BACKGROUND： A cerebral cavernous malformation-1 （CCM1） gene mutation might result in functional loss of KREV interaction trapped-1 （KRIT1）, which is related to onset of cavernous malformations （CM）. However, da...BACKGROUND： A cerebral cavernous malformation-1 （CCM1） gene mutation might result in functional loss of KREV interaction trapped-1 （KRIT1）, which is related to onset of cavernous malformations （CM）. However, data addressing sporadic CM in Chinese patients remains limited to date. OBJECTIVE： To analyze CCM1 mutation of Chinese patients with sporadic intracranial CM. DESIGN, TIME AND SETTING： Genetics experiment was performed in the Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University between January 2004 and December 2005. PARTICIPANTS： Ninety patients with sporadic CM served as the CM group, and 30 healthy subjects were considered to be the control group. METHODS： Peripheral blood was collected from patients with CM and from control group subjects Genomic DNA was extracted, and exons 8, 9, 11, 12, 13, 15, 16, 17, and 18, as well as the related introns, were amplified using polymerase chain reaction. DNA sequences were compared with GeneBank. MAIN OUTCOME MEASURES： Abnormal mutable site of CCM1 gene in the two groups. RESULTS： Four exclusive mutations of CCM1 were detected in the CM group, with a sporadic CM mutational rate of 32% （6/19）. Of the four exclusive mutations, there was one missense mutation [exon 12, 1172C→T （S391 F）], one insertion mutation [exon 8, 704insT （K246stop）], one intervening sequence mutation （IVS12-4C→T）, and one synonymous mutation （exon 17, 1875C→T）. With the exception of 1875C→T, all mutations detected in the CM group led to functional changes of the KRIT1 protein, which was encoded by the CCM1 gene. Gene mutations were not detected in the control group. CONCLUSION： Four exclusive mutations of the CCM1 gene were determined in Chinese patients with sporadic CM, which led to functional changes or loss of the encoding KRIT1 protein. KRIT1 protein is considered to be the genetic basis of CM occurrence.展开更多
目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)...目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)通路的影响。方法把MCF-7人乳腺癌细胞中NC组和AKR1C3组分别转染空质粒和AKR1C3质粒,采用MTT法检测转染后24 h、48 h、72 h细胞活力;采用流式细胞技术测定各组细胞的存活率以及早期、晚期凋亡比例;通过Transwell实验对各组细胞的迁移和侵袭能力进行检测;通过Western blot检测各组细胞PD-1、PD-L1、蛋白激酶B(protein kinase b,AKT)蛋白表达水平。使用C57BL/6小鼠构建荷瘤模型,将采用人乳腺癌MCF-7细胞转染NC质粒和AKR1C3质粒进行细胞荷瘤,每3 d测量瘤体积,持续21 d,绘制两组小鼠肿瘤生长曲线,并于实验终点测量肿瘤质量。结果相较于NC组,AKR1C3组细胞活力降低(P<0.05),并且具有时间依赖效应(P<0.05),迁移和侵袭能力降低(P<0.05),早期凋亡和晚期凋亡比例升高(P<0.05),PD-1、PD-L1、AKT蛋白表达水平降低(P<0.05)。动物实验表明,AKR1C3组小鼠肿瘤体积降低,肿瘤质量下降(P<0.05)。结论AKR1C3可以抑制人乳腺癌细胞恶性生物学行为,抑制PD-1/PDL1信号通路蛋白表达。展开更多
文摘BACKGROUND： A cerebral cavernous malformation-1 （CCM1） gene mutation might result in functional loss of KREV interaction trapped-1 （KRIT1）, which is related to onset of cavernous malformations （CM）. However, data addressing sporadic CM in Chinese patients remains limited to date. OBJECTIVE： To analyze CCM1 mutation of Chinese patients with sporadic intracranial CM. DESIGN, TIME AND SETTING： Genetics experiment was performed in the Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University between January 2004 and December 2005. PARTICIPANTS： Ninety patients with sporadic CM served as the CM group, and 30 healthy subjects were considered to be the control group. METHODS： Peripheral blood was collected from patients with CM and from control group subjects Genomic DNA was extracted, and exons 8, 9, 11, 12, 13, 15, 16, 17, and 18, as well as the related introns, were amplified using polymerase chain reaction. DNA sequences were compared with GeneBank. MAIN OUTCOME MEASURES： Abnormal mutable site of CCM1 gene in the two groups. RESULTS： Four exclusive mutations of CCM1 were detected in the CM group, with a sporadic CM mutational rate of 32% （6/19）. Of the four exclusive mutations, there was one missense mutation [exon 12, 1172C→T （S391 F）], one insertion mutation [exon 8, 704insT （K246stop）], one intervening sequence mutation （IVS12-4C→T）, and one synonymous mutation （exon 17, 1875C→T）. With the exception of 1875C→T, all mutations detected in the CM group led to functional changes of the KRIT1 protein, which was encoded by the CCM1 gene. Gene mutations were not detected in the control group. CONCLUSION： Four exclusive mutations of the CCM1 gene were determined in Chinese patients with sporadic CM, which led to functional changes or loss of the encoding KRIT1 protein. KRIT1 protein is considered to be the genetic basis of CM occurrence.
文摘目的探讨胃癌组织中EB病毒的感染状况,分析其与小核核糖核蛋白多肽A(Small nuclear ribonucleoprotein polypeptide A,SNRPA)及端粒沉默破坏因子1样蛋白(Disruptor of telomeric silencing 1-like,DOT1L)表达的相关性。方法收集2022年2月至2025年5月南阳市第一人民医院收治的280例胃癌患者的癌组织及癌旁正常组织标本。分析EB病毒感染与患者临床病理特征的关系,比较EB病毒感染阳性组与阴性组中SNRPA、DOT1L的表达水平,采用Spearman分析EB病毒感染与癌组织SNRPA、DOT1L表达的相关性,受试者工作(Receiver operating characteristic,ROC)曲线分析SNRPA、DOT1L对胃癌EB病毒感染的诊断价值。结果280例胃癌患者癌组织标本中EB病毒阳性者33例,阳性率11.79%(33/280);胃癌患者EB病毒感染与淋巴结转移相关(P<0.05);SNRPA与DOT1L在胃癌组织中的表达均高于癌旁组织,EB病毒感染组SNRPA与DOT1L的表达均高于EB病毒未感染组(P<0.05);Spearman相关性分析显示,癌组织SNRPA、DOT1L表达与EB病毒感染呈正相关(r=0.709、0.658,P<0.05)。ROC曲线显示,SNRPA、DOT1L、两种指标联合评估胃癌EB病毒感染的曲线下面积(Area Under the Curve,AUC)分别为0.807、0.773、0.886。结论EB病毒感染与胃癌患者淋巴结转移、SNRPA、DOT1L表达水平有关,联合检测SNRPA、DOT1L可提高胃癌EB病毒感染的诊断效能。
