The impact of operative approach on outcome of surgery for gastro-oesophageal tumours

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.     

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Methods/Design

A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.

Discussion

The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.

Trial registration

Dutch Trial Register, NTR1447.

     

Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment

Introduction  

Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.     

转基因香石竹中F3’5’H基因的克隆、表达和免疫学鉴定

在研究转基因香石竹品系月之霓裳（Moonshade）、月之伊人（Moonlite）中外源基因F3’5’H的表达中,本文克隆了F3’5’H全长基因1.5kb,构建获得工程菌株Escherichia coli BL21（DE3）（＋F3＇5＇H）。SDS-PAGE分析的结果显示,该菌株高效表达出F3’5’H重组蛋白,约占菌体总蛋白的30%。用经纯化的F3’5’H重组蛋白作为抗原,制备F3’5’H重组蛋白的抗血清,经ELISA免疫学分析表明,该抗血清的效价为1：25600。Western blot结果表明F3’5’H重组蛋白具有良好的IgG结合活性,且抗血清与转基因香石竹品系月之霓裳和月之伊人中的外源基因F3’5’H所表达的蛋白发生明显的抗原抗体反应。这样,月之霓裳和月之伊人用于评价转基因香石竹品系的环境安全性在我国也得到了验证。     

Polymorphism and divergence at the prune locus in Drosophila melanogaster and D. simulans

The prune locus of Drosophila melanogaster lies at the tip of the X chromosome, in a region of reduced recombination in which nearby loci show reduced variation relative to evolutionary divergence from D. simulans. DNA sequencing of prune alleles from D. melanogaster and D. simulans reveals extremely low variation in D. melanogaster but greater variation in D. simulans. Divergence between the two species is not reduced. This pattern may be explained by either positive selection leading to hitchhiking of neutral variation or background selection against deleterious mutations. The pattern of silent versus replacement polymorphism and divergence at prune is consistent with either a model of weakly deleterious selection against amino acid substitutions or balancing selection.      

Identification of a pepducin acting as S1P3 receptor antagonist

Sphingosine‐1‐phosphate (S1P) is a bioactive lipid with key functions in the immune, inflammatory, and cardiovascular systems. S1P exerts its action through the interaction with a family of five known G protein‐coupled receptors, named S1P_1–5. Among them, S1P₃ has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. KRX‐725 (compound 1) is a pepducin that mimics the effects of S1P by triggering specifically S1P₃. Here, aiming to identify novel S1P₃ antagonists, we carried out an alanine scanning analysis to address the contribution of the side chains of each amino acid residue to the peptide function. Then, deleted peptides from both the C‐ and N‐terminus were prepared in order to determine the minimal sequence for activity and to identify the structural requirements for agonistic and, possibly, antagonistic behaviors. The pharmacological results of the Ala‐scan derived compounds (2–10) suggested a high tolerance of the pepducin 1 to amino acid substitutions. Importantly, the deleted peptide 16 has the ability to inhibit, in a dose‐dependent manner, both pepducin 1‐induced vasorelaxation and fibroblast proliferation. Finally, a computational analysis was performed on the prepared compounds, showing that the supposed antagonists 16 and 17 appeared to be aligned with each other but not with the others. These results suggested a correlation between specific conformations and activities. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus

Introduction  

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients.     

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

Introduction

The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).

Methods

This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.

Results

After three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician''s global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.

Conclusions

Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.     

Identification of new polymorphic regions and differentiation of cultivated olives (<Emphasis Type="Italic">Olea europaea</Emphasis> L.) through plastome sequence comparison

Background  

The cultivated olive (Olea europaea L.) is the most agriculturally important species of the Oleaceae family. Although many studies have been performed on plastid polymorphisms to evaluate taxonomy, phylogeny and phylogeography of Olea subspecies, only few polymorphic regions discriminating among the agronomically and economically important olive cultivars have been identified. The objective of this study was to sequence the entire plastome of olive and analyze many potential polymorphic regions to develop new inter-cultivar genetic markers.