视黄酸及其受体在机体免疫中的作用

视黄酸(retinoic acid,RA)又名维甲酸是维生素A的活性衍生物,是小分子质量、脂溶性信号分子,通过与其细胞内的受体α(retinoic acid receptorα,RARα)结合发挥生物学功能,在调节生物各种进程如细胞分化、调亡、胚胎发育、再生和视力发育中发挥重要作用。研究表明在很多疾病如炎症性肠病(IBD)、肿瘤等患者体内视黄酸含量减少,给予视黄酸制剂能有效的抑制疾病的进程。目前视黄酸在机体免疫调节中发挥的作用尚不完全明确,有人认为其通过对Th1/Th2和Th17/Treg平衡的调节而发挥在机体抑制炎症的作用,而在肿瘤方面的作用机制则较为复杂。本文将对视黄酸在机体免疫中发挥的作用做一综述。     

视黄酸受体及其信号转导机制

视黄酸受体及其介导的信号传递是视黄酸作用的重要环节。本文概述了视黄酸受体的发现、结构、其与配体结合特点，及视黄酸受体介导信号转导的机制：包括与反应元件结合机制及转录激活过程中的调控机制等。     

视黄酸受体与T淋巴细胞发育

视黄酸(retinoic acid)受体属于核受体超家族，通过与其配体结合调节靶基因转录，从而发挥各种生物学效应。视黄酸受体的表达分布具有时间与空间的特异性，不同的视黄酸受体亚型的表达在T淋巴细胞发育过程中起不同作用。视黄酸受体可通过对T淋巴细胞增殖、分化和凋亡的影响而调节T淋巴细胞发育。     

视黄酸受体与T淋巴细胞发育

视黄酸 (retinoicacid)受体属于核受体超家族 ,通过与其配体结合调节靶基因转录 ,从而发挥各种生物学效应。视黄酸受体的表达分布具有时间与空间的特异性 ,不同的视黄酸受体亚型的表达在T淋巴细胞发育过程中起不同作用。视黄酸受体可通过对T淋巴细胞增殖、分化和凋亡的影响而调节T淋巴细胞发育     

视黄酸核受体γ重组腺病毒构建及其鉴定

目的 构建携带大鼠视黄酸核受体γ(retinoic acid receptor γ,RARγ)的重组腺病毒,为研究RARγ在骨髓间充质干细胞(mesenchymal stem cells,MSCs)成神经分化中的作用奠定基础.方法 体外扩增大鼠RARγ基因,将其定向克隆至腺病毒穿梭质粒pAdTrace-TOX构建重组质...     

表皮生长因子受体与雌,孕激素受体在乳腺癌组织中的表达及相互关系

本文应用碘标记的表皮生长因子，用分步离心提取部细胞膜蛋白，以标准的ＥＧＦ作竞争剂，采取放射标记结合法测定了４０例乳腺癌组织中的表皮生长因子受体水平，同时采用葡聚糖活性碳分析法测定了乳腺癌组织中的雌激素受体，孕激素受体以探讨ＥＧＦＲ表达与ＥＲ，ＰＲ在乳腺癌组织中的生物学行为及相互关系。     

视黄酸对人外周血淋巴细胞CD25分子表达影响的研究

本实验采用分子杂交及流式细胞分析技术研究了视黄酸（ｒｅｔｉｎｏｉｃａｃｉｄ，ＲＡ）对人外周血淋巴细胞ＣＤ２５分子表达和细胞功能的影响，结果显示，大剂量（２．５×１０－４ｍｏｌ／Ｌ）ＲＡ处理ＰＨＡ活化４８ｈ淋巴细胞，其ＣＤ２５ｍＲＮＡ含量、ＣＤ２５阳性细胞百分率和膜表面ＣＤ２５分子数量均显著降低，淋巴细胞大部分受阻于Ｇ０／Ｇ１期，Ｇ２＋Ｍ期细胞仅占７．６％。而适量（２．５×１０－６～２．５×１０－７ｍｏｌ／Ｌ）ＲＡ作用后ＣＤ２５分子表达和Ｇ２＋Ｍ期细胞明显增加。该研究提示ＲＡ对ＣＤ２５分子表达和淋巴细胞功能的影响有一定的剂量依赖性。     

人孕激素受体在大肠杆菌中的高效表达及应用

为了制备抗重组人孕激素受体单克隆抗体，用聚酶链反应扩增人孕激素受体氨基础编码区段，定位克隆连入主同效表达载体ＰＭＳ－３１ｂ，构建重组质粒ＰＭＳ－ＰＲａ，将其转入大肠杆菌ＰＯＰ＾２１３６，     

视黄酸及相关基因在心脏发育中的作用

视黄酸是维生素A在体内重要的生物活性形式,在胚胎和胎儿发育的关键阶段发挥着重要作用。视黄酸水平过高或过低可导致心脏发育异常,但其导致心脏畸形的确切机制尚不明确。本文就视黄酸的生物学特性、视黄酸异常导致的心脏畸形及其与相关心脏转录因子在心脏发育中的作用作一综述。     

Expression of the antigen detected by the monoclonal antibody Ca 19.9 in human breast tissues

Summary The incidence and significance of the expression of the antigen defined by the monoclonal antibody Ca 19.9 (Sialyl Le^a) has been assessed in human breast tissue. Frozen and formalin-fixed, paraffin embedded specimens of normal, hyperplastic, pregnant breast and carcinomas were examined using an immunoperoxidase technique.Ductal and acinar epithelium of normal and hyperplastic tissues showed variable reactivity in frozen sections but there was a reduction in staining in comparable samples after fixation and processing, such that in many instances only focal ductal epithelium reacted. A distinctive feature in the pregnant breast was the absence of staining in acini showing differentiated secretory activity, despite a reaction in adjacent non-secretory acini and ducts.The overall incidence of detection of the Ca 19.9 antigen in breast carcinomas was 62%, but in half of these only a small number of cells stained. A significant relationship between expression of Sialyl Le^a and poor differentiation of carcinomas was identified, but there was no correlation with local lymph node status. In contrast to the non-malignant tissue fixation and processing had little effect on the reactivity of carcinomas. It is suggested that this difference may be quantitative in nature, with malignant breast showing much greater expression, or be related to organisation of the antigen.The observations concerning carcinomas and pregnant breast indicate that the synthesis of the Ca 19.9 antigen is related to the state of differentiation and functional activity of human breast.     

Expression of Yes-associated protein (YAP) in metastatic breast cancer

The purpose of this study was to investigate the expression of Yes-associated protein (YAP) in different metastatic sites in metastatic breast cancer and to determine the clinical implications of these patterns. Immunohistochemical staining was used to investigate the expression of YAP and phospho-YAP in tissue microarrays from 122 cases of metastatic breast cancer (bone metastasis = 29, brain metastasis = 38, liver metastasis = 12, and lung metastasis = 43). The expression levels of YAP and phospho-YAP differed according to the metastatic site in metastatic breast cancer. Specifically, nuclear expression of phospho-YAP was high in brain metastasis but low in lung metastasis (P = 0.010). The effects of YAP and phospho-YAP expression on clinical outcomes were investigated by univariate analysis. This analysis showed that nuclear YAP positivity (P = 0.008) and nuclear phospho-YAP positivity (P = 0.003) were both associated with shorter overall survival. In conclusion, the level of YAP expression varies according to the metastatic site in metastatic breast cancer. Moreover, high YAP expression was correlated with poor prognosis.     

Expression of p16 and pRB in invasive breast cancer

We aimed to assess protein expressions of p16 and pRB in breast cancer and explore the clinicopathologic implications. Tissue microarray (TMA) was constructed with 406 cases of breast cancer. The cases were subgrouped into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) based on the results of immunohistochemical stains for ER, PR, HER-2, and Ki-67 and fluorescent in situ hybridization (FISH) for HER-2. One hundred and sixty-eight cases were allocated to the subgroup luminal A; 87 cases to the luminal B; 32 cases to the HER-2; and 119 cases to the TNBC. The TNBC group showed the highest negative rate for p16, and the luminal B and HER-2 groups showed the highest positive rate for p16 (P < 0.001). Alteration of p16 was the highest in the luminal B and HER-2 groups, and pRB expression rate was the highest in the HER-2 group and lowest in the luminal A group. In addition, p16(+)/pRB(+) type was the most common in the luminal B group, p16(+)/pRB(-) in the luminal A group, and p16(-)/pRB(+) in the TNBC group (P < 0.001). Altered p16/pRB(+) and non-altered p16/pRB(+) type was the most common in the luminal B, and altered p16/pRB(-) and non-altered p16/pRB(+) type was the most common in the luminal A (P < 0.001). Alteration of p16 was correlated with higher Ki67 labeling index (LI) (P = 0.013), and p16 negativity was correlated with ER negativity (P = 0.002), PR negativity (P = 0.004), and higher Ki67 LI (P < 0.001). pRB positivity was correlated with PR negativity (P = 0.009), HER-2 positivity (P = 0.001), and higher Ki-67 LI (P < 0.001). In luminal group A, p16 alteration was correlated with shorter DFS in univariate analysis (P = 0.024). In conclusion, Expression rates of p16 and pRB differ according to the molecular subgroups of breast cancer and they subsequently correlate with clnicopathologic factors.     

Primary relapse site pattern in women with triple-negative breast cancer

Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site.     

Failure of primary breast cancer neoangiogenesis to predict pattern of distant metastasis

In the present study, the primary tumor angiogenesis characteristics of 81 stage IV previously untreated breast cancers with synchronous metastasis to different distant sites (10 patients with soft tissue metastases, 31 with bone metastases, and 40 with visceral metastases) were analyzed. The primary intratumor microvessel density was assessed by immunohistochemical assay on paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody. The mean primary intratumor microvessel density (at 400× fields) was 78±39 (SD) microvessels per field. The microvessel density was not significantly related to the main clinical/pathological features of the tumor (age, cytohistological grade, DNA ploidy, diameter, and receptor status). The percentage of tumor cases with high primary intratumor microvessel density (cut-off median value of the series 73±39 microvessels/field) did not significantly differ in patients with bone, soft tissue, or visceral metastatic disease. Aanalysis of clinical outcome showed a significantly shorter time to progression and overall survival for patients with visceral metastases (P<0.001 and P<0.0002 by log-rank, respectively). Presence of visceral metastases was confirmed to be the only independent prognostic factor related to a worse TTP (hazard risk 2.15, 95% confidence interval 1.14–4.03, P<0.02) and overall survival (hazard risk 1.81, 95% confidence interval 0.98–3.35, P<0.06) by multivariate analysis. In conclusion, the assessment of neoangiogenesis of primary breast cancer by CD34 expression does not provide information predictive of different distant sites of metastasis. Received: 15 June 2001 / Accepted: 12 September 2001     

人乳腺癌组织中GATA3的表达及其临床意义

 目的：探讨乳腺癌组织中转录因子GATA3的表达及其临床意义。方法: 应用免疫组化法检测124例乳腺癌组织中GATA3的表达水平,分析其与临床病理指标的关系,探讨其在预测乳腺癌预后中的意义。结果: GATA3的低表达与雌激素受体（ER）/孕激素受体（PR）阴性、肿瘤高组织学分级、脉管癌栓、p53基因突变等表示预后较差的指标相关（P<005）,但与肿瘤大小、人表皮生长因子受体 2（HER-2）表达水平、年龄和淋巴结转移情况无关（P>005）;在全部乳腺癌组织中GATA3阳性表达率为564%,GATA3在luminal型乳腺癌中的表达率为684%,高于非luminal型乳腺癌（326%）,且差异有统计学意义（P<005）;全部乳腺癌组织中术后复发风险中危组GATA3阳性率高于复发风险高危组（P<005）。结论: 在乳腺癌组织中GATA3的表达水平与组织的分化水平及肿瘤的生物学特性相关,对指导临床治疗及评估患者的预后研究具有一定的意义。     

Expression of metabolism-related proteins in triple-negative breast cancer

To investigate the dominant metabolic type of triple-negative breast cancer (TNBC) and evaluate its clinical implication through analysis of protein expression related to glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation. Tissue samples from 129 patients with TNBC who underwent mastectomy due to invasive breast cancer from 2000 to 2005 were prepared for tissue microarray. By immunohistochemical staining of the tissue microarrays, the markers of glycolysis-related proteins (Glut-1, CAIX, MCT4), glutaminolysis-related proteins (GLS1, GDH, ASCT2), and mitochondrial enzymes (ATP synthase, SDHA and SDHB) were analyzed. Based on the results, the metabolic phenotypes were defined based on positivity for more than two of three markers for each phenotype as follows: glycolysis type (Glut-1, CAIX and MCT4), glutaminolysis type (GLS1, GDH and ASCT2) and mitochondrial type (ATP synthase, SDHA and SDHB). The percentages of samples with metabolic phenotypes of tumor and stroma of TNBC were as follows: for tumor, mitochondrial type (85.3%) > glutaminolysis type (67.4%) > glycolysis type (63.0%); and for stroma, glutaminolysis type (37.2%) > glycolysis type (16.3%) > mitochondrial type (14.0%). The most common metabolic phenotype of TNBC was glycolysis type for basal-like type and non-glycolysis type for non-basal-like type (p=0.047). The correlation between glutaminolysis and mitochondrial type was statistically significant in both tumor and stroma (p<0.001). In conclusion, tumor cells of TNBC express glycolysis and mitochondrial metabolism-related proteins. Glycolysis type is the most common phenotype of basal-like type, and reversely, non-glycolysis type is the most common phenotype of non basal-like type.     

WNT5B在乳腺癌中的表达及意义

目的:研究WNT5B在乳腺癌中的表达,初步探讨WNT5B与乳腺癌临床病理特征的关系。方法:采用real-time PCR和Western blot法检测67例乳腺癌及癌旁组织中WNT5B在mRNA和蛋白水平的表达情况,通过免疫组织化学方法检测WNT5B在乳腺癌和癌旁组织中的表达并分析WNT5B的表达与相关临床病理指标之间的关系。结果:67例乳腺癌组织标本中均有不同程度WNT5B的mRNA及蛋白表达,且WNT5B在乳腺癌组织的表达明显低于癌旁组织(P0.05);其中WNT5B在原发性肿瘤大小T≤20 mm的乳腺癌患者中的表达明显高于其在T20 mm组患者中的表达(P0.05);WNT5B的表达与乳腺癌患者腋窝淋巴结转移情况、组织学分级、相关的免疫组织化学指标(ER、PR、c-Er Bb-2、p53和Ki-67)之间无明显的相关性(P0.05)。结论:WNT5B在乳腺癌组织中的表达低于癌旁组织,WNT5B表达与乳腺癌患者原发肿瘤大小呈负相关,提示WNT5B可能作为乳腺癌预后的一个新的分子标志物,为乳腺癌的诊治提供新的思路。     

Cytology and hormonal receptors in breast cancer

Even in advanced tumors of the breast, it may be interesting to know the steroid receptor status (RS) for therapeutic and prognostic purposes. When, for clinical reasons, surgical biopsy is not advisable, a morphologic technique may be attempted on cytological material. In the past few years, we have employed the cytochemical method described by Lee (RSf) on cytological material obtained from 31 primary and 34 secondary tumors; adequate material and follow-up were available in 42 cases. Patients with positive results (strong and diffuse fluorescence of neoplastic cells) usually had better prognosis and longer disease-free interval and total duration of disease. The majority of patients responded to endocrine manipulation. In contrast, weak positivity or negative results were associated with a poorer prognosis. If these results are confirmed in larger series of cases and for longer periods of observation, the morphological evaluation of RS on cytological material could significantly contribute to the management of breast cancer patients.     

Expression of XB130 in human ductal breast cancer

Objectives: XB130 is involved in gene regulation, cell proliferation, cell survival, cell migration, and tumorigenesis. In the present study, we first evaluated the expression of the XB130 and its prognostic significance in breast cancer. Then we evaluated whether XB130 could be a target for therapy in breast cancer. Materials and methods: Immunohistochemistry was used to assess the level of XB130 protein in surgically resected, formalin-fixed, paraffin-embedded breast cancer specimens. Associations between XB130 and the postoperative prognosis of patients with breast cancer were evaluated. We evaluated the effect of XB130 inhibited by RNA interference on proliferation, invasion and apoptosis in vitro in a metastatic subclone of MCF-7 breast cancer cell line (LM-MCF-7). The effect of XB130 silencing alone or in combination with gemcitabine on LM-MCF-7 cells apoptosis was also investigated. Results: XB130 protein was present in the cytoplasm of malignant cells, and not in the normal breast tissues. There was correlation between the presence of XB130 in tumour cells and lymph node status, tumor classification and clinical stage. XB130 expression level was significantly associated with recurrence-free and overall survival. Furthermore, multivariate Cox regression analyses revealed that positive XB130 was an independent risk factor for overall survival and recurrence free survival. XB130 silencing alone inhibits tumor growth and induces apoptosis in the LM-MCF-7 cells. Depletion of the XB130 in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in LM-MCF-7 cells. Conclusions: XB130 could be useful as a prognostic marker of recurrence-free and overall survival in invasive breast cancer, as well as for the response to chemotherapy.