Garcia-de-Jalon, J.A. (José A.)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
6 results
Search Results
Now showing 1 - 6 of 6
- Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.(Nature Publishing Group, 2012) Vilas, A. (Amaia); Cigudosa, J.C. (Juan Cruz); Roman-Gomez, J. (José); San-Jose-Eneriz, E. (Edurne); Blanco-Prieto, M.J. (María José); Garate, L. (Leire); Martinez-Climent, J.A. (José Ángel); Rifon, J. J. (Jose J.); Ribera, J.M. (José María); Miranda, E. (Estibaliz); Martino-Rodriguez, A. (Alba) de; Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Rio, P. (Paula); Segura, V. (Víctor); Calasanz-Abinzano, M.J. (Maria Jose); Aguirre-Ena, X. (Xabier); Abizanda-Sarasa, G. (Gloria); Martin-Subero, J.I. (Jose Ignacio); Moreno, C. (Cristina)Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.
- Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings(Springer Verlag, 2009) Martinez-de-la-Cuesta, A. (Antonio); Sangro, B. (Bruno); Bilbao, J.I. (José I.); Martino-Rodriguez, A. (Alba) de; Garcia-de-Jalon, J.A. (José A.); Luis, E. (Esther) de; Alonso-Burgos, A. (Alberto); Diaz-Dorronsoro, L. (Lourdes)Abstract Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10–30 microspheres (15–30 lm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 lm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.
- Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction(Oxford University Press, 2010) Nasarre, E. (Emilio); Gavira, J.J. (Juan José); Perez-Ilzarbe, M. (Maitane); Macias, A. (Alfonso); Mazo, M. (Manuel); Martinez-Caro, D. (Diego); Garcia-Bolao, I. (Ignacio); Martino-Rodriguez, A. (Alba) de; Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz); Abizanda-Sarasa, G. (Gloria)Although transplantation of skeletal myoblast (SkM) in models of chronic myocardial infarction (MI) induces an improvement in cardiac function, the limited engraftment remains a major limitation. We analyse in a pre-clinical model whether the sequential transplantation of autologous SkM by percutaneous delivery was associated with increased cell engraftment and functional benefit.
- 18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis(SCHATTAUER, 2007) Marti-Climent, J.M. (Josep María); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Gavira, J.J. (Juan José); Richter, J.A. (José Ángel); Barba, J. (Joaquín); Garcia-Velloso, M. J. (María José); Ecay, M. (Margarita); Mazo, M. (Manuel); Garcia-Rodriguez, A. (Alba); Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Abizanda-Sarasa, G. (Gloria)Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.
- A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction(Oxford University Press, 2006) Belzunce, M. (Miriam); Herreros, J. (Jesús); Paramo, J.A. (José Antonio); Gavira, J.J. (Juan José); Orbe, J. (Josune); Perez-Ilzarbe, M. (Maitane); Barba, J. (Joaquín); Rabago, G. (Gregorio); Panizo, A. (Ángel); Martinez-Caro, D. (Diego); Garcia-Rodriguez, A. (Alba); Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Abizanda-Sarasa, G. (Gloria)
- Gantrez AN nanoparticles for ocular delivery of memantine: in vitro release evaluation in albino rabbits(Karger, 2012) Uixera, A. (A.); Perez, S. (S.); Bregante, M.A. (M.A.); Garcia, M.A. (M. A.); Prieto-Azcárate, E. (Elena); Puente, B. (B.); Garcia-de-Jalon, J.A. (José A.); Irache, J.M. (Juan Manuel); Pablo, L. (L.)AIM: To prepare and evaluate the in vitro release of memantine-loaded poly(anhydride) (Gantrez®) nanoparticles (NPs). The clinical safety and retinal toxicity caused by unloaded NPs after sub-Tenon and intravitreal ocular injections were also evaluated. METHODS: Preparation and characterization of this type of NP as well as the in vitro release study are described. Twenty-three healthy New Zealand rabbits were used for clinical and histological assessment after sub-Tenon and intravitreal ocular injections of unloaded NPs. RESULTS: The amount of drug associated with NPs was 55 µg of memantine/mg of NP. The release profile of memantine from this type of NPs was characterized by an initial burst effect, followed by continuous release of the drug for at least 15 days. No relevant complications were found during the clinical follow-up. The histological evaluation suggested that Gantrez NPs are well tolerated after sub-Tenon ocular injection and that signs of inflammation during the first days after intravitreal ocular injections can be considered a normal reaction of the eye's defence mechanism.