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1.
Cancer Metastasis Rev ; 41(2): 261-280, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35474500

RESUMO

Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.


Assuntos
Melanoma , Microbiota , Neoplasias Cutâneas , Dieta , Humanos , Imunoterapia , Melanoma/terapia , Neoplasias Cutâneas/terapia
2.
Front Cell Infect Microbiol ; 10: 569685, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123495

RESUMO

In vitro infection models are important for studying the effects of antimicrobials on microbial growth and metabolism. However, many models lack important biological components that resemble the polymicrobial nature of chronic wounds or infections. In this study, we developed a perfused meat model that supports the growth of the human pathogen Pseudomonas aeruginosa in a native meat microbial background to investigate the impact of antibiotics and hydrogen peroxide on polymicrobial community growth and metabolism. P. aeruginosa plays an important role as an etiological agent involved in chronic infections and is a common opportunistic pathogen. Chemical stressors in the form of hydrogen peroxide, carbenicillin, and gentamicin were perfused through the meat with polymicrobial growth on the surface. The relative abundances of P. aeruginosa and the background microbial community were analyzed by cell viability assays, and metabolic changes of the entire community in response to different antimicrobial treatments were characterized by GC-MS analysis of volatile organic compounds. The meat background community was characterized by amplicon sequencing. Relative densities of P. aeruginosa and background microbiota were similar under control conditions. Antimicrobial stressors, even at sub-inhibitory, physiologically relevant concentrations, spurred P. aeruginosa dominance of the meat surface community. Volatile metabolite ion intensity levels showed that antibacterial treatments drive changes in microbial metabolism. The abundance of the P. aeruginosa-derived metabolite, acetophenone, remained stable with treatment, whereas the relative abundances of 2-butanone, 2-nonanone, and 2-aminoacetophenone changed in response to treatment, suggesting these could serve as biomarkers of infection. Our model recapitulates some of the physiological conditions of chronic wounds and facilitates high throughput experiments without the high cost of in vivo models. Expanded use of this perfusion model will contribute to the understanding of polymicrobial growth and metabolism in the context of chronic wounds and infections.


Assuntos
Anti-Infecciosos , Microbiota , Infecções por Pseudomonas , Antibacterianos/farmacologia , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa
3.
Nat Rev Microbiol ; 10(9): 607-17, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22864264

RESUMO

Over the past decade, researchers have begun to characterize viral diversity using metagenomic methods. These studies have shown that viruses, the majority of which infect bacteria, are probably the most genetically diverse components of the biosphere. Here, we briefly review the incipient rise of a phage biology renaissance, which has been catalysed by advances in next-generation sequencing. We explore how work characterizing phage diversity and lifestyles in the human gut is changing our view of ourselves as supra-organisms. Finally, we discuss how a renewed appreciation of phage dynamics may yield new applications for phage therapies designed to manipulate the structure and functions of our gut microbiomes.


Assuntos
Bactérias/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , Biodiversidade , Biota , Trato Gastrointestinal/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Infecções Bacterianas/terapia , Bacteriófagos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Terapias Complementares/métodos , Trato Gastrointestinal/microbiologia , Humanos
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