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排序方式: 共有160条查询结果,搜索用时 15 毫秒
51.
Rocío Jimnez-Guerrero Alejandro Belmonte-Fernndez M. Luz Flores Mnica Gonzlez-Moreno Begoa Prez-Valderrama Francisco Romero Miguel . Japn Carmen Sez 《International journal of molecular sciences》2022,23(1)
The Wnt/β-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/β-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/β-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after β-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of β-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of β-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/β-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties. 相似文献
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Jaber Emami Mahboubeh Rezazadeh Mahboubeh Rostami Farshid Hassanzadeh Hojjat Sadeghi Abolfazl Mostafavi 《Drug development and industrial pharmacy》2015,41(7):1137-1147
The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and α-tocopherol succinate (α-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and α-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of α-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of αTS/PTX-loaded micelles were about 133?nm and +25.2?mV, respectively, and PTX release was completed during 6–9?d from the micelles. Furthermore, the cytotoxicity of α-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with α-TS were 110 and 188?ng/ml, respectively. 相似文献
55.
Srinivasan Shanmugam Ho Taek Im Young Taek Sohn Yong-Il Kim Jae-Hyun Park 《Drug development and industrial pharmacy》2015,41(11):1864-1876
The main objective of this study was to develop novel orally administrable tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX) prepared by fluid bed technology, and to evaluate its in vitro dissolution and in vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized composition by fluid bed technology, and characterized for solid-state properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid showed a rapid release of PTX, reaching maximum dissolution within 20?min. Finally, the PK profile of SDG-T and a reference formulation Oraxol? (oral solution formulation used in Phase I clinical study) at a dose of 60?mg orally with co-administration of P-gp inhibitor HM38101, and Taxol® at a dose of 10?mg intravenously (i.v.) was investigated in beagle dogs. The mean absolute BA% of PTX following SDG-T and Oraxol? solution was 8.23 and 6.22% in comparison to i.v. administration of Taxol®. The relative BA% of PTX from SDG-T in comparison to Oraxol? solution was 132.25% at a dose of 60?mg following oral administration. In conclusion, we have successfully prepared PTX tablets with solid dispersion granules (SDG) of amorphous PTX using fluid bed technology that could provide plasma PTX concentration in the range of 10–150?ng/mL for a period of 24?h following oral administration in dogs with a P-gp inhibitor. Hence, this could be a promising formulation for PTX oral delivery and could be used in our intended clinical studies following pre-clinical efficacy studies. 相似文献
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目的评价紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案二线治疗晚期胃癌的疗效及毒性。方法分析一线化疗失败后采用紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案作为二线化疗方案的48例晚期胃癌患者资料,评价缓解率(RR)、疾病进展时间(TTP)、总生存(OS)及不良反应。治疗方案为:紫杉醇100 mg.m-2,静脉滴注3 h;亚叶酸钙200 mg.m-2,静脉滴注2 h;随后给予氟脲嘧啶400 mg.m-2静脉推注,氟脲嘧啶2.4 g.m-2为微量泵持续泵注46 h。每2周给予1次化疗,每2次为1个疗程。结果 48例患者中,近期缓解率为22.9%,中位TTP及OS分别为3.6月和7.8月,获缓解患者中位OS明显长于未获缓解者(P〈0.05);患者耐受性良好,主要的不良反应为骨髓抑制、外周神经毒性、脱发、腹泻和肌肉关节疼痛。结论紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案二线治疗PS评分高的晚期胃癌缓解率较高,不良反应可耐受,值得进一步开展前瞻性研究证实。 相似文献
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考察三种紫杉醇脂肪乳配方的时间及温度稳定性、制备工艺对其粒径的影响以及测定脂肪乳中紫杉醇的浓度,光子相关光谱法(PCS)测试结果表明,以单一F-68作为乳化剂的脂肪乳粒径为235±15nm,PDI为0.2±0.1,Zeta电位为-35±10mV,在室温(25℃)下放置60d粒径变化不明显,较含有92%、98%蛋黄卵磷脂的脂肪乳稳定;随着高压均质压力升高,脂肪乳的粒径减小,高压均质循环次数对粒径几乎无影响;4000r/min条件下离心15min不分层,说明脂肪乳具有良好的离心稳定性。高效液相色谱(HPLC)结果表明,脂肪乳中紫杉醇的浓度为0.291mg/mL,提高初始加入量后浓度可达0.673mg/mL。 相似文献
58.
目的:观察脂质体紫杉醇联合顺铂对比白蛋白结合型紫杉醇联合顺铂一线治疗晚期非小细胞肺癌(NSCLC)的临床疗效及预后,同时评价血清乳酸脱氢酶(LDH)在预后的评价的作用。方法62例经病理学证实为晚期的NSCLC患者,按随机数字表法分为白蛋白结合型紫杉醇联合顺铂组(A组,31例)和脂质体紫杉醇联合顺铂组(B组,31例)。分析2组的疗效、不良反应及远期生存。测定血清乳酸脱氢酶(LDH),并根据化疗后血清LDH变化,分为反应组(下降)和不反应组(升高或持平)。结果A组和B组有效率分别为12.9%和25.8%,疾病控制率分别为90.3%和93.5%,2组比较差异无统计学意义(P>0.05)。A组中位PFS为17.4个月优于B组9.6个月(95%可信区间,5.2个月to19.7个月,P=0.264)。亚组分析鳞癌患者应用白蛋白结合型紫杉醇联合顺铂方案化疗优于脂质体紫杉醇联合顺铂。2组主要不良反应为骨髓抑制和消化道反应。Cox多因素分析提示性别、年龄、LDH反应性均是影响预后的独立危险因素;女患者预后较男患者好(HR=3.231,P=0.014),初治时年龄大于60岁的患者预后较好(HR=0.287,P=0.005),LDH反应组比不反应组预后好(HR=0.379,P=0.027)。结论脂质体紫杉醇联合顺铂和白蛋白结合型紫杉醇联合顺铂均为较好的治疗方案,LDH反应性可能预测晚期NSCLC患者疗效。 相似文献
59.
Yanli Zhao Yanli Li Jianjun Ge Na Li 《Drug development and industrial pharmacy》2014,40(11):1483-1493
The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p?0.05). In general, Pluronic-poly (acrylic acid)-cysteine/PL121 micelles were proven to be a potential oral drug delivery system for paclitaxel. 相似文献
60.
Ovarian cancer is one of the most dangerous gynecologic cancers worldwide, showing a high fatality rate and recurrence due to diagnosis at an advanced stage of the disease and the occurrence of chemoresistance, which weakens the therapeutic effects of the chemotherapeutic treatments. In fact, although paclitaxel and platinum-based drugs (carboplatin or cisplatin) are widely used alone or in combination to treat ovarian cancer, the occurrence of chemoresistance significantly reduces the effects of these drugs. Metformin is a hypoglycemic agent that is commonly used for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease. However, this drug also shows anti-tumor activity, reducing cancer risk and chemoresistance. This review analyzes the current literature regarding the role of metformin in ovarian cancer and investigates what is currently known about its effects in reducing paclitaxel and platinum resistance to restore sensitivity to these drugs. 相似文献