Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An IgE immunotoxin consisting of rat IgE myeloma protein, IR 162, conjugated via the heterobifunctional linking agent N-succinimidyl-3-(2-pyridyldithio)propionate to intact ricin was synthesized and evaluated. The capacity of this IgE-immunotoxin to bind to rat basophilic leukemia cells (RBL cells) and to inhibit RBL cell incorporation of [3H]leucine was assessed. The IgE-intact ricin conjugate sensitized RBL cells for histamine release after treatment with anti-IgE with a time-course of sensitization and dose-response equivalent to native IgE. Intact ricin and IgE-intact ricin were both cytotoxic to RBL cells as assessed by [3H]leucine incorporation. Lactose (50 mM) competed with intact ricin binding and toxicity such that more than 100 ng/ml ricin (8 times its IC50 in the absence of lactose) was required for ricin to kill RBL cells in the presence of lactose. Lactose (50 mM) was not able to fully inhibit 1-100 ng/ml IgE-ricin immunotoxin killing of RBL cells. Saturation of RBL cell IgE receptors by preincubation with IgE totally inhibited IgE-intact ricin-induced toxicity, in the presence of lactose, indicating that toxicity required IgE Fc receptor binding.
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PMID:IgE-immunotoxins. I. IgE-intact ricin. 244 11

Advancing biotechnology spurs the development of new pharmaceutically engineered gene delivery vehicles with the capability to target specific cell types. The low density lipoprotein (LDL) element of the terplex gene carrier is shown to be efficient in delivery to smooth muscle cells as well as inducing minimal toxicity to A7R5 cells in culture. The terplex system condensed plasmid DNA into polyplex sizes ranging from 100 to 400 nm. Terplex demonstrated higher transfection efficacy than Lipofectin. Lactose was conjugated through a poly(ethyl glycol) (PEG) spacer to poly(L-lysine) (PLL) to tailor a gene carrier capable of condensing plasmid DNA. This cationic polymer targeted Hep G2 cells preferentially in culture. The inclusion of a lactose targeting moiety greatly increased the efficacy of the gene carrier over PEG-PLL and Lipofectin. A biodegradable nanoparticle gene carrier, polysaccharide-graft-PLL and poly(D,L-lactic acid), was synthesized and characterized. The nanoparticle size was controllable by changing the copolymer concentration, where the particles could be as small as 60 nm. When polysaccharide was used in the copolymer, the nanoparticle became more DNA adsorbent. The JLI mAb was linked to PLL. This gene carrier targets the antigen confined to stage II immature cortical thymocytes for leukemia therapy. A 20,000 mw PLL backbone was sufficient for compaction of DNA. Folic acid linked to PLL through a PEG spacer is currently being studied for DNA condensation and delivery to membrane associated folate binding protein positive endothelial cancer cells.
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PMID:Tailoring new gene delivery designs for specific targets. 1076 41