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Title:Translacijski nadzor biologije raka jajčnikov
Authors:ID Sobočan, Monika (Author)
ID Takač, Iztok (Mentor) More about this mentor... New window
ID Haybaeck, Johannes (Comentor)
Files:.pdf DOK_Sobocan_Monika_2023.pdf (910,32 KB)
MD5: 51BBAD81AEB14F9D0774FDF2DBECC4E3
 
Language:Slovenian
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Rak jajčnikov (OC) se uvršča na peto mesto med vzroki za smrt žensk po vsem svetu. Razumevanje zapletenosti različnih histoloških podtipov je ključno za usmerjeno personalizirano zdravljenje bolezni. Epitelijski rak jajčnikov (EOC) je agresiven in ima omejeno preživetje brez ponovitve (RFS) po primarnem zdravljenju. Raziskovanje novih tarč za razumevanje karcinogeneze EOC v procesu translacije lahko omogoči prepoznavo novih, neodvisnih prognostičnih označevalcev in terapevtske cilje. Metode: Po in silico analizi evkariotskih faktorjev iniciacije in elongacije (eIF in eEF) so bili vzorci tkiva jajčnika (neoplastični, ne-neoplastični) pripravljeni s pomočjo tehnike tkivnih mikromrež (TMA). Nato so vzorci bili obarvani z imunohistokemičnemi barvami za translacijske označevalce. Intenzivnost/obseg barvanja je bil analiziran glede na parametre RFS in celokupnega preživetja po zdravljenju. Rezultati: Opazili smo statistično pomembno razliko v izraženosti translacijskih označevalcev med ne-neoplastičnimi in tumorskimi vzorci (mejni tumorji, EOC). Zlasti je eIF5A pomembno koreliral z RFS; eIF2G in eEF1A1 sta korelirala s celotnim preživetjem (OS) pri EOC. eIF5A je kazal povezave z eIF5B in eIF6, kar nakazuje njegovo osrednjo vlogo pri disfunkciji translacijskega mehanizma pri EOC. Zaključek: Raziskava poudarja različen translacijski profil EOC v primerjavi z benignim tkivom jajčnikov. eIF5A se kaže kot ključen pri nenormalnem translacijskem mehanizmu EOC, kar bi lahko služilo kot prognostični označevalec in terapevtski cilj.
Keywords:rak jajčnikov, evkariotski iniciacijski faktorji, evkariontski elongacijski faktorji
Place of publishing:Maribor
Year of publishing:2023
PID:20.500.12556/DKUM-85057 New window
COBISS.SI-ID:166558211 New window
Publication date in DKUM:02.10.2023
Views:738
Downloads:90
Metadata:XML DC-XML DC-RDF
Categories:MF
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:17.08.2023

Secondary language

Language:English
Title:The translational control of ovarian cancer
Abstract:Ovarian cancer (OC) ranks fifth in female global mortality. Understanding distinct histological subtype intricacies is crucial due to unique disease characteristics. High-grade epithelial ovarian cancer (EOC) is aggressive with limited recurrence-free survival (RFS) post-primary treatment. Investigating novel EOC carcinogenesis targets in translational machinery could yield independent prognostic markers and therapeutic targets. Methods: Eukaryotic initiation factors (eIFs) and elongation factors (eEFs) were identified from The Cancer Genome Atlas (TCGA) datasets. TCGA OC dataset (602 samples) was categorized by histological grades. Differential eIFs and eEFs expression in EOC was in-silico assessed. Ovarian tissue samples (neoplastic, non-neoplastic) underwent tissue microarray (TMA) preparation, followed by immunohistochemical staining for translational markers. Staining intensity/extent was statistically analyzed. Results: Significant differential expression of translational markers was observed between non-neoplastic and tumor samples (borderline tumors, EOC). Notably, eIF5A significantly correlated with RFS; eIF2G and eEF1A1 correlated with overall survival (OS) in EOC. eIF5A showed correlations with eIF5B and eIF6, indicating its central role in EOC's translation machinery dysregulation. Conclusion: Research emphasizes EOC's distinct translational profile vs. benign ovarian tissue. eIF5A emerges as pivotal in EOC's aberrant translation machinery, potentially serving as prognostic marker and therapeutic target.
Keywords:Keywords: ovarian cancer, eukaryotic initiation factor, eukaryotic elongation factor


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