52-Year-Old With Epistaxis, Hemoptysis, Hoarseness, and Weight Loss.

CLINICAL PRESENTATION: A 52-year-old man presented with hemoptysis of 2 weeks' duration. He had been experiencing hoarseness, right-sided pleuritic chest pain, subjective fevers, chills, night sweats, and 10 pounds weight loss for the previous 2 months. He additionally reported severe frontal headaches, nasal congestion, and intermittent epistaxis, which had been present for a year before his current presentation. He had worked in construction and denied tobacco or illicit drug use.

A mathematical insight into cell labelling experiments for clonal analysis.

Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single-cell resolution is still incomplete due to the technical variations in lineage-tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results.

Glucose-6-phosphatase is a key metabolic regulator of glioblastoma invasion.

UNLABELLED: Glioblastoma (GBM) remains the most aggressive primary brain cancer in adults. Similar to other cancers, GBM cells undergo metabolic reprogramming to promote proliferation and survival. Glycolytic inhibition is widely used to target such reprogramming. However, the stability of glycolytic inhibition in GBM remains unclear especially in a hypoxic tumor microenvironment. In this study, it was determined that glucose-6-phosphatase (G6PC/G6Pase) expression is elevated in GBM when compared with normal brain. Human-derived brain tumor-initiating cells (BTIC) use this enzyme to counteract glycolytic inhibition induced by 2-deoxy-d-glucose (2DG) and sustain malignant progression. Downregulation of G6PC renders the majority of these cells unable to survive glycolytic inhibition, and promotes glycogen accumulation through the activation of glycogen synthase (GYS1) and inhibition of glycogen phosphorylase (PYGL). Moreover, BTICs that survive G6PC knockdown are less aggressive (reduced migration, invasion, proliferation, and increased astrocytic differentiation). Collectively, these findings establish G6PC as a key enzyme with promalignant functional consequences that has not been previously reported in GBM and identify it as a potential therapeutic target. IMPLICATIONS: This study is the first to demonstrate a functional relationship between the critical gluconeogenic and glycogenolytic enzyme G6PC with the metabolic adaptations during GBM invasion.