Modulação da expressão de microrna’s para reprogramar o fenótipo dos macrófagos como imunoterapia anti-cancro

Macrophages play an important role in tumour progression and metastasis due to the plasticity expressed during activation, especially noticeable in vivo. Depending on the signals present in the tumour microenvironment (TME), macrophages can have a pro-inflammatory phenotype, known as M1 macrophages, or an anti-inflammatory phenotype, known as M2 macrophages. M1 macrophages are associated with the cancer-related inflammation common in the early stages of tumorigenesis. Later, signals from the TME can polarize macrophages towards an M2-like phenotype, referred as tumour-associated macrophages (TAMs), a pro-tumour response, which leads to tumour progression, angiogenesis, and metastasis. The presence of TAMs in the TME is normally linked to a poor prognosis for cancer patients. The activation state and, consequently, the functions of macrophages are tightly regulated by microRNAs (miRNAs). miRNAs regulate geneexpression after transcription and modulate many aspectsof the immune responses such as differentiation, proliferation, cells’ function, but also, cytokine responses. miRNAs can act either as oncogenes or as tumour suppressors, by affecting the polarization of macrophages. There are miRNAs involved both in the promotion or inhibition of macrophage activated phenotypes, besides miRNAs involved in differentiation. Alterations in miRNA expression can drive oncogenesis, tumour progression and metastasis, by contributing to the generation of TAMs. TAMs in conjunction with miRNAs are great therapeutic candidates. Therapeutically regulating miRNA levels may be linked to cancer treatment and to the regulation of the immune response. Reactivating pro-inflammatory genes in TAMs might help to promote tumour rejection. This project aims to compile a review of the literature concerning miRNA’s modulation towards cancer immunotherapy, but also to assess the effect of anticancer drugs in the expression of selected miRNAs, focusing on reprogramming TAMs phenotype.Os macrófagos desempenham um papel importante na progressão tumoral e metástase devido à plasticidade demonstrada durante a sua ativação, sendo especialmente percetível in vivo. Dependendo dos sinais presentes no microambiente tumoral (TME), os macrófagos podem ter um fenótipo próinflamatório, conhecidos como macrófagos M1, ou um fenótipo antiinflamatório, conhecidos como macrófagos M2. Os macrófagos M1 estão associados à inflamação comum nos estágios iniciais da tumorigénese. Posteriormente, os sinais do TME podem polarizar macrófagos em direção a um fenótipo semelhante ao dos macrófagos M2, denominados como macrófagos associados ao tumor (TAMs), uma resposta pró-tumor, que leva à progressão tumoral, angiogénese e metástase. A presença de TAMs no TME está normalmente associada a um prognóstico negativo para pacientes oncológicos. O estado de ativação e, consequentemente, as funções dos macrófagos são estritamente reguladas por microRNAs (miRNAs). Os miRNAs regulam a expressão génica após a transcrição e modulam muitos aspetos das respostas imunes, como a diferenciação, proliferação, função das células, e também, libertação de citocinas. Os miRNAs podem atuar como oncogenes ou como supressores de tumor, afetando a polarização dos macrófagos. Existem miRNAs envolvidos tanto na promoção quanto na inibição de fenótipos dos macrófagos, além de existirem miRNAs envolvidos na diferenciação celular. Alterações na expressão de miRNAs podem conduzir a oncogénese, progressão tumoral e metástase, contribuindo para a geração de TAMs. Os TAMs em conjunto com miRNAs são ótimos candidatos terapêuticos. A regulação terapêutica dos níveis de miRNA pode estar ligada ao tratamento do cancro e à regulação da resposta imune. A reativação de genes próinflamatórios nos TAMs pode ajudar a promover a rejeição do tumor. Este projeto tem como objetivo compilar uma revisão da literatura sobre a modulação de miRNAs de encontro à imunoterapia contra o cancro, mas também avaliar o efeito de compostos na expressão de miRNAs selecionados, com foco na reprogramação do fenótipo dos TAMs.Mestrado em Biologia Aplicad

Plane Gravitational Radiation from Neutrinos Source with Kalb-Ramond Coupling

In this work, we propose a model based on a non-minimal coupling of neutrinos to a Kalb-Ramond field. The latter is taken as a possible source for gravitational radiation. As an immediate illustration of this system, we have studied the case where gravitational (plane) wave solutions behave as damped harmonic oscillators.Comment: Presented at 7th Alexander Friedmann International Seminar on Gravitation and Cosmology, Joao Pessoa, Brazil, 29-05 Jul 200

Confined magneto-optical waves in graphene

The electromagnetic mode spectrum of single-layer graphene subjected to a quantizing magnetic field is computed taking into account intraband and interband contributions to the magneto-optical conductivity. We find that a sequence of weakly decaying quasi-transverse-electric modes, separated by magnetoplasmon polariton modes, emerge due to the quantizing magnetic field. The characteristics of these modes are tuneable, by changing the magnetic field or the Fermi energy.Comment: 9 pages, 7 figures. published version: text and figures revised and updated + new references and one figure adde

Metamodels of information technology best practices frameworks

This article deals with the generation and application of ontological metamodels of frameworks of best practices in IT. The ontological metamodels represent the logical structures and fundamental semantics of framework models and constitute adequate tools for the analysis, adaptation, comparison and integration of the frameworks of best practices in IT. The MetaFrame methodology for the construction of the metamodels, founded on the discipline of the conceptual metamodelling and on the extended Entity/Relationship methodology is described herein, as well as the metamodels of the best practices for the outsourcing of IT, the eSCM-SP v2.01 (eSourcing Capability Model for Service Providers) and the eSCM-CL v1.1 (eSourcing Capability Model for Client Organizations), constructed according to the MetaFrame methodology

Dilatonic, Current-Carrying Cosmic String

We study the implications of a scalar-tensorial gravity for the metric of an isolated self-gravitating superconducting cosmic string. These modifications are induced by an arbitrary coupling of a massless scalar field to the usual tensorial field in the gravitational Lagrangian. We derive the metric in the weak-field approximation and we analyse the behaviour of light in this spacetime. We end with some discussions.Comment: 12 pp, Latex, no figures, based on a talk given by M. E. X. Guimaraes at the COSMO 99, 27/9 to 02/10/99, ICTP, Trieste, I

Interação fármaco-receptor

Diagrama de esquema apresentando a interação fármaco-receptor1.0Ministério da Saúde do Brasi