| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 101 === Currently, there are several antiangiogenetic drugs targeting VEGF/VEGF receptor that were approved by the Food and Drug Administration for many cancer types, which works affectively in breast, colon cancer patients, siginificant tumor regression is observed. However, targeting the VEGF signal pathway will influence the function of endothelial cell and homeostasis, furthermore, recent research have discovered that targeting VEGF signal pathway is lacking tumor-specific toxicity, and might turn it became more resistant and turnout a more malignant cell type which would not be positive to cancer therapy. We create an anti-cancer recombinant protein which containing yeast cytosine deaminase(yCD) and human epidermal growth factor(hEGF) based on target therapy. The CD-EGF spicificly target the EGFR on the cancer cell surface, then the yCD will convert the prodrug 5-FC to 5-FU, thus there will be high 5-FU concentration around the cancer cell, it not only makes cytotoxicity better but also lower the toxicity to normal cell. The CD-EGF shows significant
regression compare with control group in MDA-MB-468 by MTT assay, and the toxicity effect decreased when the EGFR number per cell desend from MDA-MB-231, MCF-7, to MCF-10, this evidence suggest that CD-EGF obtained nice tumor cell specificity, this could prevent normal cell from effect with toxic, moreover, since it targed EGFR rather than VEGFR, so could be no adversity to endothelial function. Our result shows that that, compared with currently used antiangiogenic drugs, CD-EGF possesses potent anticancer activity with lower toxic effects to normal cell, and we believed it may became an ideal option in cancer therapy.
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