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- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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- Carmen Moran, M., et al.
(författare)
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Counter-ion effect on surfactant-DNA gel particles as controlled DNA delivery systems
- 2012
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 8:11, s. 3200-3211
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Tidskriftsartikel (refereegranskat)abstract
- The ability to entrap drugs within vehicles and subsequently release them has led to new treatments for a number of diseases. Based on an associative phase separation and interfacial diffusion approach, we developed a way to prepare DNA gel particles without adding any kind of cross-linker or organic solvent. Among the various agents studied, cationic surfactants offered particularly efficient control for encapsulation and DNA release from these DNA gel particles. The driving force for this strong association is the electrostatic interaction between the two components, as induced by the entropic increase due to the release of the respective counter-ions. However, little is known about the influence of the respective counter-ions on this surfactant-DNA interaction. Here we examined the effect of different counter-ions on the formation and properties of the DNA gel particles by mixing DNA (either single-(ssDNA) or double-stranded (dsDNA)) with the single chain surfactant dodecyltrimethylammonium (DTA). In particular, we used as counter-ions of this surfactant the hydrogen sulfate and trifluoromethane sulfonate anions and the two halides, chloride and bromide. Effects on the morphology of the particles obtained, the encapsulation of DNA and its release, as well as the haemocompatibility of these particles are presented, using counter-ion structure and DNA conformation as controlling parameters. Analysis of the data indicates that the degree of counter-ion dissociation from the surfactant micelles and the polar/hydrophobic character of the counter-ion are important parameters in the final properties of the particles. The stronger interaction with amphiphiles for ssDNA than for dsDNA suggests the important role of hydrophobic interactions in DNA.
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- Carmen Moran, M., et al.
(författare)
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Novel Biocompatible DNA Gel Particles
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:13, s. 10606-10613
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Tidskriftsartikel (refereegranskat)abstract
- Surfactants with the cationic functionality based on an amino acid structure have been used to prepare novel biocompatible devices for the controlled encapsulation and release of DNA. We report here the formation of DNA gel particles mixing DNA (either single- (ssDNA) or double-stranded (dsDNA)) with two different single-chain amino acid-based surfactants: arginine-N-lauroyl amide dihydrochloride (A LA) and N-alpha-lauroyl-arginine-methyl ester hydrochloride (LAM). The degree of DNA entrapment, the swelling/deswelling behavior, and the DNA release kinetics have been studied as a function of both the number of charges in the polar head of the amino acid-based surfactant and the secondary structure of the nucleic acid. Analysis of the data indicates a stronger interaction of ALA with DNA, compared with LAM, mainly at to the double charge carried by the former surfactant compared to the singly charged headgroup of the latter species. The stronger interaction with amphiphiles for ssDNA compared with dsDNA suggests the important role of hydrophobic interactions in DNA. Data on the microstructure of the complexes obtained from small-angle X-ray scattering (SAXS) of the particles strongly suggests a hexagonal packing. It was found that, the shorter the lattice parameter, the stronger the surfactant-DNA in and the slower the DNA release kinetics. Complexation and neutralization of DNA on the DNA gel particles was confirmed by agarose gel electrophoresis measurements.
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| 9. |
- Moran, M. C., et al.
(författare)
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Mixed protein-DNA gel particles for DNA delivery: Role of protein composition and preparation method on biocompatibility
- 2013
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 454:1, s. 192-203
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Tidskriftsartikel (refereegranskat)abstract
- Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Moran et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising long-term blood-contacting medical devices. Safety evaluation with the established cell lines revealed that, in comparison with proteins in solution, the cytotoxicity was reduced when administered in the protein-DNA systems. In comparison with large-sized particles, the cytotoxic responses of small-sized protein-DNA gel particles showed to be strongly dependent of both the protein composition and the cell line being the tumour cell line HeLa more sensitive to the deleterious effects of the mixed protein-based particles. The observed trends in haemolysis and cell viabilities were in agreement with the degree of complexation values obtained for the protein-DNA gel particles prepared by both preparation methods. (c) 2013 Elsevier B.V. All rights reserved.
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