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11.
Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransfer
Urška Kamenšek, Katja Uršič Valentinuzzi, Boštjan Markelc, Maja Čemažar, Vita Šetrajčič Dragoš, Gregor Serša, 2021, original scientific article

Abstract: In situ vaccination is a promising immunotherapeutic approach, where various local ablative therapies are used to induce an immune response against tumor antigens that are released from the therapy-killed tumor cells. We recently proposed using intratumoral gene electrotransfer for concomitant transfection of a cytotoxic cytokine tumor necrosis factor-% (TNF%) to induce in situ vaccination, and an immunostimulatory cytokine interleukin 12 (IL-12) to boost the primed immune response. Here, our aim was to test the local and systemic effectiveness of the approach in tree syngeneic mouse tumor models and associate it with tumor immune profiles, characterized by tumor mutational burden, immune infiltration and expression of PD-L1 and MHC-I on tumor cells. While none of the tested characteristic proved predictive for local effectiveness, high tumor mutational burden, immune infiltration and MHC-I expression were associated with higher abscopal effectiveness. Hence, we have confirmed that both the abundance and presentation of tumor antigens as well as the absence of immunosuppressive mechanisms are important for effective in situ vaccination. These findings provide important indications for future development of in situ vaccination based treatments, and for the selection of tumor types that will most likely benefit from it.
Keywords: in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa]
Published in DiRROS: 19.09.2022; Views: 503; Downloads: 164
.pdf Full text (1,78 MB)

12.
Real-world data on detection of germline and somatic pathogenic/likely pathogenic variants in BRCA1/2 and other susceptibility genes in ovarian cancer patients using next generation sequencing
Vida Stegel, Ana Blatnik, Erik Škof, Vita Šetrajčič Dragoš, Mateja Krajc, Brigita Gregorčič, Petra Škerl, Ksenija Strojnik, Gašper Klančar, Marta Banjac, Janez Žgajnar, Maja Ravnik-Oblak, Srdjan Novaković, 2022, original scientific article

Abstract: Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.
Keywords: BRCA, ovarian cancer, tumor genotyping, HBOC
Published in DiRROS: 06.09.2022; Views: 483; Downloads: 266
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Odpornost glioblastoma na radioterapijo : vpliv rakavih matičnih celic in mikroo[ko]lja tumorja
Barbara Breznik, Bernarda Majc, Anamarija Habič, Urška Ušeničnik, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Marija Skoblar Vidmar, Tanja Jesenko, Maja Čemažar, Tamara Lah Turnšek, Metka Novak, 2022, published scientific conference contribution (invited lecture)

Abstract: Glioblastom je najpogostejši možganski tumor pri odraslih z zelo slabo prognozo preživetja bolnikov. Ta je posledica odpornosti glioblastoma na standardno zdravljenje, ki vključuje radioterapijo in kemoterapijo. Z namenom načrtovanja učinkovitejših pristopov zdravljenja preučujemo biološke mehanizme odpornosti glioblastoma na radioterapijo s poudarkom na mikrookolju tumorja in rakavih matičnih celicah. V predkliničnih raziskavah uporabljamo napredne in personalizirane celične modele, ki posnemajo mikrookolje tumorja v bolnikih in z večjo natančnostjo napovedo odziv bolnika na zdravljenje. Hkrati so takšni modeli pomembni za testiranje novih pristopov za zdravljenje kot je imunoterapija.
Keywords: glioblastom, mikrookolje, organoidi, možganski rak, možganski tumor, onkologija
Published in DiRROS: 16.06.2022; Views: 567; Downloads: 187
.pdf Full text (89,78 KB)

17.
P14/ARF-positive malignant pleural mesothelioma : ǂa ǂphenotype with distinct immune microenvironment
Federica Pezzuto, Francesca Lunardi, Luca Vedovelli, Francesco Fortarezza, Loredana Urso, Federica Grosso, Giovanni Luca Ceresoli, Izidor Kern, Gregor Vlačić, Fiorella Calabrese, 2022, original scientific article

Abstract: Introduction: The CDKN2A gene plays a central role in the pathogenesis of malignant pleural mesothelioma (MPM). The gene encodes for two tumor suppressor proteins, p16/INK4A and p14/ARF, frequently lost in MPM tumors. The exact role of p14/ARF in MPM and overall its correlation with the immune microenvironment is unknown. We aimed to determine whether there is a relationship between p14/ARF expression, tumor morphological features, and the inflammatory tumor microenvironment. Methods: Diagnostic biopsies from 76 chemo-naive MPMs were evaluated. Pathological assessments of histotype, necrosis, inflammation, grading, and mitosis were performed. We evaluated p14/ARF, PD-L1 (tumor proportion score, TPS), and Ki-67 (percentage) by immunohistochemistry. Inflammatory cell components (CD3+, CD4+, CD8+ T lymphocytes; CD20+ B-lymphocytes; CD68+ and CD163+ macrophages) were quantified as percentages of positive cells, distinguishing between intratumoral and peritumoral areas. The expression of p14/ARF was associated with several clinical and pathological characteristics. A random forest-based machine-learning algorithm (Boruta) was implemented to identify which variables were associated with p14/ARF expression. Results: p14/ARF was evaluated in 68 patients who had a sufficient number of tumor cells. Strong positivity was detected in 14 patients (21%) (11 epithelioid and 3 biphasic MPMs). At univariate analysis, p14/ARF-positive epithelioid mesotheliomas showed higher nuclear grade (G3) (p = 0.023) and higher PD-L1 expression (≥50%) (p = 0.042). The percentages of CD4 and CD163 in peritumoral areas were respectively higher and lower in p14/ARF positive tumors but did not reach statistical significance with our sample size (both p = 0.066). The Boruta algorithm confirmed the predictive value of PD-L1 percentage for p14/ARF expression in all histotypes. Conclusions: p14/ARF-positive epithelioid mesotheliomas may mark a more aggressive pathological phenotype (higher nuclear grade and PD-L1 expression). Considering the results regarding the tumor immune microenvironment, p14/ARF-negative tumors seem to have an immune microenvironment less sensitive to immune checkpoint inhibitors, being associated with low PD-L1 and CD4 expression, and high CD163 percentage. The association between p14/ARF-positive MPMs and PD-L1 expression suggests a possible interaction of the two pathways. Confirmation of our preliminary results could be important for patient selection and recruitment in future clinical trials with anticancer immunotherapy.
Keywords: lung -- cytology -- pathology, neoplasms, malignant mesothelioma, malignant pleural mesothelioma, tumor microenvironment
Published in DiRROS: 30.05.2022; Views: 758; Downloads: 492
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18.
Temozolomid : dnevnik zdravljenja
2020, dictionary, encyclopaedia, lexicon, manual, atlas, map

Keywords: kemoterapija, onkološka zdravila, možganski tumor
Published in DiRROS: 30.07.2020; Views: 1620; Downloads: 432
.pdf Full text (248,82 KB)

19.
Zbornik
2019, proceedings of professional or unreviewed scientific conference contributions

Abstract: Kolposkopija še ostaja zelo pomemben del presejalnih programov raka materničnega vratu. Vloga in pomen kakovostne kolposkopske obravnave bosta še izrazitejši v bližnji prihodnosti, ko bodo na preizkušnji podaljšani intervali in HPV problematika v triažnem in morda presejalnem pomenu. Te spremembe sicer veliko obetajo, a hkrati zahtevajo pogoje za kakovostno opravljanje kolposkopske dejavnost, ki se v Sloveniji vse prepočasi uveljavljajo. V pričujoči publikaciji najpomembnejši slovenski strokovnjati tega področja predstavljajo najnovejša spoznanja in smernice za presejanje in diagnostiko bolezni.
Keywords: ginekologija, onkologija, humani papiloma virus, presejanje, bris materničnega vratu, predrakave spremembe, rodila, tumor, klasifikacija, vulva, nosečnost, pojasnilna dolžnost, zborniki, elektronske knjige
Published in DiRROS: 17.04.2020; Views: 4150; Downloads: 781
.pdf Full text (16,91 MB)

20.
Zbornik
2016, proceedings of professional or unreviewed scientific conference contributions

Keywords: ginekologija, onkologija, humani papiloma virus, bris materničnega vratu, rodila, tumor, klasifikacija, zborniki
Published in DiRROS: 08.04.2020; Views: 1949; Downloads: 610
.pdf Full text (9,83 MB)

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