Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.info:eu-repo/semantics/publishedVersio

Estácio de Sá e a fundação do Rio de Janeiro Estácio de Sa and the founding of Rio de Janeiro

O artigo aborda a presença de Estácio de Sá no Rio de Janeiro, bem como a sua fundação e a expulsão dos franceses, que chegaram aqui sob o comando de Villegagnon, em 1555, formando a França Antártica. Discute a participação da armada de Estácio de Sá na guerra contra os tamoios e tupiniquins em São Vicente, a fim de conseguir recursos humanos e mantimentos para retornar à luta na Guanabara. Por fim, questiona se Estácio de Sá teria sido governador ou somente capitão da cidade de São Sebastião do Rio de Janeiro.<br>The article deals with Estacio de Sa's presence in Rio de Janeiro as well as its foundation and the expulsion of the French that arrived here under the command of Villegagnon in 1555 having established the French Antarctic. It argues the participation of the Estacio de Sa armada in the war against the tamoios and tupiniquins in Sao Vicente, which had the purpose of obtaining human resources and supplies to return to the struggle in Guanabara. In the end, it questions as to whether Estacio de Sa had been governor or only captain of the city of Sao Sebastiao in Rio de Janeiro

Imagens em trânsito: as virgens de Luján e Sumampa e os circuitos coloniais na América Meridional na primeira metade do século XVII

This article seeks to analyze the materiality and part of the trajectory of two seventeenth-century terracotta statuettes - one of Nossa Senhora da Conceição and another of Nossa Senhora da Consolação - who respectively became the Virgin of Luján, patron of Argentina, and Virgen of Sumampa. Both are understood here as intertwined in the various networks and connections between the Portuguese and Spanish America in the contiguous areas of South America in the first half of the seventeenth century. In the text, we discuss a possible "Paulista" origin of these images which, in addition to an apparent coincidence, attests that the great "Peruvian space," articulated by Potosí, also included distinct regions of Portuguese America. Ii is in this expanded space marked by the traffic of people, goods and objects linked to the networks of smuggling that we follow the paths of these two images, trying to visualize how they got peculiar meanings in different contexts and environments.Neste artigo busca-se analisar a materialidade e parte da trajetória de duas imagens seiscentistas em terracota - uma de Nossa Senhora da Conceição e outra de Nossa Senhora da Consolação - que se tornaram, respectivamente, a Virgen de Luján, padroeira da Argentina, e a Virgen de Sumampa. Ambas são compreendidas aqui como entrelaçadas nas variadas redes e conexões estabelecidas entre a América portuguesa e espanhola, nos espaços contíguos da América Meridional na primeira metade do século XVII. No texto, discute-se uma possível procedência "paulista" dessas imagens, o que, para além de uma aparente casualidade, atesta como o grande "espaço peruano", articulado por Potosí, incluía também distintas regiões da América portuguesa. É nesse espaço ampliado, marcado pelo tráfego de pessoas, mercadorias e objetos atrelados às redes comerciais de contrabando, que acompanhamos os percursos dessas duas imagens, buscando visualizar como elas ganharam sentidos peculiares em ambientes e contextos diversos