Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/53629
Title: MESENCHYMAL STEM CELLS AS THERAPY AGAINST HUMAN GLIOBLASTOMA MULTIFORME
Authors: YULYANA
Keywords: mesenchymal stem cells, TRAIL, carbenoxolone, glioma, gap junction, connexin43
Issue Date: 3-Jan-2014
Source: YULYANA (2014-01-03). MESENCHYMAL STEM CELLS AS THERAPY AGAINST HUMAN GLIOBLASTOMA MULTIFORME. ScholarBank@NUS Repository.
Abstract: Prognosis for glioblastoma multiforme (GBM) patients remains dismal despite advancement in surgical techniques and standard therapies. Alternative gene therapy using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), although used extensively in cancer therapy, is of limited efficacy in GBM. Improvement in therapeutic modalities that increases therapeutic index of TRAIL is much sought after. In this study, we combined the tumor selectivity of TRAIL and tumor-homing properties of mesenchymal stem cells (MSC) with gap junction (GJ) inhibitory effect of carbenoxolone (CBX) to target orthotopic glioma. Our results showed that combined treatment of TRAIL-loaded MSC (MSC-TRAIL) and CBX enhanced glioma cell death, especially in two primary human glioma isolates that are marginally sensitive to TRAIL. CBX enhanced TRAIL-induced apoptosis through CHOP-mediated upregulation of death receptor 5 and downregulation of anti-apoptotic Bcl-2. CBX also blocked GJ communication and downregulated connexin 43. Dual arm therapy using MSC-TRAIL and CBX significantly prolonged the survival of orthotopic glioma mice by ~27% when compared with the control mice. The enhanced efficacy of MSC-TRAIL coupled with the minimal cytotoxic nature of CBX suggested a favorable clinical usage.
URI: http://scholarbank.nus.edu.sg/handle/10635/53629
Appears in Collections:Master's Theses (Open)

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