Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer

The anti-tumor activity of a newly developed Hsp90 inhibitor, NVP-AUY922 (AUY922), against non-small cell lung cancer (NSCLC) was examined. Twenty-one NSCLC cell lines were used, the somatic alterations of which were characterized. Cell proliferation was analyzed using a modified MTS assay. Expression of the client proteins was assessed using Western blotting. The cell cycle was analyzed using flow cytometry. The IC50 value of AUY922 for the NSCLC cell lines ranged from 5.2 to 860 nM (median, 20.4 nM). Based on previous data, cells with an IC50 of less than 50 nM were classified as sensitive cells and 19 of the 21 NSCLC cell lines were judged to be sensitive. The IC50 of five malignant pleural mesothelioma (MPM) cell lines revealed that the MPM cells had a significantly higher IC50 value (median, 89.2 nM; range, 22.2-24, 100 nM) than the NSCLC cells (p = 0.015). There was significant depletion of both the total and phosphorylated client proteins - EGFR, MET, HERZ and ART - at low drug concentrations (50-100 nM) in drug-sensitive cell lines. Cell-cycle analysis was performed for two sensitive cell lines, H1975 and H838. Following AUY922 treatment, an increase in the sub-G(0)-G(1) cell population, as well as appearance of cleaved PARP expression, indicated the induction of apoptosis. In conclusion, AUY922 was effective against most NSCLC cell lines, independent of the type of known molecular alteration, and appears to be a promising new drug for the treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved

The Effects of Intrauterine Injection with Prostaglandin F2α, Arachidonic Acid and Phosphate Solution on the Eggshell Formation of Japanese Quail Hen

Inhibitory effects of prostaglandin F2α, arachidonic acid and phosphate solution on the eggshell formation were investigated in Japanese quail. All injections were performed intrauterinely 8h before the predicted oviposition. Prematurely oviposited eggs distinctly presented significantly lower values of eggshell weight (64-70%) and eggshell thickness (65-70%) than those of control (p<0.01). Spontaneously oviposited eggs, of which averaged oviposition intervals were approximately 24h, also showed significantly lower values (p<0.01) than control in eggshell weight and thickness (71-79% in both). When indomethacin was pretreated, oviposition-inducing effect and inhibiting effect on eggshell formation were disappeared in injection with arachidonic acid, whereas not inhibiting effect on eggshell formation but oviposition-inducing effect only disappeared in injection with phosphate solution. These results indicated that prostaglandin and phosphate solution had the inhibitory effect on the eggshell formation

The Effect of Progesterone and Estradiol-17 β on the Pigment Accumulation of the Shell Gland in Japanese Quail Pretreated with Aminoglutethimide

Effects of the combined injection with progesterone and estradiol-17 β i.m. on the accumulation of the superficial pigment of the eggshell in the quail shell gland were investigated. Arninoglutethimide (AG, 20mg/100g BW) was administered s.c. to quail hens 10 h before the expected ovulation, followed by the administration of progesterone (0.1 mg/100 g BW) and estradiol-17 β (0.1 rng/100g BW). Pigment in the shell gland at 18 h after oviposition of the preceding egg was measured. Progesterone had increasing effect on pigment in the shell gland of both hens ovulated and failed to ovulate. The effect of combined injection with progesterone and estradiol-17 β was appeared only if ovulation was induced and estradiol-17 β was injected 1 h after oviposition of the preceding egg. These results suggested that the accumulation of pigment in the shell gland was enhanced by estradiol-17 β closely related to egg formation

Observations of Pigment Accumulation in the Epithelium of the Shell Gland and Superficial Pigmentation on the Egg Shell in Japanese Quail

The pigment accumulation in the shell gland through an ovulation cycle and the pigmentation onto the surface of egg shell were observed in Japanese quail. The pigment granules and PAS-positive material in the apical cells of the epithelium of the shell gland increased progressively as time elapsed after ovulation and decreased suddenly 2-3 hrs before the expected oviposition as the pigmentation onto the egg shell occurred. The pigment granules and PAS-positive material secreted from the cells gathered to form pigment masses between folds of mucous membrane. The pigment masses were deposited on the surface of egg shell. After the pigmentation, only the PAS-positive material was seemed to be deposited on the surface to complete the cuticle