Infecções por micobactérias não tuberculosas no Hospital Nereu Ramos, centro de referência em Santa Catarina

Esta série especial de ensaios apresenta textos produzidos pelos alunos do Programa de Pós-Graduacão em Ciências Médicas na disciplina “Seminários de Pesquisa”. Solicitou-se aos alunos que apresentassem, em primeira pessoa, sua motivação e trajetória que os conduziram ao trabalho na pós-graduação, bem como a pergunta e a metodologia de seus projetos de pesquisa, com o principal objetivo de inspirar os estudantes de graduação à carreira de pesquisadores. Neste ensaio, o mestrando apresenta seu interesse pelas infecções causadas por micobatérias não-tuberculosas em sua especialidade médica e como pretende pesquisar sobre suas características em nossa população

The Impact of Transcriptomics on the Fight against Tuberculosis: Focus on Biomarkers, BCG Vaccination, and Immunotherapy

In 1882 Robert Koch identified Mycobacterium tuberculosis as the causative agent of tuberculosis (TB), a disease as ancient as humanity. Although there has been more than 125 years of scientific effort aimed at understanding the disease, serious problems in TB persist that contribute to the estimated 1/3 of the world population infected with this pathogen. Nonetheless, during the first decade of the 21st century, there were new advances in the fight against TB. The development of high-throughput technologies is one of the major contributors to this advance, because it allows for a global vision of the biological phenomenon. This paper analyzes how transcriptomics are supporting the translation of basic research into therapies by resolving three key issues in the fight against TB: (a) the discovery of biomarkers, (b) the explanation of the variability of protection conferred by BCG vaccination, and (c) the development of new immunotherapeutic strategies to treat TB

The Impact of Transcriptomics on the Fight against Tuberculosis: Focus on Biomarkers, BCG Vaccination, and Immunotherapy

In 1882 Robert Koch identified Mycobacterium tuberculosis as the causative agent of tuberculosis (TB), a disease as ancient as humanity. Although there has been more than 125 years of scientific effort aimed at understanding the disease, serious problems in TB persist that contribute to the estimated 1/3 of the world population infected with this pathogen. Nonetheless, during the first decade of the 21st century, there were new advances in the fight against TB. The development of high-throughput technologies is one of the major contributors to this advance, because it allows for a global vision of the biological phenomenon. This paper analyzes how transcriptomics are supporting the translation of basic research into therapies by resolving three key issues in the fight against TB: (a) the discovery of biomarkers, (b) the explanation of the variability of protection conferred by BCG vaccination, and (c) the development of new immunotherapeutic strategies to treat TB

Infecções por micobactérias não tuberculosas no Hospital Nereu Ramos, centro de referência em Santa Catarina

Esta série especial de ensaios apresenta textos produzidos pelos alunos do Programa de Pós-Graduacão em Ciências Médicas na disciplina “Seminários de Pesquisa”. Solicitou-se aos alunos que apresentassem, em primeira pessoa, sua motivação e trajetória que os conduziram ao trabalho na pós-graduação, bem como a pergunta e a metodologia de seus projetos de pesquisa, com o principal objetivo de inspirar os estudantes de graduação à carreira de pesquisadores. Neste ensaio, o mestrando apresenta seu interesse pelas infecções causadas por micobatérias não-tuberculosas em sua especialidade médica e como pretende pesquisar sobre suas características em nossa população

SDF-1/CXCL12 induces directional cell migration and spontaneous metastasis via a CXCR4/Gαi/mTORC1 axis.

Multiple human malignancies rely on C-X-C motif chemokine receptor type 4 (CXCR4) and its ligand, SDF-1/CXCL12 (stroma cell-derived factor 1/C-X-C motif chemokine 12), to metastasize. CXCR4 inhibitors promote the mobilization of bone marrow stem cells, limiting their clinical application for metastasis prevention. We investigated the CXCR4-initiated signaling circuitry to identify new potential therapeutic targets. We used HeLa human cancer cells expressing high levels of CXCR4 endogenously. We found that CXCL12 promotes their migration in Boyden chamber assays and single cell tracking. CXCL12 activated mTOR (mechanistic target of rapamycin) potently in a pertussis-sensitive fashion. Inhibition of mTOR complex 1 (mTORC1) by rapamycin [drug concentration causing 50% inhibition (IC50) = 5 nM] and mTORC1/mTORC2 by Torin2 (IC50 = 6 nM), or by knocking down key mTORC1/2 components, Raptor and Rictor, respectively, decreased directional cell migration toward CXCL12. We developed a CXCR4-mediated spontaneous metastasis model by implanting HeLa cells in the tongue of SCID-NOD mice, in which 80% of the animals develop lymph node metastasis. It is surprising that mTORC1 disruption by Raptor knockdown was sufficient to reduce tumor growth by 60% and spontaneous metastasis by 72%, which were nearly abolished by rapamycin. In contrast, disrupting mTORC2 had no effect in tumor growth or metastasis compared with control short hairpin RNAs. These data suggest that mTORC1 may represent a suitable therapeutic target in human malignancies using CXCR4 for their metastatic spread.