Microarray-Based Oncogenic Pathway Profiling in Advanced Serous Papillary Ovarian Carcinoma

Introduction: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. Methodology: A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, β-Catenin, BRCA, E2F1, EGFR, ER, HER2, INFα, INFγ, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNFα, and TGFβ and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464) to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS) were analysed. Results: The GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation scor

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

Over the past century, the study of biological processes in the human body has progressed from tissue culture on glass plates to complex 3D models of tissues, organs, and body systems. These dynamic 3D systems have allowed for more accurate recapitulation of human physiology and pathology, which has yielded a platform for disease study with a greater capacity to understand pathophysiology and to assess pharmaceutical treatments. Specifically, by increasing the accuracy with which the microenvironments of disease processes are modeled, the clinical manifestation of disease has been more accurately reproduced in vitro. The application of these models is crucial in all realms of medicine, but they find particular utility in diseases related to the complex bone marrow niche. Osteoblast, osteoclasts, bone marrow adipocytes, mesenchymal stem cells, and red and white blood cells represent some of cells that call the bone marrow microenvironment home. During states of malignant marrow disease, neoplastic cells migrate to and join this niche. These cancer cells both exploit and alter the niche to their benefit and to the patient\u27s detriment. Malignant disease of the bone marrow, both primary and secondary, is a significant cause of morbidity and mortality today. Innovative study methods are necessary to improve patient outcomes. In this review, we discuss the evolution of 3D models and compare them to the preceding 2D models. With a specific focus on malignant bone marrow disease, we examine 3D models currently in use, their observed efficacy, and their potential in developing improved treatments and eventual cures. Finally, we comment on the aspects of 3D models that must be critically examined as systems continue to be optimized so that they can exert greater clinical impact in the future. © 2019 The Authors

Role of molecular agents and targeted therapy in clinical trials for women with ovarian cancer

There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference

Heterogeneity of Stem Cells in the Thyroid

Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mature thyrocytes and functional follicles for the treatment of thyroid diseases in mice. In addition, the discovery of resident thyroid progenitor cells, along with other sources of stem cells, has defined in detail the mechanisms responsible for tissue repair upon moderate or severe organ injury.In this chapter, we highlight in detail the current state of research on thyroid stem cells by focusing on (1) the description of the first experiments performed to obtain thyroid follicles from embryonic stem cells, (2) the identification of resident stem cells in the thyroid gland, and (3) the definition of the current translational in vivo and in vitro models used for thyroid tissue repair and regeneration

A global reptile assessment highlights shared conservation needs of tetrapods

Comprehensive assessments of species? extinction risks have documented the extinction crisis1 and underpinned strategies for reducing those risks2. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction3. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods4,5,6,7. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs6. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened?confirming a previous extrapolation8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods?agriculture, logging, urban development and invasive species?although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles?including most species of crocodiles and turtles?require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.Fil: Cox, Neil. No especifíca;Fil: Young, Bruce E.. No especifíca;Fil: Bowles, Philip. No especifíca;Fil: Fernandez, Miguel. George Mason University; Estados Unidos. Universidad Mayor de San Andrés; BoliviaFil: Marin, Julie. Universite de Paris 13-Nord; FranciaFil: Rapacciuolo, Giovanni. California Academy of Sciences; Estados UnidosFil: Böhm, Monika. The Zoological Society of London; Reino UnidoFil: Brooks, Thomas M.. University of The Philippines; Filipinas. University of Tasmania; AustraliaFil: Hedges, S. Blair. Temple University; Estados UnidosFil: Hilton Taylor, Craig. Biodiversity Assessment & Knowledge Team; Reino UnidoFil: Hoffmann, Michael. The Zoological Society of London; Reino UnidoFil: Jenkins, Richard K. B.. Biodiversity Assessment & Knowledge Team; Reino UnidoFil: Tognelli, Marcelo F.. No especifíca;Fil: Alexander, Graham J.. University of the Witwatersrand; SudáfricaFil: Allison, Allen. Bishop Museum; Estados UnidosFil: Ananjeva, Natalia B.. Zoological Institute; RusiaFil: Auliya, Mark. Zoological Research Museum Alexander Koenig; AlemaniaFil: 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; ArgentinaFil: Chapple, David G.. Monash University; AustraliaFil: Cisneros Heredia, Diego F.. Universidad San Francisco de Quito; EcuadorFil: Cogger, Harold G.. Australian Museum Research Institute; AustraliaFil: Colli, Guarino Rinaldi. Universidade do Brasília; BrasilFil: de Silva, Anslem. No especifíca;Fil: Eisemberg, Carla C.. Charles Darwin University; AustraliaFil: Els, Johannes. Government of Sharjah; Emiratos Arabes UnidosFil: Fong G, Ansel. Centro Oriental de Biodiversidad y Ecosistemas; CubaFil: Grant, Tandora D.. No especifíca;Fil: Hitchmough, Rodney A.. No especifíca;Fil: Iskandar, Djoko T.. Institut Teknologi Bandung; IndonesiaFil: Kidera, Noriko. Okayama University of Science; Japón. National Institute for Environmental Studies; JapónFil: Martins Pimentel, Márcio. Universidade de Sao Paulo; BrasilFil: Meiri, Shai. Universitat Tel Aviv; IsraelFil: Mitchell, Nicola J.. University of Western Australia; AustraliaFil: Molur, Sanjay. No especifíca;Fil: Nogueira, Cristiano de C.. Universidade de Sao Paulo; BrasilFil: Ortiz, Juan Carlos. Universidad de Concepción; ChileFil: Penner, Johannes. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Rhodin, Anders G. J.. Chelonian Research Foundation; Estados UnidosFil: Rivas, Gilson A.. Universidad del Zulia; VenezuelaFil: Rödel, Mark-Oliver. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Roll, Uri. Ben Gurion University of the Negev; IsraelFil: Sanders, Kate L.. University of Adelaide; AustraliaFil: Santos Barrera, Georgina. Universidad Nacional Autónoma de México; MéxicoFil: Shea, Glenn M.. University of Western Sydney; AustraliaFil: Spawls, Stephen. No especifíca;Fil: Stuart, Bryan L.. North Carolina Museum of Natural Sciences; Estados UnidosFil: Tolley, Krystal A.. University of the Witwatersrand; SudáfricaFil: Trape, Jean-François. Institut de Recherche Pour Le Développement Dakar; SenegalFil: Vidal, Marcela A.. Universidad del Bio Bio; ChileFil: Wagner, Philipp. No especifíca;Fil: Wallace, Bryan P.. No especifíca;Fil: Xie, Yan. Chinese Academy of Sciences; República de Chin