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
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
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
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
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
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
文摘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.
文摘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
文摘目的: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。
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 82073782)the Double First-Class(No.CPU2018PZQ13)of the China Pharmaceutical University+1 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(No.zdsys-202103)。
文摘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.
基金This work is supported by the Scientific Research General Project of Liaoning Provincial Department of Education(No.L2014388)the Natural Science Foundation of Liaoning Province(No.2015020753)Nature Science Foundation of China(No.81503020,No.31600767).
文摘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.
文摘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.
