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1.
目的 按照国家计划抽验要求,评价国内不同企业生产的注射用盐酸柔红霉素的质量。方法 按国家标准检验与探索性研究相结合,对抽验样品进行检验,对检验结果进行统计分析。结果 共抽取样品17批次,按国家标准检验合格率100.0%。探索性研究对主要杂质的来源与结构进行了研究;建立溶液的澄清度检查方法;对包材相容性及稳定性进行了考察。结论 目前国内注射用盐酸柔红霉素总体质量较好;现行标准有待进一步提高,建议现行标准修订有关物质检查方法,增加特定杂质的控制,增加溶液的澄清度检查;建议企业优化生产工艺,以提高产品质量。 相似文献
2.
JeongYun Choi Haeseung Lee EunJi Kwon HyeonJoon Kong OkSeon Kwon HyukJin Cha 《Molecular oncology》2021,15(2):679
The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.
Abbreviations
- AUC
- area under the curve
- AXL
- AXL receptor tyrosine kinase
- BCL2
- B‐cell lymphoma 2
- CTD2
- cancer target discovery and development
- CTGF
- connective tissue growth factor
- DEG
- differentially expressed genes
- DOXO
- doxorubicin
- EMT
- epithelial–mesenchymal transition
- Eto
- etoposide
- FDA
- Food and Drug Administration
- ITGB3
- integrin beta‐3
- MAPK
- mitogen‐activated protein kinase
- MMP2
- matrix metalloproteinase‐2
- MMP9
- matrix metalloproteinase‐9
- mRNA
- messenger RNA
- NF‐κB
- nuclear factor kappa‐light‐chain‐enhancer of activated B cells
- SBE
- SMAD binding element
- SERPINE1
- serpin family E member 1
- siRNA
- small interfering RNA
- ssGSEA
- single‐sample gene set enrichment analysis
- TCGA
- The Cancer Genome Atlas
- TGFβ
- transforming growth factor beta
- YAP
- Yes‐associated protein
- YAP8SA
- mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP
- ZEB1
- zinc finger E‐box binding homeobox 1
- ZEB2
- zinc finger E‐box‐binding homeobox 2
3.
Huda Mohammed Alkreathy Mayson H. Alkhatib Safaa Ahmed Al Musaddi Khadijah Saeed A. Balamash Nadia Nour Osman Aftab Ahmad 《Clinical and experimental pharmacology & physiology》2019,46(5):496-505
Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects. 相似文献
4.
目的 通过阿霉素(Dox)复制大鼠慢性心力衰竭(CHF)模型,观察Liguzinediol对CHF大鼠心功能的影响。方法 通过血流动力学观察Liguzinediol对Dox(腹腔注射,2 mg/kg)诱导的CHF大鼠左心室内压最大上升/下降速率(±dp/dtmax)、左心室内压(LVSP)、动脉收缩压(ASP)、动脉舒张压(ADP)和心率(HR)的变化;观察Liguzinediol对血清一氧化氮(NO)、一氧化氮合成酶(NOS)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)以及血浆中丙二醛(MDA)的影响。结果 Liguzinediol能增加LVSP、+dp/dtmax、ASP、ADP、AP、HR,降低-dp/dtmax(P<0.05~0.01);降低NO、iNOS以及MDA的浓度,同时增强了SOD的活性(P<0.05~0.01);抑制IL-6和TNF-α的生成(P<0.05~0.01)。结论 Liguzinediol可明显改善Dox诱导的CHF大鼠血流动力学指标,减少模型大鼠炎症因子的释放以及抑制氧自由基的生成。 相似文献
5.
《Journal of pharmaceutical sciences》2019,108(10):3425-3433
This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation. 相似文献
6.
Ming-Ju Hsieh Cheng Huang Chia-Chieh Lin Chih-Hsin Tang Chih-Yang Lin I-Neng Lee Hsiu-Chen Huang Jui-Chieh Chen 《Molecular carcinogenesis》2020,59(3):293-303
Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future. 相似文献
7.
目的探讨对慢性支气管炎急性发作期患者采用盐酸氨溴索联合多索茶碱治疗的临床疗效。方法选取本院收治的慢性支气管炎急性发作期患者88例为研究对象,收治时间为2018年3月-2019年3月,根据入院时间将患者随机分为两组,对照组(n=44)和观察组(n=44)。观察组患者采用盐酸氨溴索联合多索茶碱治疗,对照组采用多索茶碱治疗,对两组患者治疗后的治疗有效率以及两组患者症状改善情况进行观察比较。结果观察组患者治疗有效率(97.7%)高于对照组(84.1%),P <0.05;观察组患者症状改善情况优于对照组,P <0.05。结论盐酸氨溴索联合多索茶碱治疗慢性支气管炎急性发作期患者,临床疗效较好,改善患者症状情况。 相似文献
8.
9.
目的建立一种简便的测定脂溶性前列安栓中盐酸小檗碱含量的方法。方法采用高效液相色谱法(HPLC)测定盐酸小檗碱的含量。色谱条件为Krom asil C18柱(4.6 mm×200 mm,5μm),流动相为乙腈-0.1%磷酸溶液(50∶50)(每100m l中加入十二烷基硫酸钠0.1 g),检测波长350 nm。供试品预处理采用超声溶解法。结果盐酸小檗碱在20~200μg.m l-1范围内有良好的线性关系(r=0.9999),平均回收率为98.9%,RSD为0.5%。结论本方法可用于脂溶性前列安栓中盐酸小檗碱的含量测定,方法简便、快速、灵敏。 相似文献
10.
盐酸戊乙奎醚用于全麻术前减少腺体分泌的研究 总被引:16,自引:1,他引:15
目的评价盐酸戊乙奎醚作为全麻术前用药减少腺体分泌的有效性与安全性。方法本研究采用多中心随机双盲平行对照观察。298例全麻病人随机分为三组,术前分别肌肉注射阿托品、盐酸戊乙奎醚或注射用水,测定注射后30min唾液分泌量。用视觉模拟评分(VAS)方法测定口干程度,记录不良反应。结果给药后30min,阿托品、盐酸戊乙奎醚和注射用水组唾液分泌量分别较给药前变化(-17·64±19·53)、(-22·30±21·04)和(2·71±19·46)mg。VAS阿托品、盐酸戊乙奎醚组用药后明显增加。给药后30min,阿托品、盐酸戊乙奎醚和注射用水组HR分别较给药前变化(1·65±8·82)、(-4·30±7·01)和(-0·54±6·49)次/分。观察期间无严重不良反应。结论盐酸戊乙奎醚作为全麻术前用药,可明显减少唾液分泌,无HR增快,无明显不良反应。 相似文献