肾上腺节细胞神经瘤临床病理学分析

目的探讨肾上腺节细胞神经瘤的发病因素、病理结果、临床表现及诊疗与转归。方法对7例肾上腺节细胞神经瘤的临床表现及病理报告进行分析、讨论。结论肾上腺节细胞神经瘤是一种良性肿瘤,一般临床症状不明显。大多为体检时B超及CT检查发现的,手术切除是其主要的治疗方法,多数预后良好。病理结果一般无内分泌功能,是一种起源于原始神经嵴细胞的良性肿瘤。     

钙蛋白酶参与tau蛋白过度磷酸化及截断机制研究进展

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,临床表现为认知和记忆功能障碍。从神经病理学的角度来看,这种疾病的特征是细胞外老年斑的积累以及tau蛋白过度磷酸化导致的神经纤维缠结,局部神经元功能障碍和树突的退化。除了上述特征之外,近几十年的研究表明,钙蛋白酶(calpain)在细胞中广泛地被激活,钙蛋白酶的紊乱也是引起AD病理中tau蛋白过度磷酸化的一个重要原因。本文就钙蛋白酶生理特性和在发病过程中钙蛋白酶对蛋白的病理调控机制进行综述。     

前列腺病变组织中神经内分泌细胞的电镜与免疫组织化学特征及意义

目的　应用透射电镜技术及免疫组织化学技术对正常前列腺组织、前列腺增生及前列腺癌中神经内分泌细胞 (N ECs)进行观察 ,并探讨其超微形态诊断特点及意义。方法　对 10名正常前列腺组织、2 0例前列腺增生症及 4 0例前列腺癌组织中神经内分泌细胞通过透射电镜进行观察并与嗜铬素 (Cg A)、神经元特异性烯醇化酶 (NSE)和其他 6种激素抗体免疫组织化学染色进行对比观察。结果　前列腺癌中 32例含有神经内分泌细胞 ,依内分泌颗粒的形态不同可分为三种类型 ,前列腺增生症中神经内分泌细胞的形态与正常前列腺组织相似 ,但数量有明显变化。Cg A和 NSE的阳性率随着前列腺癌的组织学分化程度由高到低而逐渐增高 ;随着 Whitmore临床分期由 A到 D期 ,Cg A、NSE抗体的阳性率及其他 6种抗体的阳性率也逐渐增高。结论　不同的前列腺病变组织中 N ECs的类型及数量不同 ,前列腺增生症 NECs数量明显高于正常前列腺组织 ,含有 NECs的前列腺癌较不含 NECs的前列腺癌更易发生癌转移。 NECs与前列腺癌的转移及分化程度密切相关     

胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌临床病理及预后分析

　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　【摘要】目的 探讨胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的临床病理及预后。方法 回顾性分析61例胃癌伴神经内分泌分化和34例胃混合性腺神经内分泌癌患者的临床病理资料,对其组织化学及免疫组织化学染色进行观察。结果 胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌患者肿瘤发病部位、远处转移及区域淋巴结转移差异有统计学意义（P<0.05）;SyN 、CgA和CD56三者阳性表达率差异有统计学意义（P<0.05）;区域淋巴结转移和远处转移2个因素与预后相关（P<0.05）;胃混合性腺神经内分泌癌患者术后生存期短于胃癌伴神经内分泌分化患者（P<0.05）。结论 免疫组化染色对胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的确诊具有重要意义,肿瘤神经内分泌细胞数量的多少对患者预后评估及辅助治疗有指导意义。      

胃肠道神经内分泌肿瘤的临床病理探讨

目的分析胃肠道神经内分泌肿瘤的临床表现和病理特点,以提高对该类疾病的认识。方法选取2012年3月至2013年3月我院经病理证实为神经内分泌肿瘤的胃肠道病变36例,对肿瘤进行常规镜检,并做免疫组化检测。比较不同类型肿瘤的发病年龄、分布部位、临床表现及组织病理特征。结果 36例患者可分为4型,高分化神经内分泌肿瘤G1 16例、高分化神经内分泌肿瘤G2 10例、神经内分泌癌8例和混合性腺神经内分泌癌2例。其中来自前肠19例,中肠9例,后肠8例。不同类型胃肠道神经内分泌肿瘤的病理表现各有不同。结论胃肠道神经内分泌肿瘤临床表现不典型,免疫组化的合理应用可提高神经内分泌癌的诊断率新的病理学分类方法更加客观准确。     

神经系统疾病TNF测定意义探讨

对 TNF在不同神经系统疾病发病中的意义进行了分析探讨。 TNF能介导产生其他细胞因子和神经内分泌递质 ,引起酶活性和免疫功能状态的改变 ,在神经系统疾病的发病中起重要作用 ,导致疾病的发生。     

JNK信号通路与神经退行性疾病

c-JunN端蛋白激酶(JNK)是细胞功能的重要激酶,在各种刺激以及生理状态下导致神经元凋亡中起着重要的作用。JNK主要与一些神经退行性疾病有着密切的关系。理解JNK信号通路能够为将来选择JNK作为靶点干预这些疾病条件。JNK参与这些神经退行性疾病的发病机制,因此抑制其活性成为有效治疗的靶点。     

前列腺偶发癌15例诊治分析

目的讨论前列腺偶发癌的发病情况和治疗效果。方法回顾性分析2002～2007年行前列腺电切术及经膀胱前列腺摘除术440例患者的资料,术后病理诊断前列腺癌15例,14例行睾丸切除术并内分泌治疗,1例给予内分泌治疗,随访观察。结果前列腺偶发癌的检出率为3.41%,所有患者随访8个月至8年,未见前列腺癌转移及致死病例。结论前列腺偶发癌的检出率低于国内相关报道,缺乏特异性的临床表现,诊断有赖于术后病理,多数患者可采用手术及内分泌治疗。     

促肾上腺皮质激素释放激素与结肠功能

肠易激综合征(Irritable bowel syndrome)、溃疡性结肠炎、消化性溃疡等众多消化系疾病．可冈情绪、生活事件、疾病等应激因素而促发或使病情加重。越来越多的研究显示应激可影响消化道生理功能。而促肾上腺皮质激素释放激素(Corticotropin—releasing hormone，CRH)作为重要的应激激素．广泛地分布于中枢及外周组织，参与神经内分泌、自律性、行为学、炎症反应和神经精神疾病的调控。目前的研究认为CRH广泛参与消化道生理／病理活动的调控。CRH对消化道疾病特别是可因情绪等因素促发或加重病情的IBS和炎症性肠病（IBD）的发病有重要作用．认为CRH拈抗剂将是有效治疗IBS和IBD的药物。本文就CRH参与结肠渊控及与IBS关系做一综述。     

宫颈神经内分泌癌的临床病理分析

目的 探讨宫颈神经内分泌癌的临床病理分析。方法 回顾性分析我院近10年病理存档的全部宫颈神经内分泌癌4例,将患者的临床病理资料,病理切片经光镜下观察并进行免疫组化染色,结合相关文献进行分析。结果 4例宫颈神经内分泌癌病例,患者年龄33～56岁（平均年龄41岁）,临床表现为阴道出血（4/4）。组织学均为单纯型小细胞癌,肿瘤细胞呈弥漫浸润性生长,细胞体积小,大小一致,呈圆形或短梭型,胞质少、核深染、核分裂像多见（70～90/10个高倍视野）,均可见明显坏死。免疫组化表型：4例病例均同时表达CgA、CD56或Syn 3种神经内分泌标记物中的2种或以上。结论 宫颈神经内分泌癌是一种少见的高度恶性肿瘤,以小细胞癌为主,预后极差。诊断依靠其独特的形态学特征和免疫组化特点,应与宫颈转移性小细胞癌、小细胞型鳞癌及非霍奇金淋巴瘤等疾病进行鉴别诊断。     

Interaction of tobacco-specific toxicants with the neuronal alpha(7) nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders

Pulmonary neuroendocrine cells function as hypoxia-sensitive chemoreceptors, and they release peptides and biogenic amines that are important mediators of pulmonary neonatal adaptation. Some of these products additionally act as autocrine growth factors. Increased numbers of pulmonary neuroendocrine cells have been observed in several smoking-associated pediatric lung disorders such as bronchopulmonary dysplasia, cystic fibrosis, sudden infant death syndrome, and asthma. Disturbed pulmonary neuroendocrine function has been implicated in the etiology of this disease complex. One of the most common smoking-associated lung cancer types, small cell lung carcinoma, expresses phenotypic and functional features of pulmonary neuroendocrine cells. We, as well as others, have shown that the release of the autocrine growth factors 5-hydroxytryptamine (5-HT, serotonin) and mammalian bombesin/gastrin releasing peptide (MB/GRP) by cell lines derived from human small cell lung carcinoma or fetal hamster pulmonary neuroendocrine cells are regulated by a neuronal nicotinic acetylcholine receptor comprised of alpha(7) subunits. In radio-receptor assays, nicotine and the nicotine-derived carcinogenic nitrosamines NNNN. Binding of nicotine or NNK to the alpha(7) receptor resulted in calcium influx and overexpression and activation of the serine-threonine protein kinase Raf-1. In turn, this event lead to overexpression and activation of the mitogen activated (MAP) kinases extracellular signal regulated kinase 1 (ERK1) and extracellular signal regulated kinase 2 (ERK2) and stimulation of DNA synthesis accompanied by an increase in cell numbers in fetal pulmonary neuroendocrine cells and small cell carcinoma cells. Exposure of fetal pulmonary neuroendocrine cells for 6 days to NNK caused a prominant up-regulation of Raf-1. Our findings suggest that chronic exposure to nicotine and NNK in pregnant women who smoke may up-regulate the alpha(7) nicotinic receptor as well as components of its associated mitogenic signal transduction pathway, thus increasing the susceptibilities of the infants for the development of pediatric lung disorders. Similarly, up-regulation of one or several components of this nicotinic receptor pathway in smokers may be an important factor for the development of small cell lung carcinoma.     

Neuropeptides as autocrine growth factors in cancer cells

Neuropeptides can function as autocrine growth factors in cancer cells. High levels of bombesin (BB) and neurotensin (NT)-like immunoreactivity are present in small cell lung cancer (SCLC), a neuroendocrine tumor. Vasoactive intestinal peptide (VIP) stimulates and somatostatin (SST) inhibits the release of BB-like peptides from SCLC cells. BB-like peptides bind to BB(2) receptors, which are present on the cell surface. BB-like peptides stimulate the mitogen activated protein kinase (MAPK) cascade leading to increased expression of nuclear oncogenes and growth factors in SCLC cells. Due to the high density of neuropeptide receptors present on the cell surface, SST analogs have been radiolabeled to image neuroendocrine tumors. VIP receptors are present in many epithelial cancers including breast, colon, non-small cell lung cancer (NSCLC), pancreatic and prostate cancers. Due to the high density of VIP receptors on lung cancer cells, radiolabeled VIP agonists may be used to image these tumors. VIP receptor antagonists, such as VIPhybrid, inhibit the growth of cancer cell lines in vitro and in vivo. VIPhybrid and SR48692, a NT receptor antagonist, potentiate the cytotoxicity of chemotherapeutic drugs. These results suggest that neuropeptide receptor antagonists may be useful in the treatment of cancer.     

Jolkinolide B induces neuroendocrine differentiation of human prostate LNCaP cancer cell line

Euphorbia fischeriana is a Chinese herbal medicine which has been reported to possess chemotherapeutic effects, yet the underlying mechanism is unclear. In order to understand its possible anti-tumor property, we have isolated a number of chemical compounds from the roots of this plant [Phytochemistry 52 (1999) 117] and studied their in vitro effects by using human prostate LNCaP cancer cell line. Among the six compounds tested, jolkinolide B exhibited the most potent anti-proliferative activity (IC(50)=12.5 microg/mL=40 microM) and it inhibited DNA synthesis by down-regulating bromodeoxyuridine (BrdU) incorporation in LNCaP cells in a dose-dependent manner. Jolkinolide B, at concentrations up to 25 microg/mL, induced G1 arrest and neuroendocrine differentiation of LNCaP cells. Immunoblotting analysis confirmed the increased expression of neuroendocrine markers, keratin 8/18 (K8/18) and neuron specific enolase (NSE), in these cells. Apoptotic bodies and DNA fragmentation were observed by fluorescence microscopy and flow cytometry when the cells were exposed to a concentration higher than 25 microg/mL jolkinolide B. Taken all data together, jolkinolide B seems to play a role in the regulation of proliferation, differentiation, and apoptosis of LNCaP cells.     

Influence of Exposure to Extremely Low Frequency Magnetic Field on Neuroendocrine Cells and Hormones in Stomach of Rats

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatin-positive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in BaSO₄ suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.     

Monoclonal antibodies and prostate-specific membrane antigen

Efforts are increasing to identify and evaluate diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), a transmembrane protein highly expressed in all types of prostatic tissue (eg, benign epithelium, benign prostatic hyperplasia, prostatic intra-epithelial neoplasia and adenocarcinomas, with increased binding affinity for malignant cells), is becoming an increasingly important diagnostic and therapeutic marker, not only for prostate cancer, but possibly for other malignant lesions. Recent studies have demonstrated PSMA expression in endothelial cells of tumor-associated neovasculature (including carcinoma of the colon, breast, bladder, pancreas, kidney and melanoma), thus greatly expanding its possible beneficial role, especially as new anti-PSMA mAbs continue to be developed and refined. Future diagnostic and therapeutic interventions utilizing these antibodies will become increasingly important in not only prostate cancer but perhaps many other different malignancy types.     

Enzymatic changes in the male reproductive organs by delta-9-tetrahydrocannabinol

Like most psychoactive agents, cannabis and its active component delta-9-tetrahydrocan-nabinol (Δ⁹-THC) have been reported to affect the neuroendocrine axis in animals. The effect of Δ⁹-THC on some of the functionally important enzymes of the male reproductive organs are reported. The study indicates that Δ⁹-THC reduces the activities of the enzymes, β-glucuronidase, α-glucosidase acid phosphatase and fructose-6-phosphatase in a dose related manner in the testis, prostate as well as in the epididymis. It may be concluded that Δ-THC may interfere with the normal functioning of the male reproductive organs.     

Stem cell-derived in vitro models for investigating the effects of endocrine disruptors on developing neurons and neuroendocrine cells

Neuroendocrine cells are a set of specialized hormone-releasing neurons that control most vital functions in humans and wildlife, such as growth, reproduction, metabolism, and stress responses. Increasing evidence points to neuroendocrine cells as the primary neuronal target of endocrine disruptors. Endocrine disruption appears to be most significant during prenatal and early postnatal development. However, limitations with traditional cell culture models of neuronal development led to a lack of understanding regarding the mechanisms by which endocrine disruptors affect neurodevelopment. In recent years, Stem Cell-derived neuronal models have become available and may offer distinct advantages over other in vitro model systems for investigating the effects of endocrine disruptors on the developing brain. Further, recently new models of Stem Cell-derived neuroendocrine cells that may provide more effective ways for studying the effects of endocrine disruptors directly on developing neuroendocrine cells in vitro were developed. This constitutes a review of currently available cell models of developing neurons that have been used to investigate in vitro effects of endocrine disruptors on developing brain. The review also presents recently developed models of Stem Cell-derived neuroendocrine cells that might be used to investigate in vitro effects of endocrine disruptors and their mechanisms of action directly on the developing neuroendocrine cells.     

Neuropeptide receptor status in human tumor cell lines

Tumor types expressing a neuroendocrine phenotype secrete neuropeptides with paracrine or autocrine growth factor activity. The efficacy of these paracrine or autocrine loops depends on the expression of specific receptors on tumor cells. Once specific receptors are identified, specific neuropeptide antagonists disrupting paracrine and autocrine loops could be potential treatments in neuropeptide-secreting tumors. In the present study, 11 human tumor cell lines representing astrocytoma, lymphoma, and pancreatic, prostate, lung and colon carcinomas were examined for expression of five different neuropeptide receptors (cholecystokinin, neurotensin, vasopressin, tachykinine substance P and cannabinoid) using RT-PCR and radioligand binding. The presence of various neuropeptide receptors in different human cancer cell lines supports development of new antitumor treatments based on disruption of neuropeptide autocrine growth pathways.     

Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro prostate cell models

Prostate cancer is the most commonly diagnosed malignancy in the United States, as well as in the Western world, and the second leading cause of male cancer death in the United States. Despite its high incidence, the molecular and genetic events involved in prostate cancer progression remain poorly understood. A hurdle in understanding the molecular genetic changes in prostate cancer has been the difficulty in establishing premalignant lesions and primary prostate tumors as in vitro cell cultures. Primary epithelial cells grow for a finite life span and then senesce. Immortalization is defined by continuous growth of otherwise senescing cells and is believed to represent an early stage in tumor progression. In order to examine these early stages, we and others have developed in vitro models of prostate epithelial cell immortalization. Because prostate cancer is a multistep, progressive disease with a typical onset later in life and with an usually high number of latent cases that do not develop into clinically manifest cancer, the steps in the progression to malignancy are of particular interest. To understand the many factors that are suspected to contribute to the development of this malignancy, there is a need for an in vitro multistep human prostate epithelial culture system. These models have been extremely important in identifying genetic and molecular changes involved in prostate cancer progression. Recently, novel human cell culture models for the study of prostate cancer have been developed. Successful establishment of primary prostate cancer cell lines from patients' familial and sporadic prostate cancer has been accomplished using telomerase, the gene that prevents cellular senescence. The novel models will be useful for identification and characterization of prostate cancer genes and will provide the new means for testing for chemoprevention and chemotherapeutic agents.