鼻咽癌组织中bcl—2,bax和p53的表达及其与瘤细胞？…

目的;了解鼻咽癌细胞中瘤细胞ｂｃｌ－２、ｂａｘ和ｐ５３的表达及其与瘤细胞凋亡指数的关系。方法：对３８例未经治疗的鼻咽癌组织,应用免疫组化ＬＳＡＢ法检测瘤ｂｃｌ－２、ｂａｘ和ｐ５３的表达;末端标记细胞死亡检测法（ＴＵＮＥＬ）计算癌细胞的凋亡指数。结果：（１）３７例（９７．４％）中有９０％左右的瘤细胞呈ｂｃｌ－２过表达;（２）３８例（１００％）中有７０％左右的瘤细胞过表达ｂａｘ;（３）２９例（７６．３     

c-erbB-2、p53、bcl-2和nm23-H1在肺癌中的表达

目的：探讨ｃｅｒｂＢ２、ｐ５３、ｂｃｌ２和ｎｍ２３Ｈ１基因在肺癌发生发展过程中的作用。方法：用免疫组化ＡＢＣ法对原发性肺癌组织中４种基因的表达和突变进行检测。结果：５８例肺癌中,３１例（５３４５％）ｐ５３过度表达,１８例（３１０３％）ｂｃｌ２过度表达。ｃｅｒｂＢ２与ｎｍ２３Ｈ１在１０例小细胞肺癌（ＳＣＬＣ）中未见表达。而在４８例非小细胞肺癌（ＮＳＣＬＣｓ）中两者过度表达率均为５０％。ｃｅｒｂＢ２与ｎｍ２３Ｈ１表达呈正相关（Ｐ＜００５）。腺癌ｎｍ２３Ｈ１的表达明显高于鳞癌（Ｐ＜００５）。ｐ５３、ｂｃｌ２蛋白表达在肺癌分化程度中呈负相关（Ｐ＜００５）。ｎｍ２３Ｈ１、ｐ５３和ｂｃｌ２的表达与患者的生存率有关（Ｐ＜００５）。结论：ｃｅｒｂＢ２、ｐ５３、ｂｃｌ２和ｎｍ２３Ｈ１基因蛋白产物的检测对肺癌患者的诊治和预后评估有积极意义。     

角化棘皮瘤细胞凋亡和bcl-2、bax表达及其相互关系

目的：探讨角化棘皮瘤（ｋｅｒａｔｏａｃａｎｔｈｏｍａ, Ｋ Ａ） 在细胞凋亡方面的生物学特点。方法：用末端脱氧核苷酰转移酶（ Ｔｄ Ｔ）介导的ｄ Ｕ Ｔ Ｐ 生物素缺口末端标记技术（ Ｔ Ｕ Ｎ Ｅ Ｌ） ,原位检测２０ 例角化棘皮瘤中凋亡细胞;应用免疫组织化学技术检测皮损部位ｂａｘ 和ｂｃｌ２ 基因产物的表达。结果： Ｋ Ａ 中８０ ％ （１６／２０） 瘤中心出现凋亡细胞。３０ ％ （６／２０） 肿瘤边缘ｂｃｌ２ 呈弱阳性染色。全部病例ｂａｘ 染色阳性。细胞凋亡指数与ｂａｘ 表达强度显著正相关（ ｒ＝ ０６８０ , Ｐ＝ ０００１） ,与ｂｃｌ２ 表达强度显著负相关（ｒ ＝ － ０６１８ , Ｐ＝ ０００４） 。结论：细胞凋亡为角化棘皮瘤的典型生物学特征,可能在 Ｋ Ａ 的自然消退中发挥重要作用。     

乳腺癌中凋亡与细胞增殖及Rb、bcl-2、c-myc蛋白表达的关系

目的：了解人乳腺癌中凋亡与细胞增殖的关系,以及与相关基因蛋白表达的关系及其预后意义。方法：用免疫组化ＬＳＡＢ法检测了９０例乳腺标本（包括１３例良性乳腺病变和７７例乳腺癌）中Ｒｂ、ｂｃｌ２和ｃｍｙｃ的蛋白表达;并计数了癌组织中的凋亡指数（ＡＩ,ＴＵＮＥＬ法）和有丝分裂指数（ＭＩ）。结果：ＡＩ与ＭＩ呈显著的正相关（ｒ＝０８１,Ｐ＜００１）;ＡＩ、ＭＩ和Ｒｂ蛋白表达与肿瘤大小和组织学分级有关,ＡＩ、ＭＩ低和ｂｃｌ２的高表达与５年生存率有关,ｃｍｙｃ的表达仅与组织学等级有关（Ｐ＜００５）;Ｒｂ表达与ＡＩ、ＭＩ均有关（Ｐ＜００１）,而ｂｃｌ２的表达仅与ＡＩ有关（Ｐ＜００５）。结论：乳腺癌中凋亡与细胞增殖和ｂｃｌ２表达有关,提示凋亡在具有不同生长潜能的亚群的克隆性选择中发挥重要作用。Ｒｂ与凋亡的关系提示细胞凋亡与细胞周期有关。     

肝细胞癌及癌旁肝组织中bcl-2和p53蛋白表达与端粒酶活性的相关性研究

目的：探讨ｂｃｌ２ 和ｐ５３ 蛋白的表达与端粒酶活性的相关性及其与 Ｈ Ｃ Ｃ 发生的关系。方法：利用端粒酶原位标记法显示端粒酶活性,采用 Ｓ Ｐ 法免疫组化技术检测ｂｃｌ２ 和ｐ５３ 蛋白。结果：端粒酶在 Ｈ Ｃ Ｃ 中的阳性率（９１７ ％ ） 显著高于癌旁肝组织（５８３ ％ ）（ Ｐ＜ ００５） ,端粒酶活性强度与 Ｈ Ｃ Ｃ 分化程度无关（ Ｐ＞ ００５） ;癌组织中ｂｃｌ２ 和ｐ５３ 蛋白的阳性率均高于癌旁组织（ Ｐ＜ ００１） ; Ｈ Ｃ Ｃ 和癌旁组织中端粒酶活性程度随ｂｃｌ２ 蛋白表达增强而升高,并呈明显正相关,但与ｐ５３ 蛋白表达强度无明显相关性。结论：ｂｃｌ２ 蛋白的过度表达可能是端粒酶激活的重要途径之一,ｂｃｌ２ 蛋白过度表达可能通过激活端粒酶使肝细胞恶性转化导致 Ｈ Ｃ Ｃ 发生,而ｐ５３ 基因突变可能对端粒酶的激活无直接影响。     

胶质瘤p53、bcl-2、MDM2表达与细胞增殖和凋亡的关系

目的：研究胶质瘤中ｐ５３ 、ｂｃｌ２ 、ＭＤＭ２ 表达与细胞增殖和凋亡的关系。方法：对４８ 例胶质瘤用免疫组化法检测ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白表达;以Ｋｉ６７ 标记指数和ＡｇＮＯＲ 计数检测其增殖活性;用ＴＵＮＥＬ 法检测细胞凋亡。结果：ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白表达阳性率分别为４７－９ ％ 、３５－８ ％ 及１２－５ ％ ,细胞增殖活性随肿瘤ｐ５３ 、ｂｃｌ２、ＭＤＭ２ 表达水平增高而增高,细胞凋亡则相反。结论：ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白过表达与细胞增殖失控、凋亡抑制关系密切,在胶质瘤恶性进展中起重要作用。     

反义bcl-2 DNA促进裸鼠荷人鼻咽癌细胞株CNE2-baxα凋亡

目的：在裸鼠活体水平上观察ｂｃｌ－２反义寡聚核苷酸（ａｎｔｉｓｅｎｓｅ ｉｏｌｉｇｏｄｅｏｘｙｎｕｃｌｅｏｔｉｄｅ,ＡＳＯＮ）对鼻咽癌细胞株ＣＮＥ２－ｂａｘα凋亡的影响。方法;ＤＮＡ合成仪合成２２ｎｔ ＡＳＯＮ片段,ＲＴ－ＰＣＲ检测ｂｃｌ－２表达,电镜观察细胞凋亡。结果;反义ｂｃｌ－２ ＤＮＡ片段局部注射ＣＮＥ２－ｂａｘα致瘤组织,ＲＴ－ＰＣＲ检测肿瘤组织中ｂｃｌ－２表达被封闭,电镜观察视野下可见     

食管癌变过程中p53、c-myc、bcl-2表达及其与细胞凋亡的关系

目的：探讨食管癌变过程中肿瘤抑制基因ｐ５３和癌基因ｃ－ｍｙｃ、ｂｃｌ－２的变化及其与细胞凋亡的关系。方法：采用免疫组化法（ＡＢＣ）检测２７９例食管粘膜活检组织中ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２的表达以及细胞凋亡的变化。结果：从食管正常上皮到基底细胞增生、间变和癌，ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２免疫阳性表达率及细胞凋亡发生率和细胞凋亡指数（ＡＩ）均呈升高趋势，而且在同一阶段病变，ｐ５３和ｃ－ｍｙｃ阳性表达时凋亡指数高于其阴性表达，而ｂｃｌ－２阳性表达时凋亡指数低于其阴性表达。结论：在食管癌变过程中可能有多种肿瘤抑制基因和癌基因参与，细胞凋亡在食管癌变过程中可能有重要的生物学意义。     

角化棘皮细胞凋亡和bcl—2,bax表达及其相互关系

目的：探讨角化棘皮瘤（ｋｅｒａｔｏａｃａｎｔｈｏｍａ，ＫＡ）在细胞凋亡方面的生物学特点。方法：用末端脱氧核苷酰转移酶（ＴｄＴ）介导的ｄ－ＵＴＰ生物素缺口末端标记技术（ＴＵＮＥＬ），原位检测２０例角化棘皮瘤中凋亡细胞；应用免疫组织化学技术检测皮损部位ｂａｘ和ｂｃｌ－２基因产物的表达．结果：ＫＡ中８０％（１６／２０）瘤中心出现凋亡细胞。３０％（６／２０）肿瘤边缘ｂｃｌ－２呈弱阳性染色。全部病例ｂａｘ染     

bcl-2、p53表达与乳腺癌预后的关系

目的：探讨ｂｃｌ２ 、ｐ５３ 表达与乳腺癌预后的关系。方法：应用免疫组化ＬＳＡＢ法检测６４ 例乳腺癌及３０ 例乳腺良性病变的表达。分析ｂｃｌ２、ｐ５３ 与乳腺癌组织学分级、腋淋巴结转移、复发和预后的关系。结果：ｂｃｌ２ 与ｐ５３ 表达之间差异有显著性,呈负相关（ Ｐ＜ ０－０５） 。ｂｃｌ２ 和ｐ５３ 表达与组织学分级有关（ Ｐ＜ ０－０５） ,ｂｃｌ２ 表达随分级增加阳性率降低,ｐ５３ 则相反。ｐ５３ 表达与腋淋巴结转移有关（ Ｐ＜ ０－０５） 。ｂｃｌ２ 表达与腋淋巴结转移无关（ Ｐ＞ ０－０５） 。ｐ５３ 表达复发组明显高于无复发组（ Ｐ＜０－０５）;ｂｃｌ２ 表达与有无复发无关（Ｐ＞０－０５）。ｐ５３ 表达阳性率≤５ 年生存组明显高于＞ ５ 年生存组,呈负相关（ Ｐ＜ ０－０５）;ｂｃｌ２ 表达与生存期无关（Ｐ＞ ０－０５） 。结论：ｂｃｌ２ 表达与预后无关,其阳性表达可反映肿瘤属分化较好或属早期阶段。ｐ５３ 可单独作为预后指标;ｐ５３ 表达与预后呈负相关。     

Effects of ultra-marathon on circulating DNA and mRNA expression of pro- and anti-apoptotic genes in mononuclear cells

We investigated the effects of an ultra-marathon on cell-free plasma DNA as well as on mRNA expression of pro-apoptotic (Bax, Bad), anti-apoptotic (Bcl-2) and cell-protective (Hsp70, Hsp27 and Hsp32) genes in mononuclear blood cells (MNCs). Blood samples were drawn from 14 athletes before and immediately after 6-h run. In addition, blood samples were also collected and analyzed 2 and 24 h after the end of the run. Levels of plasma DNA were significantly increased immediately after the marathon (P < 0.001) and were still higher 2 h later (P < 0.005), but significantly lower than those immediately after the race (P < 0.05). Cell-free plasma DNA returned to pre-race levels 24 h after the run. mRNA expressions of Hsp70, Hsp32 and Bax significantly increased in MNCs after the race, whereas Hsp27 and Bad mRNA expression levels showed no significant changes. Bcl-2 expressions decreased immediately after the race (P < 0.001), but increased in the 24 h later (P < 0.05). We conclude that apoptotic ladders of cell-free DNA following exhaustive exercise originate from apoptotic cells and that not only skeletal muscle cells but also leukocytes contribute to this phenomenon. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Incidence of SUC-RTM telomeric repeated genes in brewing and wild wine strains of Saccharomyces

When over-expressed, RTM yeast genes confer resistance to the toxicity of molasses. They are found in distiller's and baker's industrial yeasts in multiple copies, scattered on the telomeres and physically linked to the telomeric SUC genes. Because these genes are absent from some laboratory strains, we explored the genomes of other industrial yeasts (brewing strains) and wine wild strains. A collection of 47 wine yeast strains (S. cerevisiae and S. bayanus) and 15 brewing strains, lager, ale and possible ancestors (S. monacensis, S. paradoxus and S. carlsbergensis) were screened for the presence of RTM genes. Only three wine strains and all brewing strains proved to contain RTM sequences in different copy numbers. PCR and chromosome blotting confirm the presence of SUC sequences in tandem with RTM. Moreover, analysis of the entire S. cerevisiae genome sequence shows that three other, non-telomeric, genes related to RTM are scattered on different chromosomes. Received: 4 December 1996     

铜绿假单胞菌噬菌体PaP3全基因组在感染宿主菌PA3过程中的分时期表达研究

目的明确铜绿假单胞菌噬菌体PaP3在感染宿主菌PA3后其全基因组的分时期表达模式。方法利用基因芯片检测噬菌体PaP3在感染宿主菌PA3后不同时间(5 min,10 min,20 min,30 min,80 min)其全基因组(含71个预测的ORF)在转录水平的表达谱变化,并进行非监督层次聚类(hierarchical clustering)分析。利用蛋白质合成抑制剂氯霉素(Cm)和DNA复制抑制剂磷酸乙酸(PAA)实验确定PaP3全基因组的分时期表达情况。结果根据时间表达模式的不同,PaP3全基因组可分为3大类:15个早期基因(ORF 71-57)、35个中期基因(ORF 56-22)及21个晚期基因(ORF 21-1)。在PaP3基因组结构中,这3类基因各自串联分布且可能受不同的操纵子调控。结论 PaP3感染过程中其早期、中期及晚期基因随时间有序表达,为深入了解噬菌体基因表达模式及生命复制周期奠定基础,并为了解噬菌体与宿主及机体免疫系统的的相互作用提供了基础。     

Dlx and Other Homeobox Genes in the Morphological Development of the Dentition

The dentition is a segmental system whose evolution and morphology bears analogy to the evolution of segmentation in the vertebral column and limb. Combinatorial expression of members of the large “Hox” class of homeobox regulatory genes has been shown to play an important role in positional specification in these skeletal systems. This raises the possibility that homeobox genes are also used for positional specification in the dentition, and several homeobox genes are known to be expressed in developing teeth. To identify additional dentally expressed homeobox genes, cDNA from from murine tooth germs at 9.5, 14.5, and 17.5 days gestational age was amplified by PCR using sets of degenerate primers to the homeodomains of 18 different classes of homeobox genes. Amplification products were cloned and sequenced and compared to known gene sequences. To date this approach has confirmed the presence of Msx1, Msx2, Dlx1, and Dlx2, and identified several other homeobox genes not previously known to be expressed in teeth: Dbx, MHox, and Mox2A, plus an additional Dlx gene, Dlx7. The Msx and Dlx genes are the best current candidates for a combinatorial mechanism that controls the differentiation of structures within and between teeth, and perhaps also the evolution of those structures.     

Clinical significance of p16 protein expression loss and aberrant p53 protein expression in pancreatic cancer

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.     

Catalog of 300 SNPs in 23 genes encoding G-protein coupled receptors

We previously published a series of detailed maps of single nucleotide polymorphisms (SNPs) in the genomic regions of 209 gene loci encoding drug metabolizing enzymes, transporters, receptors, and other potential drug targets. In addition to the maps reported earlier, we provide here high-resolution SNP maps of 23 genes encoding G-protein coupled receptors in the Japanese population. A total of 300 SNPs were identified through screening of these loci; 83 in four adenosine receptor family genes, 45 in three adrenergic receptor family genes, 22 in three EDG receptor family genes, 29 in three melanocortin receptor family genes, 22 in two somatostatin receptor family genes, 21 in five anonymous G protein-coupled receptor family genes, and 78 in the others (AVPR1B, OXTR, and TNFRSF1A). We also discovered a total of 33 genetic variations of other types. Of the 300 SNPs, 132 (44%) appeared to be novel on the basis of comparisons with the dbSNP database of the National Center for Biotechnology Information (US) or with previous publications. The maps constructed in this study will serve as an additional resource for studies of complex genetic diseases and drug-response phenotypes to be mapped by linkage-disequilibrium association analyses.     

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:391–397, 1999. © 1999 Wiley-Liss, Inc.