Delivery of AIB1 siRNA by Ca2+/PEI/heparin composite nanoparticles effectively inhibits the growth of human breast cancer.

Here, a novel carrier fabricated by the interaction of negatively charged heparin and positively charged PEI and Ca2+ was investigated to deliver AIB1 siRNA into breast cancer cells both in vitro and in vivo. Ca2+/PEI/heparin nanoparticles were prepared by simply mixing heparin, PEI and CaCl2 aqueous solution. Heparin in the Ca2+/PEI/heparin nanoparticles (40.9% heparin, w/w) decreased the cytotoxicity of PEI. According to the MTT assay, Ca2+/PEI/heparin NPs are superior to commercial Lipofectamine 2000 considering the safety. The Ca2+/PEI/heparin NPs are able to deliver siAIB1 into breast cancer cells as effectively as Lipofectamine 2000 both in vitro and in vivo. The in vivo experiment also indicated that the NF-κB/BCL-2 signal pathway might be the downstream signal pathway of AIB1 in regulating breast cancer proliferation and progression.

Use of a collagen-sealing device in hepatic resection: a comparative analysis to standard resection technique.

BACKGROUND: Blood transfusion has been reported as an independent risk factor for poor outcome after liver resection in spite of its well known benefits. Refinements in parenchymal dissection have been pursued to reduce blood loss and transfusion. A collagen-sealing device (CSD) has recently been touted as an alternative technique that aids in blood conservation. We report the results of our initial series of patients undergoing a CSD-assisted resection and present a historical comparison. PATIENTS AND METHODS: Consecutive patients who were undergoing liver resection at a single tertiary cancer centre were enrolled in this study. The Ligasure Atlas device (Valleylab Inc., Division of Tyco Healthcare) was used for parenchymal division in the CSD group. Known blood conservation techniques (i.e. low central venous pressure, ultrasonic dissection, Pringle clamp) were standardized in both groups. Clinical and outcome variables including operative time, estimated blood loss and transfusion requirements were collected. All statistical analyses were performed with SAS version 8.2e. RESULTS: In all, 28 consecutive patients underwent CSD-assisted hepatic resection between October 2003 and September 2004. The control group included 188 patients treated between January 1991 and September 2003. In the CSD group, we observed a reduction in mean estimated blood loss (930 vs 1450 ml, p=0.002) and mean transfusion requirements (0.46 vs 1.19 units, p=0.002). There was no increase in operative time with the new instrument (326 vs 363 min, p=0.167). DISCUSSION: Use of a CSD has the potential to further reduce blood loss and transfusion requirements without increasing operative time.

Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer.

With the use of the PFA-100 platelet function analyzer to evaluate primary hemostasis in whole blood, measured as closure time (CT), neonates had shorter CTs than members of an adult control group. Multivariate analysis of measures that contribute to primary hemostasis showed that higher hematocrits and increased ristocetin cofactor activity were the best correlates for CTs of cord blood. These 2 factors may also enhance primary hemostasis in vivo and compensate for the impaired platelet function of the newborn.

Impaired signal transduction in neonatal platelets.

Previous in vitro studies of cord blood platelets from full-term and preterm neonates have demonstrated decreased responses to most physiologic agonists. This hyporesponsiveness is, in part, related to both deficient synthesis of, and response to, an important mediator of platelet function, thromboxane A2(TxA2). The poor response of neonatal platelets to TxA2 is not due to differences in TxA2 receptor binding characteristics, when compared with platelets from adult controls. Therefore, the postreceptor signal transduction pathway was investigated. The TxA2 receptor is linked via the trimeric GTP-binding protein, Gq, to phospholipase C-beta (PLC beta), and stimulation of platelets with the stable TxA2 mimetic, U46619, leads to activation of PLC beta and subsequent intracellular signaling events. U46619-induced 32P-phosphatidic acid formation, an index of PLC beta activation, was decreased in platelets of neonates (166 +/- 10%) when compared with adult controls (206 +/- 22%) (p < 0.05). Mobilization of intracellular calcium was impaired in platelets of newborns (175 +/- 49 nM) in comparison to adult controls (506 +/- 130 nM) (p < 0.01), after stimulation with U46619. U46619-stimulated GTPase activity was blunted in platelet membrane fractions from full-term neonates and almost absent in platelet membranes from preterm infants. Immunoblotting studies of the platelet membrane fractions, quantified by densitometric analysis, showed that levels of the G alpha q subunit were not significantly different between adult and neonate, and were not the cause of the marked differences in GTPase activity. These data suggest that signal transduction through the TxA2 receptor is affected by decreased activity of Gq in platelets of neonates, and that this defect in signal transduction through PLC beta contributes to the observed poor response of newborns' platelets to TxA2 and consequently to TxA2-dependent agonists such as collagen.