Josipa Marin Lovrić
Ime i prezime: dr. sc. JOSIPA MARIN LOVRIĆ, dr. med.
Naslov disertacije: „IZRAŽAJ BILJEGA STANIČNOG CIKLUSA I PROLIFERACIJSKIH ČIMBENIKA TIJEKOM RAZVOJA LJUDSKOG OKA I INTRAOKULARNE TUMORIGENEZE”
Mentorica: prof. dr. sc. KATARINA VUKOJEVIĆ
Datum obrane: 2. veljače 2023.
Poveznnica: https://repozitorij.mefst.unist.hr/islandora/object/mefst%3A1696/datastream/PDF/view
Kvalifikacijski znanstveni radovi za doktorsku disertaciju:
Marin Lovrić J, Filipović N, Znaor L, Rančić A, Petričević J, Kunac N, Šoljić V, Saraga-Babić M, Vukojević K. Expression of Cell Cycle Markers and Proliferation Factors during Human Eye Embryogenesis and Tumorigenesis. Int J Mol Sci. 2022;23(16):9421.
doi: 10.3390/ijms23169421.
SAŽETAK:
Izražaji biljega p19, Ki-67, MSX1, MSX2, PDL1, pRB, CYCLINA2, citokeratina 8 i vimentina kvantitativno su i semikvantitativno analizirani u histološkim presjecima ljudskog oka u razvoju u 8. tjednu i postnatalnom oku te u retinoblastomu i u različitim uvealnim melanomima korištenjem dvostruke imunofluorescencije. Imunoreaktivnost p19 karakterizira mrežnične i/ili žilnične stanice u zdravim i tumorskim tkivima: izražaj je bio niži u postnatalnoj mrežnici nego u mrežnici i retinoblastomu u razvoju, dok je bio visok u epiteloidnim melanomima. Izražaj Ki67 bio je visok u oku u razvoju, retinoblastomu i melanomima žilnice. Izražaj MSX1 i MSX2 bio je sličan u oku u razvoju i retinoblastomu, dok izražaja nije bilo u postnatalnom oku. Njihov različit izražaj bio je očit između epiteloidnog i miksoidnog melanoma. Slično, PDL1 je bio odsutan u epiteloidnim melanomima, dok je bio visoko izražen u tkivima u razvoju i tumorskim tkivima. Izražaj pRB i CYCA2 bio je karakterističan za uzorke oka u razvoju i tumoru, ali ne i u zdravom postnatalnom oku. Izražaj citokeratina 8 i vimentina u korelaciji je s izražajem u epitelu i mezenhimu u razvoju oka i neoplazmi. Uočene razlike u izražaju analiziranih biljega koreliraju s podrijetlom i stupnjem stanične diferencijacije uzoraka tkiva. Fina ravnoteža izražaja mogla bi igrati ulogu u razvoju ljudskog oka i tumorigenezi oka. Stoga bi razumijevanje njihova odnosa i međudjelovanja moglo otvoriti nove puteve za potencijalne terapijske intervencije i bolje razumijevanje mehanizama koji leže u osnovi razvojne plastičnosti oka i nastanka neoplazmi.
SUMMARY:
The expression pattern of the markers p19, Ki-67, MSX1, MSX2, PDL1, pRB, CYCLINA2, citokeratin 8 and vimentin was quantitatively and semiquantitatively analyzed in histologic sections of the developing and postnatal human eye at week 8, in retinoblastoma, and in various uveal melanomas post hoc studies by double immunofluorescence. The p19 immunoreactivity characterized retinal and/or choroidal cells in healthy and tumor tissues: expression was lower in the postnatal retina than in the developing retina and retinoblastoma, whereas it was high in epithelioid melanomas. Ki67 expression was high in the developing eye, retinoblastoma, and choroidal melanomas. MSX1 and MSX2 expression was similar in the developing eye and retinoblastoma, whereas it was absent in the postnatal eye. Their different expression was evident between epithelioid and myxoid melanomas. Similarly, PDL1 was absent in epithelioid melanomas, whereas it was highly expressed in developing and tumor tissues. Expression of pRB and CYCA2 was characteristic of developing and tumorous eye samples but not of the healthy postnatal eye. Cytokeratin 8 and vimentin expression correlated with epithelial and mesenchymal expression in eye development and neoplasm. The observed expression differences of the analyzed markers correlate with the origin and stage of cell differentiation of the tissue samples. The fine balance of expression could play a role in both human eye development and ocular tumorigenesis. Therefore, understanding their relationship and interplay could open new avenues for potential therapeutic interventions and a better understanding of the mechanisms underlying the developmental plasticity of the eye and the development of neoplasms.
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