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.     

子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究

目的 研究雌激素（ER）、孕激素（PR）及癌基因（cerbB-2）、凋亡抑制基因（Bcl-2）在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB．2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达，子宫肌层异位内膜ER阳性表达率97．5％，PR阳性率97．5％，cerbB-2阳性率82．5％，Bcl-2阳性率62．5％。在位内膜和异位内膜ER、PR均呈阳性，阳性率比较差异无统计学意义（P〉0．05）。异位内膜cerbB-2的强阳性率高于在位内膜，差异有统计学意义（P〈0．05）。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性（P〈0．05）。结论 ER、PR与cerbB．2、Bcl-2在异位内膜高表达，提示这些生物学指标在子宫腺肌症发生发展中发挥作用。     

Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060)     

雌、孕激素对IL-6基因在子宫内膜表达的影响

为了进一步了解白介素－６（ＩＬ－６）在生殖过程中的作用，应用斑点杂交和原位杂交方法，研究ＩＬ－６在小鼠子宫内膜的基因表达和雌、孕激素对这种表达的影响。实验证明，正常动情前期子宫内膜间质细胞有ＩＬ－６ｃＲＮＡ基因表达，切除动物卵巢，即可消除这种表达。如给去卵巢动物２ｍｇ孕激素加１０ｎｇ雌激素或２０ｍｇ孕激素加１００ｎｇ雌激素，它们的光密度（ＩＯＤ）值分别可达到２．３和２．５。结果证明，子宫内膜间质细胞是产生细胞因子ＩＬ－６的主要细胞之一，并受卵巢激素的调控。     

LHRH-A对孕中期大鼠抗妊娠作用的研究

本文观察了[D-Ala⁶,Pro⁹-Ethylamide¹⁰]-LHRH(LHRH-A)对孕中期大鼠的抗妊娠作用。结果显示:在孕9～11d sc 200μg/d LHRH-A,血浆孕酮水平自第二次给药后明显下降(P<0.05),给药大鼠均流产终止妊娠;LHRH-A的抗妊娠作用可被醋酸甲地孕酮所拮抗;LHRH-A对体外培养的假孕大鼠和孕d 9大鼠黄体细胞分泌孕酮有明显的直接抑制作用。     

子宫内膜息肉中雌、孕激素受体的表达

目的检测子宫内膜息肉雌激素受体(ER)、孕激素受体(PR)的表达,探索子宫内膜息肉形成的原因及机制。方法子宫内膜息肉48例为观察组,正常子宫内膜36例为对照组,采用免疫组化SP法,行半定量分析,检测ER、PR的表达。结果增殖期的息肉组织中PR表达的评分结果为(2.89±2.16),低于增殖内膜的评分(4.04±1.73),差异有统计学意义(P<0.05);分泌期的内膜息肉中ER表达的评分结果为(3.80±1.64),高于分泌期内膜中的评分(2.64±1.45),差异有统计学意义(P<0.05)。结论增殖期的子宫内膜息肉中PR的表达降低及分泌期的息肉中ER表达增高可能参与了子宫内膜息肉的形成及发展。     

无排卵性功能失调性子宫出血患者子宫内膜雌、孕激素受体及基质金属蛋白酶表达变化的研究

目的研究无排卵性功能失调性子宫出血(功血)患者子宫内膜雌激素受体(ER)、孕激素受体(PR)、IV型胶原、基质金属蛋白酶-9(MMP-9)及其抑制物-1(TIMP-1)的表达,探讨无排卵性功血的发病机制。方法采用免疫组化法检测20例正常增殖期子宫内膜(对照组)和66例无排卵性功血患者(病例组)子宫内膜腺上皮和基质细胞ER、PR、IV型胶原、MMP-9及TIMP-1表达。结果病例组子宫内膜腺上皮和基质ER、PR表达高于对照组(P<0.05),MMP-9水平明显增加(P<0.05),MMP-9/TIMP-1比值升高(P<0.01),IV型胶原含量明显下降(P<0.01)。相关分析显示,无排卵性功血患者子宫内膜MMP-9水平与ER、PR均呈正相关(r=0.605,P<0.05;r=0.697,P<0.05)。结论无排卵性功血患者子宫内膜出血原因可能与雌激素作用下ER、PR表达失调有关,且MMP-9水平异常升高,导致细胞外基质过度降解,临床表现为子宫不规则出血。     

多发性硬化患者中IL-12和孕酮的检测及其临床意义

目的检测IL-12和孕酮在多发性硬化(MS)患者中的水平,探讨男、女性多发性硬化患者存在的发病机制,比较男、女性MS患者在临床上发病的差异。方法采用酶联免疫(ELISA)法检测60例MS患者的脑脊液和40例患者血液中IL-12的水平,应用放射免疫法测定40例MS患者血液中孕酮的含量,并与40例正常对照组比较(以上标本男女各半)。结果男、女性MS患者血液中和脑脊液IL-12的含量明显高于正常对照组(P<0.01);女性患者血液中孕酮的含量明显低于正常对照组(P<0.01),男性患者血液中孕酮的含量与正常对照组差别不明显(P>0.05);女性患者血液中孕酮对IL-12的含量存在负相相关作用(r=-0.80,P<0.01),男性相关作用不明显(r=-0.38,P>0.05)。结论IL-12参与多发性硬化的发病过程;孕酮可能是男、女性患者发病差异性的原因之一。     

208例卵巢上皮性恶性肿瘤雌激素及孕激素受体分析

用葡聚糖－活性炭单点饱和分析法测定２０８例卵巢上皮性恶性肿瘤组织雌激素及孕激素受体（ＥＲ，ＰＲ），结果显示，ＥＲ和ＰＲ均量在内膜样癌明显高于浆液性、粘液性及透明细胞癌；ＥＲ和ＰＲ阳性率在内膜样癌及浆液性癌高于粘液性及透明细胞癌；ＥＲ和ＰＲ含量与卵巢恶性肿瘤组织分化程度、月经状况有关，而与临床期别无明显关联。某些卵巢恶性肿瘤ＥＲ和ＰＲ含量较高，尤以ＰＲ升高明显。提示有内分泌治疗的可能，卵巢恶性肿瘤病人ＥＲ和ＰＲ同时阳性，其生存时间较长。