Master's Theses

Date of Award

2015

Document Type

Thesis

Department

Biology

First Advisor

Shubha Govind

Second Advisor

Michelle Juarez

Keywords

Inflammation, Canar, Asprin

Abstract

Chronic inflammation is a fundamental condition underlying many human disease pathologies including diabetes, cancer, and neurodegeneration. Indeed, one of the most commonly-used anti-inflammatory drugs, aspirin, has been shown to be effective in the treatment of many cancers. To understand the mechanistic linkages between inflammation and cancer, we used Drosophila models in which hyperactive immune signaling causes overproliferation of the hematopoietic system leading to the production of inflammatory blood tumors. In mutant animals, hematopoietic cells divide uncontrollably and exhibit pre-mature differentiation giving rise to large sticky cells. Some mutant cells infiltrate and adhere to cells of the fat body. The fat body is a large organ in fly larvae and akin to the mammalian liver. In wild type larvae, hematopoietic cells exhibit limited rounds of division, and circulating cells in the hemolymph do not stick to fat body. Our hypothesis was that if the biochemistry and genetic circuitry underlying inflammation biology in flies is conserved, then aspirin administration should have the same therapeutic effects on tumor growth and infiltration in fly mutants as it does in humans. Here we show that sublethal levels of systemically-administered aspirin improve viability of mutants and reduce the size and abundance of blood tumors. The accompanying infiltration of blood cells on larval fat body cells of mutants is also reduced. These results support our hypothesis and suggest that the mechanisms underlying aspirin’s effects in flies may be similar with those in mammals. These studies underscore the value of the Drosophila model system and present exciting possibilities for uncovering shared mechanisms.

Available for download on Friday, January 01, 2021

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