生长抑制因子（inhibitor of growth，ING）家族是新近发现的一组重要的肿瘤抑制基因。目前发现ING基因家族至少有5个成员：ING1～ING5，每个成员可能都具有多个不同的mRNA转录剪接体。近年来，ING基因家族的抑癌功能及其机制正受到越...生长抑制因子（inhibitor of growth，ING）家族是新近发现的一组重要的肿瘤抑制基因。目前发现ING基因家族至少有5个成员：ING1～ING5，每个成员可能都具有多个不同的mRNA转录剪接体。近年来，ING基因家族的抑癌功能及其机制正受到越来越多的关注。展开更多
2021年10月8日,浙江大学基础医学院、浙江大学医学院附属第二医院蔡志坚教授团队在《细胞外囊泡杂志》(Journal of Extracellular Vesicles)在线发表了题为“Neddylation of Coro1a determines the fate of multivesicular bodies andbi...2021年10月8日,浙江大学基础医学院、浙江大学医学院附属第二医院蔡志坚教授团队在《细胞外囊泡杂志》(Journal of Extracellular Vesicles)在线发表了题为“Neddylation of Coro1a determines the fate of multivesicular bodies andbiogenesis of extracellular vesicles”的研究论文(DOI:10.1002/jev2.12153)。该文首次揭示了蛋白质拟素化修饰参与调控细胞外囊泡的生成,并鉴定出首个晚期内体/多囊泡体膜上通过直接结合RAS癌基因家族成员7(Rab7)并介导Rab7招募的哺乳动物蛋白,从而以全新的视角展示细胞外囊泡生成调控的机制及囊泡胞内运输的过程。研究人员明确拟素化的Coro1a定位于多囊泡体膜,并与Rab7直接结合,介导其多囊泡体的招募。展开更多
AIM： To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer （HNPCC） in suspected Chinese patients. METHODS： Five independent Chinese ki...AIM： To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer （HNPCC） in suspected Chinese patients. METHODS： Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction （PCR） and denaturing high-performance liquid chromatography （DHPLC）. Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool （BLAST）, and tested in the corresponding family members by direct DNA sequencing. RESULTS： Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC （HNPCCS） kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred＇s proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION： Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.展开更多
Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the ...Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the following four criteria:family history,recurrent nosebleeds,mucocutaneous telangiectasis,and arteriovenous malformations(AVM)in the brain,lung,liver and gastrointestinal(GI)tract.Although epistaxis is themost common presenting symptom,AVMs affecting the lungs,brain and GI tract provoke a more serious outcome.Heterozygous mutations in endoglin,activin receptor-like kinase 1(ACVRL1;ALK1),and SMAD4,the genes involved in the transforming growth factor-βfamily signaling cascade,cause HHT.We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes,proven to be caused by bleeding from multiple gastric angiodysplasia.Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach.Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia.The patient has been admitted several times with episodes of hemoptysis and hematochezia.One year ago,the patient was hospitalized due to right-sided weakness,which was caused by left basal ganglia hemorrhage as the part of HHT presentation.In family history,the patient's mother and elder sister had died,due to intracranial hemorrhage,and his eldest son has been suffered from recurrent epistaxis for 20 years.A genetic study revealed a mutation in exon 3 of ALK1(c.199C>T;p.Arg67Trp)in the proband and his eldest son presenting epistaxis.展开更多
文摘2021年10月8日,浙江大学基础医学院、浙江大学医学院附属第二医院蔡志坚教授团队在《细胞外囊泡杂志》(Journal of Extracellular Vesicles)在线发表了题为“Neddylation of Coro1a determines the fate of multivesicular bodies andbiogenesis of extracellular vesicles”的研究论文(DOI:10.1002/jev2.12153)。该文首次揭示了蛋白质拟素化修饰参与调控细胞外囊泡的生成,并鉴定出首个晚期内体/多囊泡体膜上通过直接结合RAS癌基因家族成员7(Rab7)并介导Rab7招募的哺乳动物蛋白,从而以全新的视角展示细胞外囊泡生成调控的机制及囊泡胞内运输的过程。研究人员明确拟素化的Coro1a定位于多囊泡体膜,并与Rab7直接结合,介导其多囊泡体的招募。
基金The Special Funds of China Education Ministry for Returnees, No. 2003-14
文摘AIM： To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer （HNPCC） in suspected Chinese patients. METHODS： Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction （PCR） and denaturing high-performance liquid chromatography （DHPLC）. Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool （BLAST）, and tested in the corresponding family members by direct DNA sequencing. RESULTS： Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC （HNPCCS） kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred＇s proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION： Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.
基金Supported by A grant of the South Korea Healthcare technology R and D Project,Ministry for Health,Welfare and Family Affairs,South Korea,No.A080588-23in part by a grant from the World Class University(WCU by Korean Ministry of Education,Science and Technology)(to Oh SP)
文摘Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the following four criteria:family history,recurrent nosebleeds,mucocutaneous telangiectasis,and arteriovenous malformations(AVM)in the brain,lung,liver and gastrointestinal(GI)tract.Although epistaxis is themost common presenting symptom,AVMs affecting the lungs,brain and GI tract provoke a more serious outcome.Heterozygous mutations in endoglin,activin receptor-like kinase 1(ACVRL1;ALK1),and SMAD4,the genes involved in the transforming growth factor-βfamily signaling cascade,cause HHT.We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes,proven to be caused by bleeding from multiple gastric angiodysplasia.Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach.Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia.The patient has been admitted several times with episodes of hemoptysis and hematochezia.One year ago,the patient was hospitalized due to right-sided weakness,which was caused by left basal ganglia hemorrhage as the part of HHT presentation.In family history,the patient's mother and elder sister had died,due to intracranial hemorrhage,and his eldest son has been suffered from recurrent epistaxis for 20 years.A genetic study revealed a mutation in exon 3 of ALK1(c.199C>T;p.Arg67Trp)in the proband and his eldest son presenting epistaxis.
