RESUMO
The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease, and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. Substantial evolution occurs within the prostate, resulting in branching into multiple spatially intermixed lineages. One dominant lineage emerges that initiates and drives systemic metastasis, where polyclonal seeding between sites is common. Routes to metastasis differ between patients, and likely genetic drivers of metastasis distinguish the metastatic lineage from the lineage that remains confined to the prostate within each patient. Body fluids capture features of the dominant lineage, and subclonal expansions that occur in the metastatic phase are non-uniformly represented. Cerebrospinal fluid analysis reveals lineages not detected in blood-borne DNA, suggesting possible clinical utility.
Assuntos
Linhagem da Célula , Biópsia Líquida , Neoplasias da Próstata/patologia , Líquidos Corporais/metabolismo , Cromossomos Humanos Par 8/genética , Células Clonais , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Loci Gênicos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , FilogeniaRESUMO
The osmotic pressure of the rumen contents and also of the blood was altered by intraruminal administration of water or hypertonic solutions. It was found that alterations in osmotic pressure were accompanied by inverse changes in the flow rate of mixed saliva. Intravenous infusion of hypertonic solutions, causing elevation of the osmotic pressure of the blood without affecting that of the rumen, also caused a reduction of salivary secretion rate. The flow rates of both parotid and residual saliva were affected. When strongly hypertonic solutions of sodium or potassium salts were infused into the rumen, or sodium salts or urea were infused into the blood, the concentration of those substances increased in the saliva. Other treatments had little effect on salivary composition.
