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91.
Background
Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.Methodology/Principal Findings
We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼−11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.Conclusions/Significance
In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration. 相似文献92.
Gene conversion plays the major role in controlling the stability of large tandem repeats in yeast. 总被引:15,自引:0,他引:15 下载免费PDF全文
The genomic stability of the rDNA tandem array in yeast is tightly controlled to allow sequence homogenization and at the same time prevent deleterious rearrangements. In our study, we show that gene conversion, and not unequal sister chromatid exchange, is the predominant recombination mechanism regulating the expansion and contraction of the rDNA array. Furthermore, we found that RAD52, which is essential for gene conversion, is required for marker duplication stimulated in the absence of the two yeast type I topoisomerases. Our results have implications for the mechanisms regulating genomic stability of repetitive sequence families found in all eukaryotes. 相似文献
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94.
目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与中国北方人群脑膜瘤发病的相关性。方法:选择2012年1月-2013年12月在黑龙江省哈尔滨医科大学附属第二医院的第一、三病房接受手术治疗的脑膜瘤患者317例(实验组)及320例非脑膜瘤患者(对照组)为研究对象,利用聚合酶链反应限制性多态性片段长度(PCR-RFLP)检测和比较两组MTHFR两个单核苷酸多态性位点(C677T、A1298C)各种基因型(CC、CT、TT)的分布情况及等位基因的频率。结果:两组MTHFR的C677T中CC基因型的频率和TT基因型的频率比较有显著性差异(CC:OR=2.012,95%CI=1.460-2.772;TT:OR=0.399,95%CI=0.254-0.628,P0.05),实验组MTHFR的(0.450)C677T中的T等位基因频率明显高于对照组(0.320)(OR=0.529,95%CI=0.420-0.666,P0.05)。两组A1298C的等位基因分布比较没有统计学差别(P0.05)。结论:MTHFR基因的C677T中TT等位基因提示潜在的易患脑膜瘤的风险,而CC等位基因会降低中国北方人群患脑膜瘤的风险。 相似文献
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96.
Mammalian Genome - Microglia activation and its mediated neuroinflammation play an important role in the pathological process of various central nervous system injuries and diseases. Previous... 相似文献
97.
Nucleolin mediated pro‐angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post‐transcriptional regulation of VEGF‐A and MMP‐9 下载免费PDF全文
98.
Yuexian Li Cheng Sun Yonggang Tan Heying Zhang Yuchao Li Huawei Zou 《International journal of biological sciences》2021,17(2):635
Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a potential target for improving radiosensitivity.Materials and Methods: The radiosensitivity of NSCLC cells was evaluated by flow cytometry, colony formation assays, immunofluorescence, and Western blotting. Bioinformatics assay was used to identify the effect of ITGB1 and YAP1 expression in NSCLC tissues.Results: ITGB1 mRNA and protein expression levels were higher in H460R than in the parental H460 cells. We observed lower clonogenic survival and cell viability and a higher rate of apoptosis of ITGB1-knockdown A549 and H460R cells than of wild type cells post-irradiation. Transfection with an ITGB1 short hairpin (sh) RNA enhanced radiation-induced DNA damage and G2/M phase arrest. Moreover, ITGB1 induced epithelial-mesenchymal transition (EMT) of NSCLC cells. Silencing ITGB1 suppressed the expression and intracellular translocation of Yes-associated protein 1 (YAP1), a downstream effector of ITGB1.Conclusions: ITGB1 may induce radioresistance via affecting DNA repair and YAP1-induced EMT. Taken together, our data suggest that ITGB1 is an attractive therapeutic target to overcome NSCLC cell radioresistance. 相似文献
99.
龟纹瓢虫幼虫的食物搜索行为 总被引:9,自引:1,他引:9
本试验采用Nakamuta(1982)装置研究龟纹瓢虫Propylea japonica(Thunberg)幼虫的食饵搜索行为,结果表明:1.五种刺激均能激发搜索行为由广域型转换为地域集中型;2.摄食时间与GUT呈正相关;3.摄食的最后一个食饵大小决定GUT的长短;4.摄食后0—15秒的搜索速度小、弯曲角度大. 相似文献
100.