<p>The aim
of this study is to identify metabolic transformations in breast cancer through
urinary volatile organic compounds in mammary pad or bone tumor mice models.
Subsequently, it focuses on investigating the efficacy of therapeutic intervention
through identified potential biomarkers. Methods for monitoring tumor development
and treatment responses have technologically advanced over the years leading to
significant increase in percent survival rates. Although these modalities are
reliable, it would be beneficial to observe disease progression from a new perspective
to gain greater understanding of cancer pathogenesis. Analysis of cellular energetics
affected by cancer using bio-fluids can non-invasively help in prognosis and
selection of treatment regimens. The hypothesis is altered profiles of urinary volatile
metabolites is directly related to disrupted metabolic pathways. Additionally,
effectiveness of treatments can be indicated through changes in concentration
of metabolites. In this ancillary experiment, mouse urine specimens were
analyzed using gas chromatography-mass spectrometry, an analytical chemistry
tool in identifying volatile organic compounds. Female BALB/c mice were
injected with 4T1.2 murine breast tumor cells in the mammary fat pad.
Consecutively, 4T1.2 cells were injected in the right iliac artery of BALB/c
mice and E0771 tumor cells injected in the tibia of C57BL/6 mice to model bone
tumor. The effect of two different modes of treatment: chemical drug and
mechanical stimulation was investigated through changes in compound profiles.
Chemical drug therapy was conducted with dopamine agents, Triuoperazine,
Fluphenazine and a statin, Pitavastatin. Mechanical stimulation included tibia
and knee loading at the site of tumor cell injection were given to mice. A biological
treatment mode included administration of A5 osteocyte cell line. A set of
potential volatile organic compounds biomarkers differentiating mammary pad or
bone confined tumors from healthy controls was identified using forward feature
selection. Effect of treatments was demonstrated through hierarchical heat maps
and multivariate data analysis. Compounds identified in series of experiments
belonged to the class of terpenoids, precursors of cholesterol molecules. Terpene
synthesis is a descending step of mevalonate pathway suggesting its potential
role in cancer pathogenesis. This thesis demonstrates the ability of urine
volatilomics to indicate signaling pathways inflicted in tumors. It proposes a
concept of using urine to detect tumor developments at two distinct locations
as well as to monitor treatment efficacy.</p><br>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/8049566 |
| Date | 12 October 2021 |
| Creators | MEGHANA SHARAD TELI (6640691) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/Urinary_Volatile_Organic_Compounds_for_Detection_of_Breast_Cancer_and_Monitoring_Chemical_and_Mechanical_Cancer_Treatments_in_Mice/8049566 |
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