Medicine and Health Sciences Commons^™

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Targeting Cancer Metabolism With Ketosis And Hyperbaric Oxygen, Angela M. Poff

USF Tampa Graduate Theses and Dissertations

Cancer cells exhibit an abnormal metabolic phenotype characterized by glycolysis and lactate fermentation in the presence of oxygen, a phenomenon known as the Warburg effect. This dysregulated metabolism plays an important role in every aspect of cancer progression, from tumorigenesis to invasion and metastasis. The Warburg effect is a common phenotype shared by most, if not all, cancer types. It is especially prominent in metastatic tumors, which are notoriously resistant to treatment and responsible for the majority of cancer-related deaths. Thus, metabolic therapies which target the Warburg effect could offer novel therapeutic options for most cancer patients, including those with …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Mechanisms Underlying Distinct Egfr Versus Fgfr-3 And -1 Dependency In Human Bladder Cancer Cells, Tiewei Cheng

Dissertations & Theses (Open Access)

The epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) are activated by gene amplification, mutation and overexpression in bladder cancer, which drives tumor development and progression. Both EGFR and FGFR inhibitors are currently being tested in clinical trials. However, bladder cancer (BC) cells show remarkably heterogeneous sensitivities to both inhibitors, and the molecular determinants of this heterogeneity are presently unclear. Therefore, in this study, using selective EGFR and FGFR inhibitors in BC cells, we demonstrated that FGFR3 and FGFR1 play largely non-overlapping roles in mediating proliferation and invasion in the distinct “epithelial” and “mesenchymal” subsets of human …

Role Of Talin1 Phosphorylation In Beta1 Integrin Activation And Prostate Cancer Metastasis, Jung-Kang Jin

Dissertations & Theses (Open Access)

Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind and activate integrins but the mechanism by which this occurs is unknown. As integrin activation and overexpression of talins promote prostate cancer metastasis, understanding the mechanism by which talins activate integrins will better elucidate their roles in Prostate cancer metastasis. Phosphorylation of talins on serine 425 has been associated with β1 integrin functions. Work in this dissertation tested the hypothesis that increased talin1 S425 phosphorylation was required for β1 integrin activation and promotion of prostate cancer metastasis.

I first used shRNA to …

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

Electronic Thesis and Dissertation Repository

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 …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

Is Surgical Spinal Decompression For Supratentorial Gbm Symptomatic Drop Down Metastasis Warranted? A Case Report And Review Of Literature, Muhammad Babar Khan, Muhammad Riaz, Muhammad Ehsan Bari

Medical College Documents

Background: Symptomatic spinal metastasis from an intracranial primary
glioblastoma multiforme (GBM) is very rare. Our literature search identified a total
of 42 such patients of which 11 were treated with surgical decompression for spinal metastasis with only one such report from the pediatric age group. Previous studies have reported variable outcomes after surgical management.

Case Description: We report the case of a 16‑year‑old boy who underwent
surgical spinal decompression for spinal metastasis after intracranial GBM. The
patient regained motor and autonomic function following surgery and reported
improvement in pain. We also present findings from a literature review using …

Adaptation Of Semiautomated Circulating Tumor Cell (Ctc) Assays For Clinical And Preclinical Research Applications, Lori E. Lowes, Benjamin D. Hedley, Michael Keeney, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC …

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …

A Novel Link Between Abl Family Kinases And Nm23-H1 During Metastatic Progression, Leann S. Fiore

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cancer patient mortality is caused by the ability of tumor cells to invade the extracellular matrix and metastasize. Our lab was the first to identify the role of Abl family of non-receptor tyrosine kinases (c-Abl and Arg) in the progression of solid tumor cancers. In our previous studies, we showed that high c-Abl/Arg activity promotes proliferation, invasion, and metastasis in melanoma and breast cancer cells lines. Here, we demonstrate that our previous findings are clinically relevant by showing increased c-Abl/Arg kinase activity in primary melanoma tumor tissue in comparison to low activity as compared to benign nevi. Additionally, in breast …

Choroidal Metastasis From Leiomyosarcoma In Two Cases, Eric Feinstein, Swathi Kaliki, Carol L Shields, Hormoz Ehya, Jerry A Shields

Wills Eye Hospital Papers

Leiomyosarcoma is a malignant tumor of mesenchymal cells and is the most common soft-tissue sarcoma. Leiomyosarcoma is a notably rare tumor in the ophthalmic region and can be of primary, secondary or metastatic origin. To the best of our knowledge, there has only been one published case of leiomyosarcoma metastasis to the choroid. In this case study, we report two cases of primary leiomyosarcoma with metastasis to the choroid of the eye. Both cases displayed systemic metastasis and showed response to high dose plaque radiotherapy. Despite its prevalence as the leading form of sarcoma, leiomyosarcoma rarely metastasizes to the ocular …

Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley

All ETDs from UAB

Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors combine to influence an individual's predilection for breast cancer and related metastatic tumor formation. The genetic component, in particular, has become the focus of many emergent studies. A renewed focus on cancer metabolism and the Warburg effect has similarly cast a spotlight on the role, if any, of the mitochondrion in directing disease progression. Analysis of the direct contribution of mitochondrial DNA on tumorigenicity is made possible through the use of mitochondrial-nuclear exchange (MNX) mice in which nuclei from normal FVB mice (the background strain of the tg: …

Role Of Micro Rna 148/152 Family In Cancer Progression, Anusha Chaparala

Theses and Dissertations

Micro RNA are small single stranded RNA that regulate the expression of various genes. MiRNA guide the mRNA disintegrating RISC complex to the complimentary sequence in the target mRNA. Each micro RNA has multiple targets and can play a different biological role depending on the population of targets at the particular stage of the cell or a physiological state. Several miRNA show elevated or decreased levels of expression in various cancers because of their role in tumor initiation and progression. MiRNA belonging to mir148/152 family are examples of such MicroRNA. This family includes miR148a, miR148b and miR152. MiR148a and miR152 …

Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft

All ETDs from UAB

Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …

Accuracy Of Magnetic Resonance Imaging In Pretreatment Lymph Node Assessment For Gynecological Malignancies, Saira Naz Sufian, Imrana Masroor, Waseem Mirza, Zainab Hussain, Saima Hafeez, Zafar Sajjad

Department of Radiology

Objective: To determine the accuracy of magnetic resonance imaging (MRI) in detection of metastasis in pelvic and para-aortic lymph nodes from different gynecological malignancies.MATERIALS AND Methods: This retrospective cross sectional analytic study was conducted at the Department of Diagnostic Radiology, Aga Khan University Hospital Karachi Pakistan from January 2011 to December 2012. A sample of 48 women, age range between 20-79 years, fulfilling inclusion criteria were included. All patients had histopathologically proven gynecological malignancies in the cervix, endometrium or ovary and presented for a pretreatment MRI to our radiology department.Results: MRI was 100% sensitive and had a 100% positive predictive …