Cellular inhibitor of apoptosis protein 1 (cIAP1) stability contributes to YM155 resistance in human gastric cancer cells.

YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells.

Thermosensitive and biocompatible cyclotriphosphazene micelles.

A new class of thermosensitive micellar cyclotriphosphazenes has been synthesized by stepwise nucleophilic substitutions of hexachlorocyclotriphosphazene with a hydrophilic methoxy poly(ethylene glycol) (MPEG) and a hydrophobic oligopeptide selected from tetra- to hexapeptides, and characterized by means of multinuclear ((1)H, (31)P) NMR spectroscopy, elemental analysis, and dynamic light scattering (DLS) method. All the amphiphilic trimers were found to form stable micelles by self-assembly in aqueous solution and to exhibit a lower critical solution temperature in the range of 20-48 degrees C in water depending on the hydrophilic to hydrophobic balance of the side groups. The micelles formed from the trimers bearing MPEG350 and a tetra- or pentapeptide were found to have a mean diameter of 13-14 nm, while, surprisingly, the trimers bearing longer MPEG550 and hexapeptides have shown remarkable contraction of their micelle size to a mean diameter of 7-8 nm, probably due to the strong intermolecular hydrophobic interactions among the hexapeptide groups of the trimers.

Synthesis and characterization of biocompatible poly(organophosphazenes) aiming for local delivery of protein drugs.

Biocompatible and thermosensitive poly(organophosphazenes) with a lower critical solution temperature (LCST) below body temperature have been designed with the aim for the local delivery of peptide and protein drugs. These polymers could be synthesized by introducing short chain tri- or tetraethylene glycol as a hydrophilic group and a dipeptide, GlyGluEt2 as a hydrophobic group into the polyphosphazene backbone. The local tolerance tests using rabbits have shown that our polymers are biocompatible.