Publications (78) View all
-
Article: Neuregulin in heart failure
[show abstract] [hide abstract]
ABSTRACT: Trastuzumab is a monoclonal antibody to the ErbB2 (Her2nue) receptor over-expressed in Her2+ breast cancer. Trastuzumab-related cardiotoxicity has revealed the importance of ErbB2 signaling in the heart. Neuregulin (NRG-1) is an important stress-mediated paracrine growth factor that signals through the family of ErbB receptors to promote cardioprotection (myocyte cell survival, proliferation, differentiation, hypertrophy, and angiogenesis). Animal models with disrupted NRG/ErbB signaling fail to develop normally or result in impaired cardiac function post-natally. Pre-clinical animal studies and early-phase human studies suggest that recombinant NRG-1 holds promise as a new therapy for the treatment of various forms of heart failure. Much work is needed to further understand the exact mechanisms of cardiac repair and to find a safe mode of application for recombinant NRG-1 in heart failure. Trastuzumab ist ein monoklonaler Antikörper gegen den bei Brustkrebs überexprimierten ErbB2(Her2neu)-Rezeptor. Die Trastuzumab-bedingte Kardiotoxizität unterstreicht die Bedeutung des ErbB2-Signalwegs im Herzen. Neuregulin(NRG-1) ist ein wichtiger stressinduzierter parakriner Wachstumsfaktor, der über ErbB-Rezeptoren kardioprotektiv wirkt. Dies kann als verbesserte Überlebensrate der Myozyten, Proliferation, Differenzierung, Hypertrophie und Angiogenese erfasst werden. Tiermodelle mit unterbrochenem NRG/ErbB-Signalweg zeigen Entwicklungsstörungen und eine eingeschränkte postnatale kardiale Funktion. Präklinische Tierstudien und erste Untersuchungen am Menschen weisen darauf hin, dass rekombinantes NRG-1 ein vielversprechender neuer therapeutischer Ansatz für die Behandlung verschiedener Formen der Herzinsuffizienz ist. Um die zugrunde liegenden Mechanismen der kardialen Reparation und eine sichere Anwendung von rekombinanten NRG-1 bei Herzinsuffizienz zu klären, sind noch viele Untersuchungen erforderlich. KeywordsCardiotoxicity–Glial growth factor–Neuregulin–Cardiomyopathy–Novel therapy SchlüsselwörterKardiotoxizität–Glialer Wachstumsfaktor–Neuregulin–Kardiomyopathie–Innovative TherapieHerz 04/2012; 36(4):306-310. · 0.92 Impact Factor -
Article: Neuregulin in heart failure : reverse translation from cancer cardiotoxicity to new heart failure therapy.
[show abstract] [hide abstract]
ABSTRACT: Trastuzumab is a monoclonal antibody to the ErbB2 (Her2nue) receptor over-expressed in Her2(+) breast cancer. Trastuzumab-related cardiotoxicity has revealed the importance of ErbB2 signaling in the heart. Neuregulin (NRG-1) is an important stress-mediated paracrine growth factor that signals through the family of ErbB receptors to promote cardioprotection (myocyte cell survival, proliferation, differentiation, hypertrophy, and angiogenesis). Animal models with disrupted NRG/ErbB signaling fail to develop normally or result in impaired cardiac function post-natally. Pre-clinical animal studies and early-phase human studies suggest that recombinant NRG-1 holds promise as a new therapy for the treatment of various forms of heart failure. Much work is needed to further understand the exact mechanisms of cardiac repair and to find a safe mode of application for recombinant NRG-1 in heart failure.Herz 06/2011; 36(4):306-10. · 0.92 Impact Factor -
Article: Late cardiac effects of cancer treatment.
[show abstract] [hide abstract]
ABSTRACT: Cardiac toxicities from cancer therapy can become evident many years after treatment, and these late cardiac effects can have a profound impact on cancer survivors. There are a myriad of potential cardiovascular complications from cancer therapy, but these can be grouped into three main categories. First, vascular conditions including atherosclerosis, thrombosis, and hypertension predominate. Second, cardiac structural problems, especially valvular degeneration, can have a dramatic impact long term. Lastly, and most importantly, cardiac dysfunction and heart failure are potentially common late cardiac effects and can certainly be prevented or detected early during active cancer therapy to result in optimal outcomes. Future research on late cardiac effects in cancer survivors needs to include advanced cardiac imaging techniques, novel cardiac biomarkers, and genetic determinants of response to cancer treatment.Journal of Clinical Oncology 09/2012; 30(30):3657-64. · 18.37 Impact Factor -
Article: Cardiovascular toxicity profiles of vascular-disrupting agents.
[show abstract] [hide abstract]
ABSTRACT: Vascular-disrupting agents (VDAs) represent a new class of chemotherapeutic agent that targets the existing vasculature in solid tumors. Preclinical and early-phase trials have demonstrated the promising therapeutic benefits of VDAs but have also uncovered a distinctive toxicity profile highlighted by cardiovascular events. We reviewed all preclinical and prospective phase I-III clinical trials published up to August 2010 in MEDLINE and the American Association of Cancer Research and American Society of Clinical Oncology meeting abstracts of small-molecule VDAs, including combretastatin A4 phosphate (CA4P), combretastatin A1 phosphate (CA1P), MPC-6827, ZD6126, AVE8062, and ASA404. Phase I and II studies of CA1P, ASA404, MPC-6827, and CA4P all reported cardiovascular toxicities, with the most common cardiac events being National Cancer Institute Common Toxicity Criteria (version 3) grade 1-3 hypertension, tachyarrhythmias and bradyarrhythmias, atrial fibrillation, and myocardial infarction. Cardiac events were dose-limiting toxicities in phase I trials with VDA monotherapy and combination therapy. Early-phase trials of VDAs have revealed a cardiovascular toxicity profile similar to that of their vascular-targeting counterparts, the angiogenesis inhibitors. As these agents are added to the mainstream chemotherapeutic arsenal, careful identification of baseline cardiovascular risk factors would seem to be a prudent strategy. Close collaboration with cardiology colleagues for early indicators of serious cardiac adverse events will likely minimize toxicity while optimizing the therapeutic potential of VDAs and ultimately enhancing patient outcomes.The Oncologist 07/2011; 16(8):1120-30. · 3.91 Impact Factor -
Article: Heart disease in cancer patients: a burgeoning field where optimizing patient care is requiring interdisciplinary collaborations.
Heart Failure Clinics 07/2011; 7(3):xxi-xxiii.
