tbuckley/cabot-search huggingface dataset:
307 Interaction of anti-PD-1/PD-1 immunocomplexes with human FcRs: binding properties and functional implication
Authors: Elena Daveri, Elena Luison, Viviana Vallacchi, Barbara Vergani, Veronica Huber, Agata Cova, Biagio Eugenio Leone, Marina Garassino, Mariangela Figini, Licia Rivoltini
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Rescue of exhausted T cell immunity through the inhibition of PD-1/PD-L1 interaction is a pillar of immunotherapeutic anti-PD-1 monoclonal antibodies (mAbs), as Nivolumab and Pembrolizumab. Despite the IgG4 subclass, anti-PD-1 mAbs can bind different FcγRs and trigger immunosuppressive activity in FcR-expressing myeloid cells. This effect is evident when anti-PD-1 mAbs engage soluble PD-1 (sPD-1) forming a stable sPD-1-antiPD-1mAb immune complex (PD-1 IC). In the present study we dissect the process by investigating which of the FcγRs displays the highest affinity for monomeric or complexed Nivolumab. In addition, methods for detecting and quantifying PD-1 ICs in plasma of patients treated with PD-1 blockers mAbs are under development for clinical application. Methods By surface plasmon resonance (SRP) (BiacoreTM T200, Cytiva), the interaction of FcγRI/CD64, FcγRIIa/CD32a, FcγRIIb/CD32b, FcγRIIIa/CD16a and FcγRIIIb/CD16b with anti-PD1 Nivolumab and the corresponding PD-1-IC has been evaluated, and their cellular localization has been assessed by confocal microscopy. Further, sPD-1 and PD-1 IC has been determined by customized ELISAs and western blot approaches in plasma of anti-PD-1 mAb-treated patients. Results The binding of anti-PD1 and PD-1-IC occurred with all the FcγRs tested, albeit sensorgrams revealed diverse degrees of affinity. No major difference in the overall affinity of the monomeric anti-PD-1 versus PD-1 IC is observed for FcγRI/CD64, FcγRIIa/CD32a, FcγRIIb/CD32b. Instead, the dissociation phase was clearly slowest for PD-1 IC with respect to the monomeric mAb in FcγRIIIa/CD16a and FcγRIIIb/CD16b binding studies. Nevertheless, only PD-1 IC undergoes internalization when interacting with human FcγR+ myeloid cells in vitro, through pathways that does not appear to lead to lysosomal co-localization. Customized ELISA for PD-1 IC quantification has been developed to detect the complex after enrichment of plasma IgG4 by specific matrix. Data concerning the evaluation of PD-1 IC concentration in plasma of cancer patients treated with Nivolumab, will be presented. Conclusions Despite the IgG4 subclass is expected to display the lowest binding affinity to Fcγs, we report here that anti-PD-1 therapeutic antibodies bind significantly to CD16, CD32 and CD64, particularly if stabilized in the IC form by engaging soluble PD-1. This evidence, if occurring in vivo, could introduce novel functional properties to these therapeutic agents, with potential detrimental effects on their clinical efficacy. Our findings imply that tools to antagonize PD-1-related exhaustion by Fc-null mAbs or non-mAb-based strategies could be preferred to engage full-fledged antitumor immune responses without unwanted effects related to FcR triggering.
High Drug Costs Hurt Health Outcomes—One Way or Another
Authors: Stephen M. Downs
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Applicability of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) to Predict Outcomes of Acute Myeloid Leukemia Patients Older Than 60 Years Undergoing Non-Myeloablative Allogeneic Stem Cell Transplantation
Authors: Donata Backhaus, Madlen Jentzsch, Dominic Brauer, Julia Schulz, Vladan Vucinic, Georg-Nikolaus Franke, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind
Journal: Blood (2021)
간경변증 : 간섬유화 기전 및 항섬유화 치료
Authors: 백용한 ( Young Han Paik )
Journal: Clinical and Molecular Hepatology (2008)

Liver cirrhosis results from chronic liver injuries that cause the accumulation of extracellular matrix and progression of hepatic fibrosis. Hepatic fibrogenesis is a dynamic process and hepaitc stellate cells exert a critical role in the development of hepatic fibrosis. Due to increasing understading the molecular mechanisms of hepatic fibrogenesis, several effective anti-fibrotic therapies have been emerging. However, lack of sensitive and liver-specific biomarker of hepatic fibrosis has been a limitation for conducting human clinical trials with antifibrotic agents. In this review, the mechanisms of hepatic fibrosis and antifibrotic therapies in human were briefly reviewed.
Inflammation and Immune Response in Arrhythmogenic Cardiomyopathy: State-of-the-Art Review
Authors: Babken Asatryan, Angeliki Asimaki, Andrew P. Landstrom, Mohammed Y. Khanji, Katja E. Odening, Leslie T. Cooper, Francis E. Marchlinski, Anna R. Gelzer, Christopher Semsarian, Tobias Reichlin, Anjali T. Owens, C. Anwar A. Chahal
Journal: Circulation (2021)

Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium, predominantly caused by genetic defects in proteins of the cardiac intercalated disc, particularly, desmosomes. Transmission is mostly autosomal dominant with incomplete penetrance. ACM also has wide phenotype variability, ranging from premature ventricular contractions to sudden cardiac death and heart failure. Among other drivers and modulators of phenotype, inflammation in response to viral infection and immune triggers have been postulated to be an aggravator of cardiac myocyte damage and necrosis. This theory is supported by multiple pieces of evidence, including the presence of inflammatory infiltrates in more than two-thirds of ACM hearts, detection of different cardiotropic viruses in sporadic cases of ACM, the fact that patients with ACM often fulfill the histological criteria of active myocarditis, and the abundance of anti-desmoglein-2, antiheart, and anti-intercalated disk autoantibodies in patients with arrhythmogenic right ventricular cardiomyopathy. In keeping with the frequent familial occurrence of ACM, it has been proposed that, in addition to genetic predisposition to progressive myocardial damage, a heritable susceptibility to viral infections and immune reactions may explain familial clustering of ACM. Moreover, considerable in vitro and in vivo evidence implicates activated inflammatory signaling in ACM. Although the role of inflammation/immune response in ACM is not entirely clear, inflammation as a driver of phenotype and a potential target for mechanism-based therapy warrants further research. This review discusses the present evidence supporting the role of inflammatory and immune responses in ACM pathogenesis and proposes opportunities for translational and clinical investigation.
Neutralizing Antibody Responses Against Sars-Cov-2 in Patients with Plasma Cell Disorders Who Are on Active Treatment after Two Doses of mRNA Vaccination
Authors: Al-Ola Abdallah, Zahra Mahmoudjafari, Meera Mohan, Joseph P. McGuirk, Cassie Remker, Margaret Foss, Ellie Karloff, Heather Fitch, Ghulam Rehman Mohyuddin, Shebli Atrash
Journal: Blood (2021)
A Globally Applicable "Triple AAA" Risk Model for Essential Thrombocythemia Based on Age, Absolute Neutrophil Count, and Absolute Lymphocyte Count
Authors: Ayalew Tefferi, Giuseppe Gaetano Loscocco, Faiqa Farrukh, Natasha Szuber, Francesco Mannelli, Animesh D. Pardanani, Curtis A. Hanson, Valerio De Stefano, Tiziano Barbui, Paola Guglielmelli, Naseema Gangat, Alessandro Vannucchi
Journal: Blood (2021)
Inhibiting Mitochondrial Complex II Exposes a Novel Metabolic Vulnerability in Acute Myeloid Leukemia
Authors: Alessia Roma, Matthew Tcheng, Nawaz Ahmed, Sarah Walker, Preethi Jayanth, Mark D. Minden, Kristin Hope, Praveen P. Nekkar Rao, Jessica Luc, Andrew C. Doxey, Julie A. Reisz, Angelo D'Alessandro, Paul A. Spagnuolo
Journal: Blood (2021)
Activation of Pyruvate Kinase-R with Etavopivat (FT-4202) Is Well Tolerated, Improves Anemia, and Decreases Intravascular Hemolysis in Patients with Sickle Cell Disease Treated for up to 12 Weeks
Authors: R. Clark Clark Brown, Santosh L. Saraf, Kimberly Cruz, Modupe Idowu, Theodosia A. Kalfa, James Geib, Sanjeev Forsyth, Patricia Schroeder, Eric Wu, Patrick Kelly, Marilyn J. Telen
Journal: Blood (2021)
Treatment Free Remission in Patients with Chronic Phase CML: A Single Center Experience
Authors: Quinto J Gesiotto, Akriti G Jain, Somedeb Ball, Lisa Nodzon, Amanda Rodriguez, Rami S. Komrokji, David A. Sallman, Eric Padron, Andrew T. Kuykendall, Onyee Chan, Jeffrey E. Lancet, Javier Pinilla Ibarz, Kendra Sweet
Journal: Blood (2021)
Hypomethylating Therapy Does Not Improve Outcome of Therapy-Related Myeloid Neoplasm Including TP53 Mutated and Complex Karyotype Subgroups
Authors: Rakchha Chhetri, Kirsty Sharplin, William Proudman, Monika M Kutyna, Siddarth Nayar, Deepak Singhal, David M Ross, Michelle Damin, Akash Kalro, Peter G Bardy, Daniel Thomas, Mithun V. Shah, Devendra Hiwase
Journal: Blood (2021)
Patients with Multiple Myeloma on Anti-CD38 or Anti-BCMA Based Regimens and Patients with Waldenstrom's Macroglobulinemia Under Rituximab or BTK Inhibitors Have a Poor Humoral Response Following COVID-19 Vaccination
Authors: Evangelos Terpos, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Alexandros Briasoulis, Sentiljana Gumeni, Panagiotis Malandrakis, Despina Fotiou, Eleni-Dimitra Papanagnou, Magdalini Migkou, Foteini Theodorakakou, Maria Roussou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Ioannis P. Trougakos, Efstathios Kastritis, Meletios-Athanasios Dimopoulos
Journal: Blood (2021)
VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects
Authors: Miriam Bazan-Peregrino, Rocio Garcia-Carbonero, Berta Laquente, Rafael Álvarez, Ana Mato-Berciano, Marta Gimenez-Alejandre, Sara Morgado, Alba Rodríguez-García, Maria V Maliandi, M Carmen Riesco, Rafael Moreno, Mireia M Ginestà, Mercedes Perez-Carreras, Joan B Gornals, Susana Prados, Sofía Perea, Gabriel Capella, Ramon Alemany, Ramon Salazar, Emma Blasi, Carmen Blasco, Manel Cascallo, Manuel Hidalgo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer. Methods VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1×10 11 viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography. Results VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption. Conclusions VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma. Trial registration number EudraCT number: 2012-005556-42 and NCT02045589 .
Selective Targeting of Splicing Factor Mutant Hematopoietic Stem and Progenitor Cells Via STAT3 Inhibition
Authors: Kathryn S Potts, Rosannah C. Cameron, Noura Ghazale, Varun Gupta, Juan Martin Barajas, LaShanale Wallace, Ana Leal-Cervantes, Srinivas Aluri, Kith Pradhan, Mia McKinstry, Xiaoying Bai, Gaurav S Choudhary, Aditi Shastri, Amit Verma, Esther A. Obeng, Teresa V. Bowman
Journal: Blood (2021)
The Experience of the Cooperation in Science and Technology European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias (COST EuNet-INNOCHRON) Action and the Sweden Experience in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Era
Authors: Michail Spanoudakis, David C. Dale, Emily Tran, Marije Bartels, Suncica Kapor, Daniela Guardo, Jelena Roganovic, Joanne Yacobovich, Christer Nilsson, Carlo Dufour, Helen A. Papadaki, Jan Palmblad
Journal: Blood (2021)
Molecular Characterization of Diffuse Large B-Cell Lymphoma Associated to Hepatitis C Virus Infection
Authors: Roberta Sciarra, Caterina Cristinelli, Michele Merli, Marco Lucioni, Silvia Zibellini, Roberta Riboni, Virginia Valeria Ferretti, Silvia Uccella, Caterina Zerbi, Benedetta Bianchi, Daniela Furlan, Maurizio Bonfichi, Manuel Gotti, Chiara Varraso, Sara Fraticelli, Irene Defrancesco, Marco Frigeni, Tanja Lazic, Giuseppina Ferrario, Fausto Sessa, Francesco Passamonti, Marco Paulli, Luca Arcaini
Journal: Blood (2021)
The BMP/SMAD Pathway Is a Key Mediator of Leukemic Transformation of TP53-Mutant Post-MPN AML
Authors: Bing Li, Wenbin An, Hua Wang, Aishwarya Krishnan, Shoron Mowla, Timour Baslan, Richard Koche, Wenbin Xiao, Scott Lowe, Ross L. Levine, Raajit Rampal
Journal: Blood (2021)
TNFα Controls the Delicate Balance between Erythropoiesis and Stem Cell Exhaustion during Inflammatory Stress
Authors: Amaliris Guerra, Vania Lo Presti, Ana Catarina Martins, Carlo Castruccio Castracani, Ritama Gupta, Rea Oikonomidou, Emir O'Hara, Carla Casu, Laura Bennett, Robert Paulson, Peter Kurre, Stefano Rivella, Raffaella Gozzelino
Journal: Blood (2021)
Abstract 11815: Statin Intolerance is Predicted by Intolerance to Multiple Others Drugs: Results of a Large Real-World Experience
Authors: Jeffrey L Anderson, Viet T Le, Tami L Bair, Stacey Knight, Brianna Ronnow, Joseph B Muhlestein, Kirk U Knowlton, Benjamin D Horne
Journal: Circulation (2021)

Background: Dealing with statin intolerance represents a major clinical challenge. Controlled clinical trials suggest that a large percentage of statin intolerance may be due to a “nocebo effect”, wherein adverse reactions are linked to pill ingestion irrespective of actual pill content (e.g., SAMSON trial). We tested whether statin intolerance was associated with intolerance to other medications in a large real-world experience. We hypothesized that statin intolerance would be associated with multiple drug intolerances. Methods: We searched Intermountain Healthcare medical records between January 2002 and February 2021 for patients (pts) with a listed intolerance or allergy to 1 or more statins. We compared these to a control group of randomly selected pts not exposed to statins but taking one or more other oral medications. A second control group included all patients taking and tolerating statin therapy. We compared the number of recorded drug allergies/intolerances in the statin intolerant group with those in the 2 control groups. Results: Characteristics of patients in the 3 groups are shown in the Table. On average, statin intolerant patients had 3.64 additional listed drug allergies/intolerances (beyond statins), compared to 1.31 in non-statin exposed controls and 1.81 in the statin tolerant population (both p&lt;.001). Conclusion: In this large real-world experience, statin intolerance was strongly associated with intolerance to multiple other medications. Although some patients may have a true intolerance to multiple medications, including statins, patients with multiple drug intolerances may also suffer from a generalized nocebo effect. In either case, noting a patient’s tendency toward multiple drug intolerances can alert clinicians to an increased intolerance risk when initiating a statin and can lead to preemptive medical and educational interventions aimed at reducing this risk.
AGILE: A Global, Randomized, Double-Blind, Phase 3 Study of Ivosidenib + Azacitidine Versus Placebo + Azacitidine in Patients with Newly Diagnosed Acute Myeloid Leukemia with an <i>IDH1</i> Mutation
Authors: Pau Montesinos, Christian Recher, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Giambattista Bertani, Michael Heuser, Rodrigo T. Calado, Andre C. Schuh, Su-Peng Yeh, Scott R. Daigle, Jianan Hui, Vickie Zhang, Shuchi S. Pandya, Diego A. Gianolio, Stephane de Botton, Hartmut Döhner
Journal: Blood (2021)
Abstract 9159: Mindfulness Training, Cognitive Function and Interoceptive Awareness in Heart Failure Outpatients: Preliminary Findings
Authors: Elena Salmoirago-blotcher, Kristen Walaska, Dyuti Trivedi, Shira Dunsiger, Daniel Levine, Christopher Breault, Jia-Rong Wu, Ronald Cohen
Journal: Circulation (2021)

Introduction: Cognitive impairment affects up to 2/3 of patients with heart failure (HF) and is an important barrier to HF self-care. Adequate interoceptive awareness (the ability to sense and interpret signals from within the body) is also relevant in this context, in that it allows patients to recognize the worsening of symptoms, receive treatment sooner, and prevent hospital re-admissions. As a secondary analysis from a single arm pilot RCT (NCT03571581), we explored effects of phone-delivered Mindfulness Training (MT) on cognitive function and interoceptive awareness in outpatients with NYHA class I-III HF. Methods: Participants received a weekly, 30-minute phone-delivered MT session for 8 weeks integrated with daily guided individual practice. Assessments of memory, attention, and executive function (NIH Toolbox); interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness/MAIA), and exercise capacity (6-min walk test/6MWT), were conducted at baseline and end of treatment (EOT). Results: We enrolled 33 patients (32% women; 32% minorities; mean age 62 years). Baseline cognitive function was normal. At EOT, we observed improvements in all the cognitive domains considered (Table 1A; p &lt;.05 for the Flanker test) and in MAIA scores (p &lt; .05 - Table 1B). 6MWT distance increased from 349.9 (92.6) to 377.7 (97) meters, p &lt;.05). Conclusions: MT was associated with improvements in cognitive function, interoceptive awareness, and functional status. If confirmed in a large RCT, these findings could pave the way to the integration of MT into rehabilitation programs to improve clinical outcomes in this vulnerable population.
FLT3 Inhibitors Upregulate CXCR4 and E-Selectin Ligands and CD44 <i>Via</i> ERK Suppression in AML Cells, and Blockade of CXCR4 and E-Selectin Signaling with GMI-1359 Overcomes AML Resistance to Quizartinib <i>in Vitro</i> and <i>In Vivo</i>
Authors: Yannan Jia, Mahesh Basyal, Lauren B Ostermann, Kyung Hee Chang, Qi Zhang, William E. Fogler, John L. Magnani, Marina Konopleva, Weiguo Zhang, Michael Andreeff
Journal: Blood (2021)
Managing conflicts of interest in healthcare: the new frontier
Authors: Susan Chimonas, Deborah Korenstein
Journal: BMJ (2021)

Our research team spent countless hours examining over 500 original research reports to identify, characterise, and map all documented ties between the medical products industry and the individuals, institutions, and activities in the healthcare ecosystem.1 Our goal was to move beyond discrete ties to understand the full network of relationships through which industry can influence care delivery. We were struck by the incredible breadth and variety of industry targets and strategies. Beyond these superficial findings, however, our map exposes the deeper structure that underlies these potential conflicts of interest—the stable, patterned system of direct industry ties and indirect, “downstream” interrelationships that consistently incentivise some choices and opportunities while discouraging or curbing others. The result: seemingly unlimited …
Tumor-Confirmed Follicular Lymphoma Mutations Are Detectable in Peripheral Blood Years Prior to Clinical Diagnosis
Authors: Joseph G Schroers-Martin, Joanne Soo, Gabriel Brisou, Florian Scherer, David M. Kurtz, Brian Sworder, Michael S. Khodadoust, Michael C. Jin, Agnès Bru, Chih Long Liu, Henning Stehr, Paolo Vineis, Yasodha Natkunam, Lauren R Teras, Joo Y. Song, Bertrand Nadel, Maximilian Diehn, Sandrine Roulland, Ash A. Alizadeh
Journal: Blood (2021)
Perfecting CAR Engraftment to a Tee (Cell) through Characterization of Single Cell Transcriptome Product and Understanding Neurotoxicity
Authors: Wesley Wilson, Fei Miao, Alfred L Garfall, Dexiu Bu, Elena J Orlando, Jennifer L Brogdon, Iulian Pruteanu-Malinici, Adam D Cohen, Michael C. Milone
Journal: Blood (2021)
Intensified Cytarabine Dose during Consolidation Therapy in AML Patients Under 65 Years Is Not Associated with Survival Benefit
Authors: Maher Hanoun, Leo Ruhnke, Michael Kramer, Kerstin Schäfer-Eckhard, Björn Steffen, Tim Sauer, Stefan W. Krause, Christoph Schliemann, Martin Kaufmann, Mathias Haenel, Edgar Jost, Tim H Brummendorf, Lars Fransecky, Sabrina Kraus, Hermann Einsele, Dirk Niemann, Andreas Neubauer, Johannes Kullmer, Ruth Seggewiss-Bernhard, Martin Goerner, Gerhard Held, Ulrich Kaiser, Sebastian Scholl, Hans Christian Reinhardt, Uwe Platzbecker, Claudia D. Baldus, Carsten Mueller-Tidow, Martin Bornhaeuser, Hubert Serve, Christoph Rollig
Journal: Blood (2021)