dc.contributor.advisor | Janković-Veličković, Ljubinka | |
dc.contributor.other | Krstić, Miljan | |
dc.contributor.other | Škodrić Radojević, Dobrila | |
dc.creator | Stojnev, Slavica | |
dc.date.accessioned | 2020-10-12T09:06:58Z | |
dc.date.available | 2020-10-12T09:06:58Z | |
dc.date.issued | 2020-07-06 | |
dc.identifier.uri | http://eteze.ni.ac.rs/application/showtheses?thesesId=7547 | |
dc.identifier.uri | https://fedorani.ni.ac.rs/fedora/get/o:1668/bdef:Content/download | |
dc.identifier.uri | http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70052&RID=17631241 | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/17492 | |
dc.description | Bladder cancer is the most frequent malignant tumor of the urinary
tract. It represents a significant burden to the healthcare system due to
necessity of lifelong cystoscopic controls, and management of
recurrent disease. More than 90% of bladder cancers are urothelial
carcinomas. Dysregulation of transforming growth factor beta (TGF-
β) signaling pathways plays important role in tumor development and
progression. Activation of TGF-β and cell death receptors involves
common pathways in the activation of caspases and induction of
apoptosis. The significance of immunohistochemical expression of
TGF-β and death receptors in urothelial bladder cancer has not been
fully elucidated. This study comprised 647 urothelial bladder cancers
obtained by transurethral resection that were immunohistochemically
analyzed to the expression of TGF-β1 and death receptors DR4, DR5,
and FAS. The expression of Smad4, a protein with the central role in
TGF-β canonical pathway signal transmission, and EZH2, an
epigenetic regulator involved in TGF-β signalization, was also
analyzed. Association assessment between the markers’ expression
and clinicopathological parameters and follow-up data was
performed. High TGF-β1 expression in urothelial cancer was
significantly associated with high tumor grade and advanced stage,
while the reduction/loss of death receptors’ expression correlated to
muscle-invasive disease. High Smad4 expression was associated with
tumor recurrence. Cancer-specific mortality was directly linked to
high TGF-β1 and EZH2 expression, and inversely to DR4, FAS, and
Smad4 expression. High TGF-β1 was associated with shorter overall
survival of the patients, while high expression of DR4 and FAS in
tumor cells correlated with less aggressive phenotype of the tumor,
and longer overall survival. The present study identified the
expression of TGF-β1, FAS, and EZH2 as independent prognostic
factors in urothelial bladder cancer, where high TGF-β1 and EZH2
expression indicates shorter survival and poor prognosis, while high
FAS receptor expression imparts protective aspect and is linked to
longer overall survival. Further insight into knowledge about complex
roles and significance of TGF-β and death receptors, as well as the
analysis of their expression in urothelial bladder cancer, may have
important implications for prognostic stratification of the patients and
in deciding about their clinical management. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Нишу, Медицински факултет | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175092/RS// | |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Универзитет у Нишу | sr |
dc.subject | Urotelni karcinom mokraćne bešike | sr |
dc.subject | Urothelial bladder cancer | en |
dc.subject | transformišući faktor rasta beta | sr |
dc.subject | receptori smrti | sr |
dc.subject | imunohistohemija | sr |
dc.subject | ukupno preživljavanje | sr |
dc.subject | prognoza | sr |
dc.subject | transforming growth factor beta | en |
dc.subject | death receptors | en |
dc.subject | immunohistochemistry | en |
dc.subject | overall survival | en |
dc.subject | prognosis | en |
dc.title | Analiza ekspresije transformišućeg faktora rasta beta i ćelijskih receptora smrti u urotelnom karcinomu mokraćne bešike i njihov prognostički značaj | sr |
dc.type | doctoralThesis | en |
dc.rights.license | BY-NC-ND | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/65884/Disertacija.pdf | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/65885/Stojnev_Slavica_M.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_17492 | |