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排序方式: 共有160条查询结果,搜索用时 11 毫秒
101.
Dai Koguchi Kazumasa Matsumoto Masaomi Ikeda Yuriko Shimizu Marie Nakamura Yutaka Shiono Hiroki Katsumata Yuichi Sato Masatsugu Iwamura 《International journal of molecular sciences》2022,23(20)
An investigation of alternatives to immune checkpoint inhibitors for advanced urothelial cancer (aUC), with biologic information, is urgently needed. Clinical data for 53 patients who received gemcitabine–paclitaxel therapy (GP) as 2nd-line chemotherapy for aUC refractory to platinum-based chemotherapy were retrospectively reviewed. The efficacy and tolerability of GP were evaluated, and the predictive value of phosphoglycerate kinase 1 (PGK1) immunostained in surgical specimens was investigated for treatment outcomes in 1st- and 2nd-line chemotherapy. GP was associated with an objective response rate of 35.8% and a median overall survival duration of 12.3 months. Multivariate analysis showed that PS2 and 1st- and 2nd-line non-response are independent predictors of worse progression-free survival and that PS2 and 1st-line non-response are independent predictors of worse overall survival. Adverse events were manageable, and no therapy-related deaths occurred. Non-response rates to 1st-line chemotherapy were significantly higher in patients with a high expression of PGK1 in the nucleus than in those with low expression (p = 0.006). Our study demonstrates the efficacy and tolerability of 2nd-line GP for patients with aUC who are refractory to platinum-based chemotherapy. Moreover, PGK1 in the nucleus was predictive values for resistance to platinum-based chemotherapy in aUC. 相似文献
102.
Naike Casagrande Cinzia Borghese Francesco Agostini Cristina Durante Mario Mazzucato Alfonso Colombatti Donatella Aldinucci 《International journal of molecular sciences》2021,22(6)
A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-β, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse. 相似文献
103.
紫杉醇长循环脂质体的制备及其药动学研究 总被引:5,自引:0,他引:5
目的制备紫杉醇长循环脂质体并观察其在大鼠体内的药动学.方法用薄膜分散法制备紫杉醇长循环脂质体;HPLC法测定血浆中紫杉醇的药物浓度;用3P97程序计算药动学参数.结果脂质体粒径为(106.5±1.7)nm,包封率为(87.5士2.5)%,紫杉醇长循环脂质体和紫杉醇注射液的血药浓度-时间曲线均符合二室模型,药动参数t1/2β分别为(7.32±1.24)h和(0.32±0.06)h,AUC分别为(23.85±1.20)μg·h·mL-1和(5.08±0.45)μg·h·mL-1.结论与紫杉醇注射液相比,紫杉醇长循环脂质体显著延长了紫杉醇在血液循环系统中的驻留时间,具有长效作用. 相似文献
104.
采用甲醇-水体系脱脂除杂法对紫杉醇提取液的初分离工艺进行了研究。通过单因素和正交实验考察了甲醇体积分数、脱脂时间和脱脂温度3个因素对脱脂效果的影响。结果表明,各因素的影响程度为脱脂温度>甲醇体积分数>脱脂时间,确定最佳工艺条件为:甲醇溶液体积分数40%、脱脂时间10 h、脱脂温度12℃。在此条件下,杂质去除率为31.2%,紫杉醇回收率为89.6%。此工艺使紫杉醇在损失较小的情况下达到了理想的初分离效果,具有操作简便、成本低、环境污染小等特点,适于大规模应用。 相似文献
105.
Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy
Takehiro Kawashiri Mizuki Inoue Kohei Mori Daisuke Kobayashi Keisuke Mine Soichiro Ushio Hibiki Kudamatsu Mayako Uchida Nobuaki Egashira Takao Shimazoe 《International journal of molecular sciences》2021,22(16)
Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important. 相似文献
106.
Lisha Wei Yanxia Ji Wei Gong Zhenqiao Kang Meng Meng 《Drug development and industrial pharmacy》2015,41(8):1343-1352
Paclitaxel (PTX) is a natural broad-spectrum anticancer drug with poor aqueous solubility. PTX nanocrystals were formulated to improve the water solubility, and PTX nanosuspensions were prepared using anti-solvent precipitation, and then organic solvent and surfactants were removed by filtering through a vacuum system. The physical characterization of PTX nanocrystals were measured by transmission electron microscope, X-ray diffraction and differential scanning calorimetry. In addition, saturation solubility, in vitro release, stability and pharmacokinetic characteristics were examined. The average particle size of PTX nanocrystals was ~200?nm, and they had a stable potential and a uniform distribution. Paclitaxel nanocrystals can effectively improve drug solubility and in vitro release. PTX pharmacokinetic and tissue distribution studies were compared after intravenous administration of nanocrystals versus a commercial injection formulation. PTX nanocrystals were rapidly distributed with a longer elimination phase. Moreover, tissue distribution indicated that PTX nanocrystals are mainly absorbed by the liver and spleen and may offer reduced renal and cardiovascular toxicity which may reduce side effects. 相似文献
107.
《Drug development and industrial pharmacy》2013,39(8):1187-1196
Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(?-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films. 相似文献
108.
采用聚(乳酸-羟基乙酸)共聚物(PLGA)纳微球装载紫杉醇,并用壳聚糖季铵盐(HTCC)对PLGA微球表面进行镀层修饰,比较了修饰前后载药微球的形貌、粒径、电位、载药率、释药行为和细胞杀伤效果. 结果表明,修饰后微球表面圆整光滑,平均粒径为882 nm,载药率可达5.15%,包埋率达70.46%,体外释药22 d累积释药率为70.17%,与修饰前没有显著性差异;但修饰后微球表面电荷由修饰前的-14.8 mV翻转为+36.7 mV,肿瘤细胞对PLGA和HTCC-PLGA载药微球的内吞量分别是Taxol?的5.6和9.7倍,且HTCC-PLGA载药微球对细胞杀伤效果显著,是一种有潜力的难溶性药物递送系统. 相似文献
109.
110.
红豆杉是广谱抗肿瘤药物——紫杉醇的天然来源,国际市场对紫杉醇的需求量逐年增长,我国虽然红豆杉储量已超过世界储量二分之一,出口量约占世界总产量四分之一,但出口产值仅占世界紫杉醇总产值十分之一,因此,如何在现有基础上快速提高红豆杉产品附加值并建立完整的高附加值产业链是我国红豆杉产业发展的关键。在此基础上,本研究对红豆杉资源储量、产品类型、产品质量控制及其分析检测方法、技术瓶颈及产业规模等进行了调研,对我国当前红豆杉产业存在的野生资源稀少、人工资源缺乏统一规划布局以及缺乏高附加值产品等问题的原因进行了分析,对红豆杉产业未来资源储量、技术创新方向及产业发展规划提出了建议,可为红豆杉资源绿色产业化发展提供理论基础和数据支持。 相似文献