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Homo sapiens

ABSTRACT: Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity

PROVIDER: PRJNA306880 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3053570_1.fastq.gz	Fastqsanger.gz
	SRR3053570_2.fastq.gz	Fastqsanger.gz
	SRR3053561_1.fastq.gz	Fastqsanger.gz
	SRR3053561_2.fastq.gz	Fastqsanger.gz
	SRR3053571_1.fastq.gz	Fastqsanger.gz

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Homo sapiens

Project description:Human induced pluripotent stem cell–derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity

| PRJNA315804 | ENA

Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity

Project description:Doxorubicin (Adriamycin) is an anthracycline chemotherapy agent effective in treating a wide range of malignancies1 with a well-established dose-response cardiotoxic side-effect that can lead to heart failure2-4. Even at relatively low cumulative doses of 200–250 mg/m2, the risk of cardiotoxicity is estimated at 7.8% to 8.8%4,5. Doxorubicin-induced cardiotoxicity (DIC) can range from asymptomatic reductions in left ventricular ejection fraction (LVEF) to highly symptomatic heart failure6,7. At present, it is not possible to predict which patients will be affected by DIC or adequately protect patients who are at risk for suffering this devastating side-effect8. Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate individual patients’ predilection to DIC at the single cell level. hiPSC-CMs derived from breast cancer patients who suffered clinical DIC are consistently more sensitive to doxorubicin toxicity, demonstrating decreased cell viability, mitochondrial/metabolic function, calcium handling, and antioxidant pathway gene expression, along with increased reactive oxygen species (ROS) production compared to hiPSC-CMs from patients who did not experience DIC. Together, our data indicate that hiPSC-CMs are a suitable platform for identifying and verifying the genetic basis and molecular mechanisms of DIC.

2016-04-18 | GSE76314 | GEO

mRNA array profiling on human pluripotent stem cell-derived cardiomyocytes exposed to doxorubicin

Project description:Cardiomyocytes derived from human pluripotent stem cells were exposed to the cardiotoxic drug Doxorubicin in order to assess the utility of this cell system as a model for drug-induced cardiotoxicity. Cells are exposed to different concentrations of doxorubicin for up to 48 hours followed by a 12 days recovery period.

2017-12-19 | E-MTAB-6045 | biostudies-arrayexpress

MicroRNA array profiling on human pluripotent stem cell-derived cardiomyocytes exposed to doxorubicin

2017-10-28 | E-MTAB-6052 | biostudies-arrayexpress

E-GEOD-39870

Project description:Transcription profiling by array of MCF7 breast cancer cells after treatment with doxorubicin

2025-01-24 | E-GEOD-39870 | ExpressionAtlas

E-GEOD-34309

Project description:Gene expression profiles of fibroblasts and fibroblast-reprogrammed induced pluripotent stem cells (iPSCs) from childhood cerebral adrenoleukodystrophy patients and healthy controls

2025-01-24 | E-GEOD-34309 | ExpressionAtlas

A safety screening platform for individualized cardiotoxicity assessment

Project description:Cardiotoxicity remains a major cause of drug withdrawal, partially due to lacking predictability of animal models. Additionally, risk of cardiotoxicity following treatment of cancer patients is treatment limiting. It is unclear which patients will develop heart failure following therapy. Human pluripotent stem cell (hPSC)-derived cardiomyocytes present an unlimited cell source and may offer individualized solutions to this problem. We developed a platform to predict molecular and functional aspects of cardiotoxicity. Our platform can discriminate between the different cardiotoxic mechanisms of existing and novel anthracyclines Doxorubicin (DOXO), Aclarubicin (ACLA) and Amrubicin (AMR). DOXO and ACLA unlike AMR substantially affected the transcriptome, mitochondrial membrane integrity, contractile force and transcription factor availability. Cardiomyocytes recovered fully within two or three weeks, corresponding to the intermittent clinical treatment regimen. Our system permits the study of hPSC-cardiomyocyte recovery and the effects of accumulated dose after multiple dosing, allowing individualized cardiotoxicity evaluation, which effects millions of cancer patients treated with anthracyclines annually.

2023-10-01 | GSE232331 | GEO

Epigenome analysis of doxorubicin-induced cardiotoxicity before and after treatemt of breast cancer patients

Project description:Epigenome analysis of doxorubicin-induced cardiotoxicity before and after treatemt of breast cancer patients

| PRJNA741405 | ENA

Effect of doxorubicin and SPEDOX-6 on human iPSC-derived cardiac spheroids comprised of cardiomyocytes, endothelial cells, and fibroblasts.

Project description:The chemotherapeutic doxorubicin (DOX) detrimentally impacts the heart during cancer treatment. This necessitates development of non-cardiotoxic delivery systems that retain DOX anticancer efficacy. We utilized human induced pluripotent stem cell-derived multi-lineage cardiac spheroids (hiPSC-CSs) to compare the anticancer efficacy and reduced cardiotoxicity of single protein encapsulated doxorubicin (SPEDOX-6), to standard unformulated (UF) DOX using RNA-sequencing. The cardiac spheroids are comprised of hiPSC-derived cardiomyocytes (hiPSC-CMs), hiPSC-derived endothelial cells (ECs), and hiPSC-derived cardiac fibroblasts (CFs) at an 8:1:1 ratio.

2023-07-01 | GSE235470 | GEO

Trastuzumab-associated cardiotoxicity in Patient Specific iPSC-derived cardiomyocytes from HER2+ breast cancer patients

Project description:Trastuzumab is a monoclonal targeted therapy widely used to treat human epidermal growth factor receptor 2 (HER2+) over expressed breast cancer which confers an aggressive cancer type and comprises ~25% of breast cancer. Trastuzumab yields improved breast cancer related outcomes, but survival benefits are in part offset by cardiotoxicity - as evidenced by 10-15% of patients develop cardiomyopathy and 2-4% develop congestive heart failure. Approximately 20-30% of patients have either temporary or permanent discontinuation of trastuzumab therapy due to its cardiotoxicity, raising concern for inadequate cancer treatment and recurrence. Current screening strategies for trastuzumab-induced cardiotoxicity rely on non-invasive imaging such as echocardiography, but conventional imaging techniques provide limited a priori risk stratification for cardiotoxicity. We have utilized patient-specific iPSC-CMs derived from HER2+ breast cancer patients with and without evidence of TIC as a model to better elucidate the mechanisms of Trastuzumab-indued cardiotoxicity.

2024-06-05 | GSE264120 | GEO

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