Benavides, C. (Carolina)

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2009 - 200912010 - 20133

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    Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer
    (Mary Ann Liebert, 2012) Garcia-Aragoncillo, E. (Eva); Quetglas, J.I. (José Ignacio); Ortiz-de-Solorzano, C. (Carlos); Hervas-Stubbs, S. (Sandra); Prieto, J. (Jesús); Bortolanza, S. (Sergia); Hernandez-Alcoceba, R. (Rubén); Benavides, C. (Carolina); Buñuales, M. (María); Raquel
    Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors for the delivery of therapeutic genes, with the aim of extending the antitumor effect beyond direct cytolysis. Transgene expression using these vectors is usually intense but short-lived, and repeated administrations are hampered by the rapid appearance of neutralizing antibodies (NAbs). We have studied the performance of monocytes as cell carriers to improve transgene expression in cancer models established in athymic mice and immunocompetent Syrian hamsters. Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were loaded with replication-competent adenovirus-expressing luciferase. Intravenous administration of these cells caused a modest increase in transgene expression in tumor xenografts, but this effect was virtually lost in hamsters. In contrast, intratumoral administration of HM-1 cells allowed repeated cycles of expression and achieved partial protection from NAbs in preimmunized hamsters bearing pancreatic tumors. To explore the therapeutic potential of this approach, HM-1 cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant antitumor effect in the hamster model, and transgene expression was detected following each administration, in contrast with the rapid neutralization of the free virus. We propose monocytes as carriers for multiple intratumoral administrations of armed OAVs.
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    Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy
    (BioMed Central, 2009) González-Aseguinolaza, G. (Gloria); Zabala, M. (Maider); Ortiz-de-Solorzano, C. (Carlos); Alzuguren, P. (Pilar); Crettaz, J. (Julien); Kramer, M.G. (María Gabriela); Prieto, J. (Jesús); Hernandez-Alcoceba, R. (Rubén); Benavides, C. (Carolina); Gonzalez-Aparicio, M. (Manuela)
    BACKGROUND: Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies. RESULTS: A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival. CONCLUSION: We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.
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    Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia
    (Elsevier, 2013) Blanco-Prieto, M.J. (María José); Ortiz-de-Solorzano, C. (Carlos); Grama, C.R. (Charitra N.); Tamayo, E. (Esther); Ravi-Kumar, M.N.V. (M.N.V.); Benavides, C. (Carolina); Prosper-Cardoso, F. (Felipe); Formiga, F.R. (Fabio R.); Simon-Yarza, T. (Teresa); Lana, H. (Hugo)
    Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI.
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    New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction
    (Public Library of Science, 2012) Ortiz-de-Solorzano, C. (Carlos); Iglesias-García, O. (Olalla); Corbacho, D. (David); Albiasu, E. (Edurne); Castaño, S. (Sara); Muñoz-Barrutia, A. (Arrate); Benavides, C. (Carolina); Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz)
    In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction.