الفهرس 
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Abstract
Most colorectal cancer develop first as colorectal polyps, which are growth inside the colon or rectum that may be cancerous. This is a terrible disease, which can inflict innumerable stomach disorder such as diarrhea, constipation, stomachache, vomiting, lack of energy, and most devasting of all, death.
Oxidative stress includes a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. Permanent modifications of genetic material resulting from oxidative damage represents the first step involved in mutagenesis, and aging. DNA damage can result in either arrest or induction of transcription, induction of signal transduction pathways, replication errors, and genomic instability, all of which are associated with key players in the process of carcinogenesis.
Colorectal cancer patients were found to have significantly lower selenium and significantly higher serum manganese and iron levels compared to controls. Studies of selenium status in patients with colorectal cancer found that both plasma levels of selenium, and plasma glutathione peroxidase levels were significantly lower than healthy subjects.
TNF- α also induces DNA damage through inhibition of DNA repair enzymes and stimulation of inducible nitric oxide synthetase (iNOS) result in increased production of ROS via iNOS an effect that is known to augument tumor development. In addition, individuals having an advanced stage of disease have higher levels of TNF-α in comparison to those at earlier phases.
This study was conducted on 30 patients with colorectal cancer and 10 healthy control.
Blood samples were taken on EDTA from patients after fasting 12h. The plasma was separated by centrifugation at 300g and preserved at -80°C tell proceed.
All cases were subjected to full clinical examination and the following laboratory investigation:
1- Determination of total GPx activity, selenium-dependent GPx, and non selenium-dependent GPx activity.
2- Determination of selenium by atomic absorption.
3- Determination of tumor necrosis factor-alpha by ELISA.
4- Determination of alanine amino transferase and aspartate aminotransferase.
5- Determination of urea and cretainine.
The following results were obtained from the present study:
1- Level of GPx in colorectal cancer patients showed a significant decrease by 40% (p < 0.001) compared to control group.
2- The levels of se-dependent GPx and non se-dependent GPx in colorectal cancer patients showed a significant decrease by 80% (p < 0.001) and 11% (p < 0.05) successively compared to control group.
3- Level of se in the plasma of colorectal cancer patients showed a significant decrease by (36%) compared to control group.
4- Level of TNF- concentration showed a significant increase by 312% in colorectal cancer patients compared to control group.
5- In control group we found a +ve correlation between GPx and non-selenium dependent GPx, also a –ve correlation between se- dependent GPx and non-se dependent GPx.
6- In patient group we found a +ve correlation between GPx and non-se dependent GPx.
Oxygen radical could be formed in excess in chronic disease of the gastrointestinal tract. The main sources of oxidants in the gut is probably phagocytes, which are accumulated in the mucus of the patient with bowel disease and could generate oxidants upon activation, which might contribute to the increased risk of cancer.
Antioxidant potential in all cases of gastrointestinal tract cancer has been unbalanced which has lead to increase in reactive oxygen species action and enhancement of lipid peroxidation and cancer procoagulant generation.
Selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer.
The gastrointestinal glutathione peroxidase (GI-GPx) is believed to prevent absorption of hyDROPeroxide. GI-GPx is expressed in intestine together with the other glutathione peroxidase isoenzymes. In colorectal cancer, GI-GPx expression depend on the stage of malignant transformation.
Trace elements have an important influences as component of many enzymes on a large number of biological processes. They have some regulatory functions and they may affect immune reactions and free radical generation. Selenium has effects on key cellular events of tumorigenesis, such as cell proliferation and apoptosis and the possible complex mechanisms underlying these effects are emerging in increasing numbers.
Selenium appears to have a protective effect against some cancers e.g. colon cancer. Supplementation of cells with selenium results in the increased expression of various selenoproteins including GPX1.
Studies of selenium status in patients with stomach and colorectal cancer found that both plasma levels of selenium and plasma glutathione peroxidase levels were significantly lower than healthy subjects.
Colorectal cancer development is associated with a shift in host immunity with suppression of the cell mediated immune system (CMT) and a predominance of humoral immunity (HI). Tumor progression is also associated with increased rates of cell proliferation and apoptosis. This may reflect change in the host immune regulatory function in the adeno-carcinoma sequences.
Several mechanisms have been proposed to explain the role of TNF- in inflammation. TNF- activates NF-kB which swiches on the transcription of inflammatory response genes that increases the release of proinflamtion cytokines, chemokines, and proteases in epithelial cells and macrophages. NF-KB regulates several genes involved in cell transformation, proliferation, and angiogenesis.
NF-KB activation has been linked to carcinogenesis process because of its role in differentiation, inflammation and cell growth.
TNF may also affect genome integrity via inhibition of cytochrome P450 or glutathione S-transferase isoenzymes. The oxidative stress in chronic inflammation may induce DNA damage tolerance, translation synthesis and cause high rates of carcinogen induced mutation.
Levels of cytokine production vary between individuals and this variation may have a genetic basis.