Molecular aspects of pituitary tumorigenesis

Os tumores hipofisários, adenomas em sua quase totalidade, são de ocorrência freqüente, representando 10% a 15% de todas as neoplasias intracranianas. Estas lesões são classificadas em microadenomas (< 10 mm) ou macroadenomas (> 10 mm) e como secretoras ou quiescentes (não-funcionantes). Estes tumores são capazes de secretar, de maneira autônoma, os hormônios adenohipofisários, como o hormônio de crescimento (GH), a prolactina (PRL), o hormônio adrenocorticotrófico (ACTH), o hormônio tireotrófico (TSH), o hormônio folículo estimulante (FSH) e o hormônio luteinizante (LH). A ocorrência de metástase, caracterizando um carcinoma hipofisário, é bastante rara, mas são relativamente comuns tumores de comportamento agressivo que exibem sinais de invasão local. Embora a sua patogênese ainda não seja plenamente caracterizada, muitos mecanismos moleculares envolvidos na tumorigênese hipofisária já foram desvendados. Nesta revisão, serão descritos avanços consideráveis realizados na última década relativos à compreensão dos fatores envolvidos na progressão tumoral, incluindo a participação de oncogenes, supressores tumorais e fatores de crescimento.Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10% to 15% of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intents to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors

Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective

Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR) cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic structure for mouse P-gp was obtained. However, for decades the design of new P-gp inhibitors employed mainly ligand-based approaches (SAR, QSAR, 3D-QSAR and phar macophore studies), and structure-based studies used P-gp homology models. However, some of those results are still the pillars used as a starting point for the design of potential P-gp inhibitors. Here, pharmacophore mapping, (Q)SAR, 3D-QSAR and homology modeling, for the discovery of P-gp inhibitors are reviewed. The importance of these methods for understanding mechanisms of drug resistance at a molecular level, and design P-gp inhibitors drug candidates are discussed. The examples mentioned in the review could provide insights into the wide range of possibilities of using CADD methodologies for the discovery of efficient P-gp inhibitors.info:eu-repo/semantics/publishedVersio

Combustion Synthesis of Ultrafine Powders of Co3O4 for Selective Surfaces of Solar Collectors

Solar selective paints, with the addition of Co3O4 as a pigment, are used to improve energetic efficiency in solar collectors. Although Co3O4has been obtained by different methods, references about combustion synthesis are scarce. Co3O4 powders have been synthesized by stoichiometric and non-stoichiometric routes using aspartic acid (Asp) or tri-hydroxi-methyl-aminomethane (Tris) as fuels. The samples were calcined in air at 500 °C. They were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectrum and the specific surface area of the samples was determined by means of the Brunauer–Emmett–Teller technique. The optical properties of pigments were assessed by means of a spectrophotometer. In all cases, powders exhibited the crystalline structure of Co3O4. A minimum crystallite average size of 29 nm was observed for powders obtained by the “stoichiometric/Asp” combustion route, while a maximum value of 41 nm was stated for powders obtained by the “non-stoichiometric/Asp” combustion process. The average particle size ranged between 50 and 100 nm. The powders obtained by the“stoichiometric/Asp” method were selected to study their optical properties; their solar absorption value was 86%. Solar selective surfaces composed by Co3O4 pigments and an alkyd resin were obtained and applied over copper or aluminum substrates. In both cases, solar absorptance was of 93% and comparable with similar solar selective surfaces, but the thermal emittance value was higher than 90%, as a consequence of the large width of the films

Folic acid-mesoporous silicon nanoparticles enhance the anticancer activity of the p73-activating small molecule LEM2

Many drugs with anticancer potential fail in their translation to the clinics due to problems related to pharmacokinetics. LEM2 is a new dual inhibitor of MDM2/mutp53-TAp73 interactions with interesting in vitro anticancer activity, which opens new hopes as an unconventional anticancer therapeutic strategy against cancers lacking p53 or with impaired p53 pathways. As others xanthone derivatives, LEM2 has limited aqueous solubility, posing problems to pursue in vivo assays, and therefore limiting its potential clinical translation. In this work, a mesopomus silicon (PSi)-based nanodelivery system was developed with folate functionalization (APTES-TCPSi-PEG-FA) for targeted delivery, which successfully increased LEM2 solubility when compared to bulk LEM2, evidenced in payload release study. Such effect was reflected on the increase of LEM2 cytotoxicity in HCT116 and MDA-MB-231 cancer cells when treated with LEM2-loaded APTES-TCPSi-PEG-FA, by reducing cell viability lower than 50% in comparison with bulk LEM2. Despite the reduced LEM2 loading degree, which still limits its application in further in vivo assays, the results obtained herein recognize PSi-based nanodelivery systems as a promising strategy to improve LEM2 anticancer activity and bioavailability, which will be relevant for the potential use of this potent TAp73 activator in anticancer therapy.Peer reviewe

Antifouling Marine Coatings with a Potentially Safer and Sustainable Synthetic Polyphenolic Derivative

The development of harmless substances to replace biocide-based coatings used to prevent or manage marine biofouling and its unwanted consequences is urgent. The formation of biofilms on submerged marine surfaces is one of the first steps in the marine biofouling process, which facilitates the further settlement of macrofoulers. Anti-biofilm properties of a synthetic polyphenolic compound, with previously described anti-settlement activity against macrofoulers, were explored in this work. In solution this new compound was able to prevent biofilm formation and reduce a pre-formed biofilm produced by the marine bacterium, Pseudoalteromonas tunicata. Then, this compound was applied to a marine coating and the formation of P. tunicata biofilms was assessed under hydrodynamic conditions to mimic the marine environment. For this purpose, polyurethane (PU)-based coating formulations containing 1 and 2 wt.% of the compound were prepared based on a prior developed methodology. The most effective formulation in reducing the biofilm cell number, biovolume, and thickness was the PU-based coating containing an aziridine-based crosslinker and 2 wt.% of the compound. To assess the marine ecotoxicity impact of this compound, its potential to disrupt endocrine processes was evaluated through the modulation of two nuclear receptors (NRs), peroxisome proliferator-activated receptor gamma (PPAR gamma), and pregnane X receptor (PXR). Transcriptional activation of the selected NRs upon exposure to the polyphenolic compound (10 mu M) was not observed, thus highlighting the eco-friendliness towards the addressed NRs of this new dual-acting anti-macro- and anti-microfouling agent towards the addressed NRs

Analysis of tourism in Campania as a tool for the development of high-quality cultural services for sightseers: The “Reale Osservatorio Vesuviano” case history

The purpose of this work is to identify the guidelines for the development and diversification of the cultural touristic offer achievable at the Reale Osservatorio Vesuviano (ROV). Founded in 1841, it is the oldest volcano observatory in the world and it has always had the vocation for scientific-naturalistic and formative tourism. The present study investigates the connections between the sociology of tourism and the ROV’s sustainability and competitiveness as a tourist destination. Here it is performed a study of the tourist flow, based on the sociology of tourism and on the correct processing of data sets, distinguishing the ''statistical information on tourism" from "tourism statistics", as such a study is the basis of a proper market strategy in different sectors. Tourism remains, in fact, an important phenomenon in world economy: despite the economic crisis of recent years, international tourist arrivals show a positive development of the trend in all the major sub-areas into which the large international areas are traditionally divided. The principles for a future marketing plan were outlined after collecting all the relevant information. The plan was designed to enhance the overall touristic offer of the ROV, never ceasing to consider the integration of natural- scientific aspects and cultural events to be offered within the observatory itself.Published64-872TM. Divulgazione Scientifica6TM. Poli Museali1VV. AltroN/A or not JC

Combustion synthesis of ultrafine powders of Co₃O₄ for selective surfaces of solar collectors

Solar selective paints, with the addition of Co₃O₄ as a pigment, are used to improve energetic efficiency in solar collectors. Although Co3O4 has been obtained by different methods, references about combustion synthesis are scarce. Co₃O₄ powders have been synthesized by stoichiometric and non-stoichiometric routes using aspartic acid (Asp) or tri-hydroxi-methyl-aminomethane (Tris) as fuels. The samples were calcined in air at 500 °C. They were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectrum and the specific surface area of the samples was determined by means of the Brunauer–Emmett–Teller technique. The optical properties of pigments were assessed by means of a spectrophotometer. In all cases, powders exhibited the crystalline structure of Co₃O₄. A minimum crystallite average size of 29 nm was observed for powders obtained by the “stoichiometric/Asp” combustion route, while a maximum value of 41 nm was stated for powders obtained by the “nonstoichiometric/ Asp” combustion process. The average particle size ranged between 50 and 100 nm. The powders obtained by the “stoichiometric/Asp” method were selected to study their optical properties; their solar absorption value was 86%. Solar selective surfaces composed by Co₃O₄ pigments and an alkyd resin were obtained and applied over copper or aluminum substrates. In both cases, solar absorptance was of 93% and comparable with similar solar selective surfaces, but the thermal emittance value was higher than 90%, as a consequence of the large width of the films.Centro de Investigación y Desarrollo en Ciencias Aplicada

Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor

Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido