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Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.

Purpose: To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages., Materials and Methods: From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed., Results: Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found., Conclusion: Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance., (© RSNA, 2015.)

Cardiovascular diseases (CVDs) are some of the leading causes of death and bypass surgery is one of the common treatment options for the critical CVD patients. There is no ideal material available for arterial bypass surgery. Herein, a fibroin and keratin porous membrane was prepared by electro-spinning and proposed for tissue-engineered vascular grafts (TEVGs). The purified fibroin (F) and keratin (K) were mixed in different weight ratios of 9 : 1 (FK91), 8 : 2 (FK82), and 7 : 3 (FK73) to obtain a membrane. The SEM images revealed that the electro-spinned membranes have a fibrous interconnected porous structure. The average diameter of the membrane F, FK91, FK82 and FK73 was 5.74 ± 1.04, 4.20 ± 1.19, 2.94 ± 0.81 and 2.27 ± 0.65 μm, respectively. The ultimate tensile strength (UTS) of F, FK91, FK82 and FK73 was 2.09 ± 0.06, 2.02 ± 0.06, 1.81 ± 0.10 and 1.74 ± 0.12 MPa, respectively. The contact angle of F, FK91, FK82 and FK73 was 72.55 ± 0.55°, 66.39 ± 0.90°, 43.47 ± 0.04° and 33.65 ± 2.83°, respectively. The wettability results were in agreement with those of the cell adhesion to the electro-spinning membranes. The attached HUVECs on the developed membranes showed no cytotoxicity. The immunocytochemistry staining and qPCR analysis showed that the phenotype of the keratin-fibroin membrane was not altered. The results of the ultimate tensile strength, cell adhesion and microstructure revealed that FK82 is similar to native vessels and could be considered as a potential material for TEVGs.

The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.

Colorectal carcinoma (CRC) is characterized by unlimited proliferation and suppression of apoptosis, selective advantages for tumor survival, and chemoresistance. Lipopolysaccharide (LPS) signaling is involved in both epithelial homeostasis and tumorigenesis, but the relative roles had by LPS receptor subunits CD14 and Toll-like receptor 4 (TLR4) are poorly understood. Our study showed that normal human colonocytes were CD14(+)TLR4(-), whereas cancerous tissues were CD14(+)TLR4(+), by immunofluorescent staining. Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes. WT mice intracolonically administered a TLR4 antagonist displayed tumor reduction associated with enhanced apoptosis in cancerous tissues. Mucosa-associated LPS content was elevated in response to CRC induction. Epithelial apoptosis induced by LPS hypersensitivity in TLR4-mutant mice was prevented by intracolonic administration of neutralizing anti-CD14. Moreover, LPS-induced apoptosis was observed in primary colonic organoid cultures derived from TLR4 mutant but not WT murine crypts. Gene silencing of TLR4 increased cell apoptosis in WT organoids, whereas knockdown of CD14 ablated cell death in TLR4-mutant organoids. In vitro studies showed that LPS challenge caused apoptosis in Caco-2 cells (CD14(+)TLR4(-)) in a CD14-, phosphatidylcholine-specific phospholipase C-, sphingomyelinase-, and protein kinase C-ζ-dependent manner. Conversely, expression of functional but not mutant TLR4 (Asp299Gly, Thr399Ile, and Pro714His) rescued cells from LPS/CD14-induced apoptosis. In summary, CD14-mediated lipid signaling induced epithelial apoptosis, whereas TLR4 antagonistically promoted cell survival and cancer development. Our findings indicate that dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to carcinogenesis, and provide novel strategies for intervention against colorectal cancer.

Purpose: The purpose of the study is to evaluate the influence of respiratory-induced vena caval hemodynamic changes on filter migration/penetration., Materials and Methods: After placement of either a Gunther Tulip or Celect IVC filter, 101 consecutive patients scheduled for filter retrieval were prospectively enrolled in this study. Pre-retrieval CT scans were used to assess filter complications and to calculate cross-sectional area in three locations: at level of filter strut fixation, 3 cm above and 3 cm below. A 3D finite element simulation was constructed on these data and direct IVC pressure was recorded during filter retrieval. Cross-sectional areas and pressures of the vena cava were measured during neutral breathing and in Valsalva maneuver and identified filter complications were recorded. A statistical analysis of these variables was then performed., Results: During Valsalva maneuvers, a 60 % decrease of the IVC cross-sectional area and a fivefold increase in the IVC pressure were identified (p < 0.001). There was a statistically significant difference in the reduction of the cross-sectional area at the filter strut level (p < 0.001) in patient with filter penetration. Difficulty in filter retrieval was higher in penetrated or tilted filters (p < 0.001; p = 0.005). 3D computational models showed significant IVC deformation around the filter during Valsalva maneuver., Conclusion: Caval morphology and hemodynamics are clearly affected by Valsalva maneuvers. A physiological reduction of IVC cross-sectional area is associated with higher risk of filter penetration, despite short dwell times. Physiologic data should be used to improve future filter designs to remain safely implanted over longer dwell times.

Gut microbiota and lipopolysaccharide (LPS) signaling have been associated with colon cancer development. Our recent findings demonstrated that LPS receptor subunits expressed on colonocytes have antagonistic roles in cell death and tumorigenesis: epithelial toll-like receptor 4 (TLR4) confers resistance to the apoptosis induced by its co-receptor CD14 and contributes to epithelial transition to cancer.

MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated from the single miRNA hairpin precursor. However, current miRNA annotations lack comprehensive 5p-arm/3p-arm feature annotations. Among known human mature miRNAs, only half of them are annotated with arm features. This generated ambiguous results in many miRNA-Sequencing (miRNA-Seq) studies. In this report, we have interrogated the TCGA (the Cancer Genome Atlas) miRNA expression datasets with an improved, fully annotated human 5p-arm and 3p-arm miRNA reference list. By utilizing this comprehensive miRNA arm-feature annotations, enhanced determinations and clear annotations were achieved for the miRNA isoforms (isomiRs) recognized from the sequencing reads. In the gastric cancer (STAD) dataset, as an example, 32 5p-arm/3p-arm OPEN ACCESS J. Clin. Med. 2015, 4 1799 specific miRNAs were found to be down-regulated and 24 5p-arm/3p-arm specific miRNAs were found to be up-regulated. We have further extended miRNA biomarker discoveries to additional TCGA miRNA-Seq datasets and provided extensive expression information on 5p-arm/3p-arm miRNAs across multiple cancer types. Our results identified several miRNAs that could be potential common biomarkers for human cancers.

Background: Systemic thrombolysis for acute pulmonary embolism (PE) carries up to a 20% risk of major bleeding, including a 2% to 5% risk of hemorrhagic stroke. We evaluated the safety and effectiveness of catheter-directed therapy (CDT) as an alternative treatment of acute PE., Methods: One hundred one consecutive patients receiving CDT for acute PE were prospectively enrolled in a multicenter registry. Massive PE (n = 28) and submassive PE (n = 73) were treated with immediate catheter-directed mechanical or pharmacomechanical thrombectomy and/or catheter-directed thrombolysis through low-dose hourly drug infusion with tissue plasminogen activator (tPA) or urokinase. Clinical success was defined as meeting all the following criteria: stabilization of hemodynamics; improvement in pulmonary hypertension, right-sided heart strain, or both; and survival to hospital discharge. Primary safety outcomes were major procedure-related complications and major bleeding events., Results: Fifty-three men and 48 women (average age, 60 years [range, 22-86 years]; mean BMI, 31.03 ± 7.20 kg/m2) were included in the study. The average thrombolytic doses were 28.0 ± 11 mg tPA (n = 76) and 2,697,101 ± 936,287 International Units for urokinase (n = 23). Clinical success was achieved in 24 of 28 patients with massive PE (85.7%; 95% CI, 67.3%-96.0%) and 71 of 73 patients with submassive PE (97.3%; 95% CI, 90.5%-99.7%). The mean pulmonary artery pressure improved from 51.17 ± 14.06 to 37.23 ± 15.81 mm Hg (n = 92) (P < .0001). Among patients monitored with follow-up echocardiography, 57 of 64 (89.1%; 95% CI, 78.8%-95.5%; P < .0001) showed improvement in right-sided heart strain. There were no major procedure-related complications, major hemorrhages, or hemorrhagic strokes., Conclusions: CDT improves clinical outcomes in patients with acute PE while minimizing the risk of major bleeding. At experienced centers, CDT is a safe and effective treatment of both acute massive and submassive PE., Trial Registry: ClinicalTrials.gov; No.: NCT01097928; URL: www.clinicaltrials.gov.

MicroRNAs are derived from endogenous stem-loop precursors, and play important roles in various biological processes. From next-generation sequencing data, it is suggested that both the 5p-arm and 3p-arm of mature miRNAs could be generated from a single miRNA hairpin precursor; however, the current miRNA databases fail to provide comprehensive arm annotation features, which could result in ambiguous and incomplete analyses. In the present report, we have annotated over 99.7% of miRNAs with the correct 5p-arm and 3p-arm features. The length distribution of all annotated miRNAs is around 22 nucleotides; however, the 5p-arm miRNAs seem to be longer than those of the 3p-arm, which is evident in the 23-nucleotide group. Our study effort generates comprehensive miRNA arm-feature annotation which can be utilized for better interrogation of miRNAs. In further analysis of human gastric cancer tissues, we identified 38 down-regulated miRNAs and 22 up-regulated arm-specific miRNAs using this new comprehensives miRNA list., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Epidermal growth factor receptor (EGFR) is often constitutively stimulated in many cancers owing to the binding of ligands such as epidermal growth factor (EGF). Therefore, it is necessary to investigate the interaction between EGFR and its targeting biomolecules. The main aim of this study was to estimate the binding affinity and adhesion force of two targeting molecules, anti-EGFR monoclonal antibody (mAb LA1) and the peptide GE11 (YHWYGYTPQNVI), with respect to EGFR and to compare these values with those obtained for the ligand, EGF. Surface plasmon resonance (SPR) was used to determine the equilibrium dissociation constant (KD) for evaluating the binding affinity. Atomic force microscopy (AFM) was performed to estimate the adhesion force. In the case of EGFR, the KD of EGF, GE11, and mAb LA1 were 1.77 × 10-7, 4.59 × 10-4 and 2.07 × 10-9, respectively, indicating that the binding affinity of mAb LA1 to EGFR was higher than that of EGF, while the binding affinity of GE11 to EGFR was the lowest among the three molecules. The adhesion force between EGFR and mAb LA1 was 210.99 pN, which is higher than that observed for EGF (209.41 pN), while the adhesion force between GE11 and EGFR was the lowest (59.51 pN). These results suggest that mAb LA1 binds to EGFR with higher binding affinity than EGF and GE11. Moreover, the adhesion force between mAb LA1 and EGFR was greater than that observed for EGF and GE11. The SPR and AFM experiments confirmed the interaction between the receptor and targeting molecules. The results of this study might aid the screening of ligands for receptor targeting and drug delivery.

A 46-year-old woman underwent inferior vena cava filter placement before bariatric surgery and returned within 6 months for routine removal. She complained of a 1-week history of severe chest pain, and during retrieval, two fractured filter components were identified including one arm in the right ventricle. The filter body and one fragment were successfully retrieved, but the fragment in the right ventricle was refractory to percutaneous retrieval. During open-heart surgery, the fragment was found traversing through the ventricular wall resulting in cardiac tamponade. Electron microscopic fragment analysis revealed high-cycle metal fatigue indicating the filter design failed to withstand this patient's natural inferior vena cava biomechanical motions., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Elastic fibers are major constituents of the extracellular matrix (ECM) in dynamic tissues in the human body, and regulation of elastin and fibrillin-1 expression mediates the formation of these fibers. Traditional assays for the measurement of elastin and fibrillin-1, such as western blotting, Luna staining and immunostaining, are relatively complex and time-consuming. Thus, a relatively simple assay system that also provides rational results is urgently needed. In the study, we aimed to develop a human cell-based assay system that can be used to analyze functional compounds using the promoters of elastin (ELN) and fibrillin-1 (FBN1) genes integrated with a secreted alkaline phosphatase (SEAP) reporter in normal human fibroblast cells. We used this system to assess anti-aging compounds. We used several regulators of elastinogenesis, including retinol, coenzyme Q10, deoxyArbutin and Elestan(TM) (Manilkara multinervis leaf extract), to verify the efficacy of this assay system. Our results demonstrate that this assay system can be used as a fast and realistic method for identifying anti-aging components for future use in foods, cosmetics and drugs.

Purpose: To optimize surveillance schedules for the detection of recurrent hepatocellular carcinoma (HCC) after liver-directed therapy., Materials and Methods: New methods have emerged that allow quantitative analysis and optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. These methods were applied to 1,766 consecutive chemoembolization, radioembolization, and radiofrequency ablation procedures performed on 910 patients between 2006 and 2011. Computed tomography or magnetic resonance imaging performed just before repeat therapy was set as the time of "recurrence," which included residual and locally recurrent tumor as well as new liver tumors. Time-to-recurrence distribution was estimated by Kaplan-Meier method. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay., Results: Recurrence is 6.5 times more likely in the first year after treatment than in the second. Therefore, screening should be much more frequent in the first year. For eight time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared with published schedules and is cost-effective., Conclusions: The calculated optimal surveillance schedules include shorter-interval follow-up when there is a higher probability of recurrence and longer-interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay or diagnostic delay can be optimized within a specified acceptable cost., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Aim: To study changes produced within the inferior vena cava (IVC) during respiratory movements and identify their possible clinical implications., Methods: This study included 100 patients (46 women; 54 men) over 18 years of age who required an abdominal computed tomography (CT) and central venous access. IVC cross-sectional areas were measured on CT scans at three levels, suprarenal (SR), juxtarenal (JR) and infrarenal (IR), during neutral breathing and again during the Valsalva maneuver. All patients were instructed on how to perform a correct Valsalva maneuver. In order to reduce the total radiation dose in our patients, low-dose CT protocols were used in all patients. The venous blood pressure (systolic, diastolic and mean) was invasively measured at the same three levels with neutral breathing and the Valsalva maneuver during venous port implantation. From CT scans, three-dimensional models of the IVC were constructed and a collapsibility index was calculated for each patient. These data were then correlated with venous pressures and cross-sectional areas., Results: The mean patient age was 51.64 ± 12.01 years. The areas of the ellipse in neutral breathing were 394.49 ± 85.83 (SR), 380.10 ± 74.55 (JR), and 342.72 ± 49.77 mm(2) (IR), and 87.46 ± 18.35 (SR), 92.64 ± 15.36 (JR) and 70.05 ± 9.64 mm(2) (IR) during the Valsalva (Ps < 0.001). There was a correlation between areas in neutral breathing and in the Valsalva maneuver (P < 0.05 in all areas). Large areas decreased more than smaller areas. The collapsibility indices were 0.49 ± 0.06 (SR), 0.50 ± 0.04 (JR) and 0.50 ± 0.04 (IR), with no significant differences in any region. Reconstructed three-dimensional models showed a flattening of the IVC during Valsalva, adopting an ellipsoid cross-sectional shape. The mean pressures with neutral breathing were 9.44 ± 1.78 (SR), 9.40 ± 1.44 (JR) and 8.84 ± 1.03 mmHg (IR), and 81.08 ± 21.82 (SR), 79.88 ± 19.01 (JR) and 74.04 ± 16.56 mmHg (IR) during Valsalva (Ps < 0.001). There was a negative correlation between cross-sectional caval area and venous blood pressure, but this was not statistically significant in any of the cases. There was a significant correlation between diastolic and mean pressures measured during neutral breathing and in Valsalva., Conclusion: Respiratory movements have a major influence on IVC dynamics. The increase in intracaval pressure during Valsalva results in a significant decrease in the IVC cross-sectional area.

Antibiotic usage promotes intestinal colonization of antibiotic-resistant bacteria. However, whether resistant bacteria gain dominance in enteric microflora or disseminate to extraintestinal viscera remains unclear. Our aim was to investigate temporal diversity changes in microbiota and transepithelial routes of bacterial translocation after antibiotic-resistant enterobacterial colonization. Mice drinking water with or without antibiotics were intragastrically gavaged with ampicillin-resistant (Amp-r) nonpathogenic Escherichia coli (E. coli) and given normal water afterward. The composition and spatial distribution of intestinal bacteria were evaluated using 16S rDNA sequencing and fluorescence in situ hybridization. Bacterial endocytosis in epithelial cells was examined using gentamicin resistance assay and transmission electromicroscopy. Paracellular permeability was assessed by tight junctional immunostaining and measured by tissue conductance and luminal-to-serosal dextran fluxes. Our results showed that antibiotic treatment enabled intestinal colonization and transient dominance of orally acquired Amp-r E. coli in mice. The colonized Amp-r E. coli peaked on day 3 postinoculation and was competed out after 1 wk, as evidenced by the recovery of commensals, such as Escherichia, Bacteroides, Lachnospiraceae, Clostridium, and Lactobacillus. Mucosal penetration and extraintestinal dissemination of exogenous and endogenous enterobacteria were correlated with abnormal epithelial transcytosis but uncoupled with paracellular tight junctional damage. In conclusion, antibiotic-induced enteric dysbiosis predisposes to exogenous infection and causes systemic dissemination of both antibiotic-resistant and commensal enterobacteria through transcytotic routes across epithelial layers. These results may help explain the susceptibility to sepsis in antibiotic-resistant enteric bacterial infection., (Copyright © 2014 the American Physiological Society.)

Abnormal bacterial adherence and internalization in enterocytes have been documented in Crohn disease, celiac disease, surgical stress, and intestinal obstruction and are associated with low-level interferon (IFN)-γ production. How commensals gain access to epithelial soma through densely packed microvilli rooted on the terminal web (TW) remains unclear. We investigated molecular and ultrastructural mechanisms of bacterial endocytosis, focusing on regulatory roles of IFN-γ and myosin light chain kinase (MLCK) in TW myosin phosphorylation and brush border fanning. Mouse intestines were sham operated on or obstructed for 6 hours by loop ligation with intraluminally administered ML-7 (a MLCK inhibitor) or Y27632 (a Rho-associated kinase inhibitor). After intestinal obstruction, epithelial endocytosis and extraintestinal translocation of bacteria were observed in the absence of tight junctional damage. Enhanced TW myosin light chain phosphorylation, arc formation, and brush border fanning coincided with intermicrovillous bacterial penetration, which were inhibited by ML-7 and neutralizing anti-IFN-γ but not Y27632. The phenomena were not seen in mice genetically deficient for long MLCK-210 or IFN-γ. Stimulation of human Caco-2BBe cells with IFN-γ caused MLCK-dependent TW arc formation and brush border fanning, which preceded caveolin-mediated bacterial internalization through cholesterol-rich lipid rafts. In conclusion, epithelial MLCK-activated brush border fanning by IFN-γ promotes adherence and internalization of normally noninvasive enteric bacteria. Transcytotic commensal penetration may contribute to initiation or relapse of chronic inflammation., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Expression of α-amylase genes in rice is induced not only by sugar starvation and gibberellin (GA) but also by O2 deficiency. Promoters of two rice α-amylase genes, αAmy3 and αAmy8, have been shown to direct high-level production of recombinant proteins in rice suspension cells and germinated seeds. In the present study, we modified the cis-acting DNA elements within the sugar/GA response complex (SRC/GARC) of αAmy8 promoter. We found that addition of a G box and duplicated TA box leads to high-level expression of αAmy8 SRC/GARC and significantly enhances αAmy8 promoter activity in transformed rice cells and germinated transgenic rice seeds. We also show that these modifications have drastically increased the activity of αAmy8 promoter in rice seedlings under hypoxia. Our results reveal that the G box and duplicated TA box may play important roles in stimulating promoter activity in response to hypoxia in rice. The modified αAmy8 promoter was used to produce the recombinant human epidermal growth factor (hEGF) in rice cells and hypoxic seedlings. We found that the bioactive recombinant hEGF are stably produced and yields are up to 1.8% of total soluble protein (TSP) in transformed rice cells. The expression level of synthetic hEGF containing preferred rice codon usage comprises up to 7.8% of TSP in hypoxic transgenic seedlings. Our studies reveal that the modified αAmy8 promoter can be applicable in establishing a novel expression system for the high-level production of foreign proteins in transgenic rice cells and seedlings under hypoxia.

This research investigated the electrocoagulation of municipal solid waste incineration (MSWI) fly ash at a liquid-to-solid ratio (L/S) of 20:1. The leachate that was obtained from this treatment was recovered for reutilization. Two different anodic electrodes were investigated, and two unit runs were conducted. In Unit I, the optimum anode was chosen, and in Unit II, the optimum anode and the recovered leachate were used to replace deionized water for repeating the same electrocoagulation experiments. The results indicate that the aluminum (Al) anode performed better than the iridium oxide (IrO2) anode. The electrocoagulation technique includes washing with water, changing the composition of the fly ash, and stabilizing the heavy metals in the ash. Washing with water can remove the soluble salts from fly ash, and the fly ash can be converted into Friedel's salt (3CaO·Al2O3·CaCl2·10H2O) under an uniform electric field and the sacrificial release of Al(+3) ions, which stabilizes the toxic heavy metals and brings the composition of the fly ash to within the regulatory limits of the toxicity characteristic leaching procedure (TCLP). Use of the Al anode to manage the MSWI fly ash and the leachate obtained from the electrocoagulation treatment is therefore feasible., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The phenyl-amino-thiazole (PAT) templates of methoxylbenzoyl-aryl-thiazole are potent agents against cancer by inhibiting tubulin polymerization in the nanomolar range. Herein, a radioiodinated PAT, [(123)I]-PAT 1, was prepared via a tributylstannyl precursor and [(123)I]iodide through electrophilic aromatic radioiodination. Radiolabelling of [(123)I]-PAT 1 was achieved in less than 15 min, with a radiochemical purity of over 99%. The accumulated radioactivity in tumor cellular uptake experiments suggested that [(123) I]-PAT could serve as a potential radioprobe for targeting tumor cells., (Copyright © 2014 John Wiley & Sons, Ltd.)

FleQ is a master regulator that controls bacterial flagellar gene expression. It is a unique enhancer-binding protein or repressor protein comprising an N-terminal FleQ domain, an AAA(+)/ATPase σ54-interaction domain and a helix-turn-helix DNA-binding domain. FleN is a putative ATPase with a deviant Walker A motif that works together with FleQ by binding to the FleQ N-terminal domain to fully express pel, psl and cdr operons in the presence of c-di-GMP to enhance biofilm formation. Stenotrophomonas maltophilia is an emerging human pathogen that causes fatal infections in humans. In order to understand the interaction between the FleN and FleQ domains and its effect on S. maltophilia biofilm formation, determination of the FleQ-c-di-GMP and FleN-FleQ-c-di-GMP complex structures was embarked upon. Towards this goal, the FleQ N-terminal domain from S. maltophilia was first cloned and expressed in Escherichia coli. Native and SeMet-labelled FleQ domains were successfully crystallized and diffracted to resolutions of 2.08 and 2.58 Å, respectively.

A 48-year-old man presented with symptomatic inferior vena cava (IVC) occlusion from a chronically thrombosed and embedded Vena Tech LGM filter resulting in exercise intolerance from diminished cardiac preload and postthrombotic syndrome from chronic venous insufficiency. The patient was treated using a new PRIME technique--Piecemeal Removal by Intentional MEchanical fracture--to achieve successful filter retrieval 16 years after implantation. Removal of the obstructing filter permitted endovascular IVC recanalization with restoration of venous outflow and alleviation of venous obstructive symptoms. Cardiac preload was restored, allowing the patient to resume long-distance running, and he successfully completed a half-marathon 3 months after treatment., (© SIR, 2013.)

Background: Although chronically implanted inferior vena cava filters may result in filter-related morbidity, there is currently no routine option for removing such filters when they become firmly embedded along the vena cava endothelium., Methods and Results: During a 3-year period, 100 consecutive patients were prospectively enrolled in a single-center study. There were 42 men and 58 women (mean age, 46 years; limits, 18-76 years). Retrieval indications included filter-related acute inferior vena cava thrombosis, chronic inferior vena cava occlusion, and pain from retroperitoneal or bowel penetration. Filter retrieval was also performed to prevent risks from prolonged implantation and to potentially eliminate the need for lifelong anticoagulation. After standard methods failed, photothermal tissue ablation was attempted with a laser sheath powered by a 308-nm xenon chloride excimer laser. Applied forces were recorded with a digital tension meter before and during laser activation. Laser-assisted retrieval was successful in 98.0% (95% confidence interval [CI], 93.0%-99.8%) with mean implantation of 855 days (limits, 37-6663 days; >18 years). The following filter types were encountered in this study: Günther-Tulip (n=34), Celect (n=12), Option (n=17), Optease (n=20, 1 failure), TrapEase (n=6, 1 failure), Simon-Nitinol (n=1), 12F Stainless Steel Greenfield (n=4), and Titanium Greenfield (n=6). The average force during failed standard retrievals was 7.2 versus 4.6 pounds during laser-assisted retrievals (P<0.0001). The major complication rate was 3.0% (95% CI, 0.6%-8.5%), the minor complication rate was 7.0% (95% CI, 0.3%-13.9%), and there were 4 adverse events (2 coagulopathic hemorrhages, 1 renal infarction, and 1 cholecystitis; 4.0%; 95% CI, 1.1%-9.9%) at mean follow-up of 500 days (limits, 84-1079 days). Scar tissue ablation was histologically confirmed in 96.0% (95% CI, 89.9%-98.9%). Successful retrieval allowed cessation of anticoagulation in 30 of 30 (100%) patients and alleviated morbidity in 23 of 24 patients (96%)., Conclusions: Excimer laser-assisted removal is effective in removing embedded inferior vena cava filters refractory to standard retrieval and high force. This method can be safely used to prevent and alleviate filter-related morbidity., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01158482.

This study evaluated a radioiodinated deoxycytidine analog, (131)I-5-iodo-2'-deoxycytidine ([(131)I]ICdR), as a novel proliferation probe and compared it with (131)I-5-iodo-2'-deoxyuridine ([(131)I]IUdR) in a NG4TL4 sarcoma-bearing mouse model. As an imaging agent, the biological characteristics of [(123)I]IUdR is not satisfactory due to its metabolic instability and short biological half-life in vivo. With [(123)I]ICdR/SPECT it was possible to clearly delineate the tumor lesion at 1h post-injection (tumor-to-muscle ratio 7.74) in tumor-bearing mice. The results of biodistribution were consistent with those observed in scintigraphic imaging. This study demonstrated that [(131)I]ICdR is a more promising SPECT probe than [(131)I]IUdR for imaging proliferation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cancer cells may survive under oxygen and nutrient deprivation by metabolic reprogramming for high levels of anaerobic glycolysis, which contributes to tumor growth and drug resistance. Abnormally expressed glucose transporters (GLUTs) are colocalized with hypoxia (Hx) inducible factor (HIF)1α in peri-necrotic regions in human colorectal carcinoma. However, the underlying mechanisms of anti-necrotic resistance conferred by glucose metabolism in hypoxic cancer cells remain poorly understood. Our aim was to investigate signaling pathways of Hx-induced necroptosis and explore the role of glucose pyruvate metabolite in mechanisms of death resistance. Human colorectal carcinoma cells were Hx exposed with or without glucose, and cell necroptosis was examined by receptor-interacting protein (RIP)1/3 kinase immunoprecipitation and (32)P kinase assays. Our results showed increased RIP1/3 complex formation and phosphorylation in hypoxic, but not normoxic cells in glucose-free media. Blocking RIP1 signaling, by necrostatin-1 or gene silencing, decreased lactodehydrogenase (LDH) leakage and plasma membrane disintegration. Generation of mitochondrial superoxide was noted after hypoxic challenge; its reduction by antioxidants inhibited RIP signaling and cell necrosis. Supplementation of glucose diminished the RIP-dependent LDH leakage and morphological damage in hypoxic cells, whereas non-metabolizable sugar analogs did not. Hypoxic cells given glucose showed nuclear translocation of HIF1α associated with upregulation of GLUT-1 and GLUT-4 expression, as well as increase of intracellular ATP, pyruvate and lactate levels. The glucose-mediated death resistance was ablated by iodoacetate (an inhibitor to glyceraldehyde-3-phosphate dehydrogenase), but not by UK5099 (an inhibitor to mitochondrial pyruvate carrier), suggesting that glycolytic pathway was involved in anti-necrotic mechanism. Lastly, replacing glucose with cell-permeable pyruvate derivative also led to decrease of Hx-induced necroptosis by suppression of mitochondrial superoxide in an energy-independent manner. In conclusion, glycolytic metabolism confers resistance to RIP-dependent necroptosis in hypoxic cancer cells partly through pyruvate scavenging of mitochondrial free radicals.

Purpose: To evaluate clinical outcomes, characterize adherent tissue, and analyze inferior vena cava (IVC) filter fractures in patients undergoing complex retrieval for management of filter-related complications. To elucidate mechanisms of filter fracture by radiographic and electron microscopic (EM) evaluation., Materials and Methods: Over 2.5 years, 50 consecutive patients with fractured and/or penetrating filter components were prospectively enrolled into a single-center study. There were 19 men and 31 women (mean age, 42 y; range, 15-73 y). All patients underwent complex filter retrieval after failure of standard methods, and retrieval indications along with resultant clinical outcomes were evaluated. Specimens with adherent tissue underwent histologic analysis, and all fractured components were studied with EM., Results: Retrieval was successful in all 50 cases (mean implantation, 815 d; range, 20-2,599 d) among the following filters: G2X (n = 23),G2 (n = 9), Eclipse (n = 3), Recovery (n = 4), ALN (n = 1), Celect (n = 7), OptEase (n = 2), and Simon Nitinol (n = 1). Mean indwell time in fractured filters (n = 31) was 1,082 days, versus 408 days in nonfractured filters (n = 19; P = .00169). Neointimal hyperplasia/fibrosis was seen in 46 of 48 specimens with adherent tissue (96%). Among 61 fractured components from conical filters, 35 had extravascular penetration whereas 26 remained intravascular (11 free-floating in IVC, 15 embolized centrally), and EM revealed fracture modes of high-cycle fatigue (n = 53), overload (n = 6), and indeterminate (n = 2). Following retrieval, previously prescribed lifelong anticoagulation was discontinued in 30 of 31 patients (97%). Filter-related symptoms from IVC occlusion, component embolization, and penetration-induced abdominal pain, duodenal injury, and/or small-bowel volvulus were alleviated in all 26 cases (100%). There were no long-term complications at a mean follow-up of 371 days (range, 67-878 d)., Conclusions: The risk of filter fracture increases after 408 days (ie,>1 y) of implantation and is associated with symptomatic extravascular penetration and/or intravascular embolization. Complex methods can be used to safely remove these devices, alleviate filter-related morbidity, and allow cessation of anticoagulation., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells. Because EGF is the major in vivo competitor to PHA-E in clinical application, PHA-E must be proved that has better affinity to EGFR than EGF. This study would focus on how PHA-E tightly bind to EGFR and the results would compare with EGF. The adhesion force, measured by AFM, between EGFR and PHA-E was 207.14±74.42 pN that was higher than EGF (183.65±86.93 pN). The equilibrium dissociation constant of PHA-E and EGF to EGFR was 2.4 10(-9)±1.4 10(-9) and 7.3 10(-8)±2.7 10(-8), respectively, that could evaluate binding affinity. The result showed that binding affinity of PHA-E to EGFR was one order higher than EGF to EGFR. In the results of flow cytometer and confocal microscope, we found binding efficiency of EGF to EGFR was decrease as the concentration of PHA-E increased. In the analysis of Western blot, treatment of A-549 cells with PHA-E resulted in a dose-dependent decrease in EGFR phosphorylation. In conclusion, we found that PHA-E had better adhesion force and binding affinity to EGFR than that of the EGF. The interaction between PHA-E and EGFR could block EGF binding and then inhibit EGFR phosphorylation. PHA-E could be developed into a new target molecule for lung cancer treatment that could be immobilized on the drug carrier to guide therapeutic particles to the tumor site.

The periodic expression and destruction of several cyclins are the most important steps for the exact regulation of cell cycle. Cyclins are degraded by the ubiquitin-proteasome system during cell cycle. Besides, a short sequence near the N-terminal of cyclin B called the destruction box (D-box; CDB) is also required. Fluorescent-protein-based reporter gene system is insensitive to analysis because of the overly stable fluorescent proteins. Therefore, in this study, we use human CDB fused with both enhanced green fluorescent protein (EGFP) at C-terminus and red fluorescent protein (RFP, DsRed) at N-terminus in the transfected human melanoma cells to examine the effects of CDB on different fluorescent proteins. Our results indicated that CDB-fused fluorescent protein can be used to examine the slight gene regulations in the reporter gene system and have the potential to be the system for screening of functional compounds in the future.

This work demonstrated a-Si:H thin-film solar cells with backside TiO(2)/ SiO(2) distributed Bragg reflectors (DBRs) for applications involving building-integrated photovoltaics (BIPVs). Selectively transparent solar cells are formed by adjusting the positions of the DBR stop bands to allow the transmission of certain parts of light through the solar cells. Measurement and simulation results indicate that the transmission of blue light (430 ~500 nm) with the combination of three DBR mirrors has the highest increase in conversion efficiency.

Purpose: Compression of the left common iliac vein (CIV; LCIV) is a known risk factor for lower-extremity deep vein thrombosis (DVT). This study was performed to model the probability of DVT based on LCIV diameter and apply this to a quantitative DVT risk factor scoring system., Materials and Methods: Medical records were used to identify female patients younger than 45 years of age who were diagnosed with lower-extremity DVT (n = 21) and age-matched control subjects (n = 26) who presented to the emergency department with abdominal pain. Minimum CIV diameters were measured on computed tomography. Based on published reporting standards, 13 risk factors were scored for patients diagnosed with left-sided DVT and for control subjects. The association between vein diameter and DVT was examined by Mann-Whitney test. Odds of DVT based on vein diameter was assessed by logistic regression., Results: Mean minimum LCIV diameters were 4.0 mm for patients with DVT and 6.5 mm for patients without DVT (P = .001). The odds of left DVT increased by a factor of 1.68 for each millimeter decrease in LCIV diameter (odds ratio = 1.68; P = .006; 95% confidence interval, 1.16-2.43). As the risk factor score increased, the relationship between diameter and risk for DVT became stronger; identical LCIV diameters were associated wtih a higher probability of developing DVT if the risk factor score was higher., Conclusions: Stenosis of the LCIV was found to be a strong independent risk factor for development of DVT. Moreover, each millimeter decrease in CIV diameter increased the odds of DVT by a factor of 1.68., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Cyclic di-GMP (c-di-GMP) is a novel secondary-messenger molecule that is involved in regulating a plethora of important bacterial activities through binding to an unprecedented array of effectors. Proteins with a canonical PilZ domain that bind c-di-GMP play crucial roles in regulating flagellum-based motility. In contrast, noncanonical type II PilZ domains that do not effectively bind c-di-GMP regulate twitching motility, which is dependent on type IV pili (T4P). Recent data indicate that T4P biogenesis is initiated via the interaction of a noncanonical type II PilZ protein with the GGDEF/EAL-domain protein FimX and the pilus motor protein PilB at high c-di-GMP concentrations. However, the molecular details of such interactions remain to be elucidated. In this manuscript, the first hetero-complex crystal structure between a type II PilZ protein and the EAL domain of the FimX protein (FimX(EAL)) from Xanthomonas campestris pv. campestris (Xcc) in the presence of c-di-GMP is reported. This work reveals two novel conformations of monomeric c-di-GMP in the XccFimX(EAL)-c-di-GMP and XccFimX(EAL)-c-di-GMP-XccPilZ complexes, as well as a unique interaction mode of a type II PilZ domain with FimX(EAL). These findings indicate that c-di-GMP is sufficiently flexible to adjust its conformation to match the corresponding recognition motifs of different cognate effectors. Together, these results represent a first step towards an understanding of how T4P biogenesis is controlled by c-di-GMP at the molecular level and also of the ability of c-di-GMP to bind to a wide variety of effectors.

Purpose: We evaluated the safety and effectiveness of alternative endovascular methods to retrieve embedded optional and permanent filters in order to manage or reduce risk of long-term complications from implantation. Histologic tissue analysis was performed to elucidate the pathologic effects of chronic filter implantation., Methods: We studied the safety and effectiveness of alternative endovascular methods for removing embedded inferior vena cava (IVC) filters in 10 consecutive patients over 12 months. Indications for retrieval were symptomatic chronic IVC occlusion, caval and aortic perforation, and/or acute PE (pulmonary embolism) from filter-related thrombus. Retrieval was also performed to reduce risk of complications from long-term filter implantation and to eliminate the need for lifelong anticoagulation. All retrieved specimens were sent for histologic analysis., Results: Retrieval was successful in all 10 patients. Filter types and implantation times were as follows: one Venatech (1,495 days), one Simon-Nitinol (1,485 days), one Optease (300 days), one G2 (416 days), five Günther-Tulip (GTF; mean 606 days, range 154-1,010 days), and one Celect (124 days). There were no procedural complications or adverse events at a mean follow-up of 304 days after removal (range 196-529 days). Histology revealed scant native intima surrounded by a predominance of neointimal hyperplasia and dense fibrosis in all specimens. Histologic evidence of photothermal tissue ablation was confirmed in three laser-treated specimens., Conclusion: Complex retrieval methods can now be used in select patients to safely remove embedded optional and permanent IVC filters previously considered irretrievable. Neointimal hyperplasia and dense fibrosis are the major components that must be separated to achieve successful retrieval of chronic filter implants.

Purpose: To determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice., Materials and Methods: The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session., Results: Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories., Conclusions: This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

c-di-GMP is a major secondary-messenger molecule in regulation of bacterial pathogenesis. Therefore, the c-di-GMP-mediated signal transduction network is of considerable interest. The PilZ domain was the first c-di-GMP receptor to be predicted and identified. However, every PilZ domain binds c-di-GMP with a different binding affinity. Intriguingly, a noncanonical PilZ domain has recently been found to serve as a mediator to link FimX(EAL) to the PilB or PilT ATPase to control the function of type IV pili (T4P). It is thus essential to determine the structure of the FimX(EAL)-PilZ complex in order to determine how the binding of c-di-GMP to the FimX(EAL) domain induces conformational change of the adjoining noncanonical PilZ domain, which may transmit information to PilB or PilT to control T4P function. Here, the preparation and preliminary X-ray diffraction studies of the XccFimX(EAL)-c-di-GMP and XccFimX(EAL)-c-di-GMP-XccPilZ complexes from Xcc (Xanthomonas campestris pv. campesteris) are reported. Detailed studies of these complexes may allow a more thorough understanding of how c-di-GMP transmits its effects through the degenerate EAL domain and the noncanonical PilZ domain., (© 2012 International Union of Crystallography)

Acute pulmonary embolism (PE) is the third most common cause of death among hospitalized patients. Treatment escalation beyond anticoagulation therapy is necessary in patients with massive PE (defined by hemodynamic shock) as well as in many patients with submassive PE (defined by right ventricular strain). The best current evidence suggests that modern catheter-directed therapy to achieve rapid central clot debulking should be considered as an early or first-line treatment option for patients with acute massive PE; and emerging evidence suggests a catheter-directed thrombolytic infusion should be considered as adjunctive therapy for many patients with acute submassive PE. This article reviews the current approach to endovascular therapy for acute PE in the context of appropriate diagnosis, risk stratification, and management of acute massive and acute submassive PE., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively evaluate the impact of C-arm CT on radiation exposure to hepatocellular carcinoma (HCC) patients treated by chemoembolization., Materials and Methods: Patients with HCC (N = 87) underwent digital subtraction angiography (DSA; control group) or combined C-arm CT/DSA (test group) for chemoembolization. Dose-area product (DAP) and cumulative dose (CD) were measured for guidance and treatment verification. Contrast agent volume and C-arm CT utility were also measured., Results: The marginal DAP increase in the test group was offset by a substantial (50%) decrease in CD from DSA. Use of C-arm CT allowed reduction of DAP and CD from DSA imaging (P = .007 and P = .017). Experienced operators were more efficient in substituting C-arm CT for DSA, resulting in a negligible increase (7.5%) in total DAP for guidance, compared with an increase of 34% for all operators (P = .03). For treatment verification, DAP from C-arm CT exceeded that from DSA, approaching that of conventional CT. The test group used less contrast medium (P = .001), and C-arm CT provided critical or supplemental information in 20% and 17% of patients, respectively., Conclusions: Routine use of C-arm CT can increase stochastic risk (DAP) but decrease deterministic risk (CD) from DSA. However, the increase in DAP is operator-dependent, thus, with experience, it can be reduced to under 10%. C-arm CT provides information not provided by DSA in 33% of patients, while decreasing the use of iodinated contrast medium. As with all radiation-emitting modalities, C-arm CT should be used judiciously., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Before yttrium-90 ((90)Y) radioembolization administration, the authors consolidated arterial inflow by embolizing variant hepatic arteries (HAs) to make microsphere delivery simpler and safer. The present study reviews the technical and clinical success of these consolidation procedures., Materials and Methods: Preparatory and treatment angiograms were retrospectively analyzed for 201 patients. Variant HAs were coil-embolized during preparatory angiography to simplify arterial anatomy. Collateral arterial perfusion of territories previously supplied by variant HAs was evaluated by digital subtraction angiography (DSA), C-arm computed tomography (CT), and technetium-99m ((99m)Tc)-macroaggregated albumin (MAA) scintigraphy, and by follow-up evaluation of regional tumor response., Results: A total of 47 variant HAs were embolized in 43 patients. After embolization of variant HAs, cross-perfusion into the embolized territory was depicted by DSA and by C-arm CT in 100% of patients and by (99m)Tc-MAA scintigraphy in 92.7%. Uniform progressive disease prevented evaluation in 33% of patients, but regional tumor response in patients who responded supported successful delivery of microspheres to the embolized territories in 95.5% of evaluable patients., Conclusions: Embolization of variant HAs for consolidation of hepatic supply in preparation for (90)Y radioembolization promotes treatment of affected territories via intrahepatic collateral channels., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Cell adhesion efficiency is one of the key factors affecting the results of manufacturing tissue engineering constructs. High efficiency is required for seeding low proliferation cells onto scaffolds. In this study, we designed a strategy to improve the efficiency of cell adhesion using hydrophobic cell culture environment to enhance cells adhering to a scaffold. Cells have lower affinity to the surface of polydimethylsiloxane (PDMS) than tissue culture polystyrene (TCPS) plates. When cells were cultured with gelatin microspheres or chitosan films in a PDMS-coated plate instead of a normal TCPS plate, there was a significant increase in cell attachment efficiency. Cells cultured in the PDMS-coated system tended to selectively attach onto the gelatin microspheres or chitosan films, which are relatively more hydrophilic than the PDMS surface. However, minimal cell attachment on gelatin microspheres or chitosan films was observed when gelatin microspheres or chitosan films were placed in normal TCPS plate. Cell counting experiments with gelatin microspheres in the PDMS-coated system resulted in a cell attachment efficiency of 89.8% after 1 day of cultivation, whereas the cell attachment efficiency was less than 1% in normal TCPS plate. The results demonstrate that the method is easy to use and could be useful for fast cultivation of cell-scaffold constructs., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: To evaluate the safety and effectiveness of the excimer laser sheath technique for removing embedded inferior vena cava (IVC) filters., Materials and Methods: Over 12 months, 25 consecutive patients undergoing attempted IVC filter retrieval with a laser-assisted sheath technique were prospectively enrolled into an institutional review board-approved study registry. There were 10 men and 15 women (mean age 50 years, range 20-76 years); 18 (72%) of 25 patients were referred from an outside hospital. Indications for retrieval included symptomatic filter-related acute caval thrombosis (with or without acute pulmonary embolism), chronic IVC occlusion, and bowel penetration. Retrieval was also performed to remove risks from prolonged implantation and potentially to eliminate need for lifelong anticoagulation. After failure of standard methods, controlled photothermal ablation of filter-adherent tissue with a Spectranetics laser sheath and CVX-300 laser system was performed. All patients were evaluated with cavography, and specimens were sent for histologic analysis., Results: Laser-assisted retrieval was successful in 24 (96%) of 25 patients as follows: 11 Günther Tulip (mean 375 days, range 127-882 days), 4 Celect (mean 387 days, range 332-440 days), 2 Option (mean 215 days, range 100-330 days), 4 OPTEASE (mean 387 days, range 71-749 days; 1 failed 188 days), 2 TRAPEASE (mean 871 days, range 187-1,555 days), and 2 Greenfield (mean 12.8 years, range 7.2-18.3 years). There was one (4%) major complication (acute thrombus, treated with thrombolysis), three (12%) minor complications (small extravasation, self-limited), and one adverse event (coagulopathic retroperitoneal hemorrhage) at follow-up (mean 126 days, range 13-302 days). Photothermal ablation of filter-adherent tissue was histologically confirmed in 23 (92%) of 25 patients., Conclusions: The laser-assisted sheath technique appears to be a safe and effective tool for retrieving embedded IVC filters, including permanent types, with implantation ranging from months to > 18 years., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Nonviral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multifunctional nanomicelles for both drug and gene delivery application. Polyethylenimine (PEI) was modified by grafting stearic acid (SA) and further formulated to polymeric micelles (PEI-SA) with positive surface charge for gene delivery evaluation. Our results showed that PEI-SA micelles provided high siRNA binding efficiency and exhibited low cytotoxicity compared with unmodified PEI. siRNA delivered by PEI-SA carriers also demonstrated significantly higher cellular uptake efficiency and stability even in the presence of serum proteins when compared with free siRNA. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. In the animal intratumoral model study, the combination of co-delivering doxorubicin and vascular endothelial growth factor (VEGF) siRNA delivered by PEI-SA micelles showed a promising effect on anti-tumor growth. The amphiphilic structure of PEI-SA micelles provides advantages for multifunctional tasks; such that hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and hydrophobic core can serve as a payload for hydrophobic drugs, making it truly a promising multifunctional vehicle for both genetic and chemotherapy application., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Deregulation of apoptosis will influence the balance of cell proliferation and cell death, resulting in various fatal diseases that can include cancer. In prior research reports related to cancer therapy, phytohemagglutinin, a lectin extracted from red kidney beans, demonstrated the ability to inhibit the growth of human cancer cells. However, one of its isoforms, erythroagglutinating, has yet to be evaluated on its anticancer effects., Methods: PHA-E was used to induce apoptosis of A-549 lung cancer cells and the possible signal transduction pathway was elucidated, as measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, G6PD release assay, flow cytometry, and Western blot analysis., Results: PHA-E treatment caused a dose-dependent increase of cell growth inhibition and cytotoxicity on A-549 cells. In annexin V/propidium iodide [i.e., PI] and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)/PI assay, we found that the rate of apoptotic cells was raised as the concentration of PHA-E increased. Treatment of A-549 cells with PHA-E resulted in enhancing the release of cytochrome c, which thus activated an increase in caspase 9 and caspase 3, the upregulation of Bax and Bad, the downregulation of Bcl-2 and phosphorylated Bad, and finally the inhibition of the epidermal growth factor receptor and its downstream signal pathway PI3K/Akt and MEK/ERK., Conclusions: PHA-E can induce growth inhibition and cytotoxicity of lung cancer cells, which is mediated through an activation of the mitochondria apoptosis pathway. These results suggest that PHA-E can be developed into a new therapeutic treatment that can be applied as an effective anti-lung cancer drug in the near future.

Purpose: To test the hypothesis that a common iliac vein (CIV) stenosis may impair embolization of a large deep venous thrombosis (DVT) to the lungs, decreasing the incidence of a symptomatic pulmonary embolism (PE)., Materials and Methods: Between January 2002 and August 2007, 75 patients diagnosed with unilateral DVT were included in a single-institution case-control study. Minimum CIV diameters were measured 1 cm below the inferior vena cava (IVC) bifurcation on computed tomography (CT) images. A significant stenosis in the CIV ipsilateral to the DVT was defined as having either a diameter 4 mm or less or a greater than 70% reduction in lumen diameter. A symptomatic PE was defined as having symptoms and imaging findings consistent with a PE. The odds of symptomatic PE versus CIV stenosis were assessed using logistic regression models. The associations between thrombus location, stenosis, and symptomatic PE were assessed using a stratified analysis., Results: Of 75 subjects, 49 (65%) presented with symptomatic PE. There were 17 (23%) subjects with a venous lumen 4 mm or less and 12 (16%) subjects with a greater than 70% stenosis. CIV stenosis of 4 mm or less resulted in a decreased odds of a symptomatic PE compared with a lumen greater than 4 mm (odds ratio [OR] 0.17, P = .011), whereas a greater than 70% stenosis increased the odds of DVT involving the CIV (OR 7.1, P = .047)., Conclusions: Among patients with unilateral DVT, those with an ipsilateral CIV lumen of 4 mm or less have an 83% lower risk of developing symptomatic PE compared with patients with a CIV lumen greater than 4 mm., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

An inferior vena cava (IVC) filter became embedded within the IVC of a 45-year-old man after prolonged implantation. Because of incorporation of the filter legs within the caval endothelium, the filter was densely adherent and could not be sheathed using standard retrieval methods. In this patient, the authors performed percutaneous filter retrieval using an excimer laser sheath technique for circumferential ablation of dense fibrotic tissue between the filter and IVC. Endovascular laser ablation allowed facile separation of the filter from the IVC, without tearing of the tissues, and the filter was removed successfully without complication., (Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To enhance the educational experience among residents rotating through interventional radiology (IR) by encouraging ownership and responsibility., Materials and Methods: In May 2006, the authors implemented changes in resident education in IR that included increased clinical responsibilities, structured didactics, and greater hands-on experience, including call. Residents were assigned as first assistants, ownership of cases was encouraged, and assignment to a week on the consult service was instituted to help residents better understand all aspects of IR practice. Additional faculty recruitment and program expansion ensured the same high level of training for the fellowship program. Evaluations were reviewed every year (July 1, 2007-June 30, 2009) for hands-on training, daily teaching, didactic conferences, and overall effectiveness of the clinical service. A graduated scale of 1-5 was used., Results: In 2009, 3 years after the curricular changes were made, the quality of hands-on training, daily case reviews and consults, didactics, and overall education had markedly improved with 89%, 71%, 65%, and 82% of the residents rating these respective aspects of the training as "above expectations" (4 on a scale of 5) or "superior" (5 on a scale of 5) compared with 77%, 23%, 20%, and 60% in 2005-2006. Three years after the changes, the impact of these changes on recruitment patterns also showed improvement, with 28.6% of the class of 2010 pursuing a fellowship in IR., Conclusions: Increasing resident ownership, responsibility, and hands-on experience improves resident education in IR, which, in turn, promotes interest in the field., (Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.)