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Madrid, Spain

Soini E.J.O.,ESiOR Oy | Garcia San Andres B.,PharmaMar | Joensuu T.,International Comprehensive Cancer Center Docrates
Annals of Oncology | Year: 2011

Background: To assess the cost-effectiveness of trabectedin compared with end-stage treatment (EST) after failure with anthracycline and/or ifosfamide in metastatic soft tissue sarcoma (mSTS). Design: Analysis was carried out using a probabilistic Markov model with trabectedin → EST and EST arms, three health states (stable disease, progressive disease and death) and a lifetime perspective (3% annual discount rate). Finnish resources (drugs, mSTS, adverse events and travelling) and costs (year 2008) were used. Efficacy was based on an indirect comparison of the STS-201 and European Organisation for Research and Treatment of Cancer trials. QLQ-C30 scale scores were mapped to 15D, Short Form 6D and EuroQol 5D utilities. The outcome measures were the cost-effectiveness acceptability frontier, incremental cost per life year gained (LYG) and quality-adjusted life year (QALY) gained and the expected value of perfect information (EVPI). Results: Trabectedin → EST was associated with 14.0 (95% confidence interval 9.1-19.2) months longer survival, €36 778 higher costs (€32 816 using hospital price for trabectedin) and €31 590 (€28 192) incremental cost per LYG with an EVPI of €3008 (€3188) compared with EST. With a threshold of €50 000 per LYG, trabectedin → EST had 98.5% (98.2%) probability of being cost-effective. The incremental cost per QALY gained with trabectedin → EST was €42 633-47 735 (€37 992-42 819) compared with EST. The results were relatively insensitive to changes. Conclusion: Trabectedin is a potentially cost-effective treatment of mSTS patients. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2008-3-2-07 | Award Amount: 4.98M | Year: 2009

The Project aims at the mining of individual enzymes and metabolic pathways from extremophilic marine organisms and the metagenomes from microbial communities from peculiar marine environments and consequent funnelling the new enzymatic reactions and processes towards the new biotechnological applications. Project builds up on the scientific and technological excellence of individual academic and industrial partners, and beyond that, on application of the state-of-the-art technologies for archiving, molecular screening for the activities (using a unique Surface Plasmon Resonance screening platform), protein structure elucidation, enzyme engineering and directed evolution and establishing new biotechnological processes (biocatalysis, synthesis of fine chemicals, etc.). Marine sampling hotspots to produce the metagenomic resources for their further exploration will cover the whole diversity of marine microbial life at its limits (hypersaline, low and high temperature, high pressure and low water activity conditions, etc.). Individual enzymes interacting with the substrates will be identified, and in case they are new, hyperexpressed and crystallized and their structures will be elucidated. Consequently, the most promising candidates will be scored against the chiral substrates of relevance for biocatalysis and their ability to perform in water-free systems will be evaluated, the directed evolution will be implemented to improve the performance, and specificity of the enzymes. A comprehensive bioinformatic survey throughout the whole tree of cellular life will reveal and suggest the new candidates homologous to the discovered new proteins, from other organisms to be cloned and assayed. The implementation of the set of new enzymes in the biotechnological processes for fine chemical synthesis and drug discovery will be conducted in a strong alliance with competent industrial partners.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.90M | Year: 2013

Marine sponges harbour extremely diverse populations of microbes, and are world record holders for the production of a plethora of bioactive molecules. Previous studies, however, aiming at the growth of sponges or their associated microbes for the production of bioactive compounds to supply biological material for clinical trials, have been largely unsuccessful. BLUEPHARMTRAIN is a multi-disciplinary alliance of 20 academic and industrial partners that will excel in research and training through integration of complementary expertise in cell biology, microbiology, natural product chemistry, genomics & transcriptomics (omics) and socio-economics. We will adopt cutting-edge omics technologies to give a new boost to the more traditional disciplines: microbial isolation, cell culture and natural product chemistry to go beyond the current scientific frontiers. For example, metagenomic and transcriptomic data will be applied to identify the metabolic potential and restrictions of -yet- uncultured microbes and will serve for the design of tailor-made cultivation conditions. In addition, heterologous expression of bioactive gene clusters and enzymes able to perform unusual modifications will serve as an alternative strategy to unlock the bioactive potential of sponges. Thus we aim to develop an extensive technology platform that is applicable for obtaining a wide variety of bioactive compounds from distinct sponges and their microbes. BLUEPHARMTRAIN will provide a complementary set of experimental and conceptual local and network-wide training modules and workshops to 15 young researchers. The recruited fellows will work towards personalized training plans to meet individual needs and interests, generating a critical mass of young researchers in the emerging field of blue biotechnology. The presence of a large consortium of versatile biotechnology, pharmaceutical and consultancy firms ensures a good balance between academic and transferable skills acquired by the fellows.


Bueren-Calabuig J.A.,University of Alcala | Giraudon C.,French Institute of Health and Medical Research | Galmarini C.M.,PharmaMar | Egly J.M.,French Institute of Health and Medical Research | Gago F.,University of Alcala
Nucleic Acids Research | Year: 2011

The difference in melting temperature of a double-stranded (ds) DNA molecule in the absence and presence of bound ligands can provide experimental information about the stabilization brought about by ligand binding. By simulating the dynamic behaviour of a duplex of sequence 5′- d(TAATAACGGATTATT)5′-d(AATAATCCGTTATTA) in 0.1M NaCl aqueous solution at 400K, we have characterized in atomic detail its complete thermal denaturation profile in <200ns. A striking asymmetry was observed on both sides of the central CGG triplet and the strand separation process was shown to be strongly affected by bonding in the minor groove of the prototypical interstrand crosslinker mitomycin C or the monofunctional tetrahydroisoquinolines trabectedin (Yondelis®), Zalypsis® and PM01183®. Progressive helix unzipping was clearly interspersed with some reannealing events, which were most noticeable in the oligonucleotides containing the monoadducts, which maintained an average of 6bp in the central region at the end of the simulations. These significant differences attest to the demonstrated ability of these drugs to stabilize dsDNA, stall replication and transcription forks, and recruit DNA repair proteins. This stabilization, quantified here in terms of undisrupted base pairs, supports the view that these monoadducts can functionally mimic a DNA interstrand crosslink. © 2011 The Author(s). Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.2-02 | Award Amount: 11.97M | Year: 2012

Marine microorganisms form an almost untapped resource of biotechnological potential. However, its use is hindered by the low success rate of isolation of novel microorganisms and often by poor growth efficiency. Hence, the vast majority of marine microorganisms has not been cultivated and is often considered as unculturable. MaCuMBA aims at improving the isolation rate and growth efficiency of marine microorganisms from conventional and extreme habitats, by applying innovative methods, and the use of automated high throughput procedures. The approaches include the co-cultivation of interdependent microorganisms, as well as gradient cultures and other methods mimicking the natural environment, and the exploitation of cell-to-cell communication. Signaling molecules produced by microorganisms may be necessary for stimulating growth of the same or other species, or may prevent their growth. Signaling molecules also represent an interesting and marketable product. MaCuMBA will make use of high throughput platforms such Cocagne, using gel micro-droplet technology, or MicroDish in which many thousands of cultures are grown simultaneously. Various single-cell isolation methods, such as optical tweezers, will aid the isolation of specific target cells. Isolated microorganisms as well as their genomes will be screened for a wide range of bioactive products and other properties of biotechnological interest, such as genetic transformability. Growth efficiency and expression of silent genes of selected strains will be increased also by using the clues obtained from genomic information. MaCuMBA is targeted to SMEs and industry and they make a significant part of the consortium, ensuring that the project focuses on the interests of these partners. Moreover, MaCuMBA has adopted a comprehensive and professional exploitation, dissemination, implementation, and education strategy, ensuring that MaCuMBAs results and products will be directed to end-users and stakeholders.

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