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Two-step Enzymatic Synthesis of Guanine Arabinoside 被引量:5
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作者 魏晓琨 丁庆豹 +2 位作者 欧伶 张鹭 王昌禄 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2008年第6期934-937,共4页
The chemical synthesis of Guanine arabinoside (ara-G) is extremely complex, time-consuming, and seriously polluted. A two-step enzymatic synthesis process was developed to acquire ara-G easily. 2,6-Diaminopurine ara... The chemical synthesis of Guanine arabinoside (ara-G) is extremely complex, time-consuming, and seriously polluted. A two-step enzymatic synthesis process was developed to acquire ara-G easily. 2,6-Diaminopurine arabinoside (ara-DA) was first synthesized with purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase produced by Enterobacter aerogenes DGW-07. The conversion yield of ara-DA could reach above 90% when the reaction liquid contained 30 mmol·L^-1 uracil arabinoside as arabinose donor, 10 mmol·L^- 1 2,6-diaminopurine as arabinose acceptor in pH 7.0 20 mmol·L^-1 phosphate buffer, and reacted at 60℃ for 48h. Then, ara-DA was effectively transformed into ara-G with adenylate deaminase produced by Aspergillus oryzae DAW-01. The total process had no complex separation and purification. 展开更多
关键词 guanine arabinoside 2 6-diaminopurine arabinoside purine nucleoside phosphorylase pyrimidine nucleoside phosphorylase adenylate deaminase Enterobacter aerogenes Aspergillus oryzae
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Pharmaceutical Characteristics of Daunorubicin Stealth Liposomes
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作者 张华 齐宪荣 张强 《Journal of Chinese Pharmaceutical Sciences》 CAS 2001年第4期200-202,共3页
This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were exa... This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were examined. Visible spectrophotometry and the HPLC method were established for determination of the DNR in the DNRSL. The release of DNR from DNRSL in HBS (pH 7.5) and rat serum at 37 oC were examined. The results showed that the DNRSL had high entrapment efficiency (>85%), small size and slow release. 展开更多
关键词 Stealth liposomes daunorubicin Entrapment efficiency Drug release in vitro
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Induction of nucleoside phosphorylase in Enterobacter aerogenes and enzymatic synthesis of adenine arabinoside 被引量:5
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作者 Xiao-kun WEI Qing-bao DING +3 位作者 Lu ZHANG Yong-li GUO Lin OU Chang-lu WANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第7期520-526,共7页
Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP cou... Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5′-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced. 展开更多
关键词 Nucleoside phosphorylase (NPase) Enterobacter aerogenes CYTIDINE Cytidine 5'-monophosphate (CMP) Adenine arabinoside
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INHIBITION OF NF-κB ACTIVITY ENHANCED CYTOSINE ARABINOSIDE INDUCED APOPTOSIS IN LEUKEMIC CELL LINE HL60-N
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作者 许小平 史剑慧 +3 位作者 吕书晴 张宗梁 张劲松 程文英 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2003年第3期172-176,共5页
Objective: To explore the effects of dexamethasone (DXM) and vincristine (VCR) on cytosine arabinoside (Ara-C) induced apoptosis and activation of nuclear factor-k-gene binding (NF-kB) in leukemic cell line HL60-n. M... Objective: To explore the effects of dexamethasone (DXM) and vincristine (VCR) on cytosine arabinoside (Ara-C) induced apoptosis and activation of nuclear factor-k-gene binding (NF-kB) in leukemic cell line HL60-n. Methods: Apoptosis of HL60-n cells was analysed by TdT-mediated X-dUTP nick and end labeling (TUNEL) and DNA electrophoresis. NF-kB activity of HL60-n cells was detected by electrophoretic mobility shift assay (EMSA). Results: There was slight activation of NF-kB in HL60-n cells without drug induction. Ara-C at 1 mmol/L significantly enhanced the activation of NF-kB in HL60-n cells. The level of NF-kB activation induced by DXM at 1 mmol/L or VCR at 0.1 mmol/L had no significant difference compared with that of the control group. However, in HL60-n cells pre-treated with 1 mmol/L of DXM or 0.1 mmol/L of VCR, the activation of NF-kB induced by 1 mmol/L of Ara-C was significantly suppressed with inhibition rates of 31.0% and 47.0%, respectively. The apoptosis rates of HL60-n cells induced by 1.0 mmol/L, 10 mmol/L and 100 mmot/L Ara-C were 45.003.16%, 61.883.40% and 77.624.75%, respectively. The apoptotic rates of HL60-n cells induced by DXM at 1 mmol/L or VCR at 0.1 mmol/L were similar to that of the control group. However, either DXM at 1 mmol/L or VCR at 0.l mmol/L could enhance the apoptosis of HL60-n cells induced by Ara-C at 1 mmol/L with rates of 39.1% and 59.2%, respectively. Conclusion: Ara-C can induce apoptosis and activation of NF-kB in HL60-n cells. The mechanism of increased apoptosis of HL60-n cells by DXM or VCR may be related to suppression of NF-kB activation. 展开更多
关键词 Leukemia cell HL-60 NF-KB APOPTOSIS Cytosine arabinoside
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Different influence of Arac combined with idarubicin and with daunorubicin on malignant molecule expression of acute myelocytic leukemia
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作者 Abudourexiti Nuerbiya Tuerhong Weinila +1 位作者 Yimingniyazi Nueramina Palerdan Aisha 《Journal of Hainan Medical University》 2018年第5期27-30,共4页
Objective:To study the different influence of idarubicin + Arac (IA) therapy and daunorubicin + Arac (DA) therapy on malignant molecule expression of acute myelocytic leukemia. Methods: A total of 56 patients who were... Objective:To study the different influence of idarubicin + Arac (IA) therapy and daunorubicin + Arac (DA) therapy on malignant molecule expression of acute myelocytic leukemia. Methods: A total of 56 patients who were diagnosed with acute myelocytic leukemia in Kashgar Prefecture First People's Hospital between January 2014 and September 2017 were selected as the research subjects and randomly divided into IA group and DA group, and the expression levels of proliferation genes, apoptosis genes and invasion genes in bone marrow tissue were determined after they accepted two courses of different chemotherapy regimens. Results:After two courses of chemotherapy, Daxx, CDX2, MCL1, BCL2, SOX4, S100A6, MMP9, N-cadherin, ICAM-1 and SDF-1 protein expression in bone marrow tissue of IA group were significantly lower than those of DA group whereas SHIP1, Bax and C/EBP protein expression were significantly higher than those of DA group.Conclusion:IA solution for acute myelocytic leukemia can be more effective than DA solution to inhibit the expression of proliferation and invasion genes and increase the expression of apoptosis genes. 展开更多
关键词 Acute myelocytic LEUKEMIA IDARUBICIN daunorubicin ARAC MALIGNANT MOLECULE
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New Octadecanoyl Diterpenoid Arabinoside from Conyza blinii 被引量:1
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作者 CHEN Lei SU Yan-fang TU Guang-zhong 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2009年第4期458-460,共3页
A new octadecanoyl diterpenoid glycoside,(E)-8α,15-dihydroxy-15-(3S-hydroxy-octadecanoyl)-13-labdene-8-O-α-L-arabinopyranoside(1),was isolated from the aerial parts of Conyza blinii,and the structure was ident... A new octadecanoyl diterpenoid glycoside,(E)-8α,15-dihydroxy-15-(3S-hydroxy-octadecanoyl)-13-labdene-8-O-α-L-arabinopyranoside(1),was isolated from the aerial parts of Conyza blinii,and the structure was identified on the basis of a detailed spectroscopic analysis,including 2D NMR spectrometry and HRESI-MS. 展开更多
关键词 Conyza blinii DITERPENOID LABDANE arabinoside
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The Effect of Liposome Encapsulated Daunorubicin on Rabbit Eyes after Extracapsular Lens Extraction 被引量:4
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作者 Mingxing Wu, Huaming Li, Shaozhen Li, Junwen ZengZhongshan Ophthalmic Center, Sun Yet-sen University of Medical Sciences, Guangzhou 510060, China 《眼科学报》 2000年第3期189-193,共5页
Purpose: To investigate the effect of liposome encapsulated daunorubicin (DNR) on rabbit eyes when it was used in prevention of posterior capsule opacification (PCO). Methods: The liposome encapsulated DNR was prepare... Purpose: To investigate the effect of liposome encapsulated daunorubicin (DNR) on rabbit eyes when it was used in prevention of posterior capsule opacification (PCO). Methods: The liposome encapsulated DNR was prepared by modified freeze-thawing method. Each eye was injected with 0. 1 ml liposomes (0. 2 mg/ml and 20 μg/ml DNR) into the capsular bag during the extracapsular lens extraction (ECLE) in 10 rabbit eyes respectively. The phosphate buffer solution (PBS) was injected as control. Besides biomicroscope observation and histology examination of all eyes, the concentration of DNR in aqueous humor was also determined by high performance liquid chromatography (HPLC).Results: The morphology of liposome encapsulated DNR were similar to the blank liposome with round or ellipse shape. The encapsulated effeciency of liposome encapsulated DNR was 45. 1%. The inflammatory response was much more severe both in 0. 2 mg/ml and 20μg/ml DNR group than the control after liposome injection. All eyes in DNR group 展开更多
关键词 柔毛霉素 脂质体 毒性
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急性髓系白血病患儿柔红霉素耐药与PD-L1蛋白表达相关
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作者 宋丽丽 管玉洁 +1 位作者 马平 李宁 《基础医学与临床》 CAS 2024年第6期833-839,共7页
目的研究急性髓系白血病(AML)患儿柔红霉素(DNR)耐药与程序性死亡受体配体-1(PD-L1)蛋白表达的相关性。方法选取2016年1月至2022年12月郑州大学附属儿童医院收治的110例AML患儿骨髓样本作为研究组,以50名骨髓正常供体骨髓样本作为对照... 目的研究急性髓系白血病(AML)患儿柔红霉素(DNR)耐药与程序性死亡受体配体-1(PD-L1)蛋白表达的相关性。方法选取2016年1月至2022年12月郑州大学附属儿童医院收治的110例AML患儿骨髓样本作为研究组,以50名骨髓正常供体骨髓样本作为对照组。培养人AML细胞系HL60、THP-1、U-937、Molm-13,Western blot检测PD-L1蛋白表达量。构建LV-PD-L1-shRNA、LV-PD-L1-WT-OE慢病毒载体,分析PD-L1对Molm-13细胞DNR耐药的影响及机制。结果研究组PD-L1蛋白表达量高于对照组,AML细胞系中PD-L1蛋白表达量高于健康骨髓单个核细胞(BMMC)(P<0.05),PD-L1表达与AML患儿白细胞计数、骨髓原始细胞比率、预后危险分层、两个标准化学治疗方案后疾病缓解情况有关(P<0.05)。PD-L1高表达组总生存率低于PD-L1低表达组(P<0.05)。与LV-PD-L1-WT-OE组比较,LV-PD-L1-shRNA组PD-L1 mRNA表达量降低、细胞增殖活性降低、凋亡率升高(P<0.05),LV-PD-L1-shRNA可提高Molm-13细胞对DNR的敏感性。TCGA数据库分析显示,6-磷酸葡萄糖脱氢酶(G6PD)可能为PD-L1潜在的目标基因。结论PD-L1在儿童AML中高表达,与患儿化疗耐药有关,其可能通过调控G6PD引起DNR耐药。 展开更多
关键词 儿童急性髓系白血病 柔红霉素 耐药 程序性死亡受体配体-1
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Augmented efficacy and the mechanism of a combined use of daunorubicin with rofecoxib in treatment of triple-negative breast cancer
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作者 赵曜 张婧莹 +3 位作者 胡英杰 吴佳栓 卜英子 吕万良 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2016年第6期438-447,共10页
Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor-2(HER2). A regular chemotherapy cannot eradicate t... Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor-2(HER2). A regular chemotherapy cannot eradicate triple-negative breast cancer. In the present study, we aimed to develop a combined use of daunorubicin and rofecoxib to treat triple-negative breast cancer, and reveal the underlying mechanisms. A gradient elution HPLC-UV method was developed for quantification, and the evaluations were performed on the triple-negative breast cancer MDA-MB-231 cells using a high content screening system. The results demonstrated that daunorubicin alone was insensitive to the triple negative breast cancer cells, while the combined use of daunorubicin and rofecoxib was able to effectively kill these triple-negative cancer cells, exhibiting a rofecoxib concentration-dependent manner. The mechanism revealed that the augmented anticancer efficacy was associated with direct killing effect, inducing apoptosis and inducing autophagy by the combination treatment. Besides, the apoptosis signaling pathways were correlated to a cascade of reactions by activating apoptotic enzyme caspase family and by suppressing anti-apoptotic gene expressed protein Bcl-2 family. In conclusion, this study provided a fundamental evidence for further developing the combined use of daunorubicin and rofecoxib formulation, hence offering a promising strategy for eradicating the triple negative breast cancer. 展开更多
关键词 daunorubicin ROFECOXIB Triple-negative breast cancer APOPTOSIS AUTOPHAGY
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程序性死亡配体1在儿童急性髓系白血病中的表达及对耐药的影响
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作者 马平 田亮 +6 位作者 周建文 毛彦娜 栗春香 何永艳 王亚峰 平玉豪 刘炜 《安徽医药》 CAS 2024年第7期1446-1450,共5页
目的研究程序性死亡配体1(PD-L1)在儿童初治急性髓系白血病(AML)中的表达及对白血病细胞耐药的影响。方法收集2020年1月至2021年1月郑州大学附属儿童医院血液肿瘤科收治的初诊40例AML病儿骨髓标本,收集同期进行骨髓检查正常病儿的骨髓标... 目的研究程序性死亡配体1(PD-L1)在儿童初治急性髓系白血病(AML)中的表达及对白血病细胞耐药的影响。方法收集2020年1月至2021年1月郑州大学附属儿童医院血液肿瘤科收治的初诊40例AML病儿骨髓标本,收集同期进行骨髓检查正常病儿的骨髓标本18例作为正常对照组,比较两组骨髓中PD-L1的表达量,并分析初治AML病儿PD-L1的表达量与其临床特征之间的关系;慢病毒构建PD-L1过表达、干扰PD-L1表达的AML细胞,细胞活力检测试剂盒(CCK8)检测细胞增殖能力,并计算细胞对柔红霉素的药物敏感性;凋亡实验检测经柔红霉素诱导的细胞凋亡水平。结果与正常对照组0.887±0.064相比,初治儿童AML病儿骨髓单个核细胞PD-L1的表达量2.927±0.271显著增高(t=7.34,P<0.001);根据一个疗程诱导化疗是否达完全缓解(CR),将初治AML病儿一个疗程达CR者定义为CR组,将未达CR者定义为NR组,相较于CR组的2.346±0.190,NR组PD-L1基因的表达量5.249±0.662显著增高(t=4.22,P=0.003);病儿不同发病年龄,性别,法、美、英(FAB)分型,白细胞计数,预后分层间PD-L1基因相对表达量比较均差异无统计学意义(P>0.05),而1个疗程诱导化疗是否达CR与PD-L1基因相对表达量差异有统计学意义(P=0.018);过表达PD-L1的Molm-13细胞对柔红霉素具有更高的IC50值,更低的凋亡率;干扰PD-L1表达的THP1细胞对柔红霉素具有更低的IC50值,更高的凋亡率。结论PD-L1在初治AML病儿中表达增高,且PD-L1的高表达与1个疗程诱导治疗是否达CR显著相关;PD-L1可以促进AML细胞增殖、抑制凋亡,从而导致化疗耐药。 展开更多
关键词 白血病 髓样 急性 程序性死亡配体1 儿童 化疗耐药 柔红霉素
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嘌呤核苷磷酸化酶/嘧啶核苷磷酸化酶共表达及固定化催化合成阿糖核苷
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作者 刘玉雪 张震 +2 位作者 胡晓静 王振宇 刘国生 《生物加工过程》 CAS 2024年第2期139-146,共8页
将嘌呤核苷磷酸化酶(PNP)和尿苷磷酸化酶(UP)进行共表达和双酶固定化,提高生物法合成阿糖核苷过程中底物转化率和催化剂稳定性。首先,构建大肠杆菌内源(PNP)和(UP)过表达工程菌,考察工程菌催化不同阿糖核苷之间转化的效率。将PNP和UP双... 将嘌呤核苷磷酸化酶(PNP)和尿苷磷酸化酶(UP)进行共表达和双酶固定化,提高生物法合成阿糖核苷过程中底物转化率和催化剂稳定性。首先,构建大肠杆菌内源(PNP)和(UP)过表达工程菌,考察工程菌催化不同阿糖核苷之间转化的效率。将PNP和UP双酶固定化,并对固定化双酶进行回收利用,考察重复使用过程中固定化双酶的催化效率。结果表明:工程菌催化阿糖尿苷和腺嘌呤生成阿糖腺苷的反应最高转化率可达93.6%。固定化双酶催化合成阿糖2,6-二氨基嘌呤核苷的最高转化率可达99.8%。重复回收使用固定化双酶19次后对底物的转化率达到60.6%,累计有效催化时长可达684 h。PNP和UP的双酶耦合体系能高效催化阿糖核苷之间的转化,固定化修饰有利于延长酶的使用寿命,为生物法生产核苷类似物提供重要科学参考。 展开更多
关键词 嘌呤核苷磷酸化酶 嘧啶核苷磷酸化酶 阿糖核苷 固定化酶 生物催化
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干扰TRIM59表达对慢性粒细胞白血病K562细胞柔红霉素化疗敏感性的影响及作用机制研究
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作者 王菁 王振杰 李占霞 《中国实验血液学杂志》 CSCD 北大核心 2024年第1期45-51,共7页
目的:探讨干扰三元基序59(TRIM59)表达对慢性粒细胞白血病K562细胞柔红霉素(DNR)化疗敏感性的影响及相关分子机制。方法:采用RT-q PCR法检测慢性粒细胞白血病患者骨髓组织和K562细胞中TRIM59 m RNA表达水平。用脂质体转染法将TRIM59特... 目的:探讨干扰三元基序59(TRIM59)表达对慢性粒细胞白血病K562细胞柔红霉素(DNR)化疗敏感性的影响及相关分子机制。方法:采用RT-q PCR法检测慢性粒细胞白血病患者骨髓组织和K562细胞中TRIM59 m RNA表达水平。用脂质体转染法将TRIM59特异性小干扰RNA(si-TRIM59)转染至K562细胞,并用DNR处理细胞。CCK-8法检测细胞增殖,流式细胞术检测细胞凋亡,Western blot法检测凋亡相关蛋白和Wnt/β-catenin信号通路相关蛋白表达。结果:与初治时骨髓组织相比,化疗耐药时患者骨髓组织中TRIM59 m RNA表达水平升高(P<0.05)。与对照组比较,si-TRIM59组和DNR组细胞增殖抑制率、细胞凋亡率均显著升高(P<0.05);细胞中Bax、Caspase3、Cleaved-Caspase3蛋白表达量均显著升高,而Bcl-2、Wnt3α、GSK-3β蛋白表达量、p-β-catenin/β-catenin比值均显著降低(P<0.05)。与si-TRIM59组和DNR组比较,si-TRIM59+DNR组细胞增殖抑制率、细胞凋亡率均显著升高(P<0.05);细胞中Bax、Caspase3、Cleaved-Caspase3蛋白表达量均显著升高,而Bcl-2、Wnt3α、GSK-3β蛋白表达量、p-β-catenin/β-catenin比值均显著降低(P<0.05)。结论:干扰TRIM59表达可增强K562细胞对DNR的化疗敏感性,其作用机制可能与调控Wnt/β-catenin信号通路相关。 展开更多
关键词 TRIM59 慢性粒细胞白血病 柔红霉素 WNT/Β-CATENIN信号通路 增殖 凋亡
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Targeted co-delivery of daunorubicin and cytarabine based on the hyaluronic acid prodrug modified liposomes 被引量:1
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作者 George Frimpong Boafo Yejiao Shi +11 位作者 Qingqing Xiao Kosheli Thapar Magar Makhloufi Zoulikha Xuyang Xing Chao Teng Emmanuel Brobbey Xiaotong Li Xiaohong Jiang Xiaochun Wang Yi Yang Samuel Kesse Wei He 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第10期4600-4604,共5页
Breast cancer is the most prevalent cancer in women,and it was hard to prevent or diagnose at an early stage.Thus,it is imperative to develop advanced therapeutics for effective treatment.Herein,a targeted daunorubici... Breast cancer is the most prevalent cancer in women,and it was hard to prevent or diagnose at an early stage.Thus,it is imperative to develop advanced therapeutics for effective treatment.Herein,a targeted daunorubicin(DNR)and cytarabine(ara-C)co-delivery system was developed by modifying the ara-C loaded liposomes(LIP-ara-C)with the hyaluronic acid-DNR(HA-DNR)prodrugs.The co-assembled hybrid nanoparticles(HA-DNR/LIP-ara-C HNPs)exhibited good serum and storage stability with an average diameter of approximately 100 nm.By specifically binding to the CD44 receptors that overexpressed on cancer cells,these HNPs could be uptake via endocytosis and accumulate intracellularly,in which an optimized DNR and ara-C combination at a molar ratio of 1:5 could generate enhanced synergistic effects with reduced dose-related toxicity on cancer cells. 展开更多
关键词 Breast cancer daunorubicin CYTARABINE CO-DELIVERY Liposomes
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Melt electrospinning of daunorubicin hydrochloride-loaded poly (ε-caprolactone) fibrous membrane for tumor therapy 被引量:1
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作者 He Lian Zhaoxu Meng 《Bioactive Materials》 SCIE 2017年第2期96-100,共5页
Daunorubicin hydrochloride is a cell-cycle non-specific antitumor drug with a high therapeutic effect.The present study outlines the fabrication of daunorubicin hydrochloride-loaded poly (ε-caprolactone)(PCL) fibrous... Daunorubicin hydrochloride is a cell-cycle non-specific antitumor drug with a high therapeutic effect.The present study outlines the fabrication of daunorubicin hydrochloride-loaded poly (ε-caprolactone)(PCL) fibrous membranes by melt electrospinning for potential application in localized tumor therapy.The diameters of the drug-loaded fibers prepared with varying concentrations of daunorubicin hydrochloride(1, 5, and 10 wt%) were 2.48 ± 1.25, 2.51 ± 0.78, and 2.49 ± 1.58 μm, respectively. Fluorescenceimages indicated that the hydrophobic drug was dispersed in the hydrophilic PCL fibers in theiraggregated state. The drug release profiles of the drug-loaded PCL melt electrospun fibrous membraneswere approximately linear, with slow release rates and long-term release periods, and no observed burstrelease. The MTT assay was used to examine the cytotoxic effect of the released daunorubicin hydrochlorideon HeLa and glioma cells (U87) in vitro. The inhibition ratios of HeLa and glioma cells followingtreatment with membranes prepared with 1, 5, and 10 wt% daunorubicin hydrochloride were 62.69%,76.12%, and 85.07% and 62.50%, 77.27%, and 84.66%, respectively. Therefore, PCL melt electrospun fibrousmembranes loaded with daunorubicin hydrochloride may be used in the local administration ofoncotherapy. 展开更多
关键词 Melt electrospinning Drug delivery system Poly(ε-caprolactone) daunorubicin hydrochloride Tumor therapy
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Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation 被引量:1
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作者 Akimasa Seno Akifumi Mizutani +9 位作者 Kazuki Aizawa Ryoma Onoue Junko Masuda Naotaka Ochi Saki Taniguchi Tatsuyuki Sota Yuki Hiramoto Taisuke Michiue Neha Nair Masaharu Seno 《Cancer Drug Resistance》 2019年第2期335-350,共16页
Aim:To identify a drug that can effectively eliminate these cancer stem cells(CSCs)and determine its mode of action.Methods:CSCs were obtained from mouse induced pluripotent stem cells(miPSCs)using cancer cell-conditi... Aim:To identify a drug that can effectively eliminate these cancer stem cells(CSCs)and determine its mode of action.Methods:CSCs were obtained from mouse induced pluripotent stem cells(miPSCs)using cancer cell-conditioned media.Drug screening was performed on these cells or after transplantation into mice.Apoptosis was analyzed by flow cytometry and western blotting.Results:Drug screening studies showed that daunorubicin,a topoisomerase II inhibitor,is specifically cytotoxic to miPS-CSCs.Daunorubicin-induced apoptosis was found to be associated with p53 accumulation,activation of the caspase cascade,and oligonucleosomal DNA fragmentation.Treatment with the caspase inhibitor abolished daunorubicin-induced DNA fragmentation and was therefore considered to act downstream of caspase activation.This was also suppressed by treatment with a Ca2+-specific chelator,which suggested that CAD endonuclease does not contribute.Moreover,no obvious ICAD reduction/degradation was detected.Conclusion:Daunorubicin effectively eliminated CSCs,which are dependent on the p53/caspase signaling cascade.The current findings provided the basis for further studies on CSC-targeted drugs for the development of cancer treatment strategies. 展开更多
关键词 daunorubicin cancer stem cell DNA fragmentation
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C_(19)-Diterpenoid alkaloid arabinosides from an aqueous extract of the lateral root of Aconitum carmichaelii and their analgesic activities 被引量:13
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作者 Qinglan Guo Huan Xia +5 位作者 Xianhua Meng Gaona Shi Chengbo Xu Chenggen Zhu Tiantai Zhang Jiangong Shi 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2018年第3期409-419,共11页
Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by ... Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg(i.p.), as compared with the black control, compounds 1, 2, and 4–6 exhibited analgesic effects with 465.6% inhibitions against acetic acid-induced writhing of mice. Structure–activity relationship was also discussed. 展开更多
关键词 RANUNCULACEAE Aconitum carmichaelii C19-diterpenoid alkaloid arabinoside Aconicarmichosides E-L Analgesic effect Structure–activity relationship
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阿糖胞苷对原代培养的大鼠海马和大脑皮层神经元生物学特性的影响
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作者 戴嘉华 孙卫文 +4 位作者 赖梅菁 邱美茜 张文浩 徐恩 詹丽璇 《广州医科大学学报》 2023年第6期1-10,共10页
目的:探讨阿糖胞苷(Ara-C)不同浓度、不同介入时间以及不同处理时长对原代培养的大鼠海马和大脑皮层神经元纯度及活性的影响。方法:取孕16~18 d的胎鼠海马及皮层组织进行原代神经元培养,培养后48 h分别加入浓度为0、2.5、5、7.5、10μmo... 目的:探讨阿糖胞苷(Ara-C)不同浓度、不同介入时间以及不同处理时长对原代培养的大鼠海马和大脑皮层神经元纯度及活性的影响。方法:取孕16~18 d的胎鼠海马及皮层组织进行原代神经元培养,培养后48 h分别加入浓度为0、2.5、5、7.5、10μmol/L的Ara-C处理24 h,检测不同浓度的Ara-C对原代神经元生物学特性的影响;培养后24、48、72、96及120 h,加入5μmol/L的Ara-C处理24 h,检测Ara-C不同介入时间对原代神经元生物学特性的影响;培养后48 h,加入5μmol/L的Ara-C处理0、6、12、24、48 h,检测Ara-C不同处理时长对原代神经元生物学特性的影响。培养后第8天倒置显微镜下观察细胞的形态及生长状况,免疫荧光检测微管相关蛋白2(MAP2)、神经纤维酸性蛋白(GFAP)的表达,并计算MAP2阳性细胞占细胞总数的比例。使用细胞计数试剂盒8(CCK-8)检测神经元细胞活性。结果:与对照组(0μmol/L)相比,Ara-C浓度为5μmol/L组海马神经元纯度达89.8%、细胞活性为48.6%。与对照组相比,种板后48 h加入Ara-C获得的海马神经元纯度为96.2%,细胞活性为44.8%。与对照组(0 h)相比,Ara-C处理12 h组获得的海马神经元的纯度为90.8%,细胞活性为47.5%。在大鼠原代培养的皮层神经元中,与对照组(0μmol/L)相比,给予不同浓度的Ara-C(2.5、5、7.5、10μmol/L)处理,原代皮层神经元纯度的差异无统计学意义(P>0.05)。与对照组相比,给予不同介入时间(24、48、72、96、120 h)的Ara-C处理,皮层神经元纯度的差异无统计学意义(P>0.05)。与对照组(0 h)相比,给予不同时长(6、12、24、48h)的Ara-C处理,仅Ara-C处理24 h后皮层神经元纯度稍增高(P<0.05)。结论:在大鼠原代海马神经元的早期培养过程中,种板后48 h加入5μmol/L Ara-C处理12 h得到的海马神经元的纯度与活性最佳,而在大鼠原代皮层神经元培养中无需添加Ara-C即可获得较高纯度和活性的神经元。 展开更多
关键词 海马和皮层神经元 原代培养 阿糖胞苷
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柔红霉素联合阿糖胞苷治疗急性髓系白血病的效果及安全性分析 被引量:2
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作者 周静 《中国实用医药》 2023年第4期124-126,共3页
目的分析在急性髓系白血病(AML)治疗中,予以柔红霉素(DNR)+阿糖胞苷(Ara-C)联合干预的临床价值。方法72例AML患者,依据随机数字表法分为A组及B组,每组36例。A组予以单一DNR治疗,B组在A组基础上联合Ara-C(DNR+Ara-C)治疗。对比两组患者... 目的分析在急性髓系白血病(AML)治疗中,予以柔红霉素(DNR)+阿糖胞苷(Ara-C)联合干预的临床价值。方法72例AML患者,依据随机数字表法分为A组及B组,每组36例。A组予以单一DNR治疗,B组在A组基础上联合Ara-C(DNR+Ara-C)治疗。对比两组患者的治疗效果、血液学指标及不良反应发生率。结果B组治疗总有效率91.67%高于A组的72.22%,差异具有统计学意义(P<0.05)。两组患者粒细胞缺乏(粒缺)最低值、粒缺持续时间、血小板(PLT)最低值、PLT缺乏持续时间、PLT输注量、血红蛋白(Hb)输注量对比,差异无统计学意义(P>0.05)。A组口腔感染、恶心呕吐、肠胃炎、泌尿系统感染、肝肾功能受损、皮肤感染、上呼吸道感染、肺部感染、败血症发生率分别为22.22%、19.44%、27.78%、27.78%、16.67%、22.22%、11.11%、11.11%、5.56%,B组分别为5.56%、13.89%、8.33%、8.33%、2.78%、5.56%、8.33%、0、2.78%。B组口腔感染、肠胃炎、泌尿系统感染、肝肾功能受损、皮肤感染、肺部感染发生率低于A组,差异具有统计学意义(P<0.05);两组恶心呕吐、上呼吸道感染、败血症发生率对比,差异无统计学意义(P>0.05)。结论在AML治疗中,予以DNR+Ara-C干预效果确切,可促进患者病症的改善,并减少用药期间不良反应的发生,提升治疗安全性,可行推广应用。 展开更多
关键词 柔红霉素 阿糖胞苷 急性髓系白血病 临床效果 安全性
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微小RNA-29b靶向卷曲蛋白6参与急性髓系白血病细胞柔红霉素耐药的分子机制 被引量:1
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作者 赖思含 何莹 易海 《武警医学》 CAS 2023年第4期295-300,共6页
目的探究微小RNA-29b(miR-29b)靶向卷曲蛋白6(FZD6)参与急性髓系白血病(AML)细胞柔红霉素(DNR)耐药的分子机制。方法CCK-8检测AML细胞系在不同DNR浓度下的生存能力,实时定量聚合酶链反应(qRT-PCR)检测AML细胞系中miR-29b的表达。选取TH... 目的探究微小RNA-29b(miR-29b)靶向卷曲蛋白6(FZD6)参与急性髓系白血病(AML)细胞柔红霉素(DNR)耐药的分子机制。方法CCK-8检测AML细胞系在不同DNR浓度下的生存能力,实时定量聚合酶链反应(qRT-PCR)检测AML细胞系中miR-29b的表达。选取THP-1细胞为研究对象,分为Control组(正常培养)、miR-NC mimics组(转染miR-NC mimics)、miR-29b mimics组(转染miR-29b mimics)、miR-29b mimics+pcDNA组(转染miR-29b mimics和pcDNA)、miR-29b mimics+pcDNA-FZD6组(转染miR-29b mimics和pcDNA-FZD6),转染24 h后使用10 mM DNR处理培养24 h。qRT-PCR和免疫印迹(Western blot)检测各组DNR处理的THP-1细胞中miR-29b和FZD6表达水平。生物信息学和双荧光素酶报告基因预测并检测miR-29b和FZD6靶向关系。CCK-8、Edu法和流式细胞术分别检测DNR处理的各组THP-1细胞增殖和凋亡情况。结果AML细胞系对DNR的耐药性是呈浓度依赖性的,qRT-PCR结果显示,miR-29b在AML细胞系THP-1(1.00±0.05)、KG-1(1.87±0.16)、HL-60(2.96±0.21)及Kasumi-1(3.73±0.29)中的表达逐渐增高(P<0.05)。双荧光素酶报告基因检测、qRT-PCR及Western blot证明miR-29b可直接负靶向FZD6(0.32±0.04,0.37±0.05,0.48±0.06,P<0.05)。miR-29b过表达可使AML细胞对DNR的耐药性减弱,抑制细胞增殖,增强细胞凋亡能力(43.59±5.24,21.97±3.13,P<0.05)。上调FZD6可一定程度上逆转上调miR-29b表达对THP-1细胞增殖和凋亡的影响(65.21±6.39,38.26±4.09,P<0.05)。结论miR-29b通过靶向抑制FZD6降低AML细胞对DNR的耐药性。 展开更多
关键词 微小RNA-29b 卷曲蛋白6 急性髓系白血病 柔红霉素 耐药
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LncRNA PVT1调控miR-1207-5p/FMNL2对HL-60细胞凋亡及化疗敏感性的影响 被引量:1
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作者 郭毅刚 宋斌 +4 位作者 胡平 张荣耀 陈旭 易琼 万楚成 《中国药业》 CAS 2023年第3期44-49,共6页
目的探讨长链非编码RNA浆细胞瘤转化迁移基因1(LncRNA PVT1)对HL-60细胞生物学行为及柔红霉素敏感性的影响。方法将HL-60细胞分为对照组、miR-NC组、PVT1-siRNA组、miR-1207-5p inhibitor组和miR-1207-5p mimic组。除对照组细胞不处理外... 目的探讨长链非编码RNA浆细胞瘤转化迁移基因1(LncRNA PVT1)对HL-60细胞生物学行为及柔红霉素敏感性的影响。方法将HL-60细胞分为对照组、miR-NC组、PVT1-siRNA组、miR-1207-5p inhibitor组和miR-1207-5p mimic组。除对照组细胞不处理外,其余各组细胞分别将miR-NC,PVT1-siRNA,miR-1207-5p inhibitor,miR-1207-5p mimic转染到HL-60细胞中。采用萤光素酶检测试剂分析LncRNA PVT1对微小RNA-1207-5p(miR-1207-5p)和同源形成素样蛋白2(FMNL2)的调控作用,CCK-8法检测细胞存活率,改良Matrigel Boyden室测定法测定细胞侵袭性,划痕实验检测细胞迁移力,流式细胞术检测细胞凋亡率,MTT法检测细胞对柔红霉素敏感性,实时逆转录定量聚合酶链式反应(RT-qPCR)法检测miR-1207-5p和FMNL2 mRNA表达水平,免疫印迹(Western blot)法检测FMNL2蛋白表达水平。结果萤光素酶分析结果显示,LncRNA PVT1与miR-1207-5p、miR-1207-5p与FMNL2均存在靶向调节作用;与对照组比较,PVT1-siRNA组LncRNA PVT1表达水平显著降低(P<0.05),miR-1207-5p表达水平显著升高(P<0.05)。与对照组比较,miR-1207-5p inhibitor组细胞存活率、迁移率、侵袭数均显著降低,细胞凋亡率、FMNL2 mRNA和蛋白表达水平均显著升高(P<0.05);miR-1207-5p mimic组细胞存活率、迁移率、侵袭数均显著升高,细胞凋亡率、FMNL2 mRNA和蛋白表达水平均显著降低(P<0.05)。与对照组比较,相同质量浓度(0,0.5,1,2,4,8μg/mL)柔红霉素作用下PVT1-siRNA组HL-60细胞活力均显著升高(P<0.05)。结论沉默LncRNA PVT1可使miR-1207-5p表达增加,从而抑制FMNL2表达,导致HL-60细胞恶性生物学行为概率升高,同时降低细胞对柔红霉素的敏感性。 展开更多
关键词 白血病 长链非编码RNA浆细胞瘤转化迁移基因1 微小RNA-1207-5p/同源形成素样蛋白2通路 柔红霉素
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