26 results on '"Šarčević B"'
Search Results
2. PO-341 The role of cancer/testis antigens from MAGE-A family and NY-ESO-1 in ductal carcinoma in situ (DCIS)
- Author
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Roguljic, A., Juretic, A., Spagnoli, G., Sarcevic, B., Banovic, M., and Oreskovic, L. Beketic
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- 2018
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3. 429 (PB-062) - Elevated Bcl-2 expression as an independent prognostic marker for decreased overall survival in patients with triple-negative breast cancer
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Beketic Oreskovic, L., Ozretic, P., Alvir, I., Vujaskovic, Z., Rendic-Miocevic, Z., Roguljic, A., and Sarcevic, B.
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- 2018
- Full Text
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4. Cutaneous appendage tumors in bioptic material obtained at the University hospital for tumors in Zagreb in the 1988-1992 period
- Author
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Jurić G, Knežević F, Šeparović V, Šarčević B, Kosanović S, Krušlin B
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integumentary system ,skin ,cutaneous appendage tumors ,biopsy - Abstract
In 5-year period there were 4606 skin biopsies. Benign cutaneous tumors were diagnosed in 1704 and malignant in 2164 cases. Benign appendage tumors were diagnosed in 86 cases(5, 0% of all benign skin tumors), more frequent in women (62, 5%) with most common type pilomatricoma, found in 40 cases (46, 5%). There were only 4 cases of malignant cutaneous appendage (0, 2% of all malignant skin tumors), 3 of them sweat glang carcinoma and 1 sebaceous carcinoma.
- Published
- 1996
5. Patohistološki kriteriji za određivanje diferenciranosti ekstenzivne intraduktalne komponente (EIC) u karcinomima dojke
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Šarčević B, Šeparović R, Krušlin B, Knežević F, Orešić V, Štajcer-Štitić V
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ekstenzivna intraduktalna komponenta (EIC) ,karcinom dojke - Abstract
ekstenzivne intraduktalne komponente (EIC) u karcinomima dojke
- Published
- 1996
6. Prognostic value of prominent DCIS component in the breast-conserving therapy of stage I and II invasive ductal breast cancer
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Šeparović, V., primary, Šarčević, B., additional, Šeparović, R., additional, Ores̆ić, V., additional, Nola, N., additional, Vrdoljak, M., additional, and Krus̆lin, B., additional
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- 1999
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7. 770 poster PROGNOSTIC SIGNIFICANCE OF CARBONIC ANHYDRASE IX (CA IX) IN BREAST CANCER PATIENTS TREATED WITH RADIOTHERAPY
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Beketic-Oreskovic, L., Ozretic, P., Rabbani, Z., Jackson, I., Sarcevic, B., Levanat, S., Maric, P., and Vujaskovic, Z.
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- 2011
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8. Značenje nekih kliničkih i histoloških varijabli za prognozu medularnog karcinoma štitne žlijezde
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Šeparović V, Šarčević B, Kralj Z, Tiška-Rudman Lj, Knežević F, Kosanović S
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histologija ,karcinom štitnjače - Abstract
Značenje nekih kliničkih i histoloških varijabli za prognozu medularnog karcinoma štitne žlijezde
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- 1989
9. Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site,Kliničke preporuke za dijagnozu, liječenje ipraćenje bolesnika oboljelih od raka nepoznata primarnog podrijetla
- Author
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Bišof, V., Juretić, A., Dragan Trivanović, Dintinjana, R. D., Šarčević, B., Jakić-Razumović, J., Ban, M., Bošković, L., Miše, B. P., Bura, M., and Stančić-Rokotov, D.
10. INTERLABORATORY CONCORDANCE IN HER-2 POSITIVE BREAST CANCER
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Nives Jonjić, Mustać, E., Tomić, S., Jakić Razumović, J., Šarčević, B., Blažičević, V., Peteh Labinac, L., Švagelj, D., Kopjar, A., Lisica Šikic, N., Vrbičić, B., and Borić, I.
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Adult ,Receptor, ErbB-2 ,lcsh:R ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Pathology ,Quality control ,lcsh:Medicine ,Breast Neoplasms ,Clinical Laboratory Services ,Middle Aged ,Immunohistochemistry ,Quality ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Patologija ,Gene Expression Regulation, Neoplastic ,Carcinoma, Intraductal, Noninfiltrating ,Breast cancer ,HER-2 ,Humans ,Female ,In situ hybridization ,In situ hybridization, fluorescence - Abstract
Accurate assessment of HER -2 status is essential for identifying patients who will benefit from HER -2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER -2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER -2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER -2 positive and 12% (17/143) as HER -2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER -2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER -2 test results.
11. Mechanisms of mono- and poly-ubiquitination: Ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine
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Sadowski Martin and Sarcevic Boris
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.
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- 2010
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12. The Expression of p53/p73 Isoforms, NME and GLI in Metastatic Melanoma and Their Induction by γ-Irradiation
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Hanžić, Nikolina, Proust, Bastien Lucien Jean, Petrović, Lidija, Ozretić, Petar, Milas, Ivan, Herak Bosnar, Maja, Levanat, Slade, Slade, Neda, Beketić-Orešković, L, Kusić, Z, and Šarčević, B
- Subjects
p53, p73, NME, GLI, melanoma - Abstract
Although mutations of p53 occur infrequently in melanoma, it fails to function as a tumor suppressor. This may result from alterations in p53 family members, including the diverse isoforms of p53 and its homologue p73. Moreover, we assume that the p53 function in malignant melanoma might be altered through interactions with p53 small molecular weight and p73 isoforms, NME and GLI families of proteins. Therefore, we are studying the expression profile of p53 and its potential interaction partners (p73/NME/GLI) in metastatic melanoma and in adjacent healthy skin tissue. In the study on 30 patients with metastatic melanoma, the expression of p53, p73, NME and GLI protein families was determined by western blot analysis and quantitative RT-PCR. Protein expression analysis has shown that only Δ133p53α expression is significantly different in the two tissue types: it is poorly expressed in healthy tissue (only 12% of samples), but strongly expressed in tumor tissue (72% of samples). There is no difference of expression of other p53 isoforms between healthy and tumor tissue samples. Protein p73 is expressed in almost all tumor samples and healthy tissue samples. TAp73α and ΔNp73α, are more frequent in tumor samples and TAp73 β and ΔNp73 β, are less frequent in tumor samples than in healthy tissue samples. Proteins NME1 and NME3 are expressed in 96% of tumor samples and 70% of healthy tissue samples. Surprisingly, protein expression of NME1 and NME2 was several fold higher in tumor samples than in healthy tissue samples. GLI1 and both GLI3A and GLI3R have higher expression in tumor than in healthy tissue samples. GLI2 is expressed in only 8% of tumors and not in healthy tissue samples. Comparison of gene expression in the melanoma tissue samples and corresponding normal tissue revealed that NME2 is significantly stronger expressed in normal tissue while NME1 is expressed equally in healthy and tumor tissue. All other examined genes are significantly less expressed in the tumor tissue. To obtain higher expression of proteins of interest, we irradiated two melanoma cell lines with different mutational status of p53 (Mel505/p53mut and A375M/p53wt) with γ rays with the dose of 5 and 10 Gy. The results have shown that γ irradiation increases the level of proteins of interest to certain extent and their protein expression profile obtained after γ irradiation provide the molecular environment where the proteins possibly interact and inhibit activity of p53 in melanoma.
- Published
- 2016
13. Synthesis and application of gold nanoparticles to breast cancer cells
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Hanžić, Nikolina, Horvat, Anđela, Marijanović, Inga, Slade, Neda, Gotić, Marijan, Beketić-Orešković, L, Kusić, Z, and Šarčević, B
- Subjects
nanoparticles, x-irradiation, radiosensitation, breast cancer cells, cell cycle - Abstract
Nanoparticle-based therapies to treat cancer are widely evolving. Gold nanoparticles (GNPs) are small units that are inert and non-toxic to cells. The aim of this work was to study the radiosensitization effect of three types of GNPs to MDA-MB-231 breast cancer cells in vitro. Citrate, glutathione and aminodextran were used to modify GNPs surface and to increase their accumulation in cancer cells. All GNPs were well characterized with respect to their particle size, shape and colloidal stability in aqueous solution and cell media. Transmission electron microscopy demonstrated accumulation of GNPs in cytoplasmic vesicles, while the mass spectroscopy demonstrated the highest uptake of glutathione modified GNPs. GNPs alone show no significant effect on cell cycle demonstrated by flow cytometry and western blot analysis. As well, cells treated with GNPs in combination with x-ray irradiation show no significant effect on cell cycle. Nevertheless, long-term overall survival of cells treated with GNPs in combination with irradiation was reduced. In conclusion, we showed that GNPs have certain biological effect, but still the precise mechanism of their activity remains to be explored.
- Published
- 2016
14. Nuclear localization of NRF2 in stroma of HER2 positive and triple-negative breast cancer.
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Orešić T, Bubanović S, Ramić S, Šarčević B, and Čipak Gašparović A
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- Humans, Female, Reactive Oxygen Species, NF-E2-Related Factor 2 metabolism, Oxidative Stress, Hypoxia, Triple Negative Breast Neoplasms pathology
- Abstract
Breast cancer is one of the leading causes of cancer-related mortality in women. During tumor growth, periods of hypoxia are followed by reoxygenation due to neovascularisation leading to disturbed redox homeostasis. ROS (Reactive Oxygen Species) produced under hypoxia activate HIF1α. ROS can also activate the major antioxidant transcription factor NRF2, but also cause damage to biomolecules. Lipids are susceptible to peroxidation, as evidenced by the formation of reactive aldehydes, among which, HNE (4-hydroxynonenal) is the most studied one. Knowing that HIF1α (Hypoxia Inducing Factor 1α) is associated with breast cancer malignancy, we aimed to investigate its correlation with HNE and NRF2 (Nuclear factor erythroid 2-related factor 2). Our results show that HIF1α is activated in breast cancer, indicating an increase in ROS but not followed by HNE production. On the other hand, NRF2 was increased in all types of breast cancer suggesting that oxidative stress is present in these pathologies, but also supporting HIF1α. Interestingly, NRF2 was activated in HER2 positive and TNBC, indicating the role of stromal NRF2 in breast cancer malignancy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ana Cipak Gasparovic reports financial support was provided by Croatian Ministry of Science and Technology., (Copyright © 2023 Elsevier GmbH. All rights reserved.)
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- 2023
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15. Immunohistochemical Expression of Matrix Metalloproteinase-1 and Cyclooxygenase-2 in Cutaneous Squamous Cell and Basal Cell Carcinoma.
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Smuđ Orehovec S, Dujmović A, Mijatović D, Mance M, and Šarčević B
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- Cyclooxygenase 2, Epithelial Cells, Humans, Matrix Metalloproteinase 1, Retrospective Studies, Carcinoma, Basal Cell, Skin Neoplasms
- Abstract
The most common nonmelanoma skin cancers (NMSC) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of NMSC is 18-20 times higher than the incidence of melanoma. The Cyclooxygenase-2 (COX-2) and Matrix Metalloproteinase-1 (MMP-1) enzymes have both been linked to the development of these diseases but their exact significance is unknown. We conducted a retrospective analysis on 148 adult patients with cutaneous BCC and SCC. Cases were divided according to the sub-types of BCC and the degree of SCC differentiation. Immunohistochemical staining for COX-2 and MMP-1 was performed and analyzed to determine if the expression of these biomarkers were associated with BCC subtypes and the degree of SCC. differentiation. We did not find a significant association of the level of differentiation of SCC with the immunohistochemical expression for MMP-1 or COX-2. There was a significant association between BCC subtypes and immunohistochemical expression for MMP-1; positive expression of this enzyme reduces the odds for the infiltrative subtypes by 90%. A marginally significant association between BCC subtypes and immunohistochemical expression for COX-2 was also found. This enzyme was highly expressed in non-infiltrative basal cell carcinoma types (94%) compared with infiltrative types (71%). In conclusion, we did not find a significant predictor for SCC expression levels for either of two biomarkers, while the expression of MMP-1 in BCC was significantly inversely associated with the infiltrative type (moderate sensitivity and high specificity). Further research with larger sample sizes is needed to precisely determine the role these enzymes have in these diseases.
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- 2021
16. CHARACTERISTICS AND PROGNOSIS OF TRIPLE-NEGATIVE BREAST CANCER PATIENTS: A CROATIAN SINGLE INstitution RETROSPECTIVE COHORT STUDY.
- Author
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Tečić Vuger A, Šeparović R, Vazdar L, Pavlović M, Lepetić P, Šitić S, Bajić Ž, Šarčević B, and Vrbanec D
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- Croatia epidemiology, Disease-Free Survival, Female, Humans, Middle Aged, Prognosis, Retrospective Studies, Breast Neoplasms diagnosis, Breast Neoplasms therapy, Triple Negative Breast Neoplasms epidemiology, Triple Negative Breast Neoplasms therapy
- Abstract
Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).
- Published
- 2020
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17. POSITIVE EXPRESSION OF NEDD9 IN HEAD AND NECK CANCER IS RELATED TO BETTER SURVIVAL PERIOD.
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Ledinsky Opačić I, Gršić K, Šitić S, Penavić I, Pastorčić Grgić M, and Šarčević B
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- Aged, Female, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Adaptor Proteins, Signal Transducing metabolism, Head and Neck Neoplasms metabolism, Head and Neck Neoplasms physiopathology, Squamous Cell Carcinoma of Head and Neck metabolism, Squamous Cell Carcinoma of Head and Neck physiopathology, Survival Rate
- Abstract
The aim was to determine immunohistochemical expression of NEDD9 protein in head and neck squamous cell carcinoma (HNSCC) and the possible relation of its expression with primary tumor size (T), regional lymph node status (N), stage of disease (TNM) and survival period. A total of 131 patients with primary tumor localization in the area of oropharynx, hypopharynx and larynx, monitored for at least 5 years after initial surgical treatment were analyzed. The study included 128 male and three female patients, median age 62.0 (range 53.0-68.0) years. Of these, 105 (95%) patients showed positive NEDD9 expressed by dyed cytoplasm. There were no significant differences in NEDD9 expression according to TNM tumor status. Patients with positive NEDD9 expression had a significantly higher median (IQR) survival time 51.0 (15.0-60.0) months as compared to 22.5 (9.0-55.0) months in patients with negative NEDD9 expression (p=0.048). NEDD9 negative expression, controlled for the influence of other variables included in the Cox's proportional hazards model, had a significant hazard ratio (HR) of 2.10 (95% CI: 1.23-3.58; p=0.006). The results of our study showed that NEDD9 expression might be an independent prognostic marker in patients with HNSCC regarding data on overall survival and mortality.
- Published
- 2019
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18. PRIMARY MALIGNANT MELANOMA OF THE URINARY BLADDER: CASE REPORT.
- Author
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Kirigin M, Lež C, Šarčević B, Šoipi Š, Jaić G, Ulamec M, and Krušlin B
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- Aged, 80 and over, Female, Humans, Melanoma surgery, Treatment Failure, Urinary Bladder pathology, Urinary Bladder Neoplasms surgery, Melanoma pathology, Urinary Bladder Neoplasms pathology
- Abstract
Primary malignant melanoma of the urinary bladder is rare, with only 20 cases reported to date. We present a case of an 87-year-old woman with multiple comorbidities who presented with advanced urinary bladder neoplasm. Histopathologic analysis suggested melanoma of the urinary bladder. No previous or concurrent diagnosis of cutaneous melanoma was documented. The patient underwent transurethral resection of the tumor before and during hospitalization at our hospital but died shortly after due to widespread disease. Autopsy was not performed.
- Published
- 2019
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19. Critical evaluation of the use of total reflection X-ray fluorescence spectrometry for the analysis of whole blood samples: application to patients with thyroid gland diseases.
- Author
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Marguí E, Jablan J, Gerić M, Inić S, Domijan AM, Janušić R, Šarčević B, Queralt I, and Garaj-Vrhovac V
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- Adult, Aged, Elements, Humans, Middle Aged, Thyroid Diseases diagnosis, Thyroid Gland pathology, Blood Chemical Analysis methods, Spectrometry, X-Ray Emission methods, Thyroid Diseases blood
- Abstract
Multielemental analysis of whole blood can provide significant information for the evaluation of nutritional status and diagnosis of certain diseases as well as for the assessment of exposure to potentially toxic metals. However, the quantification of multiple elements in whole blood is not easy partly because of the wide variation in element concentrations (from ng L
-1 to g L-1 ) and the complex matrix. The aim of this work was to develop a fast, sustainable, and reliable analytical method, in combination with low-power TXRF, for multielemental analysis of blood samples. Firstly, a set of experiments were carried out to select the best diluent type and dilution factor using the control material SeronormTM Trace Elements Whole Blood L-1. A critical evaluation of the parameters affecting the sample deposition on the reflector was also carried out including a study of the shape and element distribution of the deposited residue on the reflector by micro X-ray fluorescence spectrometry. Using the best analytical conditions, limits of detection estimated were in the low milligrams per kilogram range and similar to those obtained using more complex sample treatments such as digestion. Accuracy and precision of the results were in most cases acceptable (recoveries 89-102%, RSD 6-8%, n = 5). Only underestimated values were obtained for light elements such as potassium. To prove the applicability of the method, several blood samples from control and thyroid disease patients were analyzed. Despite the fact that more samples need to be analyzed, it seems that Zn and Br contents in some of the patients are significantly higher compared to control samples. Graphical abstract.- Published
- 2019
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20. Inter-laboratory comparison of Ki-67 proliferating index detected by visual assessment and automated digital image analysis.
- Author
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Tomić S, Mrklić I, Razumović JJ, Jonjić N, Šarčević B, Blažičević V, Jurković I, Vrbičić B, Lisica Šikic N, Peteh LL, Lončarić ČT, Vučić M, Gašparov S, Švagelj D, Radiković S, and Mahovne I
- Subjects
- Automation, Laboratory standards, Automation, Laboratory statistics & numerical data, Breast Neoplasms diagnosis, Croatia, Cross-Sectional Studies, Female, Humans, Image Processing, Computer-Assisted statistics & numerical data, Immunohistochemistry, Laboratories, Hospital statistics & numerical data, Paraffin Embedding, Breast Neoplasms pathology, Cell Proliferation, Image Processing, Computer-Assisted standards, Ki-67 Antigen analysis, Laboratories, Hospital standards
- Abstract
Background: Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions., Methods: This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value., Results: When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58-0.91), and Krippendorff's alpha was 0.79 (95% CI 0.58-1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study., Conclusion: Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions.
- Published
- 2019
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21. Tuberculosis of the Oral Cavity Misdiagnosed as Precancerous Lesion.
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Vučičević Boras V, Gabrić D, Smiljanić Tomičević L, Seiwerth S, Gršić K, Šarčević B, Lončar Brzak B, Marunica E, and Glavina A
- Abstract
Introduction: The aim of this case report was to discuss an extremely rare oral lesion as a result of primary pulmonary tuberculosis., Case Report: In this case report, the patient with refractory painless ulceration at ventral surface of the tongue was described. Detailed medical history was taken followed by clinical examination of the oral mucosa and palpation of regional lymph nodes. Clinical examination revealed ulceration on the patient's ventro-lateral surface of the tongue, approximately two centimeters in diameter. Palpation of regional lymph nodes has not revealed enlargement. The toluidine blue test of the suspected lesion was performed at each control examination. Biopsy samples for histopathologic diagnosis were taken three times. The analysis of the first biopsy sample for histopathology revealed a non-specific inflammation, the second biopsy revealed a caseous necrosis without positive Ziehl-Neelsen staining and the third biopsy revealed a granulomatous inflammation which was highly suspicious of sarcoidosis. During hospitalization, the patient underwent a complete physical examination, and laboratory and radiological diagnostics. Physical chest examination revealed bilaterally coarse crepitations and laboratory findings of his complete blood count revealed normocytic anemia of chronic disease. Radiographic examination of lungs showed multiple small nodules bilaterally and positive direct sputum smear., Conclusion: Although oral tuberculosis is a rare condition, it must be taken into account in differential diagnosis of refractory painless oral ulcers., Competing Interests: Conflict of interest: Authors declare they have no conflict of interest.
- Published
- 2017
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22. Cytogenetic status and oxidative stress parameters in patients with thyroid diseases.
- Author
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Gerić M, Domijan AM, Gluščić V, Janušić R, Šarčević B, and Garaj-Vrhovac V
- Subjects
- Adult, Aged, Case-Control Studies, Chromosome Aberrations, Female, Humans, Male, Middle Aged, Thyroid Diseases genetics, Oxidative Stress, Thyroid Diseases metabolism
- Abstract
Since the incidence of cancer has increased over the years, adequate prevention programmes are needed. Thyroid cancer is one of the fastest growing cancer types in the world. In this study we performed a case-control study of 100 untreated patients with thyroid diseases (papillary thyroid cancer, follicular thyroid adenoma, and other thyroid diseases) and 100 control volunteers. Oxidative status differed among the two investigated groups. The patients' group had 1.60-fold higher concentrations of malondialdehyde and 1.26-fold higher concentrations of protein carbonyls. At the same time, the concentrations of glutathione and catalase activity were by 32% and 35% lower, respectively. A similar effect was observed for the cytogenetic status where higher comet assay tail intensity (1.84-fold) and the total numbers of chromosome aberrations (1.47-fold), micronuclei (2.32-fold), nucleoplasmic bridges (3.98-fold), and nuclear buds (2.34-fold) were detected. As for protein expression in thyroid tissue, 97.89% were positive for either B-Raf or Ret. Interestingly, the papillary thyroid cancer patients more frequently expressed B-Raf proteins compared to the follicular thyroid adenoma patients and patients with other thyroid diseases. Human biomonitoring studies enable a risk assessment of general population, such data could be used to identify risk subgroups., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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23. Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration.
- Author
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Roesley SN, Suryadinata R, Morrish E, Tan AR, Issa SM, Oakhill JS, Bernard O, Welch DR, and Šarčević B
- Subjects
- Cell Line, Tumor, Female, HEK293 Cells, Humans, Phosphorylation physiology, Breast Neoplasms metabolism, Cell Movement physiology, Cyclin-Dependent Kinase 2 physiology, Repressor Proteins metabolism
- Abstract
Expression of Breast Cancer Metastasis Suppressor 1 (BRMS1) reduces the incidence of metastasis in many human cancers, without affecting tumorigenesis. BRMS1 carries out this function through several mechanisms, including regulation of gene expression by binding to the mSin3/histone deacetylase (HDAC) transcriptional repressor complex. In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). Although CDKs are known to regulate cell cycle progression, the mutation of BRMS1 on serine 237 did not affect cell cycle progression and proliferation of MDA-MB-231 breast cancer cells; however, their migration was affected. Phosphorylation of BRMS1 does not affect its association with the mSin3/HDAC transcriptional repressor complex or its transcriptional repressor activity. The serine 237 phosphorylation site is immediately proximal to a C-terminal nuclear localization sequence that plays an important role in BRMS1-mediated metastasis suppression but phosphorylation does not control BRMS1 subcellular localization. Our studies demonstrate that CDK-mediated phosphorylation of BRMS1 regulates the migration of tumor cells.
- Published
- 2016
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24. Evaluation of p40 as a Myoepithelial Marker in Different Breast Lesions.
- Author
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Kővári B, Szász AM, Kulka J, Marušić Z, Šarčević B, Tiszlavicz L, and Cserni G
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- Adult, Aged, Biomarkers, Tumor genetics, Breast metabolism, Breast Diseases metabolism, Carcinoma, Intraductal, Noninfiltrating metabolism, Diagnosis, Differential, Epithelial Cells metabolism, Female, Humans, Immunohistochemistry, Middle Aged, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms metabolism, Adenomyoepithelioma metabolism, Biomarkers, Tumor metabolism, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Transcription Factors metabolism, Tumor Suppressor Proteins metabolism
- Abstract
Objective: The identification of myoepithelial cells (MEC) is a valuable clue in the differential diagnosis of breast lesions. A series of breast lesions with occasional absence of or decrease in the staining for some MEC markers was analyzed for the expression of a novel marker, p40, and results were compared to the p63 staining profile., Methods: Samples (n = 34) from patients with benign sclerosing lesions (n = 11), ductal carcinoma in situ (n = 13) and adenomyoepithelial lesions (n = 10) and associated normal breast tissues (n = 31) were selected to evaluate the differential expression of p40 and p63 using immunohistochemistry. Triple-negative, cytokeratin 5 (CK5)-expressing invasive breast carcinomas (n = 19) were also assessed for p40 expression., Results: Normal structures showed similar diffuse and strong MEC positivity using p40 and p63 in all 31 cases. The two antibodies performed similarly in all 34 breast lesions acknowledged to present altered expression of MEC markers; focal losses of expression occurred in a parallel fashion. CK5-positive carcinomas expressed p40 more frequently than p63 (18/19 vs. 8/19) and the staining was more marked., Conclusions: It seems that both antibodies can be used interchangeably for MEC identification, but show differences in the labeling at least in a subset of tumor cells in triple-negative carcinomas., (© 2015 S. Karger AG, Basel.)
- Published
- 2015
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25. A case-control study of genotoxicity endpoints in patients with papillary thyroid cancer.
- Author
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Gerić M, Janušić R, Šarčević B, and Garaj-Vrhovac V
- Subjects
- Adult, Carcinoma blood, Carcinoma, Papillary, Case-Control Studies, Female, Genomic Instability, Humans, Male, Micronucleus Tests, Middle Aged, Pilot Projects, Thyroid Cancer, Papillary, Thyroid Neoplasms blood, Carcinoma genetics, DNA Damage, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins c-ret genetics, Thyroid Neoplasms genetics
- Abstract
Thyroid cancer is one of the fastest growing cancer types worldwide. Using the cytokinesis-block micronucleus (CBMN) and comet assays, we performed a case-control study of 23 untreated papillary thyroid cancer (PTC) patients and 23 healthy volunteers. PTC patients showed higher basal DNA damage in peripheral blood lymphocytes. The CBMN assay indicated that the numbers of micronuclei, nuclear buds, and nucleoplasmic bridges among the cases were 2.67-, 2.79-, and 7.72-fold higher, respectively, than among the controls (p < 0.05). Comet assay tail lengths and tail intensities were 1.20- and 1.94-fold higher, respectively (p < 0.05). In additional, 14 thyroid tissues from PTC patients were probed for Raf-B and Ret expression; all samples were positive for at least one of these proteins., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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26. Molecular and structural insight into lysine selection on substrate and ubiquitin lysine 48 by the ubiquitin-conjugating enzyme Cdc34.
- Author
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Suryadinata R, Holien JK, Yang G, Parker MW, Papaleo E, and Šarčević B
- Subjects
- Amino Acid Sequence, Cyclin-Dependent Kinase Inhibitor Proteins metabolism, Models, Molecular, Molecular Sequence Data, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Substrate Specificity, Ubiquitin-Conjugating Enzymes genetics, Ubiquitination, Lysine metabolism, Saccharomyces cerevisiae Proteins metabolism, Ubiquitin metabolism, Ubiquitin-Conjugating Enzymes metabolism
- Abstract
The attachment of ubiquitin (Ub) to lysines on substrates or itself by ubiquitin-conjugating (E2) and ubiquitin ligase (E3) enzymes results in protein ubiquitination. Lysine selection is important for generating diverse substrate-Ub structures and targeting proteins to different fates; however, the mechanisms of lysine selection are not clearly understood. The positioning of lysine(s) toward the E2/E3 active site and residues proximal to lysines are critical in their selection. We investigated determinants of lysine specificity of the ubiquitin-conjugating enzyme Cdc34, toward substrate and Ub lysines. Evaluation of the relative importance of different residues positioned -2, -1, +1 and +2 toward ubiquitination of its substrate, Sic1, on lysine 50 showed that charged residues in the -1 and -2 positions negatively impact on ubiquitination. Modeling suggests that charged residues at these positions alter the native salt-bridge interactions in Ub and Cdc34, resulting in misplacement of Sic1 lysine 50 in the Cdc34 catalytic cleft. During polyubiquitination, Cdc34 showed a strong preference for Ub lysine 48 (K48), with lower activity towards lysine 11 (K11) and lysine 63 (K63). Mutating the -2, -1, +1 and +2 sites surrounding K11 and K63 to mimic those surrounding K48 did not improve their ubiquitination, indicating that further determinants are important for Ub K48 specificity. Modeling the ternary structure of acceptor Ub with the Cdc34~Ub complex as well as in vitro ubiquitination assays unveiled the importance of K6 and Q62 of acceptor Ub for Ub K48 polyubiquitination. These findings provide molecular and structural insight into substrate lysine and Ub K48 specificity by Cdc34.
- Published
- 2013
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