الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 178 |  |  |
| | | from | 178 | | |
Abstract
Bladder cancer is the most common malignancy of the urinary system and the fifth most common cause of cancer related deaths in men in western countries. In Egypt, it accounts for 7% of all Egyptian malignancies. Despite the availability of various therapeutic options, the recurrence of bladder cancer is over 50% which is the highest recurrence rate of any malignancy. Furthermore, drug resistance is still a pivotal obstacle that limits our ability to control this aggressive tumor. Consequently, the study of the underlying molecular pathways responsible for initiation, progression and invasiveness of this malignancy is a must to improve the prognosis of BC and augment the efficacy of treatment.
The current study was designed to evaluate the changes and the interplay between the markers of autophagy (ATG5 and LC3A), apoptosis (caspase-3), ER stress (CHOP) and oxidative stress (MDA) in diagnosis of bladder cancer and their role in its progression.
The study included sixty patients with urothelial bladder carcinoma who underwent either transurethral resection of bladder tumor (TURBT) (40) or radical cystectomy (RC) (20), and confirmed by histopathological analysis. A total of 80 tissue samples were collected, as there were additional 20 samples from the normal bladder urothelial tissues collected from the safety margin of the excised RC specimens only. All the tissue samples (tumor and normal) were subdivided into 3 groups; group A included 20 tissues samples with low grade urothelial tumor collected from excised TURBT specimens, group B included 40 tissue samples with high grade urothelial tumor collected from RC (20) and TURBT (20) specimens, which were further classified according to muscle invasion into 20 high grade muscle invasive (HGMI) and 20 high grade non muscle invasive (HGNMI) groups, and group C (control) which included 20 normal bladder urothelial tissue samples collected from the safety margin of excised RC specimens.
Different methods were used to measure the target markers; RT-PCR was used to measure ATG5 and caspase-3, immunohistochemical assay for LC3A, colorimetric method for MDA and ELISA assay was used to measure CHOP.
The results of the present study showed that there was statistically significant upregulation of tissue levels of ATG5, CHOP, MDA and LC3A in tumor tissue samples compared to control samples, while the caspase-3 was significantly downregulated in the tumor tissues compared with the healthy ones. Also, the tumor tissue level of MDA and LC3A SLS/OF was statistically significant higher among patients ≥ 60 years compared to patients < 60 years. There was no statistical difference in tissue levels of these markers regarding gender, smoking status and bilharziasis.
Additionally, the current study showed that there were statistically significant higher expression levels of ATG5, LC3A, CHOP and MDA in muscle invasive bladder cancer (MIBC) group compared to the non-muscle invasive bladder cancer (NMIBC) group, while caspase-3 showed significant low expression in the MIBC than the NMIBC. There were also statistically higher levels of CHOP, MDA and LC3A among patients with LN involvement compared to those with negative LN involvement. These results prove the strong association between these markers and tumor progression and aggressiveness.