Mechanism of action of EGFR mutations

The role of mutant epidermal growth factor receptor (EGFR) kinases in the growth of a host of human cancers including lung cancer is well known. The activation of wild type EGFR is primarily driven by the binding of growth factors leading to receptor dimerisation. In this paper the authors, through a series of simulation experiments, show that the wild-type EGFR kinase domain is intrinsically disordered and it becomes ordered (active) only upon dimerisation. This intrinsic disorder (partial unfolding) is a third functionally important conformation in addition to the previously identified ‘αC-out inactive’ and ‘αC-in active’ conformations. EGFR signalling involves multiple layers of controlling mechanisms; the identification of an intrinsically disordered state of EGFR kinase introduces another element critical for its function. EGFR mutations were generally assumed to give rise to spontaneous kinase activation, eliminating the dependence of the cancer mutants on dimerisation for activation. However the authors have been...
Source: Thorax - Category: Respiratory Medicine Authors: Tags: Miscellanea Source Type: research

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Conditions:   Interstitial Lung Disease;   Lung Cancer Intervention:   Sponsor:   Portsmouth Hospitals NHS Trust Recruiting
Source: - Category: Research Source Type: clinical trials
Publication date: 15 December 2019Source: Journal of Molecular Structure, Volume 1198Author(s): Bandar A. Babgi, Magda H. Abdellattif, Mostafa A. Hussien, Naser E. EltayebAbstractThe synthesis of the benzoimidazolyl-ferrocene containing compound was achieved by Knovenagel condensation of ferrocene-1-carbaldehyde and (2-benzoimidazolyl) acetonitrile. Single crystal structure of the compound showed intramolecular (hydrogen bonding) NH⋯N interactions, forming an infinite 1D-chain that propagate along the [010] direction. The titled compound exhibits two major energy bands around 360 nm and 515 nm in the UV–vis ran...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
A computer-based simulation model projected that CT lung screening in several...Read more on AuntMinnie.comRelated Reading: Biennial follow-up exams prove safe for CT lung screening Lung cancer imaging on the upswing in China CT lung screening spots cancers earlier in China CT lung screening cuts cancer mortality 51% in Japan CT lung screening may benefit racial minorities most
Source: Headlines - Category: Radiology Source Type: news
ConclusionsOverall HCAHPS satisfaction scores following lung resection for cancer were high and negatively associated with increasing length of stay. Patient satisfaction may be impacted more by the perception of effective communication during prolonged hospitalizations than by complications.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
This study aims to investigate the mechanism of M3R involved in the growth of NSCLC.Main methodsThe CRISPR/Cas9 was used to knock out (KO) the M3R gene. A real-time cell analyzer (RTCA) was used to record the proliferation of NSCLC cells. The migration and cell cycle of NSCLC cells were evaluated with scratch test and flow cytometry (FCM), respectively. Antibody microarray analysis was performed to detect the expression of proteins after antagonizing M3R and knocking out of M3R, subsequently some of these important proteins were verified by western blot.Key findingsThe proliferation and migration of NSCLC cells were inhibi...
Source: Life Sciences - Category: Biology Source Type: research
Overall survival (OS) following radiotherapy (RT) for locally-advanced non-small cell lung cancer (LA-NSCLC) remains disappointing. While some dose-escalation trials have achieved promising results [1], outcomes have been inconsistent, with median OS in better performing studies being 25 –28 months [2,3]. Surprisingly, the RTOG-0617 phase III study of concurrent chemoradiotherapy (CRT) found a sub-unity median survival ratio (MSR) of 0.71 for 74 Gy in 37 daily fractions versus 60 Gy in 30 fractions [2].
Source: Radiotherapy and Oncology - Category: Radiology Authors: Tags: Original Article Source Type: research
AbstractMHC class I-related chain A (MICA) is one of the major ligands for natural killer group 2 member D (NKG2D), which is an activating NK receptor. MICA is expressed on the surface of human epithelial tumor cells, and its shedding from tumor cells leads to immunosuppression. To activate immune response in the tumor microenvironment, we designed an anti-VEGFR2 –MICA bispecific antibody (JZC01), consisting of MICA and an anti-VEGFR2 single chain antibody fragment (JZC00) and explored its potential anti-tumor activity. JZC01 targeted vascular endothelial growth factor receptor 2 (VEGFR2) and inhibited tumorigenesis ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
SummaryPurpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer.Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5  g/day for 14 days (Group A,N = 20) or not (Group B,N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and apr...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
ConclusionsThe texture features of contrast-enhanced computed tomography image could potentially serve as radiological prognostic biomarkers for SCLC patients.
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
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