[Show abstract][Hide abstract] ABSTRACT: Rat pituitary malignant tumor cells; mGH3, show hypervascularization in in vivo xenografts and overexpress parathyroid hormone-related peptide (PTHrP) compared to original GH3 cells. To elucidate whether PTHrP is involved in tumor-derived angiogenesis, we examined the effect of PTHrP on vascular endothelial cells both in vitro and in vivo. Results of in vivo diffusion chamber assay showed a clear hypervascularization on the outer surface of diffusion chambers containing mGH3 tumor cell implants but not in those containing GH3 cells. Co-incubation with antisense PTHrP oligonucleotide (10 microM), but not sense or mismatched PTHrP oligonucleotide, suppressed hypervascularization in diffusion chambers. To further examine the role of PTHrP on endothelial cell function, PTHrP(1-34) was added at various concentrations to cultured bovine endothelial cells (BAECs) harvested from the aorta. PTHrP(1-34) did not alter the proliferation or migration of endothelial cells, but rather dose-dependently increased capillary formation by endothelial cells on the collagen gel matrix. Furthermore, 0.1 mM of 8-bromo-cAMP caused a similar increase in tube formation, which was dose-dependently inhibited by H89, a protein kinase A inhibitor. Our results indicate for the first time that PTHrP is a potential paracrine factor acting via the PKA pathway to enhance angiogenesis through capillary tube formation by endothelial cells in malignant pituitary tumors.
[Show abstract][Hide abstract] ABSTRACT: The quantity of powder food consumed by individual mice was gauged with a newly developed apparatus that includes a specialized feeding station, an electric scale, and an interface to a computer that records the weight of the powder food jar. Using the measurements that exceeded the cutoff value, that is, the threshold between a mouse feeding or drinking event and scale noise, the reconstructed data were presented as the daily pattern of feeding and drinking in time resolution of 9 to 30 min. In this system, the ratio of noise to total consumption value was less than 4%. The fractal structure and fitting curve of this time series data were also analyzed by the nonlinear least-squares method, combined with the maximum entropy method. These analyses demonstrated that the mouse feeding event has circadian and ultradian periodicity. This apparatus and system are useful tools in studying the daily feeding pattern of mice.