This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart. Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs. Superoxide production in heart sarc...

Background: Evidence suggests that interpatient variability in anthracycline metabolic rate may contribute to the cardiotoxicity associated with anthracycline-based chemotherapy. Therefore, polymorphisms in the anthracycline metabolizing enzymes have been proposed as potential biomarkers of anthracycline-induced cardiotoxicity (AIC). Methods:We have previously shown that 13 of the naturally occ...

Adjuvant chemotherapy reduces the relative risk of relapse by about 25%--independent of the nodal status. Anthracycline-containing regimens are considered standard for adjuvant chemotherapy. In single studies, superiority to CMF has only been shown for anthracycline-containing polychemotherapies with at least three substances or a sequential anthracycline-CMF therapy. Recent data show that addi...

Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC patients treated with anthracycline-only pre...

Cardiotoxicity is a well-known side effect of several cytotoxic drugs, especially of the anthracyclines and can lead to long term morbidity. The mechanism of anthracycline induced cardiotoxicity seems to involve the formation of free radicals leading to oxidative stress. This may cause apoptosis of cardiac cells or immunologic reactions. However, alternative mechanisms may play a role in anthra...

A total of 19 anthracycline derivatives were tested for their ability to interfere in vitro with the action of the human replicative DNA ligase. Only those with the sugar devoid of unmodified amino groups or with large configurational modifications were found to be inactive. Maximal inhibition of DNA-joining activity was found to require a 4'-deoxy-3'-amino sugar. Self-adenylation of DNA ligase...

Formation of compact particles from linear DNA-anthracycline complexes is accompanied by appearance of intense bands in the CD spectra in the region of absorption of DNA bases (UV-region) and in the region of absorption of anthracycline chromophores (visible region). The intense (positive or negative) bands in the region of anthracycline absorption demonstrate an ordered helical location of ant...

Surveillance of left ventricular function, part current US Food and Drug Administration recommendations for anti-human epidermal growth factor receptor 2 (anti-HER2) chemotherapy, is based on historical data involving patients who received concomitant anthracycline therapy, a key enhancer cardiac risk. More recent anti-HER2 treatment suggest that cardiotoxicity detected by screening rare usuall...

Anthracycline chemotherapy agents bind to DNA and cause cell death when they extravasate into healthy tissue. Although many approaches to managing extravasations have been studied and reported, data from two prospective clinical trials suggest that TotectTM (dexrazoxane for injection, TopoTarget USA, Inc.) is an effective anthracycline extravasation treatment. Only 1 of 54 patients with doxorub...

Anthracyclines remain an integral part of chemotherapy regimens in many adult and pediatric cancers but cause myocardial damage that may manifest as either subclinical decrements of left ventricular ejection function or overt cardiomyopathy. Anthracycline-related cardiotoxicity is doselimiting, and the risks of congestive heart failure increase with higher cumulative doses, particularly above 5...