Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application

Journal ArticleProtein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be greater in adenomatous pituitary cells than in normal human and rat pituitary cells and higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of PKC activity has been shown in a variety of tumor cells to inhibit growth in a dose-related fashion. The purpose of the current study was to determine whether hypericin, a potent inhibitor of PKC activity that may be administered clinically, alters the growth and proliferation in established pituitary adenoma lines and to determine if inhibition of PKC activity induces apoptosis, as reported in some other tumor cell types. Two established pituitary adenoma cell lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for defined periods following passage. Inhibition of growth was found to be dose dependent in all three cell lines in low micromolar concentrations of hypericin, as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine uptake studies. Concentrations of hypericin as low as 100 nM also induced apoptosis in these established lines, whereas treatment of normal human fibroblasts with a concentration of 10 mM failed to induce apoptosis. The potential use of hypericin in the therapy of pituitary adenomas warrants additional in vitro investigations with the aim of later moving toward therapeutic trials in selected patients in whom surgical or medical therapy has failed

Wind-Tunnel Tests of a 0.16-Scale Model of the Douglas MX-656 Airplane at High Subsonic Speeds

Wind tunnel tests of the 0.16-scale Douglas MX-656 model were made at low and high subsonic Mach numbers to investigate the static longitudinal- and lateral stability characteristics. The tests shows that undesirable changes in longitudinal stability at the stall were apparently caused by an altered downwash pattern at the tail. The jettisonable nose fins were highly destabilizing. Compressibility effects for the test Mach numbers were not detrimental to the longitudinal- or lateral-stability characteristics

Summary Report on the High-Speed Characteristics of Six Model Wings Having NACA 65sub1-Series Sections

A summary of the results of wind-tunnel tests to determine the high-speed aerodynamic characteristics of six model wings having NACA 65sub1-series sections is presented in this report. The 8-percent-thick wings were superior to the 10-percent and 12-percent-thick wings from the standpoint of power economy during level flight for Mach numbers above 0.76. However, airplanes that are to fly at Mach numbers below 0.76 will gain aerodynamically if the percentage thickness of the wing and the aspect ratio are both increased. The lift-curve slopes for the 8-percent-thick wings at 0.85 Mach number were roughly twice their low-speed values

Correlation of the Drag Characteristics of a Typical Pursuit Airplane Obtained from High-Speed Wind-Tunnel and Flight Tests

In order to obtain a correlation of drag data from wind-tunnel and flight tests at high Mach numbers, a typical pursuit airplane, with the propeller removed, was tested in flight at Mach numbers up to 0.755, and the results were compared with wind-tunnel tests of a 1/3-scale model of the airplane. The tests results show that the drag characteristics of the test airplane can be predicted with satisfactory accuracy from tests in the Ames 16-foot high-speed wind tunnel of the Ames Aeronautical Laboratory at both high and low Mach numbers. It is considered that this result is not unique with the airplane