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71.
Joonyoung Park Ji Eun Park Victoria E. Hedrick Karl V. Wood Connie Bonham Wooin Lee Yoon Yeo 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(16)
Nanoparticulate drug carriers exploit the enhanced permeability of tumor vasculature to achieve selective delivery of chemotherapeutic drugs. For this purpose, nanoparticles (NPs) need to circulate with a long half‐life, enter tumors via the permeable vasculature and stay in tumors via favorable interactions with tumor cells. To fulfill these requirements, albumin‐coated nanocrystal formulation of paclitaxel (PTX), Cim‐F‐alb, featuring high drug loading content, physical stability in serum, and surface‐bound albumin in its native conformation is prepared. The pharmacokinetic and biodistribution (PK/BD) profiles of Cim‐F‐alb in a mouse model of B16F10 melanoma show that Cim‐F‐alb exhibits a longer plasma half‐life and a greater PTX deposition in tumors than Abraxane by ≈1.5 and ≈4.6 fold, respectively. Biolayer interferometry analysis indicates that Cim‐F‐alb has less interaction with serum proteins than nanocrystals lacking albumin coating, indicating the protective effect of the surface‐bound albumin against opsonization in the initial deposition phase. With the advantageous PK/BD profiles, Cim‐F‐alb shows greater and longer‐lasting anticancer efficacy than Abraxane at the equivalent dose. This study demonstrates the significance of controlling circulation stability and surface property of NPs in efficient drug delivery to tumors and enhanced anticancer efficacy. 相似文献
72.
目的:比较紫杉醇联合铂类药物(TP 方案) 与环磷酰胺加铂类药物(CP 方案) 治疗Ⅲ、Ⅳ期卵巢上皮癌的疗效。方法:化疗方案每一疗程采用2 d 疗法, 每种药物d 1 或d 2 给药, 采用大剂量单次给药。对24 例Ⅲ、Ⅳ期卵巢上皮癌给予TP 方案化疗:紫杉醇剂量为135 mg·m-2, 溶于5 %GS 500 ml 中,静滴, 3 h, d 1;顺铂(DDP) 75 mg·m-2, d 2(或卡铂按AUC =5 计算所得的剂量), 前3 ~ 4 个疗程采用腹腔给药, 以后均静脉给药。30 例对照组病人采用环磷酰胺加铂类药为主的CP 方案。环磷酰胺(CTX)600 mg·m-2, 静注, d 1;阿霉素(ADM) 40 ~60 mg·m-2, 静注, d 1;长春新碱(VCR) 2 mg, 静注,d 1;DDP 60 ~ 80 mg·m-2 (或卡铂, 剂量按AUC =5 计算) 。铂类药物用药时间、途径及水化均与TP 方案相同。结果:TP 方案化疗组CR 为8 例, PR 为10例, 总有效率为75 %;CP 方案对照组CR 4 例, PR 8例, 总有效率为40 %, TP 方案化疗组有效率显著高于CP 方案化疗组(P <0.05) 。TP 治疗组中位生存期为41.5 个月, 高于CP 对照组的32.6 个月(P <0.01) 。结论:TP 方案治疗Ⅲ、Ⅳ期卵巢上皮癌疗效显著优于CP 方案。 相似文献
73.
B Qiu X Sun D Zhang Y Wang J Tao S Ou 《International journal of molecular sciences》2012,13(7):9142-9156
U87-derived stem-like cells (U87-SLCs) were cultured using serum-free stem cell media and identified by both biological behaviors and markers. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PX), in combination or alone, was used to treat U87-MG human glioma cells (U87 cells) or U87-SLCs. The results showed that TRAIL/PX cannot only synergistically inhibit U87 cells but also U87-SLCs. We observed a significantly higher apoptotic rate in U87 cells simultaneously treated with TRAIL/PX for 24 h compared to cells treated with either drug alone. Furthermore, there was a remarkably higher apoptosis rate in U87-SLCs induced by the TRAIL/PX combination compared with either drug alone. Unlike the simultaneous treatment in U87 cells, U87-SLCs were pretreated for 24 h with 1 μmol/L of PX followed by 1000 ng/mL of TRAIL. Protein assays revealed that TRAIL/PX synergy was related to DR4, cleaved caspase-8 and cleaved caspase-3 upregulation, whereas the mitochondrial pathway was not involved in TRAIL-induced apoptosis. The present study indicates that PX can sensitize U87 cells and U87-SLCs to TRAIL treatment through an extrinsic pathway of cell apoptosis. The combined treatment of TRAIL and PX may be a promising glioma chemotherapy because of its successful inhibition of U87-SLCs, which are hypothesized to influence chemotherapeutic outcomes of gliomas. 相似文献
74.
Yongfeng Tian Hua Zhang Yanmei Qin Dong Li Yang Liu Hao Wang 《Drug development and industrial pharmacy》2013,39(12):2071-2082
AbstractAs a major cause for the inefficiency of cancer chemotherapy, multidrug resistance (MDR) has become a major barrier to cancer treatment. Mitochondrion-orientated transportation of smart liposomes has been developed as a promising strategy to deliver anticancer drugs directly to tumor sites and actively target the mitochondria, so that drugs can interfere with mitochondrial function and facilitate cell apoptosis, overcoming MDR. Herein, we report a novel dual-functional paclitaxel (PTX) liposome system possessing both CD44-targeting and mitochondrial-targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of drug-resistant cancer cells. Mitochondria-targeting PTX-loaded liposomes were prepared by thin-film hydration and then coated with hyaluronic acid (HA) by electrostatic adsorption. We evaluated the characteristics of the PTX liposomes in vitro, and found that their particle size was about 100?nm and increased to ~140?nm after modification by HA. The entrapment efficiency was larger than 85%, and stability data indicated that the liposomes were physically and chemically stable for at least one week at 4?°C. We further evaluated the intake, mitochondrial targeting, ATP levels, caspase-3 activity measurement, and antitumor actives of the liposomes. The results indicated that HA-coated liposomes with mitochondria targeting had significant inhibitory effects against A549 and A549/Taxol cells, showing them to be a promising means of improving therapeutic efficacy and overcoming MDR in cancer treatment. 相似文献
75.
《分离科学与技术》2012,47(6):851-858
Six taxanes were isolated and purified from Taxus chinensis cell culture extract using high-speed counter-current chromatography. The crude cell culture extract was first treated with Al2O3 column chromatography and then divided into two parts: fraction 1 and fraction 2. 52 mg of taxuyunnanine C and 11 mg of sinenxane C were yielded from 150 mg of fraction 1. 5 mg of 9-dihydrobaccatin III, 12 mg of baccatin III, 12 mg of paclitaxel, and 17 mg baccatin VI were yielded from 150 mg of fraction 2. The purities of the six compounds were 93.51%, 98.02%, 98.61%, 97.55%, 98.93%, and 98.76%. 相似文献
76.
Alena Pastornick Silvia Rybrov Slvka Drahoov Jozef Mihalik Andrea Kreheov Andriana Pavliuk-Karachevtseva Ingrid Hodorov 《International journal of molecular sciences》2021,22(12)
Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of βIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of βIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that βIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance. 相似文献
77.
Sang‐Hyun Pyo Moon‐Suk Kim Jin‐Suk Cho Bong‐Kyu Song Byung‐Hee Han Ho‐Joon Choi 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2004,79(10):1162-1168
Paclitaxel was purified from cell cultures of Taxus chinensis by a combination of extraction, low‐pressure chromatography, precipitation and HPLC. A crude extract (purity 6.9%) was obtained by methanol extraction of plant cell cultures, followed by liquid–liquid extraction using dichloromethane. The extract was purified to greater than 32% with a 97% step yield by low‐pressure chromatography. After acetone/pentane precipitation, the resulting purity and step yield were 75.8% and 97.4%, respectively. High performance liquid chromatography steps, which were composed of an HPLC step with column‐packed ODS and an HPLC step with column‐packed silica, were applied to give over 99.5% purity with high yield. Amorphous paclitaxel with a fine particle size, which has a solubility advantage compared with the stable crystalline form, was obtained by dissolving in dichloromethane, followed by spray‐drying. Copyright © 2004 Society of Chemical Industry 相似文献
78.
Tayyebeh Ghaffari Joo-Hyun Hong Solmaz Asnaashari Safar Farajnia Abbas Delazar Hamed Hamishehkar Ki-Hyun Kim 《International journal of molecular sciences》2021,22(12)
The incidence of various types of cancer is increasing globally. To reduce the critical side effects of cancer chemotherapy, naturally derived compounds have been considered for cancer treatment. Gymnosperms are a group of plants found worldwide that have traditionally been used for therapeutic applications. Paclitaxel is a commercially available anticancer drug derived from gymnosperms. Other natural compounds with anticancer activities, such as pinostrobin and pinocembrin, are extracted from pine heartwood, and pycnogenol and enzogenol from pine bark. Gymnosperms have great potential for further study for the discovery of new anticancer compounds. This review aims to provide a rational understanding and the latest developments in potential anticancer compounds derived from gymnosperms. 相似文献
79.
Allison Podsednik Jinxia Jiang Annemarie Jacob Lin Z. Li He N. Xu 《International journal of molecular sciences》2021,22(11)
We evaluated the utility of optical redox imaging (ORI) to identify the therapeutic response of triple-negative breast cancers (TNBC) under various drug treatments. Cultured HCC1806 and MDA-MB-231 cells treated with FK866 (nicotinamide phosphoribosyltransferase (Nampt) inhibitor), FX11 (lactate dehydrogenase A inhibitor), paclitaxel, and their combinations were subjected to ORI, followed by imaging fluorescently labeled reactive oxygen species (ROS). Cell growth inhibition was measured by a cell viability assay. We found that both cell lines experienced significant NADH decrease and redox ratio (Fp/(NADH+Fp)) increase due to FK866 treatment; however, HCC1806 was much more responsive than MDA-MB-231. We further studied HCC1806 with the main findings: (i) nicotinamide riboside (NR) partially restored NADH in FK866-treated cells; (ii) FX11 induced an over 3-fold NADH increase in FK866 or FK866+NR pretreated cells; (iii) FK866 combined with paclitaxel caused synergistic increases in both Fp and the redox ratio; (iv) FK866 sensitized cells to paclitaxel treatments, which agrees with the redox changes detected by ORI; (v) Fp and the redox ratio positively correlated with cell growth inhibition; and (vi) Fp and NADH positively correlated with ROS level. Our study supports the utility of ORI for detecting the treatment responses of TNBC to Nampt inhibition and the sensitization effects on standard chemotherapeutics. 相似文献
80.
Piyush Kumar Sahu Deepak Kumar Mishra Nivrati Jain Vaibhav Rajoriya 《Drug development and industrial pharmacy》2015,41(4):640-649
Objective: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung’s epithelial cancer cells.Materials and methods: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope.Results: The M-SLNs were spherical in shape with 254?±?2.3?nm average size, positive zeta potential (3.27?mV), 79.4?±?1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48?h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site.Discussion and conclusion: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting. 相似文献