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排序方式: 共有2827条查询结果,搜索用时 15 毫秒
51.
Maria Kostaki Argyro D. Manona Irene Stavraka Penelope Korkolopoulou Georgia Levidou Eleni‐Andriana Trigka Eleftheria Christofidou Grigorios Champsas Alexandros J. Stratigos Andreas Katsambas Othon Papadopoulos Christina Piperi Athanasios G. Papavassiliou 《Experimental dermatology》2014,23(5):332-338
Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16INK4A methylation and p16INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm2 vs >5/mm2, P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16INK4A promoter and several prognostic parameters in melanomas. 相似文献
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53.
《Expert opinion on biological therapy》2013,13(5):683-696
Adenoviral cancer gene therapy approaches have resulted in promising recent results. Following only a decade of intense development, some of the crucial obstacles are now being overcome. Insufficient transduction has been the main limitation of earlier approaches. A new approach for increasing transduction of tumour cells is utilisation of replication-competent oncolytic agents, such as conditionally replicating adenoviruses (CRADs). The anti-tumour effect is caused by replication of the virus per se and, thus, replication must be restricted to tumour cells to protect normal tissues from damage. Tissue-specific promoters (TSPs) represent a powerful tool for decreasing the toxicity of cancer gene therapy to normal tissues and have previously been utilised for specific mutation compensation or delivery of prodrug-converting enzymes. However, TSPs can also be used for controlling crucial viral replication regulators and consequent restriction of replication to tumour cells. Initial clinical trials have demonstrated the safety and suggested efficacy for TSP-controlled CRADs as a novel approach for cancer gene therapy. 相似文献
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目的探讨乙型肝炎病毒(Hepatitis B Virus,HBV)前C基因区变异与HBV-DNA载量的关系。方法通过DNA扩增、基因序列分析检测21例慢性肝炎、18例肝硬化和15例肝癌血清的HBV前C区和基本核心启动子(Basic Core Promoter,BCP)基因序列,荧光定量聚合酶链反应技术定量检测血清中的HBV-DNA。结果野生株与前C区终止变异、BCP双变异以及联合变异组HBV-DNA载量测定差异无显著性(P〉0.05);BCP双变异HBV-DNA载量HBeAg(-)组显著高于HBeAg(+)组(P〉0.05)。结论前C区终止变异和BCP双变异对HBV DNA复制无明显影响。HBeAg(-)的慢性肝病患者BCP变异后HBV DNA复制明显活跃。 相似文献
57.
Goshi Shiota Ken‐ichi Harada Kenji Oyama Akihide Udagawa Takahiro Nomi Kiwamu Tanaka Atsushi Tsutsumi Naoya Noguchi Yosuke Kishimoto Yutaka Horie Takeaki Suou Hironaka Kawasaki 《Liver international》2000,20(5):415-420
Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan. 相似文献
58.
《Vaccine》2015,33(45):6085-6092
The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is highly efficient and causes few adverse events; therefore, it is used worldwide. We previously constructed recombinant vOka (rvOka) harboring the mumps virus gene. Immunizing guinea pigs with rvOka induced the production of neutralizing antibodies against the mumps virus and VZV.Here, we constructed recombinant vOka viruses containing either the respiratory syncytial virus (RSV) subgroup A fusion glycoprotein (RSV A–F) gene or RSV subgroup B fusion glycoprotein (RSV B–F) gene (rvOka-RSV A–F or rvOka-RSV B–F). Indirect immunofluorescence and Western blot analyses confirmed the expression of each recombinant RSV protein in virus-infected cells. Immunizing guinea pigs with rvOka-RSV A–F or rvOka-RSV B–F led to the induction of antibodies against RSV proteins. These results suggest that the current varicella vaccine genome can be used to generate custom-made vaccine vectors to develop the next generation of live vaccines. 相似文献
59.
目的:探讨热休克蛋白(HSP)70基因启动子区 rs1008438位点单核苷酸多态性(SNP)与高原肺水肿(HAPE)之间的关系。方法采用PCR‐DNA直接测序法检测100例HAPE组、200例健康对照组个体基因组rs1008438位点的基因分布,分析不同基因型与HAPE的关系;运用ELISA法检测不同基因型HAPE组和健康对照组白细胞细胞质和细胞核HSP70蛋白含量变化;应用蛋白质芯片技术和 EVIDENCE180全自动芯片仪分析 TNF‐α、IL‐1β、IL‐6表达水平。结果 HAPE组,健康对照组rs1008438的TT、GT、GG的基因型频率分别是76.0%、20.0%、4.0%,93.0%、6.5%、0.5%。统计处理显示,HAPE组TT基因型频率明显低于健康对照组(P<0.05);GT、GG基因型患 HAPE的危险性是 TT基因型的4.195倍,G等位基因相对 T等位基因也能明显增加 HAPE的发病风险(OR=4.178);ELISA检测结果显示,不同基因型 HAPE组 HSP70含量均高于健康对照组,且HSP70细胞核/细胞质比值TT基因型高于GT/GG基因型;蛋白质芯片检测表明,HAPE组血清中的TNF‐α、IL‐1β、IL‐6表达水平均明显高于健康对照组。结论 rs1008438位点多态性与 HAPE易感性相关,这种相关性可能是由于突变型在基因转录水平通过影响启动子活性而增强HSP70表达,从而导致HAPE的发生。 相似文献
60.
Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation. 相似文献