tbuckley/cabot-search huggingface dataset:
Abstract 148: Mst1 Mediates Cell-protective Mechanisms In The Heart Through Phosphorylation Of FoxO1 And C/EBP-beta
Authors: Yasuhiro Maejima, Peiyong Zhai, Mitsuaki Isobe, Junichi Sadoshima
Journal: Circulation Research (2013)

Forkhead box O1 (FoxO1) regulates both cell survival and death in the heart. The function of FoxO1 is modulated by posttranslational modifications, including phosphorylation. Mst1 (mammalian sterile 20-like kinase 1), a stress-activated pro-apoptotic kinase, phosphorylates FoxO1 at Ser209/216/231/232. We investigated the molecular mechanism by which FoxO1 regulates both cell survival and death in the heart. Overexpression of FoxO1 significantly suppressed, whereas downregulation of endogenous FoxO1 exacerbated, Mst1 activity and Mst1-induced apoptosis. In the presence of Mst1, FoxO1 downregulated pro-apoptotic genes, including FasL, but upregulated antioxidant genes, including catalase. Chromatin immunoprecipitation assays revealed that Mst1 attenuated FoxO1 binding to the FasL promoter, but it enhanced binding to the catalase promoter. Reporter gene assays showed that C/EBP-β binding elements, but not the FoxO binding ones, in the catalase promoter, are critical for Mst1-mediated upregulation of the catalase gene. FoxO1 interacted with C/EBP-β and their interaction was enhanced in the presence of Mst1. Mass spectrometry analyses revealed that Mst1 phosphorylates C/EBP-β at Thr 299 in its leucine zipper domain. Downregulation of endogenous C/EBP-β reversed the cell-protective effects of FoxO1 expression against Mst1-induced apoptosis. We evaluated the role of Mst1-mediated phosphorylation of FoxO1 and C/EBP-β in mediating survival and death of cardiomyocytes in response to ischemia/reperfusion (I/R). The size of myocardial infarction (MI) in left ventricle (LV) after I/R was significantly greater in cardiac-specific FoxO1 knockout ( c-FoxO1 -/- ) mice than in wild-type mice (MI/area at risk: 59±2, 41±1%, p &lt;0.05, n=6). Injection of a C/EBP-β phospho-mimetic mutant adenovirus into the LV of c-FoxO1 -/- significantly reduced the I/R-induced LV infarct size observed in c-FoxO1 -/- (50±2%, p &lt;0.05, n=6). In summary, Mst1-mediated phosphorylation of FoxO1 inhibits the DNA binding of FoxO1 to the cell death promoting genes whereas it enhances FoxO1-C/EBP-β interaction, Mst1-mediated phosphorylation of C/EBP-β, and C/EBP-β-mediated transcription, which activates cell-protective mechanisms in the heart.
A Fc-Engineered RANK-Fc Fusion Protein Neutralizes Soluble RANK Ligand and Targets Malignant Hematopoietic Cells for NK Cell Reactivity.
Authors: Benjamin J Schmiedel, Tina Baessler, Carolin Scheible, Constantin M Wende, Miyuki Azuma, Pascal Schneider, Lothar Kanz, Ludger Grosse-Hovest, Helmut R Salih
Journal: Blood (2009)
(Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis
Authors: Zhen Li, Lili Zhou, Yongping Wang, Jinhua Miao, Xue Hong, Fan Fan Hou, Youhua Liu
Journal: Journal of the American Society of Nephrology (2017)

The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro . Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α –smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling.
Association of Non-Healing Wounds, Pain and Neurochemical Alterations In Sickle Cell Disease
Authors: Josephine Anuforo, Julia Nguyen, Kathryn Luk, Silas Wallen-Friedman, Divyanshoo Kohli, Derek Vang, Marna Ericson, Donald Simone, Robert P Hebbel, Kalpna Gupta
Journal: Blood (2010)
Prediction of recurrence with the Onco<i>type</i> DX recurrence score in node-positive, HR-positive, breast cancer patients treated with adjuvant chemotherapy: Results from PACS01 trial.
Authors: Frederique Madeleine Penault-Llorca, Thomas Filleron, Bernard Asselain, Frederick L. Baehner, Pierre Fumoleau, Magali Lacroix-Triki, Steven M. Butler, Farid Jamshidian, Diana B. Cherbavaz, Steven Shak, Lise Roca, Christine Sagan, J Lemonnier, Anne-Laure Martin, Henri Hubert Roche
Journal: Journal of Clinical Oncology (2014)

11052 Background: The Recurrence Score (RS) predicts outcome in node- and node+, ER+ pts treated with endocrine therapy and predicts chemotherapy benefit. We studied the prognostic impact of RS in node+, HR+ pts treated with adjuvant chemotherapy plus endocrine therapy in PACS01 Methods: PACS01 compared FECX6 with FECX3+ docetaxel X3(FEC-D) in 1999 pts. After a protocol amendment, HR-positive pts received 5 yrs of tam after chemo. The current study includes 530 pts from the PACS01 parent trial who were central IHC HR+ with sufficient tissue for OncotypeDX. The primary objective was to estimate the association between RS and distant recurrence free interval (DRFI). Secondary endpoints included disease free survival (DFS) and overall survival (OS). Median follow-up time was 7.7 yrs Results: Of the 530 pts, 209 (39.4%) had low RS; 159 (30.0%) intermediate RS; and 162 (30.6%) high RS. 74.2% were treated with tam. In the primary analysis, RS was a significant predictor of DRFI (HR= 4.1 for a 50 point difference, P<0.001), DFS (HR=3.3, P<0.001) and OS (HR=5.0, P<0.001). In multivariate analyses, RS provided independent prognostic information beyond clinicopathologic factors including treatment, age, tumor size & grade, number of + nodes, surgery type and Ki-67 status (P<0.001). RS was a significant predictor of DRFI, DFS, and OS in both treatment arms (P<0.001). There was no statistically significant interaction between RS and treatment arm in predicting distant recurrence (P=0.79). Conclusions: The 21-gene RS maintains significant prognostic impact in HR+, node+ pts who have received FEC or FEC-D adjuvant chemotherapy. These findings emphasize the need to target pts with high residual risk for recurrence with additional therapies to overcome unfavorable biology, potential endocrine and/or chemotherapy resistance. Kaplan-Meier estimates of 5-yr DRFI, DFS, and OS. End point (95%CI) RS low n=209 RS intermediate n=159 RS high n=162 Log-rank p-value DRFI % 93.7 (89.4-96.3) 87.3 (81.0-91.6) 69.3 (61.5-75.8) p<0.001 DFS % 90.8 (86.0-94.1) 84.9 (78.3-89.6) 64.6 (56.7-71.4) p<0.001 OS % 99.0 (96.2-99.8) 95.6 (90.9-97.9) 85.6 (79.1-90.2) p<0.001
Late Onset Neutropenia Develops Selectively in Only a Subset of Patients with T Large Granular Lymphocyte Proliferation After Rituximab Treatment for Lymphoma,
Authors: Apostolia Papalexandri, Michalis Iskas, Evangelia Stalika, Leonidas Marinos, Barbara Tachynopoulou, Konstantina Kotta, Maria Papathanasiou, Aliki Tsompanakou, Kostas Stamatopoulos, Theodora Papadaki, Achilles Anagnostopoulos
Journal: Blood (2011)
Improvement Interventions
Authors: Sarah L. Szanton, Bruce Leff, Laura N. Gitlin
Journal: Annals of Internal Medicine (2015)

Letters21 April 2015Improvement InterventionsSarah L. Szanton, PhD, ANP, Bruce Leff, MD, and Laura N. Gitlin, PhDSarah L. Szanton, PhD, ANPFrom Johns Hopkins University, Baltimore, Maryland.Search for more papers by this author, Bruce Leff, MDFrom Johns Hopkins University, Baltimore, Maryland.Search for more papers by this author, and Laura N. Gitlin, PhDFrom Johns Hopkins University, Baltimore, Maryland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5071-2 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Davidoff (1) highlights the critical tension in approaches to evaluating health care improvement efforts—the tension between benefits from the rigorous comparison of static-protocol randomized, controlled trials (RCTs) versus those from QI programs that adapt to inevitable contextual challenges during implementation. These approaches have exactly opposite weaknesses. The RCT cannot adapt, and QI programs cannot conclude that observed outcomes are due to the program under investigation. Our team has an interesting vantage point from which to view this tension: We are simultaneously doing 2 tests of the same care model, CAPABLE (Community Aging in Place—Advancing Better Living for ...References1. Davidoff F. Improvement interventions are social treatments, not pills [Editorial]. Ann Intern Med. 2014;161:526-7. [PMID: 25285545] doi:10.7326/M14-1789 LinkGoogle Scholar2. Szanton SL, Thorpe RJ, Boyd C, Tanner EK, Leff B, Agree E, et al. Community aging in place, advancing better living for elders: a bio-behavioral-environmental intervention to improve function and health-related quality of life in disabled older adults. J Am Geriatr Soc. 2011;59:2314-20. [PMID: 22091738] doi:10.1111/j.1532-5415.2011.03698.x CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Johns Hopkins University, Baltimore, Maryland.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L14-0567. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoImprovement Interventions Are Social Treatments, Not Pills Frank Davidoff Improvement Interventions Are Social Treatments, Not Pills Frank Davidoff Improvement Interventions Joanne Lynn Improvement Interventions Frank Davidoff Improvement Interventions Frank Davidoff Improvement Interventions Joanne Lynn Metrics 21 April 2015Volume 162, Issue 8Page: 596-597KeywordsDisclosureElderlyHealth careMedicarePain managementPilot studiesQuality improvementStatistical methods ePublished: 21 April 2015 Issue Published: 21 April 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Increased Intestinal Permeability in Relatives of Patients With Crohn’s Disease Is Not Associated With Small Bowel Ulcerations
Authors: Christopher W. Teshima, Karen J. Goodman, Mohamed El-Kalla, Samina Turk, Wael El-Matary, Rosica Valcheva, Ronda Danchak, Marilyn Gordon, Peter Ho, Amanda Mullins, Daniel Wong, Dina Kao, Jonathan Meddings, Hien Huynh, Levinus A. Dieleman
Journal: Clinical Gastroenterology and Hepatology (2017)
A Phase 2 Clinical Study of HQK-1001 (2,2-dimethylbutyrate, sodium salt), a Fetal Hemoglobin Inducer, in Patients with Sickle Cell Disease
Authors: Abdullah Kutlar, Adlette Inati, Ali T Taher, Amal El-Beshlawy, Marvin Reid, Miguel R. Abboud, Hedy Smith, Kenneth I. Ataga, George R. Buchanan, Punam Malik, Nebu Koshy, Lynne Neumayr, Maria Aiello, Elsa Johnson, J Michael White, Richard G. Ghalie
Journal: Blood (2011)
CD74 Expression by AML Cell Lines and Bone Marrow Specimens, and Augmented In Vitro Cytotoxicity of Anti-CD74 Antibody After Interferon-Gamma (IFN-γ) Treatment
Authors: Abhinav B. Chandra, Jack Burton, Rhona Stein, Susan Chen, Nidhi Mishra, Taral Shah, Nneamaka N Enwemnwa, David Goldenberg
Journal: Blood (2010)
Correlation of Lung Clearance Index with Hyperpolarized <sup>129</sup>Xe Magnetic Resonance Imaging in Pediatric Subjects with Cystic Fibrosis
Authors: Nikhil Kanhere, Marcus J. Couch, Krzysztof Kowalik, Brandon Zanette, Jonathan H. Rayment, David Manson, Padma Subbarao, Felix Ratjen, Giles Santyr
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Pluripotent Unrestricted Somatic Stem Cells (USSC) from Cord Blood Generate Hepatocytes in Vivo, but In Vitro Convert into Immature Endodermal Precursors: The Critical Role of the Biological Niche.
Authors: Sandra Sensken, Juergen Enczmann, Thorsten Trapp, Esmail Zanjani, Peter Wernet, Gesine Koegler
Journal: Blood (2004)
A Unique Biomarker Is Associated with the Prevalence of Functional Heparin Induced Thrombocytopenia (HIT) Associated Antibodies: Results from Proteomic (ProteinChip Array) Profiling of ELISA Positive HIT Plasma Samples.
Authors: Michelle R. Kujawski, Margaret Prechel, He Zhu, Jeanine Walenga, Debra Hoppensteadt, Josephine Cunanan, Cafer Adiguzel, Jawed Fareed
Journal: Blood (2007)
Does training respiratory physicians in clinical respiratory physiology and interpretation of pulmonary function tests improve core knowledge?
Authors: M Patout, L Sesé, T Gille, B Coiffard, S Korzeniewski, E Lhuillier, A Pradel, C Tardif, A Chambellan, C Straus, S Matecki, T Perez, L Thiberville, A Didier
Journal: Thorax (2017)

Lung function tests have a major role in respiratory medicine. Training in lung function tests is variable within the European Union. In this study, we have shown that an internship in a lung function tests laboratory significantly improved the technical and diagnostic skills of French respiratory trainees.
Essentials of General Surgery
Journal: JAMA (1941)

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
OP06. GENOMIC ANALYSIS OF PAIRED PRIMARY AND RECURRENT GLIOBLASTOMA SAMPLES
Authors: Dr Lucy Stead, Dr Alexander Bruns, Dr Nora Rippaus, Mrs Ruth Morton, Dr Arundhati Chakrabarty, Dr Azzam Ismail, Dr Henry King, Mrs Kate Ashton, Mr Khaja Syed, Mr Michael Jenkinson, Mr Andrew Brodbelt, Prof Susan Short
Journal: Neuro-Oncology (2017)

Primary glioblastoma (GBM) tumours recur following treatment. This is likely due to intratumour heterogeneity (ITH), which reduces the effectiveness of cancer therapies by enabling therapy-driven tumour evolution: Darwinian selection of genotypically and/or phenotypically distinct cells (subclones) that resist treatment to seed regrowth of an even less treatable recurrence. In recent years, next generation sequencing approaches have facilitated the characterisation of subclonal genomic tumour architecture. We have applied these approaches to a pilot cohort of five paired primary and locally recurrent GBM tumours, alongside high-coverage transcriptomic profiling, in order to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. This approach may also indicate relevant targets in recurrent disease. In this preliminary cohort we see subclonal mutation patterns indicative of neutral tumour evolution but with evidence of selection of certain cell populations during therapy. The expressed, mutated genes in these expanded cell populations are enriched for EGF-EGFR signalling pathways and Wnt signalling and pluripotency, with at least one member of each of these pathways being mutated in an expanded subpopulation per tumour pair.
Nilotinib Demonstrates Superior Efficacy Compared with Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase: Results From the International Randomized Phase III ENESTnd Trial
Authors: Giuseppe Saglio, Dong-Wook Kim, Surapol Issaragrisil, Philipp D. le Coutre, Josy Reiffers, Clarisse Lobo, Ricardo Pasquini, Richard E. Clark, Timothy P. Hughes, Andreas Hochhaus, Neil J. Gallagher, Albert Hoenekopp, Mei Dong, Ariful Haque, Hagop M. Kantarjian, Richard A. Larson
Journal: Blood (2009)
Combination Therapy with Reovirus and Immunomodulatory Drugs Induces Direct Oncolytic and Immune-Mediated Killing of Multiple Myeloma Cells and Overcomes Stromal-Mediated Microenvironmental Protection
Authors: Christopher Parrish, Gina B Scott, Matt Coffey, Alan Melcher, Fiona Errington-Mais, Gordon Cook
Journal: Blood (2014)
Detection of Circulating Antigen-Specific CD8+ Lymphocytes against Leukemia Associated Antigens WT1, PR1 and Survivin Using HLA 0201 Pentamers After Allogeneic Stem Cell Transplantation.
Authors: Juana Serrano-Lopez, Joaquin Sanchez Garcia, Josefina Serrano, Carmen Martin, Rafael Rojas, Francisco Martinez, Pedro Gomez, Antonia Rodriguez, Jose Manuel Garcia-Castellano, Javier Casaño, Concepcion Herrera, Antonio P. Torres Gomez
Journal: Blood (2009)
Efficacy of Frontline 5-Azacytidine in Older AML Patient Unfit for Chemotherapy
Authors: Pierre Bories, Sarah Bertoli, Françoise Huguet, Sophie Dobbelstein, Luc Fornecker, Odile Beyne Rauzy, Véronique Demas, Ana Berceanu, Eric Delabesse, Christian Recher
Journal: Blood (2011)
Low BCL11A Expression in the Myeloma Microenvironment at Diagnosis Is Associated with Early Development of MDS Cytogenetic Abnormalities and Poor Overall Survival
Authors: Bounleut Phanavanh, Priyangi Malaviarachchi, Adam Rosenthal, Yogesh Jethava, Bart Barlogie, Jeffrey Sawyer, Joshua Epstein, Shmuel Yaccoby, Sarah K. Johnson
Journal: Blood (2014)
Abstract A15: Development of an <i>in vitro</i> 3D vessel-spheroid model for investigating cancer metastasis
Authors: Adam Munoz, Joseph Miller, Cynthia A. Reinhart-King
Journal: Cancer Research (2017)

Abstract During metastasis, cells break free from the primary tumor, migrate through the stroma and enter either the vascular or lymph systems to disseminate into secondary sites. To better understand this process, many groups have developed in vitro models of cancer metastasis using microfluidic based platforms to mimic the tumor microenvironment and the intravasation/extravasation of tumor cells. While these models have provided significant new insights into the mechanisms by which metastatic cells move across the endothelium, they are most often focused on the movement of single cells. Notably, there is significant clinical evidence to suggest that tumor cells can travel collectively though the stroma and can circulate as cell aggregates in the vasculature. Recent advances in the understanding of cancer metastasis have shown that cancer may move more aggressively as a collection of cell when traversing the extracellular matrix (ECM) of the tumor microenvironment as opposed to more studied singular cellular motif. To better mimic these collective movements, we have developed a model that incorporates the following essential elements that exist in the tumor microenvironment: a cylindrical channel lined with a confluent monolayer of endothelial cells, a metastatic tumor analog in close proximity to the channel, the ability to incorporate flow with tunable properties to simulate shear stress due to blood flow, and a tunable collagen microenvironment. Briefly, in a 3D printed cube, Type 1 collagen is added at physiological stiffness. As the collagen is polymerizing in the device, a metastatic tumor analog (spheroid) consisting of labeled MDA-MB-231 cells is placed in proximity of the vessel that is lined with endothelial cells. The platform allows for the visualization of metastatic cell intravasation using confocal microscopy. Notably, this model is easy to build and implement with fairly accessible tools and without the use of a clean room or microfabrication facilities. Importantly, going forward this model has the ability to study the cellular behavior post-intravasation due to the incorporation of physiological flows within the channel. Citation Format: Adam Munoz, Joseph Miller, Cynthia A. Reinhart-King. Development of an in vitro 3D vessel-spheroid model for investigating cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A15.
Abstract 178: Blocking the Acetylcholine Activated Inward Rectifier Potassium Current but not the Rapid Delayed Rectifier Potassium Current Restores Sinus Rhythm in the Chronically Fibrillating Sheep Heart
Authors: Marian Haburcak, Guillaume Bassil, Yoshio Takemoto, Matthew Mehlenbacher, Diana Slough, Fadi Bou Abdallah, Jose Jalife, Richard Karas, Yu-Shan Lin, Sami F Noujaim
Journal: Circulation Research (2015)

Background: The acetylcholine activated inward rectifier potassium current (IKACh) was shown to be constitutively active in chronic atrial fibrillation. Its blockade has been proposed to be a possible antifibrillatory pharmacotherapy. We therefore tested the hypothesis that blocking IKACh with the bee venom peptide tertiapin, or the small molecule chloroquine, terminates chronic AF in the sheep heart. Methods and Results: We tested our hypothesis using biochemistry, electrophysiology and molecular modeling. In patch clamp, the IC50 of IKACh block by tertiapin, and chloroquine was 60 nM, and 710 nM respectively, while dofetilde, a currently used class III antiarrhythmic, did not block the current. On the other hand, dofetilide and chloroquine blocked the rapid delayed rectifier potassium current (IKr) with an IC50 of 50nM, and 2.3 microM respectively, while tertiapine had no effects. Furthermore, molecular modeling indicated that 1 chloroquine molecule blocks the intracellular ion permeation vestibule of the tetrameric Kir3.1, a molecular correlate of IKACh, by interacting with amino acids important for the channel’s rectification. Dofetilide did not interact with Kir3.1. In vitro fluorescence measurements of chloroquine titration into the purified Kir3.1 intracellular domain protein confirmed the computational results and indicated that chloroquine directly binds Kir3.1 with a stoichiometry of 1 chloroquine molecule per Kir3.1 tetramer. Finally, optical mapping of the chronically fibrillating sheep atria showed that while tertiapine, chloroquine, and dofetilide slowed down chronic AF and prolonged the action potential, only tertiapine and chloroquine (the IKACh blockers) restored normal sinus rhythm. Conclusions: IKACh could be a more powerful anti atrial fibrillation target compared to IKr. Pharmacological blockade of IKACh with a peptide, or a small molecule similar to chloroquine could terminate chronic AF and restore normal sinus rhythm.