[Clinicopathological features of second primary lung cancer and pulmonary metastasisin patients with breast cancer].

Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions: For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.

HUWE1 plays important role in mouse preimplantation embryo development and the dysregulation is associated with poor embryo development in humans.

HUWE1 is a HECT domain containing ubiquitin ligase implicated in neurogenesis, spermatogenesis and cancer development. The purpose of the current study is to investigate the role of HUWE1 in early embryo development. Here we demonstrate that Huwe1 is expressed in both nucleus and cytoplasm of preimplantation mouse embryos as well as gametes. Hypoxia (5% O2) treatment could significantly increase Huwe1 expression during mouse embryo development process. HUWE1 knockdown inhibited normal embryonic development and reduced blastocyst formation, and increased apoptotic cell numbers were observed in the embryos of HUWE1 knockdown group. Human embryo staining result showed that reduced HUWE1 staining was observed in the poor-quality embryos. Furthermore, Western blot result showed that significantly reduced expression of HUWE1 was observed in the villi of miscarriage embryos compared with the normal control, indicating that reduced expression of HUWE1 is related to poor embryo development. Oxidative reagent, H2O2 inhibited HUWE1 expression in human sperm, indicating that HUWE1 expression in sperm is regulated by oxidative stress. In conclusion, these results suggest that HUWE1 protein could contribute to preimplantation embryo development and dysregulated expression of HUWE1 could be related to poor embryo development and miscarriage in IVF clinic.

[Effect of autophagy inhibitor combined with EGFR inhibitor on triple-negative breast cancer MDA-MB-468 and MDA-MB-231 cells].

OBJECTIVE: To investigate the effect of combined administration of autophagy inhibitor 3-methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple-negative breast cancer MDA-MB-468, MDA-MB-231 cells and estrogen receptor-positive MCF-7 cells. METHODS: All the cells were treated with 3-methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy-related protein (such as LC3) and apoptosis-related proteins (such as caspase-3 and caspase-9). RESULTS: MTT assay showed that the IC50 in the GE+ 3-MA and GE+ BAF groups were (4.1±0.2) µmol/L and (3.8±0.3) µmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) µmol/L] in MDA-MB-468 cells (P<0.05). Similarly, the IC50 in the GE+ 3-MA and GE+ BAF groups were (9.7±0.1) µmol/L and (7.7±0.2) µmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) µmol/L]in MDA-MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA-MB-468 cells in GE, GE+ 3-MA and GE+ BAF groups were (12.43±3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA-MB-231 cells of the GE, GE+ 3-MA and GE+ BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF-7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p-Akt were decreased in the combined groups than that of the gefitinib alone group, while the p-PTEN, caspase-3 and caspase-9 were increased. CONCLUSIONS: Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA-MB-468 and MDA-MB-231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA-MB-468 and MDA-MB-231 cells might be enhanced by the combination treatment through caspase cascade.

Preparation and characterization of tea polyphenols and vitamin E loaded nanoscale complex liposome.

The purpose of the present work was to prepare nanoscale complex liposome loaded both aqueous soluble drug tea polyphenols (TP) and insoluble drug vitamin E (VE) by reverse-phase evaporation method. The preparation formulation of TP-VE complex liposome was optimized by the orthogonal experiment. The entrapment efficiency of TP was (50.81 +/- 1.91)% while that of VE was (94.05 +/- 3.45)% for the optimal formulation. The results of penetration experiments of TP-VE liposome demonstrated a slight influence of the concentration of TP and the content of cholesterol on the penetration quantity of TP. These results indicate that the complex liposome offers a new approach to entrap aqueous soluble drug and poorly soluble drug, an inner liposome protection, a relatively high drug encapsulation efficiency and a sustained transdermal penetration.