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Glioblastoma is a highly malignant disease in critical need of expanded treatment options. The AURKA inhibitor alisertib exhibits antiproliferative activity against glioblastoma in vitro and in vivo. Unlike current clinically used taxane drugs, the novel taxane TPI 287 penetrates the CNS. We tested for interactions between three selective AURKA inhibitors and TPI 287 against standard U87 and U1242 cells and primary glioblastoma neurospheres using colony formation assays. Bliss and Chou-Talalay analyses were utilized to statistically test for synergism. Morphological analysis, flow cytometry and annexin V binding were employed to examine cell cycle and apoptotic effects of these drug combinations. TPI 287 not only potentiated the cytotoxicity of the AURKA inhibitors alisertib, MLN8054 and TC-A2317, but was often potently synergistic. Morphologic and biochemical analysis of the combined effects of alisertib and TPI 287 consistently revealed synergistic induction of apoptosis. While each agent alone induces a mitotic block, slippage occurs allowing some tumor cells to avoid apoptosis. Combination treatment greatly attenuated mitotic slippage, committing the majority of cells to apoptosis. Alisertib and TPI 287 demonstrate significant synergism against glioblastoma cells largely attributable to a synergistic effect in inducing apoptosis. These results provide compelling rationale for clinical testing of alisertib and/or other AURKA inhibitors for potential combination use with TPI 287 against glioblastoma and other CNS neoplasms.

4Sedgwick County Zoo, Wichita, Kansas Captive breeding programs for the rhinoceros can be enhanced by studying their reproductive physiology. To do so requires repetitive manipulations under physically controlled circumstances. To facilitate these procedures, zoos throughout the world have constructed restraint devices, or chutes. Chute designs are usually determined by the space in which they are to be situated and the budget available for their construction. In this study, eight chute designs at seven institutions were compared for efficiency in controlling rhinoceroses during ultrasonography, semen collection, and blood sampling. Procedures were conducted on 16 rhinoceroses of four species: the white rhinoceros ( Ceratotherium simum simum), the black (Diceros bicornis), the greater one-horned Asian ( Rhinoceros unicornis), and the Sumatran (Dicerorhinus sumatrensis). Chutes were evaluated for dimensions, fabricating materials, procedures to be attempted, and structural features such as shoulder restraints. Permanent, indoor, side-adjustable, passthrough chutes were determined to be the most efficient and convenient type because they saved time and reduced stress on the animals. Zoo Biol 17:343‐ 359, 1998. © 1998 Wiley-Liss, Inc.