Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination.

Block copolymer of poly(ethylene glycol)-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-P[Asp(DET)]) has been originally introduced as a promising gene carrier by forming a nanomicelle with plasmid DNA. In this study, the polyplex micelle of PEG-SS-P[Asp(DET)], which disulfide linkage (SS) between PEG and cationic polymer can detach the surrounding PEG chains upon intracellular reduction, was firstly evaluated with respect to in vivo transduction efficiency and toxicity in comparison to that of PEG-P[Asp(DET)] in peritoneally disseminated cancer model. Intraperitoneal (i.

Impaired activities of cyclic adenosine monophosphate-responsive element binding protein, protein kinase A and calcium-independent phospholipase A2 are involved in deteriorated regeneration of cirrhotic liver after partial hepatectomy in rats.

Aims:   This study is to elucidate whether cyclic adenosine monophosphate (cAMP)-mediated signal is involved in lower regenerative potential of cirrhotic liver.

Methods:   Hepatic cAMP concentration, activities of protein kinase A (PKA), c-AMP responsive element binding protein (CREB) and Ca(2+) -independent phospholipase A(2) (iPLA2) and regeneration rate were compared between rats with thioacetamide-induced cirrhotic and normal livers after two-third hepatectomy.

Results:   The liver regeneration estimated by the rates of [(3) H]-thymidine incorporation and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic group.

Chemotherapy with hybrid liposomes for human breast tumors along with apoptosis in vivo.

Hybrid liposomes (HL-n) can be prepared by dissolving both vesicular and micellar molecules in buffer solution with ultrasonication. A clear solution of HL-n composed of 95 mol% dimyristoylphosphatidylcholine (DMPC) and 5 mol% polyoxyethylenedodecyl ether (C(12)(EO)(n), n=21 and 25) having hydrodynamic diameter of 100 nm could be kept over 1 month on the basis of dynamic light scattering measurements was obtained. (1) Increases of fusion and accumulation of HL-n including NBDPC as a fluorescence probe into human breast tumor (MDA-MB-453) cell membranes were observed.