RATIONALE Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. OBJECTIVE We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined w...

Doxorubicin is the anthracycline with the widest spectrum of antitumor activity, and it has been shown that the antitumor activity is mediated in vivo by selective triggering of apoptosis in proliferating endothelial cells. We studied cultured human endothelial cells and observed that doxorubicin-induced apoptosis was mediated by p38 mitogen-activated protein kinase (MAPK). Doxorubicin-provoked...

PHILIP J TUSO, MD, FACP, has been with The Southern California Medical Group since 1993. From 1995 until present, he has served as Assistant Chief of Service for the Department of Internal Medicine. For the last two years he has been a Co-Chair for the Southern California Regional Asthma Care Management Program. He has provided leadership for improving access and service in both primary care an...

In this study, the interaction of the anthracycline antibiotic doxorubicin with DNA-HMG 1 complex was investigated employing UV/VIS spectroscopy, thermal denaturation and DNA cellulose chromatography techniques. The results indicated that the binding of doxorubicin to the protein reduces its Tm in a dose dependent manner. Although doxorubicin protects free DNA against thermal denaturation ...

Doxorubicin is one of the most effective molecules used in the treatment of various tumors. Contradictory reports often open windows to understand the role of p53 tumor suppressor in doxorubicin-mediated cell death. In this report, we provide evidences that doxorubicin induced more cell death in p53-negative tumor cells. Several cells, having p53 basal expression, showed increase in p53 DNA bin...

Doxorubicin is an effective drug against breast cancer. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. The MCF-7 human breast cancer cell line currently in use in our laboratory did not ...

Development of drug resistance is a major challenge in cancer chemotherapy using doxorubicin. By screening the collection of Saccharomyces cerevisiae deletion strains to identify doxorubicin-resistant mutants, we have discovered that the small ubiquitin-related modifier (SUMO) pathway is a major determinant of doxorubicin cytotoxicity in yeast. Mutants lacking UBA2 (SUMO activating enzyme; E1),...

Specific problematic issues addressed , page 8 Vygotsky's theory of learning and development, page 9 Subsequent developments in the Cultural-Historical Theory as a foundation for instructional practices, page 13 Description of the innovation, page 17 The authors are responsible for the choice and presentation of the facts contained in this publication and for the opinions expressed therein, whi...

PURPOSE The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo. METHODS The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen genera...

BACKGROUND Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients. METHODS Following an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long-term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were...