Objective Gastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism. Methods GEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments. Results MFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth. Conclusion MFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.

PURPOSE:To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS:Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied. The distribution and abundance of the proteins p-Akt and p-Erk expressed in these cells in response to single agents or combinatorial treatment were also investigated. In addition, the effects of trastuzumab and fulvestrant, either as single agents or in combination on tumor growth as well as on expression of the protein p-MED1 expressed in in vivo mouse xenograft models was also examined. RESULTS:Cell proliferation was increasingly inhibited by trastuzumab or fulvestrant or both, with a CI<1 and DRI>1 in both human cell lines. The rate of apoptosis increased only in the BT-474 cell line and not in the ZR-75-1 cell line upon treatment with fulvestrant and not trastuzumab as a single agent (P<0.05). Interestingly, fulvestrant, in combination with trastuzumab, did not significantly alter the rate of apoptosis (in comparison with fulvestrant alone), in the BT-474 cell line (P>0.05). Cell accumulation in the G1 phase of cell cycle was investigated in all treatment groups (P<0.05), and the combination of trastuzumab and fulvestrant reversed the effects of fulvestrant alone on p-Akt and p-Erk protein expression levels. Using ZR-75-1 or BT-474 to generate in vivo tumor xenografts in BALB/c athymic mouse models, we showed that a combination of both drugs resulted in a stronger inhibition of tumor growth (P<0.05) and a greater decrease in the levels of activated MED1 (p-MED1) expressed in tumor issues compared with the use of either drug as a single agent. CONCLUSIONS:We demonstrate that the administration of trastuzumab and fulvestrant in combination results in positive synergistic effects on both, ZR-75-1 and BT-474 cell lines. This combinatorial approach is likely to reduce physiological side effects of both drugs, thus providing a theoretical basis for the use of such combination treatment in order to resolve HR+/HER2+ triple positive breast cancer that has previously been shown to be resistant to endocrine treatment alone.

Objective: There is no universal consensus on whether gonadotropin-releasing hormone (GnRH) agonist could protect chemotherapy-induced ovarian damage in premenopausal breast cancer patients. This meta-analysis was conducted to estimate the protective effects of GnRH agonist on premenopausal breast cancer patients in details. Methods: PubMed, Cochrane Library, Embase, CNKI and the Chinese Wangfang Database, conference proceedings and clinical trials were searched to find studies reported since 2000. Heterogeneity for the eligible data was assessed and a pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results: Resumption of menses rate was improved in the GnRH agonist and chemotherapy-combination groups versus chemotherapy-alone groups (OR = 1.36, 95% CI: 1.19-1.56). Furthermore, the results indicated that spontaneous pregnancy rate was improved in the experimental groups versus the controls (OR = 1.90, 95% CI: 1.06-3.41). In addition, no publication bias was found using a Begg's funnel plot. Conclusion: The results of the current meta-analysis indicate that a GnRH agonist could improve resumption of menses rate and pregnancy rate for premenopausal breast cancer patients. However, more evaluation may be considered to prove this theory.

[目的]利用Meta分析研究吉西他滨联合顺铂(GP方案)及长春瑞滨联合顺铂(NP方案)治疗晚期乳腺癌的疗效.[方法]计算机检索万方数据库、中国知网数据库、PubMed、Cochrane Library,纳入GP方案及NP方案治疗晚期乳腺癌的随机对照研究,检索时间为2004年1月至2015年8月.由2名评价员按纳入与排除标准独立筛选文献、提取资料并评价纳入研究的方法学质量后,所有数据均用RevMan5.2软件处理.[结果]共纳入14个RCT,其中GP组545例,NP组547例.Meta分析结果显示,两组反应率(RR)(OR=1.19,95％CI:0.94～1.52)及疾病控制率(DCR) (OR=1.15,95％CI:0.87～1.53)无统计学差异.3级及以上不良反应包括白细胞减少症、血小板减少症、恶心呕吐、静脉炎.Begg漏斗图未发现发表偏倚.[结论] GP及NP方案对提高晚期乳腺癌患者RR及DCR的疗效肯定,临床效果相似,值得进一步研究.

Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.

通过分析在现代医学迅猛发展的背景下传统乳腺外科教学模式所暴露的弊端，阐述了循证医学的概念以及在传统乳腺外科教学模式引入循证医学教育的意义，并探讨了将循证医学引入乳腺外科的理论知识教学和临床实习带教中的具体方法，提出在乳腺外科教学中引入循证医学教育新模式是现代临床医学教育改革的切入点。

Objective To investigate the effectiveness of fulvestrant combined with trastuzumab on the human breast cancer cell line BT-474.Methods Inhibition of BT-474 cell proliferation at different concentrations of fulvestrant, trastuzumab and the two drugs combined was assessed using the WST-1 assay.Flow cytometry(FCM) was used to detect the cell apoptosis rates by Annexin-V/PI assay. Moreover, the effect fulvestrant and trastuzumab respectively and combinedly have on the proteins p-Akt and p-MAPK was detected by Western blot assay. Results The cell proliferation was increasingly inhibited by fulvestrant, trastuzumab or them combined when each group's drug concentration added, with a CIED50 of 0.466.When fulvestrant and trastuzumab combined, the cell apoptosis rates were distinctly increased(P<0.05).Furthermore, the level of proteins p-Akt and p-MAPK expressed in the cell BT-474 was raised by fulvestrant, but definitively reduced when fulvestrant combined with trastuzumab. Conclusion Fulvestrant synergizes trastuzumab if they combine when acing on the cell line BT-474, maybe because fulvestrant combined with trastuzumab increases the cell proliferation inhibition, promotes the cell apoptosis and restrains fulvestrant from enhancing the proteins p-Akt and p-MAPK expression.

目前，蒽环类药物广泛应用于乳腺癌的化疗，其使部分病人受益的同时也因心脏不良反应等给病人带来巨大痛苦。因此，明确预测蒽环类药物疗效的生物学指标对优化乳腺癌化疗方案显得尤为重要。拓扑异构酶Ⅱα（topoi-someraseⅡalpha，TopoⅡα）作为蒽环类药物的作用靶点，其编码基因TOP2A基因引起越来越多关注。<br>　　TOP2A基因与HER2基因相邻，定位于人类染色体17q12-21，编码TopoⅡα（分子质量约为170 ku）。TopoⅡα是TopoⅡ的1个亚基，TopoⅡ可以松解DNA的超螺旋状态，打断并重新连接DNA链，从而为DNA复制等做准备。TOP2A基因的表达依赖于细胞的增殖状态，在细胞增殖S期晚期和G2/M期表达增加，有丝分裂结束后表达减少。此外，有报告显示，在因染色体分离缺陷未能完成有丝分裂的人类细胞中，TOP2A基因不表达［1］。

Objective To study the in vivo and in vitro effects of adding oxygen carbon nanotubes (CNTs) to chemotherapy for breast cancer. Methods MCF-7 and SK-BR-3 breast cancer cells were co-cultured with paclitaxel and then exposed to oxygen-CNTs under hypoxic conditions. Cell proliferation, viability, and apoptosis rate were analyzed. Hypoxia-inducible factor-1 alpha (HIF-1α) expression was measured using reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Nude mice were used as a human breast cancer model to explore the impact of oxygen-CNTs on the in vivo chemotherapeutic effect of paclitaxel. Results Oxygen-CNTs had no significant effects on the growth of breast cancer cells under normoxia and hypoxia. However, in the hypoxic environment, oxygen-CNTs significantly enhanced the inhibitory effect of paclitaxel on cell proliferation, as well as the apoptosis rate. Under hypoxia, downregulation of HIF-1α and upregulation of caspase-3, caspase-8, caspase-9, LC3 and Beclin-1 were observed when paclitaxel was combined with oxygen-CNT. Furthermore, addition of oxygen-CNTs to chemotherapy was found to significantly reduce tumor weight in the tumor-bearing mice model. Conclusions Oxygen-CNTs can significantly increase the chemotherapeutic effect of paclitaxel on breast cancer cells. Oxygen-CNTs may be a potential chemosensitizer in breast cancer therapy.

目的:探讨缓释血管内皮生长因子(VEGF)复合支架与脂肪干细胞(ASC)应用于乳房再造的可行性.方法:制备能缓释VEGF复合支架.ELISA法检测支架释放VEGF浓度和持续性.体外提取培养ASC,WST-1法检测复合支架对ASC生长增殖的影响.流式细胞术检测ASC表面标志物CD34、CD44、CD90和CD105的表达.将复合支架和ASC植入裸小鼠背部,8周后切取植入物测量体积和重量,组织切片HE和CD31免疫组织化学染色,评估效果.结果:复合支架能连续12 d释放较高浓度的VEGF.WST-1法显示,复合支架对ASC的生长增殖无显著影响.ASC表面高表达CD44、CD90和CD105.动物实验结果显示复合支架与ASC共移植能显著减少植入物的机体吸收(P＜0.01),显著增加血管的生成(P＜0.01),减少组织坏死.结论:缓释VEGF复合支架具有良好的生物安全性.复合支架与ASC共移植再造乳房具有一定的可行性.

目的:研究叶酸修饰稀土改性载氧碳纳米管在低氧环境下对乳腺癌细胞株放疗敏感性的影响.方法:使用水溶性四唑盐法(WST-1)方法研究叶酸修饰稀土改性载氧碳纳米管对MDA-MB-231细胞与ZR-75-1细胞生长的作用,使用细胞集落形成实验研究其在低氧环境下对无叶酸培养基中MDA-MB-231细胞、有叶酸培养基中MDA-MB-231细胞及ZR-75-1细胞放疗敏感性的影响.利用流式细胞术研究叶酸修饰稀土改性载氧碳纳米管联合放疗干预MDA-MB-231乳腺癌细胞株的凋亡率的改变.利用Western Blot实验观察Bcl-2、survivin、Hif-1α、Rad51及Ku80表达水平的改变.结果:在常氧及低氧环境下,叶酸修饰稀土改性载氧碳纳米管在低于1 00 μg/ml的浓度时对乳腺癌细胞株生长无明显影响.在低氧环境下,放疗联合叶酸修饰稀土改性载氧碳纳米管组相比于单纯放疗组细胞克隆形成率有不同程度的降低,以无叶酸培养基中MDA-MB-231细胞组降低最为明显,照射剂量在2、4、6、8Gy时其细胞克隆形成率均显著降低(P＜0.05).流式细胞术显示叶酸修饰稀土改性载氧碳纳米管联合放疗后可使MDA-MB-231乳腺癌细胞株的凋亡率增加.Western Blot实验显示Bcl-2、Survivin、Hif-1α、Rad51及Ku80表达水平均降低.结论:叶酸修饰稀土改性载氧碳纳米管可在体外低氧环境下增强乳腺癌细胞株对放疗的敏感性.

The aim of this study was to assess associations between ER, Ki67, Her-2 phenotypes, molecular subtypes of breast cancer and circulating levels of lymphocyte subsets (CD4+, CD8+, NK, CD19+, CD20+) and the ratio of CD4+ to CD8+ prior to treatment. Cells from peripheral blood were counted by flow cytometry, ER, Her-2, and Ki67 expressions were detected by pathological examination, and Her-2 was also detected by FISH. We conducted a case–case comparison of 494 women with newly diagnosed breast cancer to evaluate association between levels of lymphocyte subsets in peripheral blood and breast cancer phenotypes [ER− vs. ER+; Ki67 ≥ 14 % vs. Ki67 < 14 %; Her-2+ vs. Her-2−; triple-negative breast cancer (TNBC) vs. luminal A]. Women with the highest levels of CD3+ (OR 0.45, 95 % CI 0.22–0.94), CD4+ (OR 0.22, 95 % CI 0.08–0.59), and the ratio of CD4+/CD8+ (OR 0.17, 95 % CI 0.06–0.47) were least likely to have TNBCs compared with luminal A cancers. The highest tertile of CD8+ (OR 3.67, 95 % CI 1.06–12.72) and NK (OR 2.64, 95 % CI 1.12–6.24) was significantly associated with TNBC compared with luminal A cancer. ER−, Ki67 ≥ 14 %, Her-2+ were associated with low levels of CD4+ and CD4+/CD8+ compared with ER+, Ki67 < 14 %, Her-2−. Women in the highest level of CD8+ had more likelihood to have ER− and Her-2+ compared with ER+ and Her-2−. High levels of NK cells were associated with increased risk of ER− compared with ER+ cancers. Highest levels of CD19+ and CD20+ were associated with low risk of ER−, compared with ER+ cancers. These findings show that immune function differs among different breast cancer phenotypes or subtypes and is associated with ER−, Her-2+, Ki67 ≥ 14 %, and TNBC which are likely to be aggressive phenotypes.

ABSTRACT Aim: The major obstacles of autologous fat grafting after surgery for breast cancer were low graft survival and high resorption rate. The purpose of this study was to explore adipose-derived stem cells with a new scaffold could control release vascular endothelial growth factor (VEGF) to promote transplant survival and neovascularization. Methods: Polylactic acid fiber catheters loaded with VEGF were included in a gelatin scaffold produced by freeze crosslinking. The release dose and persistence of VEGF from the tridimensional structures were determined using the enzyme-linked immunosorbent assay (ELISA). Human adipose-derived stem cells (hASCs) were extracted and expanded ex vivo, seeded to the scaffold and cultured to test the biocompatibility using the WST-1 assay. Three days after co-cultured with hASCs, the scaffolds were transplanted to the back of nude mice, the control groups were only inject hASCs, transplanted control scaffold with hASCs. Three months later, transplants volume and histology were evaluated and neovascularization was determined by the quantity of capillary and the positive of endothelial cell marker CD31 in immunohistochemistry. Results: The tridimensional structures could release VEGF stable and durable, which had no significant cytotoxicity on hASCs. The transplants volume and the capillary quantity of hASCs with the control release VEGF polylactic acid fiber catheters gelatin scaffold group was significantly larger than other two groups. Immunohistochemistry analysis revealed the transplants were rich in CD31-positive cells. Conclusions: Adipose-derived stem cells together with the control release VEGF polylactic acid fiber catheters gelatin scaffold could significantly promoted vasculogenesis and reduced absorption and necrosis after transplant. Disclosure: All authors have declared no conflicts of interest.

Male breast cancer is a rare malignant tumor, accounting for <1% of all male malignant tumors. Epidemiological risk factors for male breast cancer include family history of breast cancer, BRCA mutation, clinical disorders relating to hormonal imbalances, certain occupational, environmental exposures and alcohol. The most common clinical sign of male breast cancer is painless lump. The main pathological type of male breast tumor is invasive ductal carcinoma with high positive expression rates of hormone receptors. The prognosis of male breast cancer is much awful.

The data file includes the raw data of experiments on BT-474 and ZR-75-1 cell lines in vivo and in vitro. Results of cell absorbance were obtained by microplate reader. Data of cell apoptosis and cell cycle were analyzed by FlowJo 7.6.1 software. And results of Western blot were observed using Image Lab or got in photograph format directly.