The Experts below are selected from a list of 48897 Experts worldwide ranked by ideXlab platform
Martin E Gleave - One of the best experts on this subject based on the ideXlab platform.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and Paclitaxel in the lncap prostate tumor model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate tumor model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of Paclitaxel and whether combined antisense Bcl-2 ODN and Paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP tumor model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by Paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced Paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM Paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM Paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar Paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP tumors compared with either agent alone. By 15 weeks post castration, tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus Paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and Paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus Paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and Paclitaxel. These findings identify combined antisense Bcl-2 and Paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing Paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer. © 2001 Wiley-Liss, Inc.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and Paclitaxel in the lncap prostate tumor model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate tumor model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of Paclitaxel and whether combined antisense Bcl-2 ODN and Paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP tumor model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by Paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced Paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM Paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM Paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar Paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP tumors compared with either agent alone. By 15 weeks post castration, tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus Paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and Paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus Paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and Paclitaxel. These findings identify combined antisense Bcl-2 and Paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing Paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer.
Joshua W Parks - One of the best experts on this subject based on the ideXlab platform.
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genome sequencing and analysis of the Paclitaxel producing endophytic fungus penicillium aurantiogriseum nrrl 62431
BMC Genomics, 2014Co-Authors: Yanfang Yang, Hainan Zhao, Roberto A Barrero, Baohong Zhang, Guiling Sun, Iain W Wilson, Fuliang Xie, Kevin D Walker, Joshua W ParksAbstract:Paclitaxel (Taxol™) is an important anticancer drug with a unique mode of action. The biosynthesis of Paclitaxel had been considered restricted to the Taxus species until it was discovered in Taxomyces andreanae, an endophytic fungus of T. brevifolia. Subsequently, Paclitaxel was found in hazel (Corylus avellana L.) and in several other endophytic fungi. The distribution of Paclitaxel in plants and endophytic fungi and the reported sequence homology of key genes in Paclitaxel biosynthesis between plant and fungi species raises the question about whether the origin of this pathway in these two physically associated groups could have been facilitated by horizontal gene transfer. The ability of the endophytic fungus of hazel Penicillium aurantiogriseum NRRL 62431 to independently synthesize Paclitaxel was established by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance. The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene candidates that may be involved in Paclitaxel biosynthesis were identified by comparison with the 13 known Paclitaxel biosynthetic genes in Taxus. We found that Paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431 have evolved independently and that horizontal gene transfer between this endophytic fungus and its plant host is unlikely. Our findings shed new light on how Paclitaxel-producing endophytic fungi synthesize Paclitaxel, and will facilitate metabolic engineering for the industrial production of Paclitaxel from fungi.
Jin-hyun Kim - One of the best experts on this subject based on the ideXlab platform.
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influence of crude extract purity and pure Paclitaxel content on fractional precipitation for purification of Paclitaxel
Separation and Purification Technology, 2013Co-Authors: Jiyeon Lee, Jin-hyun KimAbstract:Abstract Fractional precipitation is a simple method for pre-purifying Paclitaxel extracted from plant cell cultures. However, the fractional precipitation process has been inherently problematic due to the lengthy precipitation time (∼3 days) that is required. In this study, we evaluated the effect of crude extract purity and pure Paclitaxel content on the behavior (purity, yield, fractional precipitation time, precipitate shape and size) of fractional precipitation to improve Paclitaxel purification efficiency. As the crude extract purity and pure Paclitaxel content were increased, the yield and purity of Paclitaxel were increased and the precipitation time and precipitate size were decreased. Furthermore, we found that the maximum amount of pure Paclitaxel content for fractional precipitation was 0.45–0.51% (w/v) regardless of the purity of crude extract.
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Evaluation of the effect of crude extract purity and pure Paclitaxel content on the increased surface area fractional precipitation process for the purification of Paclitaxel
Process Biochemistry, 2012Co-Authors: Jiyeon Lee, Jin-hyun KimAbstract:Abstract This study evaluated the effect of crude extract purity and pure Paclitaxel content on the behavior in terms of purity, yield, fractional precipitation time, and precipitate shape and size of fractional precipitation in the increased surface area fractional precipitation process for the purification of Paclitaxel. With increased pure Paclitaxel content and crude extract purity, the purity and yield of Paclitaxel were improved and the fractional precipitation time was reduced. Regardless of changes in crude extract purity and pure Paclitaxel content, it was possible to obtain a small Paclitaxel precipitate size by hindering the growth of precipitate particles using an ion exchange resin to increase the surface area. In addition, according to the type of surface-area increasing substance used, precipitate size and shape differed because of a differing affinity for the Paclitaxel particles. The lower the crude extract purity and pure Paclitaxel content, the higher the yield and the improvement in purity in the process of increased surface area fractional precipitation, with a greater effect on the decrease in Paclitaxel particle size.
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effect of ph on fractional precipitation for pre purification of Paclitaxel from plant cell cultures
Korean Journal of Chemical Engineering, 2009Co-Authors: Seulgi Kim, Jin-hyun KimAbstract:Fractional precipitation is a simple, efficient method for pre-purifying Paclitaxel from plant cell cultures of Taxus chinensis. The pH, a key process variable in fractional precipitation, was optimized in terms of the yield and purity of Paclitaxel with a fixed methanol concentration in water (61.5%, v/v), Paclitaxel content in the crude extract (0.5%, w/v), and storage time (14 hr). The maximum yield (~99%) and purity (~84.4%) of Paclitaxel were obtained at pH 8.0 with potassium phosphate buffer. The precipitate from fractional precipitation was an amorphous state Paclitaxel by analysis of XRD and SEM. Also, the particle size distribution of dried precipitate was a range of approximately 119-411 µm. The use of fractional precipitation in the pre-purification process allowed for rapid and efficient separation of Paclitaxel from interfering compounds, and dramatically increased the yield and purity of the crude Paclitaxel for subsequent purification steps.
Xiaoyan Chen - One of the best experts on this subject based on the ideXlab platform.
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bioequivalence of Paclitaxel protein bound particles in patients with breast cancer determining total and unbound Paclitaxel in plasma by rapid equilibrium dialysis and liquid chromatography tandem mass spectrometry
Drug Design Development and Therapy, 2019Co-Authors: Junling Li, Yaping Ding, Wei Li, Dafang Zhong, Xiaoyan ChenAbstract:: Background and objective: Paclitaxel protein-bound particles for injectable suspension (nab-Paclitaxel) showed many advantages in safety, effectiveness, and convenience. Different from conventional formulations, the bioequivalence evaluation of nab-Paclitaxel formulations requires to determine the total amount of Paclitaxel in plasma and the unbound Paclitaxel to reflect their in vivo disposition. This study aimed to develop an analytical method to quantify the total and unbound Paclitaxel in plasma and evaluate the bioequivalence of two formulations of nab-Paclitaxel in patients with breast cancer. Materials and methods: An open-label, randomized, two-period crossover study was completed among 24 Chinese patients with breast cancer. The patients were randomized to receive either the test formulation on cycle 1 day 1 and after 21 days in cycle 2 day 1 by the reference formulation (Abraxane®), or vice versa. Rapid equilibrium dialysis was adopted to separate the unbound Paclitaxel in human plasma. Total and unbound Paclitaxel concentrations were measured by the validated liquid chromatography-tandem mass spectrometry methods over the range of 5.00-15,000 and 0.200-200 ng/mL, respectively. The bioequivalence of the test formulation to the reference formulation was assessed using the Food and Drug Administration and European Medicines Agency guidelines. Results: All the 90% confidence intervals (CIs) of the geometric mean ratios fell within the predetermined acceptance range. The 90% CIs for the area under the concentration-time curve (AUC) from 0 h to 72 h (AUC0-t), AUC from time zero to infinity (AUC0-∞), and peak plasma concentrations (Cmax) for total Paclitaxel were 92.03%-98.05%, 91.98%-99.37%, and 91.37%-99.36%, respectively. The 90% CIs of AUC0-t, AUC0-∞, and Cmax for unbound Paclitaxel were 86.77%-97.88%, 86.81%-97.88%, and 87.70%-98.86%, respectively. Conclusion: Bioequivalence between the two nab-Paclitaxel formulations was confirmed for total and unbound Paclitaxel at the studied dose regimen.
Guiling Sun - One of the best experts on this subject based on the ideXlab platform.
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genome sequencing and analysis of the Paclitaxel producing endophytic fungus penicillium aurantiogriseum nrrl 62431
BMC Genomics, 2014Co-Authors: Yanfang Yang, Hainan Zhao, Roberto A Barrero, Baohong Zhang, Guiling Sun, Iain W Wilson, Fuliang Xie, Kevin D Walker, Joshua W ParksAbstract:Paclitaxel (Taxol™) is an important anticancer drug with a unique mode of action. The biosynthesis of Paclitaxel had been considered restricted to the Taxus species until it was discovered in Taxomyces andreanae, an endophytic fungus of T. brevifolia. Subsequently, Paclitaxel was found in hazel (Corylus avellana L.) and in several other endophytic fungi. The distribution of Paclitaxel in plants and endophytic fungi and the reported sequence homology of key genes in Paclitaxel biosynthesis between plant and fungi species raises the question about whether the origin of this pathway in these two physically associated groups could have been facilitated by horizontal gene transfer. The ability of the endophytic fungus of hazel Penicillium aurantiogriseum NRRL 62431 to independently synthesize Paclitaxel was established by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance. The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene candidates that may be involved in Paclitaxel biosynthesis were identified by comparison with the 13 known Paclitaxel biosynthetic genes in Taxus. We found that Paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431 have evolved independently and that horizontal gene transfer between this endophytic fungus and its plant host is unlikely. Our findings shed new light on how Paclitaxel-producing endophytic fungi synthesize Paclitaxel, and will facilitate metabolic engineering for the industrial production of Paclitaxel from fungi.
