共查询到20条相似文献，搜索用时 156 毫秒
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王春燕 《科技成果管理与研究》2016,(7):8-9
上海同济大学生命科学与技术学院高华研究员长期从事乳腺癌转移的研究,带领研究团队设计开发了一套高通量、全基因组水平的筛选模型,从而鉴定出一些与肿瘤转移功能直接相关的基因或microRNAs.通过临床病例分析和动物实验证实,已知的BMP信号通路抑制分子——Coco基因能够将肿瘤细胞由休眠状态诱导为活化的增殖状态,并从分子水平证明了Coco特异性调控乳腺癌的肺转移;研究揭示引发转移的肿瘤细胞具有肿瘤干细胞的特性,并且需要克服来自于靶器官的抑制肿瘤转移的信号以获得活性增殖状态. 相似文献
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DNA的甲基化作用作为一种常见的表观基因修饰方式广泛存在于生物体内,与DNA甲基化密切相关的蛋白--甲基化CpG结合蛋白(MeCPs)在DNA甲基化中起着非常显著的作用.通过浅谈DNA甲基化的作用及MeCP2的相关功能,并且构建了可表达MeCP2的载体,为进一步研究MeCP2在肿瘤和Rett综合症中的作用打下基础. 相似文献
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放化疗导致的淋巴细胞减少,改变了免疫细胞亚群的格局,启动了免疫细胞的内源性增殖,重建了一个新的免疫微环境,其机制主要与抑制肿瘤免疫的调节性T细胞比例与功能显著下调;内源性细胞因子IL-7,IL-15等供应增多,淋巴细胞离效扩增;抗原提呈细胞功能增强和以非对称性为特点的淋巴细胞自稳性增生的改变等相关,经历了淋巴细胞减少状态下肿瘤免疫格局的改变后,机体消除了抑制肿瘤免疫的重要因素,打破了肿瘤免疫耐受,肿瘤放化疗后选择合适时间点与生物治疗联合治疗,可以诱导出优于单一生物治疗的抗肿瘤效应,部分修正了以往认为放化疗导致的淋巴细胞减少不利于抗肿瘤免疫生物治疗的观念,为临束攻克肿瘤开辟新的治疗途径. 相似文献
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肿瘤多药耐药 (multidrugresistance ,MDR)是临床化疗成功最为严重的障碍 .首先阐明了新拓扑异构酶II抑制剂沙尔威辛对MDR肿瘤细胞直接的细胞毒性作用及下调mdr 1基因和P 糖蛋白的作用 .沙尔威辛能有效杀伤MDR细胞株 ,如K5 62 A0 2 ,KB VCR和MCF 7 ADR细胞 ,其杀伤能力与对相应亲本细胞相当 ,而明显强于几种临床常用的抗癌药物 .沙尔威辛下调mdr 1基因和P 糖蛋白的表达 ,但并不影响MRP和LRP基因 .其次 ,揭示了转录因子c jun的激活 ,在沙尔威辛下调K5 62 A0 2细胞内mdr 1基因表达及诱导凋亡过程中起着关键作用 .沙尔威辛增加K5 62 A0 2细胞的c jun表达明显早于其减少mdr 1基因的表达 ;c jun反义寡核苷酸消除沙尔威辛升高c jun蛋白、下调mdr 1基因表达的作用 .沙尔威辛还促进JNK和c jun磷酸化并增强转录因子AP1的DNA结合活性 .此外 ,c jun反义寡核苷酸还抑制沙尔威辛的凋亡诱导和细胞毒性作用 .最后 ,进一步研究发现沙尔威辛本身不引起MDR表型 .成功建立了对沙尔威辛具有 8 91倍耐药的A5 4 9 SAL细胞株 .该细胞株对抗代谢药产生 6.70倍的耐药 ,但对多种其他天然来源的抗肿瘤药物、烷化剂以及铂类化合物则缺乏交叉耐药性 . 相似文献
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利用同源克隆和RACE方法在商陆( Phytolacca acinosa )中得到一个推测的小G蛋白ArfGTPase激活蛋白 ArfGAP (ArfGTPase activating protein) 的全长cDNA序列 PaAGAP . PaAGAP 序列编码332个氨基酸.蛋白含有保守的锌指结构域(CX2CX16CX2C类)和C2结构域.实时荧光定量PCR表明在寒、旱、盐和重金属的不同时间胁迫下,PaAGAP可以被诱导,表达量有不同程度的上调.由此推测 PaAGAP 可能是通过快速启动转录和翻译,使ARF失活,抑制植物生长素极性运输,来参与植物逆境反应的. 相似文献
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Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in CLL subjects. Higher expressions of p53R2 (p53 dependent subunit of ribonucleotide reductase) and p53 were found in lymphocytes of chronic human lymphocytic leukemia as comparison to their normal counterparts. Inverse relation was found with p53 independent R2 subunit (in human hRRM2) of ribonucleotide reductase, which was found to be decreased from its control group. More expression of peripheral type benzodiazepine receptor, a cholesterol transporter, was noticed in isolated nuclear fraction with simultaneous increase of cholesterol concentration in cytoplasmic and nuclear compartments. A parallel increase of cholesterol in cell nucleus with increased p53R2 expression shows priority of the involvement of cholesterol in the process of cell replication. 相似文献
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通过分析13种生物120余种蛋白质的分子进化,首次揭示:配基-受体、蛋白酶-酶抑制剂、亚基-亚基等相互作用蛋白质间在纵向进化(物种间)、横向进化(不同功能蛋白质间)中均存在协同进化的规律.此结果表明,相互作用蛋白质其分子进化普遍为非随机过程,由于其相互作用为功能发挥所必需,因而彼此间以典型的达尔文选择方式进化.本文结果既弥补了中性理论中分子进化与功能方式无关的不足,亦指出达尔文选择适用于分子进化。 相似文献
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宫颈鳞状上皮癌变过程中细胞周期调节通路p14^ARF-MDM2-p53作用的研究 总被引：2，自引：0，他引：2
目的 探讨细胞周期调节p14ARF-MDM2-p53通路在宫颈上皮癌变过程中的作用.方法 采用免疫组化SP法检测18例正常宫颈上皮、48例宫颈上皮内瘤变(CIN)和23例宫颈鳞状细胞癌组织p14ARF、MDM2及p53蛋白的表达.结果 p14ARF蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为28%、42%和78%,宫颈鳞癌组表达较正常上皮和CIN组升高(P＜0.05);MDM2蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为0%、23%和43%,CIN和宫颈鳞癌组较正常宫颈上皮表达升高(P＜0.05);p53蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为6%、31%和39%,CIN及宫颈鳞癌组表达水平较正常宫颈上皮升高(P＜0.05);统计分析未发现三种蛋白的表达存在显著相关性.结论 p14ARF-MDM2-p53细胞周期调节通路与宫颈癌发生发展有关并有望用于CIN及宫颈癌的诊断. 相似文献
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Vascular function, homeostasis, and pathological development are regulated by the endothelial cells that line blood vessels. Endothelial function is influenced by the integrated effects of multiple factors, including hemodynamic conditions, soluble and insoluble biochemical signals, and interactions with other cell types. Here, we present a membrane microfluidic device that recapitulates key components of the vascular microenvironment, including hemodynamic shear stress, circulating cytokines, extracellular matrix proteins, and multiple interacting cells. The utility of the device was demonstrated by measuring monocyte adhesion to and transmigration through a porcine aortic endothelial cell monolayer. Endothelial cells grown in the membrane microchannels and subjected to 20 dynes∕cm(2) shear stress remained viable, attached, and confluent for several days. Consistent with the data from macroscale systems, 25 ng∕ml tumor necrosis factor (TNF)-α significantly increased RAW264.7 monocyte adhesion. Preconditioning endothelial cells for 24 h under static or 20 dynes∕cm(2) shear stress conditions did not influence TNF-α-induced monocyte attachment. In contrast, simultaneous application of TNF-α and 20 dynes∕cm(2) shear stress caused increased monocyte adhesion compared with endothelial cells treated with TNF-α under static conditions. THP-1 monocytic cells migrated across an activated endothelium, with increased diapedesis in response to monocyte chemoattractant protein (MCP)-1 in the lower channel of the device. This microfluidic platform can be used to study complex cell-matrix and cell-cell interactions in environments that mimic those in native and tissue engineered blood vessels, and offers the potential for parallelization and increased throughput over conventional macroscale systems. 相似文献
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酿酒酵母(Saccharomyces cerevisiae)的生长和发酵与其己糖转运蛋白家族紧密相关.酵母己糖转运蛋白家族包括Hxtlp至Hxt17p、Ga12p、以及同源蛋白Snf3p和Rgt2p这两个葡萄糖感应器.其中Hxt1p～Hxt7p对酵母生长及发酵发挥重要作用,缺失这7个蛋白的酵母无法从培养基中摄取己糖进行生长和发酵.根据对己糖的亲和力的不同,这几个转运蛋白可分为低亲和力转运子.包括Hxt1P和Hxt3p;高亲和力转运子,包括Hxt6p和Hxt7p;以及中等亲和力转运子Hxt2p和Hxt4p;而Hxt5p在生长发酵过程中没有发现有任何诱导表达.本文介绍了Hxt1p-Hxt7p等己糖转运蛋白在酵母生长发酵不同阶段中所发挥的作用,以期为构建高乙醇发酵效率的工业酵母菌株提供参考. 相似文献
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Angom Ranjana Devi Mahuya Sengupta Dipu Mani Barman Yashmin Choudhury 《Indian journal of clinical biochemistry : IJCB》2021,36(3):296
Nicotine, responsible for the addictive properties of tobacco, is widely used in nicotine replacement therapy for tobacco use cessation. We investigated the time-dependent effect of treatment with nicotine on the tumor suppressor, DNA repair and immune responses. Swiss Albino mice (laca strain) of both sexes received nicotine dissolved at a dose of 100 µg/ml in 2% sucrose for 24 weeks, by oral gavage, while age- and gender-matched controls received only 2% sucrose for the same period. Nicotine-treated and control mice were sacrificed 6, 16 and 24 weeks post-treatment, and their tissues evaluated for alterations in histology, oxidative stress, TNF-α levels, nitric oxide (NO) and myeloperoxidase (MPO) release, tumor suppressor response and DNA repair response. Statistical significance of results was determined using Students’ t test. The tissues of nicotine treated mice exhibited a large number of multinucleated and binucleated cells, enlarged nuclei and non-uniform distribution of cells, significant increase in expression of TNF-α gene and serum TNF-α, and time-dependent significant increase in lipid peroxidation, protein carbonylation, NO and MPO release when compared to age-and gender-matched controls. The mRNA expression of the tumor suppressor gene p53, its primary regulator Mdm2, and the DNA repair genes Brca2 and Ape1 were significantly elevated, but the corresponding protein levels remained largely unaltered. In conclusion, treatment with nicotine caused oxidative stress and inflammation which can cause widespread cellular damage from the very onset of treatment, without subverting the tumor suppressor and DNA repair responses.Electronic supplementary materialThe online version of this article (10.1007/s12291-020-00903-8) contains supplementary material, which is available to authorized users. 相似文献
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金属组学是继基因组学、蛋白质组学和代谢组学后提出的一种新的组
学。
本文将在介绍金属组学概念、研究方法的基础上，展望金属组学的发
展前景。 相似文献
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R. Kapoor D. B. Gundpatil B. L. Somani T. K. Saha S. Bandyopadhyay P. Misra 《Indian journal of clinical biochemistry : IJCB》2014,29(2):213-220
Cancer cells generally exhibit increased glycolysis for ATP generation (the Warburg effect). Compounds that inhibit glycolysis have potential applications in cancer treatment. dl-glyceraldehyde (DLG) and 2-Deoxyglucose (2-DG) have been proven effective in the inhibition of glucose metabolism. Ehrlich ascites carcinoma (EAC) cells were injected intraperitoneally (i.p) in 10–12 weeks old Swiss albino mice, weighing between 20 and 30 g. The anticancer activity of DLG and 2-DG were determined by tumor volume, tumor weight, viable and nonviable tumor cell count, average survival time, percentage increase in life span and tumor inhibition ratio. The blood samples were obtained for biochemical analysis after 9 days of treatment to study the effect on liver, kidney and haematological parameters. Histopathological examination of liver and kidney was also performed. One-way ANOVA test and Dunnett’s test were used for comparisons of parameters in study groups. Both DLG and 2-DG individually decreased the tumor weight, tumor volume, viable tumor cell count and significantly increased the life span of treated mice, however the combination was found to be better. The biochemical parameters of liver and kidney functions and haematological parameters were restored close to control group as compared with the EAC bearing mice. Histopathological examination of liver and kidney in EAC control group showed large areas of necrosis, congestion and mononuclear cell infiltration but such changes were not observed in liver and kidney sections observed after i.p injection of DLG and 2-DG for 9 days. Improvement was much better in the group where combination of these two drugs were used. 相似文献
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Vasanth Raj P Nitesh K Sagar Gang S Hitesh Jagani V Raghu Chandrashekhar H Venkata Rao J Mallikarjuna Rao C Udupa N 《Indian journal of clinical biochemistry : IJCB》2010,25(4):349-356
Objective of this study was to obtain a better understanding of the mechanism responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100 mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced
by intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day of catechin treatment. At the end of treatment all animals were killed and liver enzyme levels
were estimated. Dissected hepatic samples were used for histopathology, RNA isolation, expression studies of Bax, Bcl-2 and
p53 mRNA levels and mitochondrial membrane potential studies. We found that increases in the liver enzyme activity and decrease
in antioxidant enzyme activity by d-GalN were significantly restricted by oral pretreatment with catechin. Disruption of mitochondrial membrane potential, up
regulation of p53, Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with catechin. 相似文献