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Metastasis

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Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam Mar 2021

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

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Characterizing The Role Of The Neuropeptide Y-Y5r System In Breast Cancer, Jenna Kara Aug 2016

Characterizing The Role Of The Neuropeptide Y-Y5r System In Breast Cancer, Jenna Kara

Electronic Thesis and Dissertation Repository

Studies have demonstrated a correlation between stress and an increased risk of breast cancer. Neuropeptide Y (NPY) is up- regulated in chronic stress and induces proliferation and chemotaxis of 4T1 breast cancer cells via Y5 receptor (Y5R) activation. In the studies performed in this thesis, we characterize NPY-Y5R as a regulatory system that promotes breast cancer metastasis. We compared three cancer cell sublines derived from the same murine mammary fat pad tumour, that greatly differ in metastatic potential (67NR, 168FARN, and 4T1) in addition to a 4T1-Y5R knockdown established in our labs. In this thesis we demonstrate significance of up-regulation …

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Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong Apr 2016

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 …

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The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio Jun 2015

The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio

Electronic Thesis and Dissertation Repository

The majority of breast cancer deaths occur due to metastasis, with the most common site of breast cancer metastasis being bone. Previous work in our laboratory has established that stem-like breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and expression of a CD44+CD24- phenotype have enhanced metastatic capacity. This study tested the hypothesis that bone-derived osteopontin (OPN) promotes the migration and stem-like behavior of breast cancer cells. We demonstrate that bone- derived OPN promotes migration, tumorsphere-forming ability and colony-forming ability of whole population and ALDHhiCD44+CD24- breast cancer cells in bone marrow- …

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Multiparametric Imaging And Mr Image Texture Analysis In Brain Tumors, Harish A. Sharma Mar 2014

Multiparametric Imaging And Mr Image Texture Analysis In Brain Tumors, Harish A. Sharma

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Discrimination of tumor from radiation injured (RI) tissues and differentiation of tumor types using noninvasive imaging is essential for guiding surgical and radiotherapy treatments are some of the challenges that clinicians face in the course of treatment of brain tumors. The first objective in this thesis was to develop a method to discriminate between glioblastoma tumor recurrences and radiation injury using multiparametric characterization of the tissue incorporating conventional magnetic resonance imaging signal intensities and diffusion tensor imaging parameters. Our results show significant correlations in the RI that was missing in the tumor regions. These correlations may aid in differentiating between …

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The Role Of Aldhhicd44+ Cells In Breast Cancer Metastasis And Therapy Resistance, Alysha K. Croker Dec 2012

The Role Of Aldhhicd44+ Cells In Breast Cancer Metastasis And Therapy Resistance, Alysha K. Croker

Electronic Thesis and Dissertation Repository

Breast cancer is a leading cause of death in women, due primarily to ineffective treatment of metastatic disease. Despite being a lethal process, metastasis is surprisingly inefficient, with less than 0.5% of cancer cells able to successfully navigate the metastatic cascade, indicating that only a small proportion of cancer cells possess the necessary characteristics to establish metastases. Cancer stem cells (CSCs) have recently been identified in leukemia and solid tumors; however, the role of CSCs in breast cancer metastasis and therapy resistance remains poorly understood. Sub-populations of cells demonstrating stem-cell like characteristics (high expression of CSC markers and/or high ALDH …

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Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean Jul 2011

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

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From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo Apr 2011

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …

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