TopoⅡα在老年乳腺癌中的表达及其临床病理意义

目的对老年乳腺癌中TopoⅡα的表达与多个临床病理因素行相关性分析,探讨其表达的临床意义。方法应用免疫组化SP法检测南方医科大学附属南方医院近2年来所有老年乳腺癌共105例中TopoⅡα、ER、PR以及HER-2的表达情况;依据免疫组化的表达将其近似划分为LuminalA型(ER+和/或PR+,HER-2-)、LuminalB型(ER+和/或,PR+,HER-2+)、HER-2过表达型(ER-,PR-,HER-2+)和Basal-like型(ER-,PR-,HER-2-)4个分子亚型,对比TopoⅡα表达阳性率的差异。用统计学软件SPSS13.0作为统计分析的工具,TopoⅡα表达与临床病理因子的关系用卡方检验和Spearman相关分析检验。结果老年乳腺癌组织中TopoⅡα蛋白表达阳性率为62.9%,Basal-like型最高,HER-2过表达型仅次之,再次为LuminalB型,LuminalA型最低(P<0.050);阳性表达在不同组织学分期和淋巴结状态患者间差异中有统计学意义且呈正相关(P<0.050)。在不同肿瘤大小患者间差异无统计学意义。结论乳腺癌组织病理检查应根据ER、PR和HER-2的免疫组化结果行分子分型,进一步行TopoⅡα的免疫组化检测,以获得更多的预后信息,进一步指导老年乳腺癌治疗。     

乳腺癌分子标志和分子分型

乳腺癌是生物学高度异质性的肿瘤,雌激素受体(estrogen recept,ER)、孕激素受体(progester-one recept,PR)、人表皮生长因子受体2(human epidermal growth factor 2,HER-2)是目前预测预后和指导治疗重要的分子标志。随着分子生物学技术的不断进步,可以根据ER、PR、HER-2表达状态和细胞形态学可以将乳腺癌大致分成4至5个亚群,即Luminal(ER /PR )、HER-2 (ER-,PR-,HER-2 )、Basal-like(ER-,PR-,HER-2-)和Normal-like等,它们在临床治疗反应和生存方面截然不同。因此,对乳腺癌进行分子标志检测或分子分型有利于判断患者的临床预后和指导临床治疗。     

不同分子分型及临床病理特征与乳腺癌术后患者预后的关系

目的探讨不同分子分型和临床病理特征与乳腺癌术后患者预后的关系。方法收集283例乳腺癌患者的临床病理资料,根据ER、PR和HER-2的免疫组化结果,将其分成Luminal A型、Luminal B型、HER-2过表达型和三阴型4组,并进行随访。结果不同分子分型的乳腺癌患者术后5年总生存期和无病生存期,差异有统计学意义(P0.05)。两两比较结果显示,与Luminal A型相比,HER-2过表达型和三阴型乳腺癌患者术后5年无病生存期和总生存期短(P0.05)。应用Cox风险回归模型分析,肿瘤大小和淋巴结转移数目是影响乳腺癌患者术后5年总生存期和无病生存期的预后因素(P0.05);但实验未能揭示分子分型是影响乳腺癌患者术后5年总生存期和无病生存期的预后因素(P0.05)。结论肿瘤大小和淋巴结转移数目是影响乳腺癌患者术后5年总生存期和无病生存期的预后因素。     

基于数字乳腺三维断层摄影技术的乳腺癌分子亚型特征

目的:研究乳腺癌各分子亚型在数字乳腺三维断层技术(DBT)表现的特征。方法:回顾分析2013年5月~2014年10月在福建医科大学附属第二医院接受手术同时有完整的病理及免疫组化资料的乳腺癌病人78例,根据雌激素受体(ER)、孕酮受体(PR)、人表皮生长因子受体(HER-2)的表达和Ki-67将乳腺癌分为Luminal A型、Luminal B型、三阴性型和HER-2的过表达型,研究不同分子亚型乳腺癌DBT影像表现特征、临床与病理表现特征。结果:各个分子亚型是否存在肿块无统计学差异,HER-2过表达型较Luminal A型、Luminal B型肿块大,与Luminal B型比较有统计学意义,与Luminal A型比较无统计学意义;钙化分数:HER-2过表达型较Luminal A型和Luminal B型显著增高,差异有统计学意义;不同分子亚型在乳腺BI-RADS分类差异无统计学意义。Luminal B型乳腺癌淋巴结转移率明显高于其它分子分型。结论:基于乳腺三维断层摄影技术,乳腺癌分子亚型具有一定特征性。     

乳腺癌易感基因1的表达与乳腺癌亚型关系的实验研究

目的 探讨乳腺癌易基因1（BRCA1）的表达与乳腺癌分子亚型的关系.方法 运用免疫组化法检测乳腺癌组织中BRCA1的表达与雌二醇受体（ER）和人表皮生长因子受体-2（Her-2）的关系,分析BRCA1的表达在乳腺癌各亚型中的意义.结果 ER阳性和阴性时,BRCA1的阳性率分别为40.2％和60.0％,表明BRCA1表达与ER有关（P＜0.05）,与Her-2无关（P＞0.05）.在乳腺癌各分子亚型中,Luminal B型和Her-2过表达型的BRCA1阳性率（66.7％和70.0％）与Basal-like型的BRCA1阳性率（75.0％）差别无统计学意义（P＞0.05）;Luminal A型的BRCA1阳性率（23.7％）低于Basal-like型的BRCA1阳性率（75.0％）,差别具有统计学意义（P＜0.05）.结论 BRCA1在Luminal B型、Her-2过表达型和Basal-like型乳腺癌中表达较高,在Luminal A型乳腺癌中表达不高,提示BRCA1可成为治疗乳腺癌的重要靶点.     

肿瘤干细胞相关标记物CD44及CD24在乳腺癌中的表达及其意义

目的探讨肿瘤干细胞相关标记物CD44及CD24在乳腺癌组织中的表达特点、CD44+/CD24-细胞与HER-2、ER、PR、CK5/6表达的相互关系及其与临床病理因素的关系。方法采用免疫组化SP单染及双染法检测42例乳腺导管原位癌及126例乳腺浸润性导管癌组织中CD44及CD24的表达情况,检测126例乳腺浸润性导管癌组织中HER-2、ER、PR、CK5/6表达状况以进行免疫分型。结果 (1)CD44阳性定位于癌细胞膜。在浸润癌中阳性率为56.3%,在导管原位癌中阳性率为85.7%。两者差异有显著性意义(P<0.05)。在不同分化程度的乳腺浸润性癌中,CD44阳性率分别为69.2%、58.1%及44.7%,差异有显著性意义(P<0.05)。(2)CD24阳性表达于非癌性乳腺组织中小管的腔缘;在癌组织中除腔缘阳性外,可出现膜质阳性。在浸润癌中阳性率为32.5%,在导管原位癌中阳性率为64.3%。两者差异有显著性意义(P<0.05)。(3)126例浸润性导管癌中CD44+/CD24-者65例,占51.6%;CD44+/CD24-阳性细胞在Luminal A型为47.5%、Luminal B型为42.9%、HER-...     

乳腺癌原发肿瘤和复发肿瘤间ER、PR和HER-2表达不一致及其对患者生存的影响

目的探讨乳腺癌原发肿瘤和复发肿瘤组织中ER、PR和HER-2表达不一致与临床病理特征的关系及对预后的影响。方法采用免疫组化和荧光原位杂交法检测62例乳腺癌原发肿瘤和复发肿瘤组织中ER、PR和HER-2的表达,分析乳腺癌原发肿瘤和复发肿瘤组织中ER、PR和HER-2表达不一致与临床病理特征的关系及与患者生存的关系。结果在62例乳腺癌原发肿瘤和复发肿瘤组织中ER、PR和HER-2表达不一致分别为6例(9. 7%)、9例(14. 5%)和3例(4. 8%)。ER表达不一致患者的中位总生存期和中位复发后生存期分别为29个月和6个月,而ER表达一致患者的中位总生存期和中位复发后生存期分别为44个月和15个月(P=0. 021,P=0. 027)。PR及HER-2表达不一致患者与PR及HER-2表达一致患者总生存期和复发后生存期差异均无统计学意义(P均 0. 05)。结论乳腺癌原发肿瘤和复发肿瘤组织之间ER、PR和HER-2表达状态显著改变。乳腺癌ER状态不稳定提示患者预后较差。     

乳腺导管内癌分子分型应用研究

目的 采用免疫组织化学检测方法 对乳腺导管内癌进行分子分型.方法 收集50例乳腺导管内癌存档蜡块,用单克隆抗体CK5/6、CK8、CK18、34βE12、p63、S-100、SMA、CD10、CD117、EGFR、ER、PR和HER2进行免疫组织化学EnVision法染色,按照免疫表型分为5种类型:腺腔A型(ER+/PR+/HER2-)、腺腔B型(ER+/PR+/HER2+)、正常乳腺样型(ER-/PR-/HER2-且不表达基底/肌上皮标记及EGFR)、HER2过表达型(ER-/PR-/HER2+)和基底细胞样型(ER-/PR-/HER2-,且至少表达一种基底型角蛋白和(或)肌上皮标记物或EGFR).结果 腺腔A型16例(32%),腺腔B型19例(38%),HER2过表达型13例(26%),基底细胞样型2例(4%),无正常乳腺型.2例基底细胞样型,均表达CK5/6、CD117,例1同时表达SMA,例2表达CK8、CK18、34βE12、S-100,均为高级别导管内癌.结论 乳腺导管内癌可按免疫表型进行分子分型,部分导管内癌具有与基底细胞样癌相同的免疫表型,可能是基底细胞样癌的前驱病变,其诊断依赖于免疫组化检测.     

NQO1基因C609T多态性与乳腺癌分子分型的关系及意义

目的探讨乳腺癌中醌氧化还原酶1(quinone oxido reductase 1,NQO1)基因第6外显子(C609T)多态性的分布,并分析其与乳腺癌分子分型的关系。方法采用高通量Taq Man MGB实时荧光定量PCR技术对248例女性乳腺癌患者外周血中的NQO1基因C609T rs1800566位点进行基因分型检测;应用免疫组化SP法染色及FISH基因扩增技术检测ER、PR、HER-2及Ki-67的表达。结果 248例乳腺癌中,CC基因型占27.42%(68/248)、CT基因型占49.60%(123/248)、TT基因型占22.98%(57/248),符合Hardy-Weinberg遗传平衡定律(P>0.05);5例HER-2()患者未行FISH检测,予以剔除,其余行FISH检测:Luminal A型占15.2%(37/243)、Luminal B型占51.4%(125/243)、HER-2过表达型占19.8%(48/243)、基底细胞型占13.6%(33/243);携带CT和TT基因型者较携带CC基因型患者的乳腺癌组织中ER、PR阳性率明显升高(P<0.05),HER-2及Ki-67蛋白表达在两组中的差异无统计学意义(P>0.05);NQO1基因C609T多态性在不同分子分型的乳腺癌中的分布差异无统计学意义(P>0.05)。结论 NQO1基因C609T多态性与乳腺癌的分子分型无关,NQO1基因(CT+TT)在基底细胞型乳腺癌中缺失率较低,其基因多态性可为分子分型中乳腺癌的异质性提供合理解释。     

乳腺癌中EPCR的表达及其预后意义

目的观察EPCR在乳腺癌中的表达,并分析其预后意义。方法采用免疫组化Eli Vision法检测99例非特殊型浸润性乳腺癌组织中EPCR蛋白的表达,并复习相关文献。结果 EPCR在乳腺癌组织中的阳性率为36.4%,其表达与组织学分级、淋巴结转移、HER-2及Ki-67表达呈正相关,与ER、PR表达呈负相关,并在管腔A型中呈低表达,差异有统计学意义(P0.05);Kaplan-Meier单因素生存分析显示,EPCR阳性组的无瘤生存期(disease free survival,DFS)明显低于EPCR阴性组(P=0.011,Log-rank test=6.391),多因素Cox回归分析结果显示,EPCR在pN1组的乳腺癌中是独立的预后因素(hazard ratio=6.063,P=0.032)。结论 EPCR在乳腺癌中的表达与组织学高分级、淋巴结转移、HER-2阳性、高Ki-67、低ER/PR及更短的DFS相关,提示乳腺癌的不良预后。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.