• KSBB Journal
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• v.15 no.4
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• pp.366-369
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• 2000

The soluble paclitaxel was found in the supernatant of the plant cell cultures of Taxus chinensis, The percentage of soluble paclitaxel depends on paclitaxel concentration in bioreactor. As paclitaxel concentration decreases the percentage of soulbe paclitaxel increases. it is therefore important to develop a new process for the recovery of soluble paclitaxel. The use of hydrophobic resin HP20 gives nearly perfect recovery of paclitaxel in supernatant. The resin was more effective in treatment of th cell and debris free filtrate probably because of the reduced solids content In this case 3 g.l resin and 1 day reaction were enough for recovery the soluble paclitaxel in medium.

• Journal of Life Science
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• v.20 no.4
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• pp.519-527
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• 2010

Paclitaxel is known as a potent inhibitor of microtubule depolymerization. It leads to mitotic arrest and cell death by stabilizing the spindle in various cell types. Here, we investigated the effects of paclitaxel on the proliferation and cell death of rabbit articular chondrocytes. Paclitaxel inhibited proliferation in a dose- and time- dependent manner, determined by MTT assay in rabbit articular chondrocytes. We also established paclitaxel-induced G2/M arrest by fluorescent activated cell sorter (FACS) analysis. Paclitaxel increased expression of cyclin B, p53 and p21, while reducing expression of cdc2 and cdc25C in chondrocytes, as detected by Western blot analysis. Interestingly, paclitaxel showed the mitotic catastrophe that leads to abnormal nucleus division and cell death without DNA fragmentation through activation of caspase. Cell death by mitotic catastrophe in cells treated with paclitaxel was suppressed by inhibiting G1/S arrest with 2 mM thymidine. These results demonstrate that paclitaxel induces cell death via mitotic catastrophe without activation of casepase in rabbit articular chondrocytes.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.241-247
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• 2008

Paclitaxel is a taxane diterpene amide, which was first extracted from the stem bark of the western yew, Taxus brevifolia. This natural product has proven to be useful in the treatment of a variety of human neoplastic disorders, including ovarian cancer, breast and lung cancer. Paclitaxel is a highly hydrophobic drug that is poorly soluble in water. It is mainly given by intravenous administration. Therefore, The pharmaceutical formulation of paclitaxel ($Taxol^{(R)}$; Bristol-Myers Squibb) contains 50% $Cremophor^{(R)}$ EL and 50% dehydrated ethanol. However the ethanol/Cremophor EL vehicle required to solubilize paclitaxel in $Taxol^{(R)}$ has a pharmacological and pharmaceutical problems. To overcome these problems, new formulations for paclitaxel that do not require solubilization by $Cremophor^{(R)}$ EL are currently being developed. Therefore this study utilized a supercritical fluid antisolvent (SAS) process for cremophor-free formulation. To select hydrophilic polymers that require solubilization for paclitaxel, we evaluated polymers and the ratio of paclitaxel/polymers. HP-${\beta}$-CD was used as a hydrophilic polymer in the preparation of the paclitaxel solid dispersion. Although solubility of paclitaxel by polymers was increased, physical stability of solution after paclitaxel/polymer powder soluble in saline was unstable. To overcome this problem, we investigated the use of surfactants. At 1/20/40 of paclitaxel/hydrophilic polymer/ surfactant weight ratio, about 10 mg/mL of paclitaxel can be solubilized in this system. Compared with the solubility of paclitaxel in water ($1\;{\mu}g/mL$), the paclitaxel solid dispersion prepared by SAS process increased the solubility of paclitaxel by near 10,000 folds. The physicochemical properties was also evaluated. The particle size distribution, melting point and amophorization and shape of the powder particles were fully characterized by particle size distribution analyzer, DSC, SEM and XRD. In summary, through the SAS process, uniform nano-scale paclitaxel solid dispersion powders were obtained with excellent results compared with $Taxol^{(R)}$ for the physicochemical properties, solubility and pharmacokinetic behavior.

• KSBB Journal
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• v.25 no.2
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• pp.193-198
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• 2010

Cell cultures of Taxus wallichiana Zucc. were made to enhance the production of anticancer agent paclitaxel. In suspension cultures, the maximum cell growth rate in exponential growth phase was 0.14 $day^{-1}$ which was correlated to 4.96 days of cell doubling time. The production of paclitaxel was non-growth associated. The paclitaxel production was started after the exponential growth phase and increased to declined phase where the maximum concentration was observed. Various elicitors were tested to enhance the production of paclitaxel. The combination of two elicitors of jasmonic acid and cellulase increased the production of paclitaxel 1.8 and 3.1 times compared to paclitaxel production by individual elicitor respectively.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.255-264
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• 1996

Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

• KSBB Journal
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• v.15 no.4
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• pp.398-401
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• 2000

Taxiods inclusive paclitaxel were produced isolated and purified from plant cell cultures of Taxus chinensis in large-scale process. their structures were elucidated by spectroscopic analyses. These compounds were exactly identical as those in previous studies from the other biomasses of Taxus chinensis and also other species. Also the concentrations of these compounds were compared with the concentration of the paclitaxel in various batches of plant cell cultures. As paclitaxel concentration increased at the end of cell cultures. the concentrations of the other paclitaxel derivatives decreased. The profile of these taxoids production can provide information for better understanding of structure-activity relationships and biosynthesis Importantly it can be utilized as an useful parameter for the quality control of paclitaxel production.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.314-320
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• 1999

Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cells in $G_2$-M phase. Because $G_2$ and M are the most radiosensitive phase of the cell cycle, paclitaxel has potential role as a cell-cycle specific radiosensitizer. This study was peformed to see the effects of paclitaxel on the radiation-induced damage of gastric mucosa of the rat. Materials and Methods : The rats were divided into the three groups i.e., paclitaxel alone group, radiation alone group and, a combination of paclitaxel and radiation in combined group. A single intraperitoneal infusion of paclitaxel (10 mg/kg) was done in paclitaxel alone group. In radiation alone group, a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen and, a combination of a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen was given 24 hrs after paclitaxel infusion In combined group of paclitaxel and radiation. The incidence of mitosis and apoptosis as well as histologic changes of the gastric mucosa were evaluated at 6 hrs, 24 hrs, 3 days and 5 days after treatment. Results : The number of the mitosis was not increased by paclitaxel infusion. The incidence of the apoptosis was similar from 6 hrs to 3 days after paclitaxel infusion and was decreased at 5 days. Paclitaxel induced minimal glandular dilatation and cellular atypia of gastric mucosa at 24 hrs and 3 days. In irradiation group, the incidence of apoptosis was $6.0\%$ in 6 hrs and $1.25\%$ in 24 hrs after irradiation and minimal glandular dilatation and cellular atypia were noted throughout the experimental period. The incidence of apoptosis in the combined group of paclitaxel and irradiation ($4.5\%$) was significantly higher than irradiation alone group ($1.25\%$) at 3 days (p<0.05). Conclusion : Paclitaxel had no mitotic on mitotic arrest in gastric mucosa of the rat. Increased number of apoptosis in combined paclitaxel and irradiation group suggested the additive effects of paclitaxel on irradiation.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.469-475
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• 2005

The purpose of this study was to investigate the effect of a cotreatment of bamboo concentrates (Jukcho solution; 0.75, 1.5, and 3.0 mL/kg) with the chemotherapeutic agent paclitaxel on the bioavailability of orally administered paclitaxel (50 mg/kg) in rats. The effect of a pretreatment of bamboo concentrates (1.5 and 3.0 mL/kg for 1.0 h or a consecutive 3 day) was also examined. The paclitaxel plasma concentrations of rats orally administered paclitaxel plus bamboo concentrates (coadministration, 3.0 mL/kg and pretreatment, 1.5 and 3.0 mL/kg) were significantly higher than those of rats treated with paclitaxel alone. Plasma concentrations of paclitaxel in groups pretreated with bamboo concentrates for 3 day were markedly higher than those of a paclitaxel control group at the measured time points. The areas under plasma concentration-time curves (AUCs) of paclitaxel in groups pretreated with bamboo concentrates were elevated and the absolute bioavailability ($AB\%$) and relative bioavailability ($RB\%$) of paclitaxel were also significantly higher than those in the control group. The peak concentration ($C_{max}$), half-life ($t_{1/2}$), and the elimination rate constant ($K_{el}$) of paclitaxel after 3 day of pretreatment with bamboo concentrates were also significantly higher than those in the control, but the time required to reach the maximum plasma concentration ($T_{max}$) of paclitaxel was unaffected by the bamooo concentrates. Western blot analyses demonstrated that the level of CYP3A4 was increased in the livers of rats treated orally with paclitaxel, but this was reversed by pretreating with bamboo concentrates. These results show that bamboo concentrates enhance the bioavailability of orally administered paclitaxel and this effect may be associated with a diminished expression of CYP3A4 in the liver.

• The Korean Journal of Pain
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• v.26 no.2
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• pp.135-141
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• 2013

Background: Although paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration. Methods: Rats were randomly divided into 3 groups: 1) a control group, which received only vehicle; 2) a paclitaxel group, which received paclitaxel; and 3) an EP group, which received EP after paclitaxel administration. Mechanical allodynia was tested before and at 7 and 14 days after final paclitaxel administration. Fourteen days after paclitaxel treatment, DRG apoptosis was determined by activated caspase-3 immunoreactivity (IR). Results: Post-treatment with EP did not significantly affect paclitaxel-induced allodynia, although it tended to slightly reduce sensitivities to mechanical stimuli after paclitaxel administration. After paclitaxel administration, an increase in caspase-3 IR in DRG cells was observed, which was co-localized with NF200-positive myelinated neurons. Post-treatment with EP decreased the paclitaxel-induced caspase-3 IR. Paclitaxel administration or post-treatment with EP did not alter the glial fibrillary acidic protein IRs in DRG cells. Conclusions: Inhibition of apoptosis in DRG neurons by EP may not be critical in paclitaxel-induced mechanical allodynia.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.411.1-411.1
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• 2002

The purpose of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel orally coadministered in rats Paclitaxel is reported to be metabolized by cytochrome p-450(CYP3.A,)in both the liver and epithelial cells of small intestine and also absorption of paclitaxel is inhibited by p-glycoprotein efflux Pump in the intestinal mucosa. This resulted in poor orall bioavailability of paclitaxel. Area under the plasma concentration-time curve (AUC) of paclitaxel in combination with quercetin were significantly (p＜ 0.01) higher than those of control. (omitted)