A5000710007- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- bioluminescence and chemiluminescence research
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Nutrition, Genetics, and Disease
- Emergency and Acute Care Studies
- DNA and Nucleic Acid Chemistry
- Healthcare Policy and Management
- Tissue Engineering and Regenerative Medicine
- Healthcare and Venom Research
- Shoulder Injury and Treatment
- Biomedical Ethics and Regulation
- Prenatal Substance Exposure Effects
- Health Systems, Economic Evaluations, Quality of Life
- Ethics in Clinical Research
- Metabolism and Genetic Disorders
- Economic and Financial Impacts of Cancer
- Tendon Structure and Treatment
- Plant-based Medicinal Research
- Climate Change and Health Impacts
- Radiopharmaceutical Chemistry and Applications
University of Florida
2024
Tameside and Glossop Integrated Care NHS Foundation Trust
2023
Institute of Cancer Research
2023
University of Oxford
2019-2022
Hospital for Special Surgery
2020
Mayo Clinic Health System
2020
Mayo Clinic in Arizona
2020
Mayo Clinic
2020
NewYork–Presbyterian Hospital
1982
Kings County Hospital Center
1961
BACKGROUND CD47 is a novel therapeutic target in the treatment of solid‐organ and hematologic malignancies. also expressed on RBCs. Here, we report our experience RBC effects impact blood bank testing transfusion management Phase 1 trial humanized anti‐CD47 monoclonal antibody Hu5F9‐G4 relapsed or primary refractory acute myeloid leukemia (AML) (NCT02678338). STUDY DESIGN AND METHODS Nineteen patients with AML treated across five UK centers were included for analysis. Patients received...
BackgroundCardiosphere-derived cells (CDCs) ameliorate skeletal and cardiac muscle deterioration in experimental models of Duchenne muscular dystrophy. The HOPE-2 trial examined the safety efficacy sequential intravenous infusions human allogeneic CDCs late-stage dystrophy.MethodsIn this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients with dystrophy, aged 10 years or older moderate upper limb impairment, were enrolled at seven centres USA. Patients randomly...
Abstract Purpose: Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 may benefit from PARP inhibitor treatment. inhibitors also increase exogenous replication stress thereby sensitivity ataxia telangiectasia Rad3-related (ATR) protein. This phase II study examined the activity combination inhibitor, olaparib, ATR ceralasertib (AZD6738), patients with advanced TNBC. Patients Methods: TNBC on most recent biopsy who had received 1 or...
Fulvestrant is used to treat patients with hormone receptor-positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating ESR1 mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (n = 69) revealed 3/69 (4%) novel F404 (F404L, F404I, F404V), cis mutations. In silico modeling that contributes...
Introduction: Community paramedicine (CP) is an innovative care model focused on medical management for patients suffering from chronic diseases or other conditions that result in over-utilization of healthcare services. Despite their value, CP models are not widely used United States settings. More research needed to understand the feasibility and effectiveness implementing programs. Our objective was develop a program better meet needs complex, high-utilizer rural setting.Methods: We...
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<div>Abstract<p>Fulvestrant is used to treat patients with hormone receptor–positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating <i>ESR1</i> mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (<i>n</i> = 69) revealed 3/69 (4%) novel F404 (F404L,...
<div>Abstract<p>Fulvestrant is used to treat patients with hormone receptor–positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating <i>ESR1</i> mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (<i>n</i> = 69) revealed 3/69 (4%) novel F404 (F404L,...
<p>Supplementary Figure 1. Progression free survival of patients with selected mutations. Supplementary 2. H356Y does not activate estrogen signalling or alter fulvestrant sensitivity in combination L536P. 3. Acquired ESR1 F404 mutations treated Fulvestrant. 4. Expression individual ER target genes RNAseq experiment. 5. Loss F404L mutation long-term culture “E” mutant clones. 6. Response D538G+F404L models to elacestrant. 7. camizestrant. 8. 4OH tamoxifen. 9. giredestrant.</p>
<p>F404 does not activate estrogen signaling. <b>A,</b> CRISPR clones of MCF7 cells expressing <i>ESR1</i> F404L (1210T>C, edit indicated by red arrows) or D538G (1613A>G; black were identified RT-PCR followed Sanger sequencing (left-hand panels). Similarly, a second round was used to introduce (1210T>C) into clone (D6C) that expressed right-hand <b>B,</b> Estrogen-dependent growth assessed in colony formation assay. Parental and...
<p>Baseline <i>ESR1</i> mutations and fulvestrant efficacy. <b>A,</b> % Incidence of in indicated genes at baseline Cohort A (<i>n</i> = 79 assessable patients). <b>B,</b> alterations within <b>C,</b> PFS patients A, divided by Y537C mutation status (left) Y537S (right). <i>P</i> values from the log-rank test. HR >1 denotes worse for that group. WT, wild-type; mt, mutant. <b>D,</b> MCF7 cells were...
<p>Baseline <i>ESR1</i> mutations and fulvestrant efficacy. <b>A,</b> % Incidence of in indicated genes at baseline Cohort A (<i>n</i> = 79 assessable patients). <b>B,</b> alterations within <b>C,</b> PFS patients A, divided by Y537C mutation status (left) Y537S (right). <i>P</i> values from the log-rank test. HR >1 denotes worse for that group. WT, wild-type; mt, mutant. <b>D,</b> MCF7 cells were...
<p>Acquired mutations on fulvestrant. <b>A,</b> Incidence of acquired alterations (<i>n</i> = 69 assessable patients), colored by targetability the (Methods). Level 2B denotes highest level supporting evidence (“Standard care biomarker recommended National Comprehensive Cancer Network or other professional advice guidelines predictive response to an FDA-approved drug”), whereas 4 is lowest (“Compelling biochemical supports as being a drug”)....
<p>F404 does not activate estrogen signaling. <b>A,</b> CRISPR clones of MCF7 cells expressing <i>ESR1</i> F404L (1210T>C, edit indicated by red arrows) or D538G (1613A>G; black were identified RT-PCR followed Sanger sequencing (left-hand panels). Similarly, a second round was used to introduce (1210T>C) into clone (D6C) that expressed right-hand <b>B,</b> Estrogen-dependent growth assessed in colony formation assay. Parental and...
<p>Compound F404 mutations are sensitive to novel SERDs. <b>A</b>–<b>D,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type, sensitivity elacestrant (<b>A</b>), camizestrant (<b>B</b>), 4OH tamoxifen (<b>C</b>), giredestrant (<b>D</b>), assessed after 6 days treatment CellTiter Glo viability assay. <i>n</i> = 4 mean SD. <b>E,</b> Representative clonongenic assays grown...
<p>Transcriptomic analysis of <i>ESR1</i>-mutant models. <b>A,</b> Gene set enrichment (GSEA) for D538G + F404L models compared with D6C cells maintained in 1 nmol/L estradiol. Pathways are highlighted red; false discovery rate-adjusted <i>q</i> value <0.05. <b>B,</b> GSEA treated μmol/L fulvestrant 24 hours. <b>C,</b> Normalized score (NES) is shown the indicated pathways. *, False <b>D,</b> Heat map “Estrogen...
<p>Compound F404 mutations are sensitive to novel SERDs. <b>A</b>–<b>D,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type, sensitivity elacestrant (<b>A</b>), camizestrant (<b>B</b>), 4OH tamoxifen (<b>C</b>), giredestrant (<b>D</b>), assessed after 6 days treatment CellTiter Glo viability assay. <i>n</i> = 4 mean SD. <b>E,</b> Representative clonongenic assays grown...