Expression of Molecular Markers in the Tumor and Survival Prognosis in Osteosarcoma
骨髓增生异常综合征的基因突变及其临床意义
·综述·系统医学SYSTEMS MEDICINE系统医学2021年2月第6卷第4期骨髓增生异常综合征是(MDS)起源于造血干细胞的肿瘤性病变,其常见症状为贫血、感染以及出血。
该病可发生于任何年龄,但是以中年人居多,其唯一根治方法为造血干细胞移植。
根据血细胞减少和相应的症状及病态造血、细胞遗传学异常、病理学改变,MDS 的诊断不难确立。
但随着高通量测序技术的发展近年来人们对MDS 的认识进一步加深,在对MDS 进行基因检测时,发现了多个基因突变。
并且在该领域的相关研究中显示,MDS 的基因突变情况和该病的预后有着密切的关系。
现阶段研究中已经获得证实的观点认为,MDS 突变基因可分为6大类,具体包括了转录基因突变、RNA 剪切因子基因突变以及信号转导相关基因突变等。
这些突变的阳性率可达到90%以上,为MDS 的治疗提供了重要信息。
1基因突变1.1RNA 剪切因子基因突变在MDS 的基因突变中,以剪接体基因的体细胞突变发生率较高,其突变多以互斥的方式影响剪接致基因功能获得性突变出现新表型[1-5]。
前mRNA 剪接是真核基因表达的重要生理功能之一,剪接是由剪接体来执行,人类有两个剪接体系统:主要的U2依赖系统和次要的U12依赖系统。
剪接体是由5个核内RNA 与蛋白质组成的核内核糖核蛋白(snRNP)[6]。
SF3B1、SRSF2、U2AF1和ZRSR2为MDS 中基因突变发生率较高的剪接因子基因,编码的蛋白质都参与识别3'剪接位点[7]。
其中SF3B1负责识别前mRNA 3'端附近的分支位点,突变多发生于密码子700的错义替换,其可能会导致ABCB7剪切异常,导致带有缺陷的ABCB7蛋白使线粒体内承载了过多的血红素而出现无效造血[8]。
SF3B1突变多见于MDS 伴环形铁粒[基金项目]2020年吉林省卫生与健康科技能力提升项目(2020J105)。
[作者简介]朱亚男(1996-),女,硕士,住院医师,研究方向为血液系统疾病的临床研究。
表观遗传标记在猪分子育种中的研究与应用前景
家畜的表观基因组的研究也吸引了众多科研人员的 目光。 2012 年， Li 等 [9]利用 3 个品种猪绘制了猪脂 肪组织和肌肉组织的 DNA 甲基化图谱， 发现了 DNA 甲基化的分布情况与猪的脂肪形成有着某种相关性， 从而极大地推动了表观遗传标记在猪分子育种领域 的研究进展。然而当前表观遗传标记与猪某些重要 性状之间的关系仍未阐明，在一定程度上限制了表 观遗传标记在猪分子育种领域的应用。只有深刻理 解两者之间的联系，才有望打破猪育种过程中的技 术瓶颈，迎来猪分子育种领域的新浪潮。本文重点 介绍了表观遗传学在猪分子育种中的研究与应用前 景，以期为猪的分子育种提供一种新的方向，建立 新的分子育种策略，提高猪的育种效率。
Hereditas (Beijing)
2016 年 7 月 , 38(7): 634― 643
综 述
表观遗传标记在猪分子育种中的研究与应用前景
张轲 1，冯光德 2，张宝云 1，向伟 1，陈龙 1，杨芳 1，储明星 3，王凭青 1
1. 重庆大学生物工程学院，重庆 400030； 2. 四川铁骑力士牧业科技有限公司，绵阳 621000； 3. 中国农业科学院北京畜牧兽医研究所，农业部畜禽遗传资源与种质创新重点实验室，北京 100193
摘要: 家畜动物的表型是由基因组、表观基因组和环境等多种因素相互影响共同作用决定的。近年来，随着遗
传育种领域的迅速发展，表观遗传标记在猪分子育种中的研究受到越来越多科研人员的关注。表观遗传学是研 究基因表达发生可遗传的改变而 DNA 序列不发生改变的一门生物学分支学科，其遗传标记主要包括 DNA 甲 基化、组蛋白修饰、非编码 RNA、印记基因等。越来越多的研究表明，表观遗传标记在猪的遗传性状中发挥 着重要作用，主要通过调控与性状相关基因的表达进而达到改变生物表型的目的。然而，在当前猪分子育种领 域，表观遗传标记的作用还没有得到足够的重视，影响猪重要性状的机制还没有得到深度解析，因此在实际应 用中还缺乏足够的科学依据和可操作性。本文从营养、疾病、重要经济性状以及隔代遗传几个方面综述了表观 遗传标记在猪分子育种中的研究现状、应用前景以及遇到的挑战，以期为表观遗传标记在猪分子育种中的应用 提供较全面的理论依据。
分子标记在花卉研究中的应用现状
第26卷第2期2002年3月 南京林业大学学报(自然科学版)Journal of Nanjing Forestry University (Natural Sciences Edition ) Vol.26,No.2 Mar.,2002 分子标记在花卉研究中的应用现状Ξ蔡友铭1,武 雯2,邹惠渝2,黄敏仁2(1.上海市花卉育种中心,上海 200072;2.南京林业大学,江苏 南京,210037)摘 要:生物技术的发展给植物遗传育种研究带来了巨大的变化,DNA 分子标记技术的应用是其中最显著的变化之一。
遗传育种是花卉业发展的重要基础,也是技术创新最活跃的分支。
笔者从分子遗传图谱的构建、亲缘关系分析、农艺性状定位、标记辅助选择等4个方面阐述了分子标记在花卉育种研究中的应用。
关键词:分子标记;花卉;应用中图分类号:S722 文献标识码:A 文章编号:1000-2006(2002)02-0084-03Application of Molecular Marker in the Study of Flow ers PlantsCAI Y ou 2ming 1,WU Wen 2,ZOU Hui 2yu 2,HUAN G Min 2ren 23(1.Seeds Station of Shanghai ,Shanghai 200072,China ;2.Nanjing Forestry University ,Nanjing 210037,China )Abstract :Great changes in the study of plant genetic breeding had been brought about by the development of biotechnology ,and the application of DNA molecular marker technique is one of the most significant changes.G enetic breeding is an important base for the development of flower plant industry and also is one of the most active branches in technical innovation.The application of molecular marker in the study of flower plants genetic breeding such as construction of molecular genetic map ,analysis of relationship ,location of ornamental characters and marker 2assisted selection is described in this paper.K ey w ords :Molecular marker ;Flower plants ;Application分子标记是在人类基因组计划(Human G enome Initiative 简称HGI )的推动下迅速发展起来,并在各个领域得到广泛应用。
（GossypiumhirsutumL.）
T ITLEIdentification of a RAPD marker linked to a male fertility restoration gene in cotton (Gossypium hirsutum L.)Tien-Hung Lan1, Charles G. Cook2 & Andrew H. Paterson1, *1Department of Soil and Crop Sciences, Texas A&M University, College Station, TX 77843-24742USDA-ARS, Weslaco, TX 78596(*authorforcorrespondence,**********************.edu,fax:409-845-0456)K EY WORDSbulked segregant analysis, cytoplasmic male sterility, near-isogenic line, linkage mappingA BSTRACTOne RAPD marker, 6 cM away from a gene which restore male-fertility of a male-sterile cytoplasm was found in upland cotton (Gossypium hirsutum L.). This marker was discovered after screening 400 decamers to identify DNA polymorphism between near-isogenic lines and subsequently verified by bulked segregant analysis in an F2 population of 89 individuals derived from a cross between a cytoplasmic-male-sterile line and a restorer line. The RAPD marker was sub-cloned, sequenced, and mapped to a cotton high density RFLP map. The evaluation and utilization of this RAPD for tagging and ultimately cloning the fertility-restoring gene is discussed.I NTRODUCTIONCytoplasmic male sterility (CMS) is a maternally inherited trait conferring the inability to produce functional pollen because of interaction between cytoplasmic and nuclear genes. Since CMS does not affect female fertility, male sterile plants are able to set seeds as long as viable pollen are provided. The presence of certain nuclear genes, Rf (Restoring fertility), can effectively suppress the male-sterile cytoplasm and restore pollen fertility. The application of CMS/Rf system has proved to be an effective means to produce commercial F1 hybrid seed for many crops (Williams 1992). Cotton is predominantly a self-pollinated crop, however, cotton breeders have long been trying to breed F1 hybrid cotton, to harness F1 heterosis for many desirable traits such as high seedling-vigor, earliness, superior fiber quality and yield (Davis 1978), but also because F1 hybrid seeds could generate huge revenue for the seed industry (Anonymous 1985). Therefore, attempts to produce F1 hybrid cotton on a commercial scale have never stopped (Anonymous 1987). Before the introduction of the CMS/Rf system into Upland cotton, the only way to generate commercial hybrid cotton was through hand emasculation and crossing, which was economical only in China and India where labor cost are low. In US where labor costs are high, hand-crossing made the price of hybrid cotton prohibitive.The first CMS line of commercial cotton was introduced by crossing an upland cotton, G. hirsutum, as male parent, to a wild species, G. harknessii (Meyer 1973). A Rf line was also developed by transferring a nuclear restorer gene from G. harknessii into G. hirsutum simultaneously (Meyer 1975). The F1 hybrid population generated by crossing the CMS line to the Rf line showed a wide range of male fertility expression. Several CMS/Rf lines were then developed through the backcross method (Weaver and Weaver 1977). Later, a second Rf which expresses incomplete dominance, was also identified in G.barbadense (Sheetz and Weaver 1980). Identification of molecular markers closely linked to the nuclear Rf genes could help breeders to distinguish male-sterile and fertile plants prior to pollen shed. Here we report the identification of molecular markers closely-linked to the nuclear Rf gene under male-sterile cytoplasm in commercial cotton.M ATERIAL AND M ETHODA pair of cotton near-isogenic lines, HAF277 and DELCOT277 (kindly provided by R. Bridge, USDA-ARS, Stoneville, MS; Meyer 1975; Weaver and Weaver 1977; Sheetz and Weaver 1980), carrying the Rf gene and CMS respectively were used for initial RAPD-PCR screening. A single primer was used in each PCR reaction, and the PCR products were resolved in 1.6 % agarose gels using established techniques (Williams et al. 1990). An F2 segregating population comprised of 89 individuals from a cross of a CMS line, A2, and a Rf line, B418, were used for bulked segregant analysis (Giovannoni et al. 1991, Michelmore et al. 1991).Linkage analysis was performed using MapMaker (Lander et al. 1987), Macintosh version 2.0 (kindly provided by S. Tingey, DuPont), using the Kosambi centiMorgan function. A threshold of LOD 3.0 was used to test linkage.ResultRAPD screeningAfter screening 400 random decamers obtained from the University of British Columbia, 15 positive RAPDs were identified, which represent 3.75 % of the tested primers . These positive RAPDs were verified twice, on fresh DNA extractions, to avoid false-positives. We applied bulked segregant analysis (Giovannoni et al. 1991; Michelmore et al. 1991) for further exploration of the 15 positive RAPD markers identified in the near-isogenic lines. From the A2 x B418 F2 population, we chose 19 individuals that were clearly fertile, and 19 individuals that were clearly sterile to construct the DNA pools, and to avoid individuals that were of doubtful phenotype. To increase the stringency of our test, two pairs of synthetic DNA pools were constructed for each phenotype (fertile and sterile). One pair of pools contained 9 individuals each in the CMS and Rf pool, the other contained 10 individuals each. The pooled DNA was then used as template for RAPD-PCR analysis. Among the fifteen identified markers, two RAPD markers, R6952 (sequence CGGTTTCGTA ) and R6861 (sequence CGTGACAGGA), putatively distinguished between male-sterile and male-fertile pools.Two RAPD markers were then subjected to linkage analysis using the 38 F2 plants used in constructing the synthetic DNA pools. Four replicas were used, and each amplified band was scored as a dominant locus. Linkage analysis show R6861 was 24.6 cM from the Rf gene, and R6592 was 2.3 cM away.SequencingThe marker R6592 was eluted from the agarose gel, and cloned into the EcoRV site of dTTP-end-filled pBluescript(KS), then sequenced from both ends using the T3/T7 primers on a Applied Biosystem 373 DNA Sequencing System. From the end sequences of R6592, the correct RAPD primer sequence was identified (Fig. 1), and the sequence ofR6952 was deposited into Genbank with accession number AF094829 and AF094830. A blast search of R6592 in Genbank did not found any corresponding sequence at 95% confidence level.Southern AnalysisGenomic DNA of A4 and B418 was digested by BamH1, Cfo1, EcoR1, EcoRV, HindIII and XbaI, gel-separated, and blotted to Hybond N+ membrane as described (Reinisch et al. 1994). Gel-isolated R6592 and R6861 were P32 labeled and applied to the blots. However, a smear pattern was observed and no restriction-enzyme-polymorphism could be identified between A4 and B418, suggesting that both R6592 and R6861 contain repetitive sequence. Thus, R6592 was further digested with a mixture of Acc1, Cfo1, Hinf1, HindIII and EcoR1, and sub-cloned into pBluescript to try to remove the interfering repetitive sequence. One clone, R6592a14, identified a HindIII polymorphism between A4 and B418, though the background on the p32-exposed film was still pretty high. R6592a14 was then used to genotype the 89 individuals of A4 x B418 F2 population for the HindIII polymorphism. Linkage analysis revealed the distance between Rf gene and R6592 to be 6 cM (Fig 2a), not significantly different from the earlier estimate based on 38 individuals. Further, we tried to map R6592a14 in a cotton high-density linkage map based on a cross of Gossypium hirsutum and Gossypium barbadense (Reinisch et al. 1994). R6592a14 did not detect HindIII polymorphism in this population, but one of six genomic restriction fragments did detect EcoRV polymorphism. R6592a14 mapped to a linkage group that was tentatively identified as chromosome 20 (Reinisch et al. 1994), between markers pAR959 and pAR3-41 (Fig. 2b).DiscussionSince the near-isogenic lines we used have been backcrossed for at least 8 generations, the introgressed region should be less than 14.1 cM (Hanson 1959; using the average cotton chromosome length of 200 cM from Reinisch et al. 1994). This is consistent with the distance of R6592a14 to the Rf locus. The larger distance between R6861 and Rfwas unexpected, but R6861 was not extensively verified, so the estimated map distance is based on a small number of individuals.For the purpose of marker-assisted selection, the best scenario was to find tightly linked markers on both side of the target gene to reduce the risk of mis-genotyping due to single recombination events between the marker and the target gene. More markers linked to the Rf gene would be desirable and could be found either by targeted RAPD or AFLP screens, or in the course of further enrichment of the cotton map. The CMS/Rf is a potentially cost-effective way to produce F1 hybrid seeds. Rf genes have been successfully mapped in rice and common bean by RAPD/bulk segregant analysis (He et al. 1995; Zhang et al. 1997), and we provide a marker diagnostic of this important phenotype in cotton. In addition to its utilization in marker-assisted selection, this marker may serve as a starting point for positional cloning of the Rf gene.A CKNOWLEDGMENTWe thank Mark D. Burow for technical assistance. Aspects of the work described here were supported by USDA 91-37300-6570, to AHP, and Texas Higher Education Coordinating Board Award 999902-148 to AHP and Rod A. Wing.Fig. 1Partial DNA sequence of clone R6592. Primer sequences are underlined.Fig. 2a. Linkage of Rf gene and marker R6592 in G. hirsutum A2 x B418 F2 population.b. Marker R6592 mapped to cotton chromosome 20 in G. hirsutum (race palmeri) x G. barbadense “k101” primary mapping population (Reinisch et al., 1994).ReferenceAnonymous, 1985 Seed Money. Forbes 136: 219-210.Anonymous, 1987 Finger-Picking Good: Hybrid Cotton. The Economist 303: 91. Davis, D. D., 1978 Hybrid cotton: specific problems and potentials. Adv Agron 30: 129-157.Giovannoni, J., R. Wing, M. Ganal and S. Tanksley, 1991 Isolation of molecular markers from specific chromosomal intervals using DNA pools from existing mapping populations. Nucl Acids Res 19: 6553-6558.Hanson, W., 1959 Early generation analysis of lengths of heterozygous chromosome segments around a locus held heterozygous with backcrossing or selfing. Genetics 44: 833-837.He, S., Z. H. Yu, C. E. Vallejos and S. A. Mackenzie 1995 Pollen fertility restoration by nuclear gene Fr in CMS common bean: An Fr linkage map and the mode of Fr action. Theor Appl Genet 90: 1056-1062.Lander, E., P. Green, J. Abrahamson, A. Barlow, M. Daly et al., 1987 MAPMAKER: An interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1: 174-181.Meyer, V., 1975 Male sterility from Gossypium harknessii. J Hered 66: 23-27.Meyer, V. G., 1973 Fertility restorer genes for cytoplasmic male-sterility from Gossypium harknessii. Beltwide Cotton Prod. Res. Conf. Proc., p65.Michelmore, R., I. Paran and R. Kesseli, 1991 Identification of markers linked to disease-resistance genes by bulked segregant analysis: a rapid method to detect markers in specific genomic regions by using segregating populations. Proc. Natl. Acad. Sci. USA 88: 9828-9832.Reinisch, A., J.-M. Dong, C. Brubaker, D. Stelly, J. Wendel et al., 1994 A detailed RFLP map of cotton (Gossypium hirsutum x G. barbadense): Chromosome organization and evolution in a disomic polyploid genome. Genetics 138: 829-847.Sheetz, R. H., and J. B. Weaver, 1980 Inheritance of a fertility enhancer factor from Pima cotton when transferred into Upland cotton with Gossypium harknessii Brandegee. Crop Science 20: 272-275.Weaver, D., and J. Weaver, 1977 Inheritance of pollen fertility restoration in cytoplasmic male-sterile upland cotton. Crop Sci 17: 497-499.Williams, J. G. K., A. R. Kabelik, K. J. Livak, J. A. Rafalski and S. V. Tingey, 1990 DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. Nucl. Acids Res. 18: 6531-6535.Williams, M. E. L. C. S., III, 1992 Molecular Biology Of Cytoplasmic Male Sterility, pp. 23-51 in Plant Breeding Reviews, edited by J. Janick. John Wiley and Sons, Inc., New York.Zhang, G., T. S. Bharaj, Y. Lu, S. S. Virmani and N. Huang, 1997 Mapping of the Rf-3 nuclear fertility-restoring gene for WA cytoplasmic male sterility in rice using RAPD and RFLP markers. Theor Appl Genet 94: 27-33.。
“生物药”--Wharton’s jelly源间充质干细胞
“生物药”--Wharton’s jelly源间充质干细胞高连如【摘要】干细胞治疗代表生物冶疗进入到了一个崭新的时代。
间充质干细胞是存在于胚胎或成体组织中来源于中胚层具有多向分化潜能的干细胞。
由于成体间充质干细胞的质量与数量自身缺陷,使之应用受到了很大限制。
Wharton’s jelly组织,是起始于胚胎发育第13天的胚外中胚层组织。
使用基因微阵列分析及功能分析,首次发现Wharton’s jelly源间充质干细胞( Wharton’s jelly derived mesenchymal stem cells,WJMSCs)高表达胚胎早期干性基因及心肌细胞分化早期特异转录因子,可分化心肌细胞等多种细胞。
进而,应用临床级WJMSCs经冠状动脉移植治疗ST抬高型急性心肌梗死患者的随机双盲临床试验,首次证明WJMSCs可明显改善心肌活力及心脏功能。
因此,WJMSCs具有极其重要益处；无伦理涉及,有强的分化潜能,无致瘤性；加之,WJMSCs可作为产品,在任何时候病情需要时立即应用。
为此,WJMSCs作为真正意义上的干细胞族,将最有希望成为具有应用前景的干细胞生物药。
%Cell-based treatment represents a new generation in the evolution of biological therapeutics. Mesenchymal stem cells ( MSCs) are mesoderm-derived multipotent stromal cells that reside in embryonic and adult tissues. The use of adult MSCs is limited by the quality and quantity of host stem cells. Wharton’s jelly of the umbilical cord originates from the extraembryonic and/or the embryonic mesoderm at day 13 of embryonic development. Using Affymetrix GeneChip microarray and functional network analyses, we found for the first time that Wharton’s jelly-derived MSCs ( WJMSCs) , except for their expression of stemness molecular markers in common with human ESCs ( hESCs) ,exhibited a high expression of early cardiac transcription factor genes and could be in-duced to differentiate into cardiomyocyte-like cells. Further, we demonstrated for the first time that intracoronary delivery of prepared clinical-grade WJMSCs was safe in treating patients with an ST-AMI attack by double-blind, randomized controlled trial and could significantly improve myocardial viability and heart function. It is therefore important to consider the benefits of WJMSCs, which are not ethically sensitive, have differentiation potential, and do not have the worrying issue of teratoma formation. Moreover, as the off the shelf product, WJMSCs can be applied immediately, and on de-mand. Thus, WJMSCs constitute a true stem cell population and are promising cells as a biological drug for stem cell-based therapies.【期刊名称】《转化医学杂志》【年(卷),期】2016(005)004【总页数】5页(P193-197)【关键词】间充质干细胞;Wharton’s jelly源间充质干细胞;生物药物【作者】高连如【作者单位】100048 北京，海军总医院心脏中心【正文语种】中文【中图分类】R329.2+4［Abstract］Cell-based treatment represents a new generation in the evolution of biological therapeutics.Mesenchymal stem cells（MSCs）are mesoderm-derived multipotent stromal cells that reside in embryonic and adult tissues.The use of adult MSCs is limited by the quality and quantity of host stem cells.Wharton’s jelly of the umbilical cord originates from the extraembryonic and/or the embryonic mesoderm at day 13 of embryonic ing Affymetrix GeneChip microarray and functional network analyses，we found for the first time that Wharton’s jelly-derived MSCs （WJMSCs），except for their expression of stemness molecular markers in common with human ESCs （hESCs），exhibited a high expression of early cardiac transcription factor genes and could be induced to differentiate into cardiomyocyte-like cells.Further，we demonstrated for the first time that intracoronary delivery of prepared clinical-grade WJMSCs was safe in treating patients with an STAMI attack by double-blind，randomized controlled trial and could significantly improve myocardial viability and heart function.It is therefore important to consider the benefits of WJMSCs，which are not ethically sensitive，have differentiation potential，and do not have the worrying issue of teratoma formation.Moreover，as the off the shelf product，WJMSCs can be applied immediately，and on demand.Thus，WJMSCs constitute a true stem cell population and are promising cells as a biological drug for stem cell-based therapies.［Key words］Mesenchymal stem cells（MSCs）；Wharton’s jelly-derived mesenchymal stem cells（WJMSCs）；Biological drug21世纪，人类疾病治疗模式在继现代医学——药物、手术、机械辅助等手段后，一个崭新的充满希望的新理念——细胞生物治疗理论诞生了，这将给人类带来什么样的变化与影响，如此快速之进展，正如Science、Nature中所表述的“即使站在世界最前沿的科学家也难以预料”［1-2］。
李韶山教授简介
李韶山教授简介李韶山，广东省珠江学者特聘教授。
1992年在华南师范大学获理学博士学位；曾留学瑞典Lund University和Örebro University以及美国College of William & Mary。
现任华南师范大学生命科学学院副院长，生态学专业博士生导师。
多年来从事植物生理生态学研究，主要研究方向是植物紫外辐射（UV-B）效应的细胞和分子机理研究、植物对重金属污染的分子响应和生态毒理、微生物与植物根系的相互作用、以及入侵植物的生态适应性和比较基因组学研究。
已主持承担多项国家自然科学基金、教育部博士点基金、教育部留学回国人员科技项目以及广东省高层次人才项目等。
在国际、国内重要学术刊物发表的代表性论文（标注*为通讯作者）：1.Jiang Lei, Wang Yan, Li Qianfeng, Björn LO, He Junxian, Li Shaoshan*.Arabidopsis STO/BBX24 negatively regulates UV-B signaling by interacting with COP1 and repressing HY5 transcriptional activity.Cell Research, 2012, 22:1046-1057 (IF=10.526)2.Qin Rong, Zhang Huaning, Li Shaoshan, Jiang Wusheng, Liu Donghua*. Threemajor nucleolar proteins migrated from nucleolus to nucleoplasm and cytoplasm in root tip cells of Vicia faba L. exposed to aluminum. Environmental Science and Pollution Research, 2014, 21: 10736-10743（IF=2.681）3.Gong Ni, Wang Yutao, Björn L O, and Li Shaoshan*. DNA C-values of 20invasive alien species and 3 native species in south China. Archives of Biological Sciences, 2014, 66(4): 1465-1472 (IF=0.607)4.Chen Yong, Zou Shenshen, Zhou Fan, Yu Sidney, Li Shaoshan, Li Dan, SongJingzen, Li Hui, He Zhiyi, Hu Bing, Björn L O, Liang Yongheng*, Xie Zhiping, Segev Nava*. A Vps21 endocytic module regulates autophagy. Molecular Biology of the Cell, 2014, 25: 3166-3177 (IF=4.548)5.Zou Shenshen, Chen Yong, Liu Yutao, Segev N, Yu S, Ye Min, Zeng Yan, MinGaoyi, Zhu Xiaoping, Hong Bing, Björn LO, Liang Yongheng*, Li Shaoshan*, Xie Zhiping*.Trs130 and Trs65 regulate autophagy through GTPases Ypt31/32 in Saccharomyces cerevisiae.Traffic 2012, , DOI: 10.1111/tra.12024 (IF=4.919)6.Chen Da, Wang Yan, Yu Lehuan, Luo Xiaojun, Mai Bixian, Li Shaoshan*. 2013.Dechlorane plus flame retardants in terrestrial raptors from northern China.Environmental Pollution, 2013, 176: 80-86 (IF=3.746)7.Björn LO*, Li Shaoshan. Teaching about photosynthesis with simple equipment:Analysis of light-induced changes in fluorescence and reflectance of plant leaves.Photosynthesis Research, 2013, 116: 349-353 (IF=3.243)8.Björn LO*, Uvdal P, and Shaoshan Li. Ecological importance of the thermalemissivity of avian eggshells. Journal of Theoretical Biology, 2012, 301: 62-66 (IF=2.371)9.Jiang Lei, Wang Yan, Björn LO, Li Shaoshan*. UV-B-induced DNA damagemediates expression changes of cell cycle regulatory genes in Arabidopsis root tips. Planta, 2011, 233: 831-843 (IF=3.372)10.Wang Yan, Smith W, Wang Xiaodong, Li Shaoshan. Subtle biological responsesto increased CO2 concentrations by Phaeocystis globosa Scherffel, a harmful algal bloom species. Geophysical Research Letters, 2010, 37, L09604, DOI:10.1029/2010GL042666 (IF=3.204)11.Jiang Lei, Wang Yan,Björn LO, Li Shaoshan*. ArabidopsisRADICAL-INDUCED CELL DEATH1 is involved in UV-B signaling.Photochemical and Photobiolgy Sciences, 2009,8: 838-846 (IF=2.708)12.Kalbina I, Li Shaoshan, Kalbin G, Björn LO, Strid Å*. Wavelength dependenceof expression of UV-B-induced molecular markers in Arabidopsis thaliana.Functional Plant Biology, 2008, 35: 222-227 (IF=2.375)13.Jiang Lei, Wang Yan, Li Shaoshan*. Application of the comet assay to measureDNA damage induced by UV radiation in the hydrophyte, Spirodela polyrhiza.Physiologia Plantarum, 2007, 129: 652-657 (IF=2.708)14.Li Shaoshan, Kalbin G, Olsman H, Pettersson M, Engwall M, Strid Å*, Effects ofUV-B in biological and chemical systems: Equipment for wavelength dependence determination. Journal of Biochemical and Biophysical Methods, 2005, 65: 1-12 (IF=1.286)15.Li Shaoshan and Strid Å*, Anthocyanin accumulation and changes in CHS andPR-5 gene expression in Arabidopsis thaliana after removal of the inflorescence stem (decapitation). Plant Physiology and Biochemistry, 2005, 43: 521-525(IF=2.485)16.Li Shaoshan*, Wang Yan, Björn LO, Effects of temperature on UV-B-inducedDNA damage and photorepair in Arabidopsis thaliana. Journal ofEnvironmental Sciences, 2004, 16: 173-176 (IF=1.412)17.Li Shaoshan, Paulsson M, Björn LO, Temperature-dependent formation andphotorepair of DNA damage induced by UV-B radiation in suspension-cultured tobacco cells. Journal of Photochemistry and Photobiology, B: Biology, 2002,66 : 67-72 (IF=2.708)18.Li Shaoshan, Wang Yan, Wang Xiaojing, Bin Jinhua and Liu Songhao. CPDsaccumulation in relation to UV-B sensitivity in rice cultivars. Acta Botanica Sinica, 2000, 42 (6): 576-581 (IF1.395)19.汪骢跃†、王宇涛†、曾琬淋、李韶山*，钙和钾对拟南芥幼苗镉毒害的缓解作用。
SS18阳性滑膜肉瘤中ER-PR阳性亚型的临床病理研究及ALK-C-met高表达的意义
SS18阳性滑膜肉瘤中ER-PR阳性亚型的临床病理研究及ALK-C-met高表达的意义摘要：目的：本研究旨在探讨SS18阳性滑膜肉瘤中ER/PR阳性亚型的临床病理特征及ALK/C-met高表达的意义，为肿瘤的治疗和预后提供可靠依据。
方法：采用回顾性研究的方法，回顾性分析了2010年至2019年间确诊为SS18阳性滑膜肉瘤的患者的临床资料及病理检查结果，筛选出ER/PR阳性亚型的患者，通过免疫组化检测ALK 和C-met的表达情况，对患者的预后进行分析。
结果：共纳入了60例滑膜肉瘤患者，其中13例（21.7%）表现为ER/PR阳性亚型。
ALK和C-met的高表达率分别为38.5%和61.5%。
ER/PR阳性患者的平均年龄为32岁，男女比例为1:2。
临床表现以关节肿痛和运动障碍为主，病理分化程度为Ⅱ-Ⅲ级。
ALK和C-met高表达与ER/PR阳性患者、年龄、临床表现及分化程度等相关因素无明显关系。
但观察发现，ALK 和C-met的高表达与滑膜肉瘤的预后密切相关。
结论：ER/PR阳性亚型的滑膜肉瘤具有特殊的临床病理特征，ALK和C-met的高表达可作为滑膜肉瘤预后的重要指标，进一步的研究有助于为患者提供更加精准的诊疗方案和治疗策略。
关键词：SS18阳性滑膜肉瘤；ER/PR阳性亚型；ALK；C-met；临床病理特征；预后Clinical and pathological study of ER/PR-positive subtype in SS18-positive synovial sarcoma and its significance of high expression of ALK/C-metAbstract:Objective: The study aimed to investigate the clinical and pathological characteristics of ER/PR-positive subtype in SS18-positive synovial sarcoma and the significance of high expression of ALK/C-met, providing reliable basis for the treatment and prognosis of tumors.Methods: The retrospective study method was used to retrospectively analyze the clinical data and pathological examination results of patients diagnosed with SS18-positive synovial sarcoma from 2010 to 2019. ER/PR-positive subtype of patients was screened out. The expression of ALK and C-met was detected by immunohistochemistry, and the prognosis of patients was analyzed.Results: a total of 60 synovial sarcoma patients wereincluded, 13 of whom (21.7%) showed ER/PR-positive subtype. The high expression rates of ALK and C-met were 38.5% and 61.5%, respectively. The average age of ER/PR-positive patients was 32 years old, and theratio of men to women was 1:2. The clinical manifestations were mainly joint swelling and motion disorders, and the pathological differentiation degree was II-III level. The high expression of ALK and C-met was not significantly related to ER/PR-positive patients, age, clinical manifestations,differentiation degree, and other related factors. However, it was found that the high expression of ALK and C-met was closely related to the prognosis of synovial sarcoma.Conclusion: ER/PR-positive subtype of synovial sarcoma has special clinical and pathological characteristics. High expression of ALK and C-met can be used as an important indicator of the prognosis of synovial sarcoma. Further research can provide more accurate diagnosis and treatment plans and strategies for patients.Keywords: SS18-positive synovial sarcoma; ER/PR-positive subtype; ALK; C-met; clinical andpathological characteristics; prognosiIn recent years, advances in molecular diagnostic methods have revealed the complexity and heterogeneity of synovial sarcoma, paving the way for personalized treatment based on the molecular characteristics of the tumor. The ER/PR-positive subtype, which is more common in females and has lower metastatic potential, has distinct clinical and pathological features, including an earlier age of onset, a smaller tumor size, and a higher rate of lymph node involvement.Recent studies have shown that ALK and C-met play important roles in the pathogenesis and progression of synovial sarcoma. High levels of ALK expression have been associated with a poor prognosis and resistance to chemotherapy, while high levels of C-met expression have been linked to a higher rate of metastasis and decreased overall survival. Therefore, the expression levels of ALK and C-met can serve as important indicators of the prognosis of synovial sarcoma and can guide treatment decisions.Overall, the ER/PR-positive subtype of synovial sarcoma has unique clinical and pathological characteristics that distinguish it from other subtypes of this rare cancer. The identification of molecular markers such as ALK and C-met can provide valuable prognostic information that can guide thedevelopment of individualized treatment plans for patients with synovial sarcoma. Further research is needed to better understand the molecular mechanisms underlying synovial sarcoma and to develop more effective therapies for this challenging diseaseIn addition to ALK and C-met, other molecular markers have been investigated as potential prognostic indicators for synovial sarcoma. For example, the expression of EZH2, a histone methyltransferase, has been found to correlate with poor prognosis in synovial sarcoma patients (Glenisson et al., 2021). Similarly, high levels of the protein CDK6, aregulator of the cell cycle, have been associated with decreased survival in synovial sarcoma patients (Dufresne et al., 2019).The role of immunotherapy in the treatment of synovial sarcoma is also an area of active research.Preclinical studies have shown that synovial sarcoma cells express high levels of PD-L1, a protein that can inhibit immune responses, suggesting that immune checkpoint inhibitors may be effective in treating these tumors (Lee et al., 2019). However, clinical trials investigating the use of immune checkpoint inhibitors in synovial sarcoma have had mixed results, with some patients showing significant responses whileothers do not benefit from the treatment (Toulmonde et al., 2020).In addition to the development of targeted therapies and immunotherapies, efforts are also underway to improve the detection and diagnosis of synovial sarcoma. Advances in imaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), have allowed for more accurate diagnosis and staging of this disease (Brisson-Noël et al., 2018). Furthermore, the use of liquid biopsy techniques, which involve analyzing tumor DNA in the blood, may provide a non-invasive method for monitoring the progression of synovial sarcoma and detecting early signs of recurrence (Eberhardt et al., 2020).In conclusion, synovial sarcoma is a rare and aggressive cancer that poses significant challengesfor clinicians and researchers. Advances in our understanding of the molecular mechanisms underlying this disease have provided new opportunities for the development of targeted therapies and immunotherapies. However, further research is needed to improve the accuracy of diagnosis and develop more effective treatments for this devastating diseaseSynovial sarcoma is a complex disease that requires a multidisciplinary approach to diagnosis and treatment. The rarity and aggressiveness of the disease, coupled with the lack of effective treatments, make it a significant challenge for patients, clinicians, and researchers alike. Despite these challenges, recent advances in understanding the molecular and genetic mechanisms underlying the disease offer new hope for the development of effective treatments.One of the key challenges in diagnosing synovial sarcoma is distinguishing it from other soft tissue sarcomas. Accurate diagnosis is critical for determining appropriate treatment options andpredicting patient outcomes. However, the overlapping clinical and radiological features of synovial sarcoma with other sarcomas can make diagnosis challenging. Molecular diagnostics, including the use of FISH and PCR techniques, can help confirm the diagnosis and distinguish synovial sarcoma from other sarcomas.Treatment options for synovial sarcoma are currently limited, and outcomes for patients are often poor. Surgery remains the primary treatment option, and adjuvant therapies, such as radiation and chemotherapy, may be used to improve outcomes. However, the effectiveness of these treatments is limited, and thetoxicities associated with chemotherapy can be significant.Recent studies have identified new potential targets for the development of targeted therapies and immunotherapies for synovial sarcoma. These studies have identified a variety of potential molecular targets, including the SS18-SSX fusion protein, which is unique to synovial sarcoma and is thought to play a critical role in the development of the disease. Immunotherapies, such as checkpoint inhibitors and CAR T-cell therapies, have also shown promise in preclinical studies, and may offer new treatment options for patients with synovial sarcoma.In conclusion, synovial sarcoma is a challenging and complex disease that requires a multidisciplinary approach to diagnosis and treatment. While current treatment options are limited, advances in our understanding of the molecular and genetic mechanisms underlying the disease offer new opportunities for the development of effective targeted therapies and immunotherapies. Further research is needed to improve the accuracy of diagnosis and develop more effective treatments for this devastating diseaseIn conclusion, synovial sarcoma is a complex and challenging disease that requires a multidisciplinary approach to diagnosis and treatment. While current treatment options are limited, ongoing research into the molecular and genetic mechanisms of the disease offers new opportunities for targeted therapies and immunotherapies. Further research is needed to improve the accuracy of diagnosis and develop more effective treatments for this devastating disease。
胃癌前病变分子标志物筛选
基因组学与应用生物学,2020年，第39卷，第丨0期，第4797-4802页研宄报告Research Report胃癌前病变分子标志物筛选王俐勇1朱圣韬”1首都医科大学中心实验室，北京，100069;2首都医科大学附属北京友谊医院，北京市消化疾病中心，国家消化系统疾病临床医学研究中心，消 化疾病癌前病变北京市重点实验室，北京，100050* 通信作者，z h u s h e n g t a o@c c m u.e d u.c n摘要本实验旨在研究胃癌前的发生分子机制，通过建立人胃粘膜上皮细胞癌前病变细胞模型，利用高通 量测序技术在转录水平上分析胃癌前病变细胞与正常胃上皮细胞之间差异表达基因的功能及其编码蛋白的 相互作用，筛选出癌前病变相关的关键基因,将多个基因作为分子标记物，并在转录水平上检测这些基因在 胃癌细胞系的表达情况。
同时结合大样本临床数据的生存曲线和这些基因在胃癌组织中蛋白水平分析，推测 这些基因与胃腺癌的生存率密切相关。
研究结果表明这些基因有可能作为胃癌前病变诊疗分子标记物组合，这对于实现胃癌前病变分子分型，建立胃癌前病变早期诊治体系提供理论基础有重要意义。
关键词胃癌前病变，分子标记物，高通量测序，早期诊治Screening of Molecular Markers for Precancerous Lesions of Gastric CancerW a n g Liyong1Zhu Shengtao2*1 C o r e o f F a c i l i t y,C a p i t a l M e d i c a l U n i v e r s i t y,B e i j i n g,100069;2B e i j i n g K e y L a b u r a l u r y f u r P r e c a n c e r o u s L e s i o n s o f D i g e s t i v e D i s e a s e s,N a t i o n a lC e n t e r o f C l i n i c a l M e d i c i n e f o rD i g e s t i v e D i s e a s e s,B e i j i n g F r i e n d s h i p H o s p i t a l,C a p i t a l M e d i c a l U n i v e r s i t y,B e i j i n g C e n t e r o f D i g e s t i v e D i s e a s e s,B e ij i n g,100050*C o r r e s p o n d i n g a u t h o r,z h u s h e n g t a o@c c m u.e d u.c nD O I:10.13417/j.g a b.039.004797Abstract The purpose of this study i s to investigate molecular mechanism of precancerous lesions.With the cell model established by h u m a n gastric mucosal epithelial cells,differentially expressed genes between precancerous lesion cells and normal gastric epithelial cells were analyzed at transcriptional level by high-throughput sequencing,including interaction of their coding proteins.The key genes related to precancerous lesion as molecular markers were screened out and expression of these genes in gastric cancer cell lines was detected at the transcriptional level.At the same time,based on survival curve analysis of large sample clinical data and protein levels analysis of these genes in gastric cancer tissue,i t i s speculated that these genes are closely related to the survival rate of gastric adenocarcinoma,and were analyzed.The results showed that these genes m a y be used as molecular markers for the diagnosis and treatment of precancerous lesions,which provides a theoretical basis for the study of molecular typing of precancerous lesions and the establishment of early diagnosis and treatment system of precancerous lesions.Keywords Precancerous lesions of g astric cancer,Molecular marker,High-throughput sequencing,Early diagnosis胃癌(gastric cancer,G C)是威胁人类健康的重要术水平提高，以及化疗、辅助治疗和分子靶向治疗使 癌症之一，在癌症死亡中排在第2位(McClain etal.,预后显著改善，但胃癌患者总生存率并没有显著提 2017)。
中华医学会病理学会第十九次学术会议暨第三届中国病理年会日程框架
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沉默LIMK1通过Rac1-Rock1/Pak1通路增强DADS抑制人胃癌BGC823细胞增殖与迁移侵袭杨邦敏湖南省胃癌研究中心，南华大学肿瘤研究所，湖南省高校肿瘤细胞与分子病理学重点实验室--------------------------------------------------------------------------------第二分会场2013-11-0914:00-16:00 淋巴造血学组主持人:朱雄增,李文才BB01 14:00-14:30 [专题发言] 关于淋巴瘤病理分类的一些新认识李小秋复旦大学附属肿瘤医院病理科/复旦大学上海医学院肿瘤学系BB02 14:30-15:00 [专题发言] Castleman病的诊断标准建议刘勇江西省人民医院病理科BB03 15:00-15:30 [专题发言] 淋巴瘤初始事件周小鸽首都医科大学附属北京友谊医院BB04 15:30-16:00 [专题发言] 组合型淋巴造血肿瘤的病理诊断陈刚福建省肿瘤医院--------------------------------------------------------------------------------16:10-18:00 淋巴造血学组主持人:王晋芬,冯振博BB05 16:10-16:20 [论文交流] B细胞淋巴瘤LITAF基因甲基化状态及其临床意义王金洁浙江大学病理学与病理生理学，病理学与法医学研究所BB06 16:20-16:30 [论文交流] 运用IgH及TCR基因重排对淋巴瘤骨髓累及的评价及结果不符样本的原因分析叶庆南京大学医学院医学院附属鼓楼医院BB07 16:30-16:40 [论文交流] Hsa-miR-150 induces OciI-Ly10 large B cell lymphoma cell lines differentiation toward terminal B cell 严金海南方医科大学基础医学院病理学系BB08 16:40-16:50 [论文交流] PI3K/AKT通路的拷贝数变异和PI3K亚单位蛋白的异常表达与弥漫性大B细胞淋巴瘤预后差相关崔文丽复旦大学附属肿瘤医院病理科BB09 16:50-17:00 [论文交流] 滤泡变异型外周T细胞淋巴瘤1例临床病理分析及文献复习林洁南方医科大学南方医院病理科BB10 17:00-17:10 [论文交流] C-KIT突变在伴t(8;21)或inv(16)的急性髓系白血病中的研究韩聪中国医学科学院血液病医院病理中心BB11 17:10-17:20 [论文交流] 针对弥漫性大B细胞淋巴瘤的免疫表型分类结果相悖病例的预后因素研究王银萍吉林大学第一医院临床病理诊断中心BB12 17:20-17:30 [论文交流] 甲型H1N1流感重症患者免疫器官病理形态学及T、B淋巴细胞的变化特点齐晶首都医科大学病理学系--------------------------------------------------------------------------------第三分会场2013-11-0914:00-16:00 消化学组主持人:丁彦青,杜祥BB01 14:00-14:30 [专题发言] 抑癌基因Decorin在结肠癌发生和转移中的分子机制杨万才BB02 14:30-14:45 [专题发言] 结直肠癌分子病理学来茂德浙江大学医学院BB03 14:45-15:30 [专题发言] 消化系统靶向治疗的临床与病理袁瑛BB04 15:30-16:00 [专题发言] 结直肠癌患者KRAS基因、BRAF基因突变特征、错配修复基因表达缺失状态及其临床病理相关性的回顾研究叶菊香北京大学医学部病理学系北京大学第三医院病理科--------------------------------------------------------------------------------16:10-18:00 消化学组主持人:朱建善,孙振柱BB05 16:10-16:18 [论文交流] TET1通过影响5-羟甲基胞嘧啶修饰而参与肝癌的发生刘丽梅第三军医大学第一附属医院全军病理学研究所BB06 16:18-16:26 [论文交流] A study of expression of stemness markers (CD133 and epithelial cell adhesion molecule EpCAM) in prognostication of hepatocellular carcinoma 陈永鸿香港中文大学病理解剖及细胞学系BB07 16:26-16:34 [论文交流] 64例胰腺神经内分泌肿瘤的临床病理特征分析——采用WHO 2010第四版新的分类与命名系统要文青四川大学华西医院病理科BB08 16:34-16:42 [论文交流] 壶腹部肿瘤的临床病理新进展滕晓东浙江大学医学院附属第一医院BB09 16:42-16:50 [论文交流] 人乳头瘤状病毒感染及抗原加工相关转运体分子表达与食管癌发生关系的研究刘玲河北医科大学第二医院病理科BB10 16:50-16:58 [论文交流] 胃粘膜活检非肿瘤性病变的病理诊断陈国璋香港伊利沙伯医院病理医学部BB11 16:58-17:06 [论文交流] 53例炎症性肠病手术切除标本临床病理特点及鉴别诊断黄艳中山大学附属第六医院病理科BB12 17:06-17:14 [论文交流] AGR2 Is Associated with Gastric Cancer Progression and Survival of Patients 何向蕾浙江省人民医院病理科BB13 17:14-17:22 [论文交流] 日本血吸虫病传播阻断15年后人大肠肠神经系统的观察袁琳娜浙江省嘉兴市第一医院病理科BB14 17:22-17:30 [论文交流] CD133、CD44、Lgr5和CD26在结直肠癌中表达及其与预后的关系任翡复旦大学附属肿瘤医院--------------------------------------------------------------------------------第四分会场2013-11-0914:00-16:00 骨软组织学组主持人:王瑞琳,王连唐BB01 14:00-14:30 [专题发言] 骨肿瘤会诊分歧黄啸原北京积水潭医院BB02 14:30-15:00 [专题发言] 肉瘤样恶性间皮瘤王坚复旦大学附属肿瘤医院BB03 15:00-15:30 [专题发言] 2013WHO软组织肿瘤新类型贡其星江苏省人民医院BB04 15:30-16:10 [专题发言] 软组织肿瘤进展范钦和江苏省人民医院--------------------------------------------------------------------------------16:20-18:00 骨软组织学组主持人:阎晓初,陈洪军BB05 16:20-16:28 [论文交流] 硬化性纤维母细胞瘤临床病理分析宫丽华宫丽华北京积水潭医院病理科BB06 16:28-16:36 [论文交流] 血管周上皮样细胞肿瘤免疫表型研究夏秋媛南京大学医学院临床学院南京军区南京总医院病理科BB07 16:36-16:44 [论文交流] 软组织肿瘤免疫组化诊断及其相关问题阎晓初第三军医大学第一附属医院全军病理学研究所BB08 16:44-16:52 [论文交流] 32例多形性脂肪肉瘤的临床病理及分子遗传学特征分析王磊复旦大学附属肿瘤医院病理科BB09 16:52-17:00 [论文交流] 胃肠道间质瘤合并消化系统肿瘤的临床病理学及分子遗传学研究刘秋雨河南省人民医院,病理科BB10 17:00-17:08 [论文交流] 良性转移性平滑肌瘤的起源及发病机理林洁中日友好医院病理科BB11 17:08-17:16 [论文交流] 组蛋白甲基化修饰与印记基因TSSC3相互作用在骨肉瘤失巢凋亡中的作用吕杨帆第三军医大学第一附属医院全军病理学研究所BB12 17:16-17:24 [论文交流] Clinical and biological significance of hepatoma-derived growth factor in Ewing sarcoma 杨飏中山大学附属第一医院病理科--------------------------------------------------------------------------------第五分会场2013-11-0914:00-16:00 乳腺学组主持人:杨举伦,孙文勇BB01 14:00-14:30 [专题发言] The evolving roles of surgical pathologists in target specific therapy Hironobu Sasano 无BB02 14:30-15:00 [专题发言] Breast pathology report: what do clinicians want to knows? 唐平无BB03 15:00-15:40 [专题发言] 乳腺病理诊断中的常见误区和与困惑丁华野北京军区总医院BB04 15:40-16:20 [专题发言] 乳腺手术中冰冻诊断常见陷阱杨文涛复旦大学附属肿瘤医院--------------------------------------------------------------------------------16:30-18:00 乳腺学组主持人:孟刚,刘斌BB05 [论文交流] 阳离子检测技术在乳腺疾病冰冻切片诊断中的应用彭忠异广西中医药大学附属瑞康医院临床病理科BB06 [论文交流] 质谱成像技术在乳腺癌病理诊断中的应用研究毛歆歆北京协和医学院北京协和医院病理科BB07 [论文交流] 乳腺纤维上皮性肿瘤内癌临床病理学观察杨光之北京军区总医院病理科BB08 [论文交流] 乳腺微腺体腺病和起源于微腺体腺病的癌水若鸿复旦大学附属肿瘤医院病理科BB09 [论文交流] 雄激素受体（AR）在乳腺癌中的表达戚基萍哈尔滨医科大学附属第一医院病理科BB10 [论文交流] 1480例乳腺癌前哨淋巴结活检分析----前哨淋巴结状态与非前哨淋巴结转移的相关性徐晓丽复旦大学附属肿瘤医院BB11 [论文交流] 乳腺管状小叶癌临床病理及免疫组化特征包磊浙江省绍兴市妇幼保健院BB12 [论文交流] 75例起源于硬化性腺病的乳腺癌临床病理学特征分析于宝华复旦大学附属肿瘤医院病理科--------------------------------------------------------------------------------第六分会场2013-11-0914:00-16:00 病理技术和分子病理、分子靶向主持人:王德田,梁英杰BB01 14:00-14:30 [专题发言] 基于分子靶向时代的传统和现代病理技术周晓军南京军区南京总医院BB02 14:30-15:00 [专题发言] 淋巴瘤FISH应用和FISH标准化检测Yan chin 无BB03 15:00-15:30 [专题发言] 病理技术学在我国发展的新机遇王文勇第四军医大学病理学与病理生理学教研室暨西京医院病理科BB04 15:30-16:00 [专题发言] 单中心两个阶段1287例胃癌HER2免疫组化检测的回顾性分析樊祥山南京大学医学院附属鼓楼医院病理科--------------------------------------------------------------------------------16:10-18:00 病理技术和分子病理、分子靶向主持人:倪灿荣,丁伟BB05 16:10-16:18 [论文交流] 双色银染原位杂交技术检测胃癌组织HER2基因扩增李玉军青岛大学医学院附属医院病理科BB06 16:18-16:26 [论文交流] 微小组织芯片在胃癌HER-2免疫组化检测质量控制中的应用符雪莲微小组织芯片在HER-2免疫组化检测质量控制中的应用BB07 16:26-16:34 [论文交流] 非小细胞肺癌ALK重排Ventana免疫组化检测与荧光原位杂交检测的比较杨飞复旦大学附属肿瘤医院病理科BB08 16:34-16:42 [论文交流] 弹力纤维染色在评估肺癌胸膜侵犯中的意义赵兰香上海交通大学附属胸科医院病理科BB09 16:42-16:50 [论文交流] 初步建立FFPE组织LncRNA提取及检测技术程凯南京军区南京总医院BB10 16:50-16:58 [论文交流] 蛋白酶K修复石蜡切片免疫荧光染色在肾活检病理诊断中的应用李昌水宁波市鄞州第二医院（宁波市泌尿肾病医院）病理科BB11 16:58-17:06 [论文交流] 病理医生在生物样本库建设中的重要性孙孟红复旦大学附属肿瘤医院病理科组织库BB12 17:06-17:14 [论文交流] 大鼠早期肝纤维化模型建立李彬彬第二军医大学附属长征医院病理科--------------------------------------------------------------------------------第七分会场2013-11-0914:00-16:00 头颈部学组主持人:韦立新,何向蕾BB01 14:00-14:30 [专题发言] Frozen Section of Thyroid Pathology: Approach and Pitfalls 翟启辉无BB02 14:30-15:00 [专题发言] 鼻腔鼻窦炎性肌纤维母细胞瘤25例临床病理学分析刘红刚首都医科大学附属北京同仁医院病理科BB03 15:00-15:30 [专题发言] Borderline lesion of thyroid tumor, so-called well differentiated tumor of uncertain malignant potential and encapsulated follicular variant papillary thyroid carcinoma 刘志艳山东大学齐鲁医院病理科BB04 15:30-16:00 [专题发言] 214例泪腺肿瘤性占位性病变的临床病理学分析林锦镛天津市眼科医院--------------------------------------------------------------------------------16:10-18:00 头颈部学组主持人:高岩,李智BB05 16:10-16:18 [论文交流] 具有靴钉样特征的甲状腺乳头状癌临床病理观察解建军山东省青岛市城阳区人民医院病理科BB06 16:18-16:26 [论文交流] 甲状腺向胸腺或腮囊样分化的肿瘤的诊断及鉴别诊断韩昱晨,中国医科大学,病理BB07 16:26-16:34 [论文交流] GSTM1及CYP1A1基因多态性与甲状腺乳头状癌发病风险关系的研究张春亚大理学院附属医院病理科BB08 16:34-16:42 [论文交流] 甲状腺乳头状癌：病理可以走得更远—如何有效提取组织学特点告知临床白艳花北京肿瘤医院BB09 16:42-16:50 [论文交流] 涎腺恶性多形性腺瘤364例临床病理分析胡宇华上海交通大学医学院附属第九人民医院口腔医学院口腔病理科，上海市口腔医学重点实验室BB10 16:50-16:58 [论文交流] 良恶性副神经节瘤诊断新进展胡春燕复旦大学附属眼耳鼻喉科医院病理科BB11 16:58-17:06 [论文交流] 神经内分泌肿瘤的诊断分级和预后分子标记鲍方温州医科大附属第一医院病理科BB12 17:06-17:14 [论文交流] 原发皮肤“消退性”恶性黑色素瘤的临床病理特征沈旭霞复旦大学附属肿瘤医院病理科--------------------------------------------------------------------------------第八分会场2013-11-0914:00-16:00 数字病理及教学主持人:刘玉琴,卢朝晖BB01 14:00-14:30 [专题发言] 数字病理（全切片扫描图像）技术在病理诊断中的应用Thomas Bauer 无BB02 14:30-15:00 [专题发言] 未定外宾无BB03 15:00-15:30 [专题发言] 数字病理在医学教学中的应用沈岳良浙江大学紫金港校区医学院BB04 15:30-16:00 [专题发言] 远程病理会诊和质量控制平台的运行和展望陈杰中国医学科学院北京协和医学院北京协和医院病理科，国家卫生计生委病理质控评价中心--------------------------------------------------------------------------------16:10-18:00 数字病理及教学主持人:应建明,师永红BB05 16:10-16:18 [论文交流] 数字病理在病理诊断中的实际应用及数字化病理科的理念、构想、展望和挑战王国凤浙江大学医学院附属第二医院病理科BB06 16:18-16:26 [论文交流] 数字病理在临床病理科中的应用体会梅向林吉林大学第二医院病理科BB07 16:26-16:34 [论文交流] 应用数字病理分析软件分析60例乳腺癌分子分型孙亚欣吉林大学第二医院病理科BB08 16:34-16:42 [论文交流] 区域数字化病理中心建设探索及实践金惠铭宁波市临床病理诊断中心BB09 16:42-16:50 [论文交流] 建立本科医学生使用的病理解剖学电子学习平台E-learning in histopathology for undergraduate medical students 罗颖业香港沙田威尔斯亲王医院，香港中文大学医学院，病理解剖及细胞学系BB10 16:50-16:58 [论文交流] 鼓励学科交叉搭建科研平台强化教学主体突出诊断特色推进病理学科建设与发展李玉林吉林大学白求恩医学院,病理BB11 16:58-17:06 [论文交流] 病理学全日制专业学位研究生培养模式创新与实践的探讨王宽松中南大学湘雅医院病理科--------------------------------------------------------------------------------第一分会场2013-11-1008:00-10:00 女生殖学组主持人:路名芝,杨清绪BB01 08:00-08:30 [专题发言] 女性生殖系统微腺体增生及其类似病变的病理诊断周先荣复旦大学附属妇产科医院病理科BB02 08:30-09:00 [专题发言] 卵巢上皮性肿瘤的常见诊断问题陈晓端浙江大学医学院附属妇产科医院（浙江省妇女保健院、浙江省妇女医院）BB03 09:00-09:30 [专题发言] 子宫内膜癌FIGO分期中需关注的病理问题沈丹华BB04 09:30-10:00 [专题发言] 卵巢移行细胞肿瘤的病理诊断刘爱军解放军总医院--------------------------------------------------------------------------------10:10-12:00 女生殖学组主持人:杨开选,杨桂芳BB05 10:10-10:18 [论文交流] 宫颈早期浸润性癌病理诊断中的共识与争议沈旭霞复旦大学附属肿瘤医院病理科BB06 10:18-10:26 [论文交流] 子宫颈小细胞癌的免疫组化研究刘爱军解放军总医院病理科BB07 10:26-10:34 [论文交流] 微小腺体型子宫内膜样腺癌临床病理特征学分析刘霞新疆医科大学第一附属医院病理科BB08 10:34-10:42 [论文交流] 息肉样子宫内膜异位症的临床病理观察陈定宝北京大学人民医院病理科BB09 10:42-10:50 [论文交流] 卵巢低级别浆液性肿瘤（交界性浆液性肿瘤和低级别浆液性癌）合并高级别浆液性癌的临床病理学观察李岩济宁医学院附属医院病理科BB10 10:50-10:58 [论文交流] 盆腔浆液性癌诊断有关问题杨小玲湖北省肿瘤医院病理科BB11 10:58-11:06 [论文交流] 卵巢交界性Brenner瘤临床病理分析徐炼四川大学华西第二医院病理科--------------------------------------------------------------------------------第二分会场2013-11-1008:00-10:00 神经病理学组主持人:张声,于世柱BB01 08:00-08:30 [专题发言] 癫痫病理卢德宏首都医科大学附属北京宣武医院BB02 08:30-09:00 [专题发言] 胶质瘤干细胞研究卞修武第三军医大学西南医院BB03 09:00-09:30 [专题发言] 2013年WHO软组织肿瘤中的新命名神经肿瘤李青第四军医大学--------------------------------------------------------------------------------10:20-12:05 神经病理学组主持人:孔令非,王鲁平BB05 10:20-10:28 [论文交流] 脑膜瘤同一级别不同亚型Ki67蛋白表达的研究戚基萍哈尔滨医科大学附属第一医院病理科BB06 10:28-10:36 [论文交流] Cancer Enhancement Of Migration and Proliferation by GliomaStem Cells up-regulating Hedgehog Pathway in Endothelial Cells 郭德玉第三军医大学第一附属医院全军病理学研究所BB07 10:36-10:44 [论文交流] VEGFR-2在胶质瘤干细胞自我更新和血管拟态形成中的作用及其机制的研究姚小红第三军医大学第一附属医院全军病理学研究所BB08 10:44-10:52 [论文交流] 微血管分型维数在胶质瘤患者预后判断中的作用陈聪第三军医大学第一附属医院全军病理学研究所BB09 10:52-11:00 [论文交流] miR-663对胶质母细胞瘤恶性增殖表型的影响时雨第三军医大学第一附属医院全军病理学研究所BB10 11:00-11:08 [论文交流] 人小脑髓母瘤细胞系XQ0625的建立及其生物学特性的分析任勇第三军医大学第一附属医院全军病理学研究所BB11 11:08-11:16 [论文交流] β-catenin在星形细胞肿瘤中的表达与患者的预后相关张丽英第四军医大学西京医院病理科BB12 11:16-11:24 [论文交流] 血管中心性胶质瘤：９例报道并文献复习朴月善首都医科大学宣武医院病理科BB13 11:24-11:32 [论文交流] 中国星形细胞瘤患者中MGMT甲基化状态及其与IDH1突变的相关性研究常青北京大学医学部基础医学院病理系BB14 11:32-11:40 [论文交流] Investigation of the role of rhBMP2-induced differentiation in glioblastoma stem cells 曹相玫第四军医大学西京医院病理科BB15 11:40-11:48 [论文交流] c-Src、VEGF在人原发性中枢神经系统弥漫大B细胞淋巴瘤中表达及与微血管密度的相关性柯昌庶华中科技大学同济医学院附属同济医院病理研究所BB16 11:48-11:56 [论文交流] 6例手足口病死亡病例病理及EV71免疫组化研究钱洪流厦门大学医学院基础医学部病理教研室BB17 11:56-12:04 [论文交流] 中枢神经系统原发性ALK-1阳性间变性大细胞淋巴瘤肖华亮第三军医大学大坪医院野战外科研究所病理科--------------------------------------------------------------------------------第三分会场2013-11-1008:00-10:00 胸部肿瘤、儿科病理学组主持人:文继舫,黄爱民BB01 08:00-08:30 [专题发言] 几例肺部疾病的病理诊断分享王恩华中国医科大学病理教研室/一院病理科BB02 08:30-09:00 [专题发言] 肺腺癌2011年多学科分类实际应用后的再认识-80例肺腺癌临床病例及随访研究笪冀平中日友好医院病理科BB03 09:00-09:30 [专题发言] 肺癌的诊断和分类－应对靶向治疗和个体化医学的前景Diagnosing and Classification of Lung Carcinoma –in the perspective of Targeting Therapy & Personalized Medicine 杜家辉香港中文大學,病理解剖及细胞学系BB04 09:30-10:10 [专题发言] 肺癌靶向治疗的临床与病理张兰军--------------------------------------------------------------------------------10:20-12:00 胸部肿瘤、儿科病理学组主持人:金木兰,张冠军BB05 10:20-10:28 [论文交流] 肿瘤相关巨噬细胞和肿瘤干细胞在非小细胞肺癌中表达分布及预后分析陈露第三军医大学第一附属医院全军病理学研究所BB06 10:28-10:36 [论文交流] Brachyury通过诱导上皮间质转化加剧非小细胞肺癌的恶性演进王亮中国医科大学基础医学院病理教研室BB07 10:36-10:44 [论文交流] 免疫组化检测特异性分子靶点在非小细胞肺癌个体化治疗中的应用价值王艳芬南京大学医学院临床学院南京军区南京总医院病理科BB08 10:44-10:52 [论文交流] CRMP-2和IMP-3在肺癌中的表达及意义杨明华中科技大学同济医学院附属协和医院病理科BB09 10:52-11:00 [论文交流] 附壁成分在区分多灶肺腺癌原发或转移性质中的意义孙巍北京协和医学院中国医学科学院肿瘤医院病理科BB10 11:00-11:08 [论文交流] 肺腺癌IASLC/ATS/ERS国际多学科分类与预后的关联分析孙向洁复旦大学附属肿瘤医院病理科BB11 11:08-11:16 [论文交流] 肺肉芽肿性疾病的鉴别诊断易祥华上海市同济医院病理科BB12 11:16-11:24 [论文交流] Primary Central Nervous System Atypical Teratoid/ Rhabdoid Tumor in Children: report of five cases and literature review 杨敏浙江大学附属儿童医院病理科--------------------------------------------------------------------------------第四分会场2013-11-1008:00-10:00 细胞、心血管学组主持人:戚基萍,陈新山BB01 08:00-08:30 [专题发言] 2013年国际细胞病理学会议简介：分子病理学在细胞学诊断中的应用刘冬戈卫生部北京医院病理科BB02 08:30-09:00 [专题发言] 支气管刷片的分子检测吴广平中国医科大学附属第一医院BB03 09:00-09:30 [专题发言] 相同的临床诊断，不同的病理表型—360例心脏移植受心病理形态学研究赵红阜外心血管病医院病理科BB04 09:30-10:00 [专题发言] 医疗纠纷尸体剖验实施规范与探讨苏敏汕头大学医学院病理重点学科临床病理所--------------------------------------------------------------------------------10:10-12:00 细胞、心血管学组主持人:余小蒙,赵彤BB05 10:10-10:18 [论文交流] 颈部淋巴结细针穿刺误诊及漏诊原因分析刘蕾蕾南京军区南京总医院病理科BB06 10:18-10:26 [论文交流] 针吸细胞学在甲状腺乳头状癌诊断中的意义王玻玮新疆医科大学第一附属医院病理科BB07 10:26-10:34 [论文交流] CT引导的深部组织空芯针穿刺印片4500例分析陈颖复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系BB08 10:34-10:42 [论文交流] 心脏内平滑肌瘤病的临床病理分析商建峰首都医科大学附属北京安贞医院病理科BB09 10:42-10:50 [论文交流] 基因芯片技术在心血管系统疾病研究中的应用武迎首都医科大学附属北京安贞医院病理科BB10 10:50-10:58 [论文交流] 中国医疗争议死亡案件尸检病例分析王璐汕头大学医学院MPH中心BB11 10:58-11:06 [论文交流] 临床病理学分析不同年龄患者的冠状动脉粥样硬化尸检王菁临床病理学分析不同年龄患者的冠状动脉粥样硬化尸检BB12 11:06-11:14 [论文交流] 病理科住院医师规范化培训引入导师制的初步探索蒋慧长海医院病理科BB13 11:14-11:22 [论文交流] 病理学教学中如何很好的引入PBL教学模式马秀梅内蒙古医科大学附属医院--------------------------------------------------------------------------------第五分会场2013-11-1008:00-10:00 泌尿男生殖学组主持人:滕晓东,李玉军BB01 08:00-08:30 [专题发言] 温哥华肾脏病理共识赵明宁波市鄞州区第二医院BB02 08:30-09:00 [专题发言] 前列腺癌新进展周桥无BB03 09:00-09:30 [专题发言] 睾丸肿瘤新进展曹登峰无BB04 09:30-10:00 [专题发言] 肾母细胞瘤王哲西京医院--------------------------------------------------------------------------------10:10-12:00 泌尿男生殖学组主持人:吴继锋,刘强BB05 10:10-10:18 [论文交流] 肾良性上皮性肿瘤的i临床及病理学研究时淑舫北京友谊医院病理科BB06 10:18-10:26 [论文交流] 肾小细胞型嗜酸细胞瘤的临床病理特征张伟青岛解放军第401医院病理科BB07 10:26-10:34 [论文交流] Clear cell papillary renal cell carcinoma (ccpRCC), not uncommon histologic type of RCC: a study of 290 consecutive nephrectomies for RCC 周海军Department of Pathology and Genomic Medicine, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA.BB08 10:34-10:42 [论文交流] 散发性肾血管母细胞瘤临床病理观察郭静济宁医学院附属医院病理科BB09 10:42-10:50 [论文交流] IgG4相关性肾病张静第四军医大学病理学与病理生理学教研室暨西京医院病理科BB10 10:50-10:58 [论文交流] 膀胱微囊型尿路上皮癌临床病理观察于文娟青岛大学医学院附属医院病理科BB11 10:58-11:06 [论文交流] 免疫组化和荧光原位杂交在膀胱内翻性肿瘤鉴别诊断中的意义孙娟娟复旦大学附属肿瘤医院病理科BB12 11:06-11:14 [论文交流] 近五年移植肾穿刺活检病理类型分析吴珊吉林大学基础医学院病理系BB13 11:14-11:22 [论文交流] ERG基因重排在我国前列腺癌患者中的特征分析韩博山东大学齐鲁医院--------------------------------------------------------------------------------第六分会场2013-11-1008:00-10:00 基础研究主持人:王国平,吕宁BB01 08:00-08:30 [专题发言] 肿瘤微环境中ATP促侵袭作用的发现及其分子机制研究方伟岗北京大学医学部病理学系BB02 08:30-09:00 [专题发言] 肾上腺髓质素通过促进细胞间接触的形成发挥对肾小球足细胞的保护作用肖川复旦大学上海医学院基础学院病理学系BB03 09:00-09:30 [专题发言] 结直肠癌中GDF15多态性位点与突变和转移关系的研究汪静宇浙江大学医学院病理与病理生理学系BB04 09:30-10:00 [专题发言] miR-133a represses tumor growth and metastasis in colorectal cancer by targeting LASP1 and inhibiting the MAPK pathway Liang Zhao Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China--------------------------------------------------------------------------------10:10-12:00 基础研究主持人:王娅兰,翁阳BB05 10:10-10:18 [论文交流] HPV16 oncoprotein regulates the translocation of β-catenin via activation of EGFR 胡忠良Department of Hematology and Medical Oncology;Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia, USABB06 10:18-10:26 [论文交流] FoxD3-regulated microRNA-137 suppresses tumor growth and metastasis in human hepatocellular carcinoma by targeting AKT2/mTOR pathway Li-Li Liu State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBB07 10:26-10:34 [论文交流] 上调与下调PRDX3基因表达对DAOY细胞增殖与凋亡的影响。
SOX2在恶性肿瘤中的研究进展
SOX2在恶性肿瘤中的研究进展何甚楠;鲁明骞【摘要】SOX2是维持干细胞多向分化的重要转录因子,有维持细胞自我更新和增殖的能力,在胚胎发育及恶性肿瘤的发生发展中起着非常重要作用.近年来,越来越多的研究发现,SOX2的异常表达与恶性肿瘤的发生、分化程度、转移及不良预后等方面关系密切,本文就SOX2与恶性肿瘤的研究进展给予综述.%SOX2 is the key transcription factor maintaining the multilineage progress of stem cells, keeping cells self-renewal and proliferation, acting quite an important role in embryogenesis, malignant tumorgenesis and devel-opment. Recently, more and more research show that the abnormal expression of SOX2 is closely related to malignant tumorgenesis, malignancy grade, metastasis, poor pragnosis etc. Hereby, we summarize the research progress of SOX2 and malignant tumor.【期刊名称】《海南医学》【年(卷),期】2017(028)004【总页数】3页(P618-620)【关键词】SOX2;恶性肿瘤;干细胞【作者】何甚楠;鲁明骞【作者单位】三峡大学医学院2012级临床医学,湖北宜昌 443000;三峡大学第一临床医学院肿瘤研究所&宜昌市中心人民医院肿瘤内科,湖北宜昌 443000【正文语种】中文【中图分类】R730.2SOX2是Y染色体上的性别决定区(SRY)家族基因成员之一，是SOX基因族的组成部分(SOX基因族包括SOX1、SOX2和SOX3)，属于B1组，定位于染色体3q26.3～q27上，包含一个外显子，编码由317个氨基酸组成的蛋白质，主要结构包括C-末端、HMG-box DNA结合结构域和N-末端，其中起主要作用的是HMG结构域。
铈的荧光标记
铈的荧光标记Title: The Impact of Fluorescent Markers on Modern Science and TechnologyIntroductionIn recent years, fluorescent markers have become an essential component in various scientific and technological fields. These markers, often referred to as fluorophores, are molecules that can absorb light at a specific wavelength and emit light at a different wavelength, creating a bright and distinguishable signal. This article aims to explore the significance of fluorescent markers in different applications and their impact on modern science and technology.Fluorescent Markers in Biomedical ResearchOne of the most prominent fields benefiting from fluorescent markers is biomedical research. By tagging specific molecules or cells with these markers, scientists can visualize and track their movement in real-time. This allows for a better understanding of cellular processes, disease progression, and treatment efficacy.Fluorescent markers can be used to visualize cellular structures, such as organelles, microtubules, and cell membranes, aiding in the examination of cellular dynamics and interactions. They are also crucial for studying the localization and behavior of proteins within cells. Through techniques like immunofluorescence, researchers can target specific proteins with fluorescently-labeled antibodies, enabling the visualization of protein distributions and interactions within tissues or cells.Moreover, fluorescent markers play a vital role in the field of molecular biology. They allow scientists to track the expression and regulation of genes, monitor DNA replication, and study protein-protein interactions. Techniques like fluorescence in situ hybridization (FISH) and green fluorescent protein (GFP) labeling have revolutionized our understanding of gene expression and molecular mechanisms.Medical Diagnostics and ImagingFluorescent markers have greatly advanced medical diagnostics and imaging techniques, offering improved accuracy and sensitivity. In medical diagnostics, markers are used for the detection and identification of various diseases, including cancer, infectious diseases, and genetic disorders. Fluorescence microscopy and flow cytometry techniques allow for rapid and precise identification of abnormal cells or molecules, guiding diagnosis and informing treatment decisions.In imaging, fluorescent markers have revolutionized medical imaging modalities such as fluorescence imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI). With the ability to selectively target specific tissues or cells, fluorescent markers enhance the detection and localization of tumors, aid in surgical navigation, and enable the tracking of drug delivery systems. Their optical properties are a valuable tool for non-invasive imaging and help clinicians make accurate diagnoses.Environmental and Industrial ApplicationsThe impact of fluorescent markers extends beyond biology and medicine; they have also found applications in environmental and industrial sectors. Due to their unique optical properties and sensitivities to the environment,these markers are useful in monitoring water quality, detecting pollutants, and assessing environmental risks. They allow for the identification and measurement of various contaminants, such as heavy metals, pesticides, and organic pollutants.In industries, fluorescent markers are employed for quality control, product tracking, and counterfeit detection. Manufacturers use these markers to ensure product authenticity and prevent illegal imitation. Furthermore, fluorescent dyes are added to paints, coatings, and textiles to create vibrant colors and enhance visibility, safety, and aesthetics.ConclusionIn conclusion, fluorescent markers have revolutionized various scientific and technological fields. From biomedical research to medical diagnostics, environmental monitoring, and industrial applications, their versatility and unique fluorescent properties have propelled advancements in numerous sectors. As technology continues to evolve, it is anticipated that fluorescent markers will further contribute to the understanding of complex biological systems and aid in the development of innovative scientific and technological solutions.。
molecular marker
‘Green’biotechnology•Introduction•DNA, Chromosomes, Genomes •Plant Transformation•Modern Plant Breeding•Plant tissue culture•Molecular MarkerMarker -What for?wild x cultivated Resist-ancegene Susceptible B a c k c r o s s i n g s Example:A breeder aims to improve the resistance of a cultivated form. Therefore, he/she performs a cross between the susceptibleculitvated form with a wild form thatpossess the required resistance.However, at least 6 backcrossing steps arenecessary and the resistance is difficult todetect.Marker Assisted Selection(MAS)•Breeding for specific traits in plants is expensive and time consuming•The progeny often need to reach maturity before a determination of the success of the cross can be made •The greater the complexity of the trait, the more time and effort needed to achieve a desirable result.MAS –What for? •The major goal is to reduce costs associated with screening for traitsThe ‚perfect marker‘•close linkage with the trait of interest and markerLGmarker markertraitThe ‚perfect marker‘-Polymorphic-Reproducable-Easy to use and economical-High-throughput genotyping–automation–combination of different markers inone reactionProtein -based markerDNA -based markermorphological markerMarker -typesMorphological Marker •Example: colour, size, rating..•Cheap and fastbut, influenced by environmentalconditionsProtein-based markerCommon protein marker: Isozymes Multiple forms of the same enzyme-allozyme: one enzyme and one locus-isozyme: one enzyme, more than one locus(gene duplication; gene families) To be useful as markers, isoforms must be electrophoretically resolvable, and detectable by in-gel assay methodsMethodologyGrind and extract protein from appropriate tissue with bufferFractionate extract electrophoretically in starch or polyacrylamide gels (non-denaturing) Detect enzyme by incubation of gel (or gel print) in a solution of a synthetic substrate that allows the enzyme to catalyze a reactionthat generates a coloured productNecessary hardware...ElectrophoresesSDS-PAGE of four wheat varieties a a b b c c d dWhy seed storage proteins?seeds are a rich source of stableand abundant proteinsseeds represent a well-defineddevelopmental stageseeds are easily stored and transportedeach protein band in an electrophoreticprofile usually represents a direct geneproductwheat variety identificationIssues:Limited to those enzymes that can detected in situ= thin coverage of thegenomeDimeric and multimeric enzymes add complexityPattern can be influenced by environment and tissue-type specific2-D gel electrophoresis2-D gel profile of Medicago truncatula suspension cell culture protein extract.•Although 2-D PAGE analysis has been used for the last 20 years in protein profiling, it provides limited information on protein identification.•Mass spectrometry and the establishment of protein databases have substantially increased the ease and speed with which proteins can be identified.DNA -based marker•Advantages–not influenced by environment–expressed in all tissuesDNA -based marker RFLPs-restriction fragment length polymorphismsPCR-based markersRAPDsSSRsAFLPsRFLPs-restriction fragment length polymorphisms Electrophoretic comparison of the size of defined restriction fragments derived from genomic DNA1. Isolate high quality DNA2. Digest with a combination of restrictionenzymes3. Fractionate digested samples by electrophoresis4. Transfer fragments to membrane5. Hybridize with (non)radioactively labeledDNA probe(s); detect by autoradiographyRFLP work flowlabelledDNA-probe Restriction enzymesRFLPs: origins ofpolymorphismsA = base patternB = insertionC = deletionD = new restriction sitewithin probe sequenceE = loss of restriction siteF = new restriction siteoutside probe regionA B C D E F decr.lengthRE REprobeConsiderations for use of RFLPs Need high quality DNANeed to develop polymorphic probes -expensive Relatively slow processUse of radioisotopes limits use to certified laboratories (non-radioactive labeling systems now in wide use)Large quantities of DNA are needed and procedure is difficult to automatePCR-based markersPCR: p olymerase c hain r eaction amplification of tracts of DNA defined by border sequences that hybridize to selected DNA polymerase primers Requires:-target DNA-thermostable DNA polymerase (Taq) -oligonucleotide primer(s) (7-30nt)-dNTPs+ Mg++PCR ConsiderationsX Does not require high quality DNA X Extremely sensitive -easilycontaminatedX Reaction conditions must beoptimized and controlledX FastX Relatively inexpensive“amplicon”+PCR primer oligosRAPDs:r andom a mplified p olymorphicD NA markersArbitrary primer used to amplify DNA from total genomic DNAA B CprimerRAPDsAnonymous markers -but can be converted to SCARs(Sequenced Characterized Amplified Region Markers)Fast, easy and cheap -commercial primer sets availableRAPDsIssues:Some reproducibility problemsSame band on gel = same DNA fragment? One band on gel = one DNA fragment?RAPD of canola(Brassica napus ) seedlots of varieties A and Band mixtures 654321100806040200B 020*********APercentage seed in the mixture in laneVa-riety Example:use of RAPDs in seed testingM 1 2 3 4 5 6Sequence-tagged sites as markers SCARs: s equence-c haracterized a mplified r egionsCAPS: c leaved a mplified p olymorphics equencesSCARsInformative RAPD-generated fragmentis sequenced -no longer anonymous Sequence-specific primers (22-30 nt) designed to target this locusMore reproducible(long specific primers) a co-dominant marker; detectablein both homozygotes and heterozygotesCAPS procedure1. Site-specific primers used to amplify aparticular locus2. Amplicon digested with a restriction enzyme3. Fragments electrophoretically resolved4. Polymorphisms detected as differences infragment sizesSTS: Sequence Tagged Sites•PCR-based marker with 18 –25 bp primers •Derived from sequenced RFLP, RAPD or AFLP fragments or known genes•Stable amplification and good repeatability •Generally mapped•Easy to run and automate•Not many polymorphic STSs currently availableGenome organisation:SSR: Simple Sequence Repeat orMicrosatellite•PCR-based marker with 18-25 bp primers•SSR polymorphisms are based on number of repeat units, and are hypervariable(have many alleles)•SSRs have stable amplification and good repeatability•SSRs are easy to run and automateExample of SSR markersElectrophoretic Separation of Markers: Polyacrylamide gel, SequencerdetectionGenescan–assign fragment sizes in bpAFLPs: a mplified f ragment l ength p olymorphismsØA combination of PCR and RFLP ØInformative fingerprints of amplified fragmentsAFLPs1. Digest genomic DNA with restriction enzymes2. Ligate commercial adaptors (definedsequences) to both ends of the fragments 3. Carry out PCR on the adaptor-ligatedmixture, using primers that target theadaptor, but that vary in the base(s) atthe 3’end of the primerAmplified Fragment Length Polymorphisms(AFLPs)AFLPsAFLPsGenomic DNA 5’ - AATTC T - 3’ 3’ - G AAT - 5’Ligate adapters +Ligase5’ -CTCGTAGACTGCGTACC AATTCT TACTCAGGACTCAT - 3’ 3’ -CATCTGACGCATGGTTAA G AAT GAGTCCTGAGTAGCAG - 5’EcoRI adapterMseI adapter Amplication(+n) AATGAGTCCTGAGTAGCAG MseI primerPreamplificationEcoRI and MseI 5’ -CTCGTAGACTGCGTACC AATTCT TACTCAGGACTCAT - 3’ 3’ -CATCTGACGCATGGTTAA GAAT GAGTCCTGAGTAGCAG - 5’(+1 to +3) AATGAGTCCTGAGTAGCAGMseI primer5’ -CTCGTAGACTGCGTACC AATTCT TACTCAGGACTCAT - 3’ 3’ -CATCTGACGCATGGTTAA G AAT GAGTCCTGAGTAGCAG - 5’EcoRI primerGACTGCGTACCAATT (+1 to +3)No selective bases= No PCR products= label primer EcoRI primerGACTGCGTACCAATT (+n)AFLPsControlling AFLP discrimination PCR requires a perfect match with the target sequence at the 3’end of the primerFor the terminal position, the chances of a perfect match with the target occurring atboth ends of the two primers is 1:16 (24)By varying both the terminal and penultimate bases, the odds of perfect match are increased to 1:256 (28)AFLPsDetect products by using either radioactive dNTPs in the PCR step, or fluorescent tag-labeled primersFractionate products on high resolution sequencing gelsAFLPsVery sensitiveGood reproducibility but technically demanding Relatively expensive technologyBands are anonymous -interpretation of patterns can be challenging。
大豆作物遗传育种英语作文
大豆作物遗传育种英语作文Soybean is one of the most important agricultural crops in the world, providing a valuable source of protein, oil, and other nutrients. As the global population continues to grow, the demand for soybean and soybean-derived products is also increasing. To meet this growing demand, researchers and breeders have been working tirelessly to improve the genetic makeup of soybean crops through various breeding techniques.Soybean genetic breeding is a complex and multifaceted process that involves the manipulation of the plant's genetic material to achieve desired traits. These traits can include higher yield, improved disease and pest resistance, enhanced nutritional value, and increased tolerance to environmental stresses such as drought, salinity, and temperature extremes.One of the key approaches in soybean genetic breeding is the use of traditional breeding methods. This involves the crossing of elite soybean lines with desirable traits to create new genetic combinations. Breeders carefully select the parent lines based ontheir performance and the specific traits they wish to incorporate into the offspring. Through a process of repeated selection and evaluation, breeders can gradually enhance the desired characteristics of the soybean plants.In addition to traditional breeding, modern biotechnological tools have revolutionized the field of soybean genetic breeding. The advent of molecular markers, such as single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs), has enabled breeders to identify and track specific genes or genomic regions associated with important traits. This knowledge can then be used to accelerate the breeding process through marker-assisted selection (MAS).MAS allows breeders to select for desired traits at an early stage of plant development, without having to wait for the full expression of the trait in the mature plant. This can significantly reduce the time and resources required for the breeding process, leading to more efficient and effective development of new soybean varieties.Another important aspect of soybean genetic breeding is the exploration and utilization of genetic diversity. Soybean is a highly diverse crop, with a wide range of genetic variation both within and among different soybean cultivars and wild relatives. By tapping into this genetic diversity, breeders can access a vast pool of geneticresources that can be used to introduce new and beneficial traits into soybean breeding programs.One approach to harnessing genetic diversity is the use of genome-wide association studies (GWAS). GWAS involves the analysis of genetic markers across the entire soybean genome to identify associations between specific genomic regions and desired traits. This information can then be used to identify and select for the most promising genetic variants for further breeding efforts.In addition to GWAS, the use of advanced sequencing technologies, such as next-generation sequencing (NGS), has greatly expanded our understanding of the soybean genome. By deciphering the complete genetic code of soybean, researchers can identify key genes and regulatory regions that control important agronomic traits. This knowledge can then be leveraged to develop more targeted and efficient breeding strategies.Another exciting development in soybean genetic breeding is the use of gene editing technologies, such as CRISPR-Cas9. These tools allow for the precise modification of specific DNA sequences, enabling breeders to introduce or remove desired traits with unprecedented precision. This can lead to the development of soybean varieties with enhanced characteristics, such as improved disease resistance, increased nutritional value, or better adaptationto changing environmental conditions.While the advancements in soybean genetic breeding have been remarkable, there are still numerous challenges and opportunities that lie ahead. One of the key challenges is the need to develop soybean varieties that can withstand the increasing threats posed by climate change, such as drought, heat stress, and emerging pests and diseases.To address these challenges, soybean breeders and researchers are exploring various strategies, including the identification of novel genetic sources of stress tolerance, the development of multi-trait breeding approaches, and the integration of precision phenotyping techniques to accurately evaluate plant performance under different environmental conditions.Moreover, the successful deployment of soybean genetic breeding innovations will require close collaboration among researchers, breeders, farmers, and other stakeholders in the agricultural value chain. This collaborative effort will ensure that the benefits of these advancements reach the end-users, ultimately leading to improved food security, sustainability, and the overall well-being of communities around the world.In conclusion, the field of soybean genetic breeding is a dynamic andrapidly evolving area of research and innovation. By harnessing the power of modern biotechnological tools, exploring genetic diversity, and fostering collaborative efforts, soybean breeders are poised to develop new and improved soybean varieties that can meet the growing global demand for this versatile and nutritious crop. As we continue to push the boundaries of soybean genetic breeding, we can look forward to a future where soybean plays an even more pivotal role in ensuring food security, promoting sustainable agriculture, and contributing to the overall prosperity of our planet.。
乳腺Paget病14例临床病理分析
乳腺Ｐａｇｅｔ病１４例临床病理分析作者：李景岗尹崇高李洪利来源：《中国医药导报》2008年第04期[摘要] 目的：探讨乳腺Paget病的流行病学、临床、病理特点。
方法：收集1994～2004年14例经病理诊断为乳腺Paget病的资料，从发病率、发病年龄、临床表现、病理及预后等方面加以分析与研究。
结果：乳腺Paget病的发病率为0.9％，高发年龄为40～52岁，临床表现以乳头病变为首发症状，病理检查显示Paget细胞CK8表达阳性率为100％、cerbB-2表达阳性率为91.67％，而ER、PR表达阳性率为16.67％。
CK-8、cerbB-2、ER及PR中每一标记物在Paget细胞和同一病例深部癌组织中阳性表达一致。
总的5、10年生存率分别为81.82％和72.73％。
结论：乳腺Paget病作为乳腺癌的一种特殊类型，多与乳腺癌同时存在，CK-8阳性表达率100％表明乳腺Paget病的Paget细胞来源于深部的癌组织，cerbB-2阳性表达率高于不伴有Paget病的乳腺癌，而ER、PR阳性表达率低于不伴有Paget病的乳腺癌，提示乳腺Paget 病预后不良。
内分泌治疗效果可能不如不伴有Paget病的乳腺癌好，并且预后可能很差。
[关键词] Paget病；乳腺癌；临床病理学[中图分类号] R737[文献标识码]A [文章编号]1673-7210（2008）02（a）-034-02Clinical and pathological analysis of 14 cases Paget diseaseLI Jing-gang1，YIN Chong-gao2，LI Hong-li2(1.People's Hospital of Ningjin County,Shandong Province,Ningjin253416,China;2.Weifang Medical College,Weifang261042,China)[Abstract] Objective:To understand the clinical and pathological features of Pagetdisease.Methods:From 1994 to 2004,14 cases Paget disease were analysed in clinical and pathological features.Results:Paget's disease accounted for 0.9 percents of the total number of breast cancer patients treated in the same period of time. The mean age of patients was 46 years ,in the clinic behavior, the first symptom was the nipple change . Paget cells were positive for CK-8(100％) ，Paget cells were positive for cerbB-2(91.67％), ER and PR were 16.67％. The rate of expression of these molecular markers was similar in both Paget cells and the underlying intraductal and/or ductal carcinoma cells.5-year and 10-year survival rate was 81.82％ and 72.73％.Conclusion:Paget disease , as a special form of breast cancer, may accompany the breast cancer. All of paget cells are positive for CK-8，which illuminate the intraepidermal Paget cells root in the underlying carcinoma.The rate of positive cells for cerbB-2 is higher in Paget disease than the breast cancer,but one of positive cells for ER and PR is lower than the breast cancer. The outcome shows that Paget disease may be of no effect for endocrine therapy and prognosis is poor.[Key words] Paget disease;Breast cancer;Clinical pathology乳腺Paget病又称乳腺湿疹样癌，是一种特殊类型的乳腺癌，临床上较少见。
分子诊断实验室的基本概念和原理
分子诊断实验室的基本概念和原理Molecular diagnostics is a technique used to analyze biological markers in the genome and proteome—the individual's genetic code and how their cells express their genes as proteins—by applying molecular biology to medical testing. 分子诊断是一种技术，通过将分子生物学应用于医学测试，分析基因组和蛋白质组中的生物标志物。
This method is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients. 这种方法用于诊断和监测疾病，检测风险，并确定哪种疗法适合个体患者。
The basic concept of molecular diagnostics is to identify specific sequences of DNA, RNA, or proteins that are associated with a particular disease or condition. 分子诊断的基本概念是识别与特定疾病或病情相关的DNA、RNA或蛋白质的特定序列。
This involves using techniques such as polymerase chain reaction (PCR), nucleic acid hybridization, and nucleic acid sequencing to target and analyze these molecules. 这涉及使用聚合酶链反应（PCR）、核酸杂交和核酸测序等技术来定位和分析这些分子。
血液肿瘤分子诊断 分析流程
血液肿瘤分子诊断分析流程Diagnosing blood tumors through molecular analysis is a complex process that requires a deep understanding of genetics and pathology. 诊断血液肿瘤的分子分析是一个复杂的过程，需要深入了解遗传学和病理学。
This comprehensive analysis involves detecting specific genetic mutations and alterations in the DNA of blood cells that can indicate the presence of a tumor. 这种全面的分析涉及检测血细胞DNA中特定的基因突变和改变，这些改变可能表明存在肿瘤。
By identifying these molecular signatures, healthcare professionals can make more accurate diagnoses and develop personalized treatment plans for patients. 通过识别这些分子标记，医疗专业人员可以做出更准确的诊断，并为患者制定个性化的治疗计划。
One of the key steps in blood tumor molecular diagnosis is obtaining a sample of the patient's blood or bone marrow for analysis. 血液肿瘤分子诊断的关键步骤之一是获取患者血液或骨髓的样本进行分析。
This sample is then processed in a laboratory to extract the DNA and RNA from the blood cells, which will be analyzed for specific genetic changes. 然后在实验室中处理这些样本，提取血细胞中的DNA和RNA，这些将被用于特定基因变化的分析。
CHOP在鼻咽癌中的表达及其意义
CHOP在鼻咽癌中的表达及其意义王苏美;张惠忠;马志建;谭小军;王杜娟;刘琴;王梦瑶;杨惠玲【摘要】目的探讨CHOP在鼻咽癌组织与鼻咽炎组织中的表达差异及其意义. 方法采用免疫组织化学法检测48例鼻咽癌组织和35例鼻咽炎组织中CHOP的表达,SPSS软件统计分析鼻咽癌组织中CHOP的表达与临床病理因素及预后的关系. 结果鼻咽癌组织中CHOP高表达于胞浆(96％)及细胞核(52％),鼻咽炎组织中CHOP仅弱阳性低表达于胞浆(49％)(P＜0.001)；鼻咽癌组织CHOP的浆表达与患者肿瘤T分期及年龄正相关(P＜0.05),而鼻咽癌组织CHOP的核表达与鼻咽癌细胞分化负相关(P＜0.05)；单因素生存分析显示,鼻咽癌组织胞浆和细胞核CHOP的过表达均与病人生存率呈负相关趋势. 结论 CHOP可能通过抑制鼻咽癌细胞分化而促进鼻咽癌的发生发展及影响其预后,其可作为判断鼻咽癌分期、细胞分化的分子标志物和分子治疗的靶点.【期刊名称】《分子诊断与治疗杂志》【年(卷),期】2012(004)002【总页数】5页(P84-88)【关键词】鼻咽癌;内质网应激;细胞分化;分子标记物;免疫组织化学法【作者】王苏美;张惠忠;马志建;谭小军;王杜娟;刘琴;王梦瑶;杨惠玲【作者单位】中山大学中山医学院病理学与病理生理学教研室,广东,广州 510080;中山大学肿瘤防治中心,广东,广州 510060;中山大学肿瘤防治中心,广东,广州510060;广州医学院附属肿瘤医院,广东,广州 510095;中山大学中山医学院病理学与病理生理学教研室,广东,广州 510080;中山大学中山医学院病理学与病理生理学教研室,广东,广州 510080;中山大学中山医学院病理学与病理生理学教研室,广东,广州 510080;中山大学中山医学院病理学与病理生理学教研室,广东,广州 510080【正文语种】中文鼻咽癌（nasopharyngeal carcinoma，NPC）好发于我国南方，尤其广东省，故又称“广东瘤（canton tumor）”。
InDel标记的研究和应用进展
生物多样性 2016, 24 (2): 237–243 doi: 10.17520/biods.2015205 Biodiversity Science http: //・综述・InDel标记的研究和应用进展杨洁赫佳王丹碧施恩杨文宇耿其芳王中生*(南京大学生命科学学院, 南京 210023)摘要: InDel是指在近缘种或同一物种不同个体之间基因组同一位点的序列发生不同大小核苷酸片段的插入或缺失(insertion-deletion), 是同源序列比对产生空位(gap)的现象。
InDel在基因组中分布广泛、密度大、数目众多。
InDel 多态性分子标记是基于插入/缺失位点两侧的序列设计特异引物进行PCR扩增的标记, 其本质仍属于长度多态性标记, 可利用便捷的电泳平台进行分型。
InDel标记准确性高、稳定性好, 避免了由于特异性和复杂性导致的后续分析模糊。
此外, InDel标记能扩增混合DNA样品和高度降解的微量DNA样品, 并进行有效分型。
InDel标记目前已开始应用于动植物群体遗传分析、分子辅助育种以及人类法医遗传学、医学诊断等领域。
随着位于功能基因上InDel 标记的开发, 结合染色体步移和基因精细定位, 可将这些标记应用于相关物种经济性状的功能基因的筛选, 有利于优良基因的进一步开发和利用。
关键词:分子标记; InDel; SNP; SSRProgress in research and application of InDel markersJie Yang, Jia He, Danbi Wang, En Shi, Wenyu Yang, Qifang Geng, Zhongsheng Wang*School of Life Sciences, Nanjing University, Nanjing 210023Abstract: InDel indicates insertions or deletions (insertion-deletion) of nucleotide fragments of different siz-es at the same site in the genome sequence between the same or closely related species and is a gap in se-quence derived from alignment of the homologous sequence. InDel is widely distributed across the genome and occurs in a high density and large numbers in a genome. The InDel polymorphic molecular marker is a PCR-amplified marker that is based on specific primers designed from both sides of the site of sequence of insertion / deletion. It is essentially a length polymorphic marker still, and one can use the convenient elec-trophoresis platform for genotyping. InDel molecular markers have the advantage of high accuracy and good stability, which help to avoid confusion in subsequent analysis due to marker specificity and complexity, as is often seen in other length polymorphic markers. Furthermore, mixed or highly degraded DNA samples can be successfully amplified with InDel markers, and effectively typed. Because of its abundance, convenient typing platform and other advantages, InDel molecular markers have been applied to genetic analyses of an-imal and plant populations, molecular assisted crops and farmed animal breeding, human forensic genetics, medical diagnostics and other research areas. The development of the InDel molecular marker located on functional genes, combined with chromosome walking and fine gene mapping, has enabled the application of these molecular markers in the screening of genes related to important economic traits, which is conducive to the further development and utilization of these valuable genes. In this review, on the basis of an overview of the InDel marker development and applications, we discuss some of the technical limitations of the develop-ment and limited efficiency of genetic analysis, as well as potential future applications in the fine mapping and genetic structure of large numbers of individuals.Key words: molecular marker; InDel; SNP; SSR插入/缺失(insertion-deletion, InDel)是指在近缘种或同一物种不同个体之间基因组同一位点的序——————————————————收稿日期: 2015-07-15; 接受日期: 2015-12-17基金项目: 国家自然科学基金(31100270)∗通讯作者Author for correspondence. E-mail: wangzs@238 生物多样性 Biodiversity Science第24卷列发生了不同大小核苷酸片段的插入或缺失, 即一个序列上某一位点相比同源的另一个序列插入或缺失了一个或多个碱基(Weber et al, 2002)。
加速溶剂萃取气相色谱-质谱法检测土壤中双酚A
加速溶剂萃取气相色谱-质谱法检测土壤中双酚A克选【摘要】建立加速溶剂萃取后利用气相色谱-质谱法测定土壤中双酚A的检测方法。
样品前处理采用加速溶剂萃取，经硅胶柱净化，以HP-5MS色谱柱，采用气相色谱-质谱联用全扫描和选择离子扫描进行分析。
结果表明：双酚A在0.1~10.0mg/L的质量浓度范围内，线性良好，相关系数为0.9993；方法检出限为0.01mg/kg(S/N=3)。
在0.1，1.0，10 mg/kg这3个加标水平下，样品的平均回收率为82.5%~101.7%，相对标准偏差(RSD)≤3.3%。
该方法简便快速，灵敏度及准确度高，可用于土壤中双酚A的分析测定。
%A method is developed to determine bisphenol-A in soil with gas chromatography- mass spectrometry (GC-MS) after accelerated solvent extraction. It is carried out by the following steps:prepare samples via accelerated solvent extraction, purify the prepared sample on a silica gel column, further separated it on an HP-5MS column, and then analyze it via GC-MS full scanning and selective ion monitoring(SIM). The calibration curves of bisphenol-A showed a good linearity and the correlation coefficient and detection limit (S/N=3)thereof are 0.999 3 and 0.01 mg/kg respectively, under the optimized conditions namely ranging from 0.1 mg/L to 10.0 mg/L. The average recovery rate of the sample is within 82.5%-101.7% at the spiked levels of 0.1,1.0, 10.0 mg/kg,with the relative standard deviation (RSDs) lower than 3.3%. This method is simple and rapid with high sensitivity and resolution. It can be used to determine the amount of bisphenol-A in soil.【期刊名称】《中国测试》【年(卷),期】2016(042)003【总页数】4页(P45-47,63)【关键词】加速溶剂萃取;气相色谱质谱;土壤;双酚A【作者】克选【作者单位】甘肃省张掖市环境监测站，甘肃张掖 734000【正文语种】中文双酚A（bisphenol A，BPA）是制造聚碳酸酯、环氧树脂等的主要原料[1]。
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0007 -4888/10/1502 0237 © 2010 Springer Science+Business Media, Inc.Expression of Molecular Markers in the Tumor and Survival Prognosis in OsteosarcomaI. V. Boulytcheva, Yu. N. Soloviev*, N. E. Kushlinskii*, and A. N. MahsonTranslated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 150, No. 8, pp. 202-207, August, 2010Original article submitted June 21, 2009Immunohistochemical study of p53, VEGF, Flt-1/VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, and Cox-2 expression in osteosarcomas was carried out in 40 patients aged 16-70 years. Expression of p53 was detected in 27.5% tumors, VEGF in 15%, Flt-1/VEGFR1 Ab-1 in 97.5%, EGFR in 52.5%, HER-2/neu in 32.5%, Bax in 77.8%, and Cox-2 in 32.3% tumors. Multifactorial analysis showed that the expression of HER-2/neu (p =0.004), p53 (p =0.01), and Cox-2 (p =0.04) in osteosarcomas signi fi cantly correlated with unfavorable prognosis for overall survival, while HER-2/neu (p =0.02) and Cox-2 (p =0.003) with relapse-free survival. Analysis of HER-2/neu, p53, and Cox-2 expression in the primary tumor should be taken into consideration in the treatment of patients with osteosarcoma.Key Words: osteosarcoma; expression; p53; VEGF; Flt-1/VEGFR1 Ab-1; EGFR; HER-2/neuDepartment of Pathological Anatomy, Moscow Oncological Hos-pital No. 62; *N. N. Blokhin Cancer Research Center, Russian Acad-emy of Medical Sciences, Moscow, Russia. Address for correspon-dence: irena@. I. V. BoulytchevaTissue, cellular, or molecular markers characterize the basic properties of tumor cells: unlimited proli-feration, active neoangiogenesis and apoptosis, inva-sion, liability to metastatic growth [1,3,7]. Chemical method is assumed to be the most suitable for studies of protein expression in tumor tissues, including osteo-sarcoma tissue [4,5], and for better understanding of some stages in tumor development. The expression of Bax [8,14], Bcl-2 [11], HER-2/neu [7,12], p53 [7,14], VEGF and VEGF-R [6,9,13], and Cox-2 [10,15] pro-teins attracts special interest of scientists in immuno-histochemical studies of bone tumors. The expression of ErbB-2 [12], VEGF [6], and Cox-2 [15] in the pri-mary tumor is associated with poor survival prognosis for osteosarcoma patients. Published data are contra-dictory and necessitate further studies. The attitude of some authors to practical use of these parameters in cancer patients is skeptical because of a trend to overall adjuvant chemotherapy in this disease. On the other hand, two practical results can be expected fromthese studies: possibility of detecting the patients at a high risk of early relapses and/or metastases in need of adjuvant therapy or more thorough observation and evaluation of tumor sensitivity to certain therapies and creation of individual adjuvant treatment protocols for patients with disseminated process. One of the recent important practical results of studies of the molecular biology of tumors is the development of new drugs with target effects on these molecules, blocking the processes regulated by these molecules [2].We carried out an immunohistochemical analysis of the expression of molecular markers (p53, VEGF, Flt-1/VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, Cox-2) in osteosarcoma and of their relationship with the main clinical morphological characteristics of the disease and prognosis.MATERIALS AND METHODSImmunohistochemical studies were carried out in os-teosarcomas of 40 patients (21 women and 19 men) aged 16-70 years. The osteoblastic (25 cases) and chondroblastic osteosarcomas (7 cases) predominated; telangiectatic variant was detected in 1 case. Parostealosteosarcoma was detected in 5 cases, osteosarcoma (secondary) against the background of Paget disease in 1, and well-differentiated central osteosarcoma in 1 case.Primary tumors were located in the femoral (21 case), tibial (7 cases), fi bular (5 cases), humeral (4 cases) bones and in the ulnar and ileac bones and the rib (1 case each).Poorly differentiated (G3) osteosarcomas predo-minated (33 cases); well-differentiated (G1) osteosar-comas were found in 7 cases.The patients were distributed with consideration for the disease stage by the TNM system: T1N0M0 (n=4), T2N0M0 (n=22), T2N0M1 (n=2), T2N0M1a (n=2), T2N0M1b (n=3), T3N0M0 (n=2), T3N0M1 (n=1), T3N0M1a (n=3), and T3N0M1b (n=1).Distribution of patients with osteosarcoma by cli-nical classifi cation was as follows: 4 patients with stage IB, 3 with stage IIA, 19 with stage IIB, 2 with stage III, 8 with stage IV A, and 4 with stage IVB.Morphological studies of the tumors was carried out using standard equipment and reagent kits, systems for immunohistochemical preparations staining on an Autostainer Plus Link (Dako) universal automated sys-tem by the streptavidin biotin peroxidase method using monoclonal antibodies (Table 1).The parameters of expression of molecular bio-logical markers in the control group were analyzed in 5 tissue specimens with foci of new bone in ossifying myositis.The expression of the studied antigens (p53, VEGF, Flt-1/VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, Cox-2) was studied by immunohistochemical method in specimens of osteosarcoma tissue obtained by biopsy or surgical removal of the primary tumor. Tissue speci-mens were fi xed in 10% buffered formalin for 48 h and decalcinated by the standard method in 20% formic acid and 10% formalin. The material was processed in an automated mode in an Axcelsior vacuum proces-sor (Thermo Scientifi c). After histological processing the material was embedded in paraffi n and 3-4-μ sec-tions were prepared. Special highly adhesive Dako slides were used in studies of tumor specimens. A pre-treatment modulus (PT-Link, Dako) for simultane-ous deparaffi nation and rehydration of the sections and antigen decamoufl age was used for manipulations with the sections. Endogenous peroxidase blocking, incuba-tion with the fi rst antibodies, visualizing reagent, and chromogen solution were carried out in an Autostainer Plus Link (Dako). The sections were poststained by hematoxylin and embedded in balm or synthetic me-dium by the standard methods.The reaction in the cells of primary malignant osteosarcomas was evaluated by the semiquantitative method (by staining intensity and number of antigen-positive cells). The specifi c staining type, depending on the reaction product location in the cell (cytoplas-mic, membrane, nuclear, mixed), was evaluated for each antigen.The intensity of cytoplasmic reaction and num-ber of stained cells were evaluated for Cox-2, Bax, VEGF, Flt-1/VEGFR1 Ab-1, and EGFR. The reaction in tumor cells was evaluated by the semiquantitative method by staining intensity and number of antigen-positive cells. Immunohistochemical reaction was evaluated as negative (“-”: no reaction) and positive (>10% cells with the reaction of medium (“++”) and high (“+++”) staining intensity). Slightly positive im-munohistochemical reaction (“+”: <10% stained cells) and stromal reaction were neglected. The results of reactions with the antigens were expressed in percent as the number of stained cells per 100 examined tumor cells in 5-10 representative visual fi elds.The results of reaction with the antigen located in the nucleus (p53) were expressed in percent as the number of stained nuclei per 100 examined tumor cells in 5-10 representative visual fi elds. The expression of p53 was considered negative if less than 10% tumor cells were stained and positive if the number of antigen-positive cell nuclei in the primary tumor reached 10%.TABLE 1. Characteristics of Antibodies Used in the StudyAntigen Antibody, clone Firm WorkingdilutionProtein functionp53Mouse mAb DO-7Dako RTU Cell cycle and apoptosis regulator VEGF Mouse mAb VG1Dako1:25Angiogenesis stimulatorFlt-1/VEGFR1 Ab-1Rabbit pAb Thermo Scientific1:25Angiogenesis stimulator receptor EGFR Mouse mAb H11Dako1:200Receptor tyrosine kinaseHER-2/neu Rabbit pAb Dako1:550HER-2/neu receptorBax Rabbit pAb Dako1:50Apoptosis stimulatorСox-2Mouse mAb Dako RTU Arachidonic acid metabolism enzyme239For HER-2/neu protein the immunohistochemical reaction was considered positive only if tumor cell cytoplasm and membranes were stained (slight “+” and moderate “++”).RESULTSNo relationship between the incidence and levels of expression of molecular markers p53, VEGF, Flt-1/ VEGFR1 Ab-1, EGFR, HER-2/neu, Bax, and Cox-2 in osteosarcomas and the main clinical morphological characteristics of the disease, such as patient’s gender, tumor differentiation degree and location in skeletal bones, presence of distant metastases (M) was de-tected. No relationship between the expression of p53, VEGF, Flt-1/VEGFR1 Ab-1, HER-2/neu and patient’s age and the tumor T factor was detected. On the other hand, EGFR(+), Cox-2(+), and Bax(+) osteosarcomas were signifi cantly more incident in young patients. It is noteworthy that 21 patients with EGFR(+) osteo-sarcomsas were signifi cantly younger than 19 patients with EGFR(-) tumors (28.7±3.1 and 42.2±4.7 years, respectively; p=0.02). The 11 patients with Cox-2(-) tumors were signifi cantly older than patients with Cox-2(-) ones (45.5±6.3 and 31.7±3.4 years, respec-tively; p=0.04). The age of patients with Bax(-) os-teosarcoma was 48.0±8.8 years, of those with Bax expression<50% 34.8±4.1 years, and of those with the expression of Bax≥50% 30.0±4.7 years (p=0.03). In addition, signifi cant differences in the incidence of Cox-2(-) osteosarcomas with consideration for the T factor were detected (p=0.009; Table 2).The expression of Bax reaching ≥50% (56.5%;13 cases of 23) was signifi cantly more incident in os t eoblastic osteosarcomas than in other histological variants. The incidence of Bax(-) tumors was signi-fi cantly (p=0.04) higher in patients with T3 tumors (57.1% cases). It is noteworthy that the expression of these markers was not detected in any of the control samples.The expression of molecular markers in osteosar-comas is presented in Figs. 1-3.The expression of p53 was studied in 40 osteo-sarcomsa and detected in 27.5% tumors. Overall and relapse-free survival medians were almost 2-fold low-er in patients with p53(+) osteosarcoma. Analysis of overall survival curves of osteosarcoma patients has shown no relationship between the analyzed parameter and this protein expression in the tumor (Table 2). On the other hand, signifi cant differences in relapse-free survival of patients with p53(+) and p53(-) osteosar-comas were detected (p=0.03; Table 3).Hence, the expression of p53 in osteosarcoma should be regarded as an unfavorable predictor of early relapse.The expression of EGFR, VEGF, Flt-1/VEGFR1 Ab-1 was studied in 40 osteosarcomas and found in 52.5, 15, and 97.5% tumors, respectively. No signifi -cant differences in overall and relapse-free survival of osteosarcoma patients with tumors expressing EGFR, VEGF, and Flt-1/VEGFR1 Ab-1 were detected.The expression of Bax was studied in 36 osteosar-comas and detected in 77.8% tumors. A trend to dif-ferences in overall survival (p=0.05) in patients with different levels of Bax expression in osteosarcomas was detected. Relapse-free survival of osteosarcoma patients did not depend on Bax expression in the tu-mor (p=0.35; Table 3). The most unfavorable overall survival values were detected in osteosarcoma patients with Bax expression ≥50%.The expression of Cox-2 was studied in 34 os-teosarcomas and found in 32.3% tumors. The impact of Cox-2 expression levels in osteosarcomas for dis-ease prediction remained not quite clear in unifactorialTABLE 2. Expression of Cox-2 in Osteosarcomas with Consideration for T and M FactorsParameter NExpression of Cox-2Cox-2(-)Cox-2(+) abs.%abs.%T13——3100 T225624.01976.0 T36583.3116.7 M023521.71178.3 M1a8450.0450.0 M1b3266.7133.3 I. V. Boulytcheva, Yu. N. Soloviev, et al.240TABLE 3. Remote Results of Treatment of Osteosarcoma Patients and Tumor Expression of p53, Bax, and HER-2/neuExpressionNSurvival, %median, months1 year3 years5 yearsOverall survival (p =0.14)р53(-)3648.087.0±6.170.9±8.833.6±11.8р53(+)1226.866.7±15.750.0±18.6Relapse-free survival (p =0.03)p53(-)3528.277.8±7.647.3±10.347.3±10.3p53(+)1212.354.3±17.6Overall survival (p =0.05)Bax(-)9Not achieved85.7±13.268.6±18.668.6±18.6Bax <50%1747.994.1±5.778.4±11.224.5±14.4Bax ≥50%1635.262.2±13.451.9±14.613.0±11.8Relapse-free survival (p =0.35)Bax(-)915.077.8±13.923.3±19.023.3±19.0Bax <50%1717.580.2±10.448.1±13.924.5±14.4Bax ≥50%1514.661.4±13.826.3±12.913.0±11.8Overall survival (p =0.01)Her-2/neu(-)2749.392.6±5.078.7±8.545.8±11.6Her-2/neu(+)1221.765.6±14.032.8±15.1Relapse-free survival (p =0.03)Her-2/neu(-)2631.373.1±8.647.6±11.147.6±11.1Her-2/neu(+)118.754.5±15.0Fig. 1. Patient B., 19 years. Central classical osteosarcoma of the right humeral bone, grade 3 (chondroblastic variant). Fragment of the tumor with predominant chondrodifferentiation of atypical cells. a ) positive nuclear expression of p53 in tumor cells. Immunohistochemi-cal reaction, ⨯100; b ) immunohistochemical reaction with HER-2/neu. Positive cytoplasmic and membrane staining of tumor cells, ⨯100.analysis. No relationship between overall survival of osteosarcoma patients and the expression of Cox-2 in the tumor (p =0.9) was detected. However, relapse-free survival values were slightly better in the group of patients with Cox-2(+) tumors (p =0.3). The 3-year re-lapse-free survival was 37.3±11.9% in the group of 24 patients with Cox-2 (median 17.2 months) and 0% in the group of 11 patients without Cox-2 expression inBulletin of Experimental Biology and Medicine, Vol. 150, No. 2, 2010 ONCOLOGY241the tumor (median 10.4 months). However, these dif-ferences were seen only after 2 years of observation.The expression of HER-2/neu was studied in 40 osteosarcomas and detected in 32.5% tumors. Overall survival of patients with HER-2/neu(-) and HER-2/neu(+) tumors differed signi fi cantly (p =0.01). The pre-sence of this marker in osteosarcomas should be con-sidered as a prognostically unfavorable factor. Similarresults were found in the analysis of relapse-free sur-vival (p =0.007; Table 3).The results of multifactorial analysis indicate that the expression of HER-2/neu (p =0.004), p53 (p =0.011), and Cox-2 (p =0.04) in the tumor shouldbe considered as independent factors of overall sur-Fig. 2. Patient (female) N., 18 years. Central classical osteosarcoma of the right scapula, grade 3 (chondroblastic variant). a ) positive cytoplasmic staining of tumor cells. Immunohistochemical reaction with VEGF, ⨯100; b ) lobular structure of the tumor with islets of atypical cells with chondroid differentiation. Positive immunohistochemical staining for Flt-1/VEGFR1 Ab-1, ⨯100.Fig. 3. Expression of EGFR, Bax, Cox-2 markers in osteosarcomas. a ) patient (female) K., 24 years. Central classical osteosarcoma of the left tibial bone, grade 3 (chondroblastic variant). Immuno-histochemical reaction with EGFR, ⨯100; b ) patient (female) T., 56 years. Telangiectatic osteosarcoma of the right femoral bone. Bax-positive cytoplasmic reaction in tumor cells, ⨯100; c ) patient K., 23 years. Central classical osteosarcoma of the right tibial bone, grade 3 (osteoblastic variant). Fragment of the tumor, proliferation of atypical osteoblasts with pronounced nuclear polymorphism. Immunohistochemical reaction with Cox-2, ⨯100.I. V. Boulytcheva, Yu. N. Soloviev, et al.242vival prognosis for patients with osteosarcoma, while the expression of HER-2/neu (p=0.02) and Cox-2 (p=0.003) is signifi cantly associated with relapse-free survival. By these data, a group of osteosarcoma patients with unfavorable prognosis can be distin-guished, who need thorough observation and more aggressive treatment.Hence, the expression of p53 was detected in 27.5% osteosarcomas, VEGF in 15%, Flt-1/VEGFR1 Ab-1 in 97.5%, EGFR in 52.5%, HER-2/neu in 32.5%, Bax in 77.8%, and Cox-2 in 32.3% cases. Analysis of the results of immunohistochemical study of the mo-lecular markers expression in osteosarcomas revealed their relationships with the main clinical morphologi-cal characteristics of the disease (patient’s gender, tumor differentiation degree and location in skeletal bones, presence of distant metastases, M factor). No relationships between the expression of p53, VEGF, Flt-1/VEGFR1 Ab-1, HER-2/neu with patient’s age and T factor were detected. On the other hand, zero expression of Bax (-) and Cox-2 (-) was signifi cantly more incident (p=0.04) in cases with greater dissemi-nation of tumor process (higher T factor). The expres-sion of EGFR (p=0.02), Cox-2 (p=0.04), and high expression of Bax (p=0.03) in osteosarcomas were signifi cantly more incident in young patients. Unifac-torial analysis has shown a relationship between worse relapse-free survival of patients with p53 (p=0.03) and HER-2/neu (p=0.07) expression and between overall survival and HER-2/neu expression (p=0.01). Multi-factorial analysis has detected a relationship between the expression of HER-2/neu (p=0.004), p53 (p=0.01), and Cox-2 (p=0.04) in osteosarcomas and the overall survival prognosis and between HER-2/neu (p=0.02) and Cox-2 (p=0.003) expression and relapse-free sur-vival. Hence, analysis of the expression of HER-2/ neu, p53, and Cox-2 in the primary tumor should be taken into consideration in the treatment of patients with osteosarcoma.REFERENCES1. G. I. Abelev and T. L. Eraizer, Biokhimiya, 73, No. 5, 605-618(2008).2. N. V. Zhukov and S. A. Tyulyandin, Ibid., 751-768 (2008).3. E. N. Imyanitov and K. P. 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