Citations

Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. Especially, astrocytes are essential for neuronal activity in the brain. Astrocytes actively participate in synapse formation and brain information processing by releasing or uptaking gliotransmitters such as glutamate, d ‐serine, adenosine 5′‐triphosphate ( ATP ), and adenosine. In the central nervous system, adenosine plays an important role in regulating neuronal activity as well as in controlling other neurotransmitter systems such as GABA , glutamate, and dopamine. Ethanol ( E t OH ) increases extracellular adenosine levels, which regulates the ataxic and hypnotic/sedative (somnogenic) effects of E t OH . Adenosine signaling is also involved in the homeostasis of major inhibitory/excitatory neurotransmission (i.e., GABA or glutamate) through neuron–glial interactions, which regulates the effect of E t OH and sleep. Adenosine transporters or astrocytic SNARE ‐mediated transmitter release regulates extracellular or synaptic adenosine levels. Adenosine then exerts its function through several adenosine receptors and regulates glutamate levels in the brain. This review presents novel findings on how neuron–glial interactions, particularly adenosinergic signaling and glutamate uptake activity involving glutamate transporter 1 ( GLT 1), are implicated in alcoholism and sleep disorders.

Abstract A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute–supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.