pirarubicin and Arrhythmias--Cardiac

Pirarubicin (THP) is widely used in clinical antitumor therapy, but its cardiotoxicity seriously affects the therapeutic effect in patients. In the study, we investigated the role of ring finger protein 10 (RNF10) in cardiotoxicity induced by THP.. A cardiac toxicity model in Sprague-Dawley (SD) rats induced by THP was established. Changes in diet, weight, electrocardiogram (ECG), and echocardiography were observed. Serum levels of brain natriuretic peptide (BNP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT), and lactate dehydrogenase (LDH) were measured. The expression of RNF10 in myocardium was observed by immunohistochemistry. The expressions of RNF10, activator protein-1 (AP-1), mesenchyme homeobox 2 (Meox2), total nuclear factor (NF)-κB p65 (T-P65), phosphorylated NF-κB p65 (PP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and mature IL-1β were detected by Western blot. A THP-induced H9c2 myocardial cell injury model was established. RNF10 was downregulated or overexpressed by RNF10 siRNA and a RNF10 lentiviral vector, respectively. Then, cell viability was measured. The expression of RNF10 in H9c2 cells was observed by immunofluorescence. All of the above signaling pathways were verified by Western blots.. THP caused a series of cardiotoxic manifestations in SD rats. Our studies suggested that THP caused cardiac inflammation by inhibiting the expression of RNF10, while overexpression of RNF10 antagonized the cardiotoxicity induced by THP.. Our study showed RNF10 improved THP-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway. RNF10 may be a new target to treat THP-induced cardiotoxicity.

Topics: Animals; Arrhythmias, Cardiac; Cardiotoxicity; Carrier Proteins; Inflammation; Interleukin-6; Nerve Tissue Proteins; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

Thirty-five non-pretreated patients (29 male, six female) with malignant pleural mesothelioma, median age of 68.5 years (range, 29 to 78 years) and a median performance status of 80% (range, 60% to 100%) were treated with 70 mg/m2 Pirarubicin. The treatment was repeated every 3 to 4 weeks (median duration per cycle, 23 days) up to progression or severe toxicity. The median cumulative dose given was 294 mg/m2, or 4.5 cycles. All patients were evaluable regarding response. Three partial remissions were achieved, leading to a remission rate of 8.6%. The median duration of remission was 6 months. Five patients achieved minor response, and a further 14 patients were stable under treatment with Pirarubicin. The median survival time was 10.5 months. Leukocytopenia was the main dose-limiting factor and 20% of the patients experienced World Health Organization (WHO) Grades III and IV. Anemia and thrombocytopenia were mild. Nausea and vomiting, WHO Grades I and II, were observed in 46% of all patients. Alopecia, Grades I and II, was seen in 47% and Grade III in 6%. No signs of cardiac dysfunction were detectable, except for cardiac arrhythmia in four patients (11%). Pirarubicin is an active drug in the treatment of pleural mesothelioma with fewer severe side effects than doxorubicin.

Topics: Adult; Aged; Alopecia; Arrhythmias, Cardiac; Doxorubicin; Drug Evaluation; Female; Humans; Leukopenia; Male; Mesothelioma; Middle Aged; Nausea; Pleural Neoplasms; Remission Induction; Survival Rate

To investigate the detailed acute cardiotoxicity of the anthracycline antibiotics, adriamycin (ADM) and a tetrahydropyranyl derivative (THP-ADM), Holter ECG was recorded and some of the electrocardiographic parameters were analyzed. The basic rhythm was sinus rhythm in many cases except only one case which developed intermittent atrial fibrillation after the administration of ADM. No effect on the specialized conduction system was observed in either ADM or TH-PADM. In relation to the supraventricular premature beat, no increase of the pre-existing supraventricular extrasystole and fresh appearance of the supraventricular extrasystole were observed after the administration of these drugs. On the other hand, the ventricular premature beat was tended to increase after ADM administration, and the mode of appearance of the ventricular extrasystole was very dangerous and life-threatening. For example, short-run type and R on T type ventricular extrasystole were recorded. THP-ADM induced no significant increase of the ventricular extrasystole. The developed ST-T changes were seen after the administration of these drugs, but the patients complained neither the symptoms of heart failure nor stenocardia. In conclusion. THP-ADM had less cardiotoxicity than ADM.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Breast Neoplasms; Cardiac Complexes, Premature; Doxorubicin; Electrocardiography; Female; Heart; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms