乳腺癌已成为全球女性患者最大的癌症负担。在中国,近10%的女性乳腺癌患者发病与遗传相关,受多个易感基因调控。乳腺癌患者存在多发性内分泌肿瘤1型(multiple endocrine neoplasia type 1,MEN1)基因显著突变,MEN1突变女性患乳腺癌风险...乳腺癌已成为全球女性患者最大的癌症负担。在中国,近10%的女性乳腺癌患者发病与遗传相关,受多个易感基因调控。乳腺癌患者存在多发性内分泌肿瘤1型(multiple endocrine neoplasia type 1,MEN1)基因显著突变,MEN1突变女性患乳腺癌风险显著增加,发病年龄提前。关于MEN1影响乳腺癌发病与进展的系统研究仍然有限。因此,本文将基于MEN1基因和MEN1编码的menin蛋白的结构、功能作一概述,以探讨MEN1与menin在乳腺癌发生发展及内分泌治疗中的作用机制,并介绍了基于menin的乳腺癌潜在治疗靶点,旨在为乳腺癌的早期筛查及个体化防治提供理论支持和科学指导。展开更多
Patients with multiple endocrine neoplasia type 1(MEN1)mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages.Following its identification in the late 1990s,laboratories around the world,...Patients with multiple endocrine neoplasia type 1(MEN1)mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages.Following its identification in the late 1990s,laboratories around the world,including our own,used gene-targeting approaches in murine models to study the MEN1 gene and its related diseases.Subsequently,this field of research witnessed an upsurge in the use of Men1 mutant mouse models to dissect MEN1 functions.These studies led to unraveling the natural history of MEN disease,and highlighted cellular and molecular mechanisms underlying the development of the disease.In this review,we present the currently available data concerning the generation and characterization of Men1 mutant mouse models in connection with MEN1 syndrome.展开更多
目的探讨多发性内分泌腺瘤1型(MEN1)的妊娠期临床特点和管理策略。方法收集1例MEN1先证者的性别、年龄、详细病史、临床症状、体征、实验室检查、影像学检查和病理学检查数据,并收集该MEN1家系中20名成员的人口学特征、临床特征和辅助...目的探讨多发性内分泌腺瘤1型(MEN1)的妊娠期临床特点和管理策略。方法收集1例MEN1先证者的性别、年龄、详细病史、临床症状、体征、实验室检查、影像学检查和病理学检查数据,并收集该MEN1家系中20名成员的人口学特征、临床特征和辅助检查。为回顾MEN1妊娠期病例,以“Multiple Endocrine Neoplasia Type 1”和“Pregnant”为关键词在PubMed搜索,以“多发性内分泌腺瘤病”和“妊娠”在万方数据知识服务平台搜索。结果本例MEN1先证者以垂体微腺瘤(溢乳、催乳素升高)、胰腺内分泌肿瘤(低血糖)及甲状旁腺腺瘤(无症状、甲状旁腺素和血钙升高)为主要临床表现。基因分析证实MEN1基因9号外显子(CGA>TGA,Arg415Term)突变为先证者致病基因。先证者的父亲和女儿携带该致病基因并有甲状旁腺功能亢进。先证者在药物治疗垂体微腺瘤和手术治疗胰腺内分泌肿瘤、甲状旁腺腺瘤后顺利妊娠并成功分娩1名女婴,其间无再次出现溢乳和低血糖发作,血PTH和血钙水平稳定,胎儿生长发育正常。共检索到相关英文病例报道7例,中文病例1例。总结既往文献报道的8例MEN1妊娠期病例,所有MEN1患者均于育龄期起病。甲状旁腺、胰腺和垂体是最常出现临床症状的内分泌腺体,多数患者存在家族史和相应的MEN1基因突变,其中7例患者在严密病情监测和治疗下成功分娩。结论临床医师对妊娠期MEN1患者的积极检测和诊疗,将有助于改善MEN1患者及其子代的预后。展开更多
文摘乳腺癌已成为全球女性患者最大的癌症负担。在中国,近10%的女性乳腺癌患者发病与遗传相关,受多个易感基因调控。乳腺癌患者存在多发性内分泌肿瘤1型(multiple endocrine neoplasia type 1,MEN1)基因显著突变,MEN1突变女性患乳腺癌风险显著增加,发病年龄提前。关于MEN1影响乳腺癌发病与进展的系统研究仍然有限。因此,本文将基于MEN1基因和MEN1编码的menin蛋白的结构、功能作一概述,以探讨MEN1与menin在乳腺癌发生发展及内分泌治疗中的作用机制,并介绍了基于menin的乳腺癌潜在治疗靶点,旨在为乳腺癌的早期筛查及个体化防治提供理论支持和科学指导。
基金the Fondation de l’Association pour la Recherche contre le Cancer(PJA 20151203335)SCUSI 2017 program from la Région Auvergne Rhône-Alpes and the grant from Ligue contre le Cancer inter-régionale 2018.
文摘Patients with multiple endocrine neoplasia type 1(MEN1)mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages.Following its identification in the late 1990s,laboratories around the world,including our own,used gene-targeting approaches in murine models to study the MEN1 gene and its related diseases.Subsequently,this field of research witnessed an upsurge in the use of Men1 mutant mouse models to dissect MEN1 functions.These studies led to unraveling the natural history of MEN disease,and highlighted cellular and molecular mechanisms underlying the development of the disease.In this review,we present the currently available data concerning the generation and characterization of Men1 mutant mouse models in connection with MEN1 syndrome.
文摘目的探讨多发性内分泌腺瘤1型(MEN1)的妊娠期临床特点和管理策略。方法收集1例MEN1先证者的性别、年龄、详细病史、临床症状、体征、实验室检查、影像学检查和病理学检查数据,并收集该MEN1家系中20名成员的人口学特征、临床特征和辅助检查。为回顾MEN1妊娠期病例,以“Multiple Endocrine Neoplasia Type 1”和“Pregnant”为关键词在PubMed搜索,以“多发性内分泌腺瘤病”和“妊娠”在万方数据知识服务平台搜索。结果本例MEN1先证者以垂体微腺瘤(溢乳、催乳素升高)、胰腺内分泌肿瘤(低血糖)及甲状旁腺腺瘤(无症状、甲状旁腺素和血钙升高)为主要临床表现。基因分析证实MEN1基因9号外显子(CGA>TGA,Arg415Term)突变为先证者致病基因。先证者的父亲和女儿携带该致病基因并有甲状旁腺功能亢进。先证者在药物治疗垂体微腺瘤和手术治疗胰腺内分泌肿瘤、甲状旁腺腺瘤后顺利妊娠并成功分娩1名女婴,其间无再次出现溢乳和低血糖发作,血PTH和血钙水平稳定,胎儿生长发育正常。共检索到相关英文病例报道7例,中文病例1例。总结既往文献报道的8例MEN1妊娠期病例,所有MEN1患者均于育龄期起病。甲状旁腺、胰腺和垂体是最常出现临床症状的内分泌腺体,多数患者存在家族史和相应的MEN1基因突变,其中7例患者在严密病情监测和治疗下成功分娩。结论临床医师对妊娠期MEN1患者的积极检测和诊疗,将有助于改善MEN1患者及其子代的预后。
