tbuckley/cabot-search huggingface dataset:
Choosing an Initial Therapeutic Approach for Hypertension—Time for a Fixed-Dose Combination First?
Authors: Ann Marie Navar, Thomas J. Wang
Journal: JAMA Cardiology (2020)

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 Cardiology 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 Cardiology journal
A novel nucleolin-binding peptide for Cancer Theranostics
Authors: Jae-Hyun Kim, Chanhyung Bae, Min-Jung Kim, In-Hye Song, Jae-Ha Ryu, Jang-Hyun Choi, Choong-Jae Lee, Jeong-Seok Nam, Jae Il Kim
Journal: Theranostics (2020)

Background: Cancer-specific ligands have been of great interest as pharmaceutical carriers due to the potential for site-specific delivery. In particular, cancer-specific peptides have many advantages over nanoparticles and antibodies, including high biocompatibility, low immunogenicity, and the formation of nontoxic metabolites. The goal of the present study was the development of a novel cancer-specific ligand. Methods: Cancer-specific peptide ligands were screened using a one-bead-one-compound (OBOC) combinatorial method combined with a multiple-antigen-peptide (MAP) synthesis method. The specificity of the peptide ligands toward cancer cells was tested in vitro using a whole-cell binding assay, flow cytometry, and fluorescence confocal microscopy. The tissue distribution profile and therapeutic efficacy of a paclitaxel (PTX)-conjugated peptide ligand was assessed in vivo using xenograft mouse models. Results: We discovered that AGM-330 specifically bound to cancer cells in vitro and in vivo. Treatment with PTX-conjugated AGM-330 dramatically inhibited cancer cell growth in vitro and in vivo compared to treatment with PTX alone. The results of pull-down assay and LC-MS/MS analyses showed that membrane nucleolin (NCL) was the target protein of AGM-330. Although NCL is known as a nuclear protein, we observed that it was overexpressed on the membranes of cancer cells. In particular, membrane NCL neutralization inhibited growth in cancer cells in vitro. Conclusions: In summary, our findings indicated that NCL-targeting AGM-330 has great potential for use in cancer diagnosis and targeted drug delivery in cancer therapy.
Suppression of breast cancer metastasis by p16’s dual effect on anti-angiogenesis and anti-proliferation
Authors: Kevin T. Nash, Pushkar A. Phadke, Kedar S. Vaidya, Yujiang Jia, Haito Ding, John C. Kappes, Mary A. Accavitti-Loper, Douglas R. Hurst, Danny R. Welch
Journal: Cancer Research (2006)

4313  Blocking tumor angiogenesis may be an effective approach to suppress tumor metastasis. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis. The degree of tumor malignancy correlates with the expression of VEGF and inversely with expression of tumor suppressor gene p16 in human breast specimens. To examine whether restoring of wild-type p16 in breast cancer cells decreases VEGF gene expression and inhibits breast cancer angiogenesis and metastasis, human breast cancer cell line MDA-MB-231, MCF-7 and mouse breast cancer cell line JygMC(A) were used as models for studies. To facilitate induction of p16 expression, a replication-defective recombinant adenovirus expressing human wild-type p16 (AdRSVp16) has been generated. Our study showed that adenoviral-mediated p16 expression downregulated VEGF expression and VEGF receptor activation in breast cancer cells. AdRSVp16 inhibited in vitro cell growth of MDA-MB-231, MCF-7 and JygMC(A) at 50.4%, 58.3% and 38.5%, respectively, attenuated in vivo angiogenesis induced by MDA-MB-231 cells in Matrigel plug assay and in a dorsal air sac model. AdRSVp16 also significantly reduced tumor metastases of JygMC(A) cells in nude mice when compared to the control groups in a spontaneous metastasis assay. In addition, the effects of p16 on expression of proliferation marker PCNA, neovascularization marker CD31 and apoptosis inside the tumors were also analyzed. Moreover, the mechanism of p16-mediated downregulation of VEGF is also explored. These results demonstrate that p16 downregulates VEGF gene expression, inhibits angiogenesis, and suppresses tumor growth and metastasis in breast cancer cells. With p16’s combinative effects on inhibition of primary tumor growth and suppression of secondary tumor formation (i.e., metastasis), p16 gene therapy should provide an effective therapy for breast cancer treatment, when used in conjunction with other therapeutic modalities.
Abstract 14579: Hepatic TRIB1 Regulates ApoB Metabolism by Modulating Its Production and Catabolism
Authors: Katherine Quiroz-Figueroa, Andrea M Berrido, Cecilia Vitali, Donna Conlon, John S Millar, Robert C Bauer, Nicholas J Hand, Daniel J Rader
Journal: Circulation (2019)

Coronary artery disease (CAD) is the leading cause of death worldwide, and human genetics has proven to be a powerful approach to identify novel physiological pathways and therapeutic targets for t...
Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump for Cardiogenic Shock
Authors: Hanne Berg Ravn, Ole Kristian Lerche Helgestad, Jacob Eifer Møller
Journal: JAMA (2020)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
IL-32γ Induces M2 Macrophage Polarization with Enhanced Ability of Macrophage-Mediated Drug Resistance in Myeloma Cells through STAT3 and NF-κB Activation
Authors: Haimeng Yan, Xuanru Lin, Xi Huang, Zhang En Fan, Donghua He, Xu Ruyi, Huiyao Gu, Yi Li, Jingsong He, Qing Yi, Zhen Cai
Journal: Blood (2017)
Variant signaling topology at the cancer cell–T-cell interface induced by a two-component T-cell engager
Authors: Dina Kouhestani, Maria Geis, Saed Alsouri, Thomas G. P. Bumm, Hermann Einsele, Markus Sauer, Gernot Stuhler
Journal: Cellular and Molecular Immunology (2020)

Bispecific T-cell-engaging antibodies (BiTEs) convey antigenic information from cancer to the T-lymphocyte-associated CD3 complex, thus redirecting immune effector cells to induce target cell lysis.Since antigenic information from transformed tissues is rarely unambiguous, we recently introduced novel T-cell-engaging antibody fragments called hemibodies for the combinatorial, ultraprecise targeting of cancer. 1 Here, we report the unprecedented enhancement of the plasticity of immunological synapse (IS) formation and variant signaling topology at the cancer cell-T-cell interface induced by hemibodies compared to that induced by BiTEs.Physiologically, T lymphocytes are activated via invariant CD3 chains after binding of the T-cell receptor (TCR) to cognate antigen: HLA complexes presented by target cells within the context of the IS.This process involves a series of intracytoplasmic signaling events in T cells, which are initiated by the removal of an inhibitory phosphate moiety from Tyr505 in the SRC family protein tyrosine kinase LCK by CD45 phosphatases. 2Seconds after the dephosphorylation of LCK, the CD45 molecule is excluded from the contact zone and the newly formed central supramolecular antigen cluster (SMAC) region.This is a prerequisite for the phosphorylation of immune receptor tyrosine-based activation motifs (ITAMs) in the CD3zeta chains and the subsequent recruitment and activation of ZAP70.ZAP70 activates a number of signaling molecules to promote proliferation, exocytosis of lytic granules, and de novo synthesis of cytokines 3,4 Bispecific antibodies redirect T cells against cancer by linking tumor-associated antigens and CD3, thus mimicking the physiological T-cell activation process (Fig. 1a, left) 5,6 Although this is highly effective in eliminating tumor cells, a number of dose-limiting effects have been observed due to the expression of the antigen of interest on nontumor tissues 7 or nonspecific T-cell activation.To overcome these limitations, we developed combinatorial T-cellengaging pro-drugs named hemibodies. 1Hemibodies are complementary antibody fragments composed of an antigen-specific single-chain variable fragment (scFv) fused to either the variable heavy (VH) or the variable light chain domain (VL) of a CD3-binding paratope (Fig. 1a,right).In the situation where both hemibodies simultaneously bind to the surface of a given target cell, the variable domains align and reconstitute the CD3-binding site to redirect effector T cells.A proof of principle was performed in an HLA-mismatched, allogeneic transplantation model in vitro and in vivo by employing HLA-A2 and CD45 target antigens to uniquely tag and eliminate diseased hematopoietic cells in a leukemia patient.This combinatorial AND gate operation has been shown to differentiate hemibody-operated immunotherapy from therapy with BiTE molecules, which served as template structures.
Epidemiologic Characterization of Transfusion Recipients with Red Blood Cell Alloantibodies from Four US Regions: Evidence from the REDS-III Recipient Database
Authors: Matthew S. Karafin, Matt Westlake, Ronald G. Hauser, Christopher A. Tormey, Philip L Norris, Nareg H. Roubinian, Yanyun Wu, Steven Kleinman, Jeanne E. Hendrickson
Journal: Blood (2017)
Fructose-1, 6-bisphosphatase 1 interacts with NF-κB p65 to regulate breast tumorigenesis via PIM2 induced phosphorylation
Authors: Chao Lu, Chune Ren, Tingting Yang, Yonghong Sun, Pengyun Qiao, Xue Han, Zhenhai Yu
Journal: Theranostics (2020)

Rationale: Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor and could mediate the activities of multiple transcriptional factors via its non-canonical functions. However, the underlying mechanism of posttranscriptional modification on the non-canonical functions of FBP1 remains elusive. Methods: We employed immunoaffinity purification to identify binding partner(s) and used co-immunoprecipitation to verify their interactions. Kinase reaction was used to confirm PIM2 could phosphorylate FBP1. Overexpression or knockdown proteins were used to assess the role in modulating p65 protein stability. Mechanistic analysis was involved in protein degradation and polyubiquitination assays. Nude mice and PIM2-knockout mice was used to study protein functions in vitro and in vivo. Results: Here, we identified Proviral Insertion in Murine Lymphomas 2 (PIM2) as a new binding partner of FBP1, which could phosphorylate FBP1 on Ser144. Surprisingly, phosphorylated FBP1 Ser144 abrogated its interaction with NF-κB p65, promoting its protein stability through the CHIP-mediated proteasome pathway. Furthermore, phosphorylation of FBP1 on Ser144 increased p65 regulated PD-L1 expression. As a result, phosphorylation of FBP1 on Ser144 promoted breast tumor growth in vitro and in vivo. Moreover, the levels of PIM2 and pSer144-FBP1 proteins were positively correlated with each other in human breast cancer and PIM2 knockout mice. Conclusions: Our findings revealed that phosphorylation noncanonical FBP1 by PIM2 was a novel regulator of NF-κB pathway, and highlights PIM2 inhibitors as breast cancer therapeutics.
Dissecting the mechanism of action of intravenous immunoglobulin in human autoimmune disease: Lessons from therapeutic modalities targeting Fcγ receptors
Authors: Anthony Shock, David Humphreys, Falk Nimmerjahn
Journal: Journal of Allergy and Clinical Immunology (2020)

Since the first description of the administration of high doses of pooled serum IgG, also referred to as intravenous IgG (IVIg) therapy, as being able to ameliorate various autoimmune diseases, researchers have been investigating which molecular and cellular pathways underlie IVIg activity. Apart from trying to understand the obvious conundrum that IgG can trigger both autoimmune pathology and resolution of inflammation, the rapidly expanding use of IVIg has led to a lack of availability of this primary blood product, providing a strong rationale for developing recombinant alternatives. During the last decade, a tremendous number of novel insights into IVIg activity brought the goal of replacing IVIg within reach, at least in select indications, and has led to the initiation of several clinical trials. At the forefront of this effort is the modulation of autoantibody half-life and blocking access of autoantibodies to fragment cystallizable γ receptors (Fcγ receptors). In this rostrum article, we will briefly discuss current models of IVIg activity, followed by a more specific focus on novel therapeutic avenues that are entering the clinic and may replace IVIg in the future.
Equity in Health: Consideration of Race and Ethnicity in Precision Medicine
Authors: Todd L. Edwards, Joseph Breeyear, Jacqueline A. Piekos, Digna R. Velez Edwards
Journal: Trends in Genetics (2020)

The causes for disparities in implementation of precision medicine are complex, due in part to differences in clinical care and a lack of engagement and recruitment of under-represented populations in studies. New tools and large genetic cohorts can change these circumstances and build access to personalized medicine for disadvantaged populations.
The Expected 30-Year Benefits of Early Versus Delayed Primary Prevention of Cardiovascular Disease by Lipid Lowering
Authors: Michael J. Pencina, Karol M. Pencina, Donald Lloyd-Jones, Alberico L. Catapano, George Thanassoulis, Allan D. Sniderman
Journal: Circulation (2020)

Background: Lipid-lowering recommendations for prevention of atherosclerotic cardiovascular disease rely principally on estimated 10-year risk. We sought to determine the optimal time for initiation of lipid lowering in younger adults as a function of expected 30-year benefit. Methods: Data from 3148 National Health and Nutrition Examination Survey (2009–2016) participants, age 30 to 59 years, not eligible for lipid-lowering treatment recommendation under the most recent US guidelines, were analyzed. We estimated the absolute and relative impact of lipid lowering as a function of age, age at initiation, and non–high-density lipoprotein cholesterol (HDL-C) level on the expected rates of atherosclerotic cardiovascular disease over the succeeding 30 years. We modeled expected risk reductions based on shorter-term effects observed in statin trials (model A) and longer-term benefits based on Mendelian randomization studies (model B). Results: In both models, potential reductions in predicted 30-year atherosclerotic cardiovascular disease risk were greater with older age and higher non–HDL-C level. Immediate initiation of lipid lowering (ie, treatment for 30 years) in 40- to 49-year-old patients with non–HDL-C ≥160 mg/dL would be expected to reduce their average predicted 30-year risk of 17.1% to 11.6% (model A; absolute risk reduction [ARR], 5.5%) or 6.5% (model B; ARR 10.6%). Delaying lipid lowering by 10 years (treatment for 20 years) would result in residual 30-year risk of 12.7% (A; ARR 4.4) or 9.9% (B; ARR 7.2%) and delaying by 20 years (treatment for 10 years) would lead to expected mean residual risk of 14.6% (A; ARR 2.6%) or 13.9% (B; ARR 3.2%). The slope of the achieved ARR as a function of delay in treatment was also higher with older age and higher non–HDL-C level. Conclusions: Substantial reduction in expected atherosclerotic cardiovascular disease risk in the next 30 years is achievable by intensive lipid lowering in individuals in their 40s and 50s with non–HDL-C ≥160 mg/dL. For many, the question of when to start lipid lowering might be more relevant than whether to start lipid lowering.
Risk Stratification Based on Chronic Liver Failure Consortium Acute Decompensation Score in Patients With Child‐Pugh B Cirrhosis and Acute Variceal Bleeding
Authors: Yong Lv, Zhengyu Wang, Kai Li, Qiuhe Wang, Wei Bai, Xulong Yuan, Tianlei Yu, Jing Niu, Zhiping Yang, Xuan Zhu, Jianbo Zhao, Hui Xue, Zaibo Jiang, Yuzheng Zhuge, Chunqing Zhang, Junhui Sun, Pengxu Ding, Weixin Ren, Yingchun Li, Kewei Zhang, Wenguang Zhang, Wengang Guo, Bohan Luo, Xiaomei Li, Jie Yuan, Na Han, Ying Zhu, Chuangye He, Zhanxin Yin, Daiming Fan, Guohong Han
Journal: Hepatology (2020)

Background and Aims Optimal candidates for early transjugular intrahepatic portosystemic shunt (TIPS) in patients with Child‐Pugh B cirrhosis and acute variceal bleeding (AVB) remain unclear. This study aimed to test the hypothesis that risk stratification using the Chronic Liver Failure Consortium Acute Decompensation score (CLIF‐C ADs) may be useful to identify a subgroup at high risk of mortality or further bleeding that may benefit from early TIPS in patients with Child‐Pugh B cirrhosis and AVB. Approach and Results We analyzed the pooled individual data from two previous studies of 608 patients with Child‐Pugh B cirrhosis and AVB who received standard treatment between 2010 and 2017 in China. The concordance index values of CLIF‐C ADs for 6‐week and 1‐year mortality (0.715 and 0.708) were significantly better than those of active bleeding at endoscopy (0.633 [ P &lt; 0.001] and 0.556 [ P &lt; 0.001]) and other prognostic models. With X‐tile software identifying an optimal cutoff value, patients were categorized as low risk (CLIF‐C ADs &lt;48), intermediate risk (CLIF‐C ADs 48‐56), and high risk (CLIF‐C ADs &gt;56), with a 5.6%, 16.8%, and 25.4% risk of 6‐week death, respectively. Nevertheless, the performance of CLIF‐C ADs for predicting a composite endpoint of 6‐week death or further bleeding was not satisfactory (area under the receiver operating characteristics curve [AUC], 0.588). A nomogram incorporating components of CLIF‐C ADs and albumin, platelet, active bleeding, and ascites significantly improved the prediction accuracy (AUC, 0.725). Conclusions In patients with Child‐Pugh B cirrhosis and AVB, risk stratification using CLIF‐C ADs identifies a subgroup with high risk of death that may derive survival benefit from early TIPS. With improved prediction accuracy for 6‐week death or further bleeding, the data‐driven nomogram may help to stratify patients in randomized trials. Future external validation of these findings in patients with different etiologies is required.
Evolution of viral quasispecies during SARS-CoV-2 infection
Authors: Aude Jary, Valentin Leducq, Isabelle Malet, Stéphane Marot, Elise Klement-Frutos, Elisa Teyssou, Cathia Soulié, Basma Abdi, Marc Wirden, Valérie Pourcher, Eric Caumes, Vincent Calvez, Sonia Burrel, Anne-Geneviève Marcelin, David Boutolleau
Journal: Clinical Microbiology and Infection (2020)
THU0176 Celecoxib is associated with significant acr50/70 responses in rheumatoid arthritis (ra)
Authors: EA Tindall
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Celecoxib, a specific cyclooxygenase (COX)-2 inhibitor, has been shown to improve the signs and symptoms of RA. Because of the safety and tolerability of this agent, celecoxib administration is more sustainable, potentially producing long-term decreases in disease activity. <h3>Methods</h3> The ability of celecoxib to induce responses at the ACR20, ACR50, and ACR70 levels was determined in a pooled analysis of two placebo- and active-comparator controlled trials. In addition, radiographic data from a long-term open label safety trial were analysed for the effect of celecoxib on radiographic evidence of disease progression using the Sharp score and Sharp count. Dose titration was allowed during this trial. <h3>Results</h3> Celecoxib induced significant improvement compared to placebo at the ACR20, ACR50, and ACR70 levels at 12 weeks during the controlled trials (see Table 1 for% of responders, *p &lt; 0.05 vs placebo). Prior to entry to the long-term open label trial, the average changes in the Sharp score and count were 2.76 (95% confidence interval [CI] 0.68–4.84) units/year and 1.15 (95% CI 0.10–2.19) units/year. After entry, the average changes in the Sharp score and count were 1.72 (95% CI 1.04–2.39) units/year and 0.63 (0.40–0.87) units/year, with an average duration of follow-up of approximately 1 year. <h3>Conclusion</h3> Combined with the safety and tolerability data derived from recent studies, these data suggest that celecoxib has the potential to modify disease activity in RA with long-term use in addition to providing symptomatic benefits over shorter durations. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Responsible, practical genomic data sharing that accelerates research
Authors: James Brian Byrd, Anna C. Greene, Deepashree Venkatesh Prasad, Xiaoqian Jiang, Casey S. Greene
Journal: Nature Reviews Genetics (2020)

Data sharing anchors reproducible science, but expectations and best practices are often nebulous. Communities of funders, researchers and publishers continue to grapple with what should be required or encouraged. To illuminate the rationales for sharing data, the technical challenges and the social and cultural challenges, we consider the stakeholders in the scientific enterprise. In biomedical research, participants are key among those stakeholders. Ethical sharing requires considering both the value of research efforts and the privacy costs for participants. We discuss current best practices for various types of genomic data, as well as opportunities to promote ethical data sharing that accelerates science by aligning incentives.
The Genomic Landscape of <i>SMARCA4</i> Alterations and Associations with Outcomes in Patients with Lung Cancer
Authors: Adam J. Schoenfeld, Chai Bandlamudi, Jessica A. Lavery, Joseph Montecalvo, Azadeh Namakydoust, Hira Rizvi, Jacklynn Egger, Carla P. Concepcion, Sonal Paul, Maria E. Arcila, Yahya Daneshbod, Jason Chang, Jennifer L. Sauter, Amanda Beras, Marc Ladanyi, Tyler Jacks, Charles M. Rudin, Barry S. Taylor, Mark T.A. Donoghue, Glenn Heller, Matthew D. Hellmann, Natasha Rekhtman, Gregory J. Riely
Journal: Clinical Cancer Research (2020)

mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established.