Cancer Biology Commons^™

Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan

Dissertations and Theses (Open Access)

Despite the many advances made in breast cancer research and treatments, breast cancer remains one of the deadliest diseases plaguing women worldwide. While many findings on genetic mutations and their role in predisposing people to breast cancer have been uncovered, we are just beginning to understand the extent to which epigenetic regulators promote tumorigenic phenotypes, metastasis, and chemotherapeutic resistance. Moreover, new experimental tools offer the ability to address questions we were previously unable to assess. My project takes advantage of a new mouse model to understand the role of a proto-oncogenic, transcriptional co-regulator, TRIM24, in mammary gland development and disease. …

Identification And Utility Of Dna In Exosomes, Paul Kurywchak

Dissertations and Theses (Open Access)

Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease. …

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

Dissertations and Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …

Mtbp Inhibits The Erk1/2-Elk-1 Signaling In Hepatocellular Carcinoma, Atul Ranjan, Swathi V. Iyer, Christopher Ward, Tim Link, Francisco J. Diaz, Animesh Dhar, Ossama W. Tawfik, Steven A. Weinman, Yoshiaki Azuma, Tadahide Izumi, Tomoo Iwakuma

Toxicology and Cancer Biology Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation …

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …

Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan

Student Scholar Showcase

One in eight women in the United States will be diagnosed with breast cancer. Approximately 25-30% of these breast tumors will overexpress Human Epidermal Growth Factor Receptor 2 (HER2), associated with a worse prognosis and decreased survival rate. Stimulation of HER2 results in activation and production of many signaling molecules, ultimately resulting in increased cell division. Two of the downstream molecules activated are PI₃Kinase and, further downstream, the molecule Akt. Typically, overproduction and/or overactivation of PI₃Kinase can lead to oncogenesis. A molecule that may have a significant role in PI₃Kinase formation is VAV1. VAV1 …

Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1, Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T. Nguyen, Nsoki Phambu, Anderson Sunda-Meya

Chemistry Faculty Research

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the …

Investigating The Apoptotic Effects Of Platinum(Ii) Amine Complexes With Only One Leaving Ligand On Zebrafish Auditory End Organs, Joshua Smith

Masters Theses & Specialist Projects

The FDA-approved platinum compound, cisplatin, is commonly used as a chemotherapy drug to treat many forms of cancer. However, this compound also has several associated side-effects, including ototoxicity. This has made the development of novel platinum compounds that reduce cancer cell viability, while causing fewer and milder side-effects, an area of significant research interest. In the present study, we examined the apoptotic effects that four monofunctional platinum compounds, pyriplatin, phenanthriplatin, Pt(diethylenetriamine)Cl, and Pt(N,Ndiethyldiethylenetriamine) Cl, had on zebrafish inner ear auditory epithelial cells. We then compared the apoptotic effects of these compounds to those of cisplatin, which is a bifunctional platinum …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Hiv Suppresses Cervical Neutrophil Infiltration In Women With Normal Or Abnormal Pap Smears, Mika Caplan, Peter C. Angeletti, Duan Loy, Kandali Samwel, Daniela Gonzalez, Crispin Chisanga, Julius Mwaiselage, Asafu Munema, Brenda Bashekera, Kessy Goodwin, John Dustin Loy, John T. West, Charles Wood

UCARE: Research Products

Human immunodeficiency virus (HIV) infection of CD4+ T cells results in a weakened immune system due to decreased white blood cells, particularly multi-lobed neutrophils (neutropenia) and other granulocytes.¹ The purpose of this study was to determine whether a correlation exists between HPV/HIV status and presence of neutrophils. To test this, we used a computer software program (QuPath) to analyze neutrophil infiltration seen in pap smears of both HIV+ and HIV- patients from samples collected in Tanzania from three different sites: Bagamoyo, Chalinze, and Dar es Salaam. The software was used to quantify neutrophils per image based on the size …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick J. Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species …

Changes In The Proliferation And Gene Expression Of Huvecs In Response To Treatment With Plant Secondary Metabolites, Caleigh Howard

Seaver College Research And Scholarly Achievement Symposium

Medicinal plants have historically been a valuable source of new drugs, and Southern California possesses a rich collection of native plants which have been used as medicines by native people groups for thousands of years. Angiogenesis is the biological process of new blood-vessel growth from endothelial cells. It is an essential part of the wound-healing process, and increased angiogenesis has also been implicated in the growth of some types of cancerous tumors. In this study, extracts of the Southern Californian native plants Red shanks (Adenostoma sparsifolium) and the alkaloid extract of Jimson weed (Datura wrightii) were …

Pre-Diagnostic Biomarkers Of Metabolic Dysregulation And Cancer Mortality, Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.

METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), …

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …

Acute Loss Of Iron-Sulfur Clusters Results In Metabolic Reprogramming And Generation Of Lipid Droplets In Mammalian Cells, Daniel R. Crooks, Nunziata Maio, Andrew N. Lane, Michal Jarnik, Richard M. Higashi, Ronald G. Haller, Ye Yang, Teresa Whei-Mei Fan, W. Marston Linehan, Tracey A. Rouault

Center for Environmental and Systems Biochemistry Faculty Publications

Iron–sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant–negative variants of the primary Fe-S biogenesis scaffold protein iron–sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming …

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

The Effect Of Grapefruit Intake On Endogenous Serum Estrogen Levels In Postmenopausal Women, Kristine R. Monroe, Frank Z. Stanczyk, Kathleen Hill-Besinque, Malcolm C. Pike

Pharmacy Faculty Articles and Research

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …