Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 in a Murine Model

Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) o…

Antigens and Cytokine Genes in Antitumor Vaccines

Studies against cancer, including clinical trials, have shown that a correct activation of the immune system can lead to tumor rejection whereas incorrect signaling results in no positive effects or even anergy. We have worked assuming that two signals, GM-CSF (granulocyte and macrophage colony-stimulating factor) and tumor antigens are necessary to mediate an antitumor effective response. To study which is the ideal temporal sequence for their administration, we have used a murine model of antimelanoma vaccine employing whole B16 tumor cells or their membrane protein antigens (TMPs) in combination with gm-csf transfer before or after the antigen delivery. Our results show that: (i) When gm…

Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.

Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In prevent…

Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2'-deoxyguanosine in advanced epithelial ovarian carcinoma of a Spanish community.

In the present study, we describe the changes of antioxidant enzyme activities and other oxidative stress-related parameters in a mediterranean cohort of women affected with epithelial ovarian carcinoma (EOC). For that purpose, the most representative enzymatic activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the oxidized/reduced glutathione (GSSG/GSH) ratio have been analyzed in tumor tissue biopsies and compared with the normal tissue of the same patient. As oxidation products, the levels of malondialdehyde (MDA) as an indication of lipid peroxidation, and the DNA damaged base 8-oxo-2'-deoxyguanosine (8-oxo-dG) have been also measured. Ad…

Naked DNA delivery to whole pig cardiac tissue by coronary sinus retrograde injection employing non-invasive catheterization.

Background Hydrodynamic injection has demonstrated to be very efficient in the liver of small animals, although this procedure must be translated to the clinical practice in a milder but no less efficient way. The present study evaluates the capacity of non-invasive interventional catheterization as a procedure for naked DNA delivery to the heart in large animals. Methods Two catheters were placed in the coronary sinus: one of them to block blood circulation and the other to retrogradely inject 50 ml of a saline solution of DNA (20 µg/ml) containing the enhanced green fluorescent protein (EGFP) gene, at a flow rate of 5 ml/s. Results The results obtained show that EGFP protein, identified b…

Pig liver gene therapy by noninvasive interventionist catheterism

The efficacy of noninvasive interventionist catheterism in large animals as an alternative to the hydrodynamic procedure, described for small animals, is evaluated. Basically, gene transfer is performed by implantation and fixation of a balloon catheter within the suprahepatic vein of anesthetized pigs, through the femoral vein. The catheter tip is identified by fluoroscopy, injecting a contrast solution that marks large or small hepatic territories. Animals were injected with a 100 ml pTG7101 plasmid solution (40 microg/ml), which contains the human alpha-1 antitrypsin gene, perfused at a rate of 7.5 ml/s and efficacy and toxicity of the procedure were evaluated. The results show: (i) the …

Gubernamentalidad neoliberal y producción de conocimiento en la universidad: genealogía de una configuración subjetiva

This article claims that any questioning of the conditions related to the feasibility of critical research projects needs to be done by taking into account the process of commodification of knowledge that has developed in universities due to the incorporation of the modes of neoliberal governmentality. This is a process which redefines the value and use that we give to produced knowledge as well as the subjectivity of university collectives. The way knowledge is understood and the subjective configurations that promote instrumental ways of relating to knowledge in an individualizing and competitive environment need to be taken into account. Therefore, we consider it politically relevant to …

Cooperando desde el África Subsahariana en aliniha internacional: Redes sur-sur

Proponemos reflexionar sobre la experiencia de Aliniha, una entidad formada por asociaciones de tres países distintos, Mali, Senegal y Burkina Faso. La APFG, que actúa en Gaoua, Burkina Faso, con experiencia en la lucha contra la ablación y por los derechos de las mujeres; NÉBÉDAY que trabaja en Senegal, en la protección del medio ambiente; y CAMIDE, en Mali, con experiencia en microcréditos. Juntas están llevando a cabo un importante trabajo, complementándose en lo que cada entidad tiene más experiencia. Trabajan en regiones castigadas por la pobreza, impulsando una red de grupos de mujeres autogestionadas, basados en la formación, el conocimiento de sus derechos y la capacitación para des…

Entorno social y estrés de rol en el desarrollo del rol laboral temprano : un análisis causal

Neoliberal Governmentality and Knowledge Production in Higher Education: Genealogy of a Subjective Configuration

En este artículo, se parte de la consideración de que cualquier interrogación sobre las condiciones de posibilidad de una investigación crítica debe hacerse teniendo en cuenta el proceso de mercantilización del conocimiento, impulsado por la incorporación de los modos de gubernamentalidad neoliberal en la universidad. Proceso este que redefine el valor y el uso que se le da al conocimiento producido y redefine también las subjetividades de los colectivos universitarios: formas de entender el conocimiento y configuraciones subjetivas que promueven modos instrumentales de relacionarse con el conocimiento en un escenario individualizador y competitivo. Por ello, se considera políticamente rele…