Our results provide evidence that NP samples can be used to distinguish differences between children, but the relative abundance of organisms may differ between the nasopharynx and lower airway in pediatric patients. Studies utilizing NP samples as surrogates for the lower airway should be interpreted with caution.

BackgroundLittle is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics.MethodsSubjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed.ResultsNine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1).ConclusionsDEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH.

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Purpose: The Precision Medicine Initiative® (PMI) goal of ushering in a new and more effective era of health care that benefits all Americans requires two critical and interdependent components: a cohort assembly of one million or more Americans who reflect the diversity of the United States of America and an interdisciplinary workforce that includes nursing. The purpose of this paper is provide an example of nursing involvement in PM, specifically as related to gathering biospecimens (saliva) from vulnerable, under-studied adolescents with disruptive behavior disorders and their family members. Source(s) used: First, we provide a brief description of important concepts related to PM as well as current roles of nurses in PM. Then, we share lessons learned from our feasibility study aimed at increasing the diversity of our state-wide cohort assembly that has provided biospecimens for the Indiana Biobank. Conclusion: Nurses can definitely contribute to biobanks in support of the PMI. This paper is a call to action for nurses to take their rightful place in PM.

Background: Resistance to anti-cancer therapies results in relapsed/refractory disease of Glioblastoma (GBM) and Ewing’s Sarcoma. Up-regulation of membrane-bound complement regulatory proteins (mCRPs) CD46, CD55, and CD59 can enable solid tumors to confer resistance to antibody-mediated immunotherapy by preventing complement and antibody-dependent cytotoxicity. mCRPs’ inhibitory role in monoclonal antibody treatments for liquid tumors have been reported, but their role and regulation in solid tumors has not been explored. In the context of refractory tumors, others have reported that vascular endothelial growth factor-A (VEGF-A) can induce mCRP expression in endothelial cells. Notably, p53 mutational status induces VEGF-A and its receptor (VEGFR2) in breast cancer cell lines. To investigate potential links among p53 status, VEGF-A, and mCRP, we screened wildtype (wt-p53) and mutant p53 solid tumor cell lines for mCRP expression and VEGF-A secretion. Our data suggest that p53 mutational status is associated with expression of CD55 and VEGF-A secretion. These studies provide foundation for potentially recognizing mCRPs as immune biomarkers in solid tumors, ultimately, resulting in development of novel immunotherapies for improved clinical outcomes. Methods: Pediatric Ewing’s sarcoma (CHLA9 and CHLA10) and adult GBM (GBM10 and GBM43) cell lines differing in p53 status were selected for in vitro studies. GBM43 originates from a primary GBM, while GBM10 is from a recurrent GBM patient. Ewing’s Sarcoma cell lines, CHLA9 and CHLA10, were generated from the same patient at primary diagnosis and at relapse respectively. Western blot, and sequencing confirmed the expression and p53 mutational status. mCRP expression was evaluated using RT-PCR and flow cytometry. Milliplex platform assessed VEGF-A expression in cell supernatants. Results: Whole genome sequencing data confirmed p53 mutations in all cell lines. CHLA9 and GBM10 harbor wt-p53. CHLA10 cells have p53 deletion and GBM43 cells have a F270C p53 mutation in both alleles CD55 transcripts were undetected in wt-p53 lines (CHLA9 and GBM10), but CD55 transcripts were increased in mutant/deleted p53 lines (CHLA10 and GBM43). Flow cytometry data show increased CD55 expression in mutant p53 glioblastoma (GBM43) versus wt-p53 (GBM10) cells (p&lt;0.001). Transcript and flow cytometric analysis of CD46 and CD59 in Ewing’s sarcoma and GBM cell lines are in progress. Mutant p53 Ewing’s sarcoma and GBM cell lines secreted more VEGF-A compared to wt-p53 cell lines (p&lt;0.05 and p&lt;0.001, respectively). Conclusion: These findings highlight the importance of further investigating role of VEGF-A in regulating mCRPs in wt-p53 versus mutant p53 solid tumor cell lines. Elucidating mechanisms for mCRP regulation is critical for immune biomarker development and in facilitating the use of antibody-based therapeutic approaches for solid tumors. Citation Format: Pankita Hemant Pandya, M. R. Saadatzadeh, Jixin Ding, Barbara Bailey, Sydney Ross, Khadijeh Bijangi-Vishehsaraei, Mary E. Murray, Karen E. Pollok, Jamie L. Renbarger. Complement regulatory protein expression in solid tumors: implications for resistance to antibody-mediated immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4592. doi:10.1158/1538-7445.AM2017-4592