A5080933870- Cancer survivorship and care
- Fibromyalgia and Chronic Fatigue Syndrome Research
- COVID-19 Clinical Research Studies
- Cancer Treatment and Pharmacology
- Lymphatic System and Diseases
- Cancer-related cognitive impairment studies
- Long-Term Effects of COVID-19
- Acute Ischemic Stroke Management
- Effects of Radiation Exposure
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Myeloid Leukemia Treatments
- Tryptophan and brain disorders
- Stroke Rehabilitation and Recovery
- Cell Adhesion Molecules Research
- Exercise and Physiological Responses
- SARS-CoV-2 and COVID-19 Research
- Chronic Lymphocytic Leukemia Research
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Nutrition and Health in Aging
- Intensive Care Unit Cognitive Disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- Diabetes Treatment and Management
- NF-κB Signaling Pathways
- Childhood Cancer Survivors' Quality of Life
King's College London
2024
University Hospitals Birmingham NHS Foundation Trust
2021-2024
West Suffolk NHS Foundation Trust
2024
University of Cambridge
2024
University of Leeds
2024
University of Oxford
2023
Boston College
2020-2022
Campbell Collaboration
2021
NIHR Clinical Research Network
2021
National Institute for Health Research
2021
Kinase domain (KD) mutations of Bcr-Abl interfering with imatinib binding are the major mechanism acquired resistance in patients Philadelphia chromosome-positive leukemia. Mutations ATP loop (p-loop) have been associated a poor prognosis. We compared transformation potency five common KD mutants various biological assays. Relative to unmutated (native) Bcr-Abl, Y253F and E255K exhibited increased potency, M351T H396P were less potent, performance T315I was assay dependent. The correlated...
Abstract The JAK2V617F mutation is present in almost all patients with polycythemia vera (PV), large proportions of essential thrombocythemia and idiopathic myelofibrosis, less frequently atypical myeloproliferative disorders (MPD). We show that transplantation JAK2V617F-transduced bone marrow into BALB/c mice induces MPD reminiscent human PV, characterized by erythrocytosis, granulocytosis, extramedullary hematopoiesis, fibrosis, but not thrombocytosis. Fluorescence-activated cell sorting...
Anthracyclines including doxorubicin and daunorubicin are commonly used for the treatment of both hematologic solid tumors. Dose related adverse effects often limit effectiveness anthracyclines in chemotherapy. Drug-related systemic inflammation mediated by interleukin-1 beta (IL-1β) has been implicated contributing to these effects. The molecular mechanisms underlying anthracycline-mediated expression IL-1β release not understood. Elucidating basis which upregulate activity may present...
The HMG-I/Y gene encodes the HMG-I and HMG-Y proteins, which function as architectural chromatin binding proteins important in transcriptional regulation of several genes. Although increased expression is associated with cellular proliferation, neoplastic transformation, human cancers, role these pathogenesis malignancy remains unclear. To better understand cell growth we have been studying HMG-I/Y. promoter was cloned, sequenced, subjected to mutagenesis analysis. A c-Myc–Max consensus DNA...
Abstract Although previous studies have established a prominent role for HMGA1 (formerly HMG-I/Y) in aggressive human cancers, the of HMGA2 HMGI-C) malignant transformation has not been clearly defined. The HMGA gene family includes HMGA1, which encodes HMGA1a and HMGA1b protein isoforms, HMGA2, HMGA2. These chromatin-binding proteins function transcriptional regulation recent also suggest cellular senescence. appear to participate cell cycle transformation, whereas implicated primarily...
Abstract HMG-I/Y is overexpressed in human cancer, although a direct role for this gene transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder developed aggressive lymphoma by mean age of 4.8 months. Tumors express T-cell markers and are transplantable. also demonstrate that mRNA protein increased acute lymphocytic leukemia samples. Our results show functions as an oncogene suggest it contributes the...
Cancer chemotherapy–related symptoms such as fatigue, malaise, loss of interest in social activities, difficulty concentrating, and changes sleep patterns can lead to treatment delays, dose reductions, or termination have a profound effect on the physical, psychosocial, economic aspects quality life. Clinicians long suspected that these are similar those associated with “sickness behavior,” which is triggered by production inflammatory cytokines IL-1β, TNF-α, IL-6 macrophages other cells...
Although lung cancer is the leading cause of death worldwide, precise molecular mechanisms that give rise to are incompletely understood. Here, we show HMGA1 an important oncogene drives transformation in undifferentiated, large-cell carcinoma. First, gene overexpressed cell lines and primary human tumors. Forced overexpression induces a transformed phenotype with anchorage-independent growth cultured cells derived from normal tissue. Conversely, inhibiting expression blocks H1299...
The adverse side effects of doxorubicin, including cardiotoxicity and cancer treatment-related fatigue, have been associated with inflammatory cytokines, many which are regulated by mitogen-activated protein kinases (MAPKs). ZAK is an upstream kinase the MAPK cascade. Using mouse primary macrophages cultured from ZAK-deficient mice, we demonstrated that required for activation JNK p38 doxorubicin. Nilotinib, ponatinib sorafenib strongly suppressed doxorubicin-mediated phosphorylation MAPK....
Cancer patients undergoing treatment with systemic cancer chemotherapy drugs often experience debilitating fatigue similar to sickness behavior, a normal response infection or tissue damage caused by the production of inflammatory cytokines IL-1beta, TNF-alpha, and IL-6. The p38 mitogen activated protein kinase (p38 MAPK) plays central role in these consequently development behavior. Targeted inhibitors MAPK can reduce cytokine Several have been shown stimulate production, yet whether this...
Mounting evidence suggests fibromyalgia (FM) symptoms are influenced by dysfunction of the hypothalamicpituitary-hormonal axes (HPHA) and immune response system.The predominant FM widespread pain, fatigue, sleep disturbance, depression, stiffness exercise intolerance related to abnormal levels growth hormone (GH) reminiscent "sickness behavior"; a syndrome initiated production pro-inflammatory cytokines in various stressors.Cognizant reciprocal relationship between HPHA activity system, we...
Exercise improves cognitive function in older adults, but the underlying mechanism is largely unknown. Both lysosomal degradation and mitochondrial quality control decline with age. We hypothesized that exercise ameliorates age-related through improvement of aged hippocampus, this effect associated proteolysis. Sixteen to eighteen-month old male Sprague Dawley rats underwent swim training for 10 weeks. The regimen prevented rats, reduced oxidative stress, rejuvenated mitochondria...
We have used the yeast GAL4 two-hybrid system to examine interactions between human cytomegalovirus (HCMV) major capsid protein (MCP, encoded by UL86) and precursor assembly (pAP, UL80.5 cleaved at its carboxyl end yield AP) found that (i) pAP interacts with MCP through residues located within carboxy-terminal 21 amino acids of pAP, called conserved domain (CCD); (ii) itself a separate region, (ACD), His34 Arg52 near molecule; (iii) simian CMV (SCMV) AP can interact or replace their HCMV...