Fra-1 and c-Fos N-terminal deletion mutants impair breast tumor cell proliferation by blocking lipid synthesis activation

Tumor cells require high rates of lipid synthesis to support membrane biogenesis for their exacerbated growth. The only two proteins known that activate phospholipid synthesis are Fra-1 and c-Fos, two members of the AP-1 family of transcription factors. These proteins that are overexpressed in human breast malignant tumors increase the rate of phospholipid synthesis at the endoplasmic reticulum through a mechanism independent of their nuclear function. The aim of this study was to inhibit breast tumor cell proliferation by modulating c-Fos and Fra-1 and regulate membrane biogenesis by controlling lipid synthesis rates. The molecular mechanism by which Fra-1 and c-Fos activate phospholipid synthesis was examined. Both proteins physically associate with the rate limiting enzyme CDP-DAG synthase through their N-terminus domain and activate it through their basic domain; neither protein associates to or activates the enzyme phosphatidylinositol synthase as determined through in vitro enzymatic reactions and FRET experiments. The N-terminus domain of both proteins act as negative dominant peptides that physically associate with CDP-DAG synthase but do not activate it. Proliferation of MDA-MB231 and 4T1 cells was impaired in vitro after inducing them to proliferate in the presence of the negative dominant peptides derived from Fra-1 and c-Fos. When tumors generated in Balb/c mice with the breast tumor cell line 4T1 were treated with these negative dominant peptides, a significant reduction in tumor growth was observed. Consequently, these Fra-1 and c-Fos negative dominant peptides can be exploited as a new therapeutic strategy to impair breast tumor cell proliferation.Fil: Racca, Ana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentin

Regulation of antigenic variation in Giardia lamblia

Antigenic variation, a clonal phenotypic variation developed by microorganisms, involves the permanent switching of homologous, antigenically different cell surface molecules. In pathogenic microorganisms, antigenic variation is often described as a mechanism to evade the host immune system and therefore is responsible for the generation of chronic and/or recurrent infections. However, antigenic variation has also been involved in expanding host diversity and differential courses of the diseases. The intestinal protozoan parasite Giardia lamblia undergoes antigenic variation through the continuous exchange of approximately 200 variant-specific surface proteins. Here we review the principal issues regarding the significance of antigenic variation during Giardia infections, the particular features of the variant-specific surface proteins, and the current knowledge on the mechanisms that regulate this process, as well as the relevance of disrupting antigenic variation as a novel approach to design effective antiparasitic vaccines.Fil: Prucca, Cesar German. Universidad Catolica de Córdoba. Facultad de Medicina. Departamento de Química Biologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Rivero, Fernando David. Universidad Catolica de Córdoba. Facultad de Medicina. Departamento de Química Biologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lujan, Hugo Daniel. Universidad Catolica de Córdoba. Facultad de Medicina. Departamento de Química Biologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Adjusting the molecular clock: The importance of circadian rhythms in the development of glioblastomas and its intervention as a therapeutic strategy

Gliomas are solid tumors of the central nervous system (CNS) that originated from differentglial cells. The World Health Organization (WHO) classifies these tumors into four groups (I-IV)with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of braintumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied.Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, lookingfor higher efficiency and lower side effects, but with relatively modest results. The circadian timingsystem temporally organizes the physiology and behavior of most organisms and daily regulatesseveral cellular processes in organs, tissues, and even in individual cells, including tumor cells. Thepotentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.Fil: Wagner, Paula Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentin

The moonlighting protein c-Fos activates lipid synthesis in neurons, an activity that is critical for cellular differentiation and cortical development

Differentiation of neuronal cells is crucial for the development and function of the nervous system. This process involves high rates of membrane expansion, during which the synthesis of membrane lipids must be tightly regulated. In this work, using a variety of molecular and biochemical assays and approaches, including immunofluorescence microscopy and FRET analyses, we demonstrate that the proto-oncogene c-Fos (c-Fos) activates cytoplasmic lipid synthesis in the central nervous system and thereby supports neuronal differentiation. Specifically, in hippocampal primary cultures, blocking c-Fos expression or its activity impairs neuronal differentiation. When examining its subcellular localization, we found that c-Fos co-localizes with endoplasmic reticulum markers and strongly interacts with lipid-synthesizing enzymes, whose activities were markedly increased in vitro in the presence of recombinant c-Fos. Of note, the expression of c-Fos dominant-negative variants capable of blocking its lipid synthesis–activating activity impaired neuronal differentiation. Moreover, using an in utero electroporation model, we observed that neurons with blocked c-Fos expression or lacking its AP-1–independent activity fail to initiate cortical development. These results highlight the importance of c-Fos–mediated activation of lipid synthesis for proper nervous system development.Fil: Rodríguez Berdini, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Ferrero, Gabriel Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigación y Tecnología Química. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación y Tecnología Química; ArgentinaFil: Bustos, Julia Florentyna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Cardozo Gizzi, Andres Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Quiroga, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentin

Combining ZnPc-liposomes and chitosan on a hybrid matrix for enhanced photodynamic therapy

Photodynamic therapy is an alternative treatment for several pathologies, including cancer. This therapy uses a photosensitizer capable of producing reactive oxygen species through irradiation, promoting cellular death. A limitation of photosensitizers is their low solubility in aqueous media. Hence, developing a suitable carrier for photosensitizers for specific applications is a challenge. Cervical cancer is one of the most common cancers in women, and photodynamic therapy could be an attractive alternative therapeutic approach. In this work, we synthesized films composed of chitosan, polyvinylpyrrolidone, and liposomes containing Zn-phthalocyanine. Photophysical characterization of ZnPc incorporated into films was determined by UV–vis and fluorescence. Film properties such as swelling, mechanical properties, and water vapor permeability were performed. Finally, in vitro, photodynamic evaluation of these films was performed on HeLa cells. The results indicate that incorporating Zn-Pc-liposomes into films decreases cell viability by >95 %.Fil: Miretti, Mariana. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Baumgartner, Maria Teresa del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Martinelli, Marisa. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentin

Photodynamic therapy for glioblastoma: A light at the end of the tunnel

Glioblastomas (GBM) are considered one of the most aggressive tumors of the central nervous system. The standard treatment for GBM-diagnosed patients implies surgery, followed by radio and chemotherapy, with a survival of 12 to 15 months after treatment. Photodynamic Therapy (PDT) is an alternative approach to treating several diseases, including tumors. The study of PDT to treat GBM has been gaining attention over the last few years. In this work, we reviewed the cellular and molecular features and current treatment modalities for GBM as well as the most used photosensitizers for GBM-PDT reported in the last five years, such as porphyrins, chlorins, and phthalocyanines, and also their precursors, as in the case of aminolaevulinic acid. Moreover, an analysis of cellular targets, mechanisms mediating the response and resistance to PDT, and clinical application of this strategy for GBM treatment have been discussed.Fil: Miretti, Mariana. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: González Graglia, María Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Suárez, Agustín Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentin

The ubiquitin-activating enzyme (E1) of the early-branching eukaryote Giardia intestinalis shows unusual proteolytic modifications and play important roles during encystation

Giardia intestinalis is considered an early-branching eukaryote and is therefore a valuable model for studying primordial cellular processes. This work reports the characterization of the ubiquitin-activating enzyme (E1) during growth and different stages of trophozoite differentiation into cysts. We found that in Giardia E1 expression (both at mRNA and protein levels) is regulated during encystation. The enzyme is proteolytically processed mainly into two fragments of 68. kDa (N-terminal) and 47. kDa (C-terminal). This phenomenon has not been described for any other E1. In trophozoites, this enzyme localized at spots within the cytoplasm as detected by using polyclonal antibodies against either E1 N- or C-terminal fragments. This pattern changed during encystation into a diffuse localization throughout the cytoplasm of encysting cells. E1 localizes in mature cysts at cytoplasmic spots and in the cyst wall. Our antisense silencing experiments suggested that E1 is an essential gene for parasite viability. On the other hand, E1 over-expression greatly increased the encystation rate, indicating a relationship between E1 and Giardia differentiation. © 2012 Elsevier B.V.Fil: Niño, Carlos A.. Universidad Nacional de Colombia; ColombiaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Chaparro, Jenny. Universidad Nacional de Colombia; Colombia. Universidad de Antioquia; ColombiaFil: Lujan, Hugo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; ArgentinaFil: Wasserman, Moisés. Universidad Nacional de Colombia; Colombi

Current phthalocyanines delivery systems in photodynamic therapy: An updated review

Photodynamic therapy has emerged as an effective therapeutic alternative to treat oncological, cardiovascular, dermatological, infectious, and ophthalmic diseases. Photodynamic therapy combines the action of a photosensitizer with light in the presence of oxygen to generate reactive oxygen species, capable of reacting with cellular components, resulting in injury and, consequently, inducing cellular death. Phthalocyanines are considered good photosensitizers, although most of them are lipophilic, difficulting their administration for clinical use. A strategy to overcome the lack of solubility of phthalocyanines in aqueous media is to incorporate them into different delivery systems. The present review aimed to summarize the current status of the main drug delivery systems used for Zn and Al phthalocyanines and their effect in photodynamic therapy, reported in the last five years. Liposomes, polymeric micelles, polymeric nanoparticles, and goldnanoparticles constituted some of the most used carriers and were discussed in this review. The latest studies reported strongly suggest that the application of nanotechnologies as delivery systems allows an increase in photodynamic therapy efficacy and reduces side-effects associated with the phthalocyanine administration, which represents a hope for cancer treatments.Fil: Miretti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Tempesti, Tomas Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Baumgartner, Maria Teresa del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Zn phthalocyanines loaded into liposomes: Characterization and enhanced performance of photodynamic activity on glioblastoma cells

Photodynamic therapy (PDT) is considered a promising strategy for cancer treatment. PDT utilizes light in combination with a photosensitizer (PS) to induce several phototoxic reactions. Phthalocyanines (Pcs), a second generation of photosensitizers, have been studied in several cancer models. Among these, Pcs, have become of interest for the treatment of glioblastomas which are one of the most common and aggressive forms of tumors of the central nervous system. Due to the lipophilic nature of Pcs and their limited solubility in water, Pcs can be loaded in liposomes. In this work, we characterized liposomes of ZnPc and TAZnPc and their effectiveness to photoinactivate glioblastoma cells, was evaluated. Both Pcs show an increase in their photosensitizing activity when they were administrated in Dipalmitoylphosphatidylcholine-cholesterol liposomes compared to Pcs administrated in dimethylformamide.Fil: Miretti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Tempesti, Tomas Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Baumgartner, Maria Teresa del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Temporal regulation of tumor growth in nocturnal mammals: In vivo studies and chemotherapeutical potential

Tumors of the nervous system including glioblastoma multiforme (GBM) are the most frequent and aggressive form of brain tumors; however, little is known about the impact of the circadian timing system on the formation, growth, and treatment of these tumors. We investigated day/night differences in tumor growth after injection of A530 glioma cells isolated from malignant peripheral nerve sheath tumor (MPNSTs) of NPcis (Trp53+/−; Nf1+/−) mice. Synchronized A530 cell cultures expressing typical glial markers were injected at the beginning of the day or night into the sciatic nerve zone of C57BL/6 mice subject to a 12:12 hours light/dark (LD) cycle or after being released to constant darkness (DD). Tumors generated in animals injected early at night in the LD cycle or in DD showed higher growth rates than in animals injected diurnally. No differences were found when animals were injected at the same time with cultures synchronized 12 hours apart. Similar experiments performed with B16 melanoma cells showed higher tumor growth rates in animals injected at the beginning of the night compared to those injected in the daytime. A higher tumor growth rate than that in controls was observed when mice were injected with knocked-down clock gene Bmal1 cells. Finally, when we compared day/night administration of different doses of the proteasome inhibitor Bortezomib (0.5-1.5 mg/kg) in tumor-bearing animals, we found that low-dose chemotherapy displayed higher efficacy when administered at night. Results suggest the existence of a precise temporal control of tumor growth and of drug efficacy in which the host state and susceptibility are critical.Fil: Wagner, Paula Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Prucca, Cesar German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Velazquez, Fabiola Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Stony Brook University. Stony Brook Cancer Center and the Department of Medicine; Estados UnidosFil: Sosa Alderete, Lucas Gastón. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentin