Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events.</p> <p>Conclusion</p> <p>On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.</p

Diversification and evolutionary histories of patagonian steppe lizards

During the last two decades, regional exploration coupled with dense geographic sampling, new molecular techniques, and phylogeographic approaches have led to the discovery of unexpected hidden diversity. These data have expanded inferences about evolutionary and demographic processes to explain patterns of geographic genetic distribution, phylogenetic history, and morphological characteristics. This chapter summarizes current knowledge of species boundaries and possible underlying processes, highlighting the extent of hybridization and its possible role for the lack of strongly supported phylogenetic relationships within several species groups.Fil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Medina, Cintia Débora. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Centro Nacional Patagonico. Unidad de Administracion Territorial.; ArgentinaFil: Minoli, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Perez, Cristian Hernan Fulvio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia. Unidad de Administración Territorial; ArgentinaFil: Sites, Jack W.. University Brigham Young; Estados UnidosFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentin

Macroevolutionary diversification with limited niche disparity in a species-rich lineage of cold-climate lizards

Background: Life diversifies via adaptive radiation when natural selection drives the evolution of ecologically distinct species mediated by their access to novel niche space, or via non-adaptive radiation when new species diversify while retaining ancestral niches. However, while cases of adaptive radiation are widely documented, examples of non-adaptively radiating lineages remain rarely observed. A prolific cold-climate lizard radiation from South America (Phymaturus), sister to a hyper-diverse adaptive radiation (Liolaemus), has extensively diversified phylogenetically and geographically, but with exceptionally minimal ecological and life-history diversification. This lineage, therefore, may offer unique opportunities to investigate the non-adaptive basis of diversification, and in combination with Liolaemus, to cover the whole spectrum of modes of diversification predicted by theory, from adaptive to non-adaptive. Using phylogenetic macroevolutionary modelling performed on a newly created 58-species molecular tree, we establish the tempo and mode of diversification in the Phymaturus radiation. Results: Lineage accumulation in Phymaturus opposes a density-dependent (or ‘niche-filling’) process of diversification. Concurrently, we found that body size diversification is better described by an Ornstein-Uhlenbeck evolutionary model, suggesting stabilizing selection as the mechanism underlying niche conservatism (i.e., maintaining two fundamental size peaks), and which has predominantly evolved around two major adaptive peaks on a ‘Simpsonian’ adaptive landscape. Conclusions: Lineage diversification of the Phymaturus genus does not conform to an adaptive radiation, as it is characterised by a constant rate of species accumulation during the clade’s history. Their strict habitat requirements (rocky outcrops), predominantly invariant herbivory, and especially the constant viviparous reproduction across species have likely limited their opportunities for adaptive diversifications throughout novel environments. This mode of diversification contrasts dramatically with its sister lineage Liolaemus, which geographically overlaps with Phymaturus, but exploits all possible microhabitats in these and other bioclimatic areas. Our study contributes importantly to consolidate these lizards (liolaemids) as promising model systems to investigate the entire spectrum of modes of species formations, from the adaptive to the non-adaptive extremes of the continuum

The Patagonian Fossil Lizards

The squamates constitute a significant part of the present-day South American herpetofauna, being their fossils a crucial evidence for understanding the origin and evolution of the main clades. The fossil record of squamates in Patagonia is still scarce but it represents one of the most prolific of entire South America. An updated systematic review of the available information of Patagonian fossil lizards is summarized in this chapter. The oldest lizards of Patagonia are found as back as the Upper Cretaceous and include materials referred to two of the most diverse extant clades: Iguania and Scincomorpha. Palaeocene and Eocene interestingly do not provide any lizard specimen from this region. The record reappeared in the Late Oligocene with iguanians. A significant increasing of materials is revealed later in the Neogene. Early Miocene lizards include the first appearance of extant species (the iguanids Liolaemus and Pristidactylus, and the teiids Tupinambis and Callopistes). Late Early Miocene deposits provide materials of Pristidactylus and Tupinambis, whereas an indeterminate tupinambine of the Mid-Miocene is the youngest Neogene record of a lizard in Patagonia. Palaeoclimatic changes affected the distributional patterns of lizards in Patagonia, restricting the distribution of Pristidactylus and Tupinambis which, during the Miocene, reached localities southern than at present. The uplift of the austral Andean cordillera would have been decisive for the diversification of Liolaemus and Pristidactylus at both sides the Andes, whereas the trans-Andean teiid Callopistes had a widespread distribution in the past, reaching the Pampean Region and Patagonia, in Argentina.Fil: Albino, Adriana Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentin