目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次...目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。展开更多
AIM:To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS:A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1?(c.2T>C)and six prev...AIM:To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS:A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1?(c.2T>C)and six previously known common SLC25A13 mutations:[Ⅰ](c.851_854delGTAT),[Ⅱ](g.IVS11+1G>A),[Ⅲ](c.1638_1660dup),[Ⅳ](p.S225X),[Ⅴ](IVS13+1G>A),and[XIX](g.IVS16ins3kb)using a newly developed TaqMan and established HybProbe assay,respectively.Sanger sequencing was employed for specimens showing an aberrant peak to confirm the targeted mutation as well as the unknown aberrant peaks detected.Frequencies of the mutations identified were compared in each region.Carrier frequency and disease prevalence of citrin deficiency caused by SCL25A13 mutations were estimated.RESULTS:p.Met1?was identified in the heterozygous state in 85 individuals,giving a carrier frequency of1/18,which suggests possible selective advantage of this variant.The question of p.Met1?homozygote lethality remains unanswered which may serve as an explanation as to why this homozygote has yet to be identified in patients/controls even with high allele frequency.The p.Met1?mutation has rarely been studied in populations other than Thai and Chinese;therefore,may have been overlooked.Development of the TaqMan assay in the present study would allow a simple,rapid,and cost-effective method for mass screening.Heterozygous mutations:[XIX]and[Ⅰ]were identified in 17 individuals,giving a carrier rate of 1/90 and a calculated homozygote rate of 1/33000.Two novel variants,g.IVS11+17C>G and c.1311C>T,of unknown clinical significance were identified at low frequency.CONCLUSION:This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1?allele.展开更多
p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清...p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清楚.在本研究中,我们构建了rAd-ASPP2、rAd-ΔASPP2腺病毒,利用rAd-p53、rAd-ASPP2、rAd-ΔASPP2感染p53缺失的细胞系H1299,在MMS的作用下研究ASPP2和ΔASPP2对p53介导的细胞凋亡的影响.结果发现,p53自身过表达能明显促进肿瘤细胞的凋亡;ASPP2可显著增强p53介导的MMS引起的H1299细胞凋亡的作用;然而,ΔASPP2对p53介导的细胞凋亡没有明显影响但却显著抑制rAd-ASPP2增强的rAd-p53的促细胞凋亡作用.p53-ASPP2复合体可能改变p53蛋白的构象,促进p53和增强子Bax的结合活性.p53转录调控基因的表达研究显示,ΔASPP2的存在可显著抑制ASPP2增强p53介导的bax基因转录活性,提示ΔASPP2可能与ASPP2结合后来抑制p53的凋亡基因转录活性.展开更多
文摘目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。
基金Supported by A joint grant from Mahidol University Faculty of Science and Ramathibodi Hospital Faculty of Medicine (Jensen LT and Wattanasirichaigoon D)Mahidol University (Wattanasirichaigoon D: 49/2556)+2 种基金the Pharmacogenomics Project,the collaborative project from the Thailand Center of Excellence for Life Science and Mahidol University to Sukasem Cthe Medical Scholars Program of Mahidol University (Wongkittichote P)a recipient (Wattanasirichaigoon D) of Research Career Development Award,Faculty of Medicine Ramathibodi Hospital
文摘AIM:To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS:A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1?(c.2T>C)and six previously known common SLC25A13 mutations:[Ⅰ](c.851_854delGTAT),[Ⅱ](g.IVS11+1G>A),[Ⅲ](c.1638_1660dup),[Ⅳ](p.S225X),[Ⅴ](IVS13+1G>A),and[XIX](g.IVS16ins3kb)using a newly developed TaqMan and established HybProbe assay,respectively.Sanger sequencing was employed for specimens showing an aberrant peak to confirm the targeted mutation as well as the unknown aberrant peaks detected.Frequencies of the mutations identified were compared in each region.Carrier frequency and disease prevalence of citrin deficiency caused by SCL25A13 mutations were estimated.RESULTS:p.Met1?was identified in the heterozygous state in 85 individuals,giving a carrier frequency of1/18,which suggests possible selective advantage of this variant.The question of p.Met1?homozygote lethality remains unanswered which may serve as an explanation as to why this homozygote has yet to be identified in patients/controls even with high allele frequency.The p.Met1?mutation has rarely been studied in populations other than Thai and Chinese;therefore,may have been overlooked.Development of the TaqMan assay in the present study would allow a simple,rapid,and cost-effective method for mass screening.Heterozygous mutations:[XIX]and[Ⅰ]were identified in 17 individuals,giving a carrier rate of 1/90 and a calculated homozygote rate of 1/33000.Two novel variants,g.IVS11+17C>G and c.1311C>T,of unknown clinical significance were identified at low frequency.CONCLUSION:This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1?allele.
文摘p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清楚.在本研究中,我们构建了rAd-ASPP2、rAd-ΔASPP2腺病毒,利用rAd-p53、rAd-ASPP2、rAd-ΔASPP2感染p53缺失的细胞系H1299,在MMS的作用下研究ASPP2和ΔASPP2对p53介导的细胞凋亡的影响.结果发现,p53自身过表达能明显促进肿瘤细胞的凋亡;ASPP2可显著增强p53介导的MMS引起的H1299细胞凋亡的作用;然而,ΔASPP2对p53介导的细胞凋亡没有明显影响但却显著抑制rAd-ASPP2增强的rAd-p53的促细胞凋亡作用.p53-ASPP2复合体可能改变p53蛋白的构象,促进p53和增强子Bax的结合活性.p53转录调控基因的表达研究显示,ΔASPP2的存在可显著抑制ASPP2增强p53介导的bax基因转录活性,提示ΔASPP2可能与ASPP2结合后来抑制p53的凋亡基因转录活性.
