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  2. Matching Content Categories
  3. CMS
  4. Monthly Traffic Estimate
  5. How Does Link.springer.com Make Money
  6. Keywords
  7. Topics
  8. Questions
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We are analyzing https://link.springer.com/article/10.1007/s00395-022-00918-7.

Title:
Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients | Basic Research in Cardiology
Description:
Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20+ B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca2+ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca2+ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Education
  • Science
  • Health & Fitness

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
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How Does Link.springer.com Make Money? {💸}

We don’t know how the website earns money.

Websites don't always need to be profitable; some serve as platforms for education or personal expression. Websites can serve multiple purposes. And this might be one of them. Link.springer.com could be secretly minting cash, but we can't detect the process.

Keywords {🔍}

act, dox, patients, control, fig, ipsc, cardiac, article, treatment, ehm, cell, patient, google, scholar, human, analysis, cas, cells, expression, compared, doxdependent, supplementary, heart, increased, cardiotoxicity, actipsc, significantly, mitochondrial, myocardium, data, study, dysfunction, doxinduced, performed, stem, failure, controls, cfb, found, untreated, camkiiδ, analyzed, lines, germany, genes, göttingen, differentiations, cardiomyocytes, sercaa, conditions,

Topics {✒️}

kröner-fresenius-stiftung foundation [2017-a137] catecholamine-dependent beta-adrenergic signaling gov/ij/plugins/radial-profile modulating wnt/beta-catenin signaling act-specific dox-dependent degs pressure-induced heart disease katrin streckfuss-bömeke modeling doxorubicin-induced cardiotoxicity human ipsc-derived cardiomyocytes end-stage heart failure inducible cardiomyocyte-specific deletion dhe-derived oxidation products highly inter-individually variable act-ipsc cm exhibited peltier-cooled xc10 camera article download pdf patient-specific model system pre-cooled cardioplegic solution kos/hc-myc/hklf4 end-stage act myocardium trastuzumab-induced cardiac dysfunction dose-dependent relative increase increased dox-dependent apoptosis dox-induced heart failure pbpk-based dose modelling dox dose-dependent manner dox-dependent upregulated degs inherently immature ipsc-derivatives patient-specific gene expression cell patch-clamp technique chronic cardiotoxicity model α-myosin heavy chain patient-specific ipsc model cd20+ b-cell lymphoma cd20 + b-cell lymphoma dox-induced cardiac dysfunction nhl-b1/b2 study cardiac marker α-actinin patient-specific act model dox concentration-dependent manner dox-induced cell loss dox-dependent ros production potential cardio-protective mechanisms dox-induced stress resulted human cardiomyocytes derived β-myosin heavy chain dox-induced relative change 5 ng/ml tgf-b1 stem cell model patient-specific ipsc cm

Questions {❓}

  • Magdy T, Burmeister BT, Burridge PW (2016) Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: What is missing?

Schema {🗺️}

WebPage:
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         headline:Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients
         description:Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20+ B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca2+ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca2+ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients.
         datePublished:2022-03-08T00:00:00Z
         dateModified:2022-03-08T00:00:00Z
         pageStart:1
         pageEnd:24
         license:http://creativecommons.org/licenses/by/4.0/
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         keywords:
            Anthracyclin-induced cardiotoxicity (ACT)
            Induced pluripotent stem cells (iPSC)
            Cardiomyocytes
            Cardiac fibroblasts
            Heart failure
            Doxorubicin
            Cardiology
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ScholarlyArticle:
      headline:Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients
      description:Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20+ B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca2+ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca2+ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients.
      datePublished:2022-03-08T00:00:00Z
      dateModified:2022-03-08T00:00:00Z
      pageStart:1
      pageEnd:24
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1007/s00395-022-00918-7
      keywords:
         Anthracyclin-induced cardiotoxicity (ACT)
         Induced pluripotent stem cells (iPSC)
         Cardiomyocytes
         Cardiac fibroblasts
         Heart failure
         Doxorubicin
         Cardiology
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            name:King’s College London, British Heart Foundation Centre of Excellence
            address:
               name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
               type:PostalAddress
            type:Organization
      name:Steffen Köhne
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Rewati Tappu
      affiliation:
            name:University of Heidelberg
            address:
               name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg
            address:
               name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Jan Haas
      affiliation:
            name:University of Heidelberg
            address:
               name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg
            address:
               name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Yun Li
      affiliation:
            name:University Hospital Centre Göttingen
            address:
               name:Institute of Human Genetics, University Hospital Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Andre Sasse
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Institute of Cellular and Molecular Immunology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Celio C. X. Santos
      affiliation:
            name:King’s College London, British Heart Foundation Centre of Excellence
            address:
               name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
               type:PostalAddress
            type:Organization
      name:Ralf Dressel
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:University Medical Centre Göttingen
            address:
               name:Institute of Cellular and Molecular Immunology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Leszek Wojnowski
      affiliation:
            name:University Medical Centre Mainz
            address:
               name:Department of Pharmacology, University Medical Centre Mainz, Mainz, Germany
               type:PostalAddress
            type:Organization
      name:Gertrude Bunt
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinical Optical Microscopy, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Wiebke Möbius
      affiliation:
            name:Electron Microscopy Core Unit, Max Planck Institute for Multidisciplinary Sciences
            address:
               name:Department of Neurogenetics, Electron Microscopy Core Unit, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:University of Göttingen
            address:
               name:Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Ajay M. Shah
      affiliation:
            name:King’s College London, British Heart Foundation Centre of Excellence
            address:
               name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
               type:PostalAddress
            type:Organization
      name:Benjamin Meder
      affiliation:
            name:University of Heidelberg
            address:
               name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg
            address:
               name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Bernd Wollnik
      affiliation:
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:University Hospital Centre Göttingen
            address:
               name:Institute of Human Genetics, University Hospital Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Samuel Sossalla
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:University Medical Centre Regensburg
            address:
               name:Department of Internal Medicine 2, Cardiology, University Medical Centre Regensburg, Regensburg, Germany
               type:PostalAddress
            type:Organization
      name:Gerd Hasenfuss
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
      name:Katrin Streckfuss-Bömeke
      url:http://orcid.org/0000-0001-5137-7228
      affiliation:
            name:University Medical Centre Göttingen
            address:
               name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
               type:PostalAddress
            type:Organization
            name:Würzburg University
            address:
               name:Institute of Pharmacology and Toxicology, Würzburg University, Würzburg, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Institute of Pharmacology and Toxicology, Würzburg University, Würzburg, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Institute of Pharmacology and Toxicology, University Medical Centre Göttingen, Göttingen, Germany
      name:Department of Internal Medicine 2, Cardiology, University Medical Centre Regensburg, Regensburg, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
      name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
      name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
      name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
      name:Institute of Human Genetics, University Hospital Centre Göttingen, Göttingen, Germany
      name:Institute of Cellular and Molecular Immunology, University Medical Centre Göttingen, Göttingen, Germany
      name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Institute of Cellular and Molecular Immunology, University Medical Centre Göttingen, Göttingen, Germany
      name:Department of Pharmacology, University Medical Centre Mainz, Mainz, Germany
      name:Clinical Optical Microscopy, University Medical Centre Göttingen, Göttingen, Germany
      name:Department of Neurogenetics, Electron Microscopy Core Unit, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
      name:Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, Göttingen, Germany
      name:King’s College London, British Heart Foundation Centre of Excellence, London, UK
      name:Department of Cardiology, University of Heidelberg, Heidelberg, Germany
      name:DZHK (German Centrefor Cardiovascular Research), partner site Heidelberg, Heidelberg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Institute of Human Genetics, University Hospital Centre Göttingen, Göttingen, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Department of Internal Medicine 2, Cardiology, University Medical Centre Regensburg, Regensburg, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
      name:Institute of Pharmacology and Toxicology, Würzburg University, Würzburg, Germany

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