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Pediatric Preclinical Testing Consortium (PPTC)

ABSTRACT: Pediatric Preclinical Testing Consortium (PPTC)

PROVIDER: PRJNA400657 | ENA |

REPOSITORIES: ENA

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Dirty mice as an alternative for preclinical vaccine testing

Project description:Laboratory mice comprise an inexpensive and expeditious model organism for preclinical vaccine testing; however, vaccine immunogenicity often fails to adequately translate to humans. Recent reports indicate that reconstituting physiologic microbial experience to specific pathogen free (SPF) mice induces durable immunological changes that better recapitulate the human immune system. We examined the impact of microbial experience on responses to vaccination after cohousing laboratory mice with pet store mice. We demonstrate that human transcriptional responses to influenza vaccination are better recapitulated in cohoused mice. Induction of humoral responses by vaccination was dampened in cohoused mice and resulted in poor control upon challenge. Additionally, the establishment of protective heterosubtypic T cell immunity was compromised in cohoused mice. In summary, SPF mice exaggerated both humoral and T cell protection induced by influenza vaccines compared to cohoused mice, suggesting that reconstituting microbial experience in laboratory mice through cohousing may better inform preclinical vaccine testing.

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Epigenetic Landscape of Pediatric Ependymoma Recurrence

Project description:Pediatric ependymoma has relatively low frequencies of DNA mutations, which suggest that epigenetics may drive tumors. However, the epigenetic mechanisms for recurrent ependymoma are still poorly understood. Here, we performed longitudinal and comprehensive DNA methylation and gene expression analysis for recurrent pediatric ependymoma tumors from 10 patients, total 46 DNA methylomes (including primary tumors and matched recurrent tumors; normal pediatric brain tissues and PDOX tumors). Both RELA and PFA tumors maintained the subtype DNA methylation signatures during repeated relapses. We further identified the potential DNA methylation predictors, drivers and boosters and their potential regulated genes for recurrent ependymoma tumors. Increased DNA methylation levels within H3K4me1 enriched regions indicates disturbed functions of LSD1 gene in recurrent ependymoma tumors. Combining novel LSD1 inhibitor SYC-836 with radiation (XRT) significantly prolonged animal survival times in PDOX models of recurrent PFA ependymoma. Our PDOX models provide a unique platform for preclinical testing drugs and development of new therapy for pediatric recurrent ependymoma.

2022-07-12 | GSE156619 | GEO

Ex Vivo Lung Perfusion as a Human Platform for Preclinical Small Molecule Testing

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