Since their discovery more than 50 years ago, anthracyclines have become the mainstay for the treatment of many cancers. However, anthracyclines are associated with a risk of heart failure, with the risk proportionate to the cumulative exposure; cardiac injury appears to occur with every dose, and cardiac-biopsy specimens obtained within hours after a single dose of an anthracycline (e.g. doxor...

The anthracyclines are effective and widely used antineoplastic agents. They are used to treat many types of malignancy including acute lymphoblastic leukaemia.' Their introduction has considerably improved survival, especially in childhood cancers. Signs of cardiac toxicity may develop during, soon after or many years after a course of treatment. Early toxicity is dependent principally on the ...

Breast cancer patients who present with only locoregional lymphatic metastases have good life expectancy after treatment with surgery and adjuvant anthracyclinecontaining chemotherapy. Anthracyclines, however, can induce cardiomyopathy, and this may become clinically manifest as chronic heart failure many years after exposure. As the occurrence of this side effect is dependent on the cumulative...

The treatment of breast cancer has progressed substantially over the past 15 years. Data from randomized adjuvant trials have shown that the risk of disease recurrence and death is significantly reduced when adjuvant chemotherapy and/or hormonal therapy is added to treatment. As new strategies are incorporated, one of the continued controversies in patient management is whether adjuvant anthrac...

The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell– and T-lymphocyte–dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11bþCD11cþLy6ChighLy6G MHCIIþ dendritic cell–like antigenpresenting cells (APC) into the tumor bed, but not into lymphoid organs. Accordingl...

Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of F...

Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart f...

The chronic cardiotoxicity of the cytotoxic agents such as anthracyclines is one of the main factors, which limits their prolonged use. Clinically, this cardiotoxicity results in a cardiomyopathy with irreversible congestive heart failure, with high mortality. The molecular mechanisms, which could explain this cardiac toxicity, are complex but it seems distinct from the anticancer mechanism. Se...

Background Cardiotoxicity from cancer chemotherapy is an important cause of morbidity and mortality in breast cancer survivors. Left ventricular (LV) systolic dysfunction due to sequential use of anthracyclines and trastuzumab has been reported in up to 20-25% of patients. The pathophysiological changes associated with LV dysfunction have not been described non-invasively. We performed cardiac ...

We have studied the effects of clinically useful anthraquinones on the cardiac sarcoplasmic reticulum calcium-release channel. Micromolar concentrations of doxorubicin and other anthracyclines at the cytosolic face of the channel significantly and reversibly increase the open probability of single channels in artificial phospholipid bilayers. Lifetime analysis shows that anthracyclines and calc...