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, original scientific article Abstract: 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.
Keywords: hormonal receptors, MFUM-BrTNBC-1, MCF-7, MDA-MB-231, MDA-MB-453
Published in DKUM: 10.04.2025; Views: 0; Downloads: 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, original scientific article Abstract: 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.
Keywords: epithelial ovarian cancer, initiation and elongation factor, translational markers
Published in DKUM: 12.12.2024; Views: 0; Downloads: 6
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3. Changes in the extracellular matrix in endometrial and cervical cancer : a systematic reviewTjaša Padežnik, Anja Oleksy, Andrej Cokan, Iztok Takač, Monika Sobočan, 2023, review article Abstract: Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Keywords: extracellular matrix, endometrial cancer, cervical cancer
Published in DKUM: 02.12.2024; Views: 0; Downloads: 1
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4. Isoform-level transcriptome analysis of peripheral blood mononuclear cells from breast cancer patients identifies a disease-associated RASGEF1A isoformHelena Sabina Čelešnik, Mario Gorenjak, Martina Krušič, Bojana Crnobrnja, Monika Sobočan, Iztok Takač, Darja Arko, Uroš Potočnik, 2024, original scientific article Abstract: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.
Keywords: breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67
Published in DKUM: 26.11.2024; Views: 0; Downloads: 5
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5. Tirotoksična struma jajčnika po ablaciji ščitnice: prikaz primera laparoskopskega zdravljenjaIztok Takač, Darja Arko, Ludvik Puklavec, Rajko Kavalar, Anton Crnjac, 2009, original scientific article Abstract: 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.
Keywords: struma jajčnika, hipertiroidizem, laparoskopska operacija
Published in DKUM: 19.04.2024; Views: 185; Downloads: 2
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6. Treatment of uterine sarcomas at the Maribor University Clinical Centre between 1996 and 2011Darja Arko, Andraž Dovnik, Iztok Takač, 2013, original scientific article Abstract: Purpose: Uterine sarcomas are rare malignant tumours with a worse prognosis than endometrial carcinomas.This retrospective study was performed to determine the clinical and histologic characteristics, treatment, and outcomes in uterine sarcoma patients treated at our hospital over a 16-year period. Methods: Twenty-two patients (median age, 60.5 years) with uterine sarcomas were treated at our facility between 1996 and 2011. Information was collected from hospital and follow-up records and from the Cancer Registry of Slovenia. All tumours were classified according to the new FIGO classification for uterine sarcomas. Results: The majority of the patients presented with postmenopausal bleeding. The most common histologic subtype was leiomyosarcoma (50%), followed by carcinosarcoma (40.9%), and endometrial stromal sarcoma (9.1%). All of the patients were initially treated surgically, 21 by laparotomy and 1 laparoscopically. Eight patients were treated with postoperativeradiotherapy and 4 patients received postoperativechemotherapy. Disease progression was observed in 8 of17 patients who had sufficient followup information forthis analysis. The 5-year overall survival was 44 %.Conclusion: The overall survival of patients treated for uterine sarcomas in our study was comparatively good. Due to the small number and heterogeneity of the patients, larger multicentre trials are needed for a reliable analysis of factors influencing patient survival.
Keywords: maternični sarkom, histološke značilnosti, kirurško zdravljenje, dopolnilno zdravljenje, celokupno preživetje
Published in DKUM: 12.04.2024; Views: 211; Downloads: 8
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7. Cesarean scar pregnancy : case report and review of the literatureAndraž Dovnik, Polona Kores Testen, Lea Mlakar, Milan Reljič, Darja Arko, Iztok Takač, 2014, professional article Keywords: zapleti po carskem rezu, nosečnost v brazgotini, vaginalni ultrazvok, histerotomija
Published in DKUM: 11.04.2024; Views: 211; Downloads: 8
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8. New international federation of gynecology and obstetrics (FIGO) staging classification for cancer of the ovary, fallopian tube, and peritoneumDarja Arko, Verena Gajser, Iztok Takač, 2015, review article Keywords: klasifikacija, rak jajčnikov, jajcevodov, peritonej
Published in DKUM: 11.04.2024; Views: 151; Downloads: 10
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9. Gastric cancer in pregnancy - diagnostic and therapeutic dilemma : case reportLucija Kuder, Andraž Dovnik, Matjaž Horvat, Iztok Takač, 2016, professional article Keywords: rak želodca, nosečnost, carski rez, gastrektomija, limfadenektomija
Published in DKUM: 11.04.2024; Views: 195; Downloads: 15
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