Mecanismos no convencionales de regulación tiroidea

Fil:Juvenal, Guillermo Juan. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Deregulation of MicroRNAs Expression in Human Papillary Thyroid Carcinoma

El descubrimiento de los microRNAs (miRNAs) ha demostrado que estos se comportan como una poderosa clase de reguladores de la expresión génica. Al actuar a nivel postranscripcional, los miRNAs son capaces de modular la expresión de al menos un tercio de los RNA mensajeros codificados por el genoma. Aquí resumimos las principales alteraciones en la expresión de los genes para miRNAs identificados en el carcinoma papilar de tiroides. Se discuten también los mecanismos por los cuales la desregulación de estos miRNAs podrían estar involucrados en la transformación de las células foliculares tiroideasMicroRNAs (miRNAs) small (~22 nt) single-stranded RNA molecules that are not further translated into proteins. They can act as negative regulators of the protein-coding gene expression and may impact cell differentiation, proliferation and survival. They have been implicated in carcinogenesis. The purpose of this review is to summarize the main alterations of miRNA expression identified in thyroid papillary carcinomas, and discuss the mechanisms by which miRNA deregulation might be involved in thyroid cell transformation.Fil: Pallante, P.. Università degli Studi di Napoli Federico II; ItaliaFil: Battista, S.. Università degli Studi di Napoli Federico II; ItaliaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Fusco, A.. Università degli Studi di Napoli Federico II; Itali

Study of 6-propyl-2-thiouracil as a radioprotector for the thyroid gland

The objective of the paper was to study the application of 6-propyl-2-thiouracil (PTU) as a radioprotector for the thyroid gland. Rat thyroid epithelial cells (FRTL-5) and human colon cancer cells (ARO81-1) were exposed to γ-irradiation with or without 1 mM PTU. Radiation response was analysed by clonogenic survival assay. Cyclic AMP levels were measured by Radioimmunoassay (RIA). The results showed that PTU increased the Surviving Cell Fraction (SF) at 2 Gy significantly (p < 0.05) in both cell lines. PTU increased extracellular levels of cAMP in all the treatments in a dose- and time-dependent manner for FRTL-5 cells. In ARO81-1 cells, a peak was observed at 24 hours in extracellular levels incubated with 1 mM PTU (36.97 ± 6.74 fmol/μg prot vs. control: 17.53 ± 3.9 fmol/μg prot, p < 0.001). Forskolin and dibutyril cAMP mimicked the effect of PTU on SF. Thus PTU appears to be a radioprotector for thyroid cells and could exert its effect through cAMP.Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pagotto, Romina. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Casal, Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentin

Participation of NADPH 4 oxidase in thyroid regulation

Different factors are involved in thyroid function and proliferation such as thyrotropin (TSH), insulin, growth factors, iodide, etc. TSH and IGF1/insulin increase proliferation rate and stimulate genes involved in thyroid differentiation. In the present study, we analyse the physiological regulation of NOX4 expression by TSH, insulin and iodine, and the role of NOX4 on thyroid genes expression. Differentiated rat thyroid cells (FRTL-5) were incubated in the presence or absence of TSH/insulin and TTF2, PAX8, TPO, NIS, NOX4, TGFβ1, FOXO1/3 mRNA levels were examined by Real Time PCR. We showed that TSH and insulin repress NOX4 expression and appears to be inversely correlated with some thyroid genes. SiRNA targeted knockdown of NOX4 increased mRNA levels of TGFβ1, TPO, PAX8, TTF2, FOXO1 and FOXO3. A PI3K inhibitor (LY294002), increases the expression of NIS, TTF2 and FOXO1/3, however PI3K/AKT pathway does not regulate NOX4 expression. We observed that iodine increased NOX4 expression and knockdown of NOX4 reduced ROS and reversed the inhibitory effect of iodine on NIS, TPO, PAX8 and TTF2 expression. Our findings provide strong evidence that NOX4 could be a novel signaling modulator of TSH/insulin pathway and would have a critical role in the autoregulatory mechanism induced by iodine.Fil: Oglio, Romina. Comisión Nacional de Energía Atómica; ArgentinaFil: Salvarredi, Leonardo Andres. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rossich, Luciano Esteban. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Copelli, Silvia Beatriz. Universidad Centro de Altos Estudios en Ciencias Exactas; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer

The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. These carcinomas are well controlled with surgery followed by therapy with 131I; however, some patients do not respond to this treatment. BPA uptake was analyzed both in vitro and in nude mice implanted with cell lines of differentiated thyroid carcinoma. The boron intracellular concentration in the different cell lines and the biodistribution studies showed the selectivity of the BPA uptake by this kind of tumor.Fil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, S.. Comisión Nacional de Energía Atómica; ArgentinaFil: Cabrini, R.. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Thyroid: Iodine Beyond the Thyronines

Although thyroid gland function is mainly under the control of pituitary TSH, other factors may also play a role in this process. Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of parameters such as thyroid proliferation and function. Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iododeltalactone (IL ) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids can inhibit several thyroid parameters suggesting that these compounds may be the intermediates in the thyroid autoregulation process.Fil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Oglio, Andrea Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Rossich, Luciano Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; ArgentinaFil: Salvarredi, Leonardo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. División Bioquímica Nuclear; Argentin

6 Iodo-Delta Lactone Inhibits Angiogenesis in Human HT29 Colon Adenocarcinoma xenograft.

Introduction: Several studies have shown the antiproliferative effect of iodine and 5-hydroxy-6iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that moleculariodine (I2) and IL-δ, but not iodide (I-), exerts anti-neoplastic actions in different cancers. Theunderlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of thisstudy was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29colorectal cancer xenografts.Methodology and Results: HT29 cells were injected subcutaneously into the flanks of nude miceand IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenograftsshowed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression(p<0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (p<0.05). Toassess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry wasanalyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively(p<0.05), as well as it decreased VEGF and VEGF-R2 expression (p<0.05). Additionally, ourfindings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (p<0.01).Conclusion: The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as wellas induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase wouldproduce anti-proliferative effect on endothelial cells.Fil: Oglio, Romina. Comisión Nacional de Energía Atómica; ArgentinaFil: Buschittari, Federico. Comisión Nacional de Energía Atómica; ArgentinaFil: Salvarredi, Leonardo Andres. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Michaux, Jennifer. Université Libre de Bruxelles; BélgicaFil: Rodriguez, Carla. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Thomasz, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

Estimación de la Incidencia de Cáncer de Tiroides en Capital Federal y el Gran Buenos Aires (período 2003-2011)

La incidencia del cáncer de tiroides ha aumentado significativamente en las últimas décadas en el resto del mundo. En Argentina no existe un registro nacional de cáncer por lo que la incidencia del mismo no puede establecerse. Por lo tanto, nuestro objetivo fue estimar la incidencia de cáncer de tiroides en la población de la Ciudad Autónoma de Buenos aires y Gran Buenos Aires así como la relación por género y la histología en el período de 2003 hasta 2011. Asumiendo que la población de afiliados a la Obra Social de la Policía Federal Argentina es representativa de los habitantes de Buenos Aires y el conurbano calculamos que la incidencia es de 6,51 casos/100.000 habitantes/año, con un incremento en 25 años mayor al doble, con predominio del carcinoma papilar frente al folicular.Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.Fil: Faure, E. N.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Soutelo, Maria Jimena. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Faraj, G.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Lufti, Ruben Julio. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

Estimación de la Incidencia de Cáncer de Tiroides en Capital Federal y el Gran Buenos Aires (período 2003-2011)

La incidencia del cáncer de tiroides ha aumentado significativamente en las últimas décadas en el resto del mundo. En Argentina no existe un registro nacional de cáncer por lo que la incidencia del mismo no puede establecerse. Por lo tanto, nuestro objetivo fue estimar la incidencia de cáncer de tiroides en la población de la Ciudad Autónoma de Buenos aires y Gran Buenos Aires así como la relación por género y la histología en el período de 2003 hasta 2011. Asumiendo que la población de afiliados a la Obra Social de la Policía Federal Argentina es representativa de los habitantes de Buenos Aires y el conurbano calculamos que la incidencia es de 6,51 casos/100.000 habitantes/año, con un incremento en 25 años mayor al doble, con predominio del carcinoma papilar frente al folicular.Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.Fil: Faure, E. N.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Soutelo, Maria Jimena. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Faraj, G.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Lufti, Ruben Julio. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

Experimental studies for the personalized application of boron neutron capture therapy to the treatment of cutaneous melanoma

Background: Boron neutron capture therapy (BNCT) is a binary modality based on the nuclear reaction 10B (n, α) lithium-7 (7Li) that has been used to treat a variety of tumors, among these, cutaneous melanoma (CM). In previous boron biodistribution studies in agreement with the personalized oncology, we have demonstrated that boronophenylalanine (BPA) uptake can be correlated with the tumoral temperature and viability. The main aim of these studies was to evaluate the relationship between tumoral temperature and the response to the complete BNCT. Methods: Nude mice were implanted with human melanoma cells (Mel J) and divided into different groups (Control, NCT, BNCT I and BNCT II) and irradiated with the thermal neutron beam from RA-6 (4.96× 108/cm2/sec) during 37 and 55 minutes respectively. Tumor and body temperatures were measured by Static Infrared Imaging (SIRI), and it was performed the following up of the animals. Results: Tumor growth showed a complete growth inhibition during the first 20 days after treatment in both BNCT groups (BNCT I and BNCT II vs. Control P<0.001). Considering the analogy between the Fourier's Law of Heat Conduction and the Ohm's law of Electrical Conduction, the quantity (T_tum-T_ inf)/(T_body-T_tum) was analyzed as a function of Vf/Vi (Final volume/Initial volume) ratio. A tendency to higher values of the temperature's ratios, was observed with respect to the degree of tumor control (BNCT I with a R2 of 0.3527, BNCTII with a R2 of 0.3327) in agreement with previous boron biodistribution studies. The histology and immunohistochemical studies showed larger areas of necrosis and picnotic regions and a significant decrease of the Ki-67 antibody labeling in the BNCT II group evidencing important tumor damage. Conclusions: tumoral characteristics, especially the temperature, could be used to plan a personalized treatment for each patient. As values of correlation between temperature and tumoral response showed to be weak, we considered to explore a new model of three dimension for heat transport process.Fil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Rodriguez, Carla. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María Silvina. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Boggio, Esteban Fabián. Comisión Nacional de Energía Atómica; ArgentinaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin