Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems-based Resource.

The NCI-60 human tumor cell line panel has proved to be a useful tool for the global cancer research community in the search for novel chemotherapeutics. The publicly available cell line characterization and compound screening data from the NCI-60 assay have significantly contributed to the understanding of cellular mechanisms targeted by new oncology agents. Signature sensitivity/resistance patterns generated for a given chemotherapeutic agent against the NCI-60 panel have long served as fingerprint presentations that encompass target information and the mechanism of action associated with the tested agent. We report the establishment of a new public NCI-60 resource based on the cell line screening of a large and growing set of 175 FDA-approved oncology drugs (AOD) plus >825 clinical and investigational oncology agents (IOA), representing a diverse set (>250) of therapeutic targets and mechanisms. This data resource is available to the public (https://ioa.cancer.gov) and includes the raw data from the screening of the IOA and AOD collection along with an extensive set of visualization and analysis tools to allow for comparative study of individual test compounds and multiple compound sets.

Power and Type I errors for pairwise comparisons of means in the unequal variances case.

A Monte Carlo simulation was conducted to compare pairwise multiple comparison procedures. The number of means varied from 4 to 8 and the sample sizes varied from 2 to 500. Procedures were evaluated on the basis of Type I errors, any-pair power and all-pairs power. Two modifications of the Games and Howell procedure were shown to make it conservative. No procedure was found to be uniformly most powerful. For any pair power the Games and Howell procedure was found to be generally most powerful even when applied at more stringent levels to control Type I errors. For all pairs power the Peritz procedure applied with modified Brown-Forsythe tests was found to be most powerful in most conditions.

Power of pairwise comparisons in the equal variance and unequal sample size case.

A Monte Carlo simulation was conducted to compare five, pairwise multiple comparison procedures. The number of means varied from 4 to 6 and the sample size ratio varied from 1 to 60. Procedures were evaluated on the basis of Type I errors, any-pair power and all-pairs power. Four procedures were shown to be conservative, while the fifth provided adequate control of Type I errors only for restricted values of sample size ratios. No procedure was found to be uniformly most powerful. The Tukey-Kramer procedure was found to provide the best any-pair power provided it is applied without requiring a significant overall F test. In most cases, the Hayter-Fisher modification of the Tukey-Kramer was found to provide very good any-pair power and to be uniformly more powerful than the Tukey-Kramer when a significant overall F test is required. A partition-based version of Peritz's method usually provided the greatest all-pairs power. A modification of the Shaffer-Welsch was found to be useful in certain conditions.

Lower limb immobilization is associated with increased corticospinal excitability.

Temporary immobilization of the leg serves as a useful model for the brain's adaptive responses to casting, long-term confinement to bed rest and possibly to trauma. As part of a larger program using TMS to investigate changes associated with bed rest, we sought to determine whether casting of the leg causes brain excitability changes measurable with TMS, and the time course of resolution of these changes. In this study, eight adults wore a full leg cast for 10 days. TMS measures of motor cortex excitability were gathered before the cast was placed, and then immediately after cast removal, and 24 and 48 h later. A control group did not wear a cast and underwent the same TMS sessions. Significant excitability changes occurred and peaked at 24 h post cast removal in the TMS experimental group but not the non-casted group.