A phase II trial of DA-125, a novel anthracycline, in advanced non-small-cell lung cancer

Kang, Yoon‐Koo; Ryoo, B-Y.; Kim, Taeyou; Im, Young Hyuck; Kim, B. S.; Park, Y. H.; Lee, Choon Taek

doi:10.1007/s002800051127

Cited by 4 publications

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“…However, when the hypothalamic-pituitary-adrenal axis becomes activated in the third trimester, cortisol-mediated conversion of T4 to T3 leads to a profound increase in T3 hormone in the fetus, reaching a concentration of 0.77 nmol/L at term. (42,43) The highly active T3 hormone drives maturation by modulation of contractile protein myosin heavy chain α/β, voltage-gated potassium channels (K v 1.5, K v 4.2 and K v 4.3) and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) and downregulation of phospholamban (PLN). (44)(45)(46) Insulin receptor (INSR) and insulin-like growth factor 1-receptor (IGF1R) signaling had been reported to be of high importance in the developing heart.…”

Section: Hormonal Influence On Heart Developmentmentioning

confidence: 99%

“…In patients, cardiotoxic events are classically detected through loss of the left ventricular ejection fraction (LVEF), irregularities in ECG readings (in particular ST-T changes), changes in systolic time intervals (STI, indicating heart muscle failure) and in more recent work, the release of biomarkers in blood, such as cardiac Troponin-T and brain natriuretic peptide (BNP). (31,33,(35)(36)(37)(38)(41)(42)(43)(44)(45) Due to the year of discovery, early Doxorubicin analogues have not been tested in vitro using hPSC-cardiomyocytes to evaluate their cardiotoxicity, since these models were not available at the time. Whereas biomarker release can also be assessed in vitro using hPSC-Cardiomyocytes, other clinical read-outs are more difficult to evaluate in vitro.…”

Section: Analogues Of Doxorubicinmentioning

confidence: 99%

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Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

Slaats

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Section: Hormonal Influence On Heart Developmentmentioning

confidence: 99%

Section: Analogues Of Doxorubicinmentioning

confidence: 99%

Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

Slaats

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DA-125, a new antitumor agent, inhibits topoisomerase ii as topoisomerase poison and dna intercalator simultaneously

Seo

Lee

et al. 2004

Arch Pharm Res

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DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity. In this study, the inhibitory mechanism of DA-125 on topoisomerase was investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein complexes that were formed in the drug-treated cells were quantitated by using a glass filter assay. SV40 DNA replication intermediates that were accumulated in the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not accumulate B-dimers of SV40 DNA replication intermediates which were found in the adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked the formation of the DNA-protein complexes induced by VP16 in a dose-dependent manner. However, DA-125 blocked the formation of the DNA-protein complexes induced by VP16 up to the maximum level of the DNA-protein complexes that were induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of the DNA-protein complexes that were caused by camptothecin, a known topoisomerase I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it simultaneously has the properties of the topoisomerase II poison and the DNA intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent formation of the DNA-protein complexes. However, as a DNA intercalator, it quantitatively inhibited the formation of the DNA-protein complexes induced by a strong topoisomerase II poison VP16. Furthermore considering that the levels of the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug-binding sites of DNA than VP16 has.

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Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases

Park¹,

Chung²,

Min³

et al. 2005

Biochemical Pharmacology

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A phase II trial of DA-125, a novel anthracycline, in advanced non-small-cell lung cancer

Abstract: DA-125 at these doses and in this schedule was highly tolerable, but was not active in patients with advanced NSCLC.

Cited by 4 publications

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Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

DA-125, a new antitumor agent, inhibits topoisomerase ii as topoisomerase poison and dna intercalator simultaneously

Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases

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