Medicine and Health Sciences Commons^™

Molecular Basis For The Pharmacological Activities Of Piperlongumine Against Breast Cancer: Role Of Glucose Import, Ros, Nf-Κb And Lncrnas, Nikee Awasthee, Anusmita Shekher, Vipin Rai, Sumit Singh Verma, Shruti Mishra, Subash Chandra Gupta

Research Symposium

Background: Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) root. The activities PL against breast cancer and the underlying mechanism is not thoroughly investigated.

Aim: We examined the anti-cancer activities of PL against breast cancer cells. The molecular basis for the pharmacological activities of this alkaloid was also examined.

Methods: The breast cancer cell lines such as MCF-7, T-47D, MDA-MB-231, MDA-MB-468 and MDA-MB-453 were used during the study. We used MTT assay, clonogenic and soft agar colony formation assay for cytotoxicity. The cell cycle analysis, phosphatidylserine externalization assay, measurement of mitochondrial membrane potential, …

Development Of Surgery Guided Nir Fluorescent Probe Nanoparticles For Cancer Imaging, Neeraj Chauhan, Pallabita Chowdhury, Prashanth Kumar Bhusetty Nagesh, Elham Hatami, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Early-stage detection is crucial for successful breast cancer treatment and can significantly reduce breast cancer associated death rates. There are several diagnostic approaches available for early breast cancer diagnosis but lack tumor specificity and expose patients with radiation. Therefore, there is a crucial need to develop newer and safer imaging modalities. Indocyanine green (ICG), an FDA approved Near InfraRed (NIR) fluorescent probe-based imaging for early cancer detection and image guided surgery, has gained noticeable attention for the clinical applications as it has high sensitivity, low cost, and real-time visualization/imaging capabilities without ionizing radiation. However, ICG has several limitations associated …

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …

Screening Tcf19 And Kif18b To Determine Co-Regulation With Mybl1 In Triple Negative Breast Cancer Patient Tissues, Tyra Sharda Ivory

Theses (2016-Present)

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in …

Computational Approaches To Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data And Lineage Tracing, Sahil Seth

Dissertations & Theses (Open Access)

Tumors are highly heterogeneous and dynamic, continually adapting and evolving in response to their microenvironment as well as external perturbations. Multi-region (spatial) and single cell sequencing has enabled us to anatomize the heterogeneity further and provide evidence of its association with chemo and drug resistance. To investigate this further we took two different approaches to understand the chemo-resistance, and functional heterogeneity in Triple negative breast cancer (TNBC) and Pancreatic ductal carcinoma in situ (PDAC) from an evolutionary perspective.

The first approach was to leverage tumor profiling from an ongoing randomized clinical trial in triple-negative breast cancer (ARTEMIS) to assess mechanisms …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

Undergraduate Research Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

Microrna-26a-5p As A Potential Predictive Factor For Determining The Effectiveness Of Trastuzumab Therapy In Her-2 Positive Breast Cancer Patients, Sadra Samavarchi Tehrani, Ehsan Zaboli, Farzin Sadeghi, Soraya Khafri, Ansar Karimian, Mahnoosh Rafie, Hadi Parsian

BioMedicine

Background: Breast cancer (BC) is known as the most prevalence type of cancer among women. Trastuzumab, as a cancer drug, has been used broadly in human epidermal growth factor receptor 2 (HER-2) positive BC patients. On the other hand, accumulating evidence has demonstrated that microRNAs involved in pathogenesis BC. Hence, we aimed to investigate the effect of trastuzumab on the expression levels of microRNA-26a in HER-2positiveBC patients.

Methods: This study was conducted on HER-2 positive BC patients and HER-2 Negative BC patients. Serum expression of microRNA-26a were detected by real-time PCR. Then, we assessed the correlation of microRNA-26a level with …

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

Mechanisms And Therapeutic Interventions For Breast Cancer-Induced Fatigue And Mitochondrial Dysfunction, David Andrew Stanton

Graduate Theses, Dissertations, and Problem Reports

According to the latest statistics from the National Cancer Institute (NCI), about 1 in 8 U.S. women (~13%) will develop invasive breast cancer over the course of their lifetime. This translates to an estimated 268,600 new cases of breast cancer for the year 2019, and these diagnoses will collectively make up 15% of all new cancer cases across all cancer types. The majority of these women will experience the often-debilitating symptom of breast cancer-induced fatigue. these patients often have difficulty performing normal activities of daily living, have decreased tolerance to traditional tumor-directed therapies, and have higher rates of cancer recurrence. …

Long Noncoding Rna Ak001796 As A Mediator Of Epithelial-To-Mesenchymal Transition In Metastatic Breast Cancer, Sumayya Adib Alchalabi

Legacy Theses & Dissertations (2009 - 2024)

Long noncoding RNAs (lncRNAs) are emerging as key molecules regulating several cellular pathways and contributing to the development and progression of different diseases including cancer. The epithelial-to- mesenchymal transition (EMT), a molecular reprogramming process that plays a critical role in cancer metastasis, involves a complex interaction between protein coding and non-coding transcripts including lncRNAs. Understanding the biological significance of those lncRNAs of relatively unknown function, may help to uncover potential therapeutic targets for the aggressive subtypes of breast and other cancers. In this study, we examined the expression profiles of more than 17,000 lncRNAs in a large set of patients’ …

Cold-Inducible Rna Binding Protein (Cirp) Impedes Proliferation And Inflammation In The Pymt Mouse Model For Breast Cancer, Daniel Albino Lujan

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate gene expression by controlling mRNA export, translation, and stability. When altered, some RBPs allow cancer cells to grow, survive, and metastasize. Cold-inducible RNA binding protein (CIRP) is overexpressed in a subset of breast cancers, induces proliferation in breast cancer cell lines, and inhibits apoptosis. We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. We also assessed the effects of CIRP on breast tumorigenesis using breeding crosses with the PyMT mouse model for breast cancer. CIRP decreased proliferation at the lactational …

Breast Cancer Screening Implications Of Risk Modeling Among Female Relatives Of Atm And Chek2 Carriers, Anne E. Weidner, Mariel E. Liggin, Brenda I. Zuniga, Ann L. Tezak, Georgia L. Wiesner, Tuya Pal

Biology Student Research

Background

With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate-penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high-risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended.

Methods

Among a registry-based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first-degree …

Diet, Weight Management, Physical Activity And Ovarian & Breast Cancer Risk In Women With, Adriana M Coletta, Susan K Peterson, Leticia A Gatus, Kate J Krause, Susan M Schembre, Susan C Gilchrist, Banu Arun, Y Nancy You, Miguel A Rodriguez-Bigas, Larkin L Strong, Karen H Lu, Karen Basen-Engquist

Journal Articles

INTRODUCTION: Women with pathogenic germline gene variants in

METHODS: We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21.

RESULTS: There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk.

CONCLUSIONS: There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women …

Modulating P300 Acetylation Promotes The Rapid Degradation Of Erbb2 Mrna In Erbb2-Positive Breast Cancer Cells., Jacob Rose

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Histone deacetylase inhibitors (HDACi) are a novel class of drugs that target histone deacetylases, enzymes that by removing acetyl groups from the lysine resides of histones and many other non-histone proteins alter the cell’s chromatin structure and cellular functions, including regulation of protein translation and transcript stability. The mechanism of how these inhibitors destabilize some but not all transcripts remains incompletely understood. Our recent research has demonstrated that treatment of ERBB2-positive breast cancer cells with the HDAC1/2 selective HDACi, FK228 (Romidepsin) promotes rapid decay of various oncogenic mRNA transcripts including ERBB2 mRNA. Most recently we have demonstrated that histone acetyltransferase …

Contribution Of Retrotransposons To Breast Cancer Malignancy, Isaac D. Raplee

USF Tampa Graduate Theses and Dissertations

The components contributing to cancer progression, especially the transition from early to invasive are unknown. Consequently, the biological reasons are unclear as to why some patients diagnosed with atypia and ductal carcinoma in situ (DCIS) never progress into invasive breast cancer. The “one gene at a time” approach does not sufficiently predict progression. To elucidate the early stage progression to invasive ductal cancer, expression signature of transcripts and transposable elements in micropunched samples of formalin-fixed, paraffin embedded (FFPE) tissue was conducted. A bioinformatics pipeline to analyze poor quality, short reads (>36 nts) from RNA-Seq data was created to compare …

Novel Flexible Heteroarotinoid, Sl-1-39, Inhibits Her2-Positive Breast Cancer Cell Proliferation By Promoting Lysosomal Degradation Of Her2., Hongye Zou, Mary B. Sevigny, Shengquan Liu, David T. Madden, Maggie Louie

Natural Sciences and Mathematics | Faculty Scholarship

SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells. Molecular analyses suggest that SL-1-39 prevents S phase progression of HER2+ breast cancer cells (SKBR3 and MDA-MB-453), which is consistent with reduced expression of key cell-cycle …

Quality Of Life: Socio-Demographic And Genetic Determinants As Well As Links With Cancer Outcomes, Jeanne Pierzynski

Dissertations & Theses (Open Access)

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary …

Synthesis Of A-Cyanostilbenes And Testing Of Their Anticancer Properties, Gabrielle Cook

Honors Theses

This research project involves synthesizing cyanostilbenes and testing their anticancer properties in breast cancer cells. Breast cancer is a global issue, one that great improvement has been found in the last few decades, but also one that remains a large killer. The components of the cyanostilbene hybrids have all been shown to have anticancer properties on their own, and we would like to see if we can increase these properties by combining multiple into a single hybrid. Then these cyanostilbene compounds are tested on Her2+ human breast cancer cells. The goals is to assess whether or not the cyanostilbenes have …

Breast Cancer, Mana'olana/Hope, And The Experience Of Native Hawaiian Women, Karla Marie Calumet

Walden Dissertations and Doctoral Studies

Breast cancer is one of the leading causes of morbidity and mortality among women. A diagnosis of cancer is a stressful event that requires an individual to adapt to new stressors. The purpose of this qualitative study was to better understand the perceptions of mana'olana/hope and living with breast cancer among Native Hawaiian women. The conceptual framework of this phenomenological study was positive psychology. Data collection included in-depth interviews with 5 Native Hawaiian women who had been diagnosed with breast cancer. Data coding and analysis resulted in identification of 8 themes.

The themes included: (a) mana'olana /hope is the essence …

Benefits Of A Flexitarian Diet: Educating College Students Of Lifestyle Approaches To Reduce The Risk Of Developing Breast And Prostate Cancer, Abbigail Pace

Mahurin Honors College Capstone Experience/Thesis Projects

Practicing the Flexitarian diet, a plant-based diet, in conjunction with physical activity can promote a lifestyle consistent with the American Cancer Society’s recommendations for reducing risks of breast and prostate cancer (American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention, 2015) College students were assessed on knowledge of the relationship between diet and cancer risk prior to and after accessing information on the American Institute of Cancer Research site or the WKU Flexitarian Pinterest Page. Participants were recruited from the National Panhellenic and Interfraternity Council memberships and the International students at Western Kentucky University. Participants completed a …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations & Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …

Methylmercury Exposure Via Canned Tuna Fish Consumption And Breast Cancer, Jennifer Bodenrader

Walden Dissertations and Doctoral Studies

Widespread consumption of canned tuna fish since the 1950s may explain some of the increase in breast cancer prevalence in the United States and Europe. Although canned tuna is the primary source of human exposure to methylmercury, its role as an estrogen activating metalloestrogen has been overlooked in the etiology and incidence of breast cancer. Carcinogenic theory asserts that increased exposure to estrogen elevates the risk of breast cancer. The purpose of this population-based, case control study was to examine the association between canned tuna consumption, total blood mercury, and breast cancer in the NHANES 2003-2006 surveys. A multivariable logistic …

Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects 70-90% of the general population, primarily the immunocompromised, but has been implicated in several forms of cancer, including breast cancer. Breast cancer is the second leading cause of cancer related deaths in women in North America, usually from metastasis. Exosomes are 30-100nm vesicles produced by most cells which carry protein and RNA to cells in their microenvironment. The aim of this study is to investigate the impact of HCMV-infection of a secreted viral cytokine, cmvIL-10, on exosome production by highly metastatic breast cancer cells.

MDA-MB-231 cells were cultured in vitro, …

The Influence Of Matrix Stiffness On Extracellular Matrix Protein Expression In 3d Encapsulated Mammary Fibroblasts, Kathryn Woods

PCOM Biomedical Studies Student Scholarship

A disease that transcends all races is breast cancer, the second leading cause of death among women with cancer. One factor, which participates in breast tumor progression, is the extracellular matrix (ECM), an acellular, protein-rich entity, which drives several cell, processes shown to promote tumorigenesis. Specifically, abnormal expression patterns and cross-linking of matrix fibers induces a more dense tissue structure, which has been reported to drive breast cancer progression. Alterations in ECM expression and cross-linking are in part due to carcinoma-associated fibroblasts (CAFs), activated fibroblasts which deposit copious ECM in the breast tumor environment. The goal of this study is …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

Toxicity And Cosmesis Outcomes For Single Fraction Intra-Operative Electron Radiotherapy (Ioert) For Breast Cancer, Monica Hanna, Robert Ash, Wesley Babaran, Michele M. Carpenter, Afshin Forouzannia, Jay K. Harness, Brian Kaltenecker, Snehith Maddula, Venita Williams, Lawrence Wagman

Student Scholar Symposium Abstracts and Posters

Background: Adjuvant radiation therapy is proven to reduce local recurrence in patients with early stage breast cancer. To reduce toxicity, improve geographic accuracy, and reduce treatment time, IOERT can be utilized as an alternative to external beam radiation therapy. The study’s objective was to determine the short term toxicity and cosmesis profile of single fraction IOERT given as definitive treatment in a community setting. Materials and Methods: From Mar 2012 to Jul 2014, 84 patients (3 bilateral), ages 45-91 y.o. with stage 0-II were treated with IOERT (Mobetron, IntraOp Medical, Sunnyvale, CA). A single 21 Gy fraction was administered to …

Imbalance Between Neutrophil Elastase And Elafin Promotes Breast Cancer Growth And Progression, Joseph Anthony Caruso

Dissertations & Theses (Open Access)

Elafin, an endogenous serine protease inhibitor, is a critical component of the epithelial barrier against neutrophil elastase (NE) activity. The central hypothesis examined in this dissertation was that elafin has tumor suppressive properties in breast cancer. In support of this hypothesis, immunohistochemical (IHC) analysis revealed that elafin was downregulated in the majority of invasive breast tumors and a subset of pre-invasive ductal carcinoma in situ (DCIS) compared to elafin expression in the normal mammary epithelium. To understand the role of elafin in the mammary epithelium and the impetus for its downregulation during breast tumorigenesis, primary and immortalized human mammary epithelial …