SWI/SNF染色质重塑复合物与肾脏肿瘤

SWI/SNF复合物是一种ATP依赖的染色质重塑复合物,在肿瘤中起抑癌基因作用,其多个亚基失活与肾脏肿瘤的发生、发展关系密切,且常常提示肿瘤预后不良。该文现综述SWI/SNF复合物与肾脏肿瘤的相关研究进展,旨在阐述SWI/SNF复合物在某些肾脏肿瘤发生及演变过程中可能的作用。     

胃癌中主要SWI/SNF复合物亚基突变/缺失与临床预后及肿瘤免疫反应的关系

目的 探讨胃癌中主要SWI/SNF复合物亚基突变/缺失在预后及肿瘤免疫反应中的意义.方法 利用cBioPor-tal、LinkedOmics及TISIDB数据集统计分析胃癌中主要SWI/SNF亚基突变/缺失情况,及其与临床预后、微卫星稳定性、肿瘤突变负荷、免疫抑制分子表达及肿瘤浸润淋巴细胞的关系.结果 胃癌中SWI/S...     

ARID1A在恶性肿瘤中的研究进展

SWI/SNF是一种ATP依赖的染色质重塑复合物,ARID1A基因是SWI/SNF复合物的一个重要亚基,其功能失调可造成染色质重塑异常进而引起肿瘤等疾病的发生。ARID1A在卵巢癌、肝癌、乳腺癌、肾癌和膀胱癌等多种恶性肿瘤中频繁发生低表达或者缺失性突变,表明ARID1A是一种重要的肿瘤抑制基因。     

胃SWI/SNF复合体缺失的产甲胎蛋白腺癌临床病理学特征

目的探讨胃SWI/SNF复合体缺失的产甲胎蛋白腺癌的临床病理学特征。方法收集复旦大学附属中山医院2021年1月至2022年12月确诊的胃SWI/SNF复合体缺失的产甲胎蛋白腺癌4例, 复习其组织形态学特征、免疫组织化学、EB病毒编码的RNA(EBER)原位杂交、二代测序结果及临床治疗经过, 总结其临床病理特征及治疗, 并进行文献复习。结果 4例患者中男性3例, 女性1例, 临床主诉腹痛、嗳气和黑便, 其中3例血清甲胎蛋白显著升高, 内镜均显示溃疡型病变。镜下观察肿瘤细胞呈弥漫性片状或巢状生长, 表现为典型肝样腺癌特征;2例部分区域呈腺样生长, 腺样区域胞质透亮, 表现为肠母细胞分化。肿瘤细胞核显著异型, 可见显著大核仁, 核分裂象易见。免疫组织化学结果显示肝样腺癌标志物甲胎蛋白、GPC3和SALL4均阳性, 广谱细胞角蛋白和E-cadherin均未见缺失表达。SWI/SNF复合体亚基表达蛋白免疫组织化学检测, 即INI1(SMARCB1)、BRG1(SMARCA4)、BRM(SMARCA2)、ARID1A蛋白, 4例肝样腺癌区域及肠母细胞分化区域均为SMARCA2缺失表达, 其中1例肠...     

横纹肌样及未分化表型的肾细胞癌:32例分析提示未分化肿瘤具有与SWI/SNF复合体缺陷有关的不同于常见的分化通路

正肾细胞癌出现未分化(间变性)和横纹肌样细胞特征时被公认为预后不良,其分子机制尚未充分阐明。近期研究发现SWI/SNF染色质重塑复合体是不同器官具有未分化和横纹肌样特征癌的分子机制。本文对32例未分化肾细胞癌(均具有未分化和明显横纹肌样特征,可有或无普通型肾细胞癌成分)的分子特征进行分析。所有病例除常规肾细胞癌标志物外均加染SWI/SNF通     

SWI/SNF染色质重塑复合物在乳腺癌中的研究现状

DNA的复制、转录、修复、重组与染色质状态密切相关.染色质重塑复合物在染色质重塑过程中扮演重要作用.其中SWI/SNF复合物是最先在酵母中发现的一种多亚基复合物家族,可利用三磷酸腺苷的能量(ATP)水解重塑核小体.该复合物亚基在多种肿瘤中发生异常并可作为潜在的治疗靶点,如卵巢癌、非小细胞肺癌、视网膜母细胞瘤等.然而其在...     

BRG1和BRM蛋白在前列腺癌中的表达

目的 探讨SWI/SNF催化亚基BRG1/BRM蛋白在前列腺癌及癌旁组织中的表达以及与前列腺发生发展之间的关系.方法 采用半定量免疫组织化学法配对评价前列腺癌及癌旁组织中BRG1和BRM蛋白的表达水平,分析BRG1和BRM表达与临床病理参数之间的关系.结果 在同一病例中,癌组织BRG1平均免疫反应得分为(57.0±9.8)分,远比前列腺癌旁组织的(19.0±4.1)分高,P=0.000 17,而且这种表达的差异在高级别的肿瘤中更显著;BRM呈现异质性表达,癌组织的平均免疫反应得分为(112±17)分,低于癌旁组织的(151±19)分,P=0.0047;同一病例的癌旁组织和癌组织中BRG1和BRM表达相反;大肿瘤组中癌组织BRG1的平均免疫反应得分与相应癌旁组织的比值明显高于小肿瘤组(P=0.0112).结论 SWL/SNF复合物蛋白BRG1和BRM的异常表达与前列腺癌的发生发展有关,BRG1的表达增强可能促进前列腺癌的生长.     

SMARCA4缺失型鼻窦癌:10例SWI/SNF驱动的鼻窦恶性肿瘤遗传学谱系的扩展

正低分化鼻窦癌的分子发病机制近年来备受关注。在鼻窦未分化癌的形态学谱系中,几种未分类的癌被重新归类为具有独特遗传学特征的变异体或实体,包括NUT重排性癌和SMARCB1缺失型癌。作者进一步描述了一种罕见的鼻腔未分化癌样肿瘤,其特征是通过免疫组化染色可检测到SWI/SNF构建体SMARCA4(BRG1)的失活。     

SMARCB1/INI1缺失性肿瘤的研究进展

SMARCB1/INI1蛋白是ATP依赖性SWI/SNF染色质重塑复合物的核心亚单位蛋白之一。SMARCB1/INI1基因失活导致INI1蛋白表达缺失，是软组织肿瘤中最常失活的亚单位。SMARCB1/INI1基因缺失表达最早在恶性横纹肌样瘤(malignant rhabdoid tumor, MRT)、非典型畸胎样/横纹肌样瘤(atypical teratoid/rhabdoid tumor, AT/RT)中发现，随着免疫组化及分子病理的广泛应用，越来越多的MRT-AT/RT谱以外的SMARCB1/INI1缺陷肿瘤被报道，将其定义为SMARCB1/INI1缺失性肿瘤。研究证实，SMARCB1/INI1异常表达包括三种模式：完全缺失、镶嵌表达和表达降低。该文现对SMARCB1/INI1缺失性肿瘤的研究进展作一综述，以期为SMARCB1/INI1缺失相关肿瘤的研究、诊断及治疗提供依据。     

染色质重组子BRG1与心血管疾病的研究进展

中国心血管病死亡仍居疾病死亡构成的首位,严重威胁着人类的身体健康,探索新靶点、新机制以开发新药,对于降低心血管疾病的风险至关重要.染色质重组子BRG1 (Brahma-related gene-1)由SMARAC4基因编码,是SWI/SNF(SWItch/sucrose nonfermentable)染色质重塑复合物中核心成分,BRG1在心肌肥厚、心力衰竭、心肌梗死等多种心血管疾病的发生和发展中起到至关重要的作用.     

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.     

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.     

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.     

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.