Graduate students in the School of FCS defend theses

Alex Hurst

Retinoids Inhibit Proliferation and Invasion in Low Passage Number Colorectal Cancer Cell Lines. Monday, March 28th, 9 am, FCS 285.

Catherine Applegate

Pilot Study: Orthotopic Microinjection of Metastatic Colorectal Cancer Cells Expressing Luciferase. Tuesday, March 29th, 3 pm, FCS 285

Abstract:

Several mouse models currently exist for use in the study of colorectal cancer (CRC). These models include transgenic mice, chemically induced carcinogenesis, and xenografts of existing cancer cells or tumors into an immunocompromised mouse. Each method presents with several limitations, especially in regards to studying the natural progression and metastasis of CRC. Many models do not result in tumor metastasis and the effect of tumor microenvironment on carcinogenesis is an important consideration often overlooked when CRC tumor cells are implanted into a site other than the originating colonic tissue. A novel mouse model for studying the natural disease progression from the orthotopic, or originating, site has been described and involves the microinjection of human colorectal carcinoma cells into the cecal wall of immunocompromised mice. This method allows for the use of a mouse model that is more relevant and applicable to human studies, especially when studying the metastasis of CRC. Our laboratory has previously shown that dietary vitamin A supplementation inhibits tumor metastasis in a xenograft mouse model in which HCT-116 cells were intrasplenically injected into athymic mice. The purpose of the current study was to develop the orthotopic mouse model in our laboratory and to determine whether vitamin A supplementation had an effect on tumor growth and metastasis. Male and female Balb/c nude mice were orthotopically microinjected with HCT-116 cells expressing luciferase. Mice were fed diets with adequate vitamin A (control) and with supplemental vitamin A. Tumor incidence was measured using the IVIS Spectrum in vivo imaging system after mice were injected with ᴅ-luciferin, the substrate for luciferase. No difference in overall tumor incidence was observed between dietary groups, but mice consuming the supplemental diet exhibited tumor regression by the study endpoint. Future studies are needed to determine the mechanism by which supplemental vitamin A may result in tumor regression, but this pilot study presents promising preliminary results in a clinically relevant mouse model.

Corey Jackson

Maternal Omega-3 Fatty Acid Intake Modulates Offspring Brain Metabolism in Limbic and Mesolimbic Regions while decreasing Reactivity to Novel Enviromental Stress. Wednesday, March 30th 12:30 pm, FCS 285.

Abstract:

Omega-3 fatty acids (n-3 FAs) are considered conditionally essential for human brain development during gestation, but the precise amounts needed for optimal development are largely debated. The objective of this study was to compare the effects of two extremes of gestational and neonatal n-3 FA status, repletion and depletion, on behavior and brain metabolism later in life. The offspring of a second parturition of rats randomly assigned to diets with or without n-3 FAs were fed standard rodent diets with adequate n-3 FAs upon weaning.  The offspring consumed these diets until behavioral testing for novelty reactivity and anxiety, depressive behaviors, and learning and memory at eight weeks of age. Specifically, rat pups underwent the open field, forced swim, and holeboard tests, respectively, after which their brains were analyzed for cytochrome oxidase activity to assess differences in brain metabolism resulting from differences in maternal dietary n-3 FA intake. Rats born to dams fed n-3 FA-replete diets exhibited less reactivity to the stress of a novel environment in the open field test than those born to dams fed n-3 FA-deficient diets, but there were no treatment differences displayed in the forced swim or holeboard tests. Additionally, pups of n-3 FA-deficient dams spent more time in the center of the open field than pups of n-3 FA-replete dams [F(1,16) = 5.829, P = 0.028], suggesting increased risk-taking behaviors. Further, maternal diets replete with n-3 FAs increased metabolism in the pups’ posterior cingulate cortex and tended to increase metabolic activity in the cortical nucleus of the amygdala, often associated with emotional memories and defensive behaviors, as well as decrease activity in the nucleus accumbens shell, regularly associated with reward-seeking and fear. Pups born to n-3 FA-deficient mothers may have exhibited decreased ambulatory time in the open field test due to the decreased metabolism observed in the posterior cingulate cortex and cortical amygdala, which, we hypothesize, could lead to risk-taking responses to the new environment. Increased metabolism in the nucleus accumbens shell may have also contributed to greater reward-seeking in the new environment, as this region receives dopamine inputs along the mesolimbic pathway. These results indicate that maternal diets enriched with n-3 FAs may enable the offspring to adapt to new stressors by enhancing brain metabolism within the limbic and mesolimbic regions.

Brittany Markides

Usual Dietary Intake among Children 2-5 Years in a Community at High Risk for Obesity: Comparison to Age-Matched NHANES Data, 2009-2012

Thursday, March 31st, 3:30 pm FCS 177