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Papers by Jaheli Fuenmayor

En alergias y algunas formas de autoinmunidad es común la predominancia de la respuesta TH2 y la ... more En alergias y algunas formas de autoinmunidad es común la predominancia de la respuesta TH2 y la producción de IgE alérgeno especifica o autoreactiva. Un blanco terapéutico atractivo en estos casos es la inhibición de la producción de la forma soluble de la molécula CD23 (sCD23), un factor de proliferación de linfocitos B que coopera en el cambio de clase a IgE. Una proteína de fusión CTLA4Fce podría alcanzar este objetivo. En este trabajo se purificó y caracterizó una proteína de fusión CTLA4Fcε. También se evaluó in vitro su efecto sobre la producción de sCD23. Mediante western-blot se determinó que CTLA4Fcε es un homodímero de subunidades ecCTLA4-(Gly)5-Cε2-Cε3-Cε4 (condiciones reductoras 80kDa y no reductoras 160kDa). Mediante citometría de flujo y utilizando anticuerpos fluoromarcados bloqueantes se confirmó la unión de CTLA4Fcε a los receptores FcεRI en células CHO-3D10, y CD23, CD80 y CD86 en células RPMI‐8866. Mediante ELISA se estimó la concentración de sCD23 en sobrenadant...

$Research paper thumbnail of Fibrinolytic activity in the IgG fraction of a patient with antiphospholipid syndrome$

Journal of Thrombosis and Haemostasis

Revista Venezolana de Oncologia

Artículo de revisión 236 Rev Venez Oncol 2013;25(4):236-254 RESUMEN Los anticuerpos terapéuticos ... more Artículo de revisión 236 Rev Venez Oncol 2013;25(4):236-254 RESUMEN Los anticuerpos terapéuticos representan uno de los grupos más importantes de nuevos medicamentos para el tratamiento del cáncer. Gracias a los resultados alentadores observados en la clínica y a su relativa baja toxicidad, los anticuerpos se han convertido en el segmento de mayor crecimiento de las grandes empresas farmacéuticas. Sus propiedades terapéuticas, así como también sus limitaciones, son permanentemente evaluadas en ensayos clínicos alrededor del mundo. Esta dinámica acelerada de desarrollo y evaluación va en paralelo con los elevados costos de estos reactivos tanto para el paciente como para los sistemas de salud pública. Esta revisión tiene por finalidad organizar y actualizar la información generada en el ámbito de la terapia de tumores sólidos con anticuerpos terapéuticos y servir como herramienta crítica de consulta y documentación para clínicos e investigadores en ejercicio y en formación.

Veterinary Microbiology, 2002

Gastric Helicobacter species are widespread and have been reported in wild and domestic mammals o... more Gastric Helicobacter species are widespread and have been reported in wild and domestic mammals of different dietary habits such as humans, dogs, cats, macaques, mice, cheetahs, ferrets, swine and cattle. All have been associated with gastric pathologies. Recently, gastric Helicobacter species were shown to be widespread in cattle and swine in Europe, and there is a report of Helicobacter pylori in sheep in Italy. However, there are no reports of Helicobacter infection in the goat, another important domestic animal of human consumption. The aim of our study was to assess whether Helicobacter abomasal infection was common in goats slaughtered for human consumption. Infection was detected through PCR analysis of DNA extracted from gastric biopsies, using genus-and species-specific primers. Bovine and porcine gastric samples were also analyzed as positive controls. None of the 70 goats were positive for Helicobacter spp.; however, Candidatus Helicobacter bovis and Candidatus Helicobacter suis were detected in 85% of the bovine and 45% of the porcine samples, respectively. We discuss the possibility that goats may exhibit natural resistance to abomasal infection by Helicobacter spp. #

The Journal of Eukaryotic Microbiology, 1998

We have identified and partially purified two DNA polymerase activities from purified Trjpanosorn... more We have identified and partially purified two DNA polymerase activities from purified Trjpanosorna brucei mitochondrial extracts. The DNA polymerase activity eluted from the single-stranded DNA agarose column at 0.15 M KCI (polymerase M1) was significantly inhibited by salt concentrations greater than 100 mM. utilized Mg" in preference to Mn2+ as a cofactor on deoxytibonucleotide templates with deoxyribose primers, and in the presence of Mn" favored a tibonucleotide template with a deoxyribose primer.

Blood Coagulation & Fibrinolysis, 2014

Cancers, 2011

The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation p... more The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

Molecular Cancer Therapeutics, 2010

Treatment of human epidermal growth factor receptor 2 (HER2/neu)-expressing breast cancer patient... more Treatment of human epidermal growth factor receptor 2 (HER2/neu)-expressing breast cancer patients with a monoclonal antibody (mAb) directed against HER2/neu improves the outcome of chemotherapy. In cases in which remission is observed, antibody-dependent cell-mediated cytotoxicity (ADCC) seems to be one of the main mechanisms of anti-HER2/neu mAb action, implicating Fcγ receptors (FcγRs) in this tumoricidal activity. In vitro and in vivo studies have revealed that anti-HER2/neu-mediated ADCC is mainly accomplished by polymorphonuclear granulocytes (PMN). C5a, a cleavage product of the complement component C5, modulates FcγR expression via upregulation of activating and downregulation of inhibitory FcγRs. C5a also recruits PMNs to sites of inflammation and increases PMN survival. To enhance the recruitment and activation of C5a receptor-bearing cells into the tumor microenvironment, we developed antibody fusion proteins composed of a human IgG3 anti-HER2/neu antibody genetically fused to C5a [anti-HER2/neu IgG3-(C5a)] or to its derivative, C5a desArg [anti-HER2/neu IgG3-(C5a desArg )]. Both fusion proteins were expressed, properly assembled, and secreted by murine myeloma cells, and displayed chemotactic activity on human PMN. Under comparable conditions, anti-HER2/neu IgG3-(C5a desArg ) increased the survival of PMN more efficiently than anti-HER2/neu IgG3-(C5a) or C5a desArg . Surprisingly, incubation of the fusion proteins with breast cancer cells that overexpress HER2/neu (SK-BR-3) induced cell death at a dose at which the anti-HER2/neu IgG3 antibody was innocuous. In the presence of human peripheral blood leukocytes as effector cells, both fusion proteins induced tumor cell death more efficiently than anti-HER2/neu IgG3. These data suggest that anti-HER2/neu IgG3-(C5a) and anti-HER2/neu IgG3-(C5a desArg ) fusion proteins possess novel properties that could be useful in cancer immunotherapy. Mol Cancer Ther; 9(8); 2175-85.

Pesquisa …, 2000

This work had as objective the evaluation of the leucogram in Holstein heifers and calves experim... more This work had as objective the evaluation of the leucogram in Holstein heifers and calves experimentally infected with a Venezuelan strain of Trypanosoma vivax. The dates were analysed by the Mann-Whitney non-parametric test. The total means comparation of ...

Research papers by Jaheli Fuenmayor

Immunoglobulin (Ig)E-mediated allergy and certain autoimmune diseases are characterized by the pr... more Immunoglobulin (Ig)E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T-helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule CTLA-4 with a fragment of the IgE H-chain constant region. In SDS-PAGE/inmunoblot analyses, CTLA4Fcε appeared as a 70-kDa polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcε binds to IgE receptors FcεRI and FcεRII/CD23, as well as to CTLA-4 counter-receptors CD80 and CD86. Binding of CTLA4Fcε to FcεRII/CD23 appeared stronger than IgE's. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcε to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23-specific ELISA, CTLA4Fcε – but not IgE – induced a concentration-dependent reduction of sCD23 in culture supernatants of RPMI-8866 cells. Our results suggest that the simultaneous binding of CTLA4Fcɛ to CD23-CD80/CD86 may cause the formation of multi-molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, thus blocking sCD23 generation. CTLA4Fcε caused a concentration-dependent reduction of the lymphocyte proliferation in human PBMC samples stimulated in vitro with Con A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4Fcɛ has immunomodulatory properties on human Th2 responses.