Cell and Developmental Biology Commons^™

Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong

Doctoral Dissertations

Great strides have been made in cancer therapy in the past century, yet it remains one of the leading causes of death in the United States today. This work aimed to shed light on novel methods to treat a variety of aggressive and often chemo-resistant cancers both in vitro and in vivo. The first aim of this work was to evaluate the therapeutic efficacy of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) prodrugs compared to standard chemotherapeutic agents. Conjugation of polyMPC to drugs such as doxorubicin (Dox) can result in its improved solubility, prolonged half-life and therapeutic efficacy. PolyMPC and polyMPC-Dox (at a …

Investigating The Role Of Extracellular Matrix Proteins In Ovarian Folliculogenesis And Ovarian Cancer, Alexandra Carrier

Electronic Thesis and Dissertation Repository

The extracellular matrix (ECM) is a highly organized, dynamic structure that maintains tissue integrity and regulates biological processes involved in organ development and function. To explore the role of ECM proteins in ovarian physiology and pathology, my thesis characterizes ECM proteins aberrantly overexpressed in the Estrogen Receptor (ER)β-null (βERKO) mouse ovary and epithelial ovarian cancer (EOC). The ECM undergoes extensive physical changes, and influences numerous cell functions, throughout folliculogenesis. This study identifies a role for ERβ in ovarian development earlier than previously believed. Nidogen 2 and Collagen 11a1 are aberrantly overexpressed in βERKO ovaries as early as postnatal day 13, …

The Role Of Gdf15 In Ovarian Cancer, Daisy I. Izaguirre

Dissertations & Theses (Open Access)

Growth Differentiation Factor 15 (GDF15) is induced in situations such as stress, inflammation, treatment with non-steroidal anti-inflammatory drugs, as well as other therapeutic agents. As a secreted protein, GDF15 is seen as a potential biomarker in several types of cancer as well as in other diseases such as cardiovascular diseases, diabetes, and rheumatoid arthritis. In ovarian cancer, high GDF15 serum levels correspond to poor survival. It has further been shown to be expressed at higher levels in serum in ovarian cancer patients post-chemotherapy than pre-chemotherapy.

The overall 5-year survival for ovarian cancer is 46%, as a result of late diagnosis …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …

Exploring The Regulation And Function Of Epithelial-Mesenchymal Plasticity In Ovarian Cancer Spheroids, Samah Rafehi

Electronic Thesis and Dissertation Repository

Epithelial-mesenchymal transition (EMT) serves as a key mechanism driving tumour cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFβ) signalling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFβ signalling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a …