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1.
Am J Gastroenterol ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-39007710

ABSTRACT

INTRODUCTION: To evaluate real-world healthcare resource utilization (HCRU) and costs associated with eosinophilic esophagitis (EoE) in the United States. METHODS: Retrospective case-control cohort analysis of Optum Clinformatics claims data (January 2008-September 2020) comparing unadjusted and adjusted HCRU (visits per 1,000 patients per month) and all-cause costs (per patient per month). RESULTS: Patients with EoE incurred significantly higher monthly HCRU (adjusted Δ [95% confidence interval]: inpatient visits, 2.8 [0.1-4.0]; emergency department visits, 14.7 [4.3-32.1]; outpatient visits, 388.8 [362.1-418.0]); and costs ($581 [$421-$600]) vs matched controls (all P < 0.001). DISCUSSION: EoE imposes substantial economic burden. More effective and targeted treatments that improve outcomes for patients are needed.

2.
Mol Cell ; 83(12): 1983-2002.e11, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37295433

ABSTRACT

The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 minor intron-containing genes (MIGs) crucial for cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role of MIGs and MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling and elevated levels of U6atac, a MiS small nuclear RNA, regulate MiS activity, which is highest in advanced metastatic PCa. siU6atac-mediated MiS inhibition in PCa in vitro model systems resulted in aberrant minor intron splicing leading to cell-cycle G1 arrest. Small interfering RNA knocking down U6atac was ∼50% more efficient in lowering tumor burden in models of advanced therapy-resistant PCa compared with standard antiandrogen therapy. In lethal PCa, siU6atac disrupted the splicing of a crucial lineage dependency factor, the RE1-silencing factor (REST). Taken together, we have nominated MiS as a vulnerability for lethal PCa and potentially other cancers.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Male , Humans , Introns/genetics , Prostatic Neoplasms/metabolism , RNA Splicing/genetics , Spliceosomes/metabolism , Signal Transduction , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Cell Line, Tumor , Prostatic Neoplasms, Castration-Resistant/genetics
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