			Home About us Contact

Drug Paclitaxel (drug + paclitaxel)

Distribution by Scientific Domains

Life Sciences	80%

Selected Abstracts

Understanding cisplatin resistance using cellular models

IUBMB LIFE, Issue 11 2007
Britta Stordal
Abstract Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 ,g/ml. Cisplatin resistance in these cells correlated with increases in the antioxidant glutathione, yet treatment with buthionine sulphoximine, an inhibitor of glutathione synthesis, had no effect on resistance, suggesting that the increase in glutathione was not directly involved in cisplatin resistance. Two models were developed from H69 SCLC cells, H69-CP and H69CIS200 using 100 ng/ml or 200 ng/ml cisplatin respectively. Both cell models were 2-4 fold resistant to cisplatin, and have decreased expression of p21 which may increase the cell's ability to progress through the cell cycle in the presence of DNA damage. Both the H69-CP and H69CIS200 cells showed no decrease in cellular cisplatin accumulation. However, the H69-CP cells have increased levels of cellular glutathione and are cross resistant to radiation whereas the H69CIS200 cells have neither of these changes. This suggests that increases in glutathione may contribute to cross-resistance to other drugs and radiation, but not directly to cisplatin resistance. There are multiple resistance mechanisms induced by cisplatin treatment, even in the same cell type. How then should cisplatin-resistant cancers be treated? Cisplatin-resistant cell lines are often more sensitive to another chemotherapeutic drug paclitaxel (H69CIS200), or are able to be sensitized to cisplatin with paclitaxel pre-treatment (H69-CP). The understanding of this sensitization by paclitaxel using cell models of cisplatin resistance will lead to improvements in the clinical treatment of cisplatin resistant tumours. IUBMB Life, 59: 696-699, 2007 [source]

A Novel Micellar PEGylated Hyperbranched Polyester as a Prospective Drug Delivery System for Paclitaxel

MACROMOLECULAR BIOSCIENCE, Issue 9 2008
Christina Kontoyianni
Abstract A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg,·,mL,1, respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg,·,mL,1 concentration while LD50 was 3.5 mg,·,mL,1. Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [source]

Microfluidic Tissue Model for Live Cell Screening

BIOTECHNOLOGY PROGRESS, Issue 4 2007
Philip J. Lee
We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue-like culture and high-throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 ,m wide cell culture pocket, an artificial endothelial barrier with 2 ,m pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over 1 week in a solid tumor-like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for "flow cell" based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow-through biochemistry. Each fluidically independent tissue unit contained ,500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti-cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384-well dish for up to 5 days of continuous drug exposure. [source]

In this issue: Biotechnology Journal 12/2009

BIOTECHNOLOGY JOURNAL, Issue 12 2009
Article first published online: 14 DEC 200
Genome-scale in silico modeling Milne et al., Biotechnol. J. 2009, 4, 1653,1670 Driven by advancements in high-throughput biological technologies and the growing number of sequenced genomes, the construction of in silico models at the genome scale has provided powerful tools to investigate a vast array of biological systems and applications. Nathan Price and colleagues review comprehensively the use of such models in industrial and medical biotechnology, including biofuel generation, food production, and drug development. As such, genome-scale models can provide a basis for rational genome-scale engineering and synthetic biology. Genome-scale in silico models promise to extend their application and analysis scope to become a transformative tool in biotechnology. From metagenomics to metaproteomics Tuffin et al., Biotechnol. J. 2009, 4, 1671,1683 Metagenomics emerged in the late 1990s as a tool for accessing and studying the collective microbial genetic material in the environment and has been widely predicted to reach new dimensions of the protein sequence space. A decade on, researchers from South Africa see that while several novel enzyme activities and protein structures have been identified the greatest advancement has been made in the isolation of novel protein sequences, some of which have no close relatives, form deeply branched lineages and even represent novel families. However, there is much room for improvement in the methods employed that need to be addressed in order to access novel biocatalytic activities. Recombinant secondary metabolites Schäfer et al., Biotechnol. J. 2009, 4, 1684,1703 Plants produce a high diversity of natural products or secondary metabolites which have interesting biological properties and quite a number are of medicinal importance. Their functions range from the protection against herbivores and/or microbial pathogens to defend against abiotic stress, e.g. UV-B exposure. Because the production of valuable natural products, such as the anticancer drugs paclitaxel, vinblastine or camptothecin in plants is a costly process, biotechnological alternatives to produce these alkaloids more economically become more and more important. This review provides an overview of the state of art to produce alkaloids in recombinant microorganisms, such as bacteria or yeast. In a longterm perspective, it will probably be possible to generate gene cassettes for complete pathways, which could then be used for the production of valuable natural products in bioreactors or for metabolic engineering of crop plants. [source]

Medicinally important secondary metabolites in recombinant microorganisms or plants: Progress in alkaloid biosynthesis

BIOTECHNOLOGY JOURNAL, Issue 12 2009
Holger Schäfer
Abstract Plants produce a high diversity of natural products or secondary metabolites which are important for the communication of plants with other organisms. A prominent function is the protection against herbivores and/or microbial pathogens. Some natural products are also involved in defence against abiotic stress, e.g. UV-B exposure. Many of the secondary metabolites have interesting biological properties and quite a number are of medicinal importance. Because the production of the valuable natural products, such as the anticancer drugs paclitaxel, vinblastine or camptothecin in plants is a costly process, biotechnological alternatives to produce these alkaloids more economically become increasingly important. This review provides an overview of the state of art to produce alkaloids in recombinant microorganisms, such as bacteria or yeast. Some progress has been made in metabolic engineering usually employing a single recombinant alkaloid gene. More importantly, for benzylisoquinoline, monoterpene indole and diterpene alkaloids (taxanes) as well as some terpenoids and phenolics the proof of concept for production of complex alkaloids in recombinant Escherichia coli and yeast has already been achieved. In a long-term perspective, it will probably be possible to generate gene cassettes for complete pathways, which could then be used for production of valuable natural products in bioreactors or for metabolic engineering of crop plants. This will improve their resistance against herbivores and/or microbial pathogens. [source]