Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.
IntroductionThe incorporation of molecular genetic testing into cystic fibrosis (CF) screening programs increases the specificity of the diagnostic strategy and has the potential to decrease the rate of false-positive results. In this sense, our objective was to develop a genotyping assay that could detect 25 pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene with high sensitivity and that could be incorporated into the routine of newborn screening, complementing the current existing protocol used in our public health institution. Methods A mini-sequencing assay was standardized using single-base extension in a previously genotyped control sample. This strategy was validated in a Brazilian cohort of CF patients by Sanger sequencing.
ResultsThe inclusion of the 25 variants in the current newborn screening program increased the identification rates of two alleles from 33 to 52.43% in CF patients. This new approach was able to detect a total of 37 variants, which represents 93.01% of all mutated alleles described in the last CF Brazilian Register. Conclusions Mini-sequencing for the simultaneous detection of 25 CFTR gene variants improves the screening of Brazilian newborns and decreases the number of inconclusive cases. This method uses minimal hands-on time and is suited for rapid screening, which reduces sample processing costs.
Cystic fibrosis (CF) is a genetic disease caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are over 2,000 different pathogenic and non-pathogenic variants described in association with a broad clinical heterogeneity. In this work, we identified a novel variant S511Lfs*2 in CFTR gene that has not been reported in patients with CF. The patient was a female genotyped with c.1000C>T (legacy name: R334W) variant (pathogenic, CF-causing) and the novel variant (S511Lfs*2). We verified the amino acid sequence, the protein structure, and predicted the pathogenicity employing computational analysis. Our findings showed that S511Lfs*2 is a frameshift variant and suggest that it is associated with severe CF phenotype, as it leads to a lack of CFTR protein synthesis, and consequently the loss of its functional activity.
Este artículo propone un sistema computacional distribuido que contiene material didáctico multimedia relacionado con el uso de las ciencias exactas en la vida cotidiana. El sistema pone a disposición de la población el conocimiento generado por ciudadanos locales en el lugar en que dicho conocimiento es utilizado. El acceso al material se realiza mediante códigos QR localizados en la ciudad los cuales son leídos usando dispositivos móviles. El sistema permite a los usuarios conocer temas de ciencias exactas utilizados en la creación o uso de productos y servicios existentes en su comunidad. El conocimiento queda entonces disponible en todo momento y accesible en el lugar donde es utilizado. Este proyecto is probado en la ciudad de Poza Rica, México con la intención de fortalecer las vocaciones científicas y tecnológicas en la población y los resultados se muestran en este artículo.
This paper proposes a distributed computational system that contains multimedia didactic material related to the use of exact sciences in daily life. This system makes available the knowledge generated by local citizens to regular population in the location where that knowledge is used. The access to the material is made by using QR codes located a long the city which are read by using mobile devices. The system allows users to know about exact sciences utilized in the creation or the use of products and services available in their own community. The knowledge is then available at any moment and it is accessible in the location where it is used. This project is being tested in the city of Poza Rica, Mexico with the intention of strengthening the scientific and technological orientation in the population and the results are shown in this paper.
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