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81.
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, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: lung neoplasms, non-small cell lung carcinoma, Eastern Europe, real-world study, REFLECT study, epidermal growth factor receptor, lung cancer
Objavljeno v DiRROS: 09.09.2022; Ogledov: 518; Prenosov: 215
URL Povezava na datoteko

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Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological study
Primož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Objavljeno v DiRROS: 07.09.2022; Ogledov: 524; Prenosov: 235
.pdf Celotno besedilo (3,97 MB)
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Influence of housing conditions on reliability of immunocastration and consequences for growth performance of male pigs
Kevin Kress, Ulrike Weiler, Sonja Schmucker, Marjeta Čandek-Potokar, Milka Vrecl, Gregor Fazarinc, Martin Škrlep, Nina Batorek Lukač, Volker Stefanski, 2020, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: immunocastration, vaccination, Improvac, non-responder, immune response, housing conditions, surgical castration, boar taint, growth performance, genital tract
Objavljeno v DiRROS: 06.09.2022; Ogledov: 638; Prenosov: 228
URL Povezava na celotno besedilo

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In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery
Maša 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, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: DNA sensors, cytokines, electrotransfer, skin
Objavljeno v DiRROS: 06.09.2022; Ogledov: 602; Prenosov: 307
.pdf Celotno besedilo (7,72 MB)
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90.
Inter-person differences in isometric coactivations of triceps surae and tibialis anterior decrease in young, but not in older adults after 14 days of bed rest
Matjaž Divjak, Gašper Sedej, Nina Murks, Mitja Gerževič, Uroš Marušič, Rado Pišot, Boštjan Šimunič, Aleš Holobar, 2022, izvirni znanstveni članek

Povzetek: We examined activation patterns of the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), soleus (SO), and tibialis anterior (TA) muscles in eight older (58.4 ± 3.3 years) and seven young (23.1 ± 2.9 years) participants, before and after 14 days of horizontal bed rest. Visual feedback on the exerted muscle torque was provided to the participants. The discharge patterns of individual motor units (MUs) were studied in three repetitions of isometric plantar flexion at 30 and 60% of Maximum Voluntary Contraction (MVC), before, and 1 day after the 14-day bed rest, respectively. In the GL and GM muscles, the older participants demonstrated higher MU discharge rates than the young, regardless of the contraction level, both before and after the bed rest. In the TA and SO muscles, the differences between the older and young participants were less consistent. Detailed analysis revealed person-specific changes in the MU discharge rates after the bed rest. To quantify the coactivation patterns we calculated the correlation coefficients between the cumulative spike trains of identified MUs from each muscle, and measured the root mean square difference of the correlation coefficients between the trials of the same session (intra-session variability) and between different sessions (inter-session variability) in each participant (intra-person comparison) and across participants (inter-person comparison). In the intra-person comparison, the inter-session variability was higher than the intra-session variability, either before or after the bed rest. At 60% MVC torque, the young demonstrated higher inter-person variability of coactivation than the older participants, but this variability decreased significantly after the bed rest. In older participants, inter-person variability was consistently lower at 60% than at 30% MVC torque. In young participants, inter-person variability became lower at 60% than at 30% MVC torque only after the bed rest. Precaution is required when analyzing the MU discharge and coactivation patterns, as individual persons demonstrate individual adaptations to aging or bed rest.
Ključne besede: high density electromyography, muscle disuse, motor units, discharge rate, aging
Objavljeno v DiRROS: 05.09.2022; Ogledov: 634; Prenosov: 357
.pdf Celotno besedilo (4,31 MB)
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