The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia

In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their degradative activity. The degradative activity finally results in cancer progression. MMP-inhibitors (MMPIs) have already been designed and tested, based on the degradative role of MMPs in cancer progression. First clinical trials with MMPIs have been performed with disappointing results, showing that in order to use MMP-inhibition the mechanisms underlying MMP-expression in cancer have to be further elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular level and discusses the role for MMPs and MMP-inhibition in cancer with special focus on acute leukemia

Exploiting catalytic chain transfer polymerization for the synthesis of carboxylated latexes via sulfur‐free RAFT

We present a systematic study of incorporating carboxyl groups into latex particles to enhance colloidal stability and the physical properties of the latex. Statistical copolymers of methacrylic acid and methyl methacrylate) were synthesized via catalytic chain transfer polymerization (CCTP) in emulsion. The vinyl‐terminated oligomers were in turn successfully utilized as chain transfer agents for the formation of diblock and pseudo triblock copolymers via sulfur‐free reversible addition–fragmentation chain transfer polymerization (SF‐RAFT). These copolymers were characterized using 1H NMR, size exclusion chromatography (SEC), dynamic light scattering (DLS), dynamic mechanical analysis (DMA), contact angle measurements and matrix‐assisted laser desorption/ionization time of flight mass spectroscopy (MALDI‐TOF‐MS) techniques. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 201

Around the Tables – Contextual Factors in Healthcare Coverage Decisions Across Western Europe

Background: Across Western Europe, procedures and formalised criteria for taking decisions on the coverage (inclusion in the benefits basket or equivalent) of healthcare technologies vary substantially. In the decision documents, which display the justification of, the rationale for, these decisions, national healthcare institutes may employ ‘contextual factors,’ defined here as situation-specific considerations. Little is known about how the use of such contextual factors compares across countries. We describe and compare contextual factors as used in coverage decisions generally and 4 decision documents specifically in Belgium, England, Germany, and the Netherlands. Methods: Four group interviews with 3 experts from the national healthcare institute of each country, document and web site analysis, and a workshop with 1 to 2 of these experts per country were followed by the examination of the documents of 4 specific decisions taken in each of the 4 countries, sampled to vary widely in type of technology and decision outcome. Results: From the available decision documents, we conclude that in every country studied, contextual factors are established ‘around the table,’ ie, in deliberation. All documents examined feature contextual factors, with similar contextual factor patterns leading to similar decisions in different countries. The Dutch decisions employ the widest variety of factors, with the exception of the societal functioning of the patient, which is relatively common in Belgium, England, and Germany. Half of the final decisions were taken in another setting, with the consequence that no documentation was retrievable for 2 decisions. Conclusion: First, we conclude that in these countries, contextual factors are actively integrated in the decision document, and that this is achieved in deliberation. Conceptualising contextual factors as both situation-specific and actively-integrated affords insight into practices of contextualisation and provides an encouragement for exchange between decision-makers on more qualitative aspects of decisions. Second, the decisions that lacked a publicly acc

Expression of lipocortins in human bronchial epithelial cells: effects of IL-1β , TNF-α, LPS and dexamethasone

In this study, we investigated the expression of lipocortin I and II (annexin I and I in the human bronchial epithelium, both in vivo and in vitro. A clear expression of lipocortin I and II protein was found in the epithelium in sections of bronchial tissue. In cultured human bronchial epithelial cells we demonstrated the expression of lipocortin I and II mRNA and protein using Northern blotting, FACScan analysis and ELISA. No induction of lipocortin I or II mRNA or protein was observed after incubation with dexamethasone. Stimulation of bronchial epithelial cells with IL-1β, TNF-α or LPS for 24 h did not affect the lipocortin I or II mRNA or protein expression, although PGE2 and 6-keto-PGF1α production was significantly increased. This IL-1β- and LPS-mediated increase in eicosanoids could be reduced by dexamethasone, but was not accompanied by an increase in lipocortin I or II expression. In human bronchial epithelial cells this particular glucocorticoid action is not mediated through lipocortin I or II induction

Letter from Thomas Mason to Dr GF Story, Hobart 1849

A letter from Thomas Mason to Dr GF Story, Hobart 1849. Mason had requested JB (?) Mather to 'ship the skins', and had forwarded information to Story about this trade. Mason comments on mutual friends, such as William Galway, whose daughter had married, and Thomas Turner, who had died. From Cotton Family Papers C7/16

Health–economic Benefits of Treating Trauma in Psychosis

Background: Co-occurrence of posttraumatic stress disorder (PTSD) in psychosis (estimated as 12%) raises personal suffering and societal costs. Health–economic studies on PTSD treatments in patients with a diagnosis of a psychotic disorder have not yet been conducted, but are needed for guideline development and implementation. This study aims to analyse the cost-effectiveness of guideline PTSD therapies in patients with a psychotic disorder. Methods: This health–economic evaluation alongside a randomized controlled trial included 155 patients with a psychotic disorder in care as usual (CAU), with comorbid PTSD. Participants received eye movement desensitization and reprocessing (EMDR) (n = 55), prolonged exposure (PE) (n = 53) or waiting list (WL) (n = 47) with masked assessments at baseline (T0) and at the two-month (post-treatment, T2) and six-month follow-up (T6). Costs were calculated using the TiC-P interview for assessing healthcare consumption and productivity losses. Incremental cost-effectiveness ratios and economic acceptability were calculated for quality-adjusted life years (EQ-5D-3L-based QALYs) and PTSD ‘Loss of diagnosis’ (LoD, CAPS). Results: Compared to WL, costs were lower in EMDR (-€1410) and PE (-€501) per patient per six months. In addition, EMDR (robust SE 0.024, t = 2.14, p = .035) and PE (robust SE 0.024, t = 2.14, p = .035) yielded a 0.052 and 0.051 incremental QALY gain, respectively, as well as 26% greater probability for LoD following EMDR (robust SE = 0.096, z = 2.66, p = .008) and 22% following PE (robust SE 0.098, z = 2.28, p = .023). Acceptability curves indicate high probabilities of PTSD treatments being the better economic choice. Sensitivity analyses corroborated these outcomes. Conclusion: Adding PTSD treatment to CAU for individuals with psychosis and PTSD seem to yield better health and less PTSD at lower costs, which argues for implementation

Addition of PTK787/ZK 222584 can lower the dosage of amsacrine to achieve equal amounts of acute myeloid leukemia cell death

Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express the vascular endothelial growth factors, VEGFA and VEGFC, as well as kinase insert domain-containing receptor (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. This study investigates the role of the VEGFR inhibitor PTK787/ZK 222584 in leukemic cell death, and the possibility of an additional effect on cell death by a chemotherapeutic drug, amsacrine. In three AML cell lines and 33 pediatric AML patient samples, we performed total cell-kill assays to determine the percentages of cell death achieved by PTK787/ZK 222584 and/or amsacrine. Both drugs induced AML cell death. Using a response surface analysis, we could show that, in cell lines as well as in primary AML blasts, an equal magnitude of leukemic cell death could be obtained when lower doses of the more toxic amsacrine were combined with low dosages of the less toxic VEGFR inhibitor. This study shows that PTK787/ ZK 222584 might have more clinical potential in AML when combined with a chemotherapeutic drug such as amsacrine. In future, it will be interesting to study whether the complications and the long-term effects of chemotherapy can be reduced by lowering the dosages of amsacrine, and by replacing it with other drugs with lower toxicity profiles, such as PTK787/ZK 222584