Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment

Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer

Terrestrial behavior in titi monkeys (Callicebus, Cheracebus, and Plecturocebus) : potential correlates, patterns, and differences between genera

For arboreal primates, ground use may increase dispersal opportunities, tolerance to habitat change, access to ground-based resources, and resilience to human disturbances, and so has conservation implications. We collated published and unpublished data from 86 studies across 65 localities to assess titi monkey (Callicebinae) terrestriality. We examined whether the frequency of terrestrial activity correlated with study duration (a proxy for sampling effort), rainfall level (a proxy for food availability seasonality), and forest height (a proxy for vertical niche dimension). Terrestrial activity was recorded frequently for Callicebus and Plecturocebus spp., but rarely for Cheracebus spp. Terrestrial resting, anti-predator behavior, geophagy, and playing frequencies in Callicebus and Plecturocebus spp., but feeding and moving differed. Callicebus spp. often ate or searched for new leaves terrestrially. Plecturocebus spp. descended primarily to ingest terrestrial invertebrates and soil. Study duration correlated positively and rainfall level negatively with terrestrial activity. Though differences in sampling effort and methods limited comparisons and interpretation, overall, titi monkeys commonly engaged in a variety of terrestrial activities. Terrestrial behavior in Callicebus and Plecturocebus capacities may bolster resistance to habitat fragmentation. However, it is uncertain if the low frequency of terrestriality recorded for Cheracebus spp. is a genus-specific trait associated with a more basal phylogenetic position, or because studies of this genus occurred in pristine habitats. Observations of terrestrial behavior increased with increasing sampling effort and decreasing food availability. Overall, we found a high frequency of terrestrial behavior in titi monkeys, unlike that observed in other pitheciids

The Case of a Tropical Disease and Its Treatment: Science, Society, and Economics

The National Center for Case Study Teaching in Science has served as the repository of many a fine case study, and this recent addition to their site takes on the world of tropical disease. Created by Cathy Santanello and Jennifer Rehg of Southern Illinois University at Edwardsville, this study is set in Costa Rica and its narrative introduction will help draw students into the exploration of this "mysterious ailment". After the introduction, the case study offers up a few background websites that deal with diseases in this region of Central America, and then moves on to ask some important initial questions. The other three parts of the study are similarly organized, and they include "Quest for a New Treatment" and "The Diagnostic Dilemma"

Polyspecific Associations of Callimico Goeldii, Saguinus Labiatus, and Saguinus Fuscicollis in Acre, Brazil

441 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2003.This study examines the behavioral ecology and polyspecific associations of three New World callitrichids, Callimico goeldii (Goeldi's monkey, callimico) Saguinus labiatus (red-chested tamarin) and Saguinus fuscicollis (saddle-backed tamarin). These closely-related primates form polyspecific associations (PSAs), in which all three species feed, forage, travel, and rest together. Like monospecific groups, associations presumably function to reduce predation risk or improve foraging efficiency. Behavioral and ecological data were collected on the study species over a total of 15 months at the Fazenda Experimental Catuaba, an 820 ha rainforest site in Acre, Brazil. All three species were in association 67% of observation time, and PSAs occurred during all activities. Associations were less common during the dry season correlating with a change in each species' diet, presumably as a response to lower fruit availability. During the wet season, the diets of all three species were composed of fruit and animal prey (primarily invertebrates), while during the dry season C. goeldii fed extensively on fungus and plant exudates, and both species of Saguinus fed on more exudates and nectar. There were low levels of agonistic interactions among species, suggesting that the PSAs do not impose heavy costs due to direct contest competition. Based on species' foraging methods and habitat use, scramble competition for plant resources is likely more prevalent. Reduced association in the dry season may relate to limiting possible association costs, as may result from scramble and exploitation competition, or opportunity costs resulting from maintaining PSAs. All three species of the main study group shared an identical range of 48 ha, 23% of which overlapped the ranges of neighboring mixed groups, and overall each species used different habitat types in proportion to their estimated availability. There was no strong evidence that the associations benefitted any of the study species in terms of better defense or access to resources, although it is possible that they may be able to monitor depletion of certain plant resources while associated. The ubiquity of the associations and behavioral responses to predators suggests the associations may serve an antipredation function.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Polyspecific Associations of Callimico Goeldii, Saguinus Labiatus, and Saguinus Fuscicollis in Acre, Brazil

441 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2003.This study examines the behavioral ecology and polyspecific associations of three New World callitrichids, Callimico goeldii (Goeldi's monkey, callimico) Saguinus labiatus (red-chested tamarin) and Saguinus fuscicollis (saddle-backed tamarin). These closely-related primates form polyspecific associations (PSAs), in which all three species feed, forage, travel, and rest together. Like monospecific groups, associations presumably function to reduce predation risk or improve foraging efficiency. Behavioral and ecological data were collected on the study species over a total of 15 months at the Fazenda Experimental Catuaba, an 820 ha rainforest site in Acre, Brazil. All three species were in association 67% of observation time, and PSAs occurred during all activities. Associations were less common during the dry season correlating with a change in each species' diet, presumably as a response to lower fruit availability. During the wet season, the diets of all three species were composed of fruit and animal prey (primarily invertebrates), while during the dry season C. goeldii fed extensively on fungus and plant exudates, and both species of Saguinus fed on more exudates and nectar. There were low levels of agonistic interactions among species, suggesting that the PSAs do not impose heavy costs due to direct contest competition. Based on species' foraging methods and habitat use, scramble competition for plant resources is likely more prevalent. Reduced association in the dry season may relate to limiting possible association costs, as may result from scramble and exploitation competition, or opportunity costs resulting from maintaining PSAs. All three species of the main study group shared an identical range of 48 ha, 23% of which overlapped the ranges of neighboring mixed groups, and overall each species used different habitat types in proportion to their estimated availability. There was no strong evidence that the associations benefitted any of the study species in terms of better defense or access to resources, although it is possible that they may be able to monitor depletion of certain plant resources while associated. The ubiquity of the associations and behavioral responses to predators suggests the associations may serve an antipredation function.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD