The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Calcium and vitamin D metabolism in granulomatous diseases.

Overproduction of the active metabolite of vitamin D 1,25-dihydroxyvitamin D (1,25(OH)2D) has been described in sarcoidosis and other granulomatous diseases. High circulating concentrations of 1,25(OH)2D lead to increased intestinal absorption of calcium, possibly to enhanced bone resorption, and may result in hypercalcaemia and/or hypercalciuria. Data obtained in vivo and in vitro demonstrated that the unregulated production of 1,25(OH)2D lies within the granulomatous tissue and is controlled by glucocorticoids. This abnormal production of 1,25(OH)2D seems to be a general phenomenon of granulomatous processes, which is not exceptional in sarcoidosis, but appears seldom in tuberculosis. These abnormalities, however, are not pathognomonic of granulomatous processes, since they have been described in other diseases such as lymphomas.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe