Cercosporamide inhibits bone morphogenetic protein receptor type I kinase activity in zebrafish RESEARCH ARTICLE

This article has an associated First Person interview with the first author of the paper.
Source: DMM Disease Models and Mechanisms - Category: Biomedical Science Authors: Tags: Developmental Disorders, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

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Abstract Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas...
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
AbstractObjectivesTo investigate the value of contrast-enhanced (CE) turbo spin echo black blood (BB) sequences for imaging of therapy-naive high-grade gliomas (HGGs).MethodsConsecutive patients with histopathologically confirmed World Health Organization (WHO) grade III or IV gliomas and no oncological treatment prior to index imaging (March 2019 to January 2020) were retrospectively included. Magnetic resonance imaging (MRI)  at 3 Tesla comprised CE BB and CE turbo field echo (TFE) sequences. The lack/presence of tumor-related contrast enhancement and satellite lesions were evaluated by two readers. Sharper delineat...
Source: European Radiology - Category: Radiology Source Type: research
Authors: Sinclair G, Johnstone P, Hatiboglu MA Abstract Up until, June 13, 2020,>7,500,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and>400,000 deaths, across 216 countries, have been confirmed by the World Health Organization (WHO). With reference to the two previous beta-CoV outbreaks (SARS-CoV and middle east respiratory syndrome [MERS]), this paper examines the pathophysiological and clinical similarities seen across all three CoVs, with a special interest in the neuroinvasive capability and subsequent consequences for patients with primary or metastatic brain tumors. More wid...
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Authors: Telles JPM, Yamaki VN, Yamashita RG, Solla DJF, Paiva WS, Teixeira MJ, Neville IS Abstract Background: Patients with cancer are subject to all neurosurgical procedures of the general population, even if they are not directly caused by the tumor or its metastases. We sought to evaluate the impact of urgent neurosurgery on the survival of patients with cancer. Methods: We included patients submitted to neurosurgeries not directly related to their tumors in a cancer center from 2009 to 2018. Primary endpoints were mortality in index hospitalization and overall survival. Results: We included 410 patien...
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Conclusion: Burr hole microsurgery can treat different intracranial lesions effectively. Despite a smaller craniotomy diameter of 11-14 mm compared with keyhole approaches, surgery was successful. PMID: 33024593 [PubMed]
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Abstract Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are diseases that typically manifest in childhood and are associated with severely reduced life expectancy. However, there are currently no effective therapies for these diseases, which remain incurable. Activin receptor-like kinase-2 (ALK2), encoded by the ACVR1 gene, is a bone morphogenetic protein (BMP) type-I receptor subtype that plays an important physiological role in the development of bones, muscles, brain, and other organs. Constitutively active mutants of ALK2 have been identified as causative of FOP and inv...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research
Abstract Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) wit...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research
In this study, we characterized the ALK2 mutants R258G, G328V and F246Y, which were identified in patients with severe FOP, DIPG and unusual hereditary skeletal dysplasia, respectively. Both R258G and G328V were gain-of-function mutations, but F246Y was equivalent to wild-type ALK2.
Source: Bone - Category: Orthopaedics Authors: Tags: Full Length Article Source Type: research
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20 –25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation.
Source: Bone - Category: Orthopaedics Authors: Tags: Full Length Article Source Type: research
Abstract Activin receptor-like kinase 1 (ALK1, encoded by the gene ACVRL1) is a type I BMP/TGF-β receptor that mediates signalling in endothelial cells via phosphorylation of SMAD1/5/8. During angiogenesis, sprouting endothelial cells specialise into tip cells and stalk cells. ALK1 synergises with Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2 and thereby represses tip cell formation and angiogenic sprouting. The ALK1-Fc soluble protein fusion has entered clinic trials as a therapeutic strategy to sequester the high-affinity extracellular ligand BMP9. Here, we determined the crys...
Source: Angiogenesis - Category: Molecular Biology Source Type: research
More News: Biomedical Science | Brain Tumor | Fibrodysplasia Ossificans Progressiva | Glioma