Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-MDR1 ribozymes

Synthesis, characterization, and biomedical applications of core–shell-type stimuli-responsive nanogels – Nanogel composed of poly[2-(N,N-diethylamino)ethyl methacrylate] core and PEG tethered chains

“…Thus, the released DOX plays an essential role in antitumor activity. Furthermore, the lower antitumor activity of the free DOX compared with DOX-loaded nanogel-8k-1.0 mol% against HuH-7 cells may be due to efflux mediated by the P-glycoprotein pump [83], which would decrease the intracellular drug concentration. In sharp contrast, the DOX released from the PEG/PDEAMA nanogel may reach the nucleus before can be pumped out, since DOXloaded nanogel-8k-1.0 mol% trafficked via the endocytic pathway may release the DOX at a distance from the P-glycoprotein pump [84].…”

Strategies for reversing drug resistance

“…Included among these are the use of hammerhead ribozymes against the MDR-1 gene and MDR-1-targeted ASOs (Liu et al, 1996;Dassow et al, 2000;Huesker et al, 2002;Nagata et al, 2002). Hammerhead ribozymes are oligonucleotides that possess enzymatic endoribonucleolytic cleavage activity (Irie et al, 1997).…”

“…However, several studies have demonstrated the feasibility of using adenoviral-based constructs. Furthermore, these studies have shown that using promoters with 'tumor specificity' such as AFP and CEA, expression can be limited to cells expressing these proteins (Gao et al, 1999;Huesker et al, 2002). Although the experimental results indicate that these strategies are effective in vitro, their clinical utility will be limited if a potent small molecule inhibitor of Pgp is identified.…”

Hepatocellular carcinoma: Epidemiology and clinical aspects

“…MDR phenotype, intrinsic or acquired, is almost constantly expressed in HCC and represents one of the major problems for cancer eradication by limiting the efficacy of chemotherapy (Petraccia et al, 2003). One of the most characteristic feature of the MDR phenotype in cancer cells is the expression of a glycoprotein of 170 kDa (P-gp) (Huesker et al, 2002) that binds different hydrophobic molecules, including chemotherapic agents, and exports them out of the cell by ATP hydrolysis (Huesker et al, 2002). This phenomenon favours tumor cell survival and proliferation.…”