Abstract: A primary reason why potential anticancer drugs fail in clinical trials is the limitations of existing in vitro screening systems. The purpose of in vitro testing is to aid in the selection of efficacious compounds from a range of candidates with variable levels of the desired properties. In vitro cell-culture tumor models are the most widely used screening systems, however, they lack the complexity of the natural microenvironment of the host organism. Clearly, an effective screening system should possess qualities and organization similar to those of a natural tumor microenvironment. In an attempt to better simulate a tumor and its microenvironment sophisticated models have been developed, such as the three-dimensional cultures. In addition to these in vitro culture methods, tissue-based testing methods have been used to screen potential anticancer drugs but these methods have limited utility. This review describes the modern in vitro models used to evaluate cytotoxic substances that inhibit the growth of tumor cells and discusses their respective advantages and disadvantages.
Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins.
Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins. In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the co-stimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.