81. BAP1-defficient breast cancer in a patient with BAP1 cancer syndromeAna Blatnik, Domen Ribnikar, Vita Šetrajčič Dragoš, Srdjan Novaković, Vida Stegel, Biljana Grčar-Kuzmanov, Nina Boc, Barbara Perić, Petra Škerl, Gašper Klančar, Mateja Krajc, 2022, original scientific article Abstract: BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline BAP1 likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in BAP1 (partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.
Keywords: BAP1, breast cancer, hereditary cancer syndromes, immunotherapy
Published in DiRROS: 19.09.2022; Views: 482; Downloads: 189
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82. Real-world testing practices, treatment patterns and clinical outcomes in patients from Central Eastern Europe with EGFR-mutated advanced non-small cell lung cancer : a retrospective chart review study (REFLECT)Urška Janžič, Nina Turnšek, Mircea Dediu, Ivan Shterev Donev, Roxana Lupu, Gabriela Teodorescu, Tudor Ciuleanu, Adam Płużański, 2022, original scientific article Abstract: The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015–2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6–15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1–29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.
Keywords: lung neoplasms, non-small cell lung carcinoma, Eastern Europe, real-world study, REFLECT study, epidermal growth factor receptor, lung cancer
Published in DiRROS: 09.09.2022; Views: 518; Downloads: 216
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83. Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological studyPrimož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, original scientific article Abstract: Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Keywords: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Published in DiRROS: 07.09.2022; Views: 526; Downloads: 235
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84. The effect of dietary fibre content on skatole and indole production in faeces of immunocatrsted male pigsMaja Prevolnik, Urška Tomažin, Marjeta Čandek-Potokar, Martin Škrlep, Nina Batorek Lukač, Etienne Labussiere, 2015, published scientific conference contribution Keywords: prašiči, prehrana prašičev, vlaknine, imunokastracija
Published in DiRROS: 06.09.2022; Views: 656; Downloads: 239
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86. Influence of housing conditions on reliability of immunocastration and consequences for growth performance of male pigsKevin Kress, Ulrike Weiler, Sonja Schmucker, Marjeta Čandek-Potokar, Milka Vrecl, Gregor Fazarinc, Martin Škrlep, Nina Batorek Lukač, Volker Stefanski, 2020, original scientific article Abstract: Immunocastration is a sustainable alternative to piglet castration but faces limited market acceptance. The phenomenon of non-responders has not to date been examined in detail, but adverse and stressful housing conditions (e.g., mixing of groups) might impair the success of vaccinations. Therefore, we evaluated the influence of housing conditions on the immune response after two Improvac® vaccinations at an age of 12 and 22 weeks, respectively. Boars, immunocastrates and barrows (n = 48 each) were assigned to three different housing conditions (n = 36 enriched, n = 36 standard n = 72 repeated social mixing). Immune response was quantified by measuring GnRH-binding and its consequences for testosterone concentrations, development of the genital tract and boar taint. Growth performance was evaluated via average daily gain (ADG). GnRH-binding and testosterone levels revealed that immunocastration reliably suppressed testicular functions after the 2nd vaccination. Housing conditions did not modify testicular function but influenced ADG as animals under mixing grew slower than those under enriched conditions. Gonadal status had only a slight impact on ADG except in immunocastrates, which showed a temporarily higher ADG after the 2nd vaccination. The results show that immunocastration is a reliable procedure under different housing conditions and competitive in terms of growth performance.
Keywords: immunocastration, vaccination, Improvac, non-responder, immune response, housing conditions, surgical castration, boar taint, growth performance, genital tract
Published in DiRROS: 06.09.2022; Views: 650; Downloads: 230
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87. Properties and aromatic profile of dry-fermented sausages produced from Krškopolje pigs reared under organic and conventional rearing regimeMartin Škrlep, Marjeta Čandek-Potokar, Urška Tomažin, Nina Batorek Lukač, Mónica Flores, 2018, original scientific article Keywords: meat product quality, pif meat, dry-fermented sausages, local breeds, organic rearing regime, conventional rearing regime, aromatic profile, sousages profile, meat flavour, prašiči, prašičje meso, kastracija prašičev, imunokastracija, operativna kastracija, kakovost mesa, vonj merjasca, androstenon, okus mesa
Published in DiRROS: 06.09.2022; Views: 465; Downloads: 0 |
88. Proteomic profiles of the longissimus muscles of entire male and castrated pigs as related to meat qualityMartin Škrlep, Urška Tomažin, Nina Batorek Lukač, Klavdija Poklukar, Marjeta Čandek-Potokar, 2019, original scientific article Keywords: pigs, entire males, castrates, meat quality, proteomic profiles
Published in DiRROS: 06.09.2022; Views: 464; Downloads: 0 |
89. Aromatic profile, physicochemical and sensory traits of dry-fermented sausages produced without nitrites using pork from Krškopolje pig reared in organic and conventional husbandryMartin Škrlep, Marjeta Čandek-Potokar, Nina Batorek Lukač, Urška Tomažin, Mónica Flores, 2019, original scientific article Keywords: pig meat, dry-fermented sausage, sensory characteristics, production system
Published in DiRROS: 06.09.2022; Views: 493; Downloads: 0 |
90. In vitro and in vivo correlation of skin and cellular responses to nucleic acid deliveryMaša Omerzel, Katarina Žnidar, A. Sales Conniff, Tanja Jesenko, Boštjan Markelc, Jared Tur, Nina Semenova, Kristopher Kohena, Simona Kranjc Brezar, Loree C. Heller, Maja Čemažar, 2022, original scientific article Abstract: Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immuno- genicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines.
Keywords: DNA sensors, cytokines, electrotransfer, skin
Published in DiRROS: 06.09.2022; Views: 603; Downloads: 309
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