Biomedical subjects

Christopher Morton

Publications and source records attributed to Christopher Morton.

3 recordsLinked to original sources

PubMed2007

Credentialing preclinical pediatric xenograft models using gene expression and tissue microarray analysis.

Human tumor xenografts have been used extensively for rapid screening of the efficacy of anticancer drugs for the past 35 years. The selection of appropriate xenograft models for drug testing has been largely empirical and has not incorporated a similarity to the tumor type of origin at the molecular level. This study is the first comprehensive analysis of the transcriptome of a large set of pediatric xenografts, which are currently used for preclinical drug testing. Suitable models representing the tumor type of origin were identified. It was found that the characteristic expression patterns of the primary tumors were maintained in the corresponding xenografts for the majority of samples. Because a prerequisite for developing rationally designed drugs is that the target is expressed at the protein level, we developed tissue arrays from these xenografts and corroborated that high mRNA levels yielded high protein levels for two tested genes. The web database and availability of tissue arrays will allow for the rapid confirmation of the expression of potential targets at both the mRNA and the protein level for molecularly targeted agents. The database will facilitate the identification of tumor markers predictive of response to tested agents as well as the discovery of new molecular targets.

Cell Line, Tumor↗

PubMed2005

Meta-analyses of object naming: effect of baseline.

The neural systems sustaining object naming were examined using the activation likelihood estimation (ALE) meta-analysis approach on the results of 16 previously published studies. The activation task in each study required subjects to name pictures of objects or animals, but the baseline tasks varied. Separate meta-analyses were carried out on studies that used: (1) high-level baselines to control for speech processing and visual input; and (2) low-level baselines that did not control for speech or complex visual processing. The results of the two meta-analyses were then compared directly, revealing a double dissociation in the activation pattern for studies using high and low baselines. To interpret the differential activations, we report two new functional imaging experiments. The aim of the first was to characterize activation differences associated with visual stimuli that are typically used in baseline conditions (complex visual features, simple structures, or fixation). The aim of the second was to classify object-naming regions in terms of whether they were engaged preferentially by semantic or phonological processes. The results reveal a remarkably precise correspondence between the areas identified by the meta-analyses as affected differentially by baseline and the areas that are affected differentially by non-object structure, semantics or phonology. As expected, high-level baselines reduced object-naming activation in areas associated with the processing of complex visual features and speech production. In addition, high-level baselines increased sensitivity to activation in areas associated with semantic processing, visual-speech integration and response selection. For example, activation in the anterior temporal areas that neuropsychological studies have associated with semantic processing was more strongly activated in the context of high-level baselines. These results therefore have implications for understanding the convergence of functional imaging and neuropsychological findings.

Brain↗

PubMed2005

Developing new agents for the treatment of childhood cancer.

The development of new drugs for the treatment of childhood cancer presents novel challenges, and pediatric clinical trials of a new agent are often initiated many years after testing in adults. It is estimated that there are over 400 new entities being developed as cancer treatments, although few of these have been developed specifically for the treatment of childhood malignancies. This raises the question of how agents can be prioritized for pediatric clinical testing. In this review, the molecular characteristics of childhood cancers that may be valuable in steering choices for rational or molecularly targeted treatments are described, and the Pediatric Preclinical Testing Program, a National Cancer Institute initiative to identify agents that should be prioritized for clinical evaluation against childhood cancer, is presented.

Animals↗