Medicine and Health Sciences Commons^™

Targeting Oncogenic Mirnas With Small Molecules For Breast Cancer Therapy, Paloma Del C. Monroig

Dissertations & Theses (Open Access)

The crucial role of microRNAs (miRNAs) in cancer pathobiology has driven the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, there is a need to develop screening strategies that can target tumors in a specific way. Small molecule inhibitors represent an attractive approach to pursue this. However, the absence of molecular structures for most of the miRNAs makes it very difficult to predict which inhibitors can bind to them. Herein we designed a strategy to screen for small molecules by assesing whether they could directly bind/ interact with miR-10b/miR-21. As part of our …

Breast Cancer Rehabilitation: Clinical Examination And Outcomes Assessment, Nicole L. Stout, Shana Harrington, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman

Electronic Thesis and Dissertation Repository

Breast cancer (BC) patient management has been transformed over the last two decades due to the development and application of genome-wide technologies. The vast amounts of data generated by these assays, however, create new challenges for accurate and comprehensive analysis and interpretation. This thesis describes novel methods for fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (aCGH), and next generation DNA- and RNA-sequencing, to improve upon current approaches used for these technologies. An ab initio algorithm was implemented to identify genomic intervals of single copy and highly divergent repetitive sequences that were applied to FISH and aCGH probe design. FISH …

The Role Of Cytoplasmic Polyadenylation Element Binding Protein-2 (Cpeb-2) In Breast Cancer, Asma Hasan

Electronic Thesis and Dissertation Repository

Over-expression of inflammation associated enzyme cyclo-oxygenase (COX)-2 promotes breast cancer progression, metastasis and sustains cancer stem-like cells (SLCs) by activating prostaglandin E₂ receptor EP4. Two COX-2 induced oncogenic miRNAs, miR-655 and miR-526b, target and down-regulate the cytoplasmic polyadenylation element binding protein (CPEB)-2. Hypothesis: Down-regulation of CPEB2 promotes an aggressive breast cancer phenotype through SLC induction and epithelial to mesenchymal transition (EMT). We found that high COX-2/miRNA expressing cell lines MDAMB231 and MCF7-COX-2 had significantly lower expression of CPEB2 than MCF7 cells (low COX-2/miRNA). CPEB2 knockdown in CPEB2-high MCF7 cell line resulted in increased migratory and invasive capacity in …

Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith

Dissertations & Theses (Open Access)

Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – …

Sex Hormone-Dependent Trna Halves Enhance Cell Proliferation In Breast And Prostate Cancers., Shozo Honda, Phillipe Loher, Megumi Shigematsu, Juan P. Palazzo, Ryusuke Suzuki, Issei Imoto, Isidore Rigoutsos, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER(-) breast cancer, AR(-) prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. …

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self-Report Of Function, Motion, Strength, And Muscular Endurance, Mary Insana Fisher

Mary Insana Fisher

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment. The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Mary Insana Fisher

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

The Power Of Empowerment: An Icf-Based Model To Improve Self-Efficacy And Upper Extremity Function Of Survivors Of Breast Cancer, Mary Insana Fisher, Dana Howell

Mary Insana Fisher

Breast cancer is one of the most frequently diagnosed cancers among women. Breast cancer treatments often negatively impact the function of the arm, and quality of life and upper extremity function does not always return to a prediagnosis level. Survivors of breast cancer may also experience feelings of diminished self-efficacy related to functional deficits resulting from their physical limitations. The International Classification of Functioning (ICF) provides a framework for rehabilitation practitioners to address physical and psychological impairments, activity limitations, and participation restrictions. Patient outcomes may be improved by fostering self-efficacy through empowerment. This paper explores how the ICF model and …

Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu

Graduate Theses and Dissertations

This thesis presents numerical simulation of terahertz (THz) wave interaction with breast cancer tumor tissue sections. The obtained results are expressed in THz images of heterogeneous material that mimics the excised breast cancer tissue sections. The finite-element software package ANSYS High Frequency Structural Simulator (HFSS) was used in this work. HFSS is a full wave frequency domain three-dimensional (3D) electromagnetic simulation package. In this work, four breast cancer tissue models based on pathology images were simulated and images of the models were obtained at 1 THz. An incident Gaussian beam was raster scanned over tissue model configurations and the reflected …

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 ALDH^hiCD44⁺CD24^- breast cancer cells in bone marrow- …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations & Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Betsy Donahoe-Fillmore

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold Merriman

Harold L. Merriman

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A

Determining The Health Beliefs And Breast Cancer Fear Levels Ofwomen Regarding Mammography, Fatma Ersi̇n, Fatma Gözükara, Peri̇han Polat, Gözde Erçeti̇n, Mehmet Ekrem Bozkurt

Turkish Journal of Medical Sciences

Background/aim: Women's fears and health beliefs impact their participation in early breast cancer diagnosis approaches. This study was conducted to determine the health beliefs and fear levels of women older than 50 regarding mammography. Materials and methods: A cross-sectional study was conducted in Turkey. The study cohort consisted of 300 women selected by cluster sampling who agreed to participate in the study. A health belief model scale and breast cancer fear scale were used in data collection. Descriptive statistics, t-test, chi-square test, and correlation analysis were used in the data analysis. Results: Participants had an age average of 59.88 ± …

Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley

All ETDs from UAB

Breast cancer remains the most frequently diagnosed cancer amongst women worldwide. Despite advances in treatment, patients with more aggressive basal-like and HER2-positive cancer experience high rates of recurrence and necessitate novel therapeutic approaches. A class of inhibitors targeted against poly (ADP-ribose) polymerases (PARP), important DNA repair proteins, are effective in cancers with a defective DNA repair response. As such, extensive preclinical and clinical research has examined their efficacy in these cancers. Although this data is promising, it is only applicable to a lim-ited patient population. The main goal of this dissertation is to expand the utility of these well-tolerated drugs …

Saying ‘No’: A Biographical Analysis Of The Experiences Of Women With A Genetic Predisposition To Developing Breast/Ovarian Cancer Who Reject Risk Reducing Surgery, Doreen Molloy

Theses: Doctorates and Masters

Background: Genetic technologies have identified some of the genes implicated in cancer susceptibility. Women with mutations in breast/ovarian cancer-susceptibility genes (BRCA1 and 2) have a lifetime combined risk of breast/ovarian cancer of more than 80%. Risk reducing surgery (RRS) reduces cancer risk by as much as 90% in high risk populations. Despite this, some BRCA1/2 mutation-positive women say no to RRS.

Purpose: To illuminate an understanding of why women at high risk of developing breast/ovarian cancer say no to risk reducing surgery (RRS).

Design: Denzin’s (1989) interpretive biography was combined with Dolby-Stahl’s (1985) literary folkloristic methodology to provide a contextualised …