A5000424441- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- FOXO transcription factor regulation
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Nuclear Receptors and Signaling
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Caveolin-1 and cellular processes
- Pancreatitis Pathology and Treatment
- Pancreatic function and diabetes
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- Magnetic confinement fusion research
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Plasma Diagnostics and Applications
- TGF-β signaling in diseases
Cancer Research UK
2021-2024
Cancer Research UK Scotland Institute
2021
Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition 18 murine tissues 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals heterogeneity across tumors, identifies coordinated between immune cell subsets in pancreatic ductal adenocarcinoma. Expression CD105 demarks two stable...
<p>Release from AZD6244 treatment results in rapid acinar to ductal metaplasia KC KrasG12D/fl.</p>
<p>Early intervention with AZD6244 reduces PanIN burden in <i>Kras</i><sup>G12D/fl</sup> mice. <b>A,</b> Experimental schematic. KC were treated from day 42 for 28 days vehicle or and sampled at 70. <b>B,</b> Representative hematoxylin eosin (H&E), pERK1/2, Ki67 IHC images pancreata of mice 70 age following treatment as indicated days. four per group. Scale bar, 200 μm. <b>C,</b> Quantification grading PanINs...
<p>Increased fibrosis in wild-type Kras deficient PanINs.</p>
<p>Loss of wild-type KRAS sensitizes KPC KrasG12D/fl tumours to MEK1/2 inhibition.</p>
<div>Abstract<p>Pancreatic cancer is characterized by the prevalence of oncogenic mutations in <i>KRAS</i>. Previous studies have reported that altered <i>KRAS</i> gene dosage drives progression and metastasis pancreatic cancer. Whereas role well characterized, relevance partnering wild-type (WT) allele less understood controversial. Using <i>in vivo</i> mouse modeling cancer, we demonstrated WT KRAS restrains impact mutant dramatically impacts...
<p>Loss of WT <i>Kras</i> increases PanIN formation in the presence oncogenic <i>Kras</i>. <b>A,</b> Kaplan–Meier survival curve for human patients with PDAC <i>KRAS</i> alleles balanced and imbalanced. KRAS balanced, <i>n</i> = 47; imbalanced, 32. *, <i>P</i> 0.029, log-rank (Mantel–Cox) test. <b>B,</b> Proportion pancreatic cancer (59.5%) imbalanced (40.5%), from <b>A</b>....
<p>Acceleration of pancreatic tumour initiation after loss wild-type Kras in KPC KrasG12D/fl mice.</p>
<p>Late-stage intervention with MEK1/2 inhibition improves survival of KPC <i>Kras</i><sup>G12D/fl</sup> mice. <b>A,</b> Experimental schematic. <i>Kras</i><sup>G12D/+</sup> and mice were palpated for tumor burden, palpable burden confirmed by ultrasound imaging, treated continuously from the following day either vehicle or AZD6244. Tumor growth was monitored imaging once weekly to clinical endpoint. <b>B,</b>...
<p>Loss of WT KRAS induces increased MAPK signaling in KPC <i>Kras</i><sup>G12D/fl</sup>. <b>A,</b> Experimental schematic representing mice imaged once weekly by ultrasound from 6 weeks age to clinical endpoint follow tumor growth over time. <b>B,</b> Tumor volume relative that at initial detection <i>Kras</i><sup>G12D/+</sup> and <i>Kras</i><sup>G12D/fl</sup> aged measured imaging age....
<p>Loss of wild-type KRAS does not alter PI3K-AKT signalling.</p>
<p>MEK1/2 inhibition in KPC KrasG12D/fl mice with established tumours reverses enrichment of immune response related gene programmes.</p>
Abstract Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis pancreatic cancer. While role well characterized, relevance partnering wild-type allele less understood controversial. Using vivo mouse modelling cancer, we demonstrated restrains impact mutant dramatically impacts both KRAS-mediated tumorigenesis therapeutic response. Mechanistically, deletion Kras...
ABSTRACT TP53 is a potent tumour suppressor that coordinates diverse stress response programmes within the cell. The activity of p53 frequently context and cell type-dependent, ranges from pro-survival activities, including implementation transient cycle arrest metabolic rewiring, through to death. In addition functions, also has established roles in pathological occurs during tissue damage repair, liver. Metabolic dysfunction-associated steatohepatitis (MASH) major driver hepatocellular...