Characterization of Fast Ion Absorption of the High Harmonic Fast Wave in the National Spherical Torus Experiment

Ion absorption of the high harmonic fast wave in a spherical torus is of critical importance to assessing the viability of the wave as a means of heating and driving current. Analysis of recent National Spherical Torus Experiment (NSTX) shots has revealed that under some conditions when neutral beam and radio-frequency (RF) power are injected into the plasma simultaneously, a fast ion population with energy above the beam injection energy is sustained by the wave. In agreement with modeling, these experiments find the RF-induced fast ion tail strength and neutron rate at lower B-fields to be less enhanced, likely due to a larger beta profile, which promotes greater off-axis absorption where the fast ion population is small. Ion loss codes find the increased loss fraction with decreased B insufficient to account for the changes in tail strength, providing further evidence that this is an RF interaction effect. Though greater ion absorption is predicted with lower k(sub)||, surprisingly little variation in the tail was observed, along with a small neutron rate enhancement with higher k(sub)||. Data from the neutral particle analyzer, neutron detectors, X-ray crystal spectrometer, and Thomson scattering is presented, along with results from the TRANSP transport analysis code, ray-tracing codes HPRT and CURRAY, full-wave code and AORSA, quasi-linear code CQL3D, and ion loss codes EIGOL and CONBEAM

Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression

<p>Abstract</p> <p>Background</p> <p>Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.</p> <p>Methods</p> <p>Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored <it>in vitro </it>by the capacity of Cdk2 to phosphorylate histone H1.</p> <p>Results</p> <p>MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.</p> <p>Conclusions</p> <p>Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.</p

Characterisation of the influence of anti-gastrin, anti-epidermal growth factor, anti-oestradiol, and anti-luteinising hormone releasing hormone antibodies on the proliferation of 27 cell lines from the gastrointestinal tract.

Numerous data from published reports prove that the proliferation of gastrointestinal tumour cell lines are under the control of many hormones or growth factors, or both. Most of these publications report the influence on a very small number of cell lines of one or two such factors only. This work deals with the in vitro characterisation of the influence of the anti-gastrin, the anti-epidermal growth factor (EGF), the anti-oestradiol (E2), and the anti-luteinising hormone releasing hormone (LHRH) antibodies on the proliferation of a large series of gastrointestinal cell lines. Cell proliferation was assessed by means of the colorimetric MTT assay on a series of 27 gastrointestinal cell lines obtained from the American Type Culture Collection (ATCC). Of the 27 cell lines, the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH neutralising antibodies considerably influenced the proliferation of 13, 25, 12, and 16. No gastrointestinal cell line was unresponsive to the four antibodies simultaneously. The anti-gastrin and anti-EGF antibody induced effects on the 27 gastrointestinal cell line proliferation were significantly correlated, as was also the case for the anti-E2 and anti-LHRH antibody induced effects. Of the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH antibodies, it was the anti-EGF one that had the greatest influence, both quantitatively and qualitatively, on gastrointestinal cell proliferation. The correlation of the effects of definite anti-hormone antibodies is suggestive of a common mechanism of action for the corresponding hormones and casts some doubt on the efficiency of anti-hormone monotherapy

Targeting Na⁺/K⁺-ATPase in non-small cell lung cancer (NSCLC)

18144 Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na+/K+-ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na+/K+-ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na+/K+-ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na+/K+- ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na+/K+-ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC. No significant financial relationships to disclose. </jats:p

New calamenene sesquiterpenes from Tarenna madagascariensis.

Four calamenene sequiterpenes, (+)-(7R,10S)-15-hydroxycalamenene (3), (+)-(7R,10S)-2,15-dihydroxycalamenene (4), (+)-(7R,10S)-2-hydroxy-15-calamenal (5), (+)-(7R,10S)-15-calamenal (6), along with the amorphane sesquiterpene (+)-(1S,6R,7R,10S)-1-hydroxy-3-oxo-amorph-4-ene (16), have been isolated from the Madagascan shrub Tarenna madagascariensis (Rubiaceae) and their structures determined by spectroscopic methods and chemical correlations. Furthermore, five known related sesquiterpenes [(+)-(7R,10S)-2-hydroxycalamenene (1), (+)-(7R,10S)-3-hydroxycalamenene (2), (-)-alpha-cadinol (13), cadinenal (14), 6-epicadinenal (15)], and three known lignans [(-)-hinokinin, (-)-dihydrocubebin, (-)-cubebin] were also isolated from the same plant. This is the first report of compounds 3, 4, 5, 6, and 16 from a natural source.Journal Articleinfo:eu-repo/semantics/publishe