A5054490697- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Trypanosoma species research and implications
- ATP Synthase and ATPases Research
- Nanoplatforms for cancer theranostics
- Bacterial Genetics and Biotechnology
- Cancer Cells and Metastasis
- Neuroblastoma Research and Treatments
- RNA and protein synthesis mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Bacteriophages and microbial interactions
- Cancer-related Molecular Pathways
- Coenzyme Q10 studies and effects
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Studies on Chitinases and Chitosanases
- Virus-based gene therapy research
St James's University Hospital
2015-2024
University of Leeds
2015-2024
University of Manchester
2013-2023
Cancer Research UK Scotland Institute
2015
Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on cells results in durable antitumor activity melanoma patients. Despite high frequency brain metastases (BrM) associated poor prognosis, the mechanisms checkpoint inhibitors (ICI) metastatic tumors that develop within "immune specialized" microenvironment, remain elusive. We established a tumor transplantation model with intracranial plus extracranial (subcutaneous) tumor,...
// Nora Rippaus 1, * , David Taggart Jennifer Williams 1 Tereza Andreou Heiko Wurdak Krzysztof Wronski 2 Mihaela Lorger Institute of Cancer and Pathology, University Leeds, St. James's Hospital, LS9 7TF UK Geneflow Ltd, Elmhurst, Lichfield, Staffordshire WS13 8EX, These authors contributed equally to this work Correspondence to: Lorger, email: M.Lorger@leeds.ac.uk Keywords: metastasis-associated macrophages, tumor-associated breast cancer brain metastases, dural lymphotoxin β Received:...
Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding could pave the way novel therapeutic approaches. We used an
Abstract Background Brain metastases (BrM) develop in 20–40% of cancer patients and represent an unmet clinical need. Limited access drugs into the brain because blood-brain barrier is at least partially responsible for therapeutic failure, necessitating improved drug delivery systems. Methods Green fluorescent protein (GFP)-transduced murine nontransduced human hematopoietic stem cells (HSCs) were administered mice (n = 10 3). The HSC progeny mouse BrM patient-derived tissue 6) was...
The majority of the polytopic proteins that are synthesized at ER (endoplasmic reticulum) integrated co-translationally via Sec61 translocon, which provides lateral access for their hydrophobic TMs (transmembrane regions) to phospholipid bilayer. A prolonged association between potassium channel subunit, TASK-1 [TWIK (tandem-pore weak inwardly rectifying channel)-related acid-sensitive 1], and complex suggests translocon co-ordinates folding/assembly present in nascent chain. N-terminus both...
Background Brain metastases (BrM) affect up to 60% of patients with metastatic melanoma and are associated poor prognosis. While combined immune checkpoint blockade programmed death-1 (PD-1) cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) demonstrates intracranial efficacy in a proportion melanoma, the responses rarely durable, particularly symptomatic BrM. The brain is an immune-specialized organ regulated differently periphery. Methods Using our previously established two-site model...
Patients with glioblastoma (GBM) have a poor prognosis, and inefficient delivery of drugs to tumors represents major therapeutic hurdle. Hematopoietic stem cell (HSC)-derived myeloid cells efficiently home GBM constitute up 50% intratumoral cells, making them highly appropriate vehicles. Because are ubiquitously present in the body, we recently established lentiviral vector containing matrix metalloproteinase 14 (MMP14) promoter, which is active specifically tumor-infiltrating as opposed...
Mucopolysaccharidosis Type I (MPSI) is a rare inherited lysosomal storage disease that arises due to mutations in the IDUA gene. Defective alpha-L-iduronidase (IDUA) enzyme unable break down glucosaminoglycans (GAGs) within lysosomes and, as result, there systemic accumulation of undegraded products throughout body leading multi-system disease. Here, we characterised skeletal/craniofacial, neuromuscular and behavioural outcomes MPSI Idua-W392X mouse model. We demonstrate mice have gross...
Abstract Central nervous system metastases develop in ~15% of metastatic breast cancer patients and are associated with a very poor prognosis due to the lack effective therapies. Intracranial mainly located within brain parenchyma, skull, at leptomeninges or dura. Although simultaneous involvement multiple intracranial locations is common cancer, experimental studies have been focusing on parenchymal metastases. To address knowledge gap understanding other CNS locations, we developed...
Abstract BACKGROUND Brain metastases (BrM) are an unmet clinical need with poor prognosis. 60% of melanoma patients develop BrM. BrM strongly understudied due to frequent exclusion from trials, and hence treatment options commonly lag behind. Antibodies targeting the immune-inhibitory receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) programmed cell death 1 (PD-1) have demonstrated efficacy against Despite this, therapeutic responses highly variable, it is unknown why therapy...
Abstract BACKGROUND Up to 60% of melanoma patients develop brain metastases (BrM). These have a poor prognosis and limited treatment options. Immune checkpoint inhibitors (ICI) targeting Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) Programmed cell death protein-1 (PD-1) revolutionized the their efficacy has been also demonstrated in BrM. Our group previously that ICI (combined α-PD-1 α-CTLA-4) enhances chemokine-dependent infiltration cytotoxic T lymphocytes (CTLs) into BrMs...