- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Long-Term Effects of COVID-19
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Lymphatic System and Diseases
- SARS-CoV-2 detection and testing
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Zebrafish Biomedical Research Applications
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cancer Treatment and Pharmacology
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Colorectal Cancer Treatments and Studies
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
Regeneron (United States)
2009-2024
Pfizer (United States)
2012-2023
The Alfred Hospital
2023
Boston Children's Hospital
2021
Arizona Liver Health
2020
Target (United States)
2019
Scripps Research Institute
2013
University of Pennsylvania
2013
Johns Hopkins University
2013
Goethe University Frankfurt
2013
BackgroundRecent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.MethodsIn this ongoing, double-blind, phase 1–3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) reduce the risk of emergence treatment-resistant mutant virus. Patients were...
Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal cells. Recent publications suggest that small subset colon expresses CD133, and only these capable tumor initiation. However, the precise contribution tumor-initiating in mediating metastasis remains unknown. Therefore, temporally spatially track expression CD133 adult mice during tumorigenesis, we generated knockin lacZ reporter mouse (CD133lacZ/+), which is driven by endogenous promoters....
REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce risk hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous prevents severe acute respiratory syndrome 2 (SARS-CoV-2) infection subsequent Covid-19 in at high for because household exposure person SARS-CoV-2 is unknown. We randomly assigned, 1:1 ratio, participants (≥12 years age) who were...
In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination monoclonal antibodies casirivimab and imdevimab, reduced viral load number medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity vitro against current severe acute respiratory syndrome 2 (SARS-CoV-2) variants concern. 3 we randomly assigned outpatients Covid-19 risk factors for to receive various doses intravenous or placebo. Patients were followed through day 29. A prespecified...
Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report controls transcription of the transporter SLC16A1/MCT1 and elevated MCT1 levels are manifest in premalignant neoplastic Eμ-Myc transgenic B cells human malignancies with MYC or MYCN involvement. Notably, disrupting function leads to an accumulation intracellular rapidly disables tumor cell growth provoking marked alterations glycolytic intermediates, reductions...
Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option COVID-19. Because rapidly emerging virus mutants becoming the next major concern in fight global pandemic, it is imperative that these treatments provide coverage circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated sequence diversity spike protein monitored emergence SARS-COV-2 isolates found COVID-19 patients treated with...
Easy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection symptomatic disease and reduce viral carriage.
Angiopoietin-1 (Ang-1) and its naturally occurring antagonist angiopoietin-2 (Ang-2) are novel ligands that regulate tyrosine phosphorylation of the Tie2/Tek receptor on endothelial cells. Proper regulation is absolutely required for normal vascular development, seemingly by regulating remodeling cell interactions with supporting pericytes/smooth muscle We investigated expression Ang-1 Ang-2 in human astrocytomas situ hybridization compared them to distribution cells immunohistochemistry...
Vascular endothelial growth factor receptor 1 (VEGFR-1) is present on cells and subsets of human tumor cells, raising the hypothesis that angiogenic factors may promote both by inducing angiogenesis directly signaling through activation VEGFR-1 cells. Here, we report expressed a panel 16 breast cell lines, vasculature compartment subset carcinoma lesions, selective cancer supports downstream p44/42 mitogen-activated protein kinase (MAPK) or Akt pathways. Ligand-stimulated proliferation was...
Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development homeostasis in pathological conditions, such as cancer proliferative retinopathies. Most effects of VEGF-A mediated by VEGFR2 its coreceptor, neuropilin (NRP)-1. Here, we show that is shed from cells metalloprotease disintegrin ADAM17, whereas NRP-1 released ADAM10. enhances shedding ADAM17 but not activates via extracellular signal-regulated kinase (ERK)...
Abstract Background The clinical success of immune checkpoint inhibitors demonstrates that reactivation the human system delivers durable responses for some patients and represents an exciting approach cancer treatment. An important class preclinical in vivo models immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation studies into human, we characterized genomic, transcriptomic, protein expression a panel ten commonly used tumor cell lines grown...
Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis poorly understood, there is currently a lack of laboratory animal model to enhance our understanding. We aimed develop such using cynomolgus monkeys.Chinese-origin monkeys were dosed intravenously vehicle nivolumab 20 mg/kg plus ipilimumab 15 once...
While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates protection COVID-19 in the casirivimab + imdevimab (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and mRNA-1273 vaccine #NCT04470427). mAb trial, protective efficacy 92% (95% confidence interval (CI): 84%, 98%) is associated with a...
BACKGROUND Pancreatic carcinoma is associated with a poor prognosis, and treatment options for patients this disease are limited. The epidermal growth factor (EGF) receptor its ligands overexpressed in human pancreatic may contribute to the pathophysiology of these tumors. METHODS anti-EGF monoclonal antibody IMC-C225 was used determine effects EGF blockade on BxPC-3 cells vitro. Athymic mice bearing established (200 mm3) subcutaneous xenografts were treated (17 or 33 mg/kg every 3 days)...
The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1 (flk1; VEGFR-2, KDR) is an cell–specific tyrosine that mediates physiological and pathological angiogenesis. We hypothesized active immunotherapy approach targeting flk1 may inhibit tumor angiogenesis metastasis. To test this hypothesis, we first evaluated whether immune responses to could be elicited in mice by immunization with dendritic cells pulsed a soluble protein (DC-flk1). This generated flk1-specific...