Title
Analiza ekspresije transformišućeg faktora rasta beta i ćelijskih receptora smrti u urotelnom karcinomu mokraćne bešike i njihov prognostički značaj
Creator
Stojnev, Slavica 1981-
Copyright date
2019
Object Links
Select license
Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
License description
Dozvoljavate samo preuzimanje i distribuciju dela, ako/dok se pravilno naznačava ime autora, bez ikakvih promena dela i bez prava komercijalnog korišćenja dela. Ova licenca je najstroža CC licenca. Osnovni opis Licence: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/deed.sr_LATN. Sadržaj ugovora u celini: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/legalcode.sr-Latn
Language
Serbian
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 06.07.2020.
Other responsibilities
mentor
Janković-Veličković, Ljubinka 1960-
predsednik komisije
Krstić, Miljan
član komisije
Škodrić Radojević, Dobrila
Academic Expertise
Medicinske nauke
University
Univerzitet u Nišu
Faculty
Medicinski fakultet
Group
Katedra za patologiju
Alternative title
ǂThe ǂanalysis of expression of ransforming growth factor beta and cell death receptors in urothelial bladder cancer and their prognostic significance
Publisher
[S. S. Stojnev]
Format
209 lista
description
Beleška o autoru: list 209;
Bibliografija: listovi 176-208.
description
Pathology
Abstract (en)
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.
Authors Key words
Urotelni karcinom mokraćne bešike, transformišući faktor rasta beta,
receptori smrti, imunohistohemija, ukupno preživljavanje, prognoza
Authors Key words
Urothelial bladder cancer, transforming growth factor beta, death
receptors, immunohistochemistry, overall survival, prognosis
Classification
616.62-006.6:616-076-037(043.3)
Subject
B520, B 200
Type
Tekst
Abstract (en)
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.
“Data exchange” service offers individual users metadata transfer in several different formats. Citation formats are offered for transfers in texts as for the transfer into internet pages. Citation formats include permanent links that guarantee access to cited sources. For use are commonly structured metadata schemes : Dublin Core xml and ETUB-MS xml, local adaptation of international ETD-MS scheme intended for use in academic documents.