Review：BRCA1/2 associated hereditary breast cancer

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers. Project supported by the National Natural Science Foundation of China (No. 30772510) and the Joint Program of Ministry of Health and Zhejiang Provincal Government of China (No. WKJ2006-2-008)     

RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum

Objective  

To evaluate the predictive values of gene expressions of ribonucleotide reductase M1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum.     

Mechanisms of inherited cancer susceptibility

A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.     

乳腺癌细胞粘附分子CD_(15)的表达及其与预后因素的关系

应用免疫组化SP法对94例乳腺癌、41例乳腺良性病变和10例正常乳腺组织进行了细胞粘附分子CD_(15)检测。结果发现,CD_(15)。在乳腺癌和乳腺良性病变的阳性率分别为79.8％和58.3％,两者有显著差异性(P<0 01),10例正常乳腺组织仅4例呈CD_(15)弱阳性反应。CD_(15)表达与患者年龄和肿瘤大小无显著关系。CD_(15)表达阳性率在浸润性导管癌中显著高于单纯癌(P<0.05),组织学Ⅱ～Ⅲ级显著高于Ⅰ级者(P<0.05),临床Ⅲ一Ⅳ期显著高于Ⅰ期和Ⅱ期者(P<0.05),淋巴结转移阳性组显著高于阴性组(P<0.01)。在一组原发部位和淋巴结转移性乳腺癌配对标本中,CD_(15)表达无明显差异性。CD_(15)阳性的乳腺癌Cath-D和c-erbB-2的表达阳性率均显著高于CD_(15)阴性者(P<0.001)。结果提示,CD_(15)的表达与乳腺癌的发生发展、浸润转移及预后有密切关系。     

Parameters selection in gene selection using Gaussian kernel support vector machines by genetic algorithm

INTRODUCTION Recent techniques based on oligonucleotide or cDNA microarrays allow the expression level of thousands of genes to be monitored in parallel (Golub et al., 1999). A critically important factor for cancer diagnosis and treatment is the reliable prediction of tumor progression. A remarkable advance for mo- lecular biology and for cancer research is cDNA mi- croarray technology. cDNA microarray datasets havea high dimensionality corresponding to the large number of genes monit…     

DNA并非遗传的全部

众所周知 ,DNA是遗传信息的携带者 ,遗传现象主要是由基因决定的。但是 ,近几年来科学家发现 ,朊病毒是一种可遗传的蛋白质粒子 ;DNA甲基化也导致一些遗传现象的发生 ;性状间的相互制约也可引起不受基因控制的表型出现……这些现象说明DNA并非遗传的全部。     

ppl-空间的遗传性

对ppl-空间的遗传性质进行了探讨．获得的主要结果是：1）ppl-空间的开遗传性蕴禽遗传性;2）ppl-空间具有F,遗传性;3）完备的ppl-空间具有遗传性．     

Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1

Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.     

Studying human disease genes in Caenorhabditis elegans: a molecular genetics laboratory project

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms.     

Imbalanced expression of mitogen-activated protein kinase phosphatase-1 and phosphorylated extracellular signal-regulated kinases in lung squamous cell carcinoma

Objective  

Mitogen-activated protein kinases (MAPKs) are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 (MKP-1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK_1/2), as the key regulatory mechanism of the MAPKs, in lung squamous cell carcinoma (SCC).     

Fractionated evaluation of immunohistochemical hormone receptor expression enhances prognostic prediction in breast cancer patients treated with tamoxifen as adjuvant therapy

Objective:To compare the prognostic prediction between dichotomized and fractionated evaluations of hormone receptor expressions. Methods: Patients with stages I-III breast cancers, who received adjuvant tamoxifen, were enrolled. The expression of estrogen receptor (ER) and progesterone receptor (PR) was evaluated by immu-nohistochemistry (IHC). A fractionated score (F score), the percentage of positive-staining nuclei (0=none, 1=1%-10%, 2=11%-30%, 3=31%-50%, 4=51%-70%, and 5=71%-100%), was assigned to each...     

Human cancer genetics

Cancer is a genetic disorder.Although heredi-tary cancers account for only a small fraction of all tumors,most cancers are caused by a variable mix of heredity and environment that leads to accumulations of genetic alterations and then uncontrolled cell pro-liferations(Kops et al.,2005).In addition,genetic alteration is one of the a few most important bio-logical factors that determine the diagnosis and prognosis of different cancers and dictate the treat-ment strategies for cancer patients.Fu…     

金属硫蛋白过表达对乳腺癌化疗方案选择的影响

目的：探讨金属硫蛋白（Metallothionein,MT）在乳腺癌中过表达的意义及其与乳腺癌化疗方案选择的相关性。方法：利用SP免疫组织化学技术,检测88例乳腺癌组织中MT表达率。结果：MT在乳腺癌中总阳性率为67.05%（59/88）。MT在髓样癌、小叶癌和导管癌中的阳性率分别为41.67%,85.71%和62.50%。在浸润型乳腺癌组阳性率明显高于非浸润型癌组（P〈0.05） 在小叶癌组阳性率高于髓样癌组和导管癌组（P〈0.05） 淋巴结转移组阳性率高于非转移组（P〈0.05）。结论：MT表达与乳腺癌的病理类型及有否淋巴结转移相关,检测MT对乳腺癌化疗方案的制定有指导意义。     

乳腺癌组织中c-erbB-2、p53和nm23蛋白表达及相互关系和意义

目的　探讨c erbB 2、p53和nm2 3蛋白在乳腺癌组织中的表达与乳腺癌临床病理参数、雌激素受体 (ER)、孕激素受体 (PR)的关系。方法　应用免疫组化ABC法对 5 5例乳腺癌组织中的c erbB 2、p53和nm2 3蛋白表达进行检测。结果　 5 5例乳腺癌中c erbB 2、p53及nm2 3的阳性率分别为 49 1 % (2 7/5 5 )、47 3 % (2 6 /5 5 )和 49 1 % (2 7/5 5 ) ,c erbB 2和p53蛋白在乳腺癌中的阳性率与肿瘤病理分级及淋巴结转移有显著意义 (P <0 0 5 ) ,与雌孕激素受体状况呈负相关 (P <0 0 1 )。nm2 3蛋白在乳腺癌中的阳性率与肿瘤病理分级、淋巴结转移有密切的关系 (p <0 0 5 ) ,与雌孕激素受体状呈正相关 (p <0 0 1 )。 70 9% (3 9/5 5 )肿瘤有上述蛋白的异常表达 ,其中 49 1 % (2 7/5 5 )的肿瘤同时有多个蛋白异常表达。结论　肿瘤的多因素分析比单因素分析更有价值 ,癌基因c erbB 2、nm2 3和抑癌基因p53蛋白的表达异常及协同作用在乳腺癌的发生发展中起重要使用     

基因芯片及其应用

基因芯片又称DNA微矩阵，是一种分析大量复杂生物样品的有效工具。它可以通过光引导聚合技术、电压打印或人工直接点样制备。光蚀刻技术可以使探针密度达到10^6／cm^2。它们可以被广泛地应用于DNA序列测定、新基因的检测和突变基因的分析。在医学上，基因芯片可以被用于癌症的诊断，传染病疾病如AIDS和肝炎等的早期检测。它在新药开发上也有巨大的市场。     

原位RT-PCR检测Ig A样新基因SNC66在消化系统肿瘤组织中的表达

目的：探讨原位检测内源性基因表达产物的灵敏方法，研究IgA样新基因SNC66在消化系统肿瘤组织中的表达及其与肿瘤之间的相关性。方法：在组织切片原位逆转录反应后进行原位PCR扩增，在扩增过程中掺入地高辛标记的尿核苷酸，再用免疫组织化学的方法加以检测。比较SNC66在大肠癌、胃癌、肝癌组织与相应的正常配对组织中的表达情况。结果：10个循环时，37例大肠癌标本中有14例呈阴性，18例弱阳性，5例强阳性；20例胃癌标本中有6例呈阴性，9例弱阳性，5例强阳性；所有肝脏组织和肝癌标本都呈阴性表达。25个循环时，大肠癌10例阴性，27例强阳性；胃癌4例阴性，16例强阳性；所有肝脏组织和肝癌组织标本都呈阳性表达。相应大肠粘膜和胃粘膜标本则无论是25个循环，还是10个循环，都呈强阳性表达，但着色程度前者高于后者。结论：原位RT-PCR是一种检测内源性基因低拷贝转录产物mRNA的灵敏方法。基因SNC66是一个消化道肿瘤相关性基因，在大肠癌和胃癌组织中存在明显的表达降低或缺陷，但与肝癌之间不存在相关性。SNC66可作为侯选的消化道肿瘤的抑癌基因加以进一步研究。     

L-fuzzy相对T-1,相对T0与相对次T0分离性

定义了L-fuzzy拓扑空间中的相对T-1，相对T0与相对次T0分离性，讨论了相对T-1，相对T0与相对次T0分离性的一系列性质．证明了相对T-1，相对T0与相对次T0分离性是遗传的、传递的、弱同胚不变的及可乘性等性质，并给出了一些例子。     

The Antecedents of Menarcheal Age: Heredity, Family Environment, and Stressful Life Events

Variations in pubertal timing, specifically age at menarche, have been associated with several antecedents, both genetic and environmental. Recent research has considered a broader range of environmental stressors and their influence on the development of the reproductive system. In this investigation, the following possible antecedents were considered: ( a ) hereditary transmission, ( b ) weight and weight for height, ( c ) stressful life events, ( d ) family relations, ( e ) absence or presence of an adult male in the household, and ( f ) psychological adjustment. Subjects were 75 premenarcheal girls between the ages of 10 and 14 drawn from a larger longitudinal investigation of adolescent development. Girls were from white, well-educated, middle- to upper-middle-class families and attended private schools in a northeastern urban area. While breast development, weight, family relations, and depressive affect were predictive of age at menarche, family relations predicted age at menarche above the influence of breast development or weight. A trend for maternal age at menarche to predict adolescent's age at menarche was found. Weight for height, presence of an adult male in the household, and stressful events were not predictive of age at menarche. These complex interactions of biological and psychosocial development demonstrated here may account to some extent for the inter- and intraindividual variation observed in pubertal development.     

广义仿紧空间的遗传性和基-正规性

在这篇文章里主要研究了广义仿紧空间的遗传性和基-正规性.着重证明了：（1）设X=（lim）{ Xα,παβ,∧},｜∧｜=λ,每一个投射πα是开的且到上的,X为（遗传）λ-仿紧的,若每个Xα是可遮的,则X是（遗传）可遮的.（2）设X是基-正规空间,Y是可度量空间,则当且仅当X×Y为基-正规空间时X×Y为正规空间.     

Roles of PTBP1 in alternative splicing,glycolysis, and oncogensis

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (IncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.