Objective To evaluate effects of propranolol on the proliferation and apoptosis of in vitro cultured hemangioma endothelial cells (HemEC),and to explore their molecular mechanisms.Methods Hemangioma tissues were resected from 7 children with proliferative hemangioma,and used for in vitro culture of HemEC.Meanwhile,cultured human umbilical vein endothelial cells (HUVEC) served as controls.The 2 kinds of cells were treated with propranolol at different concentrations of 0,25,50,75,100,125 and 150 μmol/L for 24,48 and 72 hours separately.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cellular proliferative activity,and flow cytometry to determine the apoptosis rate.Some cultured HemEC were divided into 2 groups to be treated with 100 μmol/L propranolol-containing culture medium (propranolol group) and culture medium alone (blank control group),respectively,for 18 hours.Total RNA in the 2 groups was extracted separately.Differentially expressed genes in HemEC between the above 2 groups were identified by DNA microarray technology,and verified by real-time quantitative PCR.Results The treatment with 25 μmol/L propranolol for 24 and 48 hours caused a slight proliferation of HemEC (P ＜ 0.05).The survival rate of HemEC was decreased after the treatment with propranolol at the concentration of ≥ 100 μmol/L for more than 24 hours,while the proliferation of HUVEC was inhibited by the treatment with propranolol at the concentration of ≥ 100 μ mol/L for more than 48 hours.During 24-72 hours of treatment with 100-150 μmol/L propranolol,the survival rates of HemEC were significantly lower than those of HUVEC (P ＜ 0.05).After the treatment with 100-150 μmol/L propranolol,the apoptosis rate of HemEC gradually increased with the increase in treatment duration and concentrations of propranolol (all P ＜ 0.05).Compared with the blank control group,186 differentially expressed genes (＞ 1.5-fold changes) were screened out by DNA microarray technology,including 128 upregulated genes and 58 down-regulated genes.Real-time quantitative PCR showed that the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and fatty acid binding protein 3 (FABP3) in the propranolol group were (9.88 ± 2.19) and (21.90 ± 8.18) times that in the blank control group respectively (t =7.028,4.427 respectively,P ＜ 0.05).Conclusions Propranolol at high concentrations can inhibit the proliferation of HemEC and HUVEC,and its inhibitory effect on HemEC is stronger than that on HUVEC.The inhibitory effect of propranolol on HemEC may be related to the inhibition of HemEC proliferation and promotion of HemEC apoptosis.

Objective:The aim of the study is analyze the recurrence, metastasis and prognosis of early breast cancer patients and evaluate the long-term safety of tracer sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) and methylene blue (MB) in early breast cancer.Methods:A total of 394 breast cancer patients were enrolled from January 1, 2014 to December 31, 2014 in Affiliated Hospital of Chengde Medical University. The baseline data and clinical characteristics of 222 patients who met the inclusion criteria were analyzed.Results:The median follow-up time of 222 patients was 57 months. The detection rate of sentinel lymph nodes (SLNs) using ICG or MB alone was 96.4% and 84.7% ( P=0.02); the number of SLNs detected was 740 and 604 ( P<0.001); the positive SLN detection rates were 100% and 91% ( P=0.014), and the positive SLNs were 221 and 195 ( P<0.001). The local recurrence rates were 0.7% in patients without axillary lymph node dissection (ALND) and 1.4% ( P=0.57) in patients with ALND, and the distant metastasis rates were 5.3% and 15.7% ( P=0.01), respectively. The 5-year overall survival (OS) was 4.7% and 91.7% ( P=0.421), and the disease-free survival (DFS) was 90.5% and 85.9% ( P=0.285). The OS and DFS of the 222 patients were 100%, 96.8%, 94.1% and 100%, 96.4% and 89.2% respectively at 1, 3 and 5 years after operation. Multivariate COX regression model showed that age ≤50 years old, triple negative molecular classification and primary tumor >2 cm were independent risk factors for prognosis, and HR were 3.254, 7.321 and 3.507, respectively (all P<0.05). Conclusions:Sentinel lymph node biopsy with indocyanine green combined with methylene blue is a safe and reliable method for axillary staging of breast cancer. The COX regression models showed that patients with younger age, three-negative molecular type and larger primary tumor were more likely to have adverse events.

In recent years, PET-CT has an increasing importance in the diagnosis and treatment of breast cancer. PET-CT scan can be used as a noninvasive method for molecular subtyping of breast cancer, and prediction of therapeutic effect and prognosis of patients. Studies have revealed that luminal A subtype has a significantly lower maximum standard intake value (SUVmax) than the other subtypes; triple-negative and human epidermal growth factor receptor 2 (HER2) positive tumors have relatively high SUVmax than luminal B subtype, but the specificity and sensitivity of SUVmax in diagnosis of molecular subtypes are very low, so its clinical application is limited. In predicting the effectiveness of the treatment and the prognosis of the patients, the decreased uptake of fluorodeoxyglucose (FDG) is correlated with better therapeutic effect. In addition, patients with high FDG uptake have worse survival outcomes. New tracers, such asF-fluoroestradiol (F-FES) and[89Zr]trastuzumab play an important role in molecular subtyping of breast cancer.F-FES PET-CT can effectively evaluate the estrogen receptor (ER) status of breast cancer and the response to endocrine therapy.[89Zr]trastuzumab PET-CT can evaluate the expression of HER2 and localization of HER2-overexpressing tumors, but their specificities and sensitivities are also low. In this article, we review the recent advances on the correlation of PET-CT findings with molecular subtypes, treatment response and prognosis of breast cancer.