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61.
62.
Spatio-temporal tumour model for analysis and mechanism of action of intracellular drug accumulation
We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral
lesion and the tumour cell’s response to therapy. A three-compartment model is used for drug dynamics within the tumour. The
first compartment represents the extracellular space in which cells move, the second corresponds to the intracellular fluid
space (including cell membrane) which is in direct equilibrium with the extracellular space, and the third is a non-exchangeable
compartment that represents sequestered drug which is trapped in the nucleus to damage the cellular DNA, directly triggering
cell death. Analytical and numerical techniques (Finite Element Method) are used to describe the tumour’s response to therapy
and the effect of parameter variation on the drug concentration profiles in the three compartments. 相似文献
63.
蛋白激酶C对鼻咽癌细胞c-myc,c-fos表达的影响 总被引:2,自引:0,他引:2
用蛋白激酶C(PKC)抑制剂Staurosporine(ST,抑制催化亚基)与Sphingosine(SS,抑制调节亚基)处理人鼻咽癌细胞系CNE-2Z,经点印迹后扫描定量和免疫细胞化学检测c-myc、c-fos表达及其分布。结果发现:(1)c-myc蛋白:主要分布于胞浆,40.7%的细胞核与胞浆均为阳性;经SS或ST处理后,表达明显减弱,且核阳性率分别为17.3%与23.3%。扫描定量在SS组为对照组的60%±25.7%(P<0.05),ST组为对照组的55%±25.9%(P<0.05)。(2)C-fos蛋白:主要分布于胞浆,29.4%的细胞核与胞浆均为阳性,经SS或ST处理后,表达明显减弱,且核阳性率分别为9%与10.2%。扫描定量SS组为对照组的58.6%±25%(P<0.05),ST组为对照组的59.7%±26.2%(P<0.05)。结果表明:使用PKC抑制剂后,两种核癌基因产物量均有不同程度的减少,并且存在细胞内分布的改变,特别是其发挥效应的核内表达明显减少。结合我们以前所发现的PKC抑制剂明显抑制CNE—2Z细胞生长的结果,提示这些癌基因可能参与了PKC对CNE—2Z细胞生长的调节。 相似文献
64.
Steven Jay Smith Alfred Neugut Daniel Heitjan Kenneth Forde Peter Holt Regina M. Santella Luo Jiin-chyuan Walter Carney Llewelyn Ward Paul W. Brandt-rauf 《Biomarkers》2003,8(3):311-332
Aberrant p53 protein accumulation was measured immunohistologically in 342 colorectal paraffin-embedded tissue sections from 115 patients (24 with adenocarcinoma, 59 with adenoma and 32 'hospital controls'). Subjective scoring was compared with quantitative cell imaging, including dichotomous (p53+/p53-) status, ng p53mut mg-1 enterocyte protein, and tumour burden and patient body 'burden' of aberrant p53. A total of 62.5% cancer patients, 23.7% adenoma patients and 3.1% hospital controls were accorded p53+ status on the basis of p53 quantification. Quantitative p53+/p53- assignment had a stronger inverse association with survival (χ2=6.17, p=0.013, Kaplan-Meier test) than subjective 'visual estimation' (χ2=0.57, p=0.449). There was a strong inverse relationship between the p53 'body burden' and the months of post-diagnosis survival (hazard ratio=1.42, p=0.0004, Cox proportional hazards). Absolute quantification for inactivated p53 permits objective and reproducible scoring, adjusts for intra-laboratory immunostaining 'batch effects', corrects for fixation artefacts, and standardizes for inter-laboratory differences in fixation, antibody selection and staining method. Clinically, in situ quantification of p53 will permit more accurate survival prognoses and will inform therapy selection and dose. Ultimately, accurate quantitative tissue/blood p53 correlations may provide a minimally invasive and systemic surrogate measure for these same clinical purposes. 相似文献
65.
水杉人工林树冠结构及生物生产力的研究 总被引:15,自引:2,他引:15
研究了水杉人工林的树冠结构和林分生物生产力。结果表明,不同密度及林龄的林分树冠结构存在较大差异,随着树冠部位上升和林分密度增大,分枝角度逐渐减小;径阶大小与枝叶率成反比,与树冠重量成正比,径阶增大,树冠最大叶量层的集团上移,有效光合面积相对减少,树冠结构的变化直接影响到林分的生物量生产、分配分配和经济生物量,林分干、枝、叶的干物质累积趋势可用Richard方程描述;林龄增大,分配到主干的生物量比例 相似文献
66.
腺相关病毒(adeno-associated virus,AAV)本身具有抗肿瘤活性,以其为基础构建的重组腺相关病毒(rAAV)作为肿瘤基因治疗载体已应用于临床试验研究。与其他的药物一样,单一的AAV基因药物,可能无法对肿瘤这一多基因、多步骤的复杂疾病发挥有效的治疗作用。国内外实验研究发现,多种化疗药物和放疗手段,不但可以提高rAAV载体的基因表达效率,也能促进AAV病毒本身的复制;反过来,AAV可以提高肿瘤细胞对放化疗的敏感性。联合AAV与其他的肿瘤治疗策略将有助于优化肿瘤治疗效果。 相似文献
67.
腺苷酸活化蛋白激酶(AMP—activated proteinkinase,AMPK)是真核细胞内发现的一类与细胞能量代谢有关激酶家族中的一员,被称之为“能量感应器”。当细胞内AMP/ATP值升高时,AMPK被激活。研究发现,在肿瘤细胞中,活化的AMPK可协同相关抑癌因子调节细胞周期、细胞凋亡以及蛋白质合成,最终影响细胞的增殖。因而,AMPK可以通过感应细胞能量水平的变化来调节细胞增殖。这给肿瘤治疗提供了一定的启示,即以肿瘤细胞能量代谢特点而探寻抑制肿瘤细胞增殖的途径。 相似文献
68.
Alexander Knight Nicholas R Leslie Agnieszka Zagozdzon Roderick Bronson Yefim Manevich Craig Beeson Carola A Neumann 《The EMBO journal》2009,28(10):1505-1517
It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS‐induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras‐induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation‐induced inactivation. Along those lines, Prdx1 tumour suppression of Ras‐ or ErbB‐2‐induced transformation was mediated mainly via PTEN. 相似文献
69.
胃泌素是胃窦和十二指肠黏膜G细胞分泌的多肽类激素 ,主要生理作用是促进胃酸分泌和胃肠道黏膜细胞生长。研究显示胃泌素是胃肠道肿瘤细胞一种自泌性的生长因子 ,通过促进增殖、抑制凋亡、刺激浸润以及和COX-2协同作用促进肿瘤生长。胃肠道肿瘤抗胃泌素治疗途径分为分泌抑制、受体拮抗、反义寡核苷酸抑制和抗胃泌素抗体治疗。其中抗胃泌素抗体治疗具有诸多优点 ,临床研究进展顺利。 相似文献
70.
Zi‐xiang YANG Xiao‐ming CHEN Nathan P. HAVILL Ying FENG Hang CHEN 《Entomological Science》2010,13(3):351-357
Rhus gall aphids (Fordinae : Melaphidini) have a disjunct distribution in East Asia and North America and have specific host plant relationships. Some of them are of economic importance and all species form sealed galls which show great variation in shape, size, structure, and galling‐site. We present a phylogeny incorporating ten species and four subspecies of Rhus gall aphids based on 1694 base pairs of nuclear elongation factor‐1α (EF1α) and mitochondrial cytochrome oxidase subunit II (COII) DNA sequence data. The results suggest that Melaphidini is monophyletic and at the genus level, Schlechtendalia, Nurudea, and Floraphis were each monophyletic. Kaburagia and Meitanaphis were not monophyletic and therefore inconsistent with the current classification. The North American sumac gall aphid, Melaphis rhois, was most closely related to the East Asian Floraphis species, although this was poorly supported. The conservation of gall morphology with respect to aphid phylogeny rather than their host plants suggests that gall morphology is largely determined by the aphids. While there is no evidence of strict co‐speciation between the aphids and their primary host plants, switching between recently diverged host plants may be involved in the speciation process in Melaphidini. 相似文献