67 results on '"Lucy Yan"'
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2. Speak with One Voice? Examining Content Coordination and Social Media Engagement During Disasters.
- Author
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Changseung Yoo, Eunae Yoo, Lu (lucy) Yan, and Alfonso J. Pedraza Martinez
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- 2024
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3. Navigating the Digital Terrain of Prosocial Disclosures and Likability.
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Xue (Jane) Tan, Lu (lucy) Yan, and Alfonso J. Pedraza Martinez
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- 2024
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4. Spoiled for Choice? Personalized Recommendation for Healthcare Decisions: A Multiarmed Bandit Approach.
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Tongxin Zhou, Yingfei Wang, Lu (Lucy) Yan, and Yong Tan
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- 2023
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5. Turn Your Online Weight Management from Zero to Hero: A Multidimensional, Continuous-Time Evaluation.
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Tongxin Zhou, Lu Lucy Yan, Yingfei Wang, and Yong Tan
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- 2022
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6. Low-cost, microcontroller-based, two-channel piezoelectric bender device for somatosensory experiments.
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Lucy Yan and Luke E. Hallum
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- 2020
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7. How to Share Prosocial Behavior without Being Considered a Braggart?
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Jane Tan, Lu Lucy Yan, and Alfonso J. Pedraza Martinez
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- 2020
8. Understanding Physicians' Online-Offline Behavior Dynamics: An Empirical Study.
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Liuan Wang, Lu Lucy Yan, Tongxin Zhou, Xitong Guo, and Gregory R. Heim
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- 2020
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9. Understanding the Impact of Individual Users' Rating Characteristics on the Predictive Accuracy of Recommender Systems.
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Xiaoye Cheng, Jingjing Zhang 0001, and Lu Lucy Yan
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- 2020
- Full Text
- View/download PDF
10. Spoiled for Choice? Personalized Recommendation for Healthcare Decisions: A Multi-Armed Bandit Approach.
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Tongxin Zhou, Yingfei Wang, Lu Lucy Yan, and Yong Tan
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- 2020
11. Continuous Participation in Online Weight-Loss Communities: An Empirical Study.
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Lu Lucy Yan and Tong Tan
- Published
- 2018
12. The Consensus Effect in Online Health-Care Communities.
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Lu Lucy Yan and Yong Tan
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- 2017
- Full Text
- View/download PDF
13. Supplementary Methods and Tables 1 - 3 from Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors
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Lia Gore, Min Zhu, Lucy Yan, Kelly S. Oliner, Ian M. Leitch, Paula Kaplan-Lefko, Hongjie Deng, Angela Coxon, Teresa L. Burgess, Daniel Branstetter, Darrin M. Beaupre, Abraham Anderson, S. Gail Eckhardt, David S. Mendelson, Christopher J. Sweeney, and Michael S. Gordon
- Abstract
PDF file - 73K
- Published
- 2023
14. Data from Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors
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Lia Gore, Min Zhu, Lucy Yan, Kelly S. Oliner, Ian M. Leitch, Paula Kaplan-Lefko, Hongjie Deng, Angela Coxon, Teresa L. Burgess, Daniel Branstetter, Darrin M. Beaupre, Abraham Anderson, S. Gail Eckhardt, David S. Mendelson, Christopher J. Sweeney, and Michael S. Gordon
- Abstract
Purpose: The aims were to assess the safety, pharmacokinetics, maximum tolerated dose, and antitumor activity of AMG 102, a fully human hepatocyte growth factor/scatter factor (HGF/SF)–neutralizing monoclonal antibody, in patients with solid tumors.Experimental Design: Patients (N = 40) with refractory advanced solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 mg/kg AMG 102 every 2 weeks). Safety, anti–AMG 102 antibody formation, pharmacokinetics, tumor response, and exploratory biomarkers were assessed.Results: AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, and the maximum tolerated dose was not reached. Treatment-related adverse events were generally mild and included fatigue (13%), constipation (8%), nausea (8%), vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced grade 3 upper gastrointestinal hemorrhage. No anti–AMG 102 antibodies were detected, and AMG 102 had linear pharmacokinetics within the dose range investigated. Sixteen of 23 (70%) evaluable patients had a best response of stable disease with progression-free survival ranging from 7.9 to 40 weeks. Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a dose-dependent manner, whereas soluble c-Met concentrations were generally similar across doses.Conclusions: AMG 102 is safe and well tolerated, has a favorable pharmacokinetic profile, and will be further investigated as a monotherapy and in combination with other agents. Clin Cancer Res; 16(2); 699–710
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- 2023
15. Supplementary Data from Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors
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Lia Gore, Min Zhu, Lucy Yan, Kelly S. Oliner, Ian M. Leitch, Paula Kaplan-Lefko, Hongjie Deng, Angela Coxon, Teresa L. Burgess, Daniel Branstetter, Darrin M. Beaupre, Abraham Anderson, S. Gail Eckhardt, David S. Mendelson, Christopher J. Sweeney, and Michael S. Gordon
- Abstract
Supplementary Data from Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors
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- 2023
16. 1141. Phase 3 Trial (in progress) of the SYK Inhibitor Fostamatinib in Patients Hospitalized with COVID-19: Protocol and Study Implementation Updates
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Lucy Yan, Ziad Mallat, Suzana Margareth Lobo, Anuj Malik, and Wolfgang Dummer
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Infectious Diseases ,Oncology - Abstract
Background Immune dysregulation associated with COVID-19 includes immune cell activation, inflammatory cytokine release, and neutrophil extracellular trap release (NETosis), which are mediated by spleen tyrosine kinase (SYK) (Fig 1). Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, was approved for immune thrombocytopenia (ITP) in 2018, and the Phase 3 trials showed a lower than expected rate of thrombosis.1 Clinical studies showed a reduction in IL-6 in patients with rheumatoid arthritis.2 The active metabolite of fostamatinib (R406) protected against LPS-induced acute lung injury and thrombosis in mice3,4 and reduced MUC1 in a mouse model of ALI.5 Fostamatinib demonstrated abrogation of the hyperimmune response caused by anti-spike IgG,6 including reduction in hyperactivation of platelets7 and NETosis in neutrophils8 in in vitro studies using plasma from patients with severe COVID-19. A phase 2 study (NCT04579393) evaluated fostamatinib vs. placebo (all received standard of care [SOC]) in 59 hospitalized patients with COVID-19 and demonstrated reduction in mortality, ordinal scale scores, and number of days in the intensive care unit (ICU) as well as meeting the primary endpoint of safety.9 A phase 3 clinical study (NCT04629703) of fostamatinib for the treatment of COVID-19 is underway. Figure 1.Mechanism of Disease (COVID-19) and Role of SYK inhibition Methods A Phase 3, randomized, double-blind, placebo-controlled, adaptive design, multi-center study (NCT04629703) is underway to evaluate fostamatinib in 308 adult patients hospitalized with COVID-19 and on oxygen without intubation (Fig 2). Patients will receive fostamatinib 150 mg BID or placebo for 14 days; both arms receive SOC. At baseline, the clinical status score (8-point ordinal scale) had to be 5 or 6. Patients ≥ 65 years had to have ≥ 1 risk factor for severe disease and adults < 65 had to have ≥ 3. The primary outcome is days on oxygen (Day 1 to 29). Other endpoints include change in clinical status score, days in the ICU, time to hospital discharge, all-cause mortality, oxygen-free status and safety. Fostamatinib is investigational for COVID-19. Results Blinded data from this trial in progress are as of 2 December 2021. See Fig 3. Conclusion Final results of this Phase 3 trial are anticipated in 2022. Disclosures Lucy Yan, MD, PhD, Rigel Pharmaceuticals: Employee|Rigel Pharmaceuticals: Stocks/Bonds Ziad Mallat, MD, PhD, Rigel Pharmaceuticals: Advisor/Consultant Suzana Margareth Lobo, MD, PhD, Rigel Pharmaceuticals: Grant/Research Support Anuj Malik, MD, MS, Rigel Pharmaceuticals: Grant/Research Support Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals: Employee|Rigel Pharmaceuticals: Stocks/Bonds.
- Published
- 2022
17. Network Dynamics: How Can We Find Patients Like Us?
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Lu Lucy Yan, Jianping Peng, and Yong Tan
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- 2015
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18. Feeling Blue? Go Online: An Empirical Study of Social Support Among Patients.
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Lu Lucy Yan and Yong Tan
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- 2014
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19. Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis
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Claus Peter Schmitt, Winnie Sohn, Christina Taylan, Isidro B. Salusky, Jude Ngang, Lucy Yan, Bradley A. Warady, Mark A. Kroenke, and Johan Vande Walle
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medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,030232 urology & nephrology ,Cmax ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Renal Dialysis ,Internal medicine ,medicine ,Humans ,Renal Insufficiency, Chronic ,Child ,Etelcalcetide ,business.industry ,medicine.disease ,Tolerability ,Parathyroid Hormone ,Nephrology ,Child, Preschool ,Pharmacodynamics ,Pediatrics, Perinatology and Child Health ,Cohort ,Calcium ,Hyperparathyroidism, Secondary ,Secondary hyperparathyroidism ,Hemodialysis ,Peptides ,business - Abstract
Data on the safety, efficacy of etelcalcetide in children with secondary hyperparathyroidism (sHPT) are limited.This phase 1 study (NCT02833857) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) of single-dose etelcalcetide (0.035 mg/kg intravenously) in pediatric hemodialysis patients (two cohorts; 1: 12-18 years; 2: 2-12 years). Treatment-emergent adverse events (AEs), PK/PD were assessed post-dose on D1 at 10 min and 4 h, on multiple days until D10, and at end of study (D30).Etelcalcetide administered to 11 patients (mean [SD] age 10.3 [4.3] years; cohort 1, n = 6; cohort 2, n = 5) was well tolerated. AEs were consistent with established safety profiles in adults. Two patients (1 per cohort) reported treatment-related AEs (cohort 1: hypocalcemia; cohort 2: headache, paresthesia, vomiting). No serious AEs or deaths were reported. Mean serum corrected calcium (cCa) for all patients was maintained2.25 mmol/L. After etelcalcetide dosing, PK exposures declined, with mean CSingle-dose etelcalcetide (0.035 mg/kg) was well tolerated with expected PK and safety profiles. Overall pattern of changes in serum iPTH and serum calcium was similar between cohorts and consistent with expected responses to etelcalcetide.
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- 2020
20. Granger Causality of the Electroencephalogram Reveals Abrupt Global Loss of Cortical Information Flow during Propofol-induced Loss of Responsiveness
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Jamie W. Sleigh, Lucy Yan, Catherine E. Warnaby, and Rebecca M. Pullon
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Adult ,Male ,Unconsciousness ,Bivariate analysis ,Electroencephalography ,03 medical and health sciences ,0302 clinical medicine ,Granger causality ,Humans ,Hypnotics and Sedatives ,Medicine ,Coherence (signal processing) ,Propofol ,030304 developmental biology ,Cerebral Cortex ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Information flow ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Perioperative Medicine: Clinical Science ,Cerebral cortex ,Female ,Wakefulness ,Nerve Net ,business ,Neuroscience ,Anesthetics, Intravenous ,Psychomotor Performance ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: It is a commonly held view that information flow between widely separated regions of the cerebral cortex is a necessary component in the generation of wakefulness (also termed “connected” consciousness). This study therefore hypothesized that loss of wakefulness caused by propofol anesthesia should be associated with loss of information flow, as estimated by the effective connectivity in the scalp electroencephalogram (EEG) signal. Methods: Effective connectivity during anesthesia was quantified by applying bivariate Granger to multichannel EEG data recorded from 16 adult subjects undergoing a slow induction of, and emergence from, anesthesia with intravenous propofol. During wakefulness they were conducting various auditory and motor tasks. Functional connectivity using EEG coherence was also estimated. Results: There was an abrupt, substantial, and global decrease in effective connectivity around the point of loss of responsiveness. Recovery of behavioral responsiveness was associated with a comparable recovery in information flow pattern (expressed as normalized values). The median (interquartile range) change was greatest in the delta frequency band: decreasing from 0.15 (0.21) 2 min before loss of behavioral response, to 0.06 (0.04) 2 min after loss of behavioral response (P < 0.001). Regional decreases in information flow were maximal in a posteromedial direction from lateral frontal and prefrontal regions (0.82 [0.24] 2 min before loss of responsiveness, decreasing to 0.17 [0.05] 2 min after), and least for information flow from posterior channels. The widespread decrease in bivariate Granger causality reflects loss of cortical coordination. The relationship between functional connectivity (coherence) and effective connectivity (Granger causality) was inconsistent. Conclusions: Propofol-induced unresponsiveness is marked by a global decrease in information flow, greatest from the lateral frontal and prefrontal brain regions in a posterior and medial direction. Loss of information flow may be a useful measure of connected consciousness., In healthy adult volunteers, propofol anesthesia–induced loss of consciousness was associated with an abrupt, substantial, and global decrease in connectivity. These changes are comparably reversed at regain of consciousness. These observations suggest that information flow is an important indicator of wakefulness. Supplemental Digital Content is available in the text.
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- 2020
21. Learning to be Proficient? A Structural Model of User Dynamic Engagement in E-Health Interventions
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Tongxin Zhou, Yingfei Wang, Lu (Lucy) Yan, and Yong Tan
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
22. Tweet in Unison? Examining Content Coordination and Social Media Engagement during Disasters
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Changseung (Chang) Yoo, Eunae Yoo, Lu (Lucy) Yan, and Alfonso Pedraza Martinez
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
23. An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis
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Anthony A. Portale, Shahnaz Shahinfar, Edward Lee, Hao Zhang, Isidro B. Salusky, Bastian Dehmel, Lucy Yan, Bradley A. Warady, Bella Ertik, and Winnie Sohn
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Male ,medicine.medical_specialty ,Cinacalcet ,medicine.medical_treatment ,030232 urology & nephrology ,Urology ,Cmax ,Administration, Oral ,Pediatric dialysis patients ,030204 cardiovascular system & hematology ,Parathyroid hormone ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Renal Dialysis ,Chronic kidney disease ,Humans ,Medicine ,Renal Insufficiency, Chronic ,Child ,Dialysis ,Body surface area ,Dose-Response Relationship, Drug ,Calcimimetics ,business.industry ,Infant, Newborn ,Infant ,Correction ,medicine.disease ,Secondary hyperparathyroidism ,Tolerability ,Nephrology ,Child, Preschool ,Pharmacodynamics ,Pediatrics, Perinatology and Child Health ,Female ,Hyperparathyroidism, Secondary ,Original Article ,business ,Half-Life ,medicine.drug - Abstract
BackgroundCalcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.MethodsIn this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing.ResultsMedian plasma cinacalcettmaxwas 1 h (range 0.5–4.0 h); mean (SD)Cmaxand AUClastwere 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults.ConclusionsIn conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged
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- 2018
24. Understanding the Impact of Individual Users’ Rating Characteristics on the Predictive Accuracy of Recommender Systems
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Lu Lucy Yan, Jingjing Zhang, and Xiaoye Cheng
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Measure (data warehouse) ,Computer science ,business.industry ,General Engineering ,Artificial intelligence ,Recommender system ,business ,Machine learning ,computer.software_genre ,Affect (psychology) ,computer - Abstract
In this study, we investigate how individual users’ rating characteristics affect the user-level performance of recommendation algorithms. We measure users’ rating characteristics from three perspe...
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- 2019
25. Shared Minds: How Patients Use Collaborative Information Sharing via Social Media Platforms
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Xiangbin Yan, Yong Tan, Lu Lucy Yan, and Sherry X. Sun
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Information sharing ,05 social sciences ,Management Science and Operations Research ,Industrial and Manufacturing Engineering ,Social information processing ,World Wide Web ,03 medical and health sciences ,0302 clinical medicine ,Management of Technology and Innovation ,0502 economics and business ,050211 marketing ,Social media ,030212 general & internal medicine ,Psychology ,Latent variable model - Published
- 2018
26. Characterization of SGN-CD123A, A Potent CD123-Directed Antibody–Drug Conjugate for Acute Myeloid Leukemia
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Ashley Cronkite, Peter D. Senter, Eric J. Feldman, Lucy Yan Pan, Maitrayee Goswami, Fu Li, May Kung Sutherland, Weiping Zeng, John F. Valliere-Douglass, Lori Westendorf, Michelle Ulrich, Che Leung Law, Sa A. Wang, Dennis Benjamin, Kerry Klussman, Changpu Yu, Django Sussman, Roland B. Walter, Ivan Stone, Timothy S. Lewis, Mechthild Jonas, and Martha Anderson
- Subjects
0301 basic medicine ,Cancer Research ,Antibody-drug conjugate ,Immunoconjugates ,Myeloid ,THP-1 Cells ,Interleukin-3 Receptor alpha Subunit ,CHO Cells ,Mice, SCID ,Pharmacology ,Antileukemic agent ,Mice ,03 medical and health sciences ,Myelogenous ,chemistry.chemical_compound ,Cricetulus ,0302 clinical medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,Animals ,Humans ,Medicine ,Quizartinib ,business.industry ,Antibodies, Monoclonal ,Myeloid leukemia ,medicine.disease ,Xenograft Model Antitumor Assays ,Leukemia, Myeloid, Acute ,Leukemia ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,business - Abstract
Treatment choices for acute myelogenous leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. IL3 receptor alpha (IL3Rα, or CD123) is expressed on the majority of AML blasts, and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here, we report the generation and preclinical characterization of SGN-CD123A, an antibody–drug conjugate using the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation. Mechanistically, SGN-CD123A induces activation of DNA damage response pathways, cell-cycle changes, and apoptosis in AML cells. In vitro, SGN-CD123A–mediated potent cytotoxicity of 11/12 CD123+ AML cell lines and 20/23 primary samples from AML patients, including those with unfavorable cytogenetic profiles or FLT3 mutations. In vivo, SGN-CD123A treatment led to AML eradication in a disseminated disease model, remission in a subcutaneous xenograft model, and significant growth delay in a multidrug resistance xenograft model. Moreover, SGN-CD123A also resulted in durable complete remission of a patient-derived xenograft AML model. When combined with a FLT3 inhibitor quizartinib, SGN-CD123A enhanced the activity of quizartinib against two FLT3-mutated xenograft models. Overall, these data demonstrate that SGN-CD123A is a potent antileukemic agent, supporting an ongoing trial to evaluate its safety and efficacy in AML patients (NCT02848248). Mol Cancer Ther; 17(2); 554–64. ©2017 AACR.
- Published
- 2018
27. Structural characterization of a monomethylauristatin-E based ADC that contains 8 drugs conjugated at interchain cysteine residues
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Catherine M. Eakin, John F. Valliere-Douglass, Lindsay Fay, David Chiu, and Lucy Yan Pan
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Circular dichroism ,Immunoconjugates ,Chemistry ,Clinical Biochemistry ,Biophysics ,Pharmaceutical Science ,Conjugated system ,Protein tertiary structure ,Analytical Chemistry ,body regions ,Differential scanning calorimetry ,Pharmaceutical Preparations ,Immunoglobulin G ,Monomethylauristatin E ,parasitic diseases ,Drug Discovery ,Cysteine ,Protein secondary structure ,Spectroscopy ,Conjugate - Abstract
Antibody-drug conjugates (ADCs) with a drug-to-antibody ratio (DAR) of 8 are attractive as therapeutic anti-cancer agents due to the higher levels of cytotoxic payload delivered to tumors. Biophysical characterization of a DAR 8 ADC fully conjugated at all interchain cysteine residues was carried out to determine if IgG1 interchain disulfide reduction and conjugation led to structural perturbations that impacted product stability. Comparisons between the DAR 8 ADC and the unconjugated parent antibody identified minor tertiary and quaternary structural changes localized to the CL, CH1, and CH2 domains and CH2-CH3 domain interface. Stability studies of the DAR 8 ADC indicated that the structural changes had minimal impacts to product stability as demonstrated by low levels of fragmentation and aggregation under nominal storage and temperature stress stability conditions. Additionally, no detectable higher order structural changes were observed by CD or DSC in the DAR 8 ADC after 3 months at (25 °C) stability conditions. The structural and stability results support the developability of DAR 8 ADCs fully conjugated to interchain cysteines residues with an optimized and clinically relevant second generation monomethylauristatin-E (MMAE) drug-linker.
- Published
- 2021
28. Good Intentions, Bad Outcomes: The Effects of Mismatches between Social Support and Health Outcomes in an Online Weight Loss Community
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Lu Lucy Yan
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Optimal matching ,05 social sciences ,Management Science and Operations Research ,Affect (psychology) ,Outcome (game theory) ,Industrial and Manufacturing Engineering ,03 medical and health sciences ,Social support ,Seekers ,0302 clinical medicine ,Weight loss ,Management of Technology and Innovation ,0502 economics and business ,Credibility ,medicine ,050211 marketing ,Social media ,030212 general & internal medicine ,medicine.symptom ,Psychology ,Social psychology - Abstract
The United States has the highest rate of obesity in the world. To help address this problem, social support is gaining credibility as a powerful tool to facilitate weight loss because it can affect people's behavior. Although social support has long been recognized for its effectiveness in promoting health, we argue, in this study, that social support may not always lead to good outcomes. Specifically, we differentiate between support providers and support seekers, and examine whether providing and receiving support affect individuals’ weight†loss outcomes differently. By analyzing a group of individuals participating in an online weight†loss community, we show that providing and receiving support does affect weight†loss outcomes in different ways. First, the influences are dynamic. Second, while providing support is positively associated with weight†loss progress, receiving support could hinder weight†loss outcome for a person with high self†efficacy in weight†loss progress. Third, by categorizing social support into different types, we find evidence suggesting that the match between needed and received social support type also influences individuals’ performance in the weight†loss process. Furthermore, mismatches of social support could negatively affect weight†loss outcomes. These findings have implications for maximizing the usefulness of social support for participants in the online environment as well as for clinicians who refer individuals to online weight†loss communities and for those who design them.
- Published
- 2017
29. The Consensus Effect in Online Health-Care Communities
- Author
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Yong Tan and Lu Lucy Yan
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Information Systems and Management ,Individual heterogeneity ,Social network ,Social connectedness ,business.industry ,media_common.quotation_subject ,05 social sciences ,02 engineering and technology ,Management Science and Operations Research ,Computer Science Applications ,Management Information Systems ,Health problems ,020204 information systems ,Perception ,0502 economics and business ,Health care ,0202 electrical engineering, electronic engineering, information engineering ,Precommitment ,050211 marketing ,Psychology ,business ,Social psychology ,Social influence ,media_common ,Clinical psychology - Abstract
Online health-care communities have become increasingly popular among patients, enabling them to connect to a large population of patients who suffer from similar health problems and to access massive amounts of health-related information. We are interested in investigating how other patients’ consensus on treatment experiences affects patients’ perceived treatment effectiveness. In this regard, we use the cue diagnosticity framework to examine patients’ shared treatment reviews. By controlling individual heterogeneity and the inhomogeneous weighting function of social influence on patients, we find that consensus has a positive impact on patients’ perceived treatment effectiveness. This positive effect, however, is negatively moderated by the characteristics of the shared information, including volume and patients’ precommitment and social connectedness. Overall, we find that perceived treatment effectiveness is closely related to community participants’ perceptions about the treatment. These fin...
- Published
- 2017
30. Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting
- Author
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John F. Valliere-Douglass, Lucy Yan Pan, and Oscar Salas-Solano
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0301 basic medicine ,Antibody-drug conjugate ,Immunoconjugates ,Stereochemistry ,Immunology ,Peptide ,Protein Engineering ,01 natural sciences ,Mass Spectrometry ,03 medical and health sciences ,Protein structure ,Report ,Side chain ,Animals ,Humans ,Immunology and Allergy ,chemistry.chemical_classification ,Chemistry ,010401 analytical chemistry ,Antibodies, Monoclonal ,Deuterium Exchange Measurement ,Footprinting ,0104 chemical sciences ,Amino acid ,Kinetics ,030104 developmental biology ,Covalent bond ,Hydrogen–deuterium exchange - Abstract
Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in CH2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.
- Published
- 2016
31. Relative bioavailability, food effect, and safety of the single-dose pharmacokinetics of omecamtiv mecarbil following administration of different modified-release formulations in healthy subjects
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Brian Smith, Paco Alvarez, Jessica Johnson, Lucy Yan, Fady I. Malik, Christopher Banfield, Rameshraja Palaparthy, and Maria Laura Monsalvo
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Adult ,Male ,Adolescent ,Chemistry, Pharmaceutical ,Biological Availability ,030204 cardiovascular system & hematology ,Pharmacology ,030226 pharmacology & pharmacy ,Contractility ,Food-Drug Interactions ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,food effect ,Humans ,Urea ,Medicine ,Pharmacology (medical) ,modified release ,FOOD EFFECT ,Cross-Over Studies ,business.industry ,Healthy subjects ,Cardiac myosin ,Middle Aged ,Crossover study ,Bioavailability ,Omecamtiv mecarbil ,Area Under Curve ,omecamtiv mecarbil ,Female ,bioavailability ,business ,pharmacokinetics ,Research Article - Abstract
Objective: Omecamtiv mecarbil is a novel small molecule that directly activates cardiac myosin and increases cardiac contractility without increasing cardiac myocyte intracellular calcium. This study evaluated the relative bioavailability, food effect, and safety of several modified-release (MR) formulations of omecamtiv mecarbil. Methods: This was a phase 1, randomized, open-label, 4-way crossover, incomplete block-design study evaluating 5 MR formulations of omecamtiv mecarbil vs. an immediate-release (IR) formulation. Materials: Healthy subjects were randomized to 1 of 30 possible sequences: within each sequence, subjects were assigned to receive a single 25-mg dose of 2 of the 6 possible formulations in the fasting and/or fed states. Results: 65 subjects were screened and enrolled; 5 were replacement subjects. Pharmacokinetic and safety data were analyzed from 62 and 63 subjects in the fasting and fed states, respectively. Compared with the IR formulation, median tmax was longer (0.5 vs. 2 – 10 hours), and mean Cmax was lower for all 5 MR formulations (262 vs. 34 – 78 ng/mL); t1/2,z was similar (18 – 21 hours). The relative bioavailability was high (> 75%) for three MR formulations but lower ( 75%) for 3 of the five MR formulations. Food had a marginal, nonclinically meaningful effect on the pharmacokinetics of the MR formulations of omecamtiv mecarbil.
- Published
- 2016
32. Correction to: An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis
- Author
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Shahnaz Shahinfar, Winnie Sohn, Edward Lee, Hao Zhang, Bella Ertik, Anthony A. Portale, Isidro B. Salusky, Lucy Yan, Bradley A. Warady, and Bastian Dehmel
- Subjects
Body surface area ,medicine.medical_specialty ,Cinacalcet ,business.industry ,medicine.medical_treatment ,Cmax ,Urology ,medicine.disease ,Pharmacokinetics ,Tolerability ,Nephrology ,Pediatrics, Perinatology and Child Health ,medicine ,Secondary hyperparathyroidism ,business ,Dialysis ,Kidney disease ,medicine.drug - Abstract
Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects. In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing. Median plasma cinacalcet tmax was 1 h (range 0.5–4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults. In conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged
- Published
- 2018
33. Approaches to Interchain Cysteine-Linked ADC Characterization by Mass Spectrometry
- Author
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Shawna Hengel, Lucy Yan Pan, and John F. Valliere-Douglass
- Subjects
Tumor targeting ,Antibody-drug conjugate ,Immunoconjugates ,Chemistry ,Pharmaceutical Science ,Nanotechnology ,Tumor cells ,Computational biology ,Mass spectrometry ,Mass spectrometric ,Mass Spectrometry ,Characterization (materials science) ,body regions ,Drug Discovery ,Animals ,Humans ,Molecular Medicine ,Cysteine ,Higher Order Structure ,Native structure - Abstract
Therapeutic antibody-drug conjugates (ADCs) harness the cell-killing potential of cytotoxic agents and the tumor targeting specificity of monoclonal antibodies to selectively kill tumor cells. Recent years have witnessed the development of several promising modalities that follow the same basic principles of ADC based therapies but which employ unique cytotoxic agents and conjugation strategies in order to realize therapeutic benefit. The complexity and heterogeneity of ADCs present a challenge to some of the conventional analytical methods that industry has relied upon for biologics characterization. This current review will highlight some of the more recent methodological approaches in mass spectrometry that have bridged the gap that is created when conventional analytical techniques provide an incomplete picture of ADC product quality. Specifically, we will discuss mass spectrometric approaches that preserve and/or capture information about the native structure of ADCs and provide unique insights into the higher order structure (HOS) of these therapeutic molecules.
- Published
- 2014
34. Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects
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Lisa Hamilton, Thuy Vu, Gabriel Vargas, Jiyun Sunny Chen, Peiming Ma, Anne Van Hecken, Jan de Hoon, Lucy Yan, and Liviawati Wu
- Subjects
Adult ,Male ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Population ,Pharmaceutical Science ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Models, Biological ,030226 pharmacology & pharmacy ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Humans ,Medicine ,migraine ,pharmacokinetics-pharmacodynamics ,Pharmacology (medical) ,vasodilation ,education ,Skin ,education.field_of_study ,business.industry ,Organic Chemistry ,Antibodies, Monoclonal ,Blood flow ,anti-CGRP receptor ,Confidence interval ,Bioavailability ,chemistry ,Calcitonin ,Capsaicin ,dermal blood flow ,Sensory System Agents ,Molecular Medicine ,Biomarker (medicine) ,Female ,business ,Blood Flow Velocity ,030217 neurology & neurosurgery ,Research Paper ,Biotechnology - Abstract
Purpose Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. Methods Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. Results Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87–91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. Conclusions Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF. Electronic supplementary material The online version of this article (doi:10.1007/s11095-017-2183-6) contains supplementary material, which is available to authorized users.
- Published
- 2017
35. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine
- Author
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Brian Smith, Jan de Hoon, Thuy Vu, Javier Waksman, Corinne Vandermeulen, Edgar Bautista, Anne Van Hecken, Jiyun Sunny Chen, Lucy Yan, Gabriel Vargas, and Lisa Hamilton
- Subjects
Adult ,Male ,Adolescent ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Calcitonin gene-related peptide ,Pharmacology ,Placebo ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pharmacokinetics ,Double-Blind Method ,Calcitonin Gene-Related Peptide Receptor Antagonists ,Medicine ,Humans ,Pharmacology (medical) ,business.industry ,Antagonist ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Healthy Volunteers ,Migraine ,Calcitonin ,030220 oncology & carcinogenesis ,Pharmacodynamics ,Monoclonal ,Female ,business ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.
- Published
- 2016
36. FOREWORD.
- Author
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Kumar, Alok, Liu, Lucy (Yan), and Saint Clair, Julian K.
- Subjects
GEOPOLITICS ,COVID-19 pandemic - Abstract
The article reports on the the 2023 AMA Summer Academic Conference, addressing the proactive impact of marketing amidst global challenges like the COVID-19 pandemic, social inequities, climate crisis, and geopolitical events.
- Published
- 2023
37. Effect of coadministration of ketoconazole, a strong CYP3A4 inhibitor, on pharmacokinetics and tolerability of motesanib diphosphate (AMG 706) in patients with advanced solid tumors
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Jesse McGreivy, Lucy Yan, Elisabeth I. Heath, Megan Ingram, Mary Jo Pilat, Yu Nien Sun, Rebeca Melara, Li Chen, Patricia LoRusso, Jeffrey Wiezorek, and Lisa Malburg
- Subjects
Male ,Niacinamide ,Indoles ,Oligonucleotides ,Pharmacology ,Drug Administration Schedule ,Motesanib Diphosphate ,chemistry.chemical_compound ,Pharmacokinetics ,Neoplasms ,medicine ,Motesanib ,Cytochrome P-450 CYP3A ,Humans ,Pharmacology (medical) ,Adverse effect ,Aged ,Cross-Over Studies ,CYP3A4 ,business.industry ,Middle Aged ,Crossover study ,Ketoconazole ,Oncology ,chemistry ,Tolerability ,Cytochrome P-450 CYP3A Inhibitors ,Female ,business ,medicine.drug - Abstract
Motesanib diphosphate is a novel angiogenesis inhibitor selectively targeting vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor and stem cell factor receptor. The purpose of this phase 1b, drug-drug interaction study was to investigate the effect of ketoconazole, a strong inhibitor of the cytochrome P450 3A4 isoenzyme, on the pharmacokinetics and tolerability of motesanib diphosphate. Fourteen patients with advanced solid tumors refractory to standard treatment were enrolled and received motesanib diphosphate 50 mg once daily from day 1 through 15. Patients were randomized to receive a single oral dose of ketoconazole 400 mg either on day 8 (Sequence 1; n = 7) or day 15 (Sequence 2; n = 7), while pharmacokinetic samples were collected. After completion of this part (day 16), 13 patients received an escalated once-daily dose of motesanib diphosphate 125 mg. Evaluable pharmacokinetic data (n = 12) suggest that ketoconazole modestly increased motesanib exposure. The motesanib area under the concentration-time curve (AUC) from 0 to 24 h increased by 86% (90% CI, 1.50-2.29; P < 0.001) and the maximum plasma concentration (C (max)) by 35% (90% CI, 1.12-1.64; P = 0.02), compared with motesanib diphosphate administration alone. The tolerability profile (with or without ketoconazole coadministration) was consistent with that from other motesanib diphosphate monotherapy studies. Treatment-related adverse events were mild to moderate and commonly included fatigue (50% of patients), hypertension (43%), diarrhea (21%), dizziness (14%), paresthesia (14%), and vomiting (14%). Hypertension was the most common related grade 3 event (21%). No grade 4 or 5 treatment-related adverse events occurred.
- Published
- 2008
38. Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype
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Bérengère Koehl, Cédric Vrignaud, Mahmoud Mikdar, Thankam S Nair, Lucy Yang, Seyve Landry, Guy Laiguillon, Claudine Giroux‐Lathuile, Sophie Anselme‐Martin, Hanane El Kenz, Olivier Hermine, Narla Mohandas, Jean Pierre Cartron, Yves Colin, Olivier Detante, Raphaël Marlu, Caroline Le Van Kim, Thomas E Carey, Slim Azouzi, and Thierry Peyrard
- Subjects
blood group antigen ,hearing impairment ,red blood cells ,SLC44A2 ,transfusion ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens. The choline transporter‐like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil activation. By investigating alloantibodies to a high‐prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that SLC44A2 is also expressed in RBCs and carries a new blood group system. Furthermore, we identified three siblings homozygous for a large deletion in SLC44A2, resulting in complete SLC44A2 deficiency. Interestingly, the first‐ever reported SLC44A2‐deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms, and epilepsy. Furthermore, SLC44A2null individuals showed no significant platelet aggregation changes and do not suffer from any apparent hematological disorders. Overall, our findings confirm the function of SLC44A2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.
- Published
- 2023
- Full Text
- View/download PDF
39. Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting
- Author
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Pan, Lucy Yan, primary, Salas-Solano, Oscar, additional, and Valliere-Douglass, John F., additional
- Published
- 2016
- Full Text
- View/download PDF
40. Antibody structural integrity of site-specific antibody-drug conjugates investigated by hydrogen/deuterium exchange mass spectrometry
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John F. Valliere-Douglass, Lucy Yan Pan, and Oscar Salas-Solano
- Subjects
Binding Sites ,Immunoconjugates ,Chemistry ,Stereochemistry ,Protein Data Bank (RCSB PDB) ,Deuterium Exchange Measurement ,Crystallography, X-Ray ,Antibodies ,Mass Spectrometry ,Analytical Chemistry ,Residue (chemistry) ,chemistry.chemical_compound ,Biochemistry ,Pharmaceutical Preparations ,Amide ,Hydrogen–deuterium exchange ,Binding site ,Site-directed mutagenesis ,Cysteine ,Conjugate - Abstract
We present the results of a hydrogen/deuterium exchange mass spectrometric (HDX-MS) investigation of an antibody-drug conjugate (ADC) comprised of drug-linkers conjugated to cysteine residues that have been engineered into heavy chain (HC) fragment crystallizable (Fc) domain at position 239. A side-by-side comparison of the HC Ser239 wild type (wt) monoclonal antibody (mAb) and the engineered Cys239 mAb indicates that site directed mutagenesis of Ser239 to cysteine has no impact on the HDX kinetics of the mAb. According to the crystal structure of a homologous immunoglobulin G1 (IgG1) antibody (PDB: 1HZH ), the backbone amide of Ser239 is hydrogen-bonded to Val264 backbone amide in the wt-mAb studied here. Replacing Ser239 with a Cys residue does not alter the exchange kinetics of the backbone amide of Val264 suggesting that either Ser or Cys at position 239 has similar amide-hydrogen bonding with Val264. However, a small segment in CH2 domain of the ADC ((264)VDVS) was found to have a slightly increased HDX rate compared to the wt- and C239-mAb constructs. The slightly increased HDX rate of the segment (264)VDVS in ADCs indicates that the further modification of Cys239 with drug-linkers only attenuates the local backbone amide hydrogen-bonding network between Cys239 and Val264. All other regions which are proximal to the site of drug conjugation are unaffected. The results demonstrate that the site-specific drug conjugation at the engineered Cys residue at the position 239 of HC does not impact the structural integrity of antibodies. The results also highlight the utility of applying HDX-MS to ADCs to gain a molecular level insight into the impact of site-specific conjugation technologies on the higher-order structure (HOS) of mAbs. The methodology can be applied generally to site-specific ADC modalities to understand the individual contributions of site-mutagenesis and drug-linker conjugation on the HOS of therapeutic candidate ADCs.
- Published
- 2015
41. Good Intentions, Bad Outcomes: The Effects of Mismatches in Social Support and Health Outcomes in an Online Weight Loss Community
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Lu (Lucy) Yan and Yong Tan
- Subjects
Optimal matching ,business.industry ,Credence ,Sentiment analysis ,Weight change ,Public relations ,Affect (psychology) ,Social support ,Weight loss ,medicine ,Social media ,medicine.symptom ,Psychology ,business ,Social psychology - Abstract
The United States has the highest rate of obesity in the world. To help address this problem, social support is gaining credence as a powerful tool to facilitate weight loss because it can affect individuals’ behavior. Social support thus has been the focus of a significant amount of research, which has provided support for its effectiveness. In this study, however, we argue that social support may not always lead to good outcomes. Specifically, we differentiate support providers and support seekers, and examine whether the balance of needed and received social support affects individuals’ weight loss outcomes. By analyzing a group of individuals participating in an online weight loss community, we found that the adequacy of social support has a distinguishable impact on individuals’ weight change. In particular, overprovision (receiving more support than is desired) and underprovision (receiving less support than is desired) resulted in differentiable health outcomes. In addition, by categorizing social support into different types, we found evidence suggesting that the match between the types of social support requested and provided also influenced individuals’ performance in the weight loss process. These findings have implications for maximizing the usefulness of social support for participants in the online environment as well as for clinicians who refer individuals to online weight loss communities and those who design them.
- Published
- 2015
42. Continuous Participation in Online Weight-Loss Communities: An Empirical Study.
- Author
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Lu (Lucy) Yan and Yong Tan
- Subjects
WEIGHT loss ,VIRTUAL communities ,EMPIRICAL research ,LIFESTYLES ,SOCIAL support - Abstract
Although online healthcare communities are found to be helpful, the effectiveness of such communities in improving patients' long-term health management has been overlooked. In this study, we examine users' continuous participation in an online weight-loss community. Through analyzing users' activities over a 3-year period, we find that those who continuously participate are more likely to self-monitor their lifestyle, which implies that online healthcare communities are an effective means for patients' lifelong disease management. Our analysis results also show that, although users are attracted to the massive amounts of information available in online communities, it is the opportunity to participate in behavior change that leads to their continuous participation. Surprisingly, our results indicate that the exchange of social support among users is not effective in ensuring their continuous participation. These findings are useful for both users with chronic conditions and service providers. [ABSTRACT FROM AUTHOR]
- Published
- 2018
43. Conformation and dynamics of interchain cysteine-linked antibody-drug conjugates as revealed by hydrogen/deuterium exchange mass spectrometry
- Author
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Lucy Yan Pan, John F. Valliere-Douglass, and Oscar Salas-Solano
- Subjects
Immunoconjugates ,medicine.drug_class ,Stereochemistry ,Swine ,Kinetics ,Antibodies, Monoclonal ,Conjugated system ,Mass spectrometry ,Monoclonal antibody ,Mass Spectrometry ,Analytical Chemistry ,body regions ,chemistry.chemical_compound ,Monomethyl auristatin E ,chemistry ,medicine ,Animals ,Hydrogen–deuterium exchange ,Cysteine ,Conjugate - Abstract
Antibody-drug conjugates (ADCs) are protein therapeutics in which a target specific monoclonal antibody (mAb) is conjugated with drug molecules. The manufacturing of ADCs involves additional conjugation steps, which are carried out on the parent mAbs, and it is important to evaluate how the drug conjugation process impacts the conformation and dynamics of the mAb. Here, we present a comparative study of interchain cysteine linked IgG1 ADCs and the corresponding mAb by hydrogen/deuterium exchange mass spectrometry (HDX-MS). We found that ∼90% of the primary sequence of the ADC conjugated with either monomethyl auristatin E or F (vcMMAE/mcMMAF) displayed the same HDX kinetics as the mAb, indicating the ADCs and mAbs share very similar conformation and dynamics in solution. Minor increases in HDX kinetic rates were observed in two Fc regions in the ADCs relative to the mAb which indicated that both regions become more structurally dynamic and/or more solvent-accessible in the ADCs. The findings led to a subsequent inquiry into whether the local conformational changes were due to the presence of drugs on the interchain cysteine residues or the absence of intact interchain disulfides or both. To address this question, a side-by-side HDX comparison of ADCs, mAbs, reduced mAbs (containing 8 reduced interchain cysteine thiols), and partially reduced mAbs (conjugation process intermediate) was performed. Our results indicated that the slight increase in conformational dynamics detected at the two regions in the ADCs was due to the absence of intact interchain disulfide bonds and not the presence of vcMMAE or mcMMAF on the alkylated interchain cysteine residues. These results highlight the utility of HDX-MS for interrogating the higher-order structure of ADCs and other protein therapeutics.
- Published
- 2014
44. Simultaneous imaging of redox states in dystrophic neurites and microglia at Aβ plaques indicate lysosome accumulation not microglia correlate with increased oxidative stress
- Author
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Stefan Wendt, Sora Johnson, Nicholas L. Weilinger, Christopher Groten, Stefano Sorrentino, Jonathan Frew, Lucy Yang, Hyun B. Choi, Haakon B. Nygaard, and Brian A. MacVicar
- Subjects
Microglia ,Alzheimer’s disease ,Oxidative stress ,Neurodegeneration ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The inter-relationship between microglia dynamics and oxidative stress (Ox-stress) in dystrophic neurites (DNs) at Alzheimer’s Disease (AD) plaques may contribute to the pathological changes in neurons. We developed new in vivo imaging strategies to combine EGFP expression in microglia with neuronal expression of genetically encoded ratiometric redox sensors (rogRFP2 or roGFP1), and immunohistochemistry to investigate how microglia influence Ox-stress at amyloid plaques in 5xFAD AD mice. By simultaneously imaging microglia morphology and neuronal Ox-stress over time in vivo and in fixed brains we found that microglia preferentially enwrapped DNs exhibiting the greatest degree of Ox-stress. After microglia were partially depleted with the CSF1 receptor antagonist PLX3397, Ox-stress in DNs increased in a manner that was inversely correlated to the extent of coverage of the adjacent Aβ plaques by the remaining microglia. These data suggest that microglia do not create Ox-stress at Aβ plaques but instead create protective barriers around Aβ plaques possibly reducing the spread of Aβ. Intracranial injection of Aβ was sufficient to induce neuronal Ox-stress suggesting it to be the initial trigger of Ox-stress generation. Although Ox-stress is increased in DNs, neuronal survival is enhanced following microglia depletion indicating complex and multifactorial roles of microglia with both neurotoxic and neuroprotective components. Increased Ox-stress of DNs was correlated with higher LAMP1 and ubiquitin immunoreactivity supporting proposed mechanistic links between lysosomal accumulation in DNs and their intrinsic generation of Ox-stress. Our results suggest protective as well as neurotoxic roles for microglia at plaques and that the generation of Ox-stress of DNs could intrinsically be generated via lysosomal disruption rather than by microglia.In Brief: Simultaneous imaging of microglia and neuronal Ox-stress revealed a double-edged role for microglia in 5xFAD mice. Plaque associated microglia were attracted to and enwrapped Aβ plaques as well as the most highly oxidized DNs. After partial depletion of microglia, DNs were larger with greater levels of Ox-stress. Despite increased Ox-stress after microglia removal neuronal survival improved. Greater Ox-stress was correlated with increased levels of LAMP1 and ubiquitin thereby linking lysosome accumulation and Ox-stress in DNs.
- Published
- 2022
- Full Text
- View/download PDF
45. Shared Minds: How Patients Use Collaborative Web-Based Information Sharing
- Author
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Lucy Yan, Sherry Sun, Xiangbin Yan, and Yong Tan
- Subjects
Social information processing ,Knowledge management ,Marketing buzz ,business.industry ,Information seeking ,Information sharing ,Opinion leadership ,Social media ,Public relations ,Empirical evidence ,business ,Psychology ,Experiential learning - Abstract
Online social media present a unique opportunity for patients to explore their health issues, share experiential information, and fulfill their need for health. The shared knowledge provides indirect experience of the sensory aspects of a medical treatment that are not available from the description of its tangible aspects alone. In this study, we examine various forms of WOM in online healthcare communities and investigate how patients educate themselves by using other patients’ experiences. We find empirical evidence for the existence of social contagion. More important, we find that experiential learning, a concept describing substantive experience-based information seeking and sharing, is a complex process and that, surprisingly, buzz effects outweigh similarity effects in social interactions about medical information. We also examine the opinion leadership concept and the managerial implications of these findings are discussed.
- Published
- 2012
46. SGN-CD123A, a Pyrrolobenzodiazepine Dimer Linked Anti-CD123 Antibody Drug Conjugate, Demonstrates Effective Anti-Leukemic Activity in Multiple Preclinical Models of AML
- Author
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May Kung Sutherland, Changpu Yu, Ivan Stone, Peter D. Senter, Lucy Yan Pan, Mechthild Jonas, Lori Westendorf, Michelle Ulrich, Roland B. Walter, Kerry Klussman, Weiping Zeng, John F. Valliere-Douglass, Jonathan G. Drachman, Dennis Benjamin, Martha Anderson, and Django Sussman
- Subjects
Antibody-drug conjugate ,business.industry ,Immunology ,Myeloid leukemia ,Pyrrolobenzodiazepine ,Cell Biology ,Hematology ,Biochemistry ,Minimal residual disease ,Immunoconjugate ,chemistry.chemical_compound ,chemistry ,Cancer research ,Medicine ,Cytotoxic T cell ,Interleukin-3 receptor ,Stem cell ,business - Abstract
Survival expectations for acute myeloid leukemia (AML) patients remain poor, highlighting the need for further treatment options. The majority of AML blasts express CD123, the alpha subunit of the IL-3 receptor, which regulates the proliferation, survival and differentiation of hematopoietic cells. CD123 is also robustly expressed on leukemic stem cells and is a marker for minimal residual disease (MRD, Roug et al. 2012). Poor prognosis has previously been associated with elevated expression of CD123 on leukemic stem cells and blasts (Vergez et al. 2011, Testa et al. 2002). These findings identify CD123 as a rational therapeutic target in AML. Here we report the preclinical development of a novel CD123-directed immunoconjugate SGN-CD123A, consisting of a humanized anti-CD123 antibody conjugated to a highly potent DNA binding pyrrolobenzodiazepine (PBD) dimer drug via a protease-cleavable dipeptide linker. An engineered cysteine on each heavy chain attaching the PBD dimer to the antibody allows uniform drug loading of approximately two PBD dimers per antibody. Fluorescence microscopy studies show that SGN-CD123A is rapidly internalized and traffics to lysosomes within hours of binding to CD123-positive AML cells. Uptake of the antibody-drug-conjugate (ADC) induced DNA damage as measured by dose-and time-dependent increases in the phosphorylation of histone 2AX (γH2AX) and cell death associated with G2-M cell cycle arrest, caspase-3 activity, formation of cleaved poly ADP-ribose polymerase, and DNA fragmentation in target cells. The anti-leukemic activity of SGN-CD123A was assessed in cytotoxicity assays in 12 AML cell lines and 23 primary AML patient samples with variable cytogenetic abnormalities (favorable, intermediate and adverse) and multi-drug resistance (MDR) status. SGN-CD123A was highly active in 11 of 12 AML cell lines tested (mean IC50, 6 ng/ml; range of 0.02 to 38 ng/ml), including 4 of 5 MDR-positive cell lines, whereas it was inactive in CD123-negative HEL92.1.7 AML cells. SGN-CD123A was also active against 20 of 23 primary samples isolated from AML patients (mean IC50 of responsive samples, 0.8 ng/mL; range of 0.06 to 2.5 ng/ml). In both AML panels, molecular abnormalities, including the presence of a p53 mutation, FLT3-ITD, as well as MDR positivity, did not affect the in vitro cytotoxic activity of SGN-CD123A. In vivo antitumor activity was evaluated in AML xenograft models established with CD123-positive, MDR-negative Molm-13, HNT-34, and THP-1 cell lines and the MDR-positive KG-1 cell line. In all of the in vivo models, a single dose of SGN-CD123A delivered significant antitumor activity. SGN-CD123A dosed once at 10 mcg/kg yielded complete cures and significant survival advantage in the Molm-13 disseminated model of AML (p < 0.0001 compared to untreated or control ADC groups). Durable complete regressions were observed with a single dose of 25 or 75 mcg/kg in the MDR-negative HNT-34 subcutaneous model (p =0.0019 to control ADC group). In the THP-1 model, a single 100 mcg/kg dose of SGN-CD123A yielded durable complete regressions in 2 of 8 mice (p=0.0003 to untreated) whereas a higher dose of 300 mcg/kg gave complete tumor regressions in all mice (p < 0.0001 to untreated group). SGN-CD123A was also effective in a MDR-positive model of AML. A single dose of 100 mcg/kg SGN-CD123A significantly decreased tumor growth (p=0.003 to controls) whereas a single dose of 300 mcg/kg yielded durable complete regressions compared to the control groups in the KG-1 subcutaneous model of MDR-positive AML (p =0.008). Early evidence of the antitumor activity of SGN-CD123A was found in tumors harvested from THP-1 mice. Within 48h of dosing with SGN-CD123A, tumor cells showed elevated levels of the DNA damage marker γH2AX and changes in nuclear morphology. These data demonstrate that SGN-CD123A exhibits significant antitumor activity against a broad panel of primary AML samples and in preclinical models of MDR-positive AML that are characteristically resistant to chemotherapy. CD123-directed delivery of PBD may represent a promising new approach for the treatment of AML. Disclosures Sutherland: Seattle Genetics, Inc.: Employment. Yu:Seattle Genetics, Inc: Employment, Equity Ownership. Walter:Seattle Genetics, Inc: Consultancy, Research Funding. Westendorf:Seattle Genetics, Inc: Employment. Valliere-Douglass:Seattle Genetics, Inc: Employment. Pan:Seattle Genetics, Inc: Employment. Sussman:Seattle Genetics, Inc: Employment. Anderson:Seattle Genetics, Inc: Employment. Zeng:Seattle Genetics, Inc: Employment. Stone:Seattle Genetics, Inc: Employment. Klussman:Seattle Genetics, Inc: Employment. Ulrich:Seattle Genetics, Inc: Employment. Jonas:Seattle Genetics, Inc: Employment. Senter:Seattle Genetics, Inc: Employment. Drachman:Seattle Genetics, Inc: Employment. Benjamin:Seattle Genetics, Inc: Employment.
- Published
- 2015
47. Antibody Structural Integrity of Site-Specific Antibody-Drug Conjugates Investigated by Hydrogen/Deuterium Exchange Mass Spectrometry
- Author
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Pan, Lucy Yan, primary, Salas-Solano, Oscar, additional, and Valliere-Douglass, John F., additional
- Published
- 2015
- Full Text
- View/download PDF
48. Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors
- Author
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Angela Coxon, S. Gail Eckhardt, Michael S. Gordon, Daniel Branstetter, Paula Kaplan-Lefko, Min Zhu, Ian M. Leitch, David S. Mendelson, Darrin M. Beaupre, Kelly S. Oliner, Lia Gore, Christopher Sweeney, Abraham Anderson, Lucy Yan, Teresa L. Burgess, and Hongjie Deng
- Subjects
myalgia ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Maximum Tolerated Dose ,Nausea ,Rilotumumab ,Antineoplastic Agents ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Mice ,Young Adult ,Pharmacokinetics ,Refractory ,Internal medicine ,Neoplasms ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Adverse effect ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Hepatocyte Growth Factor ,Cancer ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Xenograft Model Antitumor Assays ,Oncology ,Drug Resistance, Neoplasm ,Vomiting ,Disease Progression ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Purpose: The aims were to assess the safety, pharmacokinetics, maximum tolerated dose, and antitumor activity of AMG 102, a fully human hepatocyte growth factor/scatter factor (HGF/SF)–neutralizing monoclonal antibody, in patients with solid tumors. Experimental Design: Patients (N = 40) with refractory advanced solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 mg/kg AMG 102 every 2 weeks). Safety, anti–AMG 102 antibody formation, pharmacokinetics, tumor response, and exploratory biomarkers were assessed. Results: AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, and the maximum tolerated dose was not reached. Treatment-related adverse events were generally mild and included fatigue (13%), constipation (8%), nausea (8%), vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced grade 3 upper gastrointestinal hemorrhage. No anti–AMG 102 antibodies were detected, and AMG 102 had linear pharmacokinetics within the dose range investigated. Sixteen of 23 (70%) evaluable patients had a best response of stable disease with progression-free survival ranging from 7.9 to 40 weeks. Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a dose-dependent manner, whereas soluble c-Met concentrations were generally similar across doses. Conclusions: AMG 102 is safe and well tolerated, has a favorable pharmacokinetic profile, and will be further investigated as a monotherapy and in combination with other agents. Clin Cancer Res; 16(2); 699–710
- Published
- 2010
49. Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.
- Author
-
Pan, Lucy Yan, Salas-Solano, Oscar, and Valliere-Douglass, John F.
- Published
- 2017
- Full Text
- View/download PDF
50. Conformation and Dynamics of Interchain Cysteine-Linked Antibody-Drug Conjugates as Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry
- Author
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Pan, Lucy Yan, primary, Salas-Solano, Oscar, additional, and Valliere-Douglass, John F., additional
- Published
- 2014
- Full Text
- View/download PDF
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