Multi-gene risk-score for prediction of clinical outcomes in treatment-naïve metastatic castrate resistant prostate cancer.

Background: To determine the performance of a multi-gene copy number variation (MG-CNV) risk score in metastatic tissue and plasma biospecimens from treatment-naïve metastatic castrate-resistant prostate cancer (mCRPC) patients for prediction of clinical outcomes.

Methods: mCRPC tissue and plasma cell-free DNA (cfDNA) biospecimen sequencing results obtained from publicly accessed cohorts in dbGaP, cBioPortal, and an institutional mCRPC cohort were used to develop a MG-CNV risk score derived from gains in AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1 and losses in TMPRSS2, NCOR1, ZBTB16, TP53, NKX3-1 in independent cohorts for determining overall survival (OS), progression free survival (PFS) to first-line Androgen Receptor Pathway Inhibitors (ARPIs). The range of the risk scores for each cohort was dichotomized into "high-risk" group and "low-risk" groups and association with OS/PFS determined.

Therapy-Related Myeloid Neoplasms After [Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series.

[Lu]Lu-prostate-specific membrane antigen (PSMA) therapy has a favorable toxicity profile in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapy-related myeloid neoplasm (t-MN) has been described after [Lu]Lu-DOTATATE but has not, to our knowledge, yet been reported after [Lu]Lu-PSMA. This case series describes 5 patients with mCRPC who developed t-MN after [Lu]Lu-PSMA at our institution.

Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes.

Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

Plasma Cell-Free DNA Chromatin Immunoprecipitation Profiling Depicts Phenotypic and Clinical Heterogeneity in Advanced Prostate Cancer.

Cell phenotype underlies prostate cancer presentation and treatment resistance and can be regulated by epigenomic features. However, the osteotropic tendency of prostate cancer limits access to metastatic tissue, meaning most prior insights into prostate cancer chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive chromatin immunoprecipitation of histones in plasma cell-free DNA (cfDNA) in humans may enable the capture of disparate prostate cancer phenotypes.