E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Patients with Head-and-Neck Cancer:Dysphagia and Affective Symptoms

OBJECTIVE: Affective symptoms are common in patients with head-and-neck cancer. This study determined the association between the presence of aspiration and symptoms of anxiety and depression, as well as patient characteristics in patients with head-and-neck cancer and dysphagia. METHODS: Eighty-four patients with head-and-neck cancer and dysphagia completed the Hospital Anxiety and Depression Scale and underwent a standardized fiberoptic endoscopic evaluation of swallowing. Linear regression analysis was performed to explore the associations. RESULTS: Fifty-two (61.9%) patients presented clinically relevant symptoms of anxiety or depression. Forty-eight (57.1%) patients presented with aspiration during fiberoptic endoscopic evaluation of swallowing. A significant negative association was found between the presence of aspiration and affective (anxiety and depression) symptoms (p = 0.04). Male patients presented significantly lower symptom scores of anxiety compared to females (p = 0.04). CONCLUSIONS: Clinically relevant affective symptoms were present in more than half of all patients with head-and-neck cancer and dysphagia. Surprisingly, a significant negative association was found between the presence of aspiration and these affective symptoms. Gender was also significantly associated with affective symptoms. These results suggest that there is a need for further investigation into the impact of psychological distress on patients with head-and-neck cancer and dysphagia

sj-docx-1-ine-10.1177_15910199241245166 - Supplemental material for Timing of acute carotid artery stenting for tandem lesions in patients with acute ischemic stroke: A Maastricht Stroke Quality Registry (MaSQ-Registry) study

Supplemental material, sj-docx-1-ine-10.1177_15910199241245166 for Timing of acute carotid artery stenting for tandem lesions in patients with acute ischemic stroke: A Maastricht Stroke Quality Registry (MaSQ-Registry) study by Sorina R. Simon, Robrecht R.M.M. Knapen, Martine T.B. Truijman, Robert J. van Oostenbrugge, Bart A.J.M. Wagemans, Wim H. van Zwam and Christiaan van der Leij in Interventional Neuroradiology</p

Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guérin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis