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Retinoblastoma as an Epigenetic Disease: A Proposal  [PDF]
Domenico Mastrangelo, Cosimo Loré, Giovanni Grasso
Journal of Cancer Therapy (JCT) , 2011, DOI: 10.4236/jct.2011.23049
Abstract: The aim of the present review is to give new insights into the pathogenesis of retinoblastoma, by applying the principles of Epigenetics to the analysis of clinical, epidemiological, and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, Epigenetics, as applied to the interpretation of clinical, epidemiological and biological data in retinoblastoma, can not only explain the inconsistencies of the mutational (“two hit”) model, but also open new outstanding scenarios in the fields of diagnosis, treatment and prevention of this eye tumour. This review is both a collection of literature data arguing against the role of the mutational (“two hit”) model in the genesis of retinoblastoma, and a documented evaluation of how the Epigenetic, rather than the genetic model fit the variegated phenotypic expression of the disease. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasizes the role of environment and the interaction of the environment with the genome, in generating reti-noblastoma in young children. Environmental toxicants, including radiations, wrong diets, and infectious diseases, among others, all play a major role in conditioning the degree of DNA methylation in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which, on the other hand, can be also transmit-ted from generation to generation, thus mimicking a hereditary disease. An accurate analysis of the currently available literature on both retinoblastoma and Epigenetics, coupled with the knowledge of the variegated phenotypic expression of the disease, can easily lead to the conclusion that retinoblastoma is an epigenetic, rather than a genetic disease.
Megadoses of Sodium Ascorbate Efficiently Kill HL60 Cells in Vitro: Comparison with Arsenic Trioxide  [PDF]
Domenico Mastrangelo, Lauretta Massai, Giuseppe Fioritoni, Antonio Iacone, Paolo Di Bartolomeo, Patrizia Accorsi, Tiziana Bonfini, Michela Muscettola, Giovanni Grasso
Journal of Cancer Therapy (JCT) , 2013, DOI: 10.4236/jct.2013.48162

Arsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells according to the dosage. Part of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant activity, a characteristic which ATO shares with a number of other compounds, including high doses of ascorbate (ASC). In a comparative investigation on the cytotoxic effects of both ATO and ASC on HL60 (APL) cell lines, in Vitro, we have been able to confirm the known cytotoxic effects of ATO, but, more importantly, we have demonstrated that ASC is significantly more effective than ATO, in killing these cancer cells in Vitro, when the concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations at which ASC induces oxidative damage to tumor cells. Since these plasma levels can be reached only by the intravenous administration of high doses of ASC, we propose that intravenous high doses of ASC may represent a potentially revolutionary new approach in the management of APL.

Retinoblastoma and the Genetic Theory of Cancer: An Old Paradigm Trying to Survive to the Evidence
Domenico Mastrangelo,Theodora Hadjistilianou,Sonia De Francesco,Cosimo Loré
Journal of Cancer Epidemiology , 2009, DOI: 10.1155/2009/301973
Abstract: Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called “tumor suppressor gene”, the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account.
Usos locales de las certificaciones globales: calidad, medio ambiente y trabajo seguro en forestación
Andrea Mastrangelo
Revista IDeAS : Interfaces em Desenvolvimento, Agricultura e Sociedade , 2009,
Abstract: En el NE de la Argentina la forestación es una actividad económica cuya expansión ha atraído capitales extranjeros. La inversión directa ha incentivado la integración vertical y concentración económica del proceso de producción. Encadenada a la forestación, la industria de celulosa y transformación mecánica y química de maderas invirtió en implantación (en la zona de estudio, monocultivo de coníferas) con destino creciente a la exportación: según datos del Servicio Nacional de Sanidad y Calidad Agroalimentaria (Senasa) las exportaciones de madera de pino en todas sus formas, aumentaron un 22 por ciento en el primer trimestre de 2008, respecto al a o anterior. Estas producciones rurales son transformadas en bienes de exportación por el recurso de aplicar normas internacionales de certificación. En este artículo se analiza el origen de esas normas, su contenido y su aplicación en la producción de maderas y derivados en el NO Misiones. Nos proponemos dar cuenta de lo que estas certificaciones comportan en términos de las relaciones local-global, productor-consumidor y capital- trabajo.
Structural Insight into Inhibitor of Apoptosis Proteins Recognition by a Potent Divalent Smac-Mimetic
Federica Cossu, Mario Milani, Patrice Vachette, Francesca Malvezzi, Serena Grassi, Daniele Lecis, Domenico Delia, Carmelo Drago, Pierfausto Seneci, Martino Bolognesi, Eloise Mastrangelo
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049527
Abstract: Genetic alterations enhancing cell survival and suppressing apoptosis are hallmarks of cancer that significantly reduce the efficacy of chemotherapy or radiotherapy. The Inhibitor of Apoptosis Protein (IAP) family hosts conserved proteins in the apoptotic pathway whose over-expression, frequently found in tumours, potentiates survival and resistance to anticancer agents. In humans, IAPs comprise eight members hosting one or more structural Baculoviral IAP Repeat (BIR) domains. Cellular IAPs (cIAP1 and 2) indirectly inhibit caspase-8 activation, and regulate both the canonical and the non-canonical NF-κB signaling pathways. In contrast to cIAPs, XIAP (X chromosome-linked Inhibitor of Apoptosis Protein) inhibits directly the effector caspases-3 and -7 through its BIR2 domain, and initiator caspase-9 through its BIR3 domain; molecular docking studies suggested that Smac/DIABLO antagonizes XIAP by simultaneously targeting both BIR2 and BIR3 domains. Here we report analytical gel filtration, crystallographic and SAXS experiments on cIAP1-BIR3, XIAP-BIR3 and XIAP-BIR2BIR3 domains, alone and in the presence of compound 9a, a divalent homodimeric Smac mimetic. 9a is shown to bind two BIR domains inter- (in the case of two BIR3) and intra-molecularly (in the case of XIAP-BIR2BIR3), with higher affinity for cIAP1-BIR3, relative to XIAP-BIR3. Despite the different crystal lattice packing, 9a maintains a right handed helical conformation in both cIAP1-BIR3 and XIAP-BIR3 crystals, that is likely conserved in solution as shown by SAXS data. Our structural results demonstrate that the 9a linker length, its conformational degrees of freedom and its hydrophobicity, warrant an overall compact structure with optimal solvent exposure of its two active moieties for IAPs binding. Our results show that 9a is a good candidate for pre-clinical and clinical studies, worth of further investigations in the field of cancer therapy.
Análisis del concepto de recursos naturales en dos estudios de caso en Argentina
Mastrangelo, Andrea Verónica;
Ambiente & Sociedade , 2009, DOI: 10.1590/S1414-753X2009000200009
Abstract: the concept of "natural resources", in the same way as the idea of "nature" is difficult to be thought in the social investigation, probably because its own etymology supposes some essential or unchangeable characteristic. but "natural resources" are not objectively defined, but they are related to specific social needs. so, historically and nowadays resources have been under dispute among social actors unequally positioned. in these arguments, the very notion of "natural resources" itself has been changing its meaning. in this paper "natural resources" and "renewable and non renewable" classification are reviewed through the analysis of two specific ethnographic cases in argentina, as a way of making visible what is hidden when a scientific concept, in this case a concept from the economics, takes part in the common-sense.
Self-Assembled Monolayers (SAMs): Which Perspectives in Implant Dentistry?  [PDF]
Filiberto Mastrangelo, Giulia Fioravanti, Raimondo Quaresima, Raffaele Vinci, Enrico Gherlone
Journal of Biomaterials and Nanobiotechnology (JBNB) , 2011, DOI: 10.4236/jbnb.2011.225064
Abstract: Self-assembled monolayers (SAMs) are ordered organic films formed by adsorption of an active organic coating on a solid surface. Their formation provides an alternative, highly innovative, to current traditional chemical treatments of the titanium surfaces. For this reason the structural phases, the formation and the growth of SAMs is described from a surface science point of view. Particulars are given to SAMs on titanium concerning surface morphology, chemical composition and affinity of specific head group for Ti surfaces (silanes, siloxane, phosphonates and phosphates). Preparation, coating methodologies, limitations and techniques used for the characterization of SAMs are reported. For their physicochemical characteristics and micro-nano scale features some perspectives of using SAMs in biomedical application are outlined.
An Overview of the Components of AW-IPM Campaigns against the New World Screwworm
Thiago Mastrangelo,John B. Welch
Insects , 2012, DOI: 10.3390/insects3040930
Abstract: The New World Screwworm, Cochliomyia hominivorax (Coquerel), is one of the most damaging parasites of livestock, causing millions of dollars in annual losses to producers. The fly is an obligate parasite of warm-blooded animals, including humans. After a successful 50-year eradication campaign, C. hominivorax has been eradicated from the USA, Mexico and Central America by an area-wide integrated pest management approach. Recently, Caribbean and South American countries have expressed an interest in this approach. Aiming to support forthcoming projects in these countries, this review describes the main technical components of past and ongoing AW-IPM campaigns against C. hominivorax.
RSV Fusion: Time for a New Model
Peter Mastrangelo,Richard G. Hegele
Viruses , 2013, DOI: 10.3390/v5030873
Abstract: In this review we propose a partially hypothetical model of respiratory syncytial virus (RSV) binding and entry to the cell that includes the recently discovered RSV receptor nucleolin, in an attempt to stimulate further inquiry in this research area. RSV binding and entry is likely to be a two-step process, the first involving the attachment of the virus to the cell membrane, which may be enhanced by electrostatic interactions with cellular glycoproteins/heparin and the viral G protein, and the second involving fusion to the cell membrane mediated by the viral F protein and a specific cellular fusion receptor. With our recent discovery of nucleolin as a functional fusion receptor for RSV, comes the possibility of a number of new approaches to the development of novel strategies for RSV prophylaxis and therapy, as well as raising some new questions concerning the pathobiology of RSV infection and tropism.
Agro-Biodiversity Spatial Assessment and Genetic Reserve Delineation for the Pollino National Park (Italy)  [PDF]
Giovanni Figliuolo, Domenico Cerbino
Natural Resources (NR) , 2014, DOI: 10.4236/nr.2014.57029

Ancient fruit trees, grape vines, traditional crop and garden cultivars have been inventoried in Pollino National Park by adopting a spatial sampling grid which covers 23 different municipalities (~1500 Km2) and 190 surveyed sites. Each site is a circle with a visible radius of 200 - 250 m. The spatial analysis of the diversity of plant genetic resources has been conducted with pre-fixed landscape units (size: 4 Km × 4 Km). Overall, 49 different woody long cycle (455 ancient cultivars) and 53 short cycle species (102 ancient cultivars) have been scored. Long cycle species exhibit higher cultivar richness than short cycle species. The analysis has recognized that pre-Columbian indigenous cultivars had not been displaced by the American species introduced after the 16th century. In addition, it is confirmed that small-scale poly-production, under conditions of spatial niche variation, is associated to high species and cultivar richness. The mapped realized niche, for both pre- and post-Columbian genetic resources, includes the actual genetic reserve suitable for in situ conservation of plant agro-biodiversity. Agro-biodiversity models, drivers of genetic erosion, and realistic responses to genetic erosion are outlined.

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