ABSTRACT
BACKGROUND: Doxorubicin (DOX) is one of the most important anticancer agents used in treating breast cancer. However, chronic cardiotoxicity and multidrug resistance limit the chemotherapeutic use of DOX. METHODS: This study aimed to evaluate the capability of calcium channel blocker diltiazem (DIL) to reverse DOX resistance in breast cancer MCF-7 cells and to confer protection against DOX-induced cardiotoxicity in Wistar rats. For this purpose, we explored the effects of DOX on cell cycle phase distribution and expression of ABCB1, FOXO3a, and p53 genes in the presence and absence of DIL (20 µg/ml) and studied the ability of DIL to prevent DOX-induced cardiotoxicity after a single injection of DOX (15 mg/kg) in male Wister rats. RESULTS: We found that compared with DOX alone treatment, DIL + DOX treatment down regulated the ABCB1 gene expression by > fourfold but up regulated the FOXO3a and p53 genes expression by 1.5 fold. DIL treatment conferred protection against DOX-induced cardiotoxicity, as indicated by a decrease in the levels of the cardiac enzyme creatine kinase MB and malondialdehyde and an increase in the total antioxidant capacity and glutathione peroxidase levels. These biochemical results were further confirmed by the histopathological investigation of cardiac cells, which showed normal cardiac cells with central vesicular nuclei and prevention of DOX-induced disruption of normal cardiac architecture in the DIL to DOX group. CONCLUSIONS: Taken together, our results indicate that DIL treatment can reverse the resistance of breast cancer cells to the therapeutic effects of DOX and can protect against DOX-induced cardiotoxicity in rats.
ABSTRACT
OBJECTIVES: To assess the basic knowledge on obstetric brachial plexus injury among obstetricians, pediatricians, and physio-/occupational therapists in major hospitals in Riyadh. We aimed to identify if inadequate knowledge is the reason behind delayed referrals to the Hand Clinic. Methods: This is a cross-sectional questionnaire-based study conducted at 5 major hospitals in Riyadh, Saudi Arabia between June 2015 and August 2015. A questionnaire of 6 questions (multiple choice closed-ended questions) was given to obstetricians, pediatricians, and physio-/occupational therapists' in these selected hospitals. The total score out of 6 was categorized as good, adequate, and inadequate knowledge if the score is 5-6, 3-4, and less than 3; respectively. The data were analyzed with Chi-square, fisher exact, Analysis of Variance, and Post-hoc tests where appropriate. Results: A total of 323 subjects participated in the study. For positions, the best mean score (for all 6 questions) was scored by consultants and the score was only 2.95 out of 6. For hospitals, Hospital IV scored the best mean score (2.99). The mean scores were not significantly different between different specialties. Conclusion: Inadequate knowledge seems to be a reason for delayed referrals of cases of obstetric brachial plexus injury to Hand Clinics in Riyadh, Saudi Arabia.
