Faculty of Medicine
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Item type:Publication, Incidental prostate cancer in patients undergoing radical cystoprostatectomy in treatment for bladder cancer: our five-year results(SHMSHM - AAMD, 2013); ; ; The aim of the paper was to verify the incidence and features of incidental prostate cancer in patients who underwent radical cystoprostatectomy for invasive bladder cancer. Methods and results: A total of 96 patients underwent radical cystoprostatectomy between January 2006 and December 2010 in the University Clinic of Urology in Skopje. 10 patients were excluded for incomplete data. The average age of the study group was 61.2 years (range 32-78). Prostate cancer was found in 10 (11.6%) cases. Seven patients were clinically insignificant. Conclusion: Incidentally diagnosed prostate cancer was frequently insignificant. Digital rectal examination and prostate specific antigen should be part of the diagnostic procedure in patients who undergo cystoprostatectomy. Standard RCP which include removal of bladder with prostate gland and seminal vesicles is safer for radicality and prevention of residual prostate cancer. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Management of primary bladder tumors at the University Clinic of Urology in Skopje in 2010 during one-year follow up.(2016); - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Mapping and Identification of the Urine Proteome of Prostate Cancer Patients by 2D PAGE/MS(Hindawi Limited, 2014); ; ; Proteome analysis of the urine has shown that urine contains disease-specific information for a variety of urogenital system disorders, including prostate cancer (PCa). The aim of this study was to determine the protein components of urine from PCa patients. Urine from 8 patients with clinically and histologically confirmed PCa was analyzed by conventional 2D PAGE. The MS identification of the most prominent 125 spots from the urine map revealed 45 distinct proteins. According to Gene Ontology, the identified proteins are involved in a variety of biological processes, majority of them are secreted (71%), and half of them are enzymes or transporters. Comparison with the normal urine proteome revealed 11 proteins distinctive for PCa. Using Ingenuity Pathways Analysis, we have found 3 proteins (E3 ubiquitin-protein ligase rififylin, tumor protein D52, and thymidine phosphorylase) associated with cellular growth and proliferation (p = 8.35 × 10(-4) - 3.41 × 10(-2)). The top network of functional associations between 11 proteins was Cell Death and Survival, Cell-To-Cell Signaling and Interaction, and System Development and Function (p = 10(-30)). In summary, we have created an initial proteomic map of PCa patient's urine. The results from this study provide some leads to understand the molecular bases of prostate cancer. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer(MDPI AG, 2017-12-29); Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively. In silico analysis indicated activation, binding, and cell movement of subset of immune cells as the top affected cellular functions in PCa, together with the down-regulation of Acute Phase Response Signaling and Liver X Receptor/ Retinoid X Receptor (LXR/RXR) activation pathways. The most promising biomarkers were 35, altered in PCa when compared to more than one group. Half of these have confirmed localization in normal or PCa tissues. Twenty proteins (CD14, AHSG, ENO1, ANXA1, CLU, COL6A1, C3, FGA, FGG, HPX, PTGDS, S100A9, LMAN2, ITIH4, ACTA2, GRN, HBB, PEBP1, CTSB, SPP1) are oncogenes, tumor suppressors, and multifunctional proteins with highly confirmed involvement in PCa, while 9 (AZU1, IGHG1, RNASE2, PZP, REG1A, AMY1A, AMY2A, ACTG2, COL18A1) have been associated with different cancers, but not with PCa so far, and may represent novel findings. LC-MS/MS data are available via ProteomeXchange with identifier PXD008407. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer(Springer Science and Business Media LLC, 2015-01-29); ; Zografska Chokrevska, NatashaDespite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p < 0.05), 1.8 fold variation or more in abundance, showed 41 spots, corresponding to 23 proteins. The Ingenuity Pathway Analysis showed significant association with the Acute Phase Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p < 0.05). The AUC for the individual proteins ranged from 0.723 to 0.754. The combination of HP and AMBP yielded the highest accuracy (AUC = 0.848), greater than PSA. The proposed biomarker set is quickly quantifiable and economical with potential to improve the sensitivity and specificity of PCa detection. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Erythropoietin reduces cumulative nephrotoxicity from cisplatin and enhances renal tubular cell proliferation(Macedonian Academy of Sciences and Arts, 2008-12); ; ; ; Cisplatin, a heavy metal complex, is one of the most active drugs used in the treatment of several human malignancies. However, high-dose therapy with cisplatin is limited by its cumulative nephrotoxicity. The main objectives of this study were to determine the role of recombinant human erythropoietin (Epoetin alfa) in the prevention of nephrotoxicity induced experimentally in Wistar rats by long-term administration of cisplatin (2 mg/kg/b.w./week) over eight weeks, and an evaluation of its effect on renal tubular cell proliferation. The animals were randomly assigned into three groups, each including 25 rats. Group 1 (CP) received only cisplatin (2 mg/kg/b.w./week), group 2 (CP+EPO) received cisplatin (2 mg/kg/b.w./week) and epoetin alfa (150 IE/kg/b.w./three times a week), and group 3 (control group) received only saline. During the study, the following tests for the assessment of the renal function and renal damages were performed: determination of concentration of serum creatinine and BUN and determination of total protein quantity in 24-hour urine samples. At the end of the study, the abdomen was opened and both kidneys of the rats were removed and sent for histological and morphometric analysis. Ki-67 was used as a tool to determine a proliferative index. The results obtained have shown that epoetin alfa significantly reduced the functional renal failures and renal damages, and increased toleration of high doses of cisplatin. At the same time, our results with regard to tubular proliferative index have confirmed that one of the possible mechanisms by which erythropoietin accomplishes its renoprotective effect is stimulation of tubular cell proliferation and regeneration. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9) levels as Prognostic Markers in Patients with Colorectal Cancer(University of Sarajevo Faculty of Health Sciences, 2012-12-15); ; ; ; <jats:p>Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre- and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examineMMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC) and outcome.Methods: The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively.Results: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defined points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively,than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in significant association with the CRC patients’outcome.Conclusion: The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.</jats:p> - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Measurement-oriented deep-learning workflow for improved segmentation of myelin and axons in high-resolution images of human cerebral white matter(Elsevier BV, 2019-10) - Some of the metrics are blocked by yourconsent settings
Item type:Publication, The occurrence of acute subdural haematoma and diffuse axonal injury as two typical acceleration injuries(Elsevier, 2012); ; ; ; Popevska, ZClosed head injuries have already been classified into contact injuries and acceleration–deceleration injuries. Two typical acceleration–deceleration injuries and at the same time, the two worst head injuries are acute subdural haematoma (ASDH) and diffuse axonal injury (DAI), and that is where they got their medico-legal importance. Using experiments, it has been shown that acceleration with an impact time of more than 20–25 min (which occurs in traffic accidents in real life) causes DAI, whereas an impact time of 5–10 min is more likely to produce acute subdural haematoma. The aim of this research is to show that not all, but some types of traffic accidents are more typical for the occurrence of DAI, as well as that the ASDH is not a common feature for all types of fall. The analysis conveyed covered 80 cases of closed head injuries (traffic accidents, falls and assaults) where a complete forensic medical autopsy has been undertaken, followed by a complete forensic–neuropathological examination. For the purpose of diagnosing DAI, immunohistochemistry using antibody against β-amyloid precursor protein has been involved. Results show that ASDH is more likely to occur in cases of simple fall, assaults and cyclists and DAI is more typical for vehicular traffic accidents and cases of falling from a considerable height. The paper also comprises discussion about some open questions regarding the diagnosis of DAI in the medico-legal practice. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Recommmendations for the diagnostic algorithm in lung cancer. Consensus statement of the Macedonian respiratory society and the Macedonian association of pathology(Македонско лекарско друштво = Macedonian Medical Association, 2019);