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
越来越多的证据表明,长非编码RNA在肿瘤发生发展中起着关键作用。FEZ家族锌指1反义RNA 1(FEZF1-AS1)是一种与肿瘤密切相关的长非编码RNA,对多种类型的恶性肿瘤产生致病作用,并与肿瘤患者的预后不良及化疗耐药性有关。因此,FEZF1-AS1有...越来越多的证据表明,长非编码RNA在肿瘤发生发展中起着关键作用。FEZ家族锌指1反义RNA 1(FEZF1-AS1)是一种与肿瘤密切相关的长非编码RNA,对多种类型的恶性肿瘤产生致病作用,并与肿瘤患者的预后不良及化疗耐药性有关。因此,FEZF1-AS1有可能成为一种新型的癌症临床诊断和预后生物标志物,为肿瘤治疗提供新的分子靶点。本研究利用中国知网和PubMed数据库,在中国知网中以“FEZF1-AS1”“癌症或肿瘤”为关键词,在PubMed中以“FEZF1-AS1”“cancer or tumor”为关键词,分别检索2012-01-01-2023-12-01相关文献。纳入标准:(1)FEZF1-AS1与癌症诊断与治疗;(2)FEZF1-AS1与癌症的发生发展;(3)FEZF1-AS1与癌症的耐药性。剔除标准:重复,及其发表时间较早的综述文章。最终纳入分析文献65篇。研究发现,FEZF1-AS1不仅可以通过海绵化miRNA、引发染色质表观遗传、与蛋白质相互作用、调节信号通路、与mRNA形成双链等5种机制,在胰腺癌、结直肠癌、肝癌、非小细胞肺癌、胃癌、胶质母细胞瘤、宫颈癌、卵巢癌、口腔鳞状细胞癌、喉鳞状细胞癌、视网膜母细胞瘤、骨髓瘤、骨肉瘤、乳腺癌、鼻咽癌、前列腺癌和膀胱癌等17种肿瘤的发生发展中起致病作用,而且与癌症的化疗耐药密切相关。提示FEZF1-AS1具有极好的潜力,有可能成为癌症早期诊断、治疗和改善人类癌症整体预后的重要分子标志物。展开更多
目的建立用于筛选具有抗肿瘤活性的沙利度胺衍生物的分子平台。方法从人胎肝c DNA文库中分别扩增cereblon(CRBN)和Ikaros家族锌指蛋白1(Ikaros family zinc finger protein 1,IKZF1)c DNA,并将其克隆入p XJ40-myc和pc DNA3-FLAG载体中,...目的建立用于筛选具有抗肿瘤活性的沙利度胺衍生物的分子平台。方法从人胎肝c DNA文库中分别扩增cereblon(CRBN)和Ikaros家族锌指蛋白1(Ikaros family zinc finger protein 1,IKZF1)c DNA,并将其克隆入p XJ40-myc和pc DNA3-FLAG载体中,将其转染293T细胞,通过检测沙利度胺及其衍生物对CRBN和IKZF1蛋白相互作用的改变,间接反映其在肿瘤抑制中的作用。结果 CRBN和IKZF1在293T细胞中均得到表达,沙利度胺及其两个衍生物可显著增强CRBN和IKZF1的结合。结论成功建立了用于筛选具有抗肿瘤活性的沙利度胺衍生物分子平台,初步发现2个沙利度胺衍生物可显著增强CRBN和IKZF1的结合,提示其具有潜在的抗癌活性。展开更多
Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and s...Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.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.
文摘越来越多的证据表明,长非编码RNA在肿瘤发生发展中起着关键作用。FEZ家族锌指1反义RNA 1(FEZF1-AS1)是一种与肿瘤密切相关的长非编码RNA,对多种类型的恶性肿瘤产生致病作用,并与肿瘤患者的预后不良及化疗耐药性有关。因此,FEZF1-AS1有可能成为一种新型的癌症临床诊断和预后生物标志物,为肿瘤治疗提供新的分子靶点。本研究利用中国知网和PubMed数据库,在中国知网中以“FEZF1-AS1”“癌症或肿瘤”为关键词,在PubMed中以“FEZF1-AS1”“cancer or tumor”为关键词,分别检索2012-01-01-2023-12-01相关文献。纳入标准:(1)FEZF1-AS1与癌症诊断与治疗;(2)FEZF1-AS1与癌症的发生发展;(3)FEZF1-AS1与癌症的耐药性。剔除标准:重复,及其发表时间较早的综述文章。最终纳入分析文献65篇。研究发现,FEZF1-AS1不仅可以通过海绵化miRNA、引发染色质表观遗传、与蛋白质相互作用、调节信号通路、与mRNA形成双链等5种机制,在胰腺癌、结直肠癌、肝癌、非小细胞肺癌、胃癌、胶质母细胞瘤、宫颈癌、卵巢癌、口腔鳞状细胞癌、喉鳞状细胞癌、视网膜母细胞瘤、骨髓瘤、骨肉瘤、乳腺癌、鼻咽癌、前列腺癌和膀胱癌等17种肿瘤的发生发展中起致病作用,而且与癌症的化疗耐药密切相关。提示FEZF1-AS1具有极好的潜力,有可能成为癌症早期诊断、治疗和改善人类癌症整体预后的重要分子标志物。
基金This work was supported by funds from the National Natural Science Foundation of China(31770840 to X.Ma and 31800989 to L.Xu)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(TP2017042 to X.Ma)。
文摘Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.
文摘目的探讨5-氟尿嘧啶(5-FU)对结肠癌大鼠增殖细胞核抗原(PCNA)表达及端粒酶(hTRT)活性的影响。方法取无特殊病原菌级标准健康雄性裸大鼠36只,10周龄,体重200~230 g。配制结肠癌细胞LoVo单细胞悬液腹腔注射建立结肠癌大鼠模型。将建模成功的30只结肠癌大鼠随机平分为3组-模型组、5-氟尿嘧啶1组、5-氟尿嘧啶2组,模型组予以0.3 mL 0.9%氯化钠溶液灌胃治疗;5-氟尿嘧啶1组、5-氟尿嘧啶2组给予腹腔注射5-氟尿嘧啶,剂量分别为30、60 mg/kg,1次/d,1周3次,共应用4周。测定与记录3组大鼠治疗第2周与第4周的肿瘤体积。观察与记录3组大鼠治疗第4周的结肠癌转移情况,包括局部淋巴结转移、肝转移、肺转移、腹膜转移等。采用免疫组织化学法检测平均单个视野下PCNA阳性细胞、hTRT阳性细胞比率。蛋白质印迹法检测GLI家族锌指蛋白1(Gli1)蛋白、血管内皮生长因子(VEGF)蛋白的相对表达水平。结果5-氟尿嘧啶1组、5-氟尿嘧啶2组治疗第2周与第4周的肿瘤体积均低于模型组(P<0.05),5-氟尿嘧啶2组低于5-氟尿嘧啶1组,差异均有统计学意义(P<0.05)。5-氟尿嘧啶1组、5-氟尿嘧啶2组治疗第4周的结肠癌局部淋巴结转移、肝转移、肺转移、腹膜转移率均低于模型组(P<0.05),5-氟尿嘧啶2组低于5-氟尿嘧啶1组,差异均有统计学意义(P<0.05)。5-氟尿嘧啶1组、5-氟尿嘧啶2组治疗第4周的PCNA、hTRT阳性细胞比率和Gli1、VEGF蛋白相对表达水平均低于模型组(P<0.05),5-氟尿嘧啶2组低于5-氟尿嘧啶1组,差异均有统计学意义(P<0.05)。结论5-氟尿嘧啶在结肠癌大鼠的应用具有很好的抑瘤效果,也可降低周围组织转移率,可抑制Gli1、VEGF蛋白的表达,其作用机制与抑制PCNA表达及hTRT活性具有相关性。
