肝衰竭患者外周血单个核细胞hTERT mRNA水平及其与临床预后的关系

目的探讨肝衰竭患者外周血单个核细胞（PBMCs）中人端粒酶逆转录酶（hTERT） mRNA的变化对预后的评估价值.方法采用实时荧光定量RT-PCR法检测20例正常人和60例肝衰竭患者28天内PBMCs hTERT mRNA水平.结果39例生存患者PBMCs hTERT mRNA水平在入院后依次上调,在入院时、入院后7天、14天、21天和28天分别较正常人升高了2.87、4.27、9.23、23.35和30.50倍,而死亡患者在各时间点依次下降,分别是正常人的3.01、2.08、1.21、0.28和0.06倍;PBMC hTERT mRNA水平对判断预后的ROC曲线下面积在入院时及治疗后7天、14天、21天和28天分别为0.611±0.075、0.676±0.074、0.786±0.065、0.993±0.008和0.998±0.003.结论 PBMCs hTERT mRNA水平可作为肝衰竭患者的预后判断指标,特别是在治疗14天以后.     

TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements

Dyskeratosis congenita (DC) is a rare inherited form of bone marrow failure (BMF) caused by mutations in telomere maintaining genes including TERC and TERT. Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening in an unselected population of patients with BMF at our medical center and in a selected group of patients referred from outside institutions. Less than 5% of patients with BMF had pathogenic mutations in TERC or TERT. In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated with marked telomere shortening (< 1st percentile) in peripheral blood mononuclear cells (PBMCs). In asymptomatic family members, however, telomere length was not a reliable predictor for the presence or absence of a TERC or TERT gene mutation. Telomere shortening was not pathognomonic of DC, as approximately 30% of patients with BMF due to other causes had PBMC telomere lengths at the 1st percentile or lower. We conclude that in the setting of BMF, measurement of telomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.     

不同食管病变中端粒酶活性与端粒酶RNA组分、端粒酶逆转录催化亚单位的相关性及其意义

目的　探讨不同食管病变中端粒酶活性 (TA)、端粒酶RNA组分 (hTR)及端粒酶逆转录催化亚单位 (hTERT)的表达 ,彼此间相关性及其预后意义。方法　采用TRAP 银染、原位杂交及免疫组化技术检测TA、hTR及hTERT在 38例食管鳞癌组织、15例不典型增生及 12例正常食管粘膜中的表达情况。结果　食管鳞癌TA、hTR及hTERT的阳性表达率分别为 84 2 1%( 32 /38)、71 0 5 %( 2 7/38)及 81 5 8%( 31/38) ,不典型增生组织中TA、hTR及hTERT阳性表达率分别为 6 0 0 0 %( 9/15 )、33 33%( 5 /15 )及 40 0 0 %( 6 /15 ) ,与正常组织比较 ,具有显著性差异 (P <0 0 5 ) ,TA与hTR及hTERT的表达具有相关性 (P <0 0 5 )。TA、hTR及hTERT的表达与临床病理因素无关 (P >0 0 5 )。结论　TA、hTR及hTERT在食管癌的发生发展中起着重要作用 ;hTR及hTERT能够反应端粒酶活性 ,三者均为食管鳞癌恶性表型增高的标志 ;hTR及hTERT具有独立的预后意义。     

人端粒酶催化亚单位的研究进展

人端粒酶是染色体末端的DNA蛋白酶，对维持染色体稳定至关重要，在细胞增殖、衰老、永生化及癌变中起重要作用。人端粒酶逆转录酶（hTERT）是端粒酶激活的主要限制因素，与肿瘤的发生发展密切相关，因此，认识其调控机制及在肿瘤诊治的研究广泛开展。目前，hTERT用于临床肿瘤诊断的意义已被认可，并且已有利用其进行肿瘤治疗的Ⅰ期临床试验。     

Expression of human telomerase reverse transcriptase in lymphangioleiomyomatosis

Telomerase synthesizes nucleotide hexameric repeats (telomeres) at the ends of chromosomes, replacing base sequences that are lost from these sites during each mitotic cycle and protecting these ends against the action of exonucleases and ligases. Therefore, telomerase is essential for maintaining cellular replication. To evaluate the role of telomerase in the proliferation of abnormal smooth muscle cells (lymphangioleiomyomatosis [LAM] cells) in LAM, we performed immunostaining and in situ hybridization studies to identify telomerase protein and messenger RNA (mRNA), respectively, in pulmonary (n = 18) and extrapulmonary (n = 4) lesions from 22 women with LAM (14 untreated and 8 treated with progesterone or tamoxifen). Immunoreactivity and hybridization signals for telomerase were observed in 5 to 20% of LAM cells, mostly of the spindle-shaped type, in 21 of the 22 patients, and were less intense in the treated group. Other types of cells were unreactive in both groups. Telomerase colocalized in the same cells with alpha-smooth muscle actin, but only rarely with HMB-45 antibody (a marker for epithelioid LAM cells); colocalization with proliferating cell nuclear antigen was incomplete. The telomerase-positive LAM cells may constitute the sources of renewal of LAM cells. Modulation of telomerase may be involved in the control of LAM cell proliferation.     

端粒酶及端粒酶逆转录酶在良、恶性胸腔积液中的表达及意义

目的 研究端粒酶及端粒酶逆转录酶(hTERT)在良、恶性胸腔积液中的表达,为临床诊断提供实验依据.方法 选择21例恶性胸腔积液(恶性组)及23例良性胸腔积液患者(良性组),应用重复序列扩增法-ELISA(TRAP-EUSA)法及免疫组化方法检测积液中端粒酶、hTERT及癌胚抗原(CEA)表达.结果 良性组和恶性组端粒酶表达阳性率分别为39.13%、76.19%,P<0.01;hTERT表达阳性率分别为0、80.95%,P<0.01.hTERT检测恶性胸腔积液的特异度(100%)显著高于端粒酶(60.87%),敏感度(80.95%)显著高于CEA(47.62%).结论 hTERT检测恶性胸腔积液的敏感度和特异度均较高,且其免疫组化检测方法简便易行,值得临床借鉴.