13 results match your criteria: "NJ (B.H.M.); and the Netherlands Cancer Institute[Affiliation]"
Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED.
Org Lett
August 2024
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Article Synopsis
- Microcrystal electron diffraction (microED) is a new technique for quickly analyzing small molecule crystals, particularly useful in pharmaceuticals.
- In a study involving 30 samples from Amgen Inc., researchers successfully determined the structures of 15 crystals using just 40 hours of microscope time.
- All chiral compounds analyzed had their absolute stereochemistry correctly assigned through dynamic refinement, showcasing the effectiveness of dynamic refinement in determining stereochemistry for pharmaceutical compounds.
Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.
View Article and Find Full Text PDFNIBR-LTSi is a selective LATS kinase inhibitor activating YAP signaling and expanding tissue stem cells in vitro and in vivo.
Cell Stem Cell
April 2024
Biomedical Research, Novartis Pharma AG, Basel, Switzerland. Electronic address:
Article Synopsis
- The YAP/Hippo pathway regulates organ growth and helps maintain stem cell function, with LATS kinases playing a critical role by inactivating YAP.
- A new small-molecule inhibitor, NIBR-LTSi, has been developed that selectively targets LATS kinases, activating YAP signaling and promoting tissue regeneration in laboratory settings.
- While NIBR-LTSi shows promise by enhancing liver regeneration and supporting stem cell characteristics, prolonged use may lead to excessive cell proliferation and dedifferentiation, which could limit its therapeutic benefits.
Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.
N Engl J Med
March 2024
From Barts Cancer Institute Biomedical Research Centre, Queen Mary University of London, London (T.P.); Hospital Universitario Virgen del Rocio, Seville (B.P.V.), Hospital Universitario 12 de Octubre, Madrid (D.C.), and Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Santander (I.D.) - all in Spain; Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland (S. Gupta); Klinikum Stuttgart Katharinen Hospital, Stuttgart, Germany (J.B.); St. Marianna University School of Medicine, Kawasaki, Japan (E.K.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.); Memorial Sloan Kettering Cancer Center, New York (G.I.); Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, and the Center for Oncological Research, University of Antwerp, Antwerp - both in Belgium (C.V.); Samsung Medical Center, Sungkyunkwan University School of Medicine (S.H.P.), and Severance Hospital, Yonsei University Health System (S.J.S.) - both in Seoul, South Korea; Scientific Institute for Research, Hospitalization, and Healthcare Ospedale Policlinico San Martino, Genoa, Italy (G.F.); Taichung Veterans General Hospital, Taichung, Taiwan (J.-R.L.); Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey (M.G.); the University of California, Irvine Medical Center, Orange (N.M.), and the University of California, Los Angeles Medical Center, Los Angeles (A.D.); Institut Gustave Roussy, Université Paris-Saclay, Villejuif (Y.L.), and Centre Léon Bérard, Lyon (A.F.) - both in France; Seagen, Bothell, WA (S.N., X.Y.); Astellas Pharma US, Northbrook, IL (S. Gorla); Merck, Rahway, NJ (B.H.M.); and the Netherlands Cancer Institute, Amsterdam (M.S.H.).
Background: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma.
Methods: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.
Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice.
Nat Commun
October 2023
Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Although macrophages contribute to cancer cell dissemination, immune evasion, and metastatic outgrowth, they have also been reported to coordinate tumor-specific immune responses. We therefore hypothesized that macrophage polarization could be modulated therapeutically to prevent metastasis. Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis.
View Article and Find Full Text PDFA path to translation: How 3D patient tumor avatars enable next generation precision oncology.
Cancer Cell
December 2022
Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address:
Article Synopsis
- 3D patient tumor avatars (3D-PTAs) have the potential to improve precision medicine by offering personalized insights into cancer treatment.
- There are challenges in implementing 3D-PTA technologies, including the need for standardized criteria and trial testing to prove their clinical effectiveness.
- Future advancements should focus on innovative trial designs and creating platforms that integrate diagnostics with treatment options to speed up new therapies for patients who do not respond to traditional treatments.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19.
NPJ Prim Care Respir Med
September 2022
Medical Affairs, GSK Consumer Healthcare, Warren, NJ, USA.
Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020-July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective.
View Article and Find Full Text PDFLong COVID burden and risk factors in 10 UK longitudinal studies and electronic health records.
Nat Commun
June 2022
Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
Article Synopsis
- * It found that 7.8% to 17% of reported COVID-19 cases experienced symptoms lasting over 12 weeks, with 1.2% to 4.8% suffering debilitating symptoms.
- * Key risk factors for prolonged symptoms included older age, female gender, being white, poor overall and mental health prior to the pandemic, obesity, and asthma, while other factors showed unclear correlations.
Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006.
Eur J Cancer
November 2021
Department of Medicine, Jonsson Comprehensive Cancer Center and David Geffen School of Medicine, University of California Los Angeles, 100 Medical Plaza Driveway #550, Los Angeles, CA 90095, USA. Electronic address:
Objective: Patients with melanoma and early stable disease (SD) with pembrolizumab have unclear prognosis. We present post hoc analyses of long-term outcomes for patients with early SD, partial response (PR) or complete response (CR) with pembrolizumab.
Patients And Methods: Patients who received pembrolizumab in the KEYNOTE-001 and KEYNOTE-006 studies and had SD, PR or CR at weeks 12 or 24 were included.
Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.
J Trauma Acute Care Surg
November 2020
From the Departments of Surgery (A.L.D., B.H.M., E.A.R., E.D., D.H.F., S.E.R., M.A.S., M.F.) and Emergency Medicine (J. Jui), Oregon Health and Science University, Portland, Oregon; Departments of Emergency Medicine (J.M.) and Surgery (J. Johannigman), University of Cincinnati, Cincinnati, Ohio; Departments of Surgery (B.R.H.R., E.M.B., P.K.) and Biostatistics (D.K., B.M., E.N.M., S.M., K.S., J.H.), University of Washington, Seattle, Washington; Trauma Surgery (B.T.), Texas Health Presbyterian Hospital; Department of Emergency Medicine (J.S.G.), Baylor University Medical Center, Dallas, Texas; Johns Hopkins School of Medicine (M.L.W.), Baltimore, Maryland; Department of Emergency Medicine (T.P.A., M.R.C.), Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Emergency Medicine (J.M.T., J.C.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery (S.E.R.), Scripps Memorial Hospital La Jolla, La Jolla, California; Departments of Emergency Medicine (A.H.I.) and Internal Medicine (A.H.I.), University of Texas Southwestern Medical Center, Dallas, Texas; Providence Health Care Research Institute (J.C.), Vancouver, British Columbia, Canada; Rescu, Li Ka Shing Knowledge Institute (L.J.M.), and Department of Surgery (S.R.), St. Michael's Hospital; Division of Emergency Medicine, Department of Medicine Faculty of Medicine (L.J.M.), and Department of Laboratory Medicine and Pathobiology (J.C.), University of Toronto, Toronto, Ontario, Canada; Departments of Emergency Medicine (R.J.F.) and Surgery (D.J.D.), Regions Hospital, St. Paul, Minnesota; Department of Surgery (C.W., P.L.B.), University of Alabama, Birmingham, Alabama; Department of Surgery (C.E.W., B.A.C., L.E.V.), McGovern Medical School, University of Texas Health Science Center, Houston, Texas; Department of Laboratory Medicine and Molecular Diagnostics (J.C.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Departments of Emergency Medicine (N.J.R.) and Surgery (R.R.G.), John Peter Smith Health Network, Fort Worth, Texas; Department of Surgery (M.D.Z., M.F.), Mayo Clinic, Rochester, Minnesota; British Columbia Emergency Health Services (J.M.T., R.S.), Vancouver, British Columbia, Canada; Department of Emergency Medicine (L.K., A.H.), Hennepin County Medical Center, Minneapolis, Minnesota; Department of Surgery (S.R.), St. Michael's Hospital, Toronto, Ontario, Canada; Department of Emergency Medicine (M.G.), Medical City Plano, Plano; Emergency Medicine (R.S.), Methodist Dallas Medical Center, Dallas, Texas; National Heart, Lung, and Blood Institute, National Institutes of Health (G.S.), Bethesda, Maryland; and Department of Trauma Surgery (W.W.), Texas Health Harris Methodist Hospital, Fort Worth, Texas.
Background: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI.
View Article and Find Full Text PDFEfficacy and Safety of Elbasvir/Grazoprevir in Hepatitis C Virus GT1- and GT4-Infected People Aged 65 Years or Older.
Gerontol Geriatr Med
January 2019
Merck & Co., Inc., Kenilworth, NJ, USA.
In elderly individuals aged ≥65 years with hepatitis C virus (HCV) infection, efficacious and safe HCV therapy is complicated by frequent comorbidities and concomitant medications. The aim of this analysis was to evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in people aged ≥65 years. This is an integrated retrospective analysis of EBR/GZR administered for 12 weeks in participants with HCV genotype 1 or 4 infection enrolled in 12 Phase 2/3 clinical trials.
View Article and Find Full Text PDFComment on model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients.
Blood Adv
November 2018
Clinical Pharmacometrics, Bayer AG, Wuppertal, Germany.
Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.
Circ Cardiovasc Imaging
April 2015
From the Knight Cardiovascular Center, Oregon Health and Science University, Portland (J.T.B., B.H.M., A.X., Y.Z., S.K., N.J.L., A.A., J.R.L.); and La Jolla Immunology and Allergy Institute, CA (J.M.L.).
Background: Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators.
Methods And Results: Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.