自发性树鼩乳腺肿瘤的特性(英文)

乳腺癌是严重危害女性健康的常见恶性肿瘤,建立合适的乳腺癌动物模型对于研究人类乳腺癌的生物学机制及发展新的防治方法至关重要。相对于常用的啮齿类动物,树鼩(Tupaia belangeri chinensis,tree shrew)因在进化层次上更接近于人类而可用于建立更适合的乳腺癌模型。该文详细了介绍一例树鼩自发性乳头状良性乳腺肿瘤。免疫组化结果显示该例肿瘤孕激素受体阳性且Ki-67阳性细胞比例显著增加;而活化的Caspase3阳性细胞比例较低;且肿瘤的形态和病理与人导管内乳头状肿瘤非常接近。提示利用树鼩建立乳腺肿瘤模型的可行性。     

树鼩在医学实验研究中的新进展

树鼩的许多生物学特性近似于人类,人们利用树鼩成功建立了多种人类病毒感染的动物模型,并在肿瘤、内分泌、神经、视觉等方面有相当广泛和深入的应用和研究。本文概述了树鼩在医学实验研究中的新进展。     

正常猕猴与树鼩神经系统和免疫系统组织中大麻素与阿片受体的表达

为应用猕猴和树鼩动物模型研究毒品成瘾对神经/免疫系统的影响提供基础数据,对大麻素及阿片受体在正常猕猴和树鼩神经系统和免疫系统的表达进行初步确定.采集正常猕猴和树鼩新鲜组织(皮质、小脑、脑干、海马、脊髓、脾脏),应用半定量逆转录PCR和实时定量PCR的方法检测大麻素与阿片受体mRNA在猕猴和树鼩各组织中的表达情况.猕猴脑部各区包括脾脏均表达大麻索受体1(CNR1),而大麻素受体2(CNR2)只表达于脾脏内.三类阿片受体中,mu(μ)受体表达最为广泛,在以上各组织中均有表达;delta(δ)受体表达的组织最少,只在海马表达;kappa(κ)受体表达介于两者之间,分别在皮质、小脑、脑干、脊髓中表达.在树鼩组织中,CNR1和CNR2表达于整个大脑重要脑区中,且CNR1表达量高于同一区域内CNR2表达的鼍:脾脏中CNR2的表达较高,而CNR1不表达.三类阿片受体只有检测到μ受体在脑部与脾脏表达,且在各个脑区的表达量明显高于脾脏的表达量;δ体和κ受体在被检各个组织中均无表达.总体而言,两种大麻素受体在猕猴和树鼩体内表达情况与人类和鼠的情况类似,而三类阿片受体在猕猴体内表达情况与人类吏为接近.猕猴和树鼩可能可用于人类毒品成瘾的研究;猕猴在某些神经受体的表达更接近人类,其在研究毒品成瘾的机理和对免疫系统的影响方面仍有不可替代的地位.     

树鼩何杰金氏病二例报告

树鼩(Tupaia belangeri chinensis)在我国西南地区广为分布。自从1966年埃利奥特(Elliot)等人报道1例雌性树鼩的乳腺腺癌以来,对于树鼩的自发性肿瘤报道甚少。笔者在进行120     

乳腺癌组织中FOXO1蛋白表达与细胞增殖和细胞凋亡的相关性

目的研究乳腺癌组织中FOXO1蛋白表达与细胞增殖和细胞凋亡的相关性。方法利用免疫组织化学技术检测60例乳腺浸润性导管癌、21例导管内癌、30例导管内乳头状瘤及15例正常乳腺组织中FOXO1、Ki-67及活化Caspase-3蛋白的表达。结果FOXO1及活化Caspase-3蛋白在乳腺浸润性导管癌和导管内癌中的阳性表达率和阳性表达强度均显著低于导管内乳头状瘤和正常乳腺组织。Ki-67蛋白在乳腺浸润性导管癌和导管内癌中的阳性表达率和阳性表达强度均显著高于导管内乳头状瘤和正常乳腺组织;浸润性导管癌中FOXO1、Ki-67及活化Caspase-3的表达强度与癌组织的病理学分级无关;在浸润性导管癌、导管内癌、导管内乳头状瘤及正常乳腺组织中,FOXO1蛋白的表达强度与Ki-67呈显著负相关,而与活化Caspase-3的表达强度呈显著正相关。结果 FOXO1蛋白的表达下调可能与乳腺导管癌的发生密切相关;该蛋白可能是一种细胞增殖的负性调节因子,同时亦是一种细胞凋亡促进因子,FOXO1基因有可能成为乳腺浸润性导管癌基因治疗的有效靶点。     

血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系

目的探讨血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系。方法免疫组化法检测21例乳腺增生组和68例乳腺浸润性导管癌组病灶组织内VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性标志物D2-40标记肿瘤新生淋巴管,计数肿瘤淋巴管的密度（LVD）。结果乳腺浸润性导管癌组VEGF-C的表达和淋巴管的密度（LVD）都明显高于乳腺增生组（P〈0．01）;乳腺浸润性导管癌中VEGF-C阳性组中淋巴管的密度（11．32±5．78）与VEGF-C阴性组中的淋巴管密度（8．75±3．53）,差别有统计学意义（P〈0．01）;乳腺浸润性导管癌中VEGF-C蛋白的表达和淋巴管密度（LVD）都与有无腋窝淋巴结转移及淋巴结转移个数有关（P〈0．05）。结论VEGF-C在乳腺浸润性导管癌淋巴管的生成中起着重要的作用;VEGF-C的高表达和淋巴管密度（LVD）的升高是促进乳腺导管癌淋巴结转移的重要的影响因素。     

实验动物树鼩和人类疾病的树鼩模型研究概述

动物模型在生物医学领域(如回答人体各种重大生物学问题、解析人类疾病机理和新药研发等方面)已经做出了不可替代的巨大贡献。转化医学存在的问题使得树鼩(Tupaia belangeri chinensis)实验动物重新得到重视;人类疾病的树鼩模型也再次受到越来越多的关注。该文综述了国内外特别是近年来我国树鼩研究进展,包括树鼩基础生物学及动物模型方面取得的成绩,并分析了该领域目前存在的困难和问题,探讨了未来的一些研究方向。     

乳腺癌组织中VEGF—C和p38MAPK的表达及与伴淋巴结转移的关系

目的探讨乳腺浸润性导管癌组织中血管内皮生长因子C（VEGF—C）和丝裂原激活蛋白激酶p38（p38MAPK）的表达关系,以及与乳腺浸润性导管癌淋巴结转移等生物学行为的关系。方法采用免疫组织化学sP法检测70例乳腺浸润性导管癌组织及15例癌旁正常组织中VEGF-C和p38MAPK蛋白的表达,并采用Westernblot法检测13例伴有淋巴结转移的乳腺癌及12例无淋巴结转移的乳腺癌的新鲜组织中VEGF—C和p38MAPK蛋白表达。结果VEGF—C和p38MAPK在乳腺浸润性导管癌组织中的表达（阳性率分别为67．0％和61．4％）明显高于癌旁正常组织;VEGF-C和p38MAPK蛋白在伴有淋巴结转移组的乳腺癌组织中的表达均高于无淋巴结转移组（P=0．005,P=0．005）;在乳腺浸润性导管癌组织中VEGF-C和p38MAPK表达存在显著正相关（r=0．383,P=0．001）,并与乳腺浸润性导管癌的TNM分期（P=0．019,P=0．010）有关;VEGF-C和p38MAPK蛋白表达与乳腺浸润性导管癌肿块的大小（P=0．203,P=0．086）和患者的年龄（P=0．0．266,P=0．087）无明显关系。Western blot也证实,VEGF-C和p38MAPK蛋白在有淋巴结转移组中表达高于无淋巴结转移组。结论VEGF-C和p38MAPK的蛋白表达与乳腺浸润性导管癌的淋巴结转移密切相关,其有望成为乳腺癌治疗的新靶点。     

树鼩的血相

关于树鼩(Tupaia belangeri chinensis)和它的分类至今还有争论。一些学者将其归入食虫目,另一些学者则根据其性周期和神经系统接近于灵长目的特点,又把它划归灵长目。总之,树鼩目前尚处于一个独特的位置上,其分类有待确定。 1981年有人用甲、乙型肝炎病毒感染树鼩,已见可喜的苗头。继之,轮状病毒又感染树鼩成功。在血脂代谢的研究方面,已有人将其用作动物模型。另外,G.Darai等人发现树鼩还有多种自发性肿瘤,其中之一是何杰金氏病——淋巴结恶性肿瘤,因此,树鼩也可     

乳腺浸润性导管癌组织中CAS蛋白表达的临床病理意义

目的研究乳腺浸润性导管癌组织中细胞凋亡易感蛋白（CAS）表达的临床病理意义。方法选取乳腺浸润性导管癌53例、普通导管增生20例、异型导管增生20例、导管原位癌10例、正常乳腺组织14例,应用免疫组化方法观察CAS蛋白的表达,并探讨CAS与乳腺癌临床病理因素的关系,分析CAS和HER2、ER、PR以及ki-67指数的关系。结果 CAS在正常乳腺、普通导管增生、异型导管增生、导管原位癌、浸润性导管癌中的阳性率逐渐升高,分别为14.3%、25.0%、40.0%、60%、75.5%（P=0.000）,CAS、HER2均与乳腺癌组织学分级、核分裂像、淋巴结转移有关;CAS评分与ki-67指数（r=0.439,P=0.003）和HER2评分（r=0.598,P=0.000）正相关。结论 CAS与乳腺癌的发生、发展、增殖、淋巴结转移有关,可能作为反映乳腺癌生物学行为的肿瘤标记物,CAS蛋白的表达和HER2有一定的相关性。     

Characterization of tree shrew telomeres and telomerase

The use of tree shrews as experimental animals for biomedical research is a new practice. Several recent studies suggest that tree shrews are suitable for studying cancers, including breast cancer, glioblastoma,lung cancer, and hepatocellular carcinoma. However, the telomeres and the telomerase of tree shrews have not been studied to date. Here, we characterize telomeres and telomerase in tree shrews. The telomere length of tree shrews is approximately 23 kb, which is longer than that of primates and shorter than that of mice, and it is extended in breast tumor tissues according to Southern blot and flow-fluorescence in situ hybridization(FISH) analyses. Tree shrew spleen, bone marrow, testis, ovary, and uterus show high telomerase activities, which are increased in breast tumor tissues by telomeric repeat amplification protocol assays. The telomere length becomes shorter, and telomerase activity decreases with age. The tree shrew TERT and TERC are more highly similar to primates than to rodents. These findings lay a solid foundation for using tree shrews to study aging and cancers.     

Motor Function in MPTP-Treated Tree Shrews (Tupaia belangeri chinensis)

The tree shrew, a new experimental animal model, has been used to study a variety of diseases, especially diseases of the nervous system. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the gold standard for toxin-based animal models of Parkinson’s disease (PD) because MPTP treatment replicates almost all of the pathological hallmarks of PD. Therefore, in this study, the effects of MPTP on the motor function of the tree shrew were examined. After five daily injections of a 3 mg/kg dose of MPTP, the motor function of MPTP-injected tree shrews decreased significantly, and the classic Parkinsonian symptoms of action and resting tremor, bradykinesia, posture abnormalities, and gait instability were observed in most MPTP-injected tree shrews. HPLC results also showed significantly reduced striatal dopamine and 3,4-dihydroxyphenylacetic acid levels in tree shrews after MPTP injection. Increased oxidative stress levels are usually considered to be the cause of dopaminergic neuron depletion in the presence of MPTP and were observed in the substantia nigra of MPTP-treated tree shrews, as indicated by a significant reduction in superoxide dismutase and glutathione peroxidase activity and increased levels of malondialdehyde. In addition, elevated α-synuclein mRNA levels in the midbrain of MPTP-treated tree shrews were observed. Furthermore, MPTP-treated tree shrews showed the classic Parkinsonian symptoms at a lower MPTP dosage compared with other animal models. Thus, the MPTP-treated tree shrew may be a potential animal model for studying the pathogenesis of PD.     

树鼩的动物福利措施探讨

树鼩在生物学特性、生理生化、新陈代谢和基因组等方面近似于人类,被广泛应用于生理学、病理学、病毒学、免疫学、药理学及遗传学等多个领域。迄今为止用于生物医学研究的树鼩大部分来自野生,实验树鼩尚无国家质量控制标准。为了保证树鼩引种、驯化、饲养、繁殖、质量控制及福利的规范化和科学化,提高树鼩繁殖率和成活率,本文从兽医公共卫生及实验动物科学的角度,对野生树鼩的捕捉、运输、检疫、饲养及繁育等方面的基本原则及技术操作和福利要求作一简述,为从事树鼩工作的有关人员及树鼩实验动物化研究提供参考。     

树鼩资源的开发利用与标准化研究——我国实验动物资源建设发展战略探讨

树鼩（Tupaia belangeri）作为人类疾病动物模型,被应用于人类医学实验研究的多个领域,如各种类型的病毒性肝炎模型,流感病毒、登革热病毒、轮状病毒、疱疹病毒模型,糖尿病、胆结石、癌症病模型。但是,目前我国用于实验研究的树鼩几乎全都来自野外,对它们的微生物学、寄生虫学、遗传学、环境学等质量标准没有进行控制,它们本身携带的许多病原体会对实验结果的准确性造成影响,这既不符合国家对实验动物许可证管理的要求,也不利于我国实验动物科技工作与国际接轨的发展要求。因此,应该同步开展树鼩资源的开发利用和标准研究,使之纳入实验动物许可证的有效监控和管理,改变目前使用在前、质量控制标准研究在后的被动局面。     

Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

ABSTRACT: BACKGROUND: Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. RESULTS: Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. CONCLUSIONS: Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.     

DCE-MRI参数与肿瘤新生血管的相关性的研究

目的:研究DCE-MRI(dynamic contrast-enhanced magnetic resconance imaging,DCE-MRI)参数与肿瘤新生血管的相关性。方法:应用3.0T磁共振仪对124例乳腺肿瘤患者行DCE-MR检查,经手术病理证实恶性59例;良性65例。并计算血流动力学参数K~(trans)、K_(ep)、Ve以及ADC(apparent diffusion cofficient,ADC)值。运用Person检验分析磁共振各参数值与CD31、CD105表达的微血管密度(MVD)之间的相互关系,以及与细胞增殖Ki-67的相关性。结果:K~(trans)、K_(ep)以及ADC值在恶、良性病变、正常腺体组之间两两比较有统计学差异,K~(trans)、K_(ep)值在恶性病变组最高,高于正常组织、良性病变组(P0.05)。而Ve值正常腺体、良性病变以及正常腺体组与恶性病变组两两比较有统计学意义(P0.05),良性病变与恶性病变组比较无统计学差异(P0.05)。并且K~(trans)和K_(ep)值在浸润性导管癌和导管原位癌组明显高于不典型增生组(P0.001)。相反ADC值浸润性癌和导管原位癌低于不典型增生(P0.001)。而Ve值在各组间无统计学差异(P0.05)。另外CD105、Ki-67与磁共振参数K~(trans)、K_(ep)和ADC值之间具有相关性(P0.05,r=0.563,r=-0.566)。结论:DCE-MRI成像中K~(trans)、K_(ep)和ADC值可以定量评估乳腺癌微血管密度。     

Creating animal models,why not use the Chinese tree shrew (Tupaia belangeri chinensis)?

The Chinese tree shrew (Tupaia belangeri chinensis),a squirrel-like and rat-sized mammal,has a wide distribution in Southeast Asia,South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal.There have been many studies using the tree shrew (Tupaia belangen) aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses.The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database (www.treeshrewdb.org) has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species.The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates.Hitherto,the tree shrew has been successfully used to create animal models for myopia,depression,breast cancer,alcohol-induced or non-alcoholic fatty liver diseases,herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV) infections,to name a few.The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research.In this opinion paper,I attempt to summarize the recent research advances that have used the Chinese tree shrew,with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome,a proposal for the genome-based approach for creating animal models,and the genetic manipulation of the tree shrew.With more studies using this species and the application of cutting-edge gene editing techniques,the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.     

The myoepithelial cell layer may serve as a potential trigger factor for different outcomes of stage-matched invasive lobular and ductal breast cancers

Invasive lobular cancer (ILC) tends to be significantly larger in size with significantly more positive lymph nodes, whereas ILC has a significantly more favorable outcome, compared to stage-matched invasive ductal carcinoma (IDC). The mechanism accounting for such differences remains elusive. Based on morphological, immunohistochemical, and molecular studies of over 1,000 cases of human breast cancers, we hypothesize that the differences may result from the structural and/or functional differences of their surrounding myoepithelial cell layers, which dictate lobular and ductal tumor cells to follow different pathways of invasion or metastasis. The background, rationale, supportive data, and implications of our hypothesis are presented and discussed.     

实验树鼩配合饲料的研究与应用

根据树鼩的生物学特性并参考有关实验动物饲料标准为树鼩设计和加工生产一种实验饲育饲料。结果表明该饲料能满足树鼩的健康生长、饲养繁殖和实验树鼩的营养需求。该饲料的营养成分和混合均匀度均符合地方标准,生产和饲喂方便,具有一定的应用和推广前景。