Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Natural Variation in Grain Selenium Concentration of Wild Barley, Hordeum spontaneum, Populations from Israel

Wild barley (Hordeum spontaneum), the progenitor of cultivated barley, is an important genetic resource for cereal improvement. Selenium (Se) is an essential trace mineral for humans and animals with antioxidant, anticancer, antiarthropathy, and antiviral effects. In the current study, the grain Se concentration (GSeC) of 92 H. spontaneum genotypes collected from nine populations representing different habitats in Israel was investigated in the central area of Guizhou Province, China. Remarkable variations in GSeC were found between and within populations, ranging from 0 to 0.387 mg kg−1 among the 92 genotypes with an average of 0.047 mg kg−1. Genotype 20_C from the Sede Boqer population had the highest GSeC, while genotype 25_1 from the Atlit population had the lowest. The mean value of GSeC in each population varied from 0.010 to 0.105 mg kg−1. The coefficient of variation for each population ranged from 12% to 163%. Significant correlations were found between GSeC and 12 ecogeographical factors out of 14 studied. Habitat soil type also significantly affected GSeC. The wild barley exhibited wider GSeC ranges and greater diversity than its cultivated counterparts. The higher Se grain concentrations found in H. spontaneum populations suggest that wild barley germplasm confer higher abilities for Se uptake and accumulation, which can be used for genetic studies of barley nutritional value and for further improvement of domesticated cereals

Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with mu 2

Background: Upon ligand binding, cell surface signaling receptors are internalized through a process tightly regulated by endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocytic proteins are becoming clearer, it is still unclear what determines the receptor endocytosis kinetics which is mainly regulated by the accumulation of endocytic apparatus to the activated receptors. Methodology/Principal Findings: Here we employed the kinetic analysis of endocytosis and adaptor recruitment to show that ??2, a subunit of AP2 interacts directly with phospholipase D (PLD)1, a receptor-associated signaling protein and this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstrate that the PLD1-??2 interaction requires the binding of PLD1 with phosphatidic acid, its own product. Conclusions/Significance: These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor activation and triggers the translocation of AP2 near to the activated receptor.open3

Live Imaging of Xwnt5A-ROR2 Complexes

Secreted molecules of the Wnt family regulate key decisions in embryogenesis and adult tissue homeostasis by activating a complex network of Wnt signaling pathways. Although the different branches of Wnt signaling have been studied for more than 25 years, fluorophore tagged constructs for live cell imaging of Wnt molecules activating the Wnt/β-catenin pathway have become available only recently. We have generated a fluorophore tagged Wnt construct of the Xenopus Wnt5a protein (Xwnt5A) with the enhanced green fluorescent protein (EGFP), Xwnt5A-EGFP. This construct activates non-canonical Wnt pathways in an endocytosis dependent manner and is capable of compensating for the loss of endogenous Xwnt5A in Xenopus embryos. Strikingly, non-canonical Wnt pathway activation was restricted to short-range signaling while an inhibitory effect was observed in transwell cell cultures taken as long-range signaling model sytem. We used our Xwnt5A-EGFP construct to analyze in vivo binding of Wnt5A to its co-receptor ROR2 on the microscopic and on the molecular level. On the microscopic level, Xwnt5A-EGFP clusters in the membrane and recruits ROR2-mCherry to these clusters. Applying dual-colour dual-focus line-scanning fluorescence correlation spectroscopy on dorsal marginal zone explants, we identified membrane tethered Xwnt5A-EGFP molecules binding to ROR2-mCherry molecules. Our data favour a model, in which membrane-tethered Wnt-5A recruits ROR2 to form large ligand/receptor clusters and signals in an endocytosis-dependent manner

Monoclonal antibody induced with inactived EV71-Hn2 virus protects mice against lethal EV71-Hn2 virus infection

<p>Abstract</p> <p>Background</p> <p>Enterovirus 71 (EV71) is a viral pathogen that belongs to the <it>Picornaviridae </it>family, EV71-infected children can develop severe neurological complications leading to rapid clinical deterioration and death.</p> <p>Results</p> <p>In this study, several monoclonal antibodies (MAbs) were produced by immunizing mice with the inactived EV71 Henan (Hn2) virus strain. The isolated MAbs were characterised by <it>in vitro </it>neutralizing analysis and peptide ELISA. ELISA assay showed that the neutralizing monoclonal antibody 4E8 specifically reacted with synthetic peptides which contain amino acid 240-250 and 250-260 of EV71 VP1. The <it>in vivo </it>protection assay showed that 4E8 can protect two-day-old BALB/c mice against the lethal challenge of EV71 virus.</p> <p>Conclusion</p> <p>The MAb 4E8 could be a promising candidate to be humanized and used for treatment of EV71 infection.</p

Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

<p>Abstract</p> <p>Background</p> <p>The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.</p> <p>Methods</p> <p>In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.</p> <p>Results</p> <p>Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.</p> <p>Conclusion</p> <p>These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.</p