形态定量分析及DNA含量测定在乳腺增生性疾病与乳腺癌鉴别的应用

目的　探讨形态定量分析及DNA含量测定在乳腺增生性病变与乳腺癌的鉴别诊断中的实用价值。方法　应用HE和Feulgen染色法对乳腺腺病 4 0例、乳腺癌 5 0例进行染色后 ,采用MPILAS 5 0 0多媒体病理彩色图文分析系统选择胞核面积 ,胞核周长 ,胞核直径 ,胞核体积 (包括胞核S 体积和胞核L 体积 ) ,形状因子 ,胞核圆形度 ,胞核圆球度、C 异形指数共 9项参数和DNA指数 (DI值 )进行测量 ,所获数据采用U检验进行分析。结果　乳腺增生与乳腺癌两组间细胞形态定量测定的 9项参数差异显著 (C 异形指数P <0 0 5 ,其余 8项参数均为 P <0 0 1 )。结论　细胞形态定量测定和DNA含量测定在乳腺增生性病变与乳腺癌的鉴别诊断中具有实际应用价值     

乳腺癌癌旁腺病的病理形态观察

从病理形态学角度研究了本院142例乳腺癌并存癌旁腺病的改变,并重点观察乳腺癌癌旁腺病性上皮增生、不典型增生与癌的关系。发现:全组95%以上腺病性导管上皮出现不典型增生;40.1%显示增生、不典型增生与癌的移行形态;11.3%发现腺病性小叶内上皮多中心癌变灶。由此提出腺病(尤其当出现导管上皮重度增生、不典型增生时)与乳腺癌发生有直接关系,应引起临床重视和慎重处理。     

乳腺癌患者血清Leptin水平检测及其临床意义

目的:研究瘦素(Leptin)对乳腺癌诊断的价值,为乳腺癌与乳腺良性病变的鉴别诊断提供实验依据。方法:应用放射免疫分析(RIA)分别检测46例乳腺癌、28例乳腺良性病变患者及41例正常对照组外周血中Leptin含量。结果:乳腺癌组病人血中Leptin含量(21.97±9.13ng/ml)明显高于乳腺良性病变组(16.78±5.13ng/ml)及正常对照组(12.25±2.39ng/ml),差别有显著性(P<0.01)。随着乳腺癌病情的进展,从乳腺癌Ⅰ期至Ⅳ期,Leptin水平逐渐升高,有显著性差异(P<0.01)。乳腺癌淋巴有转移组Leptin水平(26.29±8.83ng/ml),明显高于乳腺癌无淋巴转移组(16.35±6ng/ml),差异有显著性(P<0.01)。结论:Leptin的检测可作为乳腺癌诊断的实验室指标,对乳腺癌的分期和预后的评价有重要价值,对治疗方案的选择有重要的指导意义。     

Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome

Prediction of the clinical outcome of breast cancer is multi-faceted and challenging. There is growing evidence that the complexity of the tumour micro-environment, consisting of several cell types and a complex mixture of proteins, plays an important role in development, progression, and response to therapy. In the current study, we investigated whether invasive breast tumours can be classified on the basis of the expression of extracellular matrix (ECM) components and whether such classification is representative of different clinical outcomes. We first examined the matrix composition of 28 primary breast carcinomas by morphology and gene expression profiling using 22K oligonucleotide Agilent microarrays. Hierarchical clustering of the gene expression profile of 278 ECM-related genes derived from the literature divided the tumours into four main groups (ECM1-4). A set of selected differentially expressed genes was validated by immunohistochemistry. The robustness of the ECM classification was confirmed by studying the four ECM groups in a previously published gene expression data set of 114 early-stage primary breast carcinomas profiled using cDNA arrays. Univariate survival analysis showed significant differences in clinical outcome among the various ECM subclasses. One set of tumours, designated ECM4, had a favourable outcome and was defined by the overexpression of a set of protease inhibitors belonging to the serpin family, while tumours with an ECM1 signature had a poorer prognosis and showed high expression of integrins and metallopeptidases, and low expression of several laminin chains. Furthermore, we identified three surrogate markers of ECM1 tumours: MARCO, PUNC, and SPARC, whose expression levels were associated with breast cancer survival and risk of recurrence. Our findings suggest that primary breast tumours can be classified based upon ECM composition and that this classification provides relevant information on the biology of breast carcinomas, further supporting the hypothesis that clinical outcome is strongly related to stromal characteristics.     

Supplementation with Fermented Barley Extract Prevents Mammary Epithelial Cell Invasion in an Early Breast Cancer Model

Diet-based prevention of malignant transformation contributes to the maintenance of quality of life by avoiding a battle against cancer. Invasion is one of the features of malignant breast cancer, and the prevention of invasion may reduce breast cancer malignancy. A recently established early breast cancer model system showed mammary ductal dysplasia with invasion in mice. This study utilized the model system and investigated the effect of fermented barley extract (FBE), a food material. The elastic fiber layer is the outermost layer of the mammary duct. A reduction in the elastic fiber layer was observed in the mammary glands of the model system, whereas supplementation with 8% FBE containing water prevented this reduction. Moreover, we found that FBE supplementation prevented mammary epithelial cell invasion. Based on our findings, FBE might be a candidate material for a diet-based prevention of early breast cancer invasion.     

Mammary stem cells and the differentiation hierarchy: current status and perspectives

The mammary epithelium is highly responsive to local and systemic signals, which orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. Lineage tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in situ as well as long-lived unipotent cells that drive morphogenesis and homeostasis of the ductal tree. Moreover, there is accumulating evidence for a heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and both long-term and short-term repopulating cells. In parallel, diverse luminal progenitor subtypes have been identified in mouse and human mammary tissue. Elucidation of the normal cellular hierarchy is an important step toward understanding the “cells of origin” and molecular perturbations that drive breast cancer.     

Metformin Decelerates Aging and Development of Mammary Tumors in HER-2/neu Transgenic Mice

Transgenic FVB/N female mice carrying HER-2/neu mammary cancer gene received metformin (1200 mg/liter) with drinking water 5 days a week starting from the age of 2 months until natural death. Metformin slightly reduced food consumption, but did not change water consumption and dynamics of weight gain. Mean life span of mice increased by 8% (p<0.05), in 10% long-living mice it was prolonged by 13.1%, and the maximum life span was prolonged by 1 month under the effect of metformin in comparison with the control. The rate of populational aging decreased by 2.26 times. The total incidence of mammary adenocarcinoma and their multiplicity did not change under the effect of metformin, while the latency of tumor development increased and the mean diameter of tumors decreased. Hence, we first demonstrated a geroprotective effect of metformin and its suppressive effect towards the development of mammary tumors.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 6, pp. 691–694, June, 2005     

Protease Activity and Cell-Free DNA in Blood Plasma of Healthy Donors and Breast Cancer Patients

Tumor development is generally accompanied by increased protease activity and cell-free DNA (cfDNA) levels in the blood. An immunoassay for protease activity was developed based on the binding of anti-peptide antibodies onto polystyrene plates, followed by incubation with peptides and protein hydrolyzing enzymes. The data obtained demonstrate the peptide CD34-1 composed of uncharged amino acids was the best substrate for the estimation of plasma protease activity in breast cancer patients and healthy donors. Anti-CD34-1 peptide protease activity was shown to correlate with circulating DNA concentrations in cancer patients and healthy subjects (P = 0.001, r = 0.676), demonstrating the role of protease activity in the regulation of cfDNA levels.     

Extracellular DNA in Culture of Primary and Transformed Cells,Infected and Not Infected with Mycoplasma

The composition and kinetics of accumulation of extracellular DNA in cultures of primary human endotheliocytes, cervical adenocarcinoma, and mycoplasma-infected cervical adenocarcinoma cells were studied. The content of DNA bound to cell surface did not change during culturing. The concentration of extracellular DNA in culture medium increased during the lag phase and at the beginning of the exponential growth phase, which probably attests to active secretion of DNA by cells. Spontaneous extracellular DNA synthesis was observed only in cell culture infected with mycoplasma. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 67-70, January, 2009     

乳腺癌并发肥胖症患者血浆瘦素水平与乳腺癌组织中瘦素mRNA的表达及临床病理的关系

目的:检测乳腺癌并发肥胖症患者乳腺癌组织中瘦素(leptin)mRNA的表达情况和血浆leptin水平,并探讨两者之间及其与临床病理之间的关系。方法:对124例居住在武汉检查者同时采集病史、进行体格检查并留取血浆,测定其leptin水平。采用半定量逆转录-聚合酶链反应(RT-PCR)检测瘦素mRNA的表达。结果:乳腺癌并发肥胖组血浆leptin水平(12.02μg.L-1±1.23μg.L-1)显著高于乳腺良性病变并发肥胖组(9.84μg.L-1±0.98μg.L-1)及单纯肥胖组(9.79μg.L-1±1.16μg.L-1)(P<0.05)。瘦素mRNA在乳腺癌并发肥胖组中的表达水平(0.71±0.32)明显高于乳腺良性病变并发肥胖组(0.41±0.26)(P<0.05)。血浆lep-tin水平与乳腺组织中瘦素mRNA表达水平显著正相关(r=0.4220,P=0.0180)。血浆leptin和瘦素mRNA的表达与腋窝淋巴结转移、绝经、TNM分期及病理类型均无显著相关性。结论:leptin可能参与了乳腺癌的发生。     

循环DNA定量分析在乳腺癌诊断中的应用

目的:检测乳腺癌患者循环DNA含量,探讨其在肿瘤诊断中的价值。方法:收集61例乳腺癌患者、33例乳腺良性病变患者和20例健康志愿者的血浆样本,以SYBRgreenI荧光染色法抽提血浆循环DNA,行DNA定量分析。结果:乳腺癌患者、乳腺良性病变患者、健康志愿者循环DNA浓度分别为65.46士15.31ng/ml、19.29士9.54ng/ml、13.56士7.39ng/ml;乳腺癌患者显著高于乳腺良性病变患者和健康志愿者,差异有显著性意义(P<0.05)。结论:血浆肿瘤循环DNA定量分析在乳腺癌诊断中有较高的应用价值。     

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

乳癌及癌前病变细胞核内DNA定量研究

应用显微分光光度计检测40例乳癌、癌旁单纯增生、异型增生及正常导管上皮细胞核内的DNA含量,结果表明:癌细胞核内DNA含量明显高于正常和癌旁上皮,癌旁异型增生的程度与DNA含量之间有着内在联系,多倍体的出现是细胞恶变的早期表现。局部细胞癌变时DNA含量明显增高,且高于高分化腺癌。作者认为检测细胞核内DNA含量对乳癌的诊断,癌及癌前病变的分级以及早期发现癌变趋势具有重要意义。     

乳腺增生病患者精神状态的研究

目的 探讨乳腺增生病人的精神状态。方法 采用SCL-90评定60例乳腺增生女患者和60例健康妇女在月经周期4个不同时期的精神状态。结果 研究组躯体化、抑郁及焦虑因子显著高于对照组；在月经前期、分泌期、月经期等3个时期总分较对照组高；在月经期及月经前期总均分及人际关系敏感因子对照组高。结论 乳腺增生患者精神症状，主要是躯体化、抑郁、焦虑、人际关系敏感等因子与健康人存在差异。     

Mouse mammary tumor virus and mammary tumorigenesis in wild mice

The current knowledge of the distribution of the mouse mammary tumor virus (MMTV) proviral genomes and the mechanism of mammary tumorigenesis by MMTV in mice, with the main emphasis on Asian feral mice, is reviewed. The relevant earlier discoveries on the mode of MMTV transmission are summarized to provide an outline of the biology of MMTV. Finally, the viral etiology of human breast cancer will be discussed.     

Serum Interleukin-6 in Patients with Adrenal Tumors

The mean blood content of interleukin-6 in patients with adrenal tumors was much higher than in healthy donors. No correlations were revealed between interleukin-6 level, patients sex and age, stage and duration of the disease. Interleukin-6 concentration was maximum in patients with adrenocortical cancer. A negative correlation was found between interleukin-6 level and blood cortisol concentration in patients with cortisol-producing adenoma. In patients with aldosterone-producing adenoma, interleukin-6 level tended to correlate negatively with plasma renin activity.     

Extracellular DNA traps in allergic,infectious, and autoimmune diseases

Extracellular DNA traps are part of the innate immune response and are seen with many infectious, allergic, and autoimmune diseases. They can be generated by several different leukocytes, including neutrophils, eosinophils, and monocytes, as well as mast cells. Here, we review the composition of these extracellular DNA‐containing structures as well as potential mechanisms for their production and function. In general, extracellular DNA traps have been described as binding to and killing pathogens, particularly bacteria, fungi, but also parasites. On the other hand, it is possible that DNA traps contribute to immunopathology in chronic inflammatory diseases, such as bronchial asthma. In addition, it has been demonstrated that they can initiate and/or potentiate autoimmune diseases. Extracellular DNA traps represent a frequently observed phenomenon in inflammatory diseases, and they appear to participate in the cross‐talk between different immune cells. These new insights into the pathogenesis of inflammatory diseases may open new avenues for targeted therapies.