A5090211368- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- Synthesis and biological activity
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Melanoma and MAPK Pathways
- Lung Cancer Research Studies
- Neuroscience and Neuropharmacology Research
- Virus-based gene therapy research
- Medical Imaging and Pathology Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immunotherapy and Immune Responses
- Chemical Synthesis and Analysis
- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Neonatal Respiratory Health Research
The Francis Crick Institute
2018-2025
Université Toulouse III - Paul Sabatier
2020
Centre National de la Recherche Scientifique
2020
Cancer Research UK
2002-2020
AstraZeneca (United Kingdom)
2020
Frederick National Laboratory for Cancer Research
2020
Promega (United States)
2020
Institute of Cancer Research
2013-2020
Gateway Group (India)
2020
The Honourable Society of Lincoln's Inn
1994-2014
Journal Article A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins Get access Trevor D. Littlewood, Littlewood * Biochemistry Cell NucleusLondon WC2A 3PX, UK To whom correspondence should be addressed Search other works by this author on: Oxford Academic PubMed Google Scholar David C. Hancock, Hancock Paul S. Danielian, Danielian 1Molecular Endocrinology Laboratories, Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's...
Combined targeting of KRAS-G12C, mTOR, and IGF1R enhances extends the response to recently developed KRAS-G12C inhibitors in lung cancer models.
Bim (Bcl-2-interacting mediator of cell death) is a member the BH3 domain-only subgroup Bcl-2 family members, for which three splice variants have been described. expressed in many healthy types, where it maintained an inactive conformation through binding to microtubule-associated dynein motor complex. Upon certain apoptotic stimuli, released from microtubules and mediates caspase-dependent apoptosis mechanism that still unclear. Here, we identified characterized novel human mRNA. In...
Four monoclonal antibodies to glycoprotein D (gD) of herpes simplex virus (HSV) types 1 and 2 neutralized in the presence complement but exhibited diverse activities its absence. Amino acid substitutions that conferred resistance neutralization by each antibody were identified deriving nucleotide sequence gD gene from resistant mutants. Each selected a substitution different parts molecule mutants single always arose same mutation. One reacted with synthetic oligopeptide corresponding region...
Oncogenic mutations in RAS genes are very common human cancer, resulting cells with well-characterized selective advantages, but also less well-understood vulnerabilities. We have carried out a large-scale loss-of-function screen to identify that required by KRAS-transformed colon cancer cells, not derivatives lacking this oncogene. Top-scoring were then tested larger panel of KRAS mutant and wild-type cells. Cancer expressing oncogenic found be highly dependent on the transcription factor...
Abstract Using a panel of non–small cell lung cancer (NSCLC) lines, we show here that MAP-ERK kinase (MEK) and RAF inhibitors are selectively toxic for the KRAS-mutant genotype, whereas phosphoinositide 3-kinase (PI3K), AKT, mTOR not. IGF1 receptor (IGF1R) tyrosine also selectivity lines. Combinations IGF1R MEK resulted in strengthened inhibition lines showed improved effectiveness autochthonous mouse models Kras-induced NSCLC. PI3K pathway activity is dependent on basal KRAS-mutant, but not...
Abstract Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries an ageing, susceptible alveolar epithelium. Ageing risk factor for IPF and incidence has been demonstrated increase with age. Decreased (macro)autophagy age reported extensively in variety systems diseases, including IPF. However, it undetermined whether role faulty autophagy causal or coincidental context Here, we report...
The contribution of epithelial–mesenchymal transition (EMT) to human lung fibrogenesis is controversial. Here we provide evidence that ZEB1-mediated EMT in alveolar epithelial type II (ATII) cells contributes the development fibrosis by paracrine signalling underlying fibroblasts. Activation EGFR–RAS–ERK ATII induced via ZEB1. had extremely low extracellular matrix gene expression even after induction EMT, however conditioned media from undergoing RAS-induced augmented TGFβ-induced...
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study role of RAC1P29S melanoma development reveal that activates PAK, AKT, a gene expression program initiated by SRF/MRTF transcriptional pathway, which results melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous from endogenous locus develop lymphoma. When expressed only melanocytes, cooperates oncogenic or NF1-loss promote tumorigenesis. also drives...
Abstract Mutations in oncogenes such as KRAS and EGFR cause a high proportion of lung cancers. Drugs targeting these proteins tumor regression but ultimately fail to elicit cures. As result, there is an intense interest how best combine targeted therapies with other treatments, immunotherapies. However, preclinical systems for studying the interaction tumors host immune system are inadequate, part due low mutational burden genetically engineered mouse models. Here we set out develop models...
Abstract This study investigated the role of N-methyl-D-aspartate (NMDA)-type glutamatergic neurotransmission in mediating photic induction immediate-early gene expression Suprachiasmatic nucleus (SCN) Syrian hamster. Activation c-fos, c-jun and egr-1 was assessed by immunocytochemical detection their protein products. To characterize circadian basis to inductive effects light, hamsters were allowed free-run constant dim red light received a 1 h pulse at different phases relative activity...
Activating mutations in KRAS occur 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance therapy preclinical studies, the mutation does not predict patient outcome or response treatment, presumably due additional events modulating RAS pathways. To obtain a broader measure pathway activation, we developed RAS84, transcriptional signature optimised capture oncogenic activity LUAD. We report evidence activation 84% LUAD, including 65% wild-type tumours,...
Summary The production and properties of three monoclonal antibodies, designated LP1, LP4 AP2, directed against non-glycosylated polypeptides herpes simplex virus type 2 are described. LP1 is specific for polypeptide VP16 cross-reacts with HSV-1; reacts the major DNA-binding protein type-specific. AP2 capsid antigen HSV-1 HSV-2.
The discovery of mutations within genes associated with autosomal recessive Parkinson's disease allowed for the identification PINK1/Parkin regulated mitophagy as an important pathway removal damaged mitochondria. While recent studies suggest that AKT-dependent signalling regulates Parkin recruitment to depolarised mitochondria, little is known whether this can also regulate PINK1 mitochondrial accumulation and downstream mitophagy. Here, we demonstrate inhibition AKT decreases endogenous in...
Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury and/or dysfunction alveolar epithelium strongly implicated in IPF initiation, but factors that determine whether progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated zinc finger E-box-binding homeobox 1-mediated epithelial-mesenchymal transition human epithelial type II (ATII) cells augments transforming...
Intestinal barrier function in mice was assessed after acute or chronic oral administration of 15.8‐ and 5. 7‐μm synthetic spherical particles. The results failed to confirm previous reports that ingested particles rapidly appear blood. Furthermore, 15.8‐μm did not accumulate intestinal Peyer's patches, mesenteric lymph nodes, other organs the reticuloendothelial system, even maximum dosage 8 × 10 6 per day for 60 d. However, were demonstrated lungs 4.5 At 77 d termination ingestion, 5.7‐μm...