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Abstract Background Doxorubicin (DOX) is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS) play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS), a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells. Methods In this study, we used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting. Results The MTT assay and LDH release showed that treatment using GS (1–30 μM) did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 μM)-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10–30 μM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells) death did not interfere when combined GS and DOX. Conclusion These data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.

MicroRNAs are small noncoding RNAs acting as novel biomarkers of various diseases and potential regulators of protein expression and functions. Syndecan-1 is the heparan sulfate proteoglycan associated with malignancy of various cancers, including breast cancer. In this study, we proposed a experimental workflow to investigate potential microRNAs that regulate SDC1 expression and affect breast cancer cell mobility. MicroRNA candidates were selected from available Gene Expression Omnibus datasets on breast malignancy. Further in silico duplex hybridization and multiplex PCR approach were used to screen potential microRNAs. Analysis showed increased syndecan-1 expression but decreased miR-122-5p level upon breast malignancy. Western blot and in vitro luciferase assay confirmed the targeting of 3'-untranslated region of syndecan-1 and suppression of syndecan-1 expression by miR-122-5p. The suppression of syndecan-1 expression by miR-122-5p or shRNAs against syndecan-1 increased breast cancer cell mobility; while overexpression of syndecan-1 inhibited cell mobility. In further, miR-122-5p was enriched in liver cell-derived exosomes that was able to suppress syndecan-1 expression and increase cell mobility in breast cancer cells. In conclusion, our results suggested the downregulation of SDC1 by miR-122-5p or liver-cell-derived exosomes would enhance breast cancer cell mobility. Metastasis or mobility of breast cancer cells might be affected by circulating miR-122-5p and not directly correlated with progression of breast cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Purpose: To analyze longitudinal changes in each subscale of a quality of life (QOL) measure and to explore their relationships to effective QOL predictors in breast cancer surgery patients., Patients and Methods: This prospective study analyzed 172 patients at two tertiary academic hospitals. All patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at baseline and at 1 and 2 years postoperatively. The 95% confidence intervals for differences in responsiveness estimates were derived by bootstrap estimation. Scores derived by these instruments were interpreted by generalized estimating equation (GEE) before and after surgery., Results: A 2-year follow-up survey of the examined population revealed significant (P < 0.05) improvement in each QOL subscale. In both postoperative surveys, effect size was largest in the QLQ subscales for patients who had received mastectomy with reconstruction and lowest in those who had received modified radical mastectomy. After adjusting for time effects and baseline predictors, GEE approaches revealed the following explanatory variables for QOL: time, type of surgical procedure, age, chemotherapy, radiotherapy, hormone therapy, and preoperative functional status., Conclusions: When evaluating QOL after breast cancer surgery, several factors other than the surgery itself should be considered. Patients should also be advised that their postoperative QOL might depend not only on the success of their operations, but also on their preoperative functional status., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)