Biomarkeri apoptoze i ćelijske signalizacije u patogenezi kolorektalnog karcinoma

Abstract

Colorectal cancer is one of the most frequent neoplastic diseases in human population and one of the most frequent causes of death. There are a lot of pathological factors, involved in the process of colon cancer initiation, propagation and progression, among other ROS, who can activate Nuclear transcriptional factor kappa B (NF-B), who controls genes involved in tumor progression.Apoptosis is a process involved in the development of tumors, where blocking apoptosis avoids removal of malignant cells.The matrix metalloproteinase’s generally function to degrade proteoglycans and matrix glycoprotein’s and facilitate the development and metastasis of tumors. Enzymes of purine nucleotide metabolism may be very important in tumor proliferation. The aim of the present study wasthat in 50 patients with colorectal cancer to assess the levels of oxidative stress , quantitative expression of NF-B, level of apoptosis expressed in endonuclease activity and Bcl2 / Bax ratio, the activity of matrix metalloproteinase 9, and the activity of the enzyme of purine nucleotides in homogenates of tumor tissue, the tissue immediately surrounding the tumor and healthy colon tissue. The concentrations of TBARS and AOPP, and enzyme activities were determined by appropriate spectrophotometric methods, quantitative expression of NF-B, Bcl2 and Bax, and the activity of MMP-9 were determined by appropriate immunofluorescence methods. The concentrations of TBARS, AOPP, MMP-9 activity, xanthine oxidase, adenosine dezaminaze and quantitative expression of NF-B and Bcl2 in the tumor tissue increased compared to healthy colon tissue. Catalase activity and quantitative expression of Bax was decreased in tumor tissue compared to healthy colon tissue. The tissue surrounding the tumor also had significantly higher TBARS, AOPP, NF-B, Bcl2, and increased activity of MMP-9, ADA, XO compared to healthy tissue. Our results show that the tumor has an increased level of oxidative stress, increased levels of markers of proliferation, but decreased levels of apoptosis compared to healthy colon tissue. The surrounding tissue is also proliferativeactive with reduced levels of apoptosis. These facts may be relevant in determining the operating margin removal of the tumor, followed by the creation of individual therapeutic strategies in inoperable condition or in patients with bone metastases. Correlation with histological findings, tumor stage and other clinical characteristics of each patient would enable a more accurate assessment of invasiveness and aggressiveness of the tumor and the selection of appropriate therapy.