MicroRNAs in cancer treatment and prognosis

Disturbances in microRNA expression by epigenetic alterations and mutations may promote not only tumorigenesis but also tumor aggressiveness, invasion, metastasis, and resistance to chemotherapy and radiotherapy. Several studies have profiled microRNA expression in normal and tumorigenic tissues, demonstrating a unique microRNA signature, which can be used as a marker for cancer diagnosis and prognosis. This review discusses the importance of microRNAs as regulatory biomolecules involved in cancer, focusing on microRNAs related to cancer invasion, metastasis, epigenetic alterations, chemoresistance, and radioresistance. The identification of both differentially expressed microRNAs in tumors and their target genes provides new tools for gene therapy; the re-expression of microRNAs silenced by cancer development or the silencing of oncogenic microRNAs can be effective in the blockade of cancer-related cell proliferation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Italian Association for Cancer Research (AIRC)Univ Fed Sao Paulo, Dept Biochem, BR-04044020 Sao Paulo, BrazilUniv Sao Paulo, Dept Genet & Evolutionary Biol, BR-05508090 Sao Paulo, BrazilUniv Genoa, Dept Hlth Sci, I-16132 Genoa, ItalyUniv Fed Sao Paulo, Dept Biochem, BR-04044020 Sao Paulo, BrazilItalian Association for Cancer Research (AIRC): 8909Web of Scienc

Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro

E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs) reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s) other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation

The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation

The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer

Rett syndrome: analysis of MECP2 mutations in Brazilian patients.

EPM UNIFESP, Ctr Genet Med, Sao Paulo, BrazilUniv Sao Paulo, Dept Biol IB, Sao Paulo, BrazilUniv Sao Paulo, Dept Neurol FM, Sao Paulo, BrazilEPM UNIFESP, Ctr Genet Med, Sao Paulo, BrazilWeb of Scienc

Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy

Abstract Objective: develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. Method: descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. Results: the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate <80%, and was reformulated based on the participants' suggestions. All other items were considered appropriate and/or complete appropriate in the three blocks proposed: objectives - 92.38%, structure and form - 89.74%, and relevance - 94.44%. Conclusion: the face and content validation of the educative manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation

Validación de manual educativo para pacientes con cáncer de cabeza y cuello sometidos a radioterapia

Objetivo: validar o conteúdo e a aparência de manual educativo direcionado aos pacientes com câncer de cabeça e pescoço, submetidos à radioterapia. Método: pesquisa metodológica, de caráter descritivo. Utilizou-se a Teoria da Psicometria para o processo de validação, o qual foi realizado por 15 peritos na área temática do manual educativo e por dois profissionais de letras e publicidade. Foi considerado o índice de concordância de, no mínimo, 80% para se garantir a validação do material. Resultados: os itens abordados no instrumento de avaliação do manual educativo foram divididos em três blocos: objetivos, estrutura e apresentação, e relevância. Apenas um item, relacionado ao nível sociocultural do público-alvo, obteve índice de concordância <80%, tendo sido reformulado com base nas sugestões dos participantes. Todos os outros itens foram considerados adequados e/ou totalmente adequados nos três blocos propostos: objetivos - 92,38%, estrutura e apresentação - 89,74%, e relevância - 94,44%. Conclusão: o manual educativo proposto foi considerado válido quanto ao conteúdo e à aparência. Sugere-se que possa contribuir para a compreensão do processo terapêutico ao qual o paciente com câncer de cabeça e pescoço é submetido ao realizar a radioterapia, além de subsidiar a prática clínica por meio da consulta de enfermagem.Objective: develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. Method: descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. Results: the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate <80%, and was reformulated based on the participants' suggestions. All other items were considered appropriate and/or complete appropriate in the three blocks proposed: objectives - 92.38%, structure and form - 89.74%, and relevance - 94.44%. Conclusion: the face and content validation of the educative manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation.Objetivo: validar el contenido y la apariencia de manual educativo dirigido a los pacientes con cáncer de cabeza y cuello, sometidos a radioterapia. Método: investigación metodológica de carácter descriptivo. Se utilizó la Teoría de la Psicometría para el proceso de validación, el cual fue realizado por 15 peritos en el área temática del manual educativo y por dos profesionales de letras y publicidad. Fue considerado un índice de concordancia que fuese, por lo menos, de 80%, para garantizar la validación del material. Resultados: los ítems abordados en el instrumento de evaluación del manual educativo fueron divididos en tres bloques: objetivos, estructura y presentación, y relevancia. Apenas un ítem, relacionado al nivel sociocultural del público-objetivo, obtuvo un índice de concordancia <80%, habiendo sido reformulado con base en las sugestiones de los participantes. Todos los otros ítems fueron considerados adecuados y/o totalmente adecuados en los tres bloques propuestos: objetivos (92,38%), estructura y presentación (89,74%), y relevancia (94,44%). Conclusión: el manual educativo propuesto fue considerado válido en lo que se refiere al contenido y a la apariencia. Se sugiere que puede contribuir para la comprensión del proceso terapéutico, al cual el paciente con cáncer de cabeza y cuello es sometido al realizar la radioterapia, además de auxiliar la práctica clínica por medio de la consulta de enfermería

Impact of an inpatient multidisciplinary glucose control management program

ABSTRACT Objective: Glycemic control has been increasingly recognized as a critical element in inpatient care, but optimal management of blood glucose in the hospital setting remains challenging. The aims of this study were to describe and evaluate the impact of the implementation of an inpatient multidisciplinary glucose control management program on glucose control in hospitalized patients. Materials and methods: Retrospective analysis of medical records and glucose monitoring data obtained by point- of-care testing (POCT) in hospitalized patients before (May 2014) and after (June 2015 and May 2017) the implementation of the program. Results: We analyzed 6888, 7290, and 7669 POCTs from 389, 545, and 475 patients in May 2014, June 2015, and May 2017, respectively. Hyperglycemia (≥ 180 mg/ dL) occurred in 23.5%, 19.6%, and 19.3% POCTs in May 2014, June 2015, and May/2017, respectively (p < 0.001), while severe hyperglycemia (≥ 300 mg/dL) was observed in 2.5%, 2.2%, and 1.8% of them, respectively (p = 0.003). Hyperglycemia (≥ 180 mg/dL) reduced significantly from May 2014 to June 2015 (16.3%, p < 0.001) and from May 2014 to May 2017 (178%, p < 0.001). No significant changes occurred in hypoglycemic parameters. Conclusions: The implementation of an inpatient multidisciplinary glucose control management program led to significant reductions in hyperglycemic events. The key elements for this achievement were the development of institutional inpatient glycemic control protocols, establishment of a multidisciplinary team, and continuing educational programs for hospital personnel. Altogether, these actions resulted in improvements in care processes, patient safety, and clinical outcomes of hospitalized patients