Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.

Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9–93.9%. However, the concordance rate decreased to 11.8–17.1% when considering only genes with reported genomic alterations in either assay. Over 50% of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1% and 94.8%, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.

O processo de formação em saúde tem passado por diversas mudanças no contexto contemporâneo, tornando-se relevante averiguar as modalidades metodológicas e conhecer os impactos atribuídos a estas transformações. Neste sentido, o estudo tem por objetivo refletir sobre as perspectivas atuais de ensino e aprendizagem no contexto da formação em saúde e enfermagem a partir do uso da simulação enquanto metodologia ativa. Trata-se de um estudo teórico reflexivo. Para a análise dos resultados, utilizou-se a Análise de Contexto (AC). Foram utilizadas as seguintes camadas interativas: a simulação como contexto imediato, as metodologias ativas como contexto específico, educação e formação em saúde como contexto geral e a formação em saúde como metacontexto. Reflete-se sobre a simulação enquanto método dinâmico e instrumento auxiliar de ensino-aprendizagem em saúde e enfermagem. Espera-se que as reflexões tecidas permitam a construção de conceitos que circundem a complexidade da formação em saúde e, em especial, a formação em enfermagem.

Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens.

Mutually exclusive genetic alterations in the RET, RAS, or BRAF genes, which result in constitutively active mitogen-activated protein kinase (MAPK) signaling, are present in about 70% of papillary thyroid carcinomas (PTCs). However, the effect of MAPK activation on other signaling pathways involved in oncogenic transformation, such as Notch, remains unclear. In this study, we tested the hypothesis that the MAPK pathway regulates Notch signaling and that Notch signaling plays a role in PTC cell proliferation. Conditional induction of MAPK signaling oncogenes RET/PTC3 or BRAF(T1799A) in normal rat thyroid cell line mediated activation of Notch signaling, upregulating Notch1 receptor and Hes1, the downstream effector of Notch pathway. Conversely, pharmacological inhibition of MAPK reduced Notch signaling in PTC cell. Thyroid tumor samples from transgenic mice expressing BRAF(T1799A) and primary human PTC samples showed high levels of Notch1 expression. Down-regulation of Notch signaling by γ-secretase inhibitor (GSI) or NOTCH1 RNA interference reduces PTC cell proliferation. Moreover, the combination of GSI with a MAPK inhibitor enhanced the growth suppression in PTC cells. This study revealed that RET/PTC and BRAF(T1799A) activate Notch signaling and promote tumor growth in thyroid follicular cell. Taken together, these data suggest that Notch signaling may be explored as an adjuvant therapy for thyroid papillary cancer.

©2017 Universidad de Santander. Este es un artículo de acceso abierto, distribuido bajo los términos de la licencia Creative Commons Attribution (CC BY-NC 4.0), que permite el uso ilimitado, distribución y reproducción en cualquier medio, siempre que el autor original y la fuente sean debidamente citados.

Esta investigación tuvo como objetivo evaluar la calidad de vida de los pacientes con enfermedad renal crónica en hemodiálisis, así como caracterizarlos, identificar los factores que afectan e influyen en la misma. Se trata de un estudio de campo, descriptivo, transversal y cuantitativo realizado en un centro de hemodiálisis en el Alto Sertão da Paraíba, municipio Cajazeiras. Se utilizó un cuestionario sociodemográfico y el WHOQOL-BREF para evaluar los puntajes promedio y la calidad de vida de los participantes, así como la prueba de correlación de Pearson entre las variables obtenidas. La muestra estuvo conformada por 39 sujetos. La investigación incluyó a pacientes de ambos sexos: 54% hombres y 46% mujeres y tiene, con respecto a la edad, alta prevalencia de más de 51 años. En general, el dominio más afectado entre los participantes fue el dominio físico (DF), con un promedio de 59.44, y el mejor conservado fue el dominio social (DS), con un promedio de 72.87, reflejado en la Calidad de Vida (QOL) de los pacientes con IR, que mostró un promedio de 64.96. A través del test de correlación de Pearson, hubo una relación significativa entre los diversos ámbitos en los que todos los dominios mostraron una alta correlación con la calidad de vida. Llegamos a la conclusión de que los pacientes con enfermedad renal crónica en hemodiálisis tienen una calidad de vida regular, y el conocimiento de los profesionales sobre este tema es de suma importancia para alcanzar una optimización en el cuidado de los pacientes con IRC sometidos a hemodiálisis

Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14–0.31; P<0.001), the benefit of lenvatinib needs to be proved in the context of associated moderate to severe toxicities that require frequent dose reduction and delays. This article reviews the evidence supporting the use of lenvatinib as salvage therapy for radioactive iodine-refractory thyroid cancer, with a focus on the toxicity profile of this new therapy.