We sought to improve the efficacy of gemcitabine (GEM) for the treatment of advanced pancreatic malignancy via local hyperthermia potentiated via a multi-functional nanoplatform permitting both heating and drug delivery. drug service providers produced strong T2 weighted image contrast and permitted efficient heating GSK1838705A using low magnetic field intensities. The thermo-mechanical response of HPC permitted triggered GEM launch confirmed during drug release studies. During studies pancreatic malignancy cell growth was significantly inhibited (~82% reduction) with chemohyperthermia compared to chemotherapy or hyperthermia only. Using PANC-1 xenografts in nude mice the delivery of injected GEM-loaded magnetic service providers (GEM-magnetic service providers) was visualized with both MRI and fluorescent imaging techniques. Chemohyperthermia with intra-tumoral injections of GEM-magnetic service providers (followed by heating) resulted in significant raises in apoptotic cell death compared to tumors treated with GEM-magnetic service providers injections only. Chemohyperthermia with GEM-magnetic service providers offers the potential to significantly improve the restorative effectiveness of gemcitabine for the treatment of pancreatic malignancy. delivery confirmation with non-invasive imaging techniques could permit patient-specific modifications restorative regimens for improve longitudinal results. settings prior to studies inside a xenograft animal model demonstrating the feasibility of this approach for the treatment of pancreatic cancer. Number 1 Schematic describing chemical reactions for synthesis of magnetic drug service providers. 2 RESULTS 2.1 Magnetic USPIO Cluster Characteristics 7 nm USPIO nanoparticles formed 59±6 nm clusters when coupled with the polyacrylic acid (Fig. 1 and Fig. 2a). The USPIO remedy was water dispersible and stable in aqueous remedy having a surface charge of ?48.7 mV (zeta potential). Space temp superparamagnetic behavior of these USPIO clusters was taken care of with a measured saturation magnetization of 61 emu/g (supplementary Fig. S1). Number 2 TEM images of (a) USPIO clusters (b) silica-coated USPIO clusters (c) porous silica-shell USPIO clusters and (d) HPC grafted porous silica-shell USPIO clusters (providing as magnetic drug service providers) (e) FT-IR spectra of magnetic drug service providers and HPC … GSK1838705A 2.2 Temp GSK1838705A Sensitive Magnetic Drug Carrier Characteristics The USPIO clusters were encapsulated within a porous silica shell and HPC capping material to form temp sensitive magnetic drug service providers (Fig. 1). TEM images of the Si coated USPIO clusters shown a discrete core/shell structure with 59±6 nm USPIO cluster cores and a silica shell GSK1838705A 18±2 nm in thickness (Fig. 2b). These particles were further etched to provide a porous structure conducive to drug-loading; these ~5 nm pores are demonstrated within TEM image in Fig. 2c. BET surface area of the etched silica shell encapsulated USPIO clusters was 113.5 m2/g which was increased from 14.7 m2/g of non-etched silica shell encapsulated USPIO clusters with generated porous structures. Residual PVP polymer within the porous silica shell was utilized for further changes with a temp sensitive hydroxypropyl cellulose (HPC) polymer. Hydrogen IKK-gamma (phospho-Ser31) antibody GSK1838705A bonding between HPC and PVP was confirmed with FTIR spectra (Fig. 2e). Absorption bands within the FTIR spectra display hydroxyl-stretching vibrations demonstrative of hydrogen bonds between the PVP and HPC. Broad transmission bands were observed between wavelengths of 3600 and 3100 cm?1 due to the stretching of hydroxyl organizations in the spectrum of HPC. Transition bands between wavelengths of 1000 and 1100 cm?1typical for ether linkages of HPC were found only in the spectrum of the HPC grafted particles. The magnetic drug service providers including polymers silica and magnetic clusters shown a saturation magnetization of 20 emu/g. At 300 K hysteresis behavior disappeared; these drug service providers exhibited superparamagnetic behavior with no coercivity or remanence (Fig. 3a). A superparamagnetic obstructing temp (Temperature Responsive Drug Release GEM drug loading GSK1838705A effectiveness for these HPC grafted magnetic drug service providers was ~66% with initial GEM loading of 20 wt%. launch was evaluated at two different temps (37 and 45 °C) as demonstrated in Fig. 4b. At both temps a two-phase launch pattern was observed with an initial fast ‘burst’ launch followed by a relatively slower sustained launch period. Drug launch was more rapid at 45 °C with cumulative drug launch of ~37% after 180 mins; only 8 % of the drug was released over a period of 180.
Background The incidence of venous thromboembolism (VTE) among patients undergoing hepatic surgery is usually poorly defined leading to varied use of VTE prophylaxis among surgeons. indications for surgery were malignant (90.8 %) and benign lesions (9.2 %). The majority of patients underwent a minor hepatectomy (<3 Couinaud segments; =402 67.1 %) while 195 (32.6 %) patients underwent a major hepatectomy (≥3 Couinaud segments). Three hundred seven (51.3 %) patients were started on VTE chemoprophylaxis preoperatively with 407 (67.8 %) patients receiving VTE chemoprophylaxis within 24 h of surgery. Twenty-eight (4.7 %) patients developed VTE; 20 (3.3 %) had deep venous thrombosis (DVT) 11 (1.8 %) had pulmonary embolism (PE) and three (0.5 %) developed both DVTand PE. Among the VTE patients 23 (82.1 %) had received VTE chemoprophylaxis. On multivariate analyses history of VTE (odds ratio [OR] 4.51 95 % confidence interval [CI] 1.81-17.22 =0.03) prolonged operative time (OR 1.17 per additional hour 95 % CI 1.04-1.32 =0.009) and increased length of stay (LOS) (OR 1.07 95 % CI 1.02-1.12 =0.01) were indie risk factors for VTE. Conclusion VTE GSK1838705A within 90 days of hepatic resection is usually common occurring in nearly one in 20 patients. Most VTE events occurred among patients who received current best practice prophylaxis for VTE. More aggressive strategies to identify and reduce the risk of VTE in patients at highest risk of VTE including those with a history of VTE extended operative time and prolonged LOS are warranted. <0.20). For statistical analyses values less than 0.05 (two-tailed) were deemed significant. Odds ratios (OR) were presented with 95 % confidence intervals (CI). All analyses were carried out with STATA version 12.0 (StataCorp LP College Station TX GSK1838705A USA). Results Patient and Surgical Details The study cohort consisted of 599 patients who underwent a planned hepatectomy. The median individual age was 58 years (interquartile range [IQR] 49 Males (49.6 %) and females (50.4 %) were evenly distributed in the cohort. The majority of patients (=489 81.6 %) were non-Hispanic white. Most patients (=441 74.1 %) were classified as ASA 3 with an ECOG overall performance GSK1838705A status of 0 (=544 90.8 %) while a subset had benign disease (=55 9.2 %). The most common indications for surgery were colorectal liver metastasis (=243 47.7 %) non-colorectal liver metastasis (=136 26.7 %) main liver malignancy (=120 23.6 %) or benign hepatic lesion (=55 9.2 %). The majority of patients had not received any previous liver-directed therapy (=419 70 %70 %); GSK1838705A about one-quarter of patients (=128 21.4 %) had received preoperative systemic chemotherapy. Of notice patients with malignancy as an indication for surgery were more likely to have had a prior history of VTE (OR 5.24 CI 1.41-19.17 = 402 67.1 %) 195 (32.6 %) patients underwent a major hepatectomy (three or more GSK1838705A Couinaud segments) and two patients (<1 %) underwent ablation only (Table 2). Of those who underwent a minor hepatectomy 155 (38.6 GSK1838705A %) had a non-anatomic hepatic wedge resection with the remaining undergoing a single or bi-segmentectomy (=247 61.4 %). Of those who underwent a major hepatectomy 135 (69.2 %) had a hemi-hepatectomy and 60 (31.8 %) had an extended hemi-hepatectomy. Overall median operative time was 4.6 h (IQR 3.5-6.2) and median estimated blood loss was 500 ml (IQR 250-900). Table Rabbit polyclonal to CDKN2A. 2 Operative and post-operative characteristics of patients undergoing planned hepatectomy VTE Prophylaxis Type and Administration Nearly all patients (=592 98.8 %) received either mechanical and/or chemoprophylaxis during their hospitalization. The majority of patients received chemoprophylaxis (= 450 75.1 %) while 142 (23.7 %) patients received only mechanical prophylaxis (i.e. sequential compression devices); seven (1.2 %) patients did not receive any type of VTE prophylaxis. Among the subset of patients receiving chemoprophylaxis 307 (68.2 %) patients were started on chemoprophylaxis in the preoperative setting prior to surgical incision and 406 (90.2 %) patients received chemoprophylaxis within 24 h post-operatively. The mind-boggling majority of patients received subcutaneous heparin either every 8 h (= 328 54.8 %) or 12 h (=111.