Browsing by Author "Boricic, Ivan (6603959716)"

Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.

Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.

Background/aims: Background/aims: Acute viral hepatitis is complicated rarely with severe liver failure due to many factors associated with the etiology, patient age, and time of development of hepatic encephalopathy, etc. The aim of this study was to identify some of the clinical and laboratory features associated with a fatal outcome in patients dying from acute viral hepatitis in Serbia. Methods: Clinical and laboratory data from 47 patients hospitalized from January 1989 - December 2006 were reviewed retrospectively. Serological tests for hepatitis A, B, C, D, and E viruses, herpes simplex viruses, cytomegalovirus, and Epstein-Barr virus were done. Histological features were assessed from 35 liver tissues. The electronic base, SPSS for Windows (version 11.0), was used for statistical analysis. Results: The majority of the patients had alanine aminotransferase (ALT) >20x the normal value, serum bilirubin >300μmol/L, prothrombin time >25 seconds (s), and white blood cell count >12 × 10 9/L. Regression analysis revealed activity of alanine aminotransferase >20x the normal value to be associated with fulminant (p=0.015) and serum bilirubin concentration with subfulminant hepatitis (p=0.008). Hepatitis B virus was the most commonly detected virus (70%). Massive hepatocyte necrosis vs. sub-massive with bridging necrosis were found to be independent of clinical presentation. Conclusions: Hepatitis B virus infection, severe impairment of liver function tests, and confluent hepatocyte necrosis and infection characterize patients dying from acute viral hepatitis in Serbia. High activity of alanine aminotransferase reflects rapid and extensive acute viral liver injury, while deep jaundice is more common in a protracted course of the disease.

Myoepitheliomas are tumors of myoepithelial cells, most frequently diagnosed in the salivary glands. Cutaneous location is very rare, especially for malignant variant. We report a case of recurrent cutaneous myoepithelial carcinoma of the femoral region in a 51-year-old woman. Histologically, the tumor was confined to the dermis and superficial subcutaneous fat tissue, exhibiting typical multinodular pattern. The majority of tumor cells were of clear cell type, although rare epithelioid and spindle cells were also present. Nuclear atypia, mitotic activity of 12 mitoses per 10 microscopic high power fields and Ki-67 labeling index of 20%, as well as three recurrences, corroborated the malignant nature of the tumor. Immunohistochemistry showed positivity for cytokeratin, epithelial membrane antigen, vimentin, S-100 protein and myogenic markers (α-smooth muscle actin and muscle-specific actin HHF-35) in keeping with the myoepithelial cell immunophenotype. Staining for CD34, desmin and HMB-45 was negative. Myoepithelial carcinoma should be considered in the differential diagnosis of cutaneous neoplasms composed predominantly of clear cells. © 2009 John Wiley and Sons A/S.

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.

[No abstract available]

A 54-year-old female presented with the cutaneous metastases of the breast carcinoma that produced combination of pigmented zosteriform eruption on the trunk and eroded plaque on the scalp, 13 years after radical mastectomy. Histologically, zosteriform lesions displayed prominent infiltration of the epidermis in nesting or linear pattern by neoplastic cells with focal formation of intraepidermal and subepidermal vesicles due to discohesion of tumor cells and dermal edema. Examination of scalp plaque revealed ulcerations and infiltration of the epidermis with scattered basal and suprabasal malignant cells in pagetoid fashion. Immunohistochemically, tumor cells were cytokeratin 7- and estrogen receptor-positive and cytokeratin 20 negative. HMB-45 and Melan-A-stained numerous dendritic melanocytes intermingled with intraepidermal and superficial dermal tumor cells in the trunk lesion, whereas on the scalp, only occasional melanocytes surrounding intraepidermal carcinomatous cells were identified. Our case described, to our knowledge, so far unreported combination of individually rare, clinical and histological patterns of cutaneous metastases from breast carcinoma in a single patient. © Blackwell Munksgaard 2003.

Aim: To investigate the prevalence of hepatitis C virus (HCV) genotypes in Serbia and Montenegro and their influence on some clinical characteristics in patients with chronic HCV infection. Methods: A total of 164 patients was investigated. Complete history route of infection, assessment of alcohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene sequencing of 5′ NTR type-specific PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows (version 10.0) was used for univariate regression analysis with further multivariate analysis. Results: The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 (mainly the subtype 1b) was found to be independent of age in subjects older than 40 years, high viral load, more severe necro-inflammatory activity, advanced stage of fibrosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive predictive factors for the genotypes lb and 3a, respectively. Conclusion: In Serbia and Montenegro, the genotypes 1b and 3a predominate in patients with chronic HCV infection. The subtype lb is characteristic of older patients, while the genotype 3a is common in drug abusers. Association of the subtype lb with advanced liver disease, higher viral load and histological activity suggests earlier infection with this genotype and eventually its increased pathogenicity. © 2007 The WJG Press. All rights reserved.

[No abstract available]

Purpose: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. It is characterized by a high rate of recurrence, perineural invasion and development of distant metastases many years after removal of the primary tumor. Disorders of the induction of apoptosis and its cascade reactions where caspases are involved may be significant in the pathogenesis of this tumor. Methods: The immunohistochemical expression of caspase 9 and caspase 3 was analyzed by tissue microarray (TMA) in 50 cases of ACC in relation with different clinicopathological parameters (gender, age, localization, histological type and overall survival). Results: Caspase 9 was expressed in the cytoplasm and nuclei of ACC tumor cells with varying degrees of staining intensity (1+, 6%; 2+, 54%, 3+, 40%). Comparison of caspase 9 expression in tumor cells with clinicopathological parameters (gender, age, localization, histological type and overall survival) showed no statistically significant difference except that the expression was more pronounced infernales. Caspase 3 was expressed in the cytoplasm of tumor cells with varying degrees of staining intensity (1+, 22%; 2+, 36%; 3+, 42%). No correlation between the expression of caspase 3 and clinicopathological parameters was noticed. Conclusions: The expression of caspases 9 and 3 in ACC of the salivary glands can contribute in the better characterization of molecules involved in apoptosis of tumor cells.

Purpose: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. It is characterized by a high rate of recurrence, perineural invasion and development of distant metastases many years after removal of the primary tumor. Disorders of the induction of apoptosis and its cascade reactions where caspases are involved may be significant in the pathogenesis of this tumor. Methods: The immunohistochemical expression of caspase 9 and caspase 3 was analyzed by tissue microarray (TMA) in 50 cases of ACC in relation with different clinicopathological parameters (gender, age, localization, histological type and overall survival). Results: Caspase 9 was expressed in the cytoplasm and nuclei of ACC tumor cells with varying degrees of staining intensity (1+, 6%; 2+, 54%, 3+, 40%). Comparison of caspase 9 expression in tumor cells with clinicopathological parameters (gender, age, localization, histological type and overall survival) showed no statistically significant difference except that the expression was more pronounced infernales. Caspase 3 was expressed in the cytoplasm of tumor cells with varying degrees of staining intensity (1+, 22%; 2+, 36%; 3+, 42%). No correlation between the expression of caspase 3 and clinicopathological parameters was noticed. Conclusions: The expression of caspases 9 and 3 in ACC of the salivary glands can contribute in the better characterization of molecules involved in apoptosis of tumor cells.

Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 µmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

[No abstract available]

Objectives: This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. Materials and methods: Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. Results: Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673–0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). Conclusion: miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients. © 2022 Wiley Periodicals LLC.

Objectives: This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. Materials and methods: Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. Results: Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673–0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). Conclusion: miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients. © 2022 Wiley Periodicals LLC.

[No abstract available]

Background/Aims: Progression of chronic hepatitis C depends on the host and viral characteristics, duration of infection, co-infection with other viruses, etc. In this study, some of demographic, epidemiological and viral data as risk factors for a degree of liver fibrosis were evaluated. Methodology: A total of 144 patients was investigated (89 males, ages from 16-65 years) classified into two groups, with fibrosis scores 0-3 and 4-6, using the Ishak scoring system. Significant variables were entered into univariate logistic regression model and further multivariate analysis was performed. Results: There were 64% and 36% of patients with fibrosis scores 0-3 and 4-6, respectively. Gender, moderate to heavy alcohol abuse and high viral RNA were equally distributed between both groups. In univariate analysis, the age older than 40, history of intravenous drug abuse, and the genotype 1b were independently associated with different fibrosis scores. Multivariate regression analysis revealed ages older than 40 as the positive (p<0.001), and younger than 40 as the negative predictive factors for fibrosis scores 4-6 and 0-3 (p<0.001), respectively. Conclusions: Our results indicate the age over 40 at the time of liver biopsy as the important risk factor for advanced liver disease in chronic hepatitis C according to fibrosis scores. © H.G.E. Update Medical Publishing S.A.

An 83-year-old woman presented with a nodular, eroded tumor on the skin between the nose and the upper lip of 18 months' duration. There were no palpable lymph nodes and no infiltrates on chest radiography. Complete surgical excision showed a tumor measuring 65 × 40 × 30 mm. On histopathologic examination, it was composed of typical basal cell carcinoma (BCC) nodules and large sheets of oval or short spindle cells (Fig. 1a), with vesicular nuclei, distinct nucleoli, moderate pleomorphism, and pronounced mitotic activity (more than 40 mitoses/10 high-power fields). In parts abutting the upper lip, BCC nodules were found in the muscle layer, but the small salivary glands were uninvolved (Fig. 1b). Immunohistochemical analysis (Table 1) revealed a cytokeratin (CK)-positive, Ber-EP4-positive, and vimentin-negative BCC component (Fig. 2a), and a vimentin-positive, CK-negative sarcomatous component (Fig. 2b). In addition, mesenchymal tumor components were focally positive for smooth muscle actin (SMA). The BCC component showed irregular reaction with CK7, which stained some lobules and parts of individual nests (Fig. 2c). The final diagnosis was primary cutaneous carcinosarcoma. At the last visit, 3 months after operation, no signs of recurrence or metastatic spread were observed. Additional immunohistochemical analyses showed preserved membranous β-catenin staining in the BCC component, without nuclear reaction in the mesenchymal component. The labeling index (LI) is expressed as the percentage of positive cells, and is calculated from the number of positive tumor cells divided by the total number of tumor cells counted (minimum 300 cells) in the areas with most pronounced immunopositivity. Counting was performed on images taken from microscopic high-power fields with an Olympus DP70 digital camera (Olympus Corporation, Tokyo, Japan). The program analySYS (Soft Imaging System, Munster, Germany) was used, with the screen grid and the manual touch-count method. The LI values of Ki-67 and telomerase reverse transcriptase (hTERT) were higher in the sarcomatous component. hTERT displayed enhanced nucleolar localization and diffuse staining of mitotic cells. Histone deacetylase 1 (HDAC1) was expressed in a smaller percentage of cells than HDAC2, with a higher LI in the sarcomatous component. HDAC2 was the only marker analyzed that stained more cells in the BCC component (Fig. 2d). © 2008 The International Society of Dermatology.

Background & Aim. Quality of life may be reduced in patients with chronic liver diseases. The purpose of this study was to assess the impact of chronic viral liver disease on health-related quality of life (HRQOL). Patients and methods. Quality of life was prospectively investigated in 227 patients with chronic viral liver disease and 75 controls. The generic Short Form 12 questionnaire was applied to measure the HRQOL. Mental and physical component scores were expressed as numeric and categorical values (presence/absence of disability). The electronic database (SPSS for Windows) was used for statistical analysis with 95% confidence intervals. Results. Mental and physical numeric and categorical scores for the absence of disability were significantly worse in patients compared with controls. Patients were a negative predictive factor for the absence of disability on both mental and physical components while the physical component was the significant factor in multivariate regression analysis (p =0.000). There was no difference in HRQOL scores among patients with hepatitis C or B virus infection. Mental and physical numeric scores were lower in patients with cirrhosis. Liver cirrhosis predicted lower components of the absence of disability in comparison to chronic hepatitis more influencing the physical component (p =0.003). Conclusions. Chronic viral liver disease reduces and predicts a lower quality of life in comparison to a healthy population impairing more the physical component. Hepatitis viruses do not influence differently the quality of life. Liver cirrhosis has a higher negative impact on the quality of life than chronic hepatitis, especially relating to a physical component.