1. 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, izvirni znanstveni članek Opis: 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.
Ključne besede: breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67
Objavljeno v DKUM: 26.11.2024; Ogledov: 0; Prenosov: 3
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2. Izražanje izoform gena DDB2 v mononuklearnih celicah periferne krvi pri različnih podtipih raka dojke : diplomsko delo univerzitetnega študijskega programa I. stopnjeKarin Rajh, 2024, diplomsko delo Opis: Rak dojke (RD) je najpogosteje diagnosticiran rak pri ženskah in je glavni vzrok smrti zaradi raka pri ženskah po vsem svetu. Gre za heterogeno bolezen, ki se razlikuje na molekularni, histološki in klinični ravni. Ločimo več podtipov RD, ki jih delimo na podlagi histopatoloških in molekularnih značilnosti. Podtipa trojno negativni RD in HER2-pozitivni RD (TNRD in HER2+) sta na splošno bolj imunogena in povezana z boljšo odzivnostjo na imunoterapijo kot luminalna podtipa (luminalni A in B).
Analize krvi omogočajo vpogled v sistemski imunski odziv na tumorske celice. Odvzem krvi je lahko dostopna metoda pridobivanja bioloških vzorcev, ki lahko pripomore k zgodnjemu odkrivanju RD. V Centru za humano genetiko in farmakogenomiko Medicinske fakultete v Mariboru so z metodo RNA-seq opravili sekvenciranje transkriptoma imunskih celic iz periferne krvi (mononuklearnih celic periferne krvi, PBMC) pri 25 bolnicah z RD, od tega 13 s podtipom luminalni A in 12 s podtipom TNRD. Z bioinformatsko analizo transkripcijskih izoform so identificirali izoformo ENST00000378603 gena DDB2 kot potencialno pomembno, saj je pokazala značilno diferencialno izražanje med tema dvema podtipoma RD. V nasprotju z omenjeno izoformo pa so se druge izoforme gena DDB2, na primer izoforma ENST00000256996, enako izražale pri podtipih TNRD in luminalni A.
Namen te diplomske naloge je bila validacija ter razširitev teh ugotovitev z analizo izoform gena DDB2 z metodo RT-qPCR na večjem številu vzorcev, ki so vključevali 182 vzorcev bolnic z RD vseh podtipov in 37 vzorcev zdravih oseb. Da bi lahko ovrednotili izražanje izoform gena DDB2 z metodo RT-qPCR, je bilo najprej potrebno optimizirati reakcijske pogoje s specifičnimi oligonukleotidnimi začetniki za obe izoformi. Po optimizaciji reakcijskih pogojev smo z RT-qPCR izmerili izražanje izoforme ENST00000256996 pri bolnicah z RD in zdravih osebah. V nasprotju pa je bila optimizacija reakcijskih pogojev za izoformo ENST00000378603 neuspešna.
Ugotovili smo, da se izoforma ENST00000256996 statistično značilno bolj izraža v vzorcih zdravih oseb kot v vzorcih pacientk z RD, kar je v skladu z našo hipotezo, saj je produkt gena DDB2 udeležen pri popravljanju poškodb DNA, njegova odsotnost pa je povezana s kopičenjem DNA-napak in kancerogenezo. Rezultati so potrdili tudi, da se analizirana izoforma enako izraža v podtipih RD TNRD in luminalni A.
Ključne besede: Rak dojke, TNRD, PBMC, DDB2, transkripcijske izoforme, biooznačevalci
Objavljeno v DKUM: 20.09.2024; Ogledov: 0; Prenosov: 23
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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. Treatment of uterine sarcomas at the Maribor University Clinical Centre between 1996 and 2011Darja Arko, Andraž Dovnik, Iztok Takač, 2013, izvirni znanstveni članek Opis: 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.
Ključne besede: maternični sarkom, histološke značilnosti, kirurško zdravljenje, dopolnilno zdravljenje, celokupno preživetje
Objavljeno v DKUM: 12.04.2024; Ogledov: 211; Prenosov: 8
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5. Cesarean scar pregnancy : case report and review of the literatureAndraž Dovnik, Polona Kores Testen, Lea Mlakar, Milan Reljič, Darja Arko, Iztok Takač, 2014, strokovni članek Ključne besede: zapleti po carskem rezu, nosečnost v brazgotini, vaginalni ultrazvok, histerotomija
Objavljeno v DKUM: 11.04.2024; Ogledov: 211; Prenosov: 4
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6. 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, pregledni znanstveni članek Ključne besede: klasifikacija, rak jajčnikov, jajcevodov, peritonej
Objavljeno v DKUM: 11.04.2024; Ogledov: 151; Prenosov: 10
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9. Early detection of neck lymph node metastases in breast cancer patients : the role of ultrasound and fine needle biopsyJanez Rebol, Peter Balon, Peter Kokol, Boštjan Lanišnik, Iztok Takač, Andraž Dovnik, Nina Fokter Dovnik, Monika Sobočan, Darja Arko, 2019, izvirni znanstveni članek Ključne besede: metastases, neck lymph, ultrasound, fine needle biopsy, breast canser
Objavljeno v DKUM: 27.03.2024; Ogledov: 225; Prenosov: 6
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10. 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: 21
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