课题规划与实施阶段的文献查阅-2013.pptVIP

Histopathological Changes Ad/GT-TRAIL + Ad/PGK-GV16 Ad/gTRAIL Ad/CMV-GFP PBS liver function test (Fig 3A) PBSAd/CMV-GFP PBS Ad/CMV-GFP Ad/gTRAIL Ad/gTRAIL Ad/GT-TRAIL + Ad/PGK-GV16 Ad/GT-TRAIL + Ad/PGK-GV16 1, DLD-1 cancer cells treated with Ad/gTRAIL 2–4, liver samples after systemic administration of Ad/GT-TRAIL +Ad/PGK-GV16 5–7, liver samples after systemic administration of Ad/gTRAIL 8–9, liver samples after systemic administration of Ad/CMV-GFP Fig 3 In vivo Ad/gTRAIL doesn’t show more toxic effects. conclusion 1-2 Treatment of NHPHs with Ad/gTRAIL resulted in no detectable transgene expression and in minimal toxicity In vivo study on mice showed no transgene expression from Ad/gTRAIL in liver after system administration of a high dose of Ad/gTRAIL conclusion 1-1 + 1-2 4. Question 2: If Ad/gTRAIL can induce  apoptosis in cancer cells? Question 2-1: In vitro Transgene Expression and Apoptosis Induction by Ad/gTRAIL in Cancer Cells in Vitro Question 2-2: In vivo Suppression of Tumor Growth by d/gTRAIL in Vivo To answer Question 2-1 (Fig 4) Transgene Expression and Apoptosis Induction by Ad/gTRAIL in Cancer Cells in Vitro (Fig 4A) human lung cancer cell lines (A549 and H460) human colon cancer cell lines (DLD-1 and Lovo) Ad/gTRAIL Ad/CMV-GFP Ad/GT-TRAIL + Ad/PGK-GV16 Two days later, cells were harvested and analyzed for GFP expression and apoptosis by FACS. Ad/CMV-GFP or Ad/gTRAIL: similar levels of GFP-positive cells (70–90%) Ad/gTRAIL dramatically increase the number of apoptotic cells. top panel: Levels of GFP expression bottom panel: apoptotic cell death Fig 4A Ad/CMV-GFP high levels of transgene expression background levels of apoptosis Ad/GT-TRAIL + Ad/PGK-GV16 background levels of GFP-positive cells high levels of apoptosis in cancer cell