Neonatal murine engineered cardiac tissue toxicology model: Impact of dexrazoxane on doxorubicin induced injury

Publication date: Available online 18 November 2019Source: Life SciencesAuthor(s): Juan Zhen, Haitao Yu, Honglei Ji, Lu Cai, Jiyan Leng, Bradley B. KellerAbstractDoxorubicin (DOX) induced cardiotoxicity is a life-threatening side effect of chemotherapy and decreased cardiac function can present years after treatment. Despite the investigation of a broad range of pharmacologic interventions, to date the only drug shown to reduce DOX-related cardiotoxicity in preclinical studies and limited clinical trials is the iron chelating agent, dexrazoxane (DRZ), although the mechanisms responsible for DRZ mediated protection from DOX related cardiotoxicity remain unclear. Engineered cardiac tissues (ECTs) can be used for tissue repair strategies and as in vitro surrogate models to test cardiac toxicities and preventative countermeasures. Neonatal murine ECTs display cardiotoxicity in response to the environmental toxin, cadmium, and reduced cadmium toxicity with Zinc co-treatment, in part via the induction of the anti-oxidant Metallothionein (MT). We adapted our in vitro ECT model to determine the feasibility of using the ECT approach to investigate DOX-related cardiac injury and DRZ prevention. We found: (1) DOX induced dose and time dependent cell death in ECTs; (2) Zinc did not show protection from DOX cardiotoxicity; (3) MT overexpression induced by Zinc, low dose Cd pretreatment, or MT-overexpression (MT-TG) did not reduce ECT DOX cardiotoxicity; (4) DRZ reduced ECT DOX induced cel...
Source: Life Sciences - Category: Biology Source Type: research

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Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
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Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
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Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome variation profiling by genome tiling array Homo sapiens Source Type: research
AbstractImmune checkpoints inhibitors (ICIs) have been a breakthrough, with unique response and survival patterns compared with chemotherapy for patients with advanced Mismatch Repair-deficient/Microsatellite instable (dMMR/MSI) colorectal cancer, but have shown disappointing results in Mismatch Repair-proficient/Microsatellite stable (pMMR/MSS) colorectal cancer. As up to 50% of patients harboring dMMR/MSI advanced cancers will ultimately progress after PD-1 blockade, biomarkers are needed to predict response/resistance to immunotherapy and to select patients for immunomodulating combination therapies. Patients with pMMR/...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Cranio Maxillofacial Surgery - Category: ENT & OMF Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors. However, this approach risks enhancing normal tissue toxicity as much as tumor toxicity, thereby limiting its translational impact. Using NU5455, a newly identified highly selective oral inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, we found that it was indeed possible to preferentially augment the effect of targeted radiotherapy on human orthotopic lung tumors without influencing acute DNA damage or a late radiation-induced t...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Bone marrow mesenchymal stem cells (BMSCs) can partially repair chemotherapy-induced ovarian damage. However, low survival rate after transplantation hampers the therapeutic efficiency of BMSCs. Heat shock pre...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
Some of the most common symptoms experienced by cancer patients are memory problems, difficulties with multitasking, and reduced attention and concentration. Historically, cancer patients with these symptoms were often diagnosed with depression. Research over the past decade has revealed that many cancer patients experience such symptoms as a consequence of specific damage to the brain caused by either their tumor or their treatment. While radiation to the brain has long been linked to causing cognitive difficulties, the effects of chemotherapy on brain structure and function have only recently been discovered. We now know...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Brain and cognitive health Cancer Memory Radiation Source Type: blogs
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