• Bulletin of the Korean Chemical Society
• /
• v.31 no.2
• /
• pp.281-285
• /
• 2010

Hemodialysis vascular access dysfunction (HVAD) due to the aggressive development of venous neointimal hyperplasia remains a major complication for patients with synthetic arteriovenous grafts. Paclitaxel-coated expanded polytetrafluoroethylene (ePTFE) grafts effectively prevent neointimal hyperplasia and stenosis. However, perigraft inflammation or edema can be another complication of ePTFE grafts, preventing early cannulation. Three different types of ePTFE grafts, including grafts without paclitaxel coating (control group, n = 12), grafts with paclitaxel coating at a dose density of $0.61ug/mm^2$ (low concentration group, n = 12), and grafts with paclitaxel coating at a dose density of $1.15ug/mm^2$ (high concentration group, n = 12) were placed in the backs of 12 rabbits, simultaneously. Six rabbits were euthanized after one week and the remaining six were euthanized two weeks after implantation. Perigraft inflammation, graft wall inflammation, stromal cell proliferation, blood vessel formation, tissue necrosis and edema were analyzed for the grafts in each animal. Inflammation surrounding the paclitaxel-coated grafts was significantly reduced compared to the control group. Stromal cell layers were detected at the interface between the graft and the surrounding tissue in the control group, infiltrated into the graft interstices, and differentiated into myofibroblasts for graft healing. Paclitaxel-coated grafts inhibited stromal cell proliferation and infiltration into the graft wall. Tissue necrosis and edema were not detected in either of the paclitaxel-coated graft groups.

• KSBB Journal
• /
• v.14 no.1
• /
• pp.17-23
• /
• 1999

Studies were carried out to elucidate the effects of pressure, temperature and mobile phase composition on supercritical $CO_2$ chromatographic separations of paclitaxel, baccatin III, 10-deacetyl baccatin III, 7-epi-10-deacetyltaxol, cephalomanine, and 10-deacetyltaxol. High resolutions of paclitaxel, 10-deacetylbaccatin III, 10-deacetyltaxol were observed with optimized pressure, temperature, and mobile phase composition. The highest resolution between paclitaxel and 10-deacetylbaccain III was observed at 275 kg/$\textrm{cm}^2$, $40^{\circ}C$ with the mobile phase composition of gradient mixture of 3.9-3.6 mL/min $CO_2$, 0.1-0.4 mL/min methanol for 20 min. Resolutions of baccatin III, capalomannine, and 7-epi-10-deacetyltaxol were found to be low in this study. On-line coupled SFE/SFC process was applied to isolate paclitaxel from yew tree powder. As a consequence, paclitaxel with a purity of 95% was obtained with a recovery yield of 38%.

• Microbiology and Biotechnology Letters
• /
• v.41 no.2
• /
• pp.176-182
• /
• 2013

Several types of mesoporous alumina adsorbents with different physical properties were prepared by spray pyrolysis and were used for the separation/purification of the anticancer agent paclitaxel. The pore diameter of the adsorbents had a greater effect than did the surface area and the pore volume on the removal of plant-derived impurities. An appropriate pore diameter (~10.8 nm) was required for effective impurity removal. At a constant pore diameter, the surface area of the adsorbent affected not only the purity but also the yield of paclitaxel. Also, increasing the surface area of the adsorbent resulted in an increase in the adsorption of paclitaxel and impurities (biomass-derived tar and wax components). Removal of these impurities was confirmed by HPLC analysis of the absorbent after the treatment and TGA of the organic substances that were bound to the adsorbent.

• KSBB Journal
• /
• v.22 no.4
• /
• pp.197-200
• /
• 2007

This study examined the conditions of filtration and concentration of methanol extract from biomass. Filtration efficiency was improved by adding diatomaceous earth as a filter aid. The optimal amount of diatomaceous earth was 6% (w/w) to reduce the filtration time. The filtration time was reduced by 4.2% in first extraction, 30.0% in second extraction, 22.8% in third extraction, and 19.0% in fourth extraction, respectively. The optimal temperature of water bath was below 50$^{\circ}C$ for preventing paclitaxel degradation during concentration of methanol extract using a rotary evaporator. The temperature of concentrated solution in rotary evaporator was relatively low compared to bath temperature because of latent heat of evaporation. The stopping point of concentration in rotary evaporator for the following step was at a specific gravity of 0.96 of the concentrated solution in terms of the purity and yield of paclitaxel. This information is very useful for mass extraction of biomass for the recovery of paclitaxel from plant cell culture.

• Bulletin of the Korean Chemical Society
• /
• v.29 no.2
• /
• pp.422-426
• /
• 2008

Hemodialysis graft coated with paclitaxel prevents stenosis; however, large initial burst release of paclitaxel causes many negative effects such as drug toxicity and inefficient drug loss. Therefore we developed and tested a novel coating method, double dipping, to provide controlled and sustained release of paclitaxel locally. Expanded polytetrafluoroethylene (ePTFE) grafts were dipped twice into a solution of several different paclitaxel concentrations. In vitro release tests of the double dipping method showed that early burst release could be somewhat retarded and followed by sustained release for a long time. We observed the effect of paclitaxel coating by double dipping in porcine model of arterio-venous (AV) grafts between the common carotid artery and the external jugular vein. 12 weeks after constructing AV grafts, cross sections of the graft venous anastomosis were obtained and analyzed. Paclitaxel coated ePTFE grafts by double dipping were observed to prevent neointimal hyperplasia and therefore reduced stenosis of the arteriovenous hemodialysis grafts, especially at the graft venous anastomosis sites. Our results demonstrate that second dipping of ePTFE graft, which was already coated once with paclitaxel, washes off the drug on a surface of the graft and affects the ratio of paclitaxel on the surface to that of the inner space, possibly by diffusion: thus the early burst of drug can be somewhat reduced.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.14
• /
• pp.5741-5745
• /
• 2014

Purpose: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. Materials and Methods: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. Results: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment (p<0.05). Paclitaxel treatment caused cell cycle arrest and apoptosis via downregulating Bcl-2 expression. However, the effect could be abrogated by IGFBP-3 silencing. Conclusions: IGFBP-3 exhibits anti-apoptotic effects on paclitaxel-treated SGC-7901 cells via elevating Bcl-2 expression.

• KSBB Journal
• /
• v.24 no.2
• /
• pp.212-215
• /
• 2009

In this study, the process parameters of liquid-liquid extraction were optimized to obtain a high purity and yield of paclitaxel in a pre-purification step. The optimal solvent ratio (methylene chloride/concentrated methanol extract ratio), extraction times, mixing time, and standing time for liquid-liquid extraction were 0.28 (v/v), 3(times), 30 min, and 40 min, respectively. The polar impurities from the biomass extraction were efficiently removed by liquid-liquid extraction. The complete concentration of liquid-liquid extract by rotary evaporator was reliable enough to obtain a high purity and yield of paclitaxel for subsequent purification steps.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.136-136
• /
• 2002

Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance and apoptosis induced by paclitaxel. In the present study, paclitaxel sensitivity, Raf-1 activity and MAPKs activation were compared in 2 cell lines: parental human breast cancer cells and its drug resistant variant (MCF-7/Adr) cells.(omitted)

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.240.1-240.1
• /
• 2003

The purpose of this study was to investigate the effect of nifedipine (10 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (50 mg/kg) orally coadministered and pretreated in rats. The plasma concentration of paclitaxel in combination with nifedipine was significantly (p<0.05 at 10 mg/kg coadmin., p<0.01 at pretreat.) increased compared to that of control, from 2 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel with nifedipine was significantly (p＜0.05 at 10 mg/kg coadmin., p＜0.01 at pretreat.) higher than that of control (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.4
• /
• pp.1699-1702
• /
• 2014

Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.