Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of novel therapeutics for patients with bladder cancer is an important area of research, particularly considering the rather limited treatment options currently available. In this study, we designed and synthesized a conjugate of cancer-targeting selenadiazole derivative BSeC (benzo[1,2,5]selenadiazole-5-carboxylic acid) and the RGD (arginine-glycine-aspartate) peptide, which was used as a targeting molecule, using a PEI polymer as a linker. The results showed that BSeC-PEI-RGD formed core-shell spherical nanoparticles with improved stability in physiological and low pH solutions. The cancer-targeting design significantly enhanced cellular uptake of BSeC-PEI-RGD and decreased its cytotoxicity to normal cells. The nanoparticles could inhibit the migration and invasion of EJ and T24 bladder cancer cell and reduce cancer cell proliferation through the induction of reactive oxygen species (ROS)-dependent apoptosis and mitochondrial dysfunction. Further mechanistic studies using western blotting showed that BSeC-PEI-RGD triggered bladder cancer cell apoptosis by activating p38, JNK and p53 and by inactivating AKT and ERK. In summary, this study demonstrates the rational design of a polymer-based cancer-targeting nanosystem as a carrier of the selenadiazole derivative to treat bladder cancer.
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PMID:An integrin-targeting nanosystem as a carrier of the selenadiazole derivative to induce ROS-mediated apoptosis in bladder cancer cells, from rational design to action mechanisms. 3226 36

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5'-3' structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein-protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.
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PMID:Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy. 3234 13

This work describes the synthesis and characterisation of cationised dextran and pullulan modified with diethyl aminoethyl methacrylate (DEAEM) for gene delivery in cancer cells. To dextran and pullulan, PEI was conjugated to impart cationicity. These cationised polysaccharides were then modified with DEAEM monomer via Michael addition reaction and synthesised four different derivatives viz DPD I, DPD II, PPD I and PPD II. These vectors form nanocomplexes with DNA exhibiting positive zeta potential. These nanoplexes are cytocompatible in C6, HeLa and L929 cells. Transfection efficiency of these vectors was evaluated using p53 plasmid which demonstrated good transfection in cancer cells (C6 and HeLa) alone. Biodistribution studies of DPD II and PPD II in BALB/c mice shows its tendency to accumulate in liver tissue and not in any vital organs like brain, lungs and heart. In addition, these derivatives also exhibit good renal clearance.
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PMID:Cationised dextran and pullulan modified with diethyl aminoethyl methacrylate for gene delivery in cancer cells. 3256 49


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