Interindividual Variability in the Cardiac Expression of Anthracycline Reductases in Donors With and Without Down Syndrome

Quiñones-Lombraña, Adolfo; Ferguson, Daniel; Blair, Rachael Hageman; Kalabus, James; Redzematovic, Almedina; Blanco, Javier G.

doi:10.1007/s11095-013-1267-1

Cited by 18 publications

(29 citation statements)

References 37 publications

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“…Studies in heart tissue documented increased CBR1 mRNA and CBR1 protein expression in samples from donors with DS in comparison to samples from donors without DS. On average, heart tissue samples from donors with DS displayed a 1.7 fold increase in the rates of synthesis of cardiotoxic daunorubicinol 36,37 .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Hefti

Blanco²

2016

Journal of Pediatric Hematology/Oncology

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Children with Down syndrome (DS) have a 10 – 30 fold increased risk of developing acute myeloid leukemia or acute lymphoblastic leukemia. Patients with DS and leukemia are treated with the same chemotherapeutic agents as patients without DS. Treatment regimens for pediatric leukemia comprise multiple cytotoxic drugs including methotrexate, doxorubicin, vincristine, cytarabine, and etoposide. There have been reports of increased toxicity, as well as altered therapeutic outcomes in pediatric patients with DS and leukemia. This review is focused on the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS. The available literature suggests that methotrexate and thioguanine display altered pharmacokinetic parameters in pediatric patients with DS. It has been hypothesized that the variable pharmacokinetics of these drugs may contribute to the increased incidence of treatment-related toxicities seen in DS. Data from a small number of studies suggest that the pharmacokinetics of vincristine, etoposide, doxorubicin, and busulfan are similar between patients with and without DS. Definitive conclusions regarding the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS are difficult to reach due to limitations in the available studies.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Hefti

Blanco²

2016

Journal of Pediatric Hematology/Oncology

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“…Other AIC biomarkers, including growth differentiating factors-15 (GDF-15), CBR1, AKR1A1 and AKR7A2 protein, and topoisomerase2β (Top2β) were studied in different populations and can also be used 15 16. In childhood cancer survivors GDF-15, a member of TGF superfamily, can be used as a marker of AIC 17.…”

Section: Discussionmentioning

confidence: 99%

Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors

et al. 2016

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Chemotherapy-induced cardiomyopathy is one of the major possible hazards that can result from potential cardiotoxic agents while treating cancer. Prognostic risk factors include the rate of drug administration, history of hypertension, female gender, extremes of age, previous history of mediastinal irradiation, cumulative dose and pre-existing heart disease. Close monitoring of the patients, timely diagnosis, use of well-known biomarkers including cardiac troponins, NT-ProBNP and imaging studies like 2D Echo or cardiac MRI are essential. Emerging biomarkers include carbonyl reductases (CBR1 and CBR3), aldo-keto reductases (AKR, type 1A1, 1C3, 7A2) and topoisomerase2β (Top2β). β blockers and ACE inhibitors have not only been shown to slow down the progression of cardiac dysfunction but also produce symptomatic improvement. Our case report describes a patient with acute myeloblastic leukaemia who developed severe cardiomyopathy acutely after starting the anthracycline-based regimen. Nevertheless, with timely intervention her symptoms improved and subsequently she successfully received allogeneic stem cell transplantation.

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“…The postmortem to tissue recovery interval was ≤ 10 h. Samples (2 – 20 g, myocardium, left ventricle only) were frozen immediately after recovery and stored in liquid nitrogen until further processing. DS status (yes/no) was obtained from anonymous medical records and confirmed by comparative array hybridizations as described [14, 25, 26]. High quality RNA was isolated with an automatic QuickGene-810 purification system (Autogen/FujiFilm, Holliston, MA).…”

Section: Methodsmentioning

confidence: 99%

Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM)

Quiñones-Lombraña

Blanco

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The regulation of mitochondrial biogenesis is under the control of nuclear genes including the master mitochondrial transcription factor A (TFAM). Recent evidence suggests that the expression of TFAM is regulated by microRNAs (miRNAs) in various cellular contexts. Here, we show that hsa-miR-155-5p, a prominent miRNA encoded in chromosome 21, controls the expression of TFAM at the post-transcriptional level. In human fibroblasts derived from a diploid donor, downregulation of TFAM by hsa-miR-155-5p decreased mitochondrial DNA (mtDNA) content. In contrast, downregulation of TFAM by hsa-miR-155-5p did not decrease mtDNA content in fibroblasts derived from a donor with Down syndrome (DS, trisomy 21). In line, downregulation of mitochondrial TFAM levels through hsa-miR-155-5p decreased mitochondrial mass in diploid fibroblasts but not in trisomic cells. Due to the prevalence of mitochondrial dysfunction and cardiac abnormalities in subjects with DS, we examined the presence of potential associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. There were significant negative associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. These results suggest that regulation of TFAM by hsa-miR-155-5p impacts mitochondrial biogenesis in the diploid setting but not in the DS setting.

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Interindividual Variability in the Cardiac Expression of Anthracycline Reductases in Donors With and Without Down Syndrome

Cited by 18 publications

References 37 publications

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors

Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM)

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