A5074875259- Acute Myeloid Leukemia Research
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- RNA Interference and Gene Delivery
- Hematological disorders and diagnostics
- Galectins and Cancer Biology
- Cancer, Hypoxia, and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nuclear Receptors and Signaling
- Bone and Joint Diseases
- Chronic Myeloid Leukemia Treatments
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- Beetle Biology and Toxicology Studies
- Histone Deacetylase Inhibitors Research
- Cancer therapeutics and mechanisms
- Calcium signaling and nucleotide metabolism
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Lymphoma Diagnosis and Treatment
- interferon and immune responses
Newcastle University
2019-2022
University of East Anglia
2015-2019
Norwich Research Park
2015-2019
Norwich University
2017
Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move cells from their microenvironment, metabolic consequences this phenomenon yet be fully elucidated. Here, we report that multiple myeloma use mitochondrial-based metabolism as well glycolysis when located within bone marrow microenvironment. The reliance on oxidative phosphorylation was caused by intercellular mitochondrial transfer neighboring...
Phosphoinositide-3-kinase (PI3K) is an enzyme group, known to regulate key survival pathways in acute myeloid leukaemia (AML). It generates phosphatidylinositol-3,4,5-triphosphate, which provides a membrane docking site for protein kinaseB activation. PI3K catalytic p110 subunits are divided into 4 isoforms; α,β,δ and γ. The PI3Kδ isoform always expressed AML cells, whereas the frequency of PI3Kγ expression highly variable. functions these individual enzymes have not been fully resolved AML,...
Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown pharmacologic isoform-specific inhibition we investigated the role PI3K p110γ (PI3Kγ) subunit regulating MM proliferation bone marrow microenvironment-induced interactions. We compared this with p110δ (PI3kδ) combined PI3kδ/γ dual inhibition. found that cell adhesion migration were PI3Kγ-specific functions, PI3kδ...
Abstract Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated time diagnosis treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) 1.47–2.15; P 2.71 × 10 −9 ) 6p (rs3778076,...
Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient acute myeloid leukemia (AML) that was chemoresistant anthracycline and cytarabine acutely sensitive 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting long-term morphological remission. Given the role...
Abstract Introduction: Most patients diagnosed with acute myeloid leukaemia [AML] die of their disease and the average age at diagnosis is 72 years. For this reason, new therapeutic strategies tolerability in fragile, less fit population necessary for reducing mortality rate associated disease. The tumor microenvironment an emerging target search cytotoxic therapies. We have previously shown that adipocyte component bone marrow (BM) a key player blast survival, proliferation chemotherapy...
<div>Abstract<p>Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move cells from their microenvironment, metabolic consequences this phenomenon yet be fully elucidated. Here, we report that multiple myeloma use mitochondrial-based metabolism as well glycolysis when located within bone marrow microenvironment. The reliance on oxidative phosphorylation was caused by intercellular...
<p>Supplementary figures. Supplementary Fig 1A shows mitochondrial function in BMSC compared to MM cells. 1B respiration of cells cultured with succinate control. 2A percent cell engraftment NSG mice. 2B sorted human from bone marrow. 3A quantification vitro transfer 3B detection mtDNA control and rho0 BMSC. 4 various culture conditions. 5A-C TNT formation between 6 anchor points located on after coculture lines. 7 direct 8 CD38 protein expression shRNA targeted 9 KD MM1S-luc mice.</p>
<p>Supplementary methods. Contains sections on generation of rho0 stromal cells, co-culture primary BMSC and MM cells extended Seahorse extracellular flux assay methods,</p>
<p>Supplementary figures. Supplementary Fig 1A shows mitochondrial function in BMSC compared to MM cells. 1B respiration of cells cultured with succinate control. 2A percent cell engraftment NSG mice. 2B sorted human from bone marrow. 3A quantification vitro transfer 3B detection mtDNA control and rho0 BMSC. 4 various culture conditions. 5A-C TNT formation between 6 anchor points located on after coculture lines. 7 direct 8 CD38 protein expression shRNA targeted 9 KD MM1S-luc mice.</p>
<p>Supplementary methods. Contains sections on generation of rho0 stromal cells, co-culture primary BMSC and MM cells extended Seahorse extracellular flux assay methods,</p>
<div>Abstract<p>Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move cells from their microenvironment, metabolic consequences this phenomenon yet be fully elucidated. Here, we report that multiple myeloma use mitochondrial-based metabolism as well glycolysis when located within bone marrow microenvironment. The reliance on oxidative phosphorylation was caused by intercellular...