An Update on Diagnostic Laboratory Biomarkers for Multiple Sclerosis.

PURPOSE: For many patients, the multiple sclerosis (MS) diagnostic process can be lengthy, costly, and fraught with error. Recent research aims to address the unmet need for an accurate and simple diagnostic process through discovery of novel diagnostic biomarkers. This review summarizes recent studies on MS diagnostic fluid biomarkers, with a focus on blood biomarkers, and includes discussion of technical limitations and practical applicability. RECENT FINDINGS: This line of research is in its early days. Accurate and easily obtainable biomarkers for MS have not yet been identified and validated, but several approaches to uncover them are underway. Continue efforts to define laboratory diagnostic biomarkers are likely to play an increasingly important role in defining MS at the earliest stages, leading to better long-term clinical outcomes.

The natural compound obtusaquinone targets pediatric high-grade gliomas through ROS-mediated ER stress.

BACKGROUND: Pediatric high-grade gliomas (pHGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis. Treatment of pHGGs is particularly challenging given the intrinsic resistance to chemotherapy, an absence of novel therapeutics, and the difficulty of drugs to reach the tumor beds. Accumulating evidence suggests that production of reactive oxygen species (ROS) and misfolded proteins, which typically leads to endoplasmic reticulum (ER) stress, is an essential mechanism in cancer cell survival. METHODS: Several cell viability assays were used in 6 patient-derived pHGG cultures to evaluate the effect of the natural compound obtusaquinone (OBT) on cytotoxicity. Orthotopic mouse models were used to determine OBT effects in vivo. Immunoblotting, immunostaining, flow cytometry, and biochemical assays were used to investigate the OBT mechanism of action. RESULTS: OBT significantly inhibited cell survival of patient-derived pHGG cells in culture. OBT inhibited tumor growth and extended survival in 2 different orthotopic xenograft models. Mechanistically, OBT induced ER stress through abnormal ROS accumulation. CONCLUSION: Our data demonstrate the utility and feasibility of OBT as a potential therapeutic option for improving the clinical treatment of pHGGs.

Secreted Reporters for Monitoring Multiple Promoter Function.

Secreted reporter proteins are reliable modalities for monitoring of different biological processes, which can be measured longitudinally in conditioned medium of cultured cells or body fluids such as blood and urine, ex vivo. In this chapter, we will explore established secreted reporters and their applications and limitations for monitoring of promoter function. We will also describe both cell-based and blood-based assays for detecting three commonly used reporters: secreted alkaline phosphatase (SEAP ), Gaussia luciferase (Gluc), and Vargula luciferase (Vluc).

Imaging Tumor Vascularity and Response to Anti-Angiogenic Therapy Using Gaussia Luciferase.

We developed a novel approach to assess tumor vascularity using recombinant Gaussia luciferase (rGluc) protein and bioluminescence imaging. Upon intravenous injection of rGluc followed by its substrate coelenterazine, non-invasive visualization of tumor vascularity by bioluminescence imaging was possible. We applied this method for longitudinal monitoring of tumor vascularity in response to the anti-angiogenic drug tivozanib. This simple and sensitive method could be extended to image blood vessels/vasculature in many different fields.