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p53 Contributes to the Chemotherapeutic Drug Doxorubicin-Induced Cell Death in Colorectal Cancer Cell Line HCT116
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作者 Rui Deng 《Proceedings of Anticancer Research》 2024年第1期112-116,共5页
Doxorubicin is a commonly used chemotherapy drug for cancer treatment,although its effectiveness varies across different cancer types.p53 is a key factor involved in cell death induced by therapeutic agents,and it can... Doxorubicin is a commonly used chemotherapy drug for cancer treatment,although its effectiveness varies across different cancer types.p53 is a key factor involved in cell death induced by therapeutic agents,and it can be upregulated by doxorubicin,exhibiting a function of apoptosis.To further investigate the mechanism between p53 and doxorubicin,this study explored whether p53 plays a role in doxorubicin-induced cell death in the colorectal cancer line HCT116.The findings revealed that p53 was upregulated in HCT116 cells when treated with doxorubicin,and the knockdown of p53 decreased the sensitivity of HCT116 cells to doxorubicin.These results suggest that p53 plays an important role in doxorubicin-induced cell death in HCT116 cells,potentially contributing to more effective treatment approaches. 展开更多
关键词 P53 doxorubicin Knockdown of p53
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Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment
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作者 Changkyu Lee 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2023年第5期185-195,共11页
High-alkali treatment using sodium hydroxide(NaOH)injection can be a therapeutic approach for killing tumor cells.Alkalization can damage cellular structures and lead to cell death.Increased alkalinity can also enhanc... High-alkali treatment using sodium hydroxide(NaOH)injection can be a therapeutic approach for killing tumor cells.Alkalization can damage cellular structures and lead to cell death.Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin(DOX).In this study,NaOH-loaded starch implants(NST implants)were used to induce hyperalkalization(increase pH)in the tumor environment,thereby inducing necrosis and enhancing the effects of DOX.NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor.However,the administration of NaOH can have toxic side effects because it increases the pH of the entire body,not just at the tumor site.To overcome this problem,we developed an injectable NST implant,in which NaOH can be delivered directly into the tumor.This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors.Although some NaOH from NST implants can be systemically absorbed,it is neutralized by the body’s buffering effect,thereby reducing the risk of toxicity.This study also confirmed both in vitro and in vivo that DOX is more effective at killing 4T1 cells when alkalized.It has been shown that administration of DOX after injection of an NST implant can kill most tumors.Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor.In addition,alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells.Therefore,the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors. 展开更多
关键词 NAOH STARCH IMPLANT doxorubicin ALKALINIZATION Tumor
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Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers
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作者 Qin Shi Zihan Zhang +5 位作者 Wen Zhang Jingqin Ma Minjie Yang Jianjun Luo Lingxiao Liu Zhiping Yan 《Journal of Interventional Medicine》 2023年第3期121-125,共5页
Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver c... Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer. 展开更多
关键词 Liver cancer doxorubicin hydrochloride liposome Transarterial chemoembolization Microwave ablation
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Research progress on cardiotoxicity mechanism of doxorubicin and prevention and treatment of traditional Chinese medicine
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作者 SU Jing LIU Dong-ling +4 位作者 HAI Yang LIU Xiao-feng HOU Wen-qian DONG Jing-qu XU Lan 《Journal of Hainan Medical University》 CAS 2023年第15期60-66,共7页
Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At... Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At present,the mechanism of doxorubicin induced cardiotoxicity has not been fully clarified.Reducing cardiotoxicity and improving the scope of clinical application have become the focus of research in recent years.This paper reviews the mechanism of doxorubicin cardiotoxicity and the prevention and treatment of doxorubicin cardiotoxicity with traditional Chinese medicine,in order to provide reference for the combined application of doxorubicin. 展开更多
关键词 doxorubicin CARDIOTOXICITY Prevention and treatment of traditional Chinese medicine
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Nonclinical Study of the Active Components of Doxorubicin Hydrochloride Liposome Injection in Vivo
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作者 Bing Wang Wangning Zhang +4 位作者 Ping Wang Qilin Zhou Kaiyu Zhang Jiaxin Zhang Jiangwei Tian 《Pharmacology & Pharmacy》 2023年第9期363-375,共13页
Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: T... Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T<sub>1/2</sub> was (19.282 ± 10.305) h, C<sub>max</sub> was (118514.828 ± 26155.134) ng/mL, AUC<sub>0-24</sub> and AUC<sub>0-∞</sub> were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT<sub>0-24</sub> and MRT<sub>0-∞</sub> were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies. 展开更多
关键词 doxorubicin Hydrochloride Liposomes PHARMACOKINETICS LC-MS/MS
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Fabrication of an electrochemical sensor for determination of doxorubicin in human plasma and its interaction with DNA 被引量:2
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作者 Reza Hajian Zahra Tayebi Nafiseh Shams 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2017年第1期27-33,共7页
In this work, an electrochemical sensor was fabricated for determination of an anthracycline, doxorubicin(DOX) as a chemotherapy drug in plasma based on multi-walled carbon nanotubes modified platinum electrode(Pt/MWC... In this work, an electrochemical sensor was fabricated for determination of an anthracycline, doxorubicin(DOX) as a chemotherapy drug in plasma based on multi-walled carbon nanotubes modified platinum electrode(Pt/MWCNTs). DOX was effectively accumulated on the surface of modified electrode and generated a pair of redox peaks at around 0.522 and 0.647 V(vs. Ag/Ag Cl) in Britton Robinson(B-R) buffer(p H 4.0, 0.1 M). The electrochemical parameters including p H, type of buffer, accumulation time, amount of modifier and scan rate were optimized. Under the optimized conditions, there was a linear correlation between cathodic peak current and concentration of DOX in the range of 0.05–4.0 μg/m L with the detection limit of 0.002 μg/m L. The number of electron transfers(n) and electron transfer-coefficient(α) were estimated as 2.0 and 0.25, respectively. The constructed sensor displayed excellent precision, sensitivity, repeatability and selectivity in the determination of DOX in plasma. Moreover, cyclic voltammetry studies of DOX in the presence of DNA showed an intercalation mechanism with binding constant(K_b) of 1.12×10~5L/mol. 展开更多
关键词 doxorubicin MWCNTS ELECTROCHEMICAL sensor Human PLASMA doxorubicin-DNA INTERACTION
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Conventional treatments and non-PEGylated liposome encapsulated doxorubicin for visceral leishmaniasis:A scoping review 被引量:1
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作者 Soumya Ranjan Satapathy Rudra Narayan Sahoo 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2022年第7期293-307,共15页
Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcuta... Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcutaneous form.Treatment of VL includes chemotherapeutic agents which are associated with some major hurdles like toxicities,parenteral administration,high cost,parasite resistance and stability.Hence,there is an urgent requirement to develop novel chemotherapeutic agents or repurposing of existing drugs against VL.Developing formulation of new chemical entity for the treatment of VL is laborious,time consuming and associated with huge financial burden.However,screening of existing chemotherapeutic agents is a good alternative to avail cost-effective treatment option for VL.Non-PEGylated liposome encapsulated doxorubicin(Myocet®)is proposed as an alternative treatment option for VL in this review article.Here,we covered the fundamental aspects of VL,loophole associated with available current treatment strategies and non-PEGylated liposome encapsulated doxorubicin as a novel alternative formulation for treating VL,as this liposomal delivery system of doxorubicin might passively target the intra-cellular regions of macrophage. 展开更多
关键词 Visceral leishmaniasis doxorubicin Passive targeting REPOSITIONING Non-PEGylated liposome encapsulated doxorubicin RESISTANCE
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DL1106与doxorubicin和paclitaxel协同作用及其机制研究
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作者 王金华 杜冠华 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1062-1062,共1页
目的探讨DL1106与doxorubicin和paclitaxel对三阴性乳腺癌细胞协同作用效果及研究机制。方法将三阴性乳腺癌细胞MDA-MB-231和BT549分为4组,对照组,DL1106,DL1106+doxorubicin,DL1106+paclitaxel组作用24和48 h。用流式细胞仪检测细胞凋... 目的探讨DL1106与doxorubicin和paclitaxel对三阴性乳腺癌细胞协同作用效果及研究机制。方法将三阴性乳腺癌细胞MDA-MB-231和BT549分为4组,对照组,DL1106,DL1106+doxorubicin,DL1106+paclitaxel组作用24和48 h。用流式细胞仪检测细胞凋亡率和细胞周期;用JC-1检测细胞膜电位;用Caspase-Glo?3/7 assay检测细胞内胱天蛋白酶活性;用Western blotting检测细胞周期、细胞凋亡相关蛋白表达。采用si RNA技术敲低P53和PUMA的表达后检测药物联合对细胞的作用效果。结果与DL1106单独作用组细胞相比,DL1106与doxorubicin和paclitaxel联合作用组的细胞在48 h后凋亡率显著下降。DL1106与doxorubicin和paclitaxel联合作用导致细胞膜电位大幅下降并使细胞内胱天蛋白酶活性显著升高。同对照组相比,DL1106,DL1106+doxorubicin,DL1106+paclitaxel作用组的细胞均抑制MDM2的表达,促进P53和PUMA的表达。DL1106+doxorubicin,DL1106+paclitaxel协同作用抑制细胞Cyclin D1和Bcl-2的表达,促进BAX的表达。用P53si RNA和PUMA si RNA分别敲低细胞P53和PUMA的表达后,发现DL1106+doxorubicin,DL1106+paclitaxel联合作用效果明显减弱。结论 DL1106与doxorubicin和paclitaxel对三阴性乳腺癌细胞均具有协同作用,且这种协同作用通过P53/PUMA/BAX/caspase途径发挥作用。 展开更多
关键词 三阴性乳腺癌细胞 DL1106 协同作用 doxorubicin PACLITAXEL
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Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma 被引量:50
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作者 Wei Wang~1 Shu-Kui Qin~1 Bao-An Chen~2 Hui-Ying Chen~1 1 Chinese PLA Cancer Center,Chinese PLA 81 Hospital,Nanjing 210002,Jiangshu Province,China2 Affliliated Zhongda Hospital of Southeast University Medical College,Nanjing 210087,Jiangsu Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第5期702-705,共4页
INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo ... INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application. 展开更多
关键词 liver neoplasms carcinoma hepatocellular MINOR cells cultured/drug effects arsenicals/pharmacology cisplatin/pharmacology doxorubicin/pharmacology
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MiR-34a overexpression enhances the inhibitory effect of doxorubicin on HepG2 cells 被引量:9
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作者 Shun-Zhen Zheng Ping Sun +3 位作者 Jian-Ping Wang Yong Liu Wei Gong Jun Liu 《World Journal of Gastroenterology》 SCIE CAS 2019年第22期2752-2762,共11页
BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatis... BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatisfactory. Chemotherapy resistance is the most important reason for the poor outcome. Much progress has been made in the study of chemotherapy resistance of HCC;however, the specific mechanisms of progression of HCC have still only been partially established.Therefore, the mechanism of chemotherapy resistance in HCC requires more research.AIM To investigate the effect of miR-34 a expression on the growth inhibition of HepG2 cells by doxorubicin.METHODS A recombinant lentiviral vector containing miR-34 a was constructed and transfected into HepG2 cells. The expression of miR-34 a was detected by reverse transcription-polymerase chain reaction(commonly known as RT-PCR) before and after transfection. Cells were exposed to 2 μM doxorubicin or phosphatebuffered saline before and after transfection. Cell viability in each group was detected by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. Changes in expression levels of phospho(p)-p53, sirtuin(SIRT) 1,cyclin D1, cyclin-dependent kinase(CDK) 4, CDK6, BCL-2, multidrug resistance protein(MDR) 1/P glycoprotein(P-gp), and AXL were detected by Western blotting.RESULTS Recombinant lentiviral vector LV-hsa-mir-34 a was successfully constructed by restriction endonuclease digestion and sequencing. RT-PCR showed that expression of miR-34 a in HepG2 cells was significantly upregulated after transfection(P < 0.01). MTT assay showed that growth of HepG2 cells was inhibited after upregulation of miR-34 a, and viability was significantly decreased after combined treatment with doxorubicin(P < 0.01). Flow cytometry showed that the number of HepG2 cells in G1 phase increased, and G1 phase arrest was more obvious after intervention with doxorubicin(P < 0.01). The apoptosis rate of HepG2 cells was increased after upregulation of miR-34 a, and became more obvious after intervention with doxorubicin(P < 0.01). Western blotting showed that upregulation of miR-34 a combined with treatment with doxorubicin caused significant changes in the expression levels of p-p53, SIRT1, cyclin D1, CDK4,CDK6, BCL-2, MDR1/P-gp and AXL proteins(P < 0.01).CONCLUSION MiR-34 a may enhance the inhibitory effect of doxorubicin by downregulating MDR1/P-gp and AXL, which may be related to p53 expression. 展开更多
关键词 MIR-34A doxorubicin HEPATOCELLULAR carcinoma HEPG2 cells Growth INHIBITION
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PEComa of the colon resistant to sirolimus but responsive to doxorubicin/ifosfamide 被引量:8
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作者 Wolfgang Scheppach Nikolaus Reissmann +3 位作者 Thomas Sprinz Ekkehard Schippers Bjoern Schoettker Justus G Mueller 《World Journal of Gastroenterology》 SCIE CAS 2013年第10期1657-1660,共4页
A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular ep... A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable. 展开更多
关键词 PERIVASCULAR epithelioid cell tumor COLON Liver metastases Mammalian target of rapamycin inhibitor SIROLIMUS Chemotherapy doxorubicin IFOSFAMIDE
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Melatonin and Doxorubicin synergistically induce cell apoptosis in human hepatoma cell lines 被引量:9
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作者 Fan, Lu-Lu Sun, Guo-Ping +4 位作者 Wei, Wei Wang, Zhang-Gui Ge, Lei Fu, Wei-Zheng Wang, Hua 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第12期1473-1481,共9页
AIM:To investigate whether Melatonin has synergistic effects with Doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402.METHODS:The synergism of Melatonin and Dox... AIM:To investigate whether Melatonin has synergistic effects with Doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402.METHODS:The synergism of Melatonin and Doxorubicin inhibited the cell growth and induced cell apoptosis in human hepatoma cell lines HepG2 and Bel-7402.Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT)assay.Cell apoptosis was evaluated using TUNEL method and flow cytometry.Apoptosis-related protein Bax,Bcl-2 and caspase-3 expressions were measured by immunohistochemical staining.RESULTS:Treatment with Melatonin(10 -8 -10 -5 mol/L) alone had a dose-related inhibitory effect on cell proliferation but no cytotoxic effect on hepatoma cell lines HepG2 and Bel-7402.Interestingly,when combined with Doxorubicin,Melatonin significantly increased the effects of cell growth inhibition and cell apoptosis.Furthermore,TUNEL staining and flow cytometry revealed that cooperative apoptosis induction was associated with decreased expression of Bcl-2 as well as increased expression of Bax and Caspase3.CONCLUSION:The synergism of Melatonin and Doxorubicin inhibits hepatoma cell growth and induces cell apoptosis. 展开更多
关键词 MELATONIN doxorubicin Human hepatoma cell line APOPTOSIS
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Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin 被引量:5
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作者 Rifki Febriansah Dyaningtyas Dewi P.P. +3 位作者 Sarmoko Nunuk Aries Nurulita Edy Meiyanto Agung Endro Nugroho 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2014年第3期228-233,共6页
Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Meth... Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Methods:The cytotoxic properties.50%inhibition concentration(IC_(50))and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin(MCF-7/Dox)cells were determined using MTT assay.Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange.Immunocytochemistry assay was performed to determine the level and localization of Pgp.Results:Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC_(50)value of 11μmol/L.Thus,combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect(CI>1.0).Hesperidin did not increase the apoptotic induction,but decreased the Pgp expressions level when combined with doxorubicin in low concentration.Conclusions:Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC_(50)of 11μmol/L.Hesperidin did not increased the apoptotic induction combined with doxorubicin.Cochemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression. 展开更多
关键词 HESPERIDIN doxorubicin MCF-7/Dox cells line Apoptosis PGP expression
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Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment 被引量:6
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作者 Kamonrak Cheewatanakornkool Sathit Niratisai +2 位作者 Somkamol Manchun Crispin R.Dass Pornsak Sriamornsak 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2017年第6期509-520,共12页
Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin(DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with... Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin(DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape.However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character;in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors. 展开更多
关键词 MICROBEADS Thiolated PECTIN doxorubicin CONJUGATE COLORECTAL cancer
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Preparation and evaluation of poly(L-histidine) based pH-sensitive micelles for intracellular delivery of doxorubicin against MCF-7/ADR cells 被引量:6
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作者 Nan Jia Yuqing Ye +4 位作者 Qi Wang Xiuli Zhao Haiyang Hu Dawei Chen Mingxi Qiao 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2017年第5期433-441,共9页
In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intrace... In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal. 展开更多
关键词 doxorubicin(Dox) mPEG-PLA-Phis pH SENSITIVE micelles Box–Behnken design
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Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells inhibits proliferation and reduces doxorubicin resistance 被引量:3
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作者 范国昌 吴祖泽 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2000年第3期19-25,共7页
Objective: To elucidate the effect of p14ARF gene on multidrug-resistant tumor cells. Methods: We transferred a p14ARF cDNA into p53-mutated MCF-7/Adr human breast cancer cells. Results: In this report we demonstrated... Objective: To elucidate the effect of p14ARF gene on multidrug-resistant tumor cells. Methods: We transferred a p14ARF cDNA into p53-mutated MCF-7/Adr human breast cancer cells. Results: In this report we demonstrated for the first time that p14ARF expression was able to greatly inhibit the MCF-7/Adr cell proliferation. Furthermore, p14ARF expression resulted in decreases in MDR1 mRNA and P-glycoprotein production, which linked with the reducing resistance of MCF-7/Adr cells to doxorubicin. Conclusion: These results imply that drug resistance might be effectively reversed with the wild-type p14ARF expression in human breast cancer cells. 展开更多
关键词 P14ARF MDR-1 P-GLYCOPROTEIN doxorubicin BREAST cancer tumor suppression
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Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma 被引量:3
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作者 Gael Stephane Roth Yann Teyssier +4 位作者 Melodie Abousalihac Arnaud Seigneurin Julien Ghelfi Christian Sengel Thomas Decaens 《World Journal of Gastroenterology》 SCIE CAS 2020年第3期324-334,共11页
BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).D... BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).Doxorubicin is the most commonly used drug despite a low level of evidence.AIM To compare the objective response rate of idarubicin-based TACE(Ida-TACE)against doxorubicin-based TACE(Dox-TACE)in intermediate stage HCC.METHODS Between January 2012 and December 2014,all patients treated with TACE at our academic hospital were screened.Inclusion criteria were patients with Child-Pugh score A or B,a performance status below or equal to 1,and no prior TACE.Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin.Each patient treated with idarubicin was matched with two doxorubicin-treated patients.The TACE response was assessed by independent radiologists according to the mRECIST criteria.RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin.There were 93%and 87%of cirrhotic patients and 87%and 70%of Child-Pugh A in the doxorubicin and idarubicin groups,respectively.The median number of HCC per patient was two in both groups with 31%and 26%of single nodules in doxorubicin and idarubicin groups,respectively.Objective response rate after first TACE was 76.7%and 73.3%(P=0.797)with 41.7%and 40.0%complete response in doxorubicin and idarubicin groups,respectively.Progression-free survival was 7.7 mo in both groups,and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups,respectively.Safety profiles were similar in both groups,with grade 3-4 adverse events in 35%of Dox-TACE and 43%of Ida-TACEs.CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety.Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC. 展开更多
关键词 Hepatocellular carcinoma Transarterial chemoembolization IDARUBICIN doxorubicin Intermediate stage
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Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity 被引量:3
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作者 Pei-Pei LU Jie MA +6 位作者 Xiao-Peng LIANG Cai-Xia GUO Yan-Kun YANG Kun-Qi YANG Qi-Ming SHEN Li-Hong MA Xian-Liang ZHOU 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2016年第12期968-972,共5页
Xinfuli 小粒(XG ) ,一副复合中草药,有效地为心失败的处理在中国被使用超过五十年了。试图带着 导致doxorubicin 的 cardiotoxicity.MethodsSprague-Dawley 老鼠在老鼠调查效果和 Xinfuli 的内在的机制的这研究与 Doxorubicin 的 int... Xinfuli 小粒(XG ) ,一副复合中草药,有效地为心失败的处理在中国被使用超过五十年了。试图带着 导致doxorubicin 的 cardiotoxicity.MethodsSprague-Dawley 老鼠在老鼠调查效果和 Xinfuli 的内在的机制的这研究与 Doxorubicin 的 intraperitoneal 注射被对待(纪录影片, 2.5 mg/kg 每星期)为六个星期,然后随机把 intragastrically 收到了正常的管理的组划分了成四盐(控制组)或 XG 的不同剂量( 0.675 g/kg 每天, 1.35 g/kg 每天,和 2.7g/kg 每天,分别地)为六个星期。Transthoracic echocardiography 被执行室的部分弄短评估左(LVFS ) 并且在 XG 处理和组织病理学说的变化前后的左室的喷射部分(LVEF ) 也被检验。心肌的房间 apoptosis 被染色的 TUNEL 检测。相关基因和蛋白质的表达式在控制组,用 immunohistochemical staining.ResultsCompared 被分析到那些在对待的组显著地显示出的 XG 的老鼠改进了心脏的功能和更温和的心脏的组织病理学说的变化,更低的 cardiomyocyte apoptosis 索引, Bcl-2 的更高的表示和 XG 的 Bax.ConclusionsAdministration 的更低的表示与 导致doxorubicin 的 cardiotoxicity 在老鼠改进心脏的功能和组织病理学说的变化。这些效果与 cardiomyocyte apoptosis 的抑制被联系,也许经由 Bcl-2 和 Bax 蛋白质表示的规定。 展开更多
关键词 APOPTOSIS doxorubicin 心失败 草药的药
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Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than Doxil? 被引量:4
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作者 Ruoshi Zhang Yingxi Zhang +7 位作者 Yue Zhang Xin Wang Xuanming Gao Yuyan Liu Xuanbo Zhang Zhonggui He Dun Wang Yongjun Wang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2020年第3期385-396,共12页
Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot synd... Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine(BER) and doxorubicin(DOX), which was called Lipo Be Do. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, Lipo Be Do, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The Lipo Be Do significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil(P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX. 展开更多
关键词 BERBERINE doxorubicin NANOLIPOSOMES Remote loading Combination therapy Cardiotoxity
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Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients 被引量:6
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作者 Yan-Fu Zheng Xin Fu +2 位作者 Xiao-Xu Wang Xiao-Jing Sun Xiao-Dan He 《World Journal of Clinical Cases》 SCIE 2021年第33期10075-10087,共13页
BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,result... BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy. 展开更多
关键词 The cooling patch Hand-foot syndrome Pegylated liposomal doxorubicin Breast cancer Self efficacy Quality of life
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