الفهرس 
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Abstract
Cancer is one of the major causes of death all over the world. According to World health organization, more than 10 million new cases of cancer are diagnosed every year, and the statistical trends indicate that this number would double by 2020.
The present study was carried out to evaluate the antiangiogenic efficacy of Chitosan-Gallium Nanoparticles (Ch.GaNPs) either alone or combined with γ-irradiation. As tumor has systemic effects on the host, studying the antioxidant status for tumor, liver , kidney and spleen, angiogenic and antiangiogenic growth factors were evaluated. Also, histopathological and apoptotic examination of tumor, liver , kidney and spleen tissues were performed to evaluate the efficacy of the designed nanoparticles.
In vitro the cytotoxicity of Ch.GaNPs not only led to the death of Ehrlich ascite carcinoma (EACs) cells, but also led to burst of these cells at certain doses. Ch.GaNPs led to death and rupture of cells content after their death. The IC50 of Ch.GaNPs was 50 µg/ml for EACs.
In vivo experiments were performed on healthy and Ehrlich carcinoma-bearing female Swiss albino mice. Mice were randomly assigned and equally divided into 5 experimental groups of 10 mice each as follows: Control group: the mice were neither treated nor irradiated. Tumor-bearing group: each mouse in this group was inoculated subcutaneously with 0.2 ml of EAC cells (2.5x106 cells) for solid tumor induction. The animals were left without any treatment till the end of the experiment. Tumor-bearing-Irradiated group: Each mouse in this group was inoculated subcutaneously with EAC cells and each tumor-bearing mouse was exposed to a fractionated whole body γ-radiation (0.25Gy twice a week x 2 weeks)on 7th day after EAC inoculation. Chitosan-Gallium-Tumor- bearing group: in this group mice bearing EC received 10 successive Ch.GaNps doses of concentration 0.5mg/kg/day orally starting from the 7th day after EAC inoculation. Chitosan-Gallium -Tumor-bearing-Irradiated group: in which mice bearing EC were treated orally with Ch.GaNps and subjected to fractionated low doses of γ –radiation.
The results obtained can be summarized as follows
• The results of the study showed that EACs inoculation in EC bearing group resulted in observation of uncontrolled tumor growth, increased angiogenic levels (VEGF and PDGF), elevated systemic inflammation (TNF-α) and depressed tumor apoptosis (Casp-3) in serum. Also, the presence of tumor caused hepatic, renal and splenic oxidative stress which was observed through elevated LPO level, decreased GSH level and reduced GSH-Px activity.
• Treatment of mice bearing EC with Ch.GaNps and/or low doses of γ-irradiation induced tumor growth regression by decreasing the levels of the angiogenic factors (VEGF and PDGF) , reducing systemic inflammation (TNF-α) and enhancing apoptosis which is detected through the highly increased Casp-3 levels. Moreover, Ch.GaNps and/or low doses of γ-irradiation treatment showed amelioration in antioxidant levels as appeared by increased GSH content and GSH.Px enzyme activity and declined LPO levels in spleen, kidney and liver tissues.
• Histopathological findings revealed that, EACs implantation in the neck region of animals induced some load in other organs like liver which was shown as accumulation of EACs around congested portal blood vessels, caused metastasis of EACs to the kidney tissue and resulted in appearance of many megakaryocytes in white pulp of spleen tissue. Histology of the EC tissue showed groups of large, round and polygonal cells, with pleomorphic shapes, hyperchromatic nuclei and binucleation. Treatment of EC-bearing mice with Ch.GaNps and/or low doses of γ-irradiation ameliorated the histological structure of liver, kidney and spleen tissue sections, whereas, deleterious effects were observed in tumor tissue.
Conclusion
It could be concluded that Ch.GaNPS administration to mice bearing EC with or without subjection to low doses of γ-radiation, exhibited antiangiogenic activity reflected by reduction in tumor size, reduced liver, kidney and spleen oxidative stress, inhibition of angiogenesis and systemic inflammation and remarkably increased apoptosis.