1. MFUM-BrTNBC-1, a newly established patient-derived triple-negative breast cancer cell line : molecular characterisation, genetic stability, and comprehensive comparison with commercial breast cancer cell linesKristijan Skok, Lidija Gradišnik, Helena Sabina Čelešnik, Marko Milojević, Uroš Potočnik, Gregor Jezernik, Mario Gorenjak, Monika Sobočan, Iztok Takač, Rajko Kavalar, Uroš Maver, 2022, izvirni znanstveni članek Opis: Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for
approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the
disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and
performed a detailed morphological and molecular characterisation and a comprehensive comparison
with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence
microscopy were used for morphological studies; immunocytochemical staining for hormone receptor,
p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and
biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUMBrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and
unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and
displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide
excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed
from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation
from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical
to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile;
quantifiable morphological properties; and genetic stability up to (at least) the 6th passage. Ključne besede: hormonal receptors, MFUM-BrTNBC-1, MCF-7, MDA-MB-231, MDA-MB-453 Objavljeno v DKUM: 10.04.2025; Ogledov: 0; Prenosov: 3
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2. Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancerMonika Sobočan, Daniela Brunialti, S Sprung, Christoph Schatz, Jure Knez, Rajko Kavalar, Iztok Takač, Johannes Haybaeck, 2022, izvirni znanstveni članek Opis: High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery. Ključne besede: epithelial ovarian cancer, initiation and elongation factor, translational markers Objavljeno v DKUM: 12.12.2024; Ogledov: 0; Prenosov: 6
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3. Tirotoksična struma jajčnika po ablaciji ščitnice: prikaz primera laparoskopskega zdravljenjaIztok Takač, Darja Arko, Ludvik Puklavec, Rajko Kavalar, Anton Crnjac, 2009, izvirni znanstveni članek Opis: Struma ovarii is a rare type of germ cell tumor and a rare cause of ectopic thyroidal hormonal production. We report a case of laparsocopic management of a thyrotoxic struma ovarii. In a 49-year-old patient, previously treated by ablative surgery and radioactive iodine for Graves' disease, a new onset of hyperthyroidism occurred unexpectedly. A whole-body scan with 131I detected increased pelvic uptake, suggesting struma ovarii. The patient was subsequently treated with laparoscopic bilateral salpingo-oophorectomy. The postoperative course was uneventful. Histopathologic examination revealed the presence of a benign struma ovarii. Three years after treatment the patient is disease free and is receiving thyroid replacement therapy with levothyroxine. In this case the thyrotoxic struma ovarii was diagnosed preoperatively and laparoscopic surgery proved to be a useful and reliable method for ovarian ablation. Ključne besede: struma jajčnika, hipertiroidizem, laparoskopska operacija Objavljeno v DKUM: 19.04.2024; Ogledov: 185; Prenosov: 2
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4. Borrelial lymphocytoma of the areola in a 9-year-old boy: a case reportDarja Arko, Rajko Kavalar, Iztok Takač, Nina Čas-Sikošek, Vida Gavrić-Lovrec, 2023, drugi znanstveni članki Ključne besede: lymphocytoma, Lyme borreliosis, areola, histology Objavljeno v DKUM: 21.12.2023; Ogledov: 207; Prenosov: 23
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5. Analiza fenotipskih, molekularnih in genetskih lastnosti nove celične linije trojno negativnega raka dojkKristijan Skok, 2022, doktorska disertacija Opis: Rak dojk je najpogostejši rak na svetu. Eden izmed njegovih podtipov je trojno negativni rak dojk (TNRD), za katerega je značilen agresiven potek, slabša prognoza in heterogenost. V svoji doktorski nalogi predstavim novo izolirano celično linijo TNRD, poimenovano MFUM-BrTNBC1. Linija je bila celovito karakterizirana (morfološko, fenotipsko, genotipsko). Za kontrole so služile komercialne celične linije z različnimi receptorskimi profili (MCF-7, MDA-MB-231, MDA-MB-453). Primerjalne morfološke analize so bile opravljene s pomočjo mikroskopije ter biomedicinske slikovne analize. S pomočjo imunocito/histokemičnih barvanj je bila preverjena izraženost hormonskih receptorjev (estrogen, progesteron), HER2, p53 in Ki-67 statusa. Ekspresija receptorjev je bila dodatno preverjena na transkripcijski ravni s qRT-PCR metodo. Dodatno je bilo opravljeno RNA sekvenciranje za molekularno analizo. Avtentičnost celičnih linij je bila preverjena s pomočjo STR profiliranja. MFUM-BrTNBC-1 celična linija je ohranila trojno negativni receptorski status in genetsko stabilnost do vsaj 6. pasaže. Rezultati STR analize in navzkrižna preverba z mednarodnimi bazami so dokazali avtentičnost celične linije. MFUM-BrTNBC1 se je po morfologiji celic razlikovala tudi od TNRD celične linije MDA-MB-231. Razlike od komercialne linije, predstavljajo tudi glavne prednostne lasnosti MFUM-BrTNBC-1. Te so izolacija iz primarnega tumorskega tkiva, popoln izvorni zapis, mednarodno poimenovanje, celoten in edinstven STR profil ter genetska stabilnost do vsaj 6. pasaže. Ključne besede: trojno negativni rak dojk, MFUM-BrTNBC-1, rak dojk, in-vitro modeli, celične linije Objavljeno v DKUM: 29.11.2022; Ogledov: 823; Prenosov: 78
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6. Single nucleotide polymorphisms as prognostic and predictive factors of adjuvant chemotherapy in colorectal cancer of stages I and IIMatej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Borut Štabuc, 2016, pregledni znanstveni članek Opis: Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. Ključne besede: single nucleotide polymorphism, colorectal cancer, adjuvant chemotherapy Objavljeno v DKUM: 14.06.2017; Ogledov: 1434; Prenosov: 374
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7. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer : correlation with traditional prognostic factorsMaja Lampelj, Darja Arko, Nina Čas-Sikošek, Rajko Kavalar, Maja Ravnik, Barbara Jezeršek Novaković, Sarah Dobnik, Nina Fokter Dovnik, Iztok Takač, 2015, izvirni znanstveni članek Opis: Background: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.
Patients and methods: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman%s rank correlation, Mann Whitney U test and X2 test for statistical analysis.
Results: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002).
Conclusions: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated. Ključne besede: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer Objavljeno v DKUM: 05.04.2017; Ogledov: 1304; Prenosov: 156
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8. Single nucleotide polymorphisms in genes MACC1, RAD18, MMP7 and SDF-1[alpha] as prognostic factors in resectable colorectal cancerMatej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Vesna Zadnik, Stojan Potrč, Borut Štabuc, 2016, izvirni znanstveni članek Opis: Background: Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC.
Patients and methods: In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1alpha, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism.
Results: We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041).
Conclusions: Our results indicate the role of SNPs as prognostic factors in resectable CRC. Ključne besede: single nucleotide polymorphism, colorectal cancer, MACC1, RAD18, MMP7, SDF-1a Objavljeno v DKUM: 05.04.2017; Ogledov: 1682; Prenosov: 170
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9. Morphometrical analysis of the p53 tissue marker in prostatic adenocarcinoma and its relationship to Gleason score and PSA levelMiha Munda, Barbara Dariš, Tine Hajdinjak, Rajko Kavalar, Draga Štiblar-Martinčič, 2013, izvirni znanstveni članek Opis: Purpose: Prostate cancer is one of the most common malignancies worldwide. The possible prognostic value of tissue markers, such as p53, may give a better understanding of this disease, improve staging accuracy, and help in choosing optimal treatment. In this study, we examined p53 expression and its correlation with Gleason score, prostatespecific antigen (PSA) levels, and patient age in a Slovenian population. Methods: This retrospective pilot study included 25 radical prostatectomy patients. The immunohistochemical expression of p53 was determined and expressed as a p53 index. In addition, correlations between p53 index, Gleason score before and after prostatectomy, PSA level, and patient age were statistically evaluated. Results: The p53 tissue marker was unevenly distributed in prostate cancer independently of local Gleason pattern; however, its expression correlated with Gleason score after prostatectomy and showed borderline correlation with PSA. There were also statistically significant correlations between Gleason score before and after prostatectomy, PSA level, and patient age. Conclusions: Despite the low number of cases presented in this study, our results demonstrate that p53 may have predictive value in prostate cancer. Thus, p53 is a promising tissue marker that can be used as an additional diagnostic parameter. Ključne besede: rak prostate, tkivni označevalci, p53, imunohistokemija Objavljeno v DKUM: 30.12.2015; Ogledov: 1848; Prenosov: 62
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10. Žilne ektazije antruma želodca - prikaz primeraDejan Urlep, Rajko Kavalar, 2006, strokovni članek Opis: Izhodišča. Žilne ektazije antruma želodca (GAVE) ali lubenični želodec (watermelon stomach) so redek, a pomemben vzrok kronične krvavitve iz prebavne cevi in posledične slabokrvnosti. Bolezen ima svojo značilno endoskopsko in histološko sliko. Patogeneza bolezni je nepojasnjena. Cilj zdravljenja je zmanjšati kronično krvavitev do te mere, da transfuzije niso več potrebne. V literaturi so opisani poskusi zdravljenja z zdravili, endoskopskimi terapevtskimi metodami in z operacijo. Danes se pri zdravljenju GAVE najpogosteje uporablja elektrokoagulacija z argonskim plazemskim koagulatorjem in z laserjem Nd: YAG. Bolniki in metode. Prikazan je primer 77-letne bolnice z žilnimi ektazijami antruma želodca. Bolnica je bila zaradi nepojasnjenega vzroka krvavitve iz prebavne cevi in ponavljajoče se slabokrvnosti kljub nadomeščanju železa odvisna od transfuzij. Uspešno je bila zdravljena z argonsko plazemsko koagulacijo (APC). Dve leti po zdravljenju bolnica ni slabokrvna in ne potrebuje transfuzij. Zaključki. Žilne ektazije antruma želodca so pogosto nespoznane in napačno opredeljene kot erozivni gastritis. Čeprav je bolezen redka, je pomemben vzrok prikrite krvavitve iz zgornje prebavne cevi, zlasti pri starejših ženskah. Objavljeno v DKUM: 21.12.2015; Ogledov: 2647; Prenosov: 70
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