Melatonin and vitamin D-3 increase TGF-Beta 1 release and induce growth inhibition in breast cancer cell cultures

Background. Evidence has accumulated that 1,25- dihydroxyvitamin D3 [1,25-(OH)2D3] is involved in the regulation of the proliferation of breast tumor cells. For complete tumor suppression high hypercalcemic doses of 1,25-(OH)2D3 are needed. The aim of this study was to assess the effect of combined treatment of 1,25- (OH)2D3 at low doses and melatonin (MEL) on the proliferation of estrogen-responsive rat breast cancer cell line RM4. Materials and methods. RM4 cell proliferation was assessed by [3H]thymidine uptake. The presence of TGF-beta 1 in serum-free conditioned medium was determined by inhibition antibody binding assay. Results. In 17-beta E cultured RM4 cells both MEL and 1,25-(OH)2D3 alone and in combination significantly reduced [3H]thymidine incorporation in a doserelated fashion. MEL by itself was ineffective in inhibiting the FCS-cultured RM4 cells, while 1,25-(OH)2D3 strongly inhibited [3H]thymidine incorporation. Meanwhile, MEL increased the sensitivity of the FCS cultured RM4 cells to 1,25-(OH)2D3 in the combined regimen, from 20- to 100-fold. MEL significantly enhanced the TGF-beta1 secretion from RM4 cells and vitamin D3 increased the TGF-beta1 secretion in a dose dependent manner, from 2- to 7-fold. Moreover, a further enhancement of the TGF-beta1 release was obtained with the combined treatment, but only for low 1,25-(OH)2D3 concentrations. The addition of monoclonal anti-TGF-beta1 antibody to the medium of RM4 cells exposed to vitamin D3 alone or in combination with MEL increased the [3H]-thymidine uptake compared to the correspondent cells cultured without antibody.Our data point to a potential benefit of combination therapy with 1,25-(OH)2D3 and MEL in the treatment of breast cancer and suggest that the growth inhibition could be related, at least in part, to the enhanced TGF-beta-1 secretion

Usefulness of the identification of antibodies in peripheral neuropathies, neuronopathies and ganglionopathies: review

Introducción: En los últimos anos ˜ la identificación de anticuerpos y gammapatías monoclonales ha permitido comprender la fisiopatología y favorecer el diagnóstico y tratamiento de una multiplicidad de neuropatías inmunomediadas. Objetivo: Describir los anticuerpos de mayor relevancia clínica en las neuropatías, ganglionopatías y neuronopatías inmunomediadas caracterizando en cada caso su valor fisiopatológico o diagnóstico, así como la sensibilidad y especificidad de los métodos utilizados para su determinación. Desarrollo: Se analizarán los anticuerpos identificados en 1) síndrome de Guillain-Barré; 2) polineuropatía inflamatoria desmielinizante crónica (PDIC), 3) neuropatía motora con bloqueo multifocal (NMM); 4) CANOMAD (neuropatía atáxica crónica, oftalmoplejía, proteína IgM monoclonal, aglutininas frías y anticuerpos disialosil); 5) ganglionopatías y neuronopatías y la utilidad de identificar las gammapatías monoclonales. Conclusiones: Los anticuerpos y las gammapatías monoclonales son herramientas que han permitido mejorar el diagnóstico y la comprensión fisiopatológica de las neuropatías inmunomediadas y algunas criptogénicas, así como orientar el tratamiento más adecuado.Introduction: Over the last several years the identification of both antineural antibodies and monoclonal gammopathies allowed a better understanding of pathophysiology and improvement in the diagnosis and treatment of many different immune mediated neuropathies. Objective: To describe the antineural antibodies of greater clinical utility in the diagnosis of immune mediated neuropathies and neuronopathies. In each case we underline their value in either the pathophysiology or diagnosis of these disorders as well as the sensitivity and specificity of the diagnostic techniques currently in use. Development: We will review the antibodies identified in 1) Guillain-Barré syndrome; 2) Chronic inflammatory demyelinating polyneuropathy (CIDP); 3) Multifocal motor neuropathy (MMN); 4) Chronic Ataxic Neuropathy Ophthalmoplegia M-protein Agglutination Disialosyl antibodies syndrome (CANOMAD); 5) Ganglionopathies and Neuropathies and the value of identifying monoclonal gammopathies. Conclusions: The antibodies and monoclonal gammopathies are useful tools in both the diagnosis and understanding of the mechanisms involved in immune mediated and cryptogenic neuropathies and orienting treatment.Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; ArgentinaFil: Salutto, Valeria Luján. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Aguirre, Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos; ArgentinaFil: Alvarez, Valeria. Hospital Italiano. Departamento de Medicina. Servicio de Neurologia.; ArgentinaFil: Barroso, Fabio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bendersky, Mariana. Hospital Italiano. Departamento de Medicina. Servicio de Neurologia.; ArgentinaFil: Berardo, Andrés. Columbia University; Estados UnidosFil: Bettini, Mariela. Hospital Italiano; ArgentinaFil: Borrelli, Mariano M.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Chaves, Marcelo. Hospital San Martín de Paraná; ArgentinaFil: Cisneros, Elisa M.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Conti, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Crespo, José M.. Hospital Británico de Buenos Aires; ArgentinaFil: di Egidio, Mariana. Hospital Enrique Tornú; ArgentinaFil: Figueredo, María Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos San Roque de Gonnet; ArgentinaFil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Jáuregui, Agustín. Universidad Favaloro; ArgentinaFil: Landriscina, Paula. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: León Cejas, Luciana. Hospital Británico de Buenos Aires; ArgentinaFil: Martínez Perea, María del Carmen. Hospital Rivadavia; ArgentinaFil: Pirra, Laura. Universidad Favaloro; ArgentinaFil: Pivetta, Paola. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Quarracino, Cecilia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rattagan, María Lucía. Hospital Italiano; ArgentinaFil: Rey, Roberto. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Presidente Peron; ArgentinaFil: Rodriguez, Alejandro. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Rodriguez, Gabriel E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Rugiero, Marcelo. Hospital Italiano; ArgentinaFil: Tillard, Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Zuberhbuler, Paz. Hospital Alvarez; Argentin