乳腺浸润性导管癌63例临床病理分析

目的 探讨乳腺浸润性导管癌与ER、PR、C-erbB-2表达相关性.方法 应用免疫组化技术S-P法检测分析63例术后、术中病理证实为乳腺浸润性导管癌的ER、PR、C-erbB-2表达.结果 63例乳腺浸润性导管癌中ER、PR、C-erbB-2的阳性表达率分别是62.5％、67.1％、44.2％,ER、PR共同阳性率为64.2％; C-erbB-2阳性表达率与有无淋巴结转移有关;ER、PR与C-erbB-2表达呈负相关(P＜0.01).结论 ER、PR、C-erbB-2联合检测可作为乳腺癌预后指标,同时有助于制定患者术后的个体化治疗方案.     

Livin在乳腺癌中的表达及与c-erbB-2和激素受体的关系

目的 探讨Livin基因在乳腺癌中的表达及与c-erbB-2基因和激素受体之间的表达关系.方法 采用免疫组化S-P法及原位杂交技术检测Livin mRNA和其蛋白在正常乳腺组织、乳腺增生性病变、乳腺非浸润性癌和乳腺浸润性癌中表达及ER/PR和c-erbB-2的表达.结果 Livin蛋白和mRNA在正常乳腺组织、乳腺增生性病变、乳腺非浸润性癌和乳腺浸润性癌的表达阳性率之间差异显著(P<0.01),Livin蛋白与mRNA表达之间差异不显著(P>0.05).Livin表达与临床分期、淋巴结转移和患者年龄有关(P<0.05),与肿瘤大小和组织学分级无关;Livin蛋白与c-erbB-2基因在乳腺癌中的表达无相关性(P>0.05).Livin表达阳性的乳腺癌ER标记指数(32.25±34.90)%明显低于Livin表达阴性的乳腺癌(59.29±34.04)%(P<0.01),而PR的标记指数在两者之间差异不显著(P>0.05).结论 Livin基因及蛋白在乳腺癌中表达上调,提示在乳腺癌的发生、发展中起重要作用,有望成为一种有效、敏感的肿瘤标记物,可作为判断乳腺癌预后的新分子标记物和乳腺癌诱导凋亡治疗的新靶点.     

乳腺导管内增生性病变中Survivin的表达及意义

目的 探讨乳腺良性、恶性病变中Survivin的表达及临床病理特征的关系。 方 法应用免疫组织化学SP法检测23例癌旁正常乳腺组织、28 例乳腺增生组织（其中20 例普通型增生,8 例非典型增生）、8 例导管内癌、98 例浸润性癌组织Survivin 的表达。 结果非典型增生上皮和导管内癌的Survivin水平高于正常乳腺腺上皮（P＜0.01）;浸润性导管癌组织中的Survivin表达率为49.0%高于正常乳腺腺上皮（P＜0.05）;与增生的乳腺组织和导管内癌组间差异无显著性。浸润性癌中的Survivin表达与分级、腋淋巴结转移、TNM分期有关,与病人的年龄、肿瘤大小、ER、PR无关。 结论Survivin在乳腺良恶性病变不同表达,提示其在乳腺癌发生、发展中起重要作用,可以为乳腺癌的诊断、治疗和预后提供依据。      

C-erbB-2,ER和PR在乳腺浸润性导管癌中的检测及临床意义

目的 究乳腺浸润性导管癌中C-erbB-2,雌激素受体(ER)和孕激素受体(PR)的表达及其临床意义.方法 应用免疫组织化学Envision法对96例乳腺浸润性导管癌中C-erbB-2,ER和PR的检测并进行统计学分析.结果 C-erbB-2,ER和PR阳性表达率分别为45.8%,55.2%和42.7%.C-erbB-2表达与ER和PR表达呈显著负相关(P=0.0001和P=0.005).C-erbB-2阳性表达率随着肿瘤体积增大、组织学分级增高而逐渐增高,差异有统计学意义(P=0.009和P=0.0001).结论 C-erbB-2的阳性表达是乳腺癌患者预后差的指标,同时检测C-erbB-2,ER和PR对乳腺癌的诊断、治疗和判断预后具有重要意义.     

乳腺增生中医辨证与ER、PR表达的相关性

目的研究乳腺增生患者辨证分型与ER、PR表达的相关性。方法本研究顺应女性周期体内激素变化,采用荧光偏振酶免分析法(FPIA)及单克隆抗体免疫组化法(S-P法)观察各证型乳腺组织ER及PR的表达。结果 (1)乳腺增生病的ER阳性33例(占乳腺增生病约70.21%);乳腺增生病的冲任失调组ER阳性率明显高于肝郁气滞型、痰瘀互结型及正常组(P<0.05)。(2)乳腺增生病的PR阳性占31例(约65.96%);乳腺增生病的冲任失调组PR阳性率明显高于肝郁气滞型、痰瘀互阻型及正常组(P<0.05)。结论冲任失调型乳腺增生病ER、PR表达增强提示该型对性激素的敏感性增强。     

乳腺浸润性导管癌ER、PR表达的临床病理意义

目的 :探讨乳腺浸润性导管癌ER、PR表达的临床病理意义。方法 :采用免疫组织化学Envision二步法检测乳腺浸润性导管癌ER、PR表达情况。结果 :6 0例乳腺浸润性导管癌ER、PR阳性表达在乳腺癌发病年龄、肿瘤大小、有无淋巴结转移和肿瘤分级间差异均有显著性 (P <0 0 5 )。结论 :ER、PR阳性表达与乳腺浸润性导管癌的病理组织学分级、有无腋窝淋巴结转移和患者预后相关。     

乳腺增生病ER和PR表达的临床与实验研究

目的通过ER和PR表达探索乳腺增生病的癌变倾向及其预防，阐明乳癣合剂的作用机理。方法用手术切除的乳腺增生病（85例）和乳腺癌（65例）患者手术标本，及以苯甲酸雌二醇造成豚鼠乳腺增生病模型的乳腺组织标本；并对豚鼠乳腺增生病模型灌服天冬素片水溶液及乳癣合剂，观察人与豚鼠乳腺组织病理变化并检测ER和PR表达。结果临床乳腺增生病患者ER和PR阳性表达率37．6％，乳腺癌为67．7％，P〈0．001；乳癣合剂降低ER和PR阳性表达，小剂量组优于大剂量组和天冬素片组，P〈0．05。结论降低乳腺增生病发病率和ER、PR阳性表达率是乳腺癌的二级预防措施。     

乳腺癌雌孕激素受体与C-erbB-2基因、多药耐药基因MDR1(P-gp)蛋白表达及相关分析研究

目的观察乳腺癌组织中雌孕激素受体(ER、PR)与C-erbB-2基因、多药耐药基因MDR1(P-gp)的蛋白表达并探讨其相互关系.方法 用免疫组织化学法(EnVision法)对109例术前未行化疗的乳腺癌手术切除标本福尔马林固定、石蜡包埋组织进行ER、PR、C-erbB-2、MDR1(P-gp)检测,结果作统计学分析.结果 ①ER、PR阳性表达率分别为55.0%和43.1%;②C-erbB-2、MDR1(P-gp)的阳性表达率各为54.1%和15.6%,乳腺导管内癌患者的C-erbB-2阳性表达高于浸润性导管癌的患者(P<0.05);③ER、PR均阳性患者的C-erbB-2阳性表达明显低于ER、PR均阴性患者(P<0.05),ER阳性组的C-erbB-2阳性表达明显低于ER阴性组(P<0.05).结论 ER、PR与C-erbB-2基因在乳腺癌中有一定的内在联系,C-erbB-2表达与ER表达呈负相关;多药耐药基因MDR1(P-gp)的表达与ER、PR无关.     

乳腺浸润性导管癌组织中fascin的表达及预后意义

目的 探讨fascin在乳腺浸润性导管癌组织中的表达及其临床病理意义.方法 采用免疫组化法检测88例乳腺浸润性导管癌组织中fascin的表达情况,分析其与ER、PR和HER2表达及乳腺浸润性导管癌预后的关系.结果 乳腺正常导管上皮和浸润性导管癌组织中fascin的阳性率分别为9.1%(1/11)和48.86%(43/88),乳腺浸润性导管癌组织中的阳性率明显高于乳腺正常导管上皮组织(P<0.05),其阳性率与腋淋巴结转移状况、组织学分级和TNM分期呈正相关(P<0.05),并且在ER和PR阴性组中明显高于阳性组(均P＜0.05),而在HER2阳性组中明显高于阴性组(P<0.05).fascin阳性表达患者的术后生存时间明显短于阴性患者(P<0.05).结论 fascin可能在乳腺浸润性导管癌的浸润转移过程中发挥重要作用,其阳性表达提示预后较差.     

乳腺增生病动物模型的建立及ER、PR表达的观察

目的了解乳腺增生病模型大鼠的发病机制,观察病理形态及雌激素受体(ER)、孕激素受体(PR)免疫反应阳性细胞表达情况。方法将26只W istar雌性未孕大鼠随机分为对照组(13只)和模型组(13只),采用苯甲酸雌二醇联合黄体酮肌注30 d建立大鼠乳腺增生病模型,对照组仅给予大鼠肌肉注射生理盐水。观察大鼠第2、3对乳房病理组织形态(肉眼、镜下),采用免疫组化法测定大鼠第2、3对乳腺组织中ER、PR表达情况。结果模型组中第2、3对乳头高度显著增高,镜下形态符合乳腺增生症,ER、PR阳性强度、数量随着乳腺增生程度加重而增加。结论大量外源性雌二醇刺激下可使大鼠乳腺组织增生。ER、PR在乳腺中的表达情况与乳腺增生程度密切相关。     

Metabotropic glutamate receptors: an original family of G protein-coupled receptors

Summary— In 1985, we discovered a new glutamate receptor which was coupled to phospholipase C via a G protein and which was later termed metabotropic glutamate receptor (mGluR). In this review, both the diversity of mGluRs and the cellular events they control are discussed, as well as their roles in physiological regulation and brain function.     

Detection of steroid receptors in breast cancer: Relationship between EIA and IHC methods

Lerma E, Esqué C, Peiró G, Mora J, Cerdá I, Prat J. Detection of steroid receptors in breast cancer: relationship between EIA and IHC methods. Scand J Clin Lab Invest 1994; 54: 591-4

The efficiency of EIA and IHC (frozen tissue) in the detection of ER and PR in 51 breast cancers were compared. ER were detected in 51 % of cases by IHC and in 49% of tumours by EIA. PR were detected in 56.8% of cases by IHC and in 54.8% of tumours by EIA. Concordance of the results of IHC and EIA reached 78.4% in ER and 82.4% in PR detection. Discordance between IHC and EIA seems to be related to minor changes in sensibility of methods, but we cannot conclude that one of the two techniques is superior to the other in the detection of hormonal receptors. There is a common trend of association between low grade of histologic or nuclear malignancy and a high expression of hormonal receptors.     

Leukotriene receptors in atherosclerosis

Leukotriene‐forming enzymes are expressed within atherosclerotic lesions and locally produced leukotrienes exert pro‐inflammatory actions within the vascular wall by means of cell surface receptors of the BLT and CysLT receptor subtypes. The migration and accumulation of inflammatory cells that follow leukotriene receptor activation have been implicated in atherosclerosis initiation and progression. Leukotriene receptors are in addition expressed on endothelial and vascular smooth muscle cells, associated with intimal hyperplasia in early atherosclerosis and restenotic lesions after angioplasty. Taken together, recent evidence suggests that leukotriene receptors may be a potential target in the treatment of atherosclerosis and in the prevention of restenosis after coronary interventions.     

Platelet hyperreactivity, scavenger receptors and atherothrombosis

Summary.  Scavenger receptors (SRs) were initially identified as macrophage receptors that recognize modified lipoproteins. The lists of SRs, their ligands and cells expressing SRs have been significantly extended during the last two decades. What has become clear is that many ligands of SRs are present in vivo only in pathologic conditions. Several SRs have been identified on platelets with the best studied being scavenger receptors CD36 and SR-BI. Platelet SRs are multiligand receptors with properties of pattern recognition receptors. CD36 and SR-BI are exposed on resting platelets, while other SRs are rapidly expressed upon platelet activation. Thus, platelets may serve as sensors of 'pathologic ligands' in circulation. The role of platelet SRs in platelet physiology is still poorly understood. However, the data are accumulating that SR ligands, present in the circulation under pathologic conditions, interact with platelet SR and modulate platelet reactivity, thereby contributing to thrombosis and cardiovascular pathology.     

Pathogen recognition by innate receptors

Microbial infection elicits host immune responses through germline-encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are evolutionarily conserved membrane-bound PRRs that recognize a broad spectrum of microbial components. Recent studies have clarified that two classes of cytosolic receptors, retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) and nucleotide binding oligomerization domain (NOD)-like receptors (NLRs), play important roles in the cytosolic recognition of invading pathogens. After microbial infection, the host utilizes these receptors differentially to mount robust immune responses. This review will describe pathogen recognition by these receptors, signaling pathways, and their in vivo roles in innate antiviral immunity.     

Significance of the imidazoline receptors in toxicology

Introduction. The alpha-2 adrenergic (AA-2) receptor agonists and imidazolines are common exposures in the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS). Although the interaction between the AA-2 receptor and imidazoline receptors has been extensively studied, it largely remains unknown to health-care professionals. This review describes these interactions and mechanisms by which agonists affect physiologic responses binding to these receptors. Methods. Papers published in English from 1960 to 2013 were retrieved from PubMed. A total of 323 original articles were identified and 173 were included. Background. The toxicity associated with clonidine (e.g., bradycardia, miosis, and hypotension) is largely assumed to be secondary to the functional overlap of the AA-2 receptors and the mu receptors. However, the effects at the AA-2 receptor could not fully account for these symptoms. Subsequently, clonidine was found to produce its pharmacologic effect in the central nervous system (CNS) by interaction not only with the AA-2 receptor but also on selective imidazoline receptors. Imidazoline receptors. Since their discovery, three distinct classes of imidazoline receptors, also known as imidazoline binding sites or imidazoline/guanidinium receptive sites, have been characterized. Imidazoline-1 (I-1) receptors are involved in the hypotensive activity of clonidine and related compounds supporting the idea that the I-1 receptors are upstream from the AA-2 receptor and work in tandem for its effect on blood pressure. Additionally, stimulation of N-type Calcium-2 channels, G-protein inwardly rectifying potassium channel, adenosine receptors, phosphatidyl-choline-specific phospholipase C, and nicotinic receptors have been implicated to be involved. Previous studies have shown that I-1 receptors may also be involved in other physiologic responses beyond cardiac function. Imidazoline-2 (I-2) receptors interact with monoamine oxidase A and monoamine oxidase B leading to research that has focused on the effect of I-2 receptors and depression and the suggestion of a possible antidepressant action of the imidazolines. I-2 receptor ligands may have substantial antinociceptive activity and work synergistically with opioids in acute pain. Imidazoline-3 (I-3) receptors are located on the pancreatic β-cells and modulate glucose homeostasis. Imidazoline ligands. Four endogenous compounds have been found to bind and include clonidine-displacing substance, agmatine, harmane, and imidazole acetic acid. Significant interest in developing new agents with higher selectivity and affinity for I-1 receptors has resulted. Toxicology. Alpha-2 adrenoceptor and imidazoline receptor agonists such as clonidine and tetrahydrozoline are common ingestions reported to poison control centers. The most common toxic effects of clonidine are similar to those of the over-the-counter imidazolines and include CNS depression, bradycardia, hypotension, respiratory depression, miosis, hypothermia, and hypertension (early and transient). Based on their structure and subsequent studies, imidazoline receptors seem to be the primary binding site for these chemicals. Case reports typically illustrate rapid onset of action with serious side effects following ingestion of relatively small amounts. These agents have been reportedly used in drug-assisted sexual assaults. Conclusion. Much of the toxicity associated with drugs such as clonidine, guanfacine, and tetrahydrozoline are due to their binding to imidazoline receptors. Knowledge of the imidazoline receptors may lead to new therapeutic agents and inform management of patients with imidazoline overdose.     

Functional characterization of pheromone receptors in the tobacco budworm Heliothis virescens

Functional analyses of candidate Heliothis virescens pheromone odorant receptors (HvORs) were conducted using heterologous expression in Xenopus oocytes. HvOR6 was found to be highly tuned to Z9-14:Ald, while HvOR13, HvOR14 and HvOR16 showed specificity for Z11-16:Ald, Z11-16:OAc and Z11-16:OH, respectively. HvOR15, which had been considered a candidate receptor for Z9-14:Ald did not respond to any of the pheromone compounds tested, nor to 50 other general odorants. Thus, while HvOR15 is specifically expressed in H. virescens male antennae, its role in pheromone reception remains unknown. Based on our results and previous research we can now assign pheromone receptors in H. virescens males to each of the critical H. virescens agonistic pheromone compounds and two antagonistic compounds produced by heterospecific females.     

Positron emission tomography studies of brain receptors

Probing the regional distribution and affinity of receptors in the brain, in vivo, in human and non human primates has become possible with the use of selective ligands labelled with positron emitting radionuclides and positron emission tomography (PET). After describing the techniques used in positron emission tomography to characterize a ligand receptor binding and discussing the choice of the label and the limitations and complexities of the in vivo approach, the results obtained in the PET studies of various neurotransmission systems: dopaminergic, opiate, benzodiazepine, serotonin and cholinergic systems are reviewed.     

Soluble cytokine receptors in biological therapy

Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel?, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-α antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects.     

Glucocorticoid modulation of muscarinic and β-adrenergic receptors in guinea pig lung

Summary— We investigated the effect of the in vivo treatment of guinea pigs with methylprednisolone, 10 mg/kg daily, on lung muscarinic and β-adrenergic receptors. Receptor densities were assessed by saturation experiments of tritiated N-methylscopolamine and dihydroalprenolol binding to lung membranes. After 3 h of treatment, methylprednisolone induced a decrease of 19.2% ( P < 0.05) of muscarinic receptors but was without effect on β-adrenergic receptor density. After 24 h, an increase of 39.7% ( P < 0.01) and 16.9% ( P < 0.05) was observed for muscarinic and β-adrenergic receptors, respectively. For muscarinic receptors, this increase reached 53.4% ( P < 0.01) within 48 h and stayed at this level until 96 h. The increase of β-adrenergic receptors was maximal (24.9%) after 72 h and returned to the control value after 96 h. The dissociation constant (K_d) values of both ligands were not affected by the glucocorticoid treatment. Functional studies showed that the 96 h treatment did not affect the contractile response of guinea pig lung parenchymal strips to carbachol since the 50% concentration value (EC₅₀) and the maximal contraction value (E_max) were not significatively different from control values. These data show that glucocorticoids control the expression of both muscarinic and β-adrenergic receptors in guinea pig lung but with different time courses and to a larger extent for muscarinic receptors. The glucocorticoid treament did not modify the contractile response of lung strips to carbachol, confirming the absence of effect on the affinity of muscarinic receptors and suggesting that the receptor reserve exceed the increase of their density by the steroid.