. Every group of sirtuins can be found in the different regions of the cells; SIRT1 is predominantly nuclear, SIRT2 is located mainly in the cytoplasm (but it can shuttle between the nucleus and the cytoplasm), SIRT3, SIRT4, and SIRT5 are mitochondrial proteins, (SIRT3 can move from the nucleus to mitochondria during cellular stress), SIRT6 and SIRT7 are nuclear sirtuins. Sirtuins have a lot of functions in different physiological processes such as gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neu-roprotection, and healthy aging. Because of so many roles in physiological processes there is a huge interest not j...
Pathology & Oncology Research, 2014
In our study we have compared the prognostic value of two distinct methods of immunohistochemical... more In our study we have compared the prognostic value of two distinct methods of immunohistochemical Ki-67 determination, tissue microarray (TMA) and classical whole section analysis. "Cut-off" values were used according to the 2009 St. Gallen Consensus. Tissue specimens were obtained from a consecutive retrospective series of 215 female patients with primary invasive tumours. Two hundred and thirteen patients were included in the study. Data on Ki-67 was collected by both tissue microarray (TMA) and whole section analysis. Follow up data on overall (OS) and disease-free survival (DFS) were collected. Median follow-up was 95 months (range from 7.8 through 107 months). Mutual correlation of two Ki-67 determination methods was non-significant (Person's r = 0.13417; p = 0.0528). There was statistically significant association of whole section Ki-67 expression with histological and nuclear grade, progesterone receptor and HER2/neu status. The expression of Ki-67 protein in TMAs correlated only with histological and nuclear grade, but not with other traditional clinicopathological factors. Statistically significant differences in DFS (p = 0.0156) and OS (p = 0.0028) were confirmed between subgroups with low and high whole section Ki-67 expression. When subgroups with high and intermediate expression were compared, significant difference was found in DFS (p = 0.0272), but not in OS (p = 0.0624). On the other hand, there was no statistically significant difference either in DFS, or in OS, according to the expression of Ki-67 in TMAs (p = 0.6529; p = 0.7883; p = 0.7966 for DFS, and p = 0.8917; p = 0.6448; p = 0.4323 for OS, respectively). In our study, classical whole section was superior to TMA analysis in terms of prognosis and clinicopathological correlation. Our results indicate that the method used may have impact on prognostic significance of Ki-67. Further studies are needed, covering a greater number of patients and including a precisely defined stage and treatment patient cohorts, in order to solve controversies in Ki-67 assessment methodology.
Sexually Transmitted Infections, Jul 1, 2013
The aims of this study were to assess the expression of protein products of c-myc, erbB-2, p53 an... more The aims of this study were to assess the expression of protein products of c-myc, erbB-2, p53 and nm23-H1 gene in benign and malignant breast lesions, to estimate their possible coexpression and to correlate the results of immunohistochemical analysis with various clinicopathologic parameters. The method used was the immunohistochemical detection of the corresponding protein. Expression of c-myc protein was high in both malignant and benign lesions (95% and 100%). Expression of erbB-2 and mutated p53 proteins in malignant lesions was 27% and 34%. These proteins were present in benign lesions as well: 7.8% of benign lesions were positive for erbB-2 protein and 19.6% for p53 protein. The expression of nm23-H1 protein was similar in benign and malignant lesions: 47% and 54%. The coexpression of nm23-H1 and mutated p53 protein was found in 14 carcinomas (16.5%). We found a tendency of negative correlation between the expression of these two proteins. We also found a negative correlation between the size of breast carcinomas and the expression of nm23-H1, a higher proportion of nm23-H1-positive carcinomas in the group of erbB-2-negative, p53-negative carcinomas and a higher proportion of nm23-H1-positive carcinomas in the group of malignant lesions with negative axillary lymph nodes. Our results support the hypothesis that in women with breast cancer the expression of nm23-H1 gene may contribute to more favorable phenotype. We also showed that some changes found in malignant breast tumors such as the presence of mutated p53 protein and the expression of erbB-2 protein may be found in benign lesions as well.
Journal of the European Academy of Dermatology and Venereology
Inflammation is defined as an enabling characteristic of malignant growth. Many proinflammatory m... more Inflammation is defined as an enabling characteristic of malignant growth. Many proinflammatory mediators have protumor capabilities. In this review we focus on the protumor effect of cytokines and chemokines in breast cancer. We discuss the role of interleukin 1b, interleukin 6, tumor necrosis factor a, CCL2, CCL5, and CXCL12 and its receptor CXCR4 as typical mediators implicated in breast cancer progression. We also analyze the impact of transcription factor NF-kB. Proinflammatory mediators with protumor effects should be considered as therapeutic targets in breast cancer. It is challenging how to find optimal anti-cytokine and anti-chemokine regiments as a part of anticancer therapy.
Der Hautarzt, 2009
Molluscum contagiosum (MC) is a common cutaneous infection caused by the molluscipox virus (MCV) ... more Molluscum contagiosum (MC) is a common cutaneous infection caused by the molluscipox virus (MCV) and can affect both children and adults. Molluscum contagiosum is relatively frequent in children aged 1-5 years old and can be localized almost anywhere on the body, but in adults it is regarded as a sexually transmitted infection (STI). MCV can be transmitted directly from person to person or by autoinoculation. MC in adults characteristically involves the genital area but extragenital appearance can be more typically seen in patients with immunosuppressive conditions, especially in HIV/AIDS. The onset of MC in HIV-positive individuals can be regarded as a part of the immune reconstitution inflammatory syndrome (IRIS). MC probably affects both sexes equally in children, whereas it seems that in adults the incidence is more prevalent in males. Therapy is controversial but may be considerably beneficial in preventing transmission or autoinoculation. At present there is no aetiological treatment of MC and most treatment options are mechanical sometimes causing discomfort or are not sufficiently evidence-based. Attention should be given to the extragenital site of involvement in adults and HIV testing should be recommended. Both children and adults with MC should be educated to avoid scratching and skin contact with others to prevent transmission and autoinoculation. Adult patients with MC should be carefully screened for other STIs and appropriately counseled.
Tumori
Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) are key mo... more Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) are key molecules in pericellular proteolysis, a process that plays an important role in tumor invasion and metastasis. In the current study we investigated the prognostic significance of uPA and PAI-1 in primary invasive breast cancer. uPA and PAI-1 antigen levels were determined by enzyme-linked immunosorbent assay in cytosols of 177 invasive ductal carcinoma specimens. The prognostic significance of uPA and PAI-1 was assessed for overall survival. The median follow-up time was 90 months. In univariate analysis, both uPA (third versus first tertile range of values; P = 0.02; HR = 2.08) and PAI-1 (third versus first tertile; P = 0.0007; HR = 3.1) were significant prognostic markers for overall survival. In multivariate analysis only nodal status (N2 vs N0; P = 0.0001; HR = 3.94) and PAI-1 (third versus first tertile; P = 0.004; HR = 3.05) remained significant independent prognostic factors. Both ...
Pathology & Oncology Research, 2014
In our study we have compared the prognostic value of two distinct methods of immunohistochemical... more In our study we have compared the prognostic value of two distinct methods of immunohistochemical Ki-67 determination, tissue microarray (TMA) and classical whole section analysis. "Cut-off" values were used according to the 2009 St. Gallen Consensus. Tissue specimens were obtained from a consecutive retrospective series of 215 female patients with primary invasive tumours. Two hundred and thirteen patients were included in the study. Data on Ki-67 was collected by both tissue microarray (TMA) and whole section analysis. Follow up data on overall (OS) and disease-free survival (DFS) were collected. Median follow-up was 95 months (range from 7.8 through 107 months). Mutual correlation of two Ki-67 determination methods was non-significant (Person's r = 0.13417; p = 0.0528). There was statistically significant association of whole section Ki-67 expression with histological and nuclear grade, progesterone receptor and HER2/neu status. The expression of Ki-67 protein in TMAs correlated only with histological and nuclear grade, but not with other traditional clinicopathological factors. Statistically significant differences in DFS (p = 0.0156) and OS (p = 0.0028) were confirmed between subgroups with low and high whole section Ki-67 expression. When subgroups with high and intermediate expression were compared, significant difference was found in DFS (p = 0.0272), but not in OS (p = 0.0624). On the other hand, there was no statistically significant difference either in DFS, or in OS, according to the expression of Ki-67 in TMAs (p = 0.6529; p = 0.7883; p = 0.7966 for DFS, and p = 0.8917; p = 0.6448; p = 0.4323 for OS, respectively). In our study, classical whole section was superior to TMA analysis in terms of prognosis and clinicopathological correlation. Our results indicate that the method used may have impact on prognostic significance of Ki-67. Further studies are needed, covering a greater number of patients and including a precisely defined stage and treatment patient cohorts, in order to solve controversies in Ki-67 assessment methodology.
Pathology & Oncology Research, 2014
HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. T... more HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. The aim of this study was to analyze the relationship between HER-2/neu extracellular domain in the serum and the prognosis in breast cancer patients. We also correlated HER-2/neu ECD with various clinicopathological factors including steroid receptor, HER-2/neu receptor coexpression. The serum from seventy nine patients with invasive breast cancer and twenty individuals without malignancy was analyzed using the enzyme-linked immune adsorbent assay method. The cut-off value was estimated by the ROC curve analysis (15.86 μg/L). HER-2/neu ECD values in the serum of patients with breast cancer were significantly higher than in control subjects. Circulating HER-2/neu ECD was significantly associated with the histological grade of tumors and the status of axillary lymph nodes. Negative correlation was observed between HER-2/neu ECD in the serum and estrogen receptor positivity. When we analyzed HER-2/neu ECD in relation with coexpression of steroid receptor and HER-2/neu receptor in tissue, statistically higher values were found in the subgroup of patients with steroid receptor negative, HER-2/neu negative tumors than in the other subgroups. HER-2/neu ECD was not an independent factor in the univariate and multivariate analysis. However, elevated HER-2/neu ECD levels were found in patients with breast cancer possessing more aggressive phenotype.
Medical oncology (Northwood, London, England), 2010
The aim of this study was to analyze the concentration of anti-p53 antibodies in the serum of bre... more The aim of this study was to analyze the concentration of anti-p53 antibodies in the serum of breast cancer patients and to correlate these results with various clinical, pathological and biochemical parameters. We also wanted to assess the prognostic significance of these antibodies in our patients. Sera from 61 patients with breast cancer and 20 individuals without malignancies were analyzed using enzyme-linked immunoadsorbent assay. High levels of anti-p53 antibodies were detected in twenty-one (35%) breast cancer patients and one control (5%). The difference was statistically significant. We observed an inverse relationship between the anti-p53 antibodies and the age of the patients. We found significant association of anti-p53 antibodies with tumor size, histological grade of the tumors and the number of axillary lymph nodes involved. The levels of anti-p53 antibodies were higher in patients with negative estrogen and progesterone receptors in comparison with patients with posi...
Biomarkers, 2012
In this study we investigated the prognostic significance of serum matrix metalloproteinase (MMP)... more In this study we investigated the prognostic significance of serum matrix metalloproteinase (MMP)-1 levels in early-stage breast cancer patients and correlated these levels with various clinicopathologic parameters. MMP-1 levels were determined by enzyme-linked immunosorbent assay. MMP-1 serum levels in patients (n = 60) were significantly lower than in healthy subjects (n = 20, p < 0.0001). We found significant negative correlation between serum levels of MMP-1 and several negative prognostic factors of breast cancer. Kaplan-Meier analysis showed significantly shorter 5-year survival in patients with lower values of MMP-1 compared to those with high levels of MMP-1 (p = 0.0147). Our results suggest a negative prognostic role of low serum MMP-1.
Annals of Human Genetics, 2008
Charcot-Marie-Tooth disease (CMT) is the most common neuromuscular disorder. It represents a grou... more Charcot-Marie-Tooth disease (CMT) is the most common neuromuscular disorder. It represents a group of clinically and genetically heterogeneous inherited neuropathies. Here, we review the results of molecular genetic investigations and the clinical and neurophysiological features of the different CMT subtypes. The products of genes associated with CMT phenotypes are important for the neuronal structure maintenance, axonal transport, nerve signal transduction and functions related to the cellular integrity. Identifying the molecular basis of CMT and studying the relevant genes and their functions is important to understand the pathophysiological mechanisms of these neurodegenerative disorders, and the processes involved in the normal development and function of the peripheral nervous system. The results of molecular genetic investigations have impact on the appropriate diagnosis, genetic counselling and possible new therapeutic options for CMT patients.
Periodicum Biologorum
Sirtuins (SIRT) are group of enzymes that require nicotinamide adenine dinucleotide (NAD+) to cat... more Sirtuins (SIRT) are group of enzymes that require nicotinamide adenine dinucleotide (NAD+) to catalyze their reactions. These chemical compounds have mono (ADP-ribosyl) transferase or deacetylases activities, and they can be found in nearly all species. The mammalian sirtuin family is described by seven proteins, namely. Every group of sirtuins can be found in the different regions of the cells; SIRT1 is predominantly nuclear, SIRT2 is located mainly in the cytoplasm (but it can shuttle between the nucleus and the cytoplasm), SIRT3, SIRT4, and SIRT5 are mitochondrial proteins, (SIRT3 can move from the nucleus to mitochondria during cellular stress), SIRT6 and SIRT7 are nuclear sirtuins. Sirtuins have a lot of functions in different physiological processes such as gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neu-roprotection, and healthy aging. Because of so many roles in physiological processes there is a huge interest not j...
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Papers by M. Sirotković-skerlev