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核基质成分-拓扑异构酶II与肿瘤耐药 被引量:4
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作者 冯建航 许丽艳 李恩民 《肿瘤防治杂志》 2001年第6期675-677,共3页
DNA拓扑异构酶 (topoisomerase ,Topo)是核基质成分之一 ,是一种调整DNA拓扑结构的核酶 ,在DNA的复制和转录过程中发挥着重要作用 ,故而成为许多抗肿瘤化疗药物的靶。针对TopoII的抗肿瘤化疗药物同样面临着耐药问题。
关键词 dna拓扑异构酶 药物耐受性 抗药性 肿瘤
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新型3,3'-((4-氯-2H-硫色烯-3-基)亚甲基)双(1H-吲哚)类拓扑异构酶Ⅱ抑制剂的合成及抗肿瘤活性研究
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作者 梁国超 董婷婷 +3 位作者 纪海莹 王春艳 宋亚丽 张伟 《有机化学》 SCIE CAS CSCD 北大核心 2024年第6期1949-1956,共8页
对已知具有生物活性结构的基团进行对接拼合,设计合成了含双吲哚、苯并噻喃结构的3,3'-((4-氯-2H-硫色烯-3-基)亚甲基)双(1H-吲哚)类化合物.进行了目标化合物对6株肿瘤细胞的抗肿瘤实验,结果表明3,3'-((4-氯-2H-硫色烯-3-基)亚... 对已知具有生物活性结构的基团进行对接拼合,设计合成了含双吲哚、苯并噻喃结构的3,3'-((4-氯-2H-硫色烯-3-基)亚甲基)双(1H-吲哚)类化合物.进行了目标化合物对6株肿瘤细胞的抗肿瘤实验,结果表明3,3'-((4-氯-2H-硫色烯-3-基)亚甲基)双(5-甲氧基-1H-吲哚)(5b)、3,3'-((4-氯-7-甲基-2H-硫色烯-3-基)亚甲基)双(5-甲基-1H-吲哚)(5f)和3,3'-((4-氯-7-甲基-2H-硫色烯-3-基)亚甲基)双(N-甲基-2-甲基-吲哚)(5g)对肿瘤细胞抗增殖活性较好.拓扑异构酶抑制实验结果表明,化合物5b、3,3'-((4-氯-2H-硫色烯-3-基)亚甲基)双(6-氰基-1H-吲哚)(5c)、5f和5g对DNA拓扑异构酶II有选择性抑制活性,其它化合物对DNA拓扑异构酶II表现出不同程度抑制活性.分子对接研究结果表明,化合物5b和5g与DNA拓扑异构酶II产生了较为稳定的结合,具有潜在的抗肿瘤药物研究价值. 展开更多
关键词 双吲哚 抗肿瘤 dna拓扑异构酶ii 分子对接
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海南哥纳香醇甲GHM-10对L1210细胞DNA分子结构及拓扑异构酶Ⅱ活性的影响 被引量:3
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作者 何剑华 徐承熊 《药学学报》 CAS CSCD 北大核心 1999年第1期5-8,共4页
目的:研究海南哥纳香醇甲(GHM10)抑制癌细胞DNA合成的作用机制。方法:用单细胞凝胶电泳法检测GHM10对L1210细胞DNA分子的损伤,碱洗脱法测定GHM10对L1210细胞DNA单链长度的影响,用GHM... 目的:研究海南哥纳香醇甲(GHM10)抑制癌细胞DNA合成的作用机制。方法:用单细胞凝胶电泳法检测GHM10对L1210细胞DNA分子的损伤,碱洗脱法测定GHM10对L1210细胞DNA单链长度的影响,用GHM10对超螺旋pUC18DNA的解旋能力测定它对DNA拓扑异构酶II活性的影响。结果:L1210细胞用GHM10(4~10)μg·ml-1处理45h后,DNA分子受损,表现为电泳后在荧光显微镜下可见彗星状拖尾。GHM10(4~25)μg·ml-1处理L1210细胞5h,可引起DNA单链断裂。L1210细胞或从L1210细胞分离的蛋白质在用GHM10处理后,DNA拓扑异构酶II的活性均被抑制。结论:GHM10可引起L1210细胞DNA分子损伤;无论在细胞内还是细胞外,GHM10可抑制拓扑异构酶II的活性。 展开更多
关键词 抗肿瘤药 海南哥纳香醇甲 GHM-10 dna损伤 dna拓扑异构酶Ⅱ 抑瘤作用 酶测定法 单细胞电泳法 dna碱洗脱法
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THE ANTICANCER EFFECT AND ANTI-DNA TOPOISOMERASE II EFFECT OF EXTRACTS OF CAMELLIA PTILOPHYLLA CHANG AND CAMELLIA SINENSIS 被引量:3
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作者 谢冰芬 刘宗潮 +5 位作者 潘启超 梁永钜 苏秀容 王理开 张润梅 张宏达 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1994年第3期184-190,共7页
The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC... The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC-803 ) in vitro was studied using MIT assay method.The results showed that ECPC and ECS possessed significantcytotoxic effect on above three cell lines. The anticancer testin mice showed that ECPC had marked inhibitory effectagainst Ehrlich solid carcinoma(ESC) with inhibition ratesof 17. 8 48. 3% and with inhibition rates of 28. 3-54. 5% against reticular cell sarcoma(L2), and that ECShad inhibition rates of 31 . 5 -49. 4 % against ESC and 35. 8- 50% against L2. These two extracts had only marginalinhibitory effect against sarcoma- 180. The unknottingactivity of DNA topoisomerase II was inhibited completelyby ECPC and ECS at the concentration of 50 μg/ mlsuggesting that DNA topoisomerase II might be a targetenzyme of these two extracts. 展开更多
关键词 Camellia ptitophylla chang Camellia sinensis Antitumor effect Cytotoxic effect dna topoisomerase ii.
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Phylogenetic positions of several amitochondriate protozoa——Evidence from phylogenetic analysis of DNA topoisomerase II
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作者 HE De DONG Jiuhong +2 位作者 WEN Jianfan XIN Dedong LU Siqi 《Science China(Life Sciences)》 SCIE CAS 2005年第6期565-573,共9页
Several groups of parasitic protozoa, as represented by Giardia, Trichomonas, En-tamoeba and Microsporida, were once widely considered to be the most primitive extant eu-karyotic group―Archezoa. The main evidence for... Several groups of parasitic protozoa, as represented by Giardia, Trichomonas, En-tamoeba and Microsporida, were once widely considered to be the most primitive extant eu-karyotic group―Archezoa. The main evidence for this is their ‘lacking mitochondria’ and pos-sessing some other primitive features between prokaryotes and eukaryotes, and being basal to all eukaryotes with mitochondria in phylogenies inferred from many molecules. Some authors even proposed that these organisms diverged before the endosymbiotic origin of mitochondria within eukaryotes. This view was once considered to be very significant to the study of origin and evolution of eukaryotic cells (eukaryotes). However, in recent years this has been challenged by accumulating evidence from new studies. Here the sequences of DNA topoisomerase II in G. lamblia, T. vaginalis and E. histolytica were identified first by PCR and sequencing, then com-bining with the sequence data of the microsporidia Encephalitozoon cunicul and other eukaryotic groups of different evolutionary positions from GenBank, phylogenetic trees were constructed by various methods to investigate the evolutionary positions of these amitochondriate protozoa. Our results showed that since the characteristics of DNA topoisomerase II make it avoid the defect of ‘long-branch attraction’ appearing in the previous phylogenetic analyses, our trees can not only reflect effectively the relationship of different major eukaryotic groups, which is widely accepted, but also reveal phylogenetic positions for these amitochondriate protozoa, which is different from the previous phylogenetic trees. They are not the earliest-branching eukaryotes, but diverged after some mitochondriate organisms such as kinetoplastids and mycetozoan; they are not a united group but occupy different phylogenetic positions. Combining with the recent cytological findings of mitochondria-like organelles in them, we think that though some of them (e.g. diplo-monads, as represented by Giardia) may occupy a very low evo 展开更多
关键词 protozoa amitochondriate dna topoisomerase ii phylogenetic tree evolutionary position.
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HER2 and topoisomerase Ⅱα: possible predictors of response to neoadjuvant chemotherapy for breast cancer patients 被引量:7
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作者 ZHU Li LI Ya-fen CHEN Wei-guo HE Jian-rong PENG Chen-hong ZHU Zheng-gang LI Hong-wei 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第20期1965-1968,共4页
Background Surrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and t... Background Surrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study was to evaluate HER2 and topoisomerase Ⅱα (Topo Ⅱα) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients.Methods Between 1999 and 2006, seventy-six breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given in more than three cycles to this group of patients. Protein expression of HER2 and Topo Ⅱα were determined by immunohistochemistry. The primary endpoint was pathological and clinical response.Results Of 76 primary breast cancer samples, 27 (35.5%) showed overexpression of either HER2 (25%) or Topo Ⅱα protein (10.5%), whereas in 7 tumors (9.2%) both proteins were found to be overexpressed. Ten patients (13.2%) had a clinical complete response and 21 (27.6%) had a clinical partial response. Five women (6.6%) had a pathological complete response, 5 (6.6%) had microscopic residual disease, and 46 (60.5%) had macroscopic residual disease. HER2 and Topo Ⅱα overexpression was significantly associated with a favorable response (P 〈0.001 and P=0.005 respectively).Conclusion Our study suggests that HER2 and Topo Ⅱα overexpression could be predictors of the response to neoadjuvant chemothrapy in both the CEF and CMF arms. 展开更多
关键词 genes HER2 dna topoisomerase ii alpha neoadjuvant chemotherapy breast neoplasms
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耐药相关基因在非小细胞肺癌组织中的表达及其意义 被引量:5
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作者 郭杨 王永利 +2 位作者 王小玲 杨会钗 王永军 《中国肿瘤临床》 CAS CSCD 北大核心 2004年第7期391-394,共4页
目的:探讨耐药相关基因在非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法:应用免疫组化技术检测治疗前肺癌组织标本中P-gp、MRP、LRP、GST-π和TopoII表达。结果:58例治疗前NSCLC中P-gp、MRP、LRP、GST-π和TopoII阳性率分别为96.5... 目的:探讨耐药相关基因在非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法:应用免疫组化技术检测治疗前肺癌组织标本中P-gp、MRP、LRP、GST-π和TopoII表达。结果:58例治疗前NSCLC中P-gp、MRP、LRP、GST-π和TopoII阳性率分别为96.55%,67.24%,75.86%,65.52%,98.28%,并有部分共表达。癌旁正常肺组织呈阴性或弱阳性表达。性别、有无吸烟史、有无淋巴结转移及在TNM各分期中P-gp、MRP、LRP、GST-π和TopoII阳性表达无明显差异(P>0.05)。比较腺癌组与鳞癌组,MRP、LRP、GST-π阳性表达有显著性差异(P<0.05),而P-gp、TopoII阳性表达无明显差异(P>0.05);MRP、LRP、P-gp、GST-π共表达有显著性差异(字2=21.662,P<0.001);低分化腺癌、鳞癌与中、高分化腺癌、鳞癌P-gp、MRP、LRP、GST-π和TopoII阳性表达无明显差异(P>0.05)。结论:肺癌耐药为一多途径多基因参与的过程,肺腺癌原发的多药耐药机率较肺鳞癌高,联合检测肺癌组织中耐药相关基因的表达有助于判断化疗疗效及预后。 展开更多
关键词 多药耐药 P—糖蛋白 多药耐药相关蛋白 肺耐药蛋白 谷胱苷肽S转移酶 dna拓扑异构酶Ⅱ
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