Identification of serum exosomal miR-148a as a novel prognostic biomarker for breast cancer.

OBJECTIVE: Breast cancer (BC) is one of the most common malignanciesD. Li, J. Wang, L.-J. Ma, H.-B. Yang, J.-F. Jing, M.-M. Jia, X.-J. Zhang, F. Guo, J.-N. Gao affecting females. Aberrant expression of microRNAs (miRNAs) has been associated with carcinogenesis of BC. The aim of our study was to investigate the correlation of serum exosomal miR-148a expression and the clinical outcome of patients with BC. PATIENTS AND METHODS: Quantitative Real Time-Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was applied to evaluate the expression level of serum exosomal miR-148a in patients with BC, patients with benign breast tumors, and healthy controls. Then, the clinical value of serum exosomal miR-148a in BC was evaluated. RESULTS: Serum exosomal miR-148a levels were gradually downregulated from healthy controls patients with benign breast tumors to BC patients. Serum exosomal miR-148a could well distinguish BC patients from healthy volunteers. The expression level of serum exosomal miR-148a in BC patients was significantly upregulated following surgery, while dropped in the cases with disease relapse. A significant association was found between serum exosomal miR-148a levels and the tumor-node-metastasis (TNM) stage, differentiation, and lymph node metastasis in BC. In addition, BC patients with lower expression of serum exosomal miR-148a levels suffered worse overall survival and disease-free survival than those with higher expression of serum exosomal miR-148a levels. Furthermore, serum exosomal miR-148a was an independent risk factor for BC. CONCLUSIONS: Our data have demonstrated that serum exosomal miR-148a is significantly reduced in patients with BC and downregulation of serum exosomal miR-148a is closely associated with unfavorable clinical outcome of BC, indicating that serum exosomal miR-148a might serve as a promising diagnostic and prognostic biomarker for BC.

[Analysis of clinicopathological features of patients with simple breast cancer and breast cancer with thyroid cancer].

Objective: To investigate the relationship between breast cancer and thyroid cancer. Methods: A cohort of 747 female patients with stage Ⅰ-Ⅲ invasive breast cancer were enrolled in this retrospective study. The differences of clinical and pathological data were compared between the simple breast cancer group (723 cases) and the breast cancer with thyroid cancer group (24 cases), to analyze the relevant factors of second primary thyroid cancer in patients with breast cancer. Results: There were significant differences in the menstrual status and estrogen receptor (ER) status between the group of patients with breast cancer only and breast cancer patients with secondary primary thyroid cancer (P<0.05). Breast cancer patients with secondary primary thyroid cancer were more likely to be premenopausal (75%) and ER-positive (83.3%). Multivariate logistic regression analysis showed that the patient's menstrual status (compared with premenopausal patients, peri-menopausal odds ratio=0.53, 95% CI 0.07-4.25; post-menopausal odds ration=0.23, 95%CI 0.08-0.65) and body mass index (BMI, odds ratio=1.14, 95%CI 1.02-1.28) were independent risk factors for secondary primary thyroid cancer in patients with breast cancer. Conclusion: Thyroid cancer is associated with breast cancer, and is more likely to occur in obesity patients and premenopausal patients.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873.

Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor-interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR-873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases.

Effect of verbascoside on decreasing concentration of oxygen free radicals and lipid peroxidation in skeletal muscle.

AIM: To detect the effects of verbascoside on decreasing the concentration of oxygen free radicals (OFR) and lipid peroxidation in skeletal muscle resulting from exhaustive exercise. METHODS: Electron spin resonance (ESR) technique and thiobarbituric acid reaction (TBAR) method were used to detect the concentration of OFR in intact gastrocnemius muscle and the contents of milondialdehyde (MDA) in muscle homogenate. RESULTS: Verbascoside decreased the concentration of OFR (P < 0.05) and the level of lipid peroxidation (P < 0.05) in muscle caused by exercise. CONCLUSION: Verbascoside has the effects of reducing oxidative stress in muscle caused by exhaustive exercise by decreasing the concentration of free radicals and the level of lipid peroxidation.