Stepwise inhibition of T cell recruitment at post-capillary venules by orally active desulfated heparins in inflammatory arthritis.

Identification of the structure-function relationship of heparin, particularly between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory activities, is critical in order to evaluate the biological effects of heparin, especially in conjunction with modifications for oral formulation. In this study, we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic modifications have differential effects on the blocking of interactions between sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH to interfere with T cell adhesion via selectin-sLeX interactions.

Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3.

We have designed a novel peptide, TK3, composed of three functional domains, a protein transduction domain, a TAT followed by three tandem repeats of a proapoptotic peptide, and a caspase-3 cleavage site, (KLAKLAK)(2)-DEVD. TK3 was able to transduce into cells and then activate caspase-3, which in turn cleaved TK3 to release additional (KLAKLAK)(2) peptides. (KLAKLAK)(2) was well transduced by TAT into tumor cells and was able to induce apoptosis in vitro and in vivo.

The effect on porcine bile duct of a metallic stent covered with a paclitaxel-incorporated membrane.

Background: Biliary metallic stents are covered with a membrane to prevent tumor ingrowth and to prolong patency. The only function of these stents is to promote biliary drainage; they have no antitumor effect.

Methods: A metallic stent was developed that is covered with a paclitaxel-incorporated membrane.