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

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

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

Experimental studies of boronophenylalanine (10BPA) biodistribution for the individually tailored application of boron neutron capture therapy (BNCT) for malignant melanoma treatment

Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina (10BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 106 MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 2.6 mg/g in tumor, with individual values ranging between 11.7 and 52.0 mg/g of 10B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37C and 23C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R2 Z 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R2 Z 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.Fil: Carpano, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, Carla Beatriz. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Brandizzi, Daniel. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Cabrini, Romulo Luis. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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

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

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Integrating Health Into the Urban Master Plan of Vic, Barcelona: A Comprehensive Approach

Planning healthier cities is essential for public health. However, there is a gap between the insights from public health research and applications to planning practice. Based on a scoping review and in cooperation with urban planners and public health professionals, this study developed evidence-based tools and a comprehensive approach to help urban planners integrate health into the urban master plan (2017-2020) of a medium-sized city named Vic (Barcelona). The scoping review included a systematic review of the literature (PubMed, PRISMA protocol) and an advanced Google search for gray literature (2015–2017). The systematic review identified significant associations between urban planning attributes (n = 16) and health outcomes (n = 21). After critical appraisal with stakeholders, an urban and health association matrix was developed to help urban planners understand the connection between urban planning and health. The advanced Google search identified urban planning actions (n = 117) that had an impact on health outcomes. After critical appraisal with stakeholders, a healthy urban planning actions checklist (n = 68) was developed to help urban planners' decision-making on the inclusion of locally tailored health-enhancing urban planning actions into the urban master plan. From the reviewed evidence and tools, a comprehensive approach delineated a series of steps that successfully led urban planners to incorporate health-enhancing urban actions (n = 112) into the urban master plan. This translational research developed a comprehensive approach to include health in local urban planning. This might scale up to other European medium-sized cities to maximise the effectiveness of built environment interventions and monitor their health impact

Inhibition diminishes cell viability via PKC alpha (PKCa) in thyroid cancer cells

Thyroid carcinoma (TC) is the most common endocrine neoplasia.Its incidence has increased in the last 40 years worldwide. It comprises a group of tumors of different lineage and biological behavior.About half of TC are driven by an acquired activating mutation inthe BRAF oncogene. While targeted therapies have improved outcomes in melanoma patients, most TC patients become resistant orrecur suggesting that new or additive non-cross-reactive therapiesare needed. We have previously shown that PKCa mediates TSHand thyroid hormones proliferative effects in TC. Recent evidenceindicates that together PKCa overexpression and BRAF mutationshould contribute to tumorigenesis and resistance to anticancertherapies. We found that by inhibiting BRAF expression with RNAi inanaplastic TC cells with BRAF mutation, PKCa expression decreases as well, suggesting that the latter is found downstream of BRAF.Furthermore, a decrease in the expression of the cell proliferationmarker PCNA was observed in BRAF-depleted cells by westernblot analysis. Also, TC cells were sensitive to increasing doses ofthe BRAF inhibitor widely used in the clinic vemurafenib/PLX4032in a dose-dependent manner (p<0.0001) by Cell Titer Blue (CTB)assay. To begin to study the combined inhibition of PKC and BRAF,CTB assays were performed with increasing doses of vemurafenibin presence or absence of the PKC inhibitor GF109203X at selective concentrations in follicular TC cells carrying BRAF mutation. Weconfirmed the dose-dependency of vemurafenib and found that thecombination leads to a significant decrease in cell viability (p<0.5).Our results establish that the effective dual PKCa and BRAF blockade can significantly drive tumor proliferation inhibition. The results obtained could provide new therapeutic targets and alternatives tothe treatments currently used for this disease. Despite its increasingincidence and mortality in many cases, TC constitutes a very poorlystudied area in our country.Fil: Campos Haedo, Mateo Nicolas. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Díaz Albuja, Johanna Abigail. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Debernardi, Maria Mercedes. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Rosemblit, Cinthia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de FisiologíaSociedad Argentina de Inmunologí