• Proceedings of the PSK Conference
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• 2003.04a
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• pp.313.1-313.1
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• 2003

DA-125, a novel anthracycline analog containing fluorine with decreased cardiotoxicity and increased antitumor activity of adriamycin (ADM), developed by Research Laboratories of Dong-A Pharmaceutical. DA-125, water soluble prodrug of M1, is a ${\beta}$-alanine derivative of M1 (FT-ADM). DA-125 was rapidly hydrolyzed to M1, and M1 was metabolized to both M2 and M3. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.174.1-174.1
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• 2003

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives using doxorubicin as a lead compound. Doxorubicin is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of quinone compounds like Dox, its use is limited because of systemic toxicities, primarily cardiotoxicity and myelosuppression. In this study, we discuss the synthesis of isoindolobenzoquinoxaline derivatives. The quinone group of the azaanthraquinone derivatives were removed in the target compounds. (omitted)

• International Journal of Stem Cells
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• v.17 no.2
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• pp.130-140
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• 2024

Cardiac organoids have emerged as invaluable tools for assessing the impact of diverse substances on heart function. This report introduces guidelines for general requirements for manufacturing cardiac organoids and conducting cardiac organoid-based assays, encompassing protocols, analytical methodologies, and ethical considerations. In the quest to employ recently developed three-dimensional cardiac organoid models as substitutes for animal testing, it becomes imperative to establish robust criteria for evaluating organoid quality and conducting toxicity assessments. This guideline addresses this need, catering to regulatory requirements, and describes common standards for organoid quality and toxicity assessment methodologies, commensurate with current technological capabilities. While acknowledging the dynamic nature of technological progress and the potential for future comparative studies, this guideline serves as a foundational framework. It offers a comprehensive approach to standardized cardiac organoid testing, ensuring scientific rigor, reproducibility, and ethical integrity in investigations of cardiotoxicity, particularly through the utilization of human pluripotent stem cell-derived cardiac organoids.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3971-3977
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• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• Archives of Craniofacial Surgery
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• v.11 no.2
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• pp.120-123
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• 2010

Purpose: Epinephrine itself exhibits some cardiotoxicity. However, it rarely induces cardiomyopathy when used in standard doses during surgery for local hemostasis. This paper reports a rare case of stress-induced cardiomyopathy in a young woman after the local infiltration of epinephrine. Methods: Corrective rhinoplasty was planned in a 20-year-old woman. Lidocaine mixed with epinephrine 1:100,000 was injected around the skin of the nose and nasal septum after inducing anesthesia, which resulted in sinus tachycardia and hypotension. Postoperative ECG showed a T wave inversion in the lead V2 and echocardiography revealed transient hypokinesia in the cardiac apex. Cardiac enzyme was mildly elevated. Results: Symptoms and laboratory findings improved considerably, and the patient was discharged from hospital without complications on the sixth day after surgery. Conclusion: The prognosis of catecholamine-induced cardiomyopathy is generally favorable. However, it is important to be aware of the possible adverse effects of local epinephrine infiltration. This case highlights the need for caution when using epinephrine.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.9-13
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• 1998

ln an attempt to define the effects of hyperbaric oxygen treatment on the lipid peroxidation and oxygen See radical reactions in rats exposed to carbon monoxide, we studied malondialdehyde(MDA) level and activities of catalase and superoxide dismutase in the heart of the rats exposed to carbon monoxide. Male Sprague-Dawley albino rats weighing 240 to 260gm were used. Experimental groups consist of Control group (=breathing with air), HBO group(=exposed to hyperbaric oxygen(HBO, 3ATA, 100%) after air breath), CO group(=exposed to CO(3,970 ppm) after air breath), CO-Air group(=exposed to CO after air breath followed by air breath) and CO-HBO group(=exposed to CO after ai. breath followed HBO treatment). The CO group showed significantly higher MDA level, catalase activity and SOD activity as compared to that of control group. The CO-HBO group showed significantly lower MDA level as compared to that of CO group, and did not show significantly lower catalase activity and SOD activity as compared to that of CO group. These results suggest that the excessive oxygen free radicals is an important determinant in pathogenesis of Co-induced cardiotoxicity and HBO inhibits the lipid peroxidation caused by excessive oxygen free radicals in the heart of the rats exposed to carbon monoxide.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1207-1210
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• 2002

To examine the cardiotoxic effect of adriamycin on cultured rat myocardial cells, cytotoxicity was measured by MTT assay after cultured myocardial cells were grown with various concentrations of adriamycin(ADA) for 48 hours. The protective effect of Benincasae Semen(BS) on ADR-induced cardiotoxicity was also examined in these cultures. ADR decreased cell viability of cultured rat myocardial cells remarkably in a dose- and time-dependent manners. In protective effect of BS, it was very effective in blocking ADR-induced cytotoxicity. From these results, it is suggested that ADR shows cardioxicity, and the herba extract, as is very effective in preventing ADR-induced cytotoxicity on cultured rat myocardial cells.

• The Korean Journal of Nuclear Medicine
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• v.38 no.5
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• pp.331-337
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• 2004

Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MIBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with I-123 MIBG imaging nay be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.

• BMB Reports
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• v.39 no.6
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• pp.759-765
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• 2006

In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADR-treated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.