Medicine and Health Sciences Commons^™

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 …

Fibulin-2 Stabilizes Tumor Extracellular Matrix And Drives Malignant Progression Of Lung Adenocarcinoma, Brandi N. Baird

Dissertations & Theses (Open Access)

The ECM of epithelial carcinomas undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How tumors maintain ECM integrity in the face of dynamic biophysical forces is still largely unclear. This study addresses these deficiencies using mouse models of human lung adenocarcinoma. Spontaneous lung tumors were marked by disorganized basement membranes, dense collagen networks, and increased tissue stiffness. Metastasis-prone lung adenocarcinoma cells secreted fibulin-2 (Fbln2), a matrix glycoprotein involved in ECM supra-molecular assembly. Fibulin-2 depletion in tumor cells decreased the intra-tumoral abundance of matrix metalloproteinases and reduced collagen cross-linking and tumor compressive properties resulting in …

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

The Role Of Micrornas In Breast Cancer Migration, Invasion And Metastasis, Joy Tang, Fazlul H. Sarkar, Aamir Ahmad

Honors College Theses

MicroRNAs (miRNAs) are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such …

Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams

Elaine Hardman Ph.D.

Background The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …

Inhibition Of Breast Cancer Angiogenesis And Metastasis Ay Targeting Hypoxia-Inducible Factor-1Α, Chikezie O. Madu

Theses and Dissertations (ETD)

The current clinical chemotherapy agents are not ideal for breast cancer as they are not curative, but only provide a modest extension of survival with sometimes a severely adverse effect on the patient’s quality of life. There is, therefore, an urgent need to search for new and more effective anti-breast cancer drugs. However, the existing screening system is inefficient and time-consuming despite the extremely large amount of small molecule compounds in database currently available, and thereby hindering the effort for selecting new and effective anti-cancer drugs.

The majority of locally advanced solid tumors contain regions of reduced oxygen availability. Hypoxia …

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …

Roles Of Resveratrol And Genistein In Invasion And Metastasis Of Breast Cancer, Brittany Wolfe

College of Science and Health Theses and Dissertations

Breast cancer is a cellular disease characterized by the exploitation of several cellular and molecular mechanisms involved in cell proliferation, apoptosis, motility, and invasion. Effective treatment is available for non-invasive breast cancer at diagnosis, leading to a very high survival rate compared to the low survival rate for those where the breast cancer has spread. Thus, identifying effective therapies and preventative agents is imperative to successfully treat breast cancer. Since diet compromises a large component of the risk factors for breast cancer, it would be beneficial to examine dietary compounds that could potentially play a beneficial role in inhibiting cancer …

Threshold Primary Tumour Sizes For Nodal And Distant Metastases In Papillary And Follicular Thyroid Cancers., Maseeh Uz Zaman, Nosheen Fatima, Zafar Sajjad, Jaweed Akhter, Najmul Islam, Qamar Masood, Asma Ahmed

Department of Radiology

Abstract

BACKGROUND:

In papillary and follicular thyroid cancers (PTC, FTC), nodal and distant metastasis are generally considered important determinants of recurrence and survival, respectively. However, there is no consensus about the threshold primarytumour size (PTS) for these determinants. The aim of this study was to assess size relationships for developing nodal, pulmonary, bone and overall distant metastases.

METHODS:

This prospective study covered 139 (93 females and 46 males) consecutive biopsy proven patients with PTC (114/139, mean age 41.0 ± 15.7 years, M: F, 35%:65%) and FTC (25/139, mean age 39.2 ± 14.3 years, M: F: 24%:76%).

RESULTS:

Average primary tumor …

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

USF Tampa Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …

Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …

Prognostic Impact Of Matrix Metalloproteinases (Mmp-9 And Mmp-2) And Vascular Endothelial Growth Factor Expression In Non-Small Cell Lung Cancer, Ahmet Yurdakul, Nalan Akyürek, Şenay Yilmaz, Jale Karakaya, Leyla Memi̇ş, Can Öztürk

Turkish Journal of Medical Sciences

To investigate the role of matrix metalloproteinases (MMPs), MMP-9 and MMP-2, and vascular endothelial growth factor (VEGF) in metastasis and their relationship with survival. Early metastasis is the most common cause of lung cancer death. Angiogenesis and basement membrane damage are necessary for growth and invasion of the tumoral cells. VEGF, involved in angiogenic activity, and MMPs, involved in matrix destruction, are important for metastasis in lung cancer. Materials and methods: Using immunohistochemistry analysis, we evaluated MMP-9, MMP-2, and VEGF expressions in paraffin specimens from 91 patients with histopathologically confirmed non-small cell lung cancer and the relationship between MMP-9, MMP-2, …