The BCL-2 family of proteins, including anti-apoptotic members BCL-2, BCL-XL and MCL-1, are part of a complex network that controls apoptosis. BH3-mimetics such as ABT-263 inhibit anti-apoptotic BCL-2 proteins and have been developed as potential cancer therapeutics. Aurora Kinase A (AKA) is over-expressed in pancreatic cancer (PC) and controls G2-M transition during mitosis and AKA inhibitors have been developed that induce mitotic arrest. We hypothesized that mitotic arrest induced by AKA inhibition may sensitize PC to accelerated apoptosis by a BH3-mimetic. Our results demonstrated that ABT-263 plus MLN8237 treatment showed greater activity than either single drug alone, as well as strong synergism, in the inhibition of growth of pancreatic cell lines (AsPC-1, PANC-1, MIA PaCa-2, HPAF-II) and PC patient-derived organoids (PDOs). The higher efficacy of combination treatment was attributable to the higher levels of induction of apoptosis and reduction of MCL-1 in PC cells and PDOs. In addition, combination therapy was more effective than single drug in the suppression of tumor growth in AsPC-1 xenograft mouse models. Together, our findings suggest that combination therapy with ABT-263 and MLN8237 should be considered for further exploration as a novel treatment of deadly PC disease.

We report a method of creating pure 9Be+ ions by a 2+1 resonance-enhanced multiphoton ionization (REMPI) for the ionization potential of 75192.64(6) cm-1 (133 nm). The efficient generation of 9Be+ ions has been realized in a segmented linear ion trap. The average loading rates with a 10 ns, 1 mJ laser at 310 nm and 306 nm are 3.8 and 1.3 ions per pulse, respectively. This method has the advantage of reducing the electron contamination to the ion trap electrodes greatly. It also reduces the requirement of single-photon energy while satisfying the need for ionization probability and can be applied to other atoms with high ionization thresholds.

We obtain bi-component Coulomb crystals using laser-cooled 40Ca+ ions to sympathetically cool 9Be+ ions in a linear Paul trap. The shell structures of the bi-component Coulomb crystals are investigated. The secular motion frequencies of the two different ions are determined and compared with those in the single-component Coulomb crystals. In the radial direction, the resonant motion frequencies of the two ionic species shift toward each other due to the strong motion coupling in the ion trap. In the axial direction, the motion frequency of the laser-cooled 40Ca+ is impervious to the sympathetically cooled 9Be+ ions because the spatially separation of the two different ionic species leads to the weak motion coupling in the axial direction.