PKCι induces differential phosphorylation of STAT3 to modify STAT3-related signaling pathways in pancreatic cancer cells.

An increasing number of studies have documented atypical protein kinase C isoform ι (PKCι) as an oncoprotein playing multifaceted roles in pancreatic carcinogenesis, including sustaining the transformed growth, prohibiting apoptosis, strengthening invasiveness, facilitating autophagy, as well as promoting the immunosuppressive tumor microenvironment of pancreatic tumors. In this study, we present novel evidence that PKCι overexpression increases STAT3 phosphorylation at the Y705 residue while decreasing STAT3 phosphorylation at the S727 residue in pancreatic cancer cells. We further demonstrate that STAT3 phosphorylation at Y705 and S727 residues is mutually antagonistic, and that STAT3 Y705 phosphorylation is positively related to the transcriptional activity of STAT3 in pancreatic cancer cells. Furthermore, we discover that PKCι inhibition attenuates STAT3 transcriptional activity via Y705 dephosphorylation, which appears to be resulted from enhanced phosphorylation of S727 in pancreatic cancer cells. Finally, we investigate and prove that by modulating the STAT3 activity, the PKCι inhibitor can synergistically enhance the antitumor effects of pharmacological STAT3 inhibitors or reverse the anti-apoptotic side effects incited by the MEK inhibitor, thereby posing as a prospective sensitizer in the treatment of pancreatic cancer cells.

Degradation behaviors of bioabsorbable P3/4HB monofilament suture in vitro and in vivo.

The biodegradable behaviors of monofilament suture made from bacterial biopolyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) was investigated both in lipase solution and by implant into rat tergal muscles. Results showed that the monofilament suture lost its tensile strength gradually accompanied by decrease of molecular weight. The suture retained approximately 65% of its original strength after lipase degradation for 12 weeks, whereas the molecular weight decreased from 4.5 x 10(5) to 3.8 x 10(5). However, the crystallinity of the suture, after lipase degradation for 12 weeks, increased from 27 to 33%. This may ascribe to improve orientation arrangement of molecular chain in the monofilament after the fragment from amorphous regions dissolved in the buffer solution. The roughness of surface morphology increased with degradation. Rat implantation showed no remarkable tissue responses during in vivo degradation. Foreign body reactions were much milder than chromic catgut, which is one of the most common commercially available sutures.

Alternative block polyurethanes based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and poly(ethylene glycol).

A series of amphiphilic alternative block polyurethane copolymers based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) and poly(ethylene glycol) (PEG) were synthesized by a coupling reaction between P3/4HB-diol and PEG-diisocyanate, with different 3HB, 4HB, PEG compositions and segment lengths. Stannous octanoate was used as catalyst. The chemical structure, alternative block arrangement, molecular weight and distribution were systematically characterized by FTIR, (1)H NMR, GPC and composition analysis. The thermal property was studied by DSC and TGA. Platelet adhesion study revealed that the alternative block polyurethanes possess excellent hemocompatibility. CCK-8 assay illuminated that the non-toxic block polyurethanes maintain rat aortic smooth muscle cells (RaSMCs) good viability. The in-vitro degradation of the copolymers in PBS buffer solution and in lipase buffer medium was investigated. Results showed that the copolymer films exhibit different degradation patterns in different media from surface erosion to diffusion bulk collapsing. The synthetic methodology for the alternative block polyurethanes provides a way to control the exact structure of the biomaterials and tailor the properties to subtle requirements.