Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells

Timely characterization of a cancer's evolution is required to predict treatment efficacy and to detect resistance early. High content analysis of single Circulating Tumor Cells (CTCs) enables sequential characterization of genotypic, morphometric and protein expression alterations in real time over the course of cancer treatment. This concept was investigated in a patient with castrate-resistant prostate cancer progressing through both chemotherapy and targeted therapy. In this case study, we integrate across four timepoints 41 genome-wide copy number variation (CNV) profiles plus morphometric parameters and androgen receptor (AR) protein levels. Remarkably, little change was observed in response to standard chemotherapy, evidenced by the fact that a unique clone (A), exhibiting highly rearranged CNV profiles and AR+ phenotype was found circulating before and after treatment. However, clinical response and subsequent progression after targeted therapy was associated with the drastic depletion of clone A, followed by the sequential emergence of two distinct CTC sub-populations that differed in both AR genotype and expression phenotype. While AR- cells with flat or pseudo-diploid CNV profiles (clone B) were identified at the time of response, a new tumor lineage of AR+ cells (clone C) with CNV altered profiles was detected during relapse. We showed that clone C, despite phylogenetically related to clone A, possessed a unique set of somatic CNV alterations, including MYC amplification, an event linked to hormone escape. Interesting, we showed that both clones acquired AR gene amplification by deploying different evolutionary paths. Overall, these data demonstrate the timeframe of tumor evolution in response to therapy and provide a framework for the multi-scale analysis of fluid biopsies to quantify and monitor disease evolution in individual patients

Using formal specifications to support testing.

Formal methods and testing are two important approaches that assist in the development of high-quality software. While traditionally these approaches have been seen as rivals, in recent years a new consensus has developed in which they are seen as complementary. This article reviews the state of the art regarding ways in which the presence of a formal specification can be used to assist testing

Potencial evocado auditivo para diagnóstico de surdez bilateral em dois cães

O potencial auditivo evocado de tronco encefálico é um método eletrodiagnóstico não invasivo que permite avaliação objetiva do estado auditivo, da orelha média ao tronco encefálico, captando a atividade elétrica do sistema auditivo, gerada a partir de um estímulo sonoro específico. O uso desse teste não é difundido em animais no Brasil. Sendo assim, o objetivo do presente trabalho é relatar o diagnóstico de surdez bilateral em dois cães sem raça definida, com a utilização do potencial evocado auditivo de tronco encefálico.The brainstem auditory evoked potential is a noninvasive electrodiagnostic test allowing an objective assessment of the hearing status, by capturing the electrical activity of the auditory system, from the middle ear to the brainstem, generated after a specific sound stimulus is performed. The use of this test is not common in animals in Brazil. Therefore, the objective of this study is to report the diagnosis of bilateral deafness in two mongrel dogs, using the brainstem auditory evoked potential

Estudo normativo e avaliação da influência da idade no potencial evocado auditivo em cães sem raça definida

The aim of this paper was to obtain normative data of auditory evoked potentials from 34 mixed breed dogs and evaluate the age influence. The animals were divided in two groups of different ages and auditory evoked potential was performed with a 85dB stimulus intensity. Group 1 included 16 dogs between 1 and 8 years of age, and group 2 included 18 dogs with over 8 years of age. The length and head diameter were measured and there was no statistical difference between the two groups. In group 1, mean latencies of waves I, III, and V were 1.13; 2.64, and 3.45ms, and the intervals I-III, III-V, and I-V were 1.51; 0.81, and 2.32 ms, respectively. In group 2, the mean latencies of waves I, III and V were 1.15, 2.62, and 3.55ms, and the intervals I-III, III-V, and I-V were 1.47, 0.93, and 2.40ms, respectively. The latencies observed in this study were similar to previous studies conducted by other authors. It was observed that significant differences were present for wave V and intervals III-V and I-V latencies when comparing groups with different ages, consequently this characteristic must be considered during BAEP result interpretation.Aluna de pós-graduação Faculdade de Medicina Veterinária e Zootecnia FMVZ-Unesp, Botucatu, SPFaculdade de Medicina de Botucatu FMB-Unesp, Botucatu, SPFaculdade de Medicina Veterinária e Zootecnia FMVZ-Unesp, Botucatu, SPAluna de pós-graduação Faculdade de Medicina Veterinária e Zootecnia FMVZ-Unesp, Botucatu, SPFaculdade de Medicina de Botucatu FMB-Unesp, Botucatu, SPFaculdade de Medicina Veterinária e Zootecnia FMVZ-Unesp, Botucatu, S