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- All Subjects: Cancer
- Creators: School of Molecular Sciences
- Creators: Harrington Bioengineering Program
Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.
The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.
A high density 3D tumor model was utilized to recapitulate the tumor microenvironment of ductal carcinoma in vitro. The tumor model consisted of MDA-MB-231 tumors seeded within micromolded collagen wells, chemically immobilized upon a surface treated PDMS substrate. CAFs were seeded within the greater collagen structure from which the microwells were formed. The combinatorial effect of anti-fibrotic drug (Tranilast) and chemotherapy drug (Doxorubicin) were studied within 3D co culture conditions. Specifically, the combinatorial effects of the drugs on tumor cell viability, proliferation, and invasion were examined dynamically upon coculture with CAFs using the microengineered model.
The results of the study showed that the combinatorial effects of Tranilast and Doxorubicin significantly decreased the proliferative ability of tumor cells, in addition to significantly decreasing the ability of tumor cells to remain viable and invade their surrounding stroma, compared to control conditions.