Neutralizing antibodies to interferon beta in multiple sclerosis: analytical evaluation for validation of a cytopathic effect assay

BACKGROUND: Recent guidelines have recommended the use of validated assays for the measurement of neutralizing antibodies (NABs) to interferon beta (IFNbeta) in patients with multiple sclerosis (MS). In an attempt of validation, we studied the analytical performance of a bioassay based on antiviral cytopathic effect (CPE) using WISH cells and the vesicular stomatitis virus (WISH/VSV CPE). METHODS: NAB titres measured with the WISH/VSV CPE assay in 63 sera from IFNbeta-treated MS patients were compared to those obtained with the reference CPE method using A549 cells and the encephalomyocarditis virus. Binding antibodies (BABs) were measured using a capture ELISA as a screening test for NABs. RESULTS: No false-negative BAB was obtained in our patients. The between-run coefficients of variation (CVs) determined with log10 titres of the NIH anti-IFNbeta (G038-501-572) yielded good results (相似文献   

Hypoxia‐inducible factor‐1 (HIF‐1) inhibitors from the last decade (2007 to 2016): A “structure–activity relationship” perspective

Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia‐inducible factor (HIF‐1) protein leads to angiogenesis, metastasis, apoptosis resistance, and many other pro‐tumorigenic responses in cancer development. HIF‐1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia‐sensitive, a target‐specific HIF‐1 inhibitor may be a better clinical candidate in cancer drug discovery. Though no HIF‐1 inhibitor is clinically available to date, a lot of effort has been applied during the last decade in search of potent HIF‐1 inhibitors. In this review, we will summarize the structure–activity relationship of ten different chemotypes reported to be HIF‐1 inhibitors in the last decade (2007–2016), their mechanisms of action for HIF‐1 inhibition, progress in the way of target‐specific inhibitors, and problems associated with current inhibitors. It is anticipated that the results of these research on the medicinal chemistry of HIF‐1 inhibitors will provide decent information in the design and development of future inhibitors.