Medicine and Health Sciences Commons^™

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Markov Decision Process Approach To Strategize National Breast Cancer Screening Policy In Data-Limited Settings, Vijeta Deshpande

Masters Theses

Early diagnosis is a promising strategy to reduce premature mortalities and for optimal use of resources. But the absence of mathematical models specific to the data settings in LMIC’s impedes the construction of economic analysis necessary for decision-makers in the development of cancer control programs. This thesis presents a new methodology for parameterizing the natural history model of breast cancer based on data availabilities in low and middle income countries, and formulation of a control optimization problem to find the optimal screening schedule for mammography screening, solved using dynamic programming. As harms and benefits are known to increase with the …

Heterogeneity And Plasticity Of Human Breast Cancer Cells In Response To Molecularly-Targeted Drugs, Emira Bousoik, Ramina Nabiee, Farideh Amirrad, Ashley Nichols, Rebecca Witt, Parvin Mahdipoor, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Non-responsive subpopulation of tumor cells, and acquired resistance in initially responsive cells are major challenges for cancer therapy with molecularly-targeted drugs. While point mutations are considered the major contributing factor to acquired resistance, in this study we explored the role of heterogeneity and plasticity of selected human breast cancer cell lines (MDA-MB-231, MDA-MB-468, and AU565) in their initial and adjusted response, respectively, to ruxolitinib, everolimus, and erlotinib. After determination of lethal concentration for 50% cell death (LC50), cells were exposed to selected drugs using three different approaches: single exposure to 4 × LC50 and collection of surviving cells, multiple exposures …

Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria

Dissertations & Theses (Open Access)

GCN5 is the catalytic subunit in the acetyltransferase module of SAGA and ATAC, multiprotein complexes involved in the modification of histone and nonhistone proteins. GCN5 is most recognized as a co-activator of gene transcription. The SAGA complex is recruited to chromatin by transcription factors such as MYC and E2F1 where GCN5 acetylates H3K9 leading to a more open and accessible chromatin structure. Previous research has demonstrated that GCN5 also acetylates MYC, a protein that amplifies the expression of cancer-promoting genes and is frequently dysregulated in cancer, increasing its stability. Our lab has found there is a significant overlap in the …

Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs …

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 …

Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Purpose

Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of breast cancer. AMP-activated protein kinase (AMPK) is a major energy regulator that suppresses tumor growth, and 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) is a novel AMPK activator that inhibits growth and induces apoptosis in colon cancer. The purpose of this project was to test the effects of FND-4b on AMPK activation, proliferation, and apoptosis in breast cancer with a particular emphasis on TNBC.

Materials and methods

(i) Estrogen-receptor positive breast cancer (ER+BC; MCF-7, and T-47D), TNBC (MDA-MB-231 and HCC-1806), and breast cancer stem cells were treated with FND-4b for 24h. …

Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast …

Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi

Pharmacology and Nutritional Sciences Faculty Publications

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …

Development Of Multifunctional Overhauser-Enhanced Magnetic Rresonance Imaging For Concurrent In Vivo Mapping Of Tumor Interstitial Oxygenation, Acidosis And Inorganic Phosphate Concentration, Artem A. Gorodetskii, Timothy D. Eubank, Benoit Driesschaert, Martin Poncelet, Emily Ellis, Valery V. Khramtsov, Andrey A. Bobko

Faculty & Staff Scholarship

Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of …

Uncovering The Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes, Esmee Koedoot, Michiel Fokkelman, Vasiliki-Maria Rogkoti, Marcel Smid, Iris Van De Sandt, Hans De Bont, Chantal Pont, Janna E. Klip, Steven Wink, Mieke A. Timmermans, Erik A. C. Wiemer, Peter Stoilov, John A. Foekens, Sylvia E. Le Dévédec, John W. M. Martens, Bob Van De Water

Faculty & Staff Scholarship

Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential …

Vitamin D Receptor Gene Polymorphisms Knowledge And Breast Cancer In Texas, Ejike Roland Egwuekwe

Walden Dissertations and Doctoral Studies

Breast cancer is a world health problem and is a leading cause of cancer-related death among women in the United States. However, breast cancer risks were reported to be reduced through exposure to Vitamin D through its Receptors identified as the p53 target gene. The purpose of this study was to assess the associations between VDR gene polymorphisms knowledge/awareness and decisions to reduce breast cancer risks and likelihood of mammogram screening among women in Texas. Data from survey were used. Roy adaptation model was the theoretical framework that guided this quasi- experimental, quantitative research. The dependent variables were decisions to …

Effectiveness And Mechanism Of Action Of Modified Porphyrins For Photodynamic Therapy Of Triple Negative Breast Cancer Cells, Hannah Brandon

Honors Theses

Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks the three molecules typically targeted for treatment. Standard treatment methods leave much to be desired--the rates of metastasis and recurrence are high and the prognosis for most patients with TNBC is poor. One potential treatment for TNBC is photodynamic therapy (PDT), which uses compounds called photosensitizers that are taken up by all tissues in the body. The tumor is exposed to light, activating the photosensitizer and creating reactive oxygen species that cause cell death. This method is relatively pain-free, effective, and does not harm cells …

Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch

Theses and Dissertations

The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …