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91.
胃癌组织p16基因蛋白表达的意义 总被引:9,自引:4,他引:5
目的 检测 p1 6基因蛋白在胃癌组织、癌旁组织中的表达及其分布特点 ,分析其与胃癌临床病理学特征及预后的关系 .方法 采用 S- P免疫组织化学法对 53例胃癌组织及 35例癌旁组织进行 p1 6蛋白的定位观察 .结果 各病理类型胃癌组织、癌旁组织均有 p1 6基因蛋白表达 .阳性率分别为 62 .3% (33/53)和 88.6% (31 /35) ,阳性细胞的棕黄色颗粒主要位于细胞核 .胃癌 p1 6基因蛋白表达与性别、年龄、肿瘤部位在统计学上无差异 (P>0 .0 5) ;而与组织学类型、病理分级、淋巴结转移、临床病理分期在统计学上有差异 (P<0 .0 5) .p1 6蛋白阳性者 5年生存率 51 .0 %高于 p1 6蛋白阴性者 2 0 .0 % (P<0 .0 5) .结论 p1 6基因缺失和表达水平的改变与胃癌发生、发展密切相关 ,检测 p1 6基因蛋白表达可作为辅助临床判断胃癌的生物学行为及推测预后的指标 相似文献
92.
T B Vree Y A Hekster M W Tijhuis E F Termond J F Nouws 《Biopharmaceutics & drug disposition》1986,7(3):239-252
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
93.
Annemieke Smit-van Oosten Winston W. Bakker Harry van Goor 《Transplant international》2002,15(12):602-609
Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF. 相似文献
94.
人原发性肝癌中p16基因表达及CpG岛甲基化状态的研究 总被引:1,自引:0,他引:1
目的 进一步探讨人原发性肝癌中 p16基因 m RNA转录水平变化与其基因启动子区 Cp G岛甲基化的关系 ,及其在肝癌发生中的意义。方法 采用狭缝印迹杂交检测 2 0例人原发性肝癌及相应的癌旁、远癌组织及 2例正常人肝组织中 p16基因 m RNA表达水平 ,以甲基化特异性 PCR分析各组织中 p16基因启动子区 Cp G岛的甲基化状况 ,并进行统计分析。结果 2 0例人原发性肝癌中 14例 (70 % ) p16 m RNA水平比远癌组织显著降低 ;13例 (6 5 % )显示 p16基因启动子区 Cp G岛甲基化 ,其中 84 .6 % (11例 )伴 p16 m RNA转录水平降低。结论 人原发性肝癌中存在高频率的 p16基因表达失活 ,其主要机制可能是启动子区 Cp G岛甲基化抑制了基因的转录 ,在人原发性肝癌的发生发展中有重要作用。其临床诊断和治疗意义有待进一步深入研究。 相似文献
95.
p14ARF基因和核转录因子E2F-1在细胞周期调控,细胞凋亡和肿瘤发生中具有重要作用。近年来,有研究表明p14ARF在肺癌中的表达率低于正常组织,E2F-1的表达率高于正常组织。本文将就p14ARF、E2F-1与肺癌的关系进行综述。 相似文献
96.
Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene. 相似文献
97.
Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other. 相似文献
98.
Rupert R Lanzenberger Markus Mitterhauser Christoph Spindelegger Wolfgang Wadsak Nikolas Klein Leonhard-Key Mien Alexander Holik Trawat Attarbaschi Nilufar Mossaheb Julia Sacher Thomas Geiss-Granadia Kurt Kletter Siegfried Kasper Johannes Tauscher 《Neuropsychopharmacology》2007,61(9):1081-1089
BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders. 相似文献
99.
作者用同位数前体参入法及透射与扫描电镜研究了平阳霉素(博莱霉素A_5)对HeLa细胞大分子生物合成及超微结构的影响。结果显示:平阳霉素能抑制HeLa细胞DNA,RNA和蛋白质的生物合成,对DNA的抑制作用强,ID_(50DNA)为42.77μg/ml。表现为:染色质减少,核内电子密度低,核仁分离及“核仁帽”形成,细胞表面微绒毛消失或变形,最终导致质膜破裂等。作者认为,细胞膜是否为此类药物作用的靶位值得进一步研究。 相似文献
100.
Lars von Knorring Béla G. L. Almay Jan Häggendal Folke Johansson Lars Oreland Lennart Wetterberg 《European archives of psychiatry and clinical neuroscience》1986,236(3):131-138
Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet 相似文献