Exendin-4 Induces Cytotoxic Autophagy in Two Ovarian Cancer Cell Lines through Inhibition of Mtorc1 Mediated by Activation of AMPK and Suppression of Akt.

Activation of autophagy suppresses ovarian cancer (OC). This in vitro study investigated whether the anti-tumour effect of exendin-4 against OC involves modulation of autophagy and figured out the possible mechanisms of action. SKOV-3 and OVCAR-3 cells (1 × 105/ml) were cultured in DMEM medium and treated with exendin-4 in the presence or absence of chloroquine (CQ), an autophagy inhibitor. In some cases, cells were also treated with exendin- 4 with or without pre-treatment with compound C (CC), an AMPK inhibitor, or insulin-like growth factor (IGF-1), a PI3K/Akt activator. Exendin-4 increased expression of beclin-1 and LC3I/II, suppressed expression of p62, reduced cell survival, migration, and invasion, and increased cell apoptosis and LDH release in both SKOV-3 and OVCAR-3 cells. Besides, exendin-4 reduced phosphorylation of mTORC1, 6SK, 4E-BP1, and Akt but increased phosphorylation of AMPK in both cell lines. These effects were associated with down-regulation of Bcl-2, suppression of nuclear phosphorylation of NF-κB p65, and increased expression of Bax and cleaved caspases 3/8. Chloroquine completely prevented the inhibitory effects of exendin-4 on the cell survival, Bcl-2, NF-κB, and cell invasiveness and abolished its stimulation of cell apoptosis and LDH release. Moreover, only the combined treatment with IGF-1 and CC completely abolished the observed effect of exendin-4 on the expression of beclin-1, LC3I/II, p62, as well as on cell survival, apoptosis, and LDH release. Exendin-4 exhibits a potent anti-tumour cytotoxic effect in SKOV-3 and OVCAR-3 cells by activating the markers of autophagy, mediated by activation of AMPK and inhibition of Akt.

Evidence for Octupole Correlations in Multiple Chiral Doublet Bands.

Two pairs of positive-and negative-parity doublet bands together with eight strong electric dipole transitions linking their yrast positive- and negative-parity bands have been identified in ^{78}Br. They are interpreted as multiple chiral doublet bands with octupole correlations, which is supported by the microscopic multidimensionally-constrained covariant density functional theory and triaxial particle rotor model calculations. This observation reports the first example of chiral geometry in octupole soft nuclei.

Echinococcus granulosus: a seroepidemiological survey in northern Israel using an enzyme-linked immunosorbent assay.

Following an intensive health education programme, 8651 finger-prick blood samples, 4122 from a predominantly adult group attending a primary care clinic and 4529 from schoolchildren, were collected in Tamra, northern Israel. An enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) was used to detect anti-Echinococcus granulosus antibodies, using both crude and purified antigens. The seroprevalence in the adult group was 0.48% (20/4122); optical density values were 0.1-0.14 in 10 subjects, 0.15-0.19 in 9, and > or = 0.2 in one; prevalences did not differ significantly between males and females or among age groups. Twenty-six of the schoolchildren (0.57%) were seropositive, 23 with optical densities of 0.1-0.14, one of 0.15-0.19, and 2 > or = 0.2. A high correlation was observed between ELISA positivity and both positivity in the arc 5 immunoelectrophoresis test and the presence of a high titre in the indirect immunofluorescence assay. Cross reactivity was observed with sera from schistosomiasis and ancylostomiasis patients, using both crude and purified echinococcal antigens. The results indicated that the IgG ELISA, using both crude and purified antigens, was very useful for seroepidemiological screening for echinococcosis, and that this condition is an emerging disease in northern Israel.