Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described.
View Article and Find Full Text PDFMetastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, in this study we analyzed multi-organ metastases and tumor-adjacent tissues from 11 rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms.
View Article and Find Full Text PDFNeoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of mutations and signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival.
View Article and Find Full Text PDFThe COVID-19 pandemic changed the clinical research landscape in America. The most urgent challenge has been to rapidly review protocols submitted by investigators that were designed to learn more about or intervene in COVID-19. International Review Board (IRB) offices developed plans to rapidly review protocols related to the COVID-19 pandemic.
View Article and Find Full Text PDFIntroduction: Biosamples and associated clinical data accelerate translational and clinical research discoveries. A lack of high quality biosamples both stalls projects and limits research advances. In this study, we targeted a wide audience of University of California (UC) biobanking stakeholders who were either involved with the collection or the utilization of biosamples to assess the scope of their biobanking activities and their interest in virtual biobanking or cooperating in the formation of the UC-wide biorepository.
View Article and Find Full Text PDFUnlabelled: Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic lesion. The purpose of this study was to determine if blockade of both pathways would inhibit the formation these lesions in bone. Inhibition of the osteoblastic lesion with noggin and the osteolytic lesion with RANK:Fc was a successful treatment strategy to inhibit progression of mixed lung cancer lesions in bone.
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