BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,severa...BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.展开更多
BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基...BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。展开更多
基金Supported by Natural Science Foundation of Sichuan Province,No.2023NSFSC0729Wu Jieping Foundation Special Fund for Clinical Research,No.320.6750.2022-19-100+1 种基金Foundation of Key Clinical Specialty of Sichuan Province,No.2022School Foundation of Chengdu Medical College,No.CYZYB21-05.
文摘BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.
文摘BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。
文摘目的:探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)患者癌组织中支链氨基酸转氨酶1(branched-chain amino-acid transaminase 1,BCAT1)的表达及临床意义。方法:采用免疫组织化学法检测133例EOC癌组织中BCAT1表达情况,根据免疫组织化学评分分为BCAT1高表达组(n=41)及低表达组(n=92),卡方检验分析BCAT1的表达与临床病理因素间的关系,Kaplan-Meier生存曲线和对数秩检验比较BCAT1高、低表达组患者无瘤生存率及总生存率的差异,Cox比例风险模型分析影响EOC患者预后的因素。结果:BCAT1表达与宫颈癌国际妇产科联盟(Federation International of Gynecology and Obstetrics, FIGO)分期(P=0.004)、淋巴结转移(P=0.001)显著相关,与糖类抗原125(CA125)水平(P=0.538)、组织学类型(P=0.306)、年龄(P=0.524)、肿瘤大小(P=0.632)、腹水(P=0.178)无显著相关性(P>0.05)。BCAT1高表达组患者1年、3年无瘤生存率及总生存率显著低于BCAT1低表达组(P<0.001)。单因素分析示CA125(P<0.001)、肿瘤大小(P=0.003)、组织学类型(P=0.004)、淋巴结转移(P<0.001)、FIGO分期(P<0.001)和BCAT1表达(P<0.001)是影响EOC患者无瘤生存率的危险因素。多因素分析示FIGO分期(P<0.001)和BCAT1表达(P=0.013)是影响EOC患者无瘤生存率的独立危险因素。单因素分析示FIGO分期(P=0.022)、BCAT1表达(P=0.004)及淋巴结转移(P=0.046)是影响EOC患者总生存率的危险因素;多因素分析示FIGO分期(P<0.001)和BCAT1表达(P=0.025)是影响EOC患者总生存率的独立危险因素。结论:EOC癌组织中BACT1高表达,且与FIGO分期、淋巴结转移和预后显著相关,是影响EOC患者预后的分子标志物。
