Medicine and Health Sciences Commons^™

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

Dissertations & Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …

Epithelial-To-Mesenchymal Transition Leads To Disease-Stage Differences In Circulating Tumor Cell Detection And Metastasis In Pre-Clinical Models Of Prostate Cancer, Lori E. Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M. Piaseczny, Freeman Paczkowski, Alison L. Allan

Anatomy and Cell Biology Publications

Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of >= 5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch (R) system, the "gold standard" clinical platform. However, similar to 35% of metastatic PCa patients assessed by CellSearch (R) have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable …

Unique Metabolic Features Of Pancreatic Cancer Stroma: Relevance To The Tumor Compartment, Prognosis, And Invasive Potential., Erik S. Knudsen, Uthra Balaji, Elizaveta Freinkman, Peter Mccue, Agnieszka K. Witkiewicz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from …

Pyruvate Kinase Type M2 (Pkm2) Promotes Cancer Cell Metastasis Through Interacting With Twist-1, Odunayo Durojaye, Hailun Wang, Phd

Journal of Health Disparities Research and Practice

Tumor growth and metastasis are key processes in understanding tumor progression and cancer fatality. Pyruvate Kinase type M2 (PKM2) is a key enzyme that regulates glucose metabolism in cells in a biochemical pathway known as glycolysis. Glycolysis provides cells with energy (ATP) and building blocks (nucleic acids, amino acids and lipids) that are critical for cell survival and proliferation. Therefore, cancer cells rely heavily on this metabolic process to survive and thrive. PKM2 is overexpressed in most cancers, and is highly involved with cancer cell growth. Several recent studies have further revealed a potential role of PKM2 in regulating epithelial-mesenchymal …

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 …

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

Dissertations & Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found …

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations & Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …

Erbb2 And P38Γ Mapk Mediate Alcohol-Induced Increase In Breast Cancer Stem Cells And Metastasis, Mei Xu, Zhenhua Ren, Xin Wang, Ashley Comer, Jacqueline A. Frank, Zun-Ji Ke, Yi Huang, Zhuo Zhang, Xianglin Shi, Siying Wang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Background: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence.

Methods: We evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in …

Relationship Of Tumor Thickness With Neck Node Metastasis In Buccal Squamous Cell Carcinoma: An Experience At A Tertiary Care Hospital, Sadaf Qadeer Ahmed, Montasir Junaid, Sohail Awan, Moaz M. Choudhary, Maliha Kazi, Aria Masoom, Hareem Usman Khan

Department of Surgery

Introduction Squamous cell carcinoma is the most common malignancy of the head and neck, with the buccal mucosa being the most common site involved. Early locoregional metastasis is a hallmark of this disease, and early stage tumors may harbor metastatic nodes that are occult. Certain parameters can help identify high-risk patients for whom the pattern of occult nodal metastasis can be predicted. Tumor thickness is one such objective parameter. Objective To determine the relationship of tumor thickness with neck node metastasis in squamous cell carcinoma of the buccal mucosa. Methods A retrospective chart review of 102 patients with biopsy-proven squamous …

Generation Of Organ-Conditioned Media And Applications For Studying Organ-Specific Influences On Breast Cancer Metastatic Behavior, Matthew M. Piaseczny, Graciella M. Pio, Jenny E. Chu, Ying Xia, Kim Nguyen, David Goodale, Alison Allan

Anatomy and Cell Biology Publications

Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. …

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 …

An Unusual Case Of Cauda Equina Secondary To Spinal Metastasis Of Thyroid Cancer, Shabbir Akhtar, Mohammad Adeel

Department of Surgery

Abstract

INTRODUCTION:

Cauda equina secondary to metastatic follicular thyroid cancer of the lumbosacral area is a rare entity.

CASE REPORT:

We report an unusual case of a 52-year-old male who presented with backache, lower limb weakness, and perianal numbness. A CT-scan of the lumbosacral area showed an enhancing mass at the L4, L5 and S1 vertebrae. Histopathology after excision revealed a metastatic thyroid cancer. Hence, a CT scan of the neck and chest was performed which showed a nodule in the left lobe of the thyroid and a mass in the left chest wall. A total thyroidectomy and excision of …

Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis

All ETDs from UAB

Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …

The Utility Of Ebus-Tbna In Mediastinal Or Hilar Lymph Node Evaluation In Extrapulmonary Malignancy, Onur Fevzi̇ Erer, Ceyda Anar, Serhat Erol, Seri̇r Özkan

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to determine the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of mediastinal and hilar lymph nodes (LNs) in patients with known extrapulmonary malignancy. Materials and methods: Between March 2011 and August 2013, 378 EBUS-TBNA procedures were performed. Sixty-three (16.6%) of these were performed on known extrapulmonary malignancy patients. Results: There were 28 male and 35 female patients, with median ages of 65 years (min-max: 53-87) and 57 years (min-max: 39-76), respectively. From the 63 cases, 138 lymph nodes (LNs) were sampled with EBUS-TBNA (median: 2 LNs/patient; min-max: 1-4). …

Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell

All ETDs from UAB

It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …