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Előadáskivonatok / Abstracts

the release of individual exosomes into the extracellular Tobramycin and aztreonam-lysine (t.i.d.,75 mg) with 28 days
space. Recently a novel, unconventional mechanism has run in phase of Tobramycin and Tobramycin (600 mg) the
been described in vitro in which the exosome-like sEVs highest probability of being the best treatments
remain in one bloc during their secretion. Our aim was to (SUCRA:90%, 86% and 81% respectively). Almost all
examine this phenomenon in colorectal carcinoma (CRC) treatment proved to be more efficient than placebo.
cells in situ and in vitro. Conclusion: Aztreonam-lysine may be the best treatment
Materials and Methods: Immunohistochemistry option regarding FEV1% and Pseudomonas sputum density
examination of individual cancer cells were performed in in CF patients with Pseudomonas. Optimizing nutritional
metastatic CRC samples (n=38) and HT29 cell cultures. We status with proper pancreatic enzyme replacement terapy
used cytoplasmic (cytokeratin) and cell membrane (E- could reduce the risk for chronic pulmonary infections.
cadherin) markers for the identification of CRC cells, ALIX
and CD63 proteins for the detection of sEV transport. 142. TRANSCRIPTOME ANALYSES REVEALED CAMP
Samples were analyzed with confocal-, STED-, electron SIGNALING ELEMENTS IN PANCREATIC DUCTAL
microscopy (EM) and immune-EM. ORGANOIDS
Results: 3D reconstructions showed ALIX/CD63-positive Varga Á. 1,2,3,4 , Kiss A. , Madácsy T. 1,2,3,4 , Szabó V. 1,2,3,4 ,
1,3
sEV-clusters (sEVCs) with 0.62-1.94 μm (mean±SD: Jójárt B. 1,2,3,4 , Groma G. , Pallagi P. 1,2,3,4 , Maléth J. 1,2,3,4
5
1.17±0.34 μm) diameter are localized partially inside, and/or 1. I. Department of Internal Medicine, Faculty of Medicine,
outside the cytoplasm in 85.96% of migrating CRC cells. University of Szeged; 2. Department of Public Health, Faculty
STED-microscopic images showed that released sEVCs of Medicine, University of Szeged; 3. Momentum Epithelial
were composed of distinguishable ALIX-positive spheroids of Cell Signaling and Secretion Research Group; 4. HCEMM
98-150 nm diameter (mean±SD: 128.96±16.73 nm). Molecular Gastroenterology Research Group; 5. Department
EM/immune-EM images showed large (~500-1500 nm) of Dermatology, Faculty of Medicine, University of Szeged
limiting membrane-enclosed sEVCs with ALIX positivity in
HT29 cultures. Introduction: cAMP signaling is a well-known regulator of
Conclusions: Our study demonstrates in situ and in vitro that cystic fibrosis transmembrane conductance regulator
besides conventional exosome release, CRC cells also (CFTR) activity in epithelial cells thereby controlling ion and
secrete large sEVCs. SEVCs might play an important role as fluid secretion. Components of cAMP signaling are
autocrine/paracrine regulators of cancer development, which suggested to be clustered into subcellular microdomains
effect may differ from that mediated by traditionally secreted (MDs). Disturbed integrity of MDs could be a hallmark of
exosomes. various diseases, such as cystic fibrosis.
Aims: We aimed to characterize cAMP signaling elements in
141. THERAPEUTIC APPROACH OF CHRONIC primary pancreatic ductal epithelial cells.
PSEUDOMONAS AERUGINOSA INFECTION IN CYSTIC Methods: Murine pancreatic ductal organoid cultures (OCs)
FIBROSIS PATIENTS were generated under Wnt3A stimulated and withdrawn
1
1
1
1,2
Varannai O. , Gede N. , Juhász M. , Szakács Z. , conditions. Ductal origin was verified by transcriptomic
1
2
1
Dembrovszky F. , Németh D. , Hegyi P. 1,3,4 , Párniczky A. profiling and immunofluorescent labelling (IF). Cell-cycle was
1. Institute for Translational Medicine, Medical School, investigated by proliferation assay. Expression pattern of the
University of Pécs, Pécs, Hungary; 2. Heim Pál National cAMP signaling elements were characterized. Ingenuity
Institute of Pediatrics, Budapest, Hungary; 3. Division of Pathway Analysis software was applied in both conditions.
Translational Medicine, First Department of Translational Identified adenylyl cyclases (Adcy) were localized by IF.
Medicine, Medical School, University of Pécs, Pécs, Results: Transcriptome of OCs showed ductal expression
Hungary; 4. First Department of Medicine, University of pattern hallmarked by Cftr, Sox9 and Hes1. Wnt3A
Szeged, Szeged, Hungary withdrawal enhanced the ductal characteristic by resulting
significantly higher expression of adhesion molecules such
Background and aims: Exocrine insufficiency of the as Occludin and E-cadherin. A reduced cell proliferation rate
pancreas in cystic fibrosis (CF) results protein and fat was observed in Wnt3A free environment, which had no
malabsorption, deficiency of macro-and micronutrients, effect on gene expression level of adenylyl cyclase members
associated with more frequent respiratory tract infections. transcribed (Adcy3/6/8/9) in OCs. While ADCY6/3 are
Pseudomonas infection is a major determinant of morbidity located at all membrane regions of organoids, we found
and mortality in CF. basolateral ADCY9 and luminal ADCY8 localization. RNA-
Methods and materials: A Bayesian network meta-analysis seq showed the expression of (phosphodiesterases) Pde3b,
of randomized controlled trials (RCTs) was conducted to Pde4a, Pde4b and Pde4d, whereas from the A-kinase
investigate the efficacy of antipseudomonal inhalative anchoring protein (Akap) genes we detected
antibiotics in CF patients with chronic Pseudomonas Akap1/7/8/9/10/11/12/13.
infection. Main outcomes were: change in forced expiratory Conclusion: Transcriptome analysis of pancreatic OCs
volume 1 (FEV1, in %) and change in Pseudomonas identified the molecular components of cAMP signaling. We
aeruginosasputum density during 4-24 weeks of follow-up. will perform functional analysis followed by siRNA silencing
Results: Eighteen RCTs reported treatment with aztreonam- to understand cAMP signaling and in pancreatic secretion.
lysine, tobramycin, colistin, levofloxacin,
fosfomycin/tobramycin and amikacin in different doses were 143. NYELŐCSŐ SÉRÜLÉSEK NEM SEBÉSZI
eligible for inclusion. Aztreonam-lysine (t.i.d.,75 mg) with 28 KEZELÉSÉNEK LEHETŐSÉGEI
days run in phase of Tobramycin and aztreonam-lysine Vass T. , Balázs Á. , Baranyai Z. , Bán K. , Benke M. , Hritz
1
1
1
1
1
1
(b.i.d.,75 mg) with 28 days run in phase of Tobramycin and I. , Keczer B. , Szijártó A.
1
1
tobramycin inhalation powder had the highest probability of 1. Semmelweis Egyetem, I. sz Sebészeti Klinika
being the best treatment options regarding FEV1% (SUCRA:
77%, 76% and 66%, respectively). As the pathophysiological Bevezetés: A különböző eredetű nyelőcső sérülések
aspect of our study in terms of Pseudomonas sputum density ellátása nagy volumenű centrumokban is jelentős dilemma
aztreonam-lysine (b.i.d.,75 mg) with 28 days run in phase of elé állítja az erre specializált teameket. A definitív sebészi
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86 Central European Journal of Gastroenterology and Hepatology
Volume 6, Supplementum 2 / November 2020