Naslov (srp)

Ispitivanje biohemijskih i patohistoloških markera značajnih za prognozu karcinoma bubrežnih ćelija : doktorska disertacija

Autor

Radovanović, Milan, 1983-

Doprinosi

Radojević-Škodrić, Sanja, 1972-
Džamić, Zoran, 1960-
Isaković, Aleksandra, 1973-
Pekmezović, Tatjana, 1964-
Bančević, Vladimir, 1974-

Opis (srp)

Karcinom bubrežnih ćelija (RCC) je najčešći maligni tumor bubrega kod odraslih. Javlja se u 85%-90% svih malignih tumora bubrega kod odraslih. Najveća incidencija karcinoma bubrega se beležikod ljudi između 60-70 godine starosti, češće kod muškaraca (1,5:1), dok se u 7% slučajevadijagnostikuje kod osoba mlađih od 40 godina. Prema Vankuverskoj klasifikaciji iz 2004 postojetri glavna histološka podtipa karcinoma bubrežnih ćelija i to: svetloćelijski tip RCC (engl. clear cellRCC - ccRCC), papilarni tip RCC (engl. papillary RCC - pRCC) i hromofobni RCC (engl. chromophobeRCC - chRCC) pri čemu je najčešći tip ccRCC (70-85% svih RCC).Veliki problem u terapijskom pristupu RCC jeste njegova rezistencija na hemioterapiju. Imajući uvidu da je angiogeneza ključan faktor koji doprinosi napredovanju svih tumora pa i RCC, kao i daapoptoza i autofagija mogu doprineti hemorezistenciji RCC smatrali smo značajnim upravoispitivanje patohistoloških i biomolekulanih faktora kao potencijalnih markera RCC iprognostičkih faktora u odnosu na tok bolesti i njen ishod. Takođe, ispitivanjem angiogeneze,apoptoze i autofagije u različitim tipovima karcinoma bubrega bi se mogao poboljšati terapijskipristup, a samim tim i prognoza pacijenata obolelih od karcinoma bubrega, naročito onih sametastatskom bolešću.U okviru ovog istraživanja su izvedene dve studije na istom uzorku. Uzorak su činili pacijenti sapostavljenom dijagnozom RCC (90 pacijenata) i pacijenti sa ccRCC (30 pacijenata) koji su hirurškilečeni na Klinici za Urologiju Kliničkog Centra Srbije. Jedna studija je obuhvatila patohistološkoispitivanje ekspresije p53, VEGF, survivina i beta katenina u različitim podtipovima RCC (90pacijenata) i njihovu međusobnu korelaciju kao i njihovu korelaciju sa stadijumom, gradusom iishodom bolesti. Za potrebe ovog dela istraživanja je primenjena imunohistohemijska metodaprimenom metode tkivnog mikroniza (engl. tissue microarray - TMA). Druga studija je obuhvatilaispitivanje ekspresije gena i proteina uključenih u kontrolu procesa apoptoze i autofagije u ccRCCkao najčešćem tipu RCC (30 pacijenata). Za potrebe ovog segmenta istraživanja primenjene suRT-qPCR metoda i imunoblot analiza.Dobijeni rezultati su pokazali da je u tkivu RCC prisutna ekspresija p53, VEGF, survivina i betakatenina i da ekspresija ovih proliferativnih markera korelira pozitivno sa stadijumom i gradusombolesti (izuzev beta katenina koji je pokazao negativnu korelaciju). Takođe je pokazano da izmeđuanaliziranih markera nema međusobne korelacije. Istovremeno, ekspresija p53, VEGF i survivinapokazuje negativnu korelaciju sa dužim preživljavanjem dok ekspresija beta katenina pokazujepozitivnu korelaciju. U tkivu ccRCC pokazana je povećana ekspresija iRNK za p21, p27, p53tumorsupresor gene, Bax i Bad antiapoptotskih gena dok je ekspresija tumor supresora PTEN bilaviša u peritumorskom tkivu. Ekspresija iRNK za markere autofagije p62, Atg4 i Uvrag je bila viša utumorskom tkivu ccRCC...

Opis (srp)

Medicina - Epidemiologija / Medicine- Epidemiology Datum odbrane: 06.07.2022.

Opis (eng)

85% -90% of all malignant kidney tumors. The highest incidence of kidney cancer is recorded inpeople between 60-70 years of age, more often in men (1.5: 1), while in 7% of cases it isdiagnosed in people younger than 40 years. According to the 2004 Vancouver classification, thereare three main histological subtypes of renal cell carcinoma: clear cell type RCC (ccRCC), papillarytype RCC (papillary RCC) and chromophobic RCC (chRCC). ). The most common type is ccRCCwhich makes 70-85% of all RCCs.A major problem with the RCC's therapeutic approach is its resistance to chemotherapy. Giventhat angiogenesis is a key factor which contributes to the progression of all tumors, includingRCC, and that apoptosis and autophagy may contribute to RCC chemoresistance, we consideredas an important goal of this study to examine pathohistological and biomolecular factors aspotential markers of RCC and prognostic factors in relation to the course and outcome of thedisease. Also, the examination of angiogenesis, apoptosis and autophagy in different types ofkidney cancer could improve the therapeutic approach, and thus the prognosis of patients withkidney cancer, especially those with metastatic disease.Within this research, two studies were performed on the same sample. The sample included thepatients diagnosed with RCC (90 patients) and patients with ccRCC (30 patients) who weresurgically treated at the Clinic of Urology of the Clinical Center of Serbia. One study includedpathohistological examination of p53, VEGF, survivin, and beta catenin expression in differentRCC subtypes and their correlation as well as their correlation with the stage, grade, and diseaseoutcome (90 patients). In this part of the research, the immunohistochemical analysis includingthe tissue microarray (TMA) method was performed. The other study included apoptosis andautophagy related genes and proteins in the ccRCC as the most common type of RCC (30patients). In this segment of the research RT-qPCR method and immunoblot analysis were used.The obtained results demonstrate that the expression of p53, VEGF, survivin and beta catenin ispresent in RCC tissue and that the expression of these proliferative markers correlates positivelywith the stage and degree of the disease (except beta catenin which showed a negativecorrelation). No correlation was found between the analyzed markers. At the same time, theexpression of p53, VEGF and survivin shows a negative correlation with longer survival while theexpression of beta catenin shows a positive correlation. In ccRCC tissue, increased mRNAexpression was shown for p21, p27, p53 tumor suppressor genes, Bax and Bad antiapoptoticgenes while PTEN tumor suppressor expression was higher in peritumoral tissue. mRNAexpression for autophagy markers p62, Atg4, and Uvrag was higher in ccRCC tumor tissue...

Jezik

srpski

Datum

2022

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Epidemiologija

RCC, apoptosis, autophagy

OSNO - Opšta sistematizacija naučnih oblasti, Epidemiologija

RCC, apoptoza, autofagija

616.61-006-036(043.3)