Menstrual and reproductive characteristics and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities study

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR− (ER− and PR−) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR− BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR− BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

新型雌激素受体β信号通路调节因子的分离及鉴定

目的：利用酵母双杂交技术筛选与ERβ相互作用的蛋白，为进一步研究ERβ的功能奠定基础。方法：从乳腺cDNA文库中钓取ERβ-AF1 cDNA，构建诱饵蛋白载体pAS2-1-ERβ—AF1，利用酵母双杂交筛选技术，在乳腺cDNA文库中筛选与ERβ-AF1相互作用的蛋白。将含有pACT2-候选基因的酵母菌与含有pAS2—1-ERp—AF1的酵母菌进行交配实验，利用LacZ报告基因检测ERβ—AF1与候选蛋白之间是否存在相互作用。然后将ERp—AF1和候选蛋白分别构建到pGEx-KG和pET-28a上，并纯化GST-ERβ-AF1和His-侯选蛋白融合蛋白，利用GST沉淀实验进一步验证ERβ-AF1和候选蛋白的体外相互作用。结果：所获取的候选蛋白为CTGF，是CCN多肽家族成员。交配实验表明，CTGF与ERβ-AF1特异相互作用，而不与空载体或BRCT1对照相互作用。GST沉淀实验进一步验证，CTGF与ERβ、ERα均存在相互作用，但与CTGF同源性较高的NOV蛋白却不与ERβ、ERa结合。结论：CTGF和ERβ存在特异的相互作用。     

雌、孕激素受体和C-erbB-2在原发胆囊癌中的表达及意义

目的　探讨雌、孕激素受体 (ER、PgR)和C erbB 2癌基因蛋白产物在原发胆囊癌发生、发展中的作用及相互关系 ,研究它们的表达与肿瘤的病理类型、分级 ,临床分期及预后的关系 ,并为该病的临床诊治提供参考依据。方法　应用免疫组织化学法 ,检测 3 5例原发胆囊癌 ,2 0例慢性胆囊炎组织中ER、PgR和C erbB 2癌基因蛋白的表达水平。结果　在原发胆囊癌中ER、PgR和C erbB 2阳性表达率分别为 60 %、4 5 .7%和 65 .7%。ER的阳性表达与浸润及淋巴结转移密切相关 (P <0 .0 5 )。C erbB 2过度表达与胆囊癌淋巴结转移有关 (P <0 .0 5 )。ER或PgR阳性患者的累计生存率明显低于阴性者。结论　ER、PgR及C erbB 2在原发胆囊癌中的表达率显著高于其在胆囊良性病变中的表达率。ER或PgR阳性者积累生存率显著低于ER或PgR阴性者。ER可能有希望成为反映胆囊癌恶性程度和预后的一项生物学指标     

去势后大鼠海马结构一氧化氮合酶阳性神经元的变化

目的：观察去势后大鼠海马结构一氧化氮合酶（NOS）阳性神经元的变化。方法：用黄递酶组织化学染色方法观察切除双侧卵巢后雌后SD大鼠海马结构NOS阳性神经元的形态，分布的变化，并进行计算机图像分析。结果：去势后海马结构NOS阳性神经元分布变化有区域差异性；NOS阳性神经元在下托、海马（CA）一区邻近下托的部分、CA三区、CA四区（CA4）和齿状回（DG）数目明显减少，而在CA二区数目明显明显增多，CA4和DG的NOS阳性神经元平均密度降低，胞体的平均周长和平均截面积都明显减少。结论：雌激素可能通过影响海马结构NOS的表达来影响学习和记忆。     

胃癌雌激素受体表达及新一代抗受体药物在胃癌治疗中的探讨

目的　探讨胃癌雌激素受体 (ER)实际表达率 ,为临床使用新一代抗ER药物 (toremifene ,TOR)治疗胃癌提供临床病理依据。方法　用免疫组化法对 349例胃癌标本进行ER的检测 ,其中 2 99例用ABC(avidinbiotinperoxidasecomplex)法 ,5 0例用葡聚糖聚合物技术二步法进行检测。在检测ER的同时也检测 p5 3及PCNA的表达。结果　两种检测方法的ER阳性率分别为 2 .3% (7/ 2 99)及 0 % (0 / 5 0 ) ,p5 3阳性率 37.1% (111/ 2 99)及 4 6 %(2 3/ 5 0 ) ,PCNA 94 .3% (2 82 / 2 99)及 96 % (48/ 5 0 )。结论　胃癌细胞可表达ER但实际表达率很低 ,而且存在质和量的变化。tamoxifen (TAM )及TOR的抗胃癌效应需要进一步研究     

Interaction of estrogen receptor‐α ligand binding domain with nuclear proteins of aging mouse brain

After the interaction of estrogen with the ligand binding domain (LBD) of mouse estrogen receptor‐α (mERα) and hormone‐responsive elements of target genes, many nuclear proteins are recruited to regulate the expression of specific genes. Because it is not known which brain proteins interact with LBD or whether these proteins vary with age and sex, we used pull‐down assay and far Western blotting to detect five nuclear proteins of 160, 140, 87, 60, and 46 kD in the mouse brain. These interacting proteins were identified as PELP1, RIP140, PGC1α, BAF60, and ADA3, respectively. The level of PELP1, RIP140, PGC1α, and BAF60 decreased drastically in old compared with adult male mice, whereas the ADA3 level showed no significant change. PELP1, PGC1α, and BAF60 levels were lower in old male compared with female mice. Thus we report the identification and interaction of five nuclear proteins with mERα‐LBD, indicating their role in estrogen signaling and brain functions during aging. © 2009 Wiley‐Liss, Inc.     

雌激素对穹隆海马伞切断大鼠脑内nAchR的干预作用

目的以双侧穹隆-海马伞切断制作阿尔茨海默病(AD)大鼠模型,观察脑内海马CA1区和皮层区烟碱型乙酰胆碱受体(nAchR)表达的变化,探讨与AD相关的发病机制,并观察雌激素的干预作用。方法健康雌性W istar大鼠,随机分为3组:(1)穹隆-海马伞切断组;(2)雌激素治疗组;(3)假手术对照组;每组大鼠5只。在脑立体定位仪上切断穹隆-海马伞,建立模拟AD动物模型。应用免疫组织化学技术观察AD大鼠海马CA1区和皮层区的nAchR阳性细胞表达的变化,以及应用外源性雌激素的干预作用。结果与对照组大鼠脑内nAchR表达比较,穹隆-海马伞切断组大鼠脑内海马CA1区、皮层区nAchR表达显著减少(P<0.05);与穹隆-海马伞切断组比较,雌激素治疗组海马CA1区、皮层区nAchR表达显著增加(P<0.01),但与对照组比较无显著差异(P>0.05)。结论穹隆-海马伞切断组大鼠脑内海马CA1区、皮层区nAchR的阳性细胞显著减少,补充外源性雌激素治疗后,上述各脑区内的nAchR表达显著增加。nAchR的变化与AD的病理变化过程密切相关,补充雌激素可以干预这种病理过程。