Airway smooth muscle as an underutilised biomarker: a case report.

Background: Severe asthma and chronic obstructive pulmonary disease (COPD) can be challenging to manage, particularly when the clinical features may be similar. With the increased availability of advanced therapies for both entities, it is more important than ever to diagnose and phenotype accurately to inform appropriate treatment decisions. This case highlights the use of endobronchial biopsies to allow for histological evaluation of airways disease, and in particular the role of airway smooth muscle mass as an additional biomarker that could facilitate the diagnostic process.

Spread of a model invasive alien species, the harlequin ladybird Harmonia axyridis in Britain and Ireland.

Invasive alien species are widely recognized as one of the main threats to global biodiversity. Rapid flow of information on the occurrence of invasive alien species is critical to underpin effective action. Citizen science, i.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here.

Phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab with concurrent external thoracic radiotherapy in Canadian patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy.

Purpose: Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT.

Methods: Patients with stage IIB, III or IV NSCLC considered unsuitable for radical radiation or chemo-radiation received nimotuzumab weekly 8× (100, 200 or 400 mg) with radiation (30 or 36 Gy in 3 Gy fractions).

Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects.

Expression of osteopontin and HGF/met in adult soft tissue tumors.

There is a need for molecular markers that predict biological behavior of adult soft tissue tumors. Elevated levels of osteopontin (OPN) a transformation-linked protein, have been associated with poor survival in many cancers. OPN induces cell migration in cancer cells, in part through activation of the hepatocyte growth factor (HGF) receptor (Met) and its signaling pathway.

Gastrointestinal stromal tumours: etiology, pathology and clinical management.

Investigation of the regulation of cell growth, differentiation and death by signalling pathways has led to a greater understanding of how alterations in these pathways play a critical role in the development of some cancers, and has opened new opportunities for their treatment. In the present review, results with the prototype drug of this class, imatinib (Gleevec, Glivec [formerly STI571]; Novartis, Switzerland), in metastatic gastrointestinal stromal tumours are presented. The present review originated from a conference of the authors held in Montreal, Quebec in June 2003, under the sponsorship of Novartis.

ADAM 33 and its association with airway remodeling and hyperresponsiveness in asthma.

Asthma is known to be a Th2 inflammatory syndrome that leads to intermittent airway obstruction. However, the mechanisms involved in development of the clinical features remain enigmatic, although genetic elements clearly are involved. Recently, based on a large genome wide screen involving families in the United Kingdom and the United States with at least two siblings with asthma, a locus was identified that encoded for a family of proteases.

Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis.

Background: Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort.

Toll-like receptor 4 polymorphism and severity of atopy in asthmatics.

Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy.

Targeting adenosine receptors: novel therapeutic targets in asthma and chronic obstructive pulmonary disease.

Adenosine, an endogenous signaling nucleoside that modulates many physiological processes has been implicated in playing an ever increasingly important role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). All cells contain adenosine and adenine nucleotides and the cellular production of adenosine is greatly enhanced under conditions of local hypoxia as may occur in inflammatory conditions such as asthma and COPD. In 1983, it was first reported that inhaled adenosine causes dose-related bronchoconstriction in patients with both allergic and non-allergic asthma but not in healthy volunteers.

Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.

Background: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.

Objective: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.

Methods: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.

Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population.

Background: 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma.

Objective: We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility.

Methods: To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184).

Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma.

Background: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 (A/C) polymorphism has previously been reported. The role of these polymorphisms in the genetic susceptibility to asthma was examined.

Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation.

Background: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out.

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma.

Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease.

Adenosine is a purine nucleoside which mediates a variety of cellular responses relevant to asthma and COPD through interaction with specific receptors. Administration of adenosine by inhalation to patients with asthma and COPD is known to cause concentration related bronchoconstriction. Responses elicited by this purine derivative in asthma and COPD should not be considered as a mere reflection of non-specific airways hyperresponsiveness.

Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma.

Background: Adenosine induced bronchoconstriction in patients with asthma is thought to be mediated by the synthesis and release of autacoids from airway mast cells. In vitro, adenosine induced constriction of asthmatic bronchi is blocked by a combination of specific histamine and cysteinyl leukotriene receptor antagonists, but the relative contribution of these mediators in vivo is unclear. We hypothesised that adenosine induced bronchoconstriction in asthmatic patients may be blocked by pretreatment with the orally active selective cysteinyl leukotriene-1 (CysLT(1)) receptor antagonist, montelukast.

Prognostic significance of BAG-1 expression in nonsmall cell lung cancer.

The purpose of this study was to evaluate the expression of BAG-1 in a cohort of patients with nonsmall cell lung cancer (NSCLC). The intensity and subcellular distribution of BAG-1 expression were correlated with overall survival. Tumor samples were collected from 85 patients diagnosed with NSCLC between 1993-1995 in St.