Cancer stem cells in prostate cancer: implications for targeted therapy

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies. CSCs are a reservoir of cancer cells that exhibit properties of self-renewal and the ability to reestablish the heterogeneous tumor cell population. The existence of PCa stem cells offers a theoretical explanation for many uncertainties regarding PCa and also for treatment resistance and disease progression once clinical cure is achieved. Therapies targeting CSCs might therefore lead to more effective cancer treatments, divergent from a traditional anti-proliferative approach, based on tumor bulk reduction accompanied by CSC-specific inhibition. Here, we focus on reviewing the historical perspective as well as concepts regarding stem cells and CSCs in PCa. In addition, we will report possible strategies and new clinical approaches that address the CSC-based concept of tumorigenesis in PCa. (C) 2017 S. Karger AG, Base

Goiânia-GO: Um Projeto de Cidade-Jardim que não Resistiu às Forças do Progresso

Using the comparative historical method in an interdisciplinary perspective, mainly by the dialogue of history, urbanism, architecture, landscaping and education the present article intends to make, besides discussions about environmental preservation, sustainability and quality of life in an urban environment, to understand how the inhabitants of the city have been changing their way of relating to the natural environment over the years. Goiânia was conceived and designed to be, besides a city planned in the architectural style of garden cities, the future capital of Goiás that was born approached the principles of a sustainable urbanization that sought to maintain the balance between nature, economy and society. Using a varied documentation - plan and master plan elaborated by Atílio Corrêa Lima, aerial photo records, maps of the areas destined to parks and forests, urbanistic projects and master plans, urban report, population data, urbanization plans of neighborhoods, maps of legal and illegal subdivisions - the article intends to show that the construction project of Goiânia devised by Atílio Corrêa Lima presented an interaction between the city, man and nature by allocating ample spaces for the construction of squares, gardens and green areas for leisure, in view also, the preservation of natural resources essential to a city that could house up to 50 thousand inhabitants. However from 1950 the rural exodus provoking the expansion of the agricultural frontier to the Center-West led to an accelerated and disorderly expansion of Goiania, and consequently, the expansion of the urban fabric into the areas that should be of conservation and preservation.Utilizando-se do método histórico comparativo em uma perspectiva interdisciplinar, principalmente, pelo diálogo da história, urbanismo, arquitetura, paisagismo e educação o presente artigo pretende fazer, além de discussões sobre preservação ambiental, sustentabilidade e qualidade de vida em ambiente urbano, compreender como os habitantes da cidade foram mudando a sua forma de se relacionar com o meio natural ao longo dos anos. Goiânia foi pensada e idealizada para ser, além uma cidade planejada no estilo arquitetônico de cidades-jardim, a futura capital de Goiás que nascia se aproximava dos princípios de uma urbanização sustentável que procurava manter o equilíbrio entre a natureza, economia e sociedade. Utilizando-se de uma documentação variada - planta e plano diretor elaborados por Atílio Corrêa Lima, registros de fotos aéreas, mapas das áreas destinadas a parques e bosques, projetos urbanísticos e planos diretores, relatório urbanístico, dados populacionais, plantas de urbanização de bairros, mapas de loteamentos legais e ilegais - o artigo pretende mostrar que o projeto de construção de Goiânia idealizado por Atílio Corrêa Lima entrevia uma interação entre a cidade, o homem e a natureza ao destinar amplos espaços para a construção de praças, jardins e áreas verdes para o lazer, tendo em vista também, a preservação dos recursos naturais essenciais à a uma cidade que poderia abrigar até 50 mil habitantes. No entanto a partir de 1950 o êxodo rural provocando pela expansão da fronteira agrícola para o Centro-Oeste levou a uma expansão acelerada e desordenada de Goiânia, e consequentemente, a expansão da malha urbana sobre as áreas que deveriam ser de conservação e preservação

Zur Reaktion polycyclischer Alkoxysilylamide von Li, Na und K mit organischen Lewis-Basen

Unabhängig vom Liganden am Stickstoffatom (tert-Butyl oder Trimethylsilyl) reagiert das polycyclische und dimere Lithium-(alkoxysilyl)-tert-butylamid 1 bzw. Lithium-(alkoxysilyl)silylamid 2 mit den Basen Pyridin, Tetrahydrofuran bzw. Dioxan zu Säure-Base-Addukten 1a, 1b, 1c und 2a mit ähnlicher Struktur Nach der Röntgenstrukturanalyse von 1b koordiniert die Base Tetrahydrofuran über den Sauerstoff an eines der beiden Lithiumatome, während das andere von den Sauerstoff- und Stickstoff-atomen des Siloxyamidliganden umgeben ist. Die beiden Metallatome besitzen unterschiedliche Koordinationszahlen (3 und 4), wobei Li(2) aufgrund der geringeren Anzahl der Nachbarn die kürzesten Abstände bildet. Selbst ein Basenüberschuß führt nicht zur Bildung von Komplexen, bei denen die beiden Metallatome im Molekül gleichen Sättigungsgrad und gleiche Umgebung erreichen. Möglich ist dies jedoch bei der entsprechenden Natriumverbindung 3, die mit Pyridin zu der Verbindung 3a reagiert. In diesem Produkt besitzen beide Natriumatome dieselbe Koordinationssphäre mit je drei Stickstoff- und einem Sauerstoffatom als Nachbarn. Setzt man 3 mit ,-Bipyridyl um, so entsteht eine Verbindung mit Natriumatomen unterschiedlicher Umgebung. Diese erstaunliche Unsymmetrie in der Koordination der beiden Metallatome liegt bei der entsprechenden Kaliumverbindung 4a, gewonnen aus 4 und ,-Bipyridyl, nicht vor (gleichartig koordinierte Kaliumatome). Säure-Base-Addukte von 3 und 4 mit Phenanthrolin und Kronenethern waren nachzuweisen

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection