| Summary: | 碩士 === 國立清華大學 === 生醫工程與環境科學系 === 102 === Radiotherapy plays a major role in the treatment of glioblastoma multiforme (GBM).The high doses of radiation delivered in the treatment of patients with GBM, the tumors invariably recur within the irradiation field, resulting in a low cure rate. Therefore, reducing the recurrence rate after radiation therapy is urgent problem. Lab early study has demonstrated that radiation-induced brain tumor invasiveness is associated with the level of SDF-1 production by tumor cells. This study further examined if AMD3100, a drug to block the interaction of SDF-1 with its receptor CXCR4, could enhance the efficacy of radiation therapy and explored the change of tumor microenvironments after radiotherapy in a murine astrocytoma tumor model, ALTS1C1. Our first result demonstrated that the administration of AMD3100 could prolong the surviving time of tumor-bearing mice after 32 Gy of radiation therapy, but not 8 Gy of radiation therapy. The immunohistochemical (IHC) staining study further showed that the number of CD11b+ TAMs or CD68+ M2 macrophages, and the density of pericyte cells were significantly increased at 4 days after radiation therapy, but the microvascular density (MVD) and the number of F4/80+ M1 macrophages were significantly decreased. The administration of AMD3100 s significantly decreased the number of CD68+ or CD11b+ macrophages, but increased the number of F4/80+ macrophages. The MVD and the pericyte coverage rate were also decreased significantly. In summary, this study shows that tumor recurrence stimulates the bone marrow-derived cells to enter and the CD68 positive activated alternative M2 macrophages help regrowth of the tumor and the administration of AMD3100following radiotherapy can effectively block the recruitment of bone marrow-derived cells, reduce the density of blood vessels and pericyte cell coverage, and enhance the efficacy of high dose of radiation therapy for brain tumor.
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