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- W2968157430 abstract "1394 Interstitial transport is a rate-limiting step in plasmid DNA (pDNA) delivery in solid tumors. To enhance the transport, investigators have used pulsed electric fields to push pDNA through tumor tissues in vivo. However, the extent of pDNA movement is still limited, presumably due to the collagen component in extracellular matrix, which has been observed to be a major barrier to macromolecular transport. Therefore, we investigated effects of collagen remodeling on interstitial electrophoresis by pre-treatment of tumor bearing mice with a recombinant human relaxin (rh-Rlx), a peptide hormone known to induce interstitial collagen remodeling in solid tumors. In this study, two tumor lines (4T1 and B16.F10) in two different murine tumor models -- dorsal skin-fold chamber (DSC) and hind leg -- were examined. Effects of rh-Rlx on pDNA electrophoresis were measured either directly in the DSC model, or indirectly in the hind leg model via reporter gene expression. It was observed that rh-Rlx treatment reduced collagen levels in the hind leg tumors but not in the DSC tumors. This finding correlated with the results from mobility experiments, where rh-Rlx treatment enhanced gene expression in 4T1 hind leg tumors but did not increase the mobility in the DSC model. In addition, it was observed that pDNA-collagen binding could significantly limit interstitial transport. Taken together, the study demonstrated that relaxin could reduce collagen content and enhance transgene expression in hind leg tumors but had minimal effects on collagen content and pDNA electromobility in DSC tumors, suggesting that relaxin-induced enhancement in gene delivery was correlated with reduction in collagen content in solid tumors." @default.
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- W2968157430 date "2008-05-01" @default.
- W2968157430 modified "2023-09-23" @default.
- W2968157430 title "Effects of relaxin-induced collagen remodeling on electric field-mediated gene delivery" @default.
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