A5085840629- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Transgenic Plants and Applications
- Lipid Membrane Structure and Behavior
- Virus-based gene therapy research
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Drug Transport and Resistance Mechanisms
- Cancer-related Molecular Pathways
- Thyroid Cancer Diagnosis and Treatment
- Thyroid Disorders and Treatments
- RNA Interference and Gene Delivery
- Erythrocyte Function and Pathophysiology
- Growth Hormone and Insulin-like Growth Factors
- Immunotherapy and Immune Responses
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
- Microtubule and mitosis dynamics
- Cell death mechanisms and regulation
- S100 Proteins and Annexins
- Cholesterol and Lipid Metabolism
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
University College London
2007-2023
Queen Mary University of London
2005-2023
Molecular Oncology (United States)
2023
Lung Institute
2021-2022
Imperial College London
2021-2022
University College Hospital
2022
London School of Hygiene & Tropical Medicine
2022
NIHR Imperial Biomedical Research Centre
2021
National Cancer Institute
2000-2020
Center for Cancer Research
2012-2020
Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, product multidrug-resistance gene (MDR1), in normal human tissues. The protein found be concentrated a small number specific sites. Most tissues examined revealed very little P-glycoprotein. However, certain cell types liver, pancreas, kidney, colon, and jejunum showed localization In P-glycoprotein exclusively on biliary canalicular front hepatocytes apical surface epithelial cells ductules. ductules but not...
We characterized the transcriptional activity of long terminal repeat (LTR) Rous sarcoma virus by constructing a recombinant plasmid, pRSVcat, in which bacterial chloramphenicol acetyltransferase (CAT; acetyl-CoA:chloramphenicol 3-O-acetyltransferase, EC 2.3.1.28) coding sequences are placed under LTR control. find that directs relatively high levels CAT synthesis within 48 hr after calcium phosphate-mediated introduction this plasmid into CV-1 monkey kidney cells, chicken embryo...
Journal Article Expression of Multidrug Resistance Gene in Human Cancers Get access Lori J. Goldstein, Goldstein 1(Laboratory Molecular Biology, Division Cancer Biology and Diagnosis) Search for other works by this author on: Oxford Academic PubMed Google Scholar Hanan Galski, Galski Antonio Fojo, Fojo Mark Willingham, Willingham Shinn-Lian Lai, Lai 6(NCI-Navy Medical Oncology Branch, Treatment) Adi Gazdar, Gazdar Robert Pirker, Pirker 2Second ClinicGarnisongasse 13, A-1090 Vienna, Austria...
The binding and internalization of '251-epidermal growth factor ("%EGF) was studied in cultures BALB 3T3 cells using a novel method that involved removal cell-surface hormone by treatment with acetic acid under conditions did not remove internalized hormone.In control cultures, la51-EGF initially bound to its receptor on the plasma membrane then rapidly internalized.After 30 min, only 15% cell-bound remained surface.In contrast, treated dansylcadaverine retained 82% cell surface.We propose...
We have studied in detail the binding of fluorescent derivatives insulin and epidermal growth factor to 3T3 fibroblasts. used two types analogues factor: highly which seven eight rhodamine molecules or a single molecule per one factor. Both analogue retained substantial affinity as determined by radioreceptor assays biological activity. The cells labeled with were visualized sensitive video intensification microscopic system that enabled us directly observe location hormone on surface within...
Using peroxidase immunohistochemistry, we examined the distribution of P170, a multidrug transport protein, in normal tissues by use two different monoclonal antibodies (MAb). MAb MRK16 is that has been shown to react with an epitope P170 located on external face plasma membrane multidrug-resistant human cells. C219 many mammalian species, and detects cytoplasmic membrane. MRK16, have previously described localization bile canalicular hepatocytes, apical surface proximal tubular cells...
Fibroblasts contain a specific internalization pathway that carries hormones as well some proteins and viruses from the cell surface to interior. Initially, ligands bind mobile receptors are randomly distributed on surface. Next ligand-receptor complexes trapped concentrated in specialized regions of membrane termed bristle-coated pits. From pit smooth-walled vesicle containing ligand forms Because its role receptor-mediated endocytosis, this has been "receptosome."
A full-length cDNA for the human multidrug resistance gene 1 (MDR1) has been inserted into a retroviral vector containing murine Harvey sarcoma virus from which viral oncogene was deleted. Ecotropic and amphotropic produced after transfection of this psi-2 PA-12 packaging cell lines. This conferred full phenotype on mouse Viral titers up to 2 X 10(5) drug-resistant colonies per ml were observed. Infected cells became resistant colchicine, vinblastine, doxorubicin, VP16 (etoposide),...
Apoptosis, the terminal morphological and biochemical events of programmed cell death, is characterized by specific changes in surface nuclear morphology. In addition, DNA fragmentation an internucleosomal pattern detectable mass cultures apoptotic cells. However, may not necessarily be associated events. this study, we examined OVCAR-3 KB human carcinoma cells using time-lapse video phase-contrast microscopy to characterize features apoptosis response treatment with either taxol or ricin....
Two murine lysosome-associated membrane proteins, LAMP-1 of 105,000-115,000 D and LAMP-2 100,000-110,000 D, have been identified by monoclonal antibodies that bind specifically to lysosomal membranes. Both glycoproteins were distinguished as integral components solubilized detergent solutions but not various chaotropic agents. The lysosome localization was demonstrated indirect immunofluorescent staining, co-localization the antigen sites acridine orange uptake, immunoelectron microscopy....
The epidermal growth factor (EGF) receptor gene EGFR has been placed in a retrovirus vector to examine the properties of cells that experimentally overproduce full-length EGF receptor. NIH 3T3 transfected with viral DNA or infected corresponding rescued developed fully transformed phenotype vitro required both functional expression and presence medium. Cells expressing 4 x 10(5) receptors formed tumors nude mice, while control did not. Therefore, retrovirus, which had titer on was greater...
An iron efflux pump is a pivotal protein in breast cancer biology and strong independent predictor of prognosis.
ADP-ribosylation factor (ARF) is a ubiquitous, highly conserved 21-kDa GTP-binding protein, first identified in animal cells as the cofactor required for vitro of stimulatory regulatory subunit adenylate cyclase, Gs, by cholera toxin. As relevance this activity to vivo function unknown, we have taken advantage nature ARF study its Saccharomyces cerevisiae. Yeast bearing an arf1 null mutation display number phenotypes suggesting defect secretory pathway. Secreted invertase only partially...
To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers.SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 advanced mesothelioma (n = 20), ovarian 12), pancreatic 2) cancer.The initial cohort 17 received QOD x 6 MTD 18 microg/kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient)...
Niemann-Pick C1-like 1 (NPC1L1) is required for cholesterol absorption. Intestinal NPC1L1 appears to be a target of ezetimibe, absorption inhibitor that effectively lowers plasma LDL-cholesterol in humans. However, human liver also expresses NPC1L1. Hepatic function was previously unknown, but we recently discovered localizes the canalicular membrane primate hepatocytes and facilitates uptake hepatoma cells. Based upon these findings, hypothesized hepatic allows retention biliary by...
Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis. is only known mechanism export intracellular non–heme-associated iron; its stability regulated by hormone hepcidin. Although ferroportin profoundly affects concentrations in tissues important absorption trafficking, breast cancer their influence on growth prognosis have not been examined. We demonstrate here that both expressed cultured human epithelial cells regulates these cells. Further,...
Macrophage-specific Abca1 knock-out (Abca1(-)(M)(/-)(M)) mice were generated to determine the role of macrophage ABCA1 expression in plasma lipoprotein concentrations and innate immune response macrophages. Plasma lipid chow-fed Abca1(-)(M)(/-)(M) wild-type (WT) indistinguishable. Compared with WT macrophages, macrophages had a >95% reduction protein, failed efflux apoA-I, significant increase free cholesterol (FC) membrane rafts without induction endoplasmic reticulum stress....
Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) lung fibrosis suggest severe acute respiratory syndrome 2 (SARS-CoV-2) infection may lead to progressive damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned estimate the prevalence of residual abnormalities in people hospitalized with COVID-19 on basis risk strata. Methods: PHOSP–COVID-19 (Post-Hospitalization COVID-19) used capture...
Apoptosis has gained central importance in the study of many biological processes, including neoplasia, neurodegenerative diseases, and development. One limitations studies is difficulty specifically identifying individual apoptotic cells. Of specific methods developed to detect cells, most are not applicable histological sections archival paraffin-embedded tissues. Recently, advances understanding molecular events apoptosis have led realization that caspase activation by far indicator this...