A5072809262- Glioma Diagnosis and Treatment
- Hepatitis B Virus Studies
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
- Retinal Diseases and Treatments
- Hepatitis C virus research
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Angiogenesis and VEGF in Cancer
- Liver Disease Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Retinal and Optic Conditions
- Coronary Interventions and Diagnostics
- Blood groups and transfusion
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pharmacogenetics and Drug Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Erythrocyte Function and Pathophysiology
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Multiple Myeloma Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Retinal Imaging and Analysis
Virginia Commonwealth University
2025
Children's Hospital of Zhejiang University
2025
Children's Clinical University Hospital
2025
Agios Pharmaceuticals (United States)
2015-2023
Gilead Sciences (United States)
2022
Alnylam Pharmaceuticals (United States)
2022
Memorial Sloan Kettering Cancer Center
2018
Genentech
2014
Johns Hopkins University
2009
Massachusetts Institute of Technology
2009
<h3>Background</h3> Data comparing systemic exposure and vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab aflibercept following intravitreal injection are lacking. <h3>Methods</h3> Fifty-six patients with wet age-related macular degeneration received ranibizumab (0.5 mg), (1.25 or (2.0 mg). Serum pharmacokinetics plasma free VEGF were evaluated after the first third injections. <h3>Results</h3> Following dose, to was 5-, 37-, 9-fold higher than whereas, 9-,...
Purpose: To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic edema (DME), or retinal vein occlusion (RVO). Methods: Prospective, open-label, nonrandomized clinical trial AMD, DME, RVO who were antivascular endothelial growth factor (VEGF) naïve had not received anti-VEGF for ≥4 months. Patients 3 monthly intravitreal injections aflibercept 2.0 mg, bevacizumab 1.25 (0.5 mg...
Abstract Purpose: Lower grade gliomas (LGGs) are malignant brain tumors. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) a first-in-class, brain-penetrant, dual inhibitor mutant IDH1 IDH2 enzymes. Patients Methods: We conducted multicenter, open-label, phase I, dose-escalation study vorasidenib...
Abstract Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) have shown preliminary clinical activity against m IDH glioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism action recurrent low-grade glioma (IGG) select molecule for 3 testing. Primary end-point was concentration d -2-hydroxyglutarate (2-HG), metabolic product mIDH enzymes, measured tumor tissue from 49 patients with IDH1 -R132H nonenhancing gliomas following...
The phase 2 MAHALO clinical trial shows that lampalizumab reduces geographic atrophy secondary to age-related macular degeneration and implicates complement dysregulation in disease pathogenesis.
Abstract Quantitative systems pharmacology (QSP) approaches have been increasingly applied in the pharmaceutical since landmark white paper published 2011 by a National Institutes of Health working group brought attention to discipline. In this perspective, we discuss QSP context other modeling and highlight impact across various stages drug development therapeutic areas. We challenges field as well future opportunities.
Anti–factor D (AFD; FCFD4514S, lampalizumab) is a humanized IgG Fab fragment directed against factor (fD), rate-limiting serine protease in the alternative complement pathway (AP). Evaluation of AFD as potential intravitreal (IVT) therapeutic for dry age-related macular degeneration patients with geographic atrophy (GA) ongoing. However, it unclear whether IVT administration can affect systemic AP activation and potentially compromise host-immune responses. We characterized pharmacologic...
Abstract Background Disturbances in sleep have been associated with systemic inflammation and increased susceptibility to various chronic diseases. However, the specific mechanisms by which influences plasma protein expression contributes risk of inflammatory bowel disease (IBD) not fully elucidated. Methods We analysed data from 381,228 participants UK Biobank. Sleep was scored chronotype, duration, insomnia, daytime sleepiness. Adjusted odds ratios (ORs) for prevalent IBD unhealthy...
2003 Background: AG-120 (ivosidenib [IVO]) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) evaluated in 66 glioma patients (pts) an ongoing phase study. AG-881 (vorasidenib [VOR]) oral, potent, brain-penetrant mIDH1/2 52 pts In orthotopic model, IVO and VOR reduced 2-hydroxyglutarate (2-HG) by 85% 98%, respectively, despite different brain:plasma ratios (<0.04 vs 1.33). Methods: Primary endpoint: brain tumor 2-HG concentration with or treatment mIDH1...
2002 Background: Isocitrate dehydrogenase 1 and 2 mutations (mIDH1/2) occur in solid tumors including glioma, result production of the oncometabolite 2-hydroxyglutarate (2-HG), promoting tumorigenesis. AG-881 is an oral, potent, brain-penetrant inhibitor mIDH1/2 that reduces 2-HG by up to 98% glioma models. Methods: Patients (pts) with recurrent/progressive (G) non-glioma (NG) were eligible receive daily continuous 28-day cycles. Dose escalation cohorts for G NG enrolled using a Bayesian...
Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody against complement factor D (CFD), rate-limiting enzyme in the activation and amplification alternative pathway (ACP), which phase III clinical trials for treatment geographic atrophy. Understanding pharmacokinetics, pharmacodynamics, biodistribution lampalizumab following intravitreal administration ocular compartments systemic circulation limited but crucial selecting doses that provide optimal efficacy safety....
An understanding of cardiac health and disease requires knowledge the various factors that control coronary capillary blood flow. analysis flow based on a complete set actual data anatomy elasticity does not exist. Previously, branching pattern vascular geometry pig network were obtained in our laboratory. In present study, we distensibility vessels epicardial surface form pressure-diameter relationship using intravital microscopy. A mathematical model was then constructed basis measured...
Abstract BACKGROUND Ivosidenib (AG-120, IVO) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), and vorasidenib (AG-881, VOR) an oral, potent, brain-penetrant mIDH1/2. Both have been evaluated in glioma patients ongoing phase studies. In orthotopic models, IVO VOR reduced 2-hydroxyglutarate (2-HG) levels by 85% 98%, respectively, despite different brain-to-plasma ratios (< 0.04 vs 1.33). METHODS Patients with recurrent, nonenhancing, WHO-2016 grade 2/3,...
SummaryThe effectiveness of eight different assessment methods – (1) seminar, (2) closed-book mid semester test, (3) open-book mid-semester (4) problem-based assignment, (5) presentation, (6) multiple choice question (7) final examination, and (8) examination is studied in this paper. A detailed survey conducted to thoroughly understand student needs, the significance items methods. Individual interviews are gather further information clarification on survey. Relative important index (RII)...
TPS2574 Background: Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options consist of surgery followed by observation (“watch wait”) for pts with lower risk disease progression or post-operative chemo-radiotherapy (high-risk population). There no approved targeted therapies. IDH1 IDH2 mutations (m IDH1/2) occur in approximately 70% 4% LGGs, respectively, promote tumorigenesis via neomorphic production...
INTRODUCTION: Isocitrate dehydrogenase 1 and 2 mutations (mIDH1/2) occur in >70% of low-grade gliomas secondary glioblastomas, lead to genetic epigenetic dysregulation, promoting tumorigenesis. AG-881 is an oral, potent, brain-penetrant inhibitor mIDH1/2 under phase clinical evaluation other solid tumors. Here we present data from the glioma population. Patients with recurrent/progressive received daily continuous 28-day cycles. A Bayesian model was used for dose escalation. Dose-limiting...
The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit retention subsequent even the face delivery.We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast spatial loading was...