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1.
Nat Commun ; 15(1): 3431, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654015

RESUMO

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.


Assuntos
Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/dietoterapia , Neoplasias da Próstata/microbiologia , Animais , Humanos , Camundongos , Fezes/microbiologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Camundongos Endogâmicos C57BL , Ácidos Graxos Insaturados/metabolismo
2.
Lab Invest ; 103(10): 100224, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37517701

RESUMO

In an anatomical pathology laboratory, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to characterize amyloid deposits identified in formalin-fixed paraffin-embedded tissue (FFPET). However, the development of additional tests is partially limited by the lack of information the passage of time has on the proteins in FFPET. To investigate the reliability of LC-MS/MS in the analysis of old FFPET specimens, 1 bone marrow aspirate clot was analyzed by LC-MS/MS yearly from 2014 to 2018, in 3 consecutive months. Peptide-spectrum match, number of peptides identified, and percentage of the proteins covered were the parameters collected for the hemoglobin subunits alpha (HbA), beta (HbB), delta (HbD), and gamma (HbG). These proteins are constant components of the peripheral blood and are present in high and low abundance, allowing the monitorization of the performance of the test across varying protein concentrations. The hemoglobin subunits were stable over the years studied; 71% to 74% of HbA, 77% to 80% of HbB, 69% to 77% of HbD, and 57% to 63% of HbG were covered, with no statistical difference between 2014 and 2018. The number of peptides identified was also constant, 11 to 13 for HbA, 13 to 15 for HbB, 11 to 14 for HbD, and 7 to 9 for HbG. Peptide spectrum match was only slightly more variable: 209 to 327 for HbA, 569 to 1052 for HbB, 286 to 533 HbD, and 142 to 292 for HbG. In conclusion, high abundance hemoglobins, HbA and HbB, and relatively low abundance ones, HbD and HbG, are preserved in FFPET and confidently identified by LC-MS/MS for at least 5 years.


Assuntos
Formaldeído , Espectrometria de Massas em Tandem , Cromatografia Líquida , Formaldeído/química , Inclusão em Parafina/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Proteínas , Peptídeos , Subunidades de Hemoglobina/análise , Fixação de Tecidos/métodos
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