Cobomarsen, an oligonucleotide inhibitor of miR-155, slows DLBCL tumor cell growth in vitro and in vivo

MicroRNA-155, is an oncogenic miRNA, highly expressed in B-cell malignancies, particularly in the non-Germinal Center B-cell or activated B-cell subtype of Diffuse Large B-cell Lymphoma (non-GCB/ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL

Functional and Molecular Effects of Arginine Butyrate and Prednisone on Muscle and Heart in the mdx Mouse Model of Duchenne Muscular Dystrophy

The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD) is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin.In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated) mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy.These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity

En el país de nomeacuerdo : Archivos y memorias del genocidio del Estado argentino sobre los pueblos originarios, 1870-1950

Esta publicación presenta siete investigaciones sobre los procesos de sometimiento e incorporación de los pueblos originarios de las regiones patagónica, pampeana y chaqueña por parte del Estado argentino. Los autores discuten sobre conceptos centrales como los de genocidio, terrorismo y violencia de Estado. No obstante, abordan al mismo tiempo la participación de la sociedad civil en la concentración, la deportación y la distribución de indígenas, así como la acción de los mismos pueblos originarios en dichos procesos. En este último sentido, el carácter etnográfico de las investigaciones posibilita la recuperación de la memoria social silenciada en las narrativas nacionalistas y da entidad individual al proceso histórico

Challenges in drug development for muscle disease: a stakeholders' meeting

Current treatment benefits for patients with muscle disease are limited, but progress in legislative and scientific initiatives have set the stage for the development of new therapies. The MD-CARE Act (Public Law 107-84), which allocates federal resources to muscular dystrophy, was approved by Congress and signed into law by the President of the United States in 2001. This has shifted the emphasis toward translational research. To facilitate a push toward therapy for muscle disorders, the Muscular Dystrophy Association (MDA) sponsored a meeting with representatives from industry, the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and other government agencies and academia. Each contributed in different ways. The FDA helped define the necessary data to support investigational new drug (IND) applications including the design of proof-of-principle studies, outcome measures for clinical trials, and the pathway for developing surrogate measures for fast-tracking promising new drugs. The NIH, other government agencies, and the MDA described potential funding sources for translational research. Industry delineated a complementary role with academia, and academic investigators elucidated the current strengths and weaknesses of available clinical endpoints. The meeting provided a format for communication for diverse disciplines that usually have no common meeting ground, helping to lay the foundation for bringing products to market in a timely fashion

En el país de nomeacuerdo

Esta publicación presenta siete investigaciones sobre los procesos de sometimiento e incorporación de los pueblos originarios de las regiones patagónica, pampeana y chaqueña por parte del Estado argentino. Los autores discuten sobre conceptos centrales como los de genocidio, terrorismo y violencia de Estado. No obstante, abordan al mismo tiempo la participación de la sociedad civil en la concentración, la deportación y la distribución de indígenas, así como la acción de los mismos pueblos originarios en dichos procesos. En este último sentido, el carácter etnográfico de las investigaciones posibilita la recuperación de la memoria social silenciada en las narrativas nacionalistas y da entidad individual al proceso histórico.This publication presents seven investigations on the processes of submission and incorporation of the original peoples of the Patagonian, Pampa and Chaco regions by the Argentine State. The authors discuss central concepts such as genocide, terrorism and state violence. However, at the same time, they address the participation of civil society in the concentration, deportation and distribution of indigenous peoples, as well as the action of the indigenous peoples themselves in those processes. In this sense, the ethnographic nature of the investigations enables the recovery of social memory silenced in nationalist narratives and gives individual status to the historical process.Esta publicación presenta siete investigaciones sobre los procesos de sometimiento e incorporación de los pueblos originarios de las regiones patagónica, pampeana y chaqueña por parte del Estado argentino. Los autores discuten sobre conceptos centrales como los de genocidio, terrorismo y violencia de Estado. No obstante, abordan al mismo tiempo la participación de la sociedad civil en la concentración, la deportación y la distribución de indígenas, así como la agencia de los mismos pueblos originarios en dichos procesos. En este último sentido, el carácter etnográfico de las investigaciones posibilita la recuperación de la memoria social silenciada en las narrativas nacionalistas y da entidad individual al proceso histórico

Reflexiones de los autores y la editora sobre el debate

Liliana Tamagno Quiero comenzar esta segunda etapa del debate destacando la necesidad de historizar respecto del objeto de nuestra reflexión, al mismo tiempo que historizar respecto de su tratamiento desde las ciencias sociales. Esta necesidad, que aparece señalada en algunas de las ponencias, se trasforma en un ejercicio insoslayable de toda investigación científica toda vez que reconocemos que el conocimiento es acumulativo y que todo nuevo conocimiento debe contextualizarse en el “estado d..