الفهرس 
CancerOnly 14 pages are availabe for public view
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Abstract
Cancer continues to represent the largest cause of mortality in the world, the second leading cause of death worldwide next to cardiovascular disease. Cancer is uncontrolled growth and spread of abnormal cells, associated with dysregulation of apoptosis, a programmed cell death. Traditional methods of cancer therapy inflict a series of side effects. Recent years have witnessed many efforts in creating alternative cancer therapy methods that would be less invasive and would exhibit a site-specific activity. Nanoparticles, with their selective targeting capabilities and superior efficacy, are becoming increasingly important in modern cancer therapy and starting to overshadow traditional cancer therapies such as chemotherapy, radiation and surgery. ZnO nanoparticles, with their unique properties such as biocompatibility, high selectivity, enhanced cytotoxicity and easy synthesis, may be a promising anticancer agent. Oxidative stress through reactive oxygen species and induction of apoptosis may be the probable mechanism of this cytotoxic effect. The selective localization of ZnO nanoparticles towards cancer cells due to enhanced permeability and retention (EPR) effect and electrostatic interaction and selective cytotoxicity due to increased ROS show that ZnO nanoparticles can selectively target and kill cancer cells : Methotrexate was given by i.p. injection on alternate days for 2 consecutive weeks after subcutaneous implantation of Ehrlich tumor cells. At the end of the study, all mice were sacrificed by cervical decapitation. The tumor, mammary gland and liver tissues were excised, and assessment the following: 1. The effects of different treatments on tumor weight and volume. 2. Zinc content in tumor/or mammary gland and liver tissue. 3. Comet assay for DNA damage in tumor/or mammary gland. 4. Beclin1, Bcl-2 and Bax genes expression analyses by Real-time PCR (qPCR) 5. Histopathological examination. 6. Immunohistochemical investigation for Beclin1, Bcl-2 and Bax protiens expression. Results of the present study revealed the following: • Significant decrease in tumor volume in the treated groups compared to untreated Ehrlich tumor group. • Significant increase in tumor zinc levels in Groups IV, V and VI in comparison to its corresponding value in tumor / mammary gland of other groups. Furthermore, no significant different of zinc levels were detected in liver tissues of ZnO NPs-treated groups in comparison to control group. • Variable degrees of DNA damage were noticed in all treated groups. • Concomitantly, marked induction of pro-apoptotic gene, Bax in ZnO NPs-treated groups compared to untreated group and better than MTX treated group. • On the other hand, the expression level of the anti-apoptotic gene, Bcl2 was markedly downregulated in ZnO NPs-treated groups compared to untreated group and better than MTX treated group. • The expression level of the autophagy gene, Becn1 was markedly downregulated in Groups IV, V and upregulated in group VI ZnO compared to untreated group and better than MTX treated group. • Histopathological examination of tumor tissue was showed increase zones of apoptosis in the tumor tissue of ESC treated with ZnO NPs as compared with untreated ESC and better than MTX treated group. • Immunohistochemical investigations for Beclin1, Bcl-2 and Bax protiens expression confirmed the PCR result. • Administered ZnO NPs early can give better result.