Cell and Developmental Biology Commons^™

A Systematic Review Of Datasets That Can Help Elucidate Relationships Among Gene Expression, Race, And Immunohistochemistry-Defined Subtypes In Breast Cancer., Ifeanyichukwu O. Nwosu, Stephen Piccolo

Faculty Publications

Scholarly requirements have led to a massive increase of transcriptomic data in the public domain, with millions of samples available for secondary research. We identified gene-expression datasets representing 10,214 breast-cancer patients in public databases. We focused on datasets that included patient metadata on race and/or immunohistochemistry (IHC) profiling of the ER, PR, and HER-2 proteins. This review provides a summary of these datasets and describes findings from 32 research articles associated with the datasets. These studies have helped to elucidate relationships between IHC, race, and/or treatment options, as well as relationships between IHC status and the breast-cancer intrinsic subtypes. We …

Racial And Ethnic Minority Groups Are Under-Represented And Under-Reported In Guideline-Informing Heart Failure Clinical Trials, Gerardo Gamino

Undergraduate Honors Theses

Heart failure (HF) is a common cause of morbidity and mortality in the United States that may disproportionately affect certain racial/ethnic groups. Compared with White individuals, HF may affect Black individuals at a younger age with less favorable prognosis, and this excess risk may be partially explained by differences in HF risk factor burden. It is crucial for guideline informing HF clinical trials to adequately reflect the racial/ethnic diversity in the population. We assessed the extent of reporting and representation of race/ethnicity in HF clinical trials referenced in the 2013 ACC/AHA Guideline for the Management of Heart Failure and the …

Topsentinol L Trisulfate, A Marine Natural Product That Targets Basal-Like And Claudin-Low Breast Cancers, Nader N. El-Chaar, Thomas E. Smith, Gajendra Shrestha, Stephen R. Piccolo, Mary Kay Harper, Ryan M. Van Wagoner, Zhenyu Lu, Ashlee R. Venancio, Chris M. Ireland, Andrea H. Bild, Philip J. Moos

Faculty Publications

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) …

Biological Pretreatment Of Biomass For Enhanced Biogas Production, Skylar F. Van Horne

Undergraduate Honors Theses

The biogas output efficiency of controlled anaerobic digestion (AD) can be enhanced by several different pretreatment methods to produce renewable energy. According to the literature, there are pros and cons to each pretreatment method. Biological pretreatment provides environmentally safe and renewable means for enhancing biodegradability and net energy output. Current research has yet to reliably demonstrate the ability of bacterial strains, such as Caldicellulosiruptor bescii (C. bescii), to digest common waste substrates in efficient ways. Novel methods in key intermediate molecular quantification and alkalinity tracking are used here to explore C. bescii’s ability to digest lignocellulosic material in …

Comparative Efficacies Of Calmare Therapy And Transcutaneous Electrical Nerve Stimulation In Randomized Peripheral Neuropathy Subjects With Resting State Fmri Monitoring, Ty A. Bodily, Logan Edvalson, Jordan B. Peacock, Zack M. Bradshaw, Carson Hart, Cameron Ernst, Samuel Biggs, David D. Busath

Faculty Publications

Clinical reports of Calmare protocol efficacy suggest enhanced durability compared to TENS and the possibility changes in resting fMRI connectivity. The objective was to compare peripheral neuropathy pain relief and resting fMRI changes with Calmare and TENS treatments. Randomized double-blind trials performed in August 2015 and between August 2016 and November 2017, with 18 and 20 human peripheral neuropathy subjects, respectively. The initial trial examined effects of a single session while the latter trial examined the effects of a course of ten treatment sessions on consecutive weekdays. fMRI scans were examined for changes in blood flow correlations and connectivity. Subjective …

Low-Cost Diagnostics: Using Paper As A Material And Pens As An Instrument, Annie Armitstead

Undergraduate Honors Theses

Lateral flow immunoassays (LFIs) are equipment-free tests that produce results quickly using small sample volumes. Colored lines appear as the test runs, indicating the presence of a biomarker. LFIs are ideal in a variety of settings. Development of these assays can be complicated for small team operations, and tests are not sufficiently adaptable for low resource settings. If robust point-of-care tests can be developed on site, they can expand the reach of global diagnostics, improving health around the world. We report a simple empowering LFI (seLFI) that only requires treated printer paper and a plastic backing card. This eliminates the …

Functional And Transcriptomic Characterization Of Cisplatin-Resistant Ags And Mkn-28 Gastric Cancer Cell Lines, Barbara Mora-Lagos, Irene Cartas-Espinel, Ismael Riquelme, Alyssa C. Parker, Stephen R. Piccolo, Tamara Viscarra, Maria Elena Reyes, Louise Zanella, Kurt Buchegger, Carmen Ili, Priscilla Brebi

Faculty Publications

Gastric cancer (GC) is a significant cancer-related cause of death worldwide. The most used chemotherapeutic regimen in GC is based on platinum drugs such as cisplatin (CDDP). However, CDDP resistance reduces advanced GC survival. In vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize new models of CDDP-resistant GC cell lines (AGS R-CDDP and MKN-28 R-CDDP) obtained through a stepwise increasing drug doses method, in order to understand the molecular mechanisms underlying chemoresistance as well as identify new therapeutic targets for the treatment of GC. …

Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell

Theses and Dissertations

Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …

Functional And Transcriptomic Characterization Of Carboplatin-Resistant A2780 Ovarian Cancer Cell Line, Tamara Viscarra, Kurt Buchegger, Ignacio Jofre, Ismael Riquelme, Louise Zanella, Michel Abanto, Alyssa C. Parker, Stephen R. Piccolo, Juan Carlos Roa, Carmen Ili, Priscilla Brebi

Faculty Publications

Background

Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780.

Methods

The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 μM for 2 h. Once 20 cycles of exposure to …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Deborah Himes, Sarah H. Davis, Jane Lassetter Phd, Rn, Neil E. Peterson, Margaret F. Clayton, Wendy C. Birmingham, Anita Y. Kinney

Faculty Publications

Purpose: Knowledge of breast cancer genetics is critical for those at increased hereditary risk who must make decisions about breast cancer screening options. This descriptive study explored theory-based relationships among cognitive and emotional variables related to knowledge of breast cancer genetics in cancer families. Methods: Participants included first-degree relatives of women with breast cancer who had received genetic counseling and testing. Study participants themselves did not have breast cancer and had not received genetic counseling or testing. Data were collected by telephone interviews and surveys. Variables analyzed included numeracy, health literacy, cancer-related distress, age, education, and the reported amount of …

Computational Modelling Of Peptides Containing Non-Standard Amino Acids, David W. Kastner

Undergraduate Honors Theses

Peptides represent a class of abundant and potent pharmaceutic compounds. Despite their appeal, the design, synthesis, and engineering of biologically relevant peptides remain a challenge. Chapter 1 introduces the various computational methods that will be used. Chapter 2 focuses on the incorporation of a special class of amino acids called bulky dehydroamino acids into the turn of β-hairpins to proteolytically stabilize peptides. Our results suggest that dehydroamino acids confer proteolytic stability by favoring a more folded state. Chapter 3 describes the structural calculations of a rare anticancer peptide called Yaku’amide using a combined molecular mechanics/quantum mechanics hybrid method. The …

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox

Undergraduate Honors Theses

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that …

Using Non Stem-Cells To Understand Early Tumor Growth, Jake Hogan, Heiko Enderling, Joel Brown, Robert A. Gatenby

Library/Life Sciences Undergraduate Poster Competition 2018

Tumors of similar size and shape can exhibit different responses to the same treatment. Targeted therapy aims to better treat these tumors by classifying them according to genotypic traits. A better understanding of how tumor traits such as non-stem cells influence tumor growth could improve targeted therapy. We hypothesize that the production of non-stem cells may aid tumor growth in avascular tumors (tumors lacking blood vessels).

Membrane Expression Of Thymidine Kinase 1 And Potential Clinical Relevance In Lung, Breast, And Colorectal Malignancies, Evita G. Weagel, Weston Burrup, Roman Kovtun, Edwin J. Valazquez, Abigail M. Felsted, Michelle H. Townsend, Zachary E. Ence, Erica Suh, Stephen Piccolo, K. Scott Weber, Richard A. Robison, Kim Oneill

Faculty Publications

Background: Lung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance. …

Differential Expression Of Mtor Related Molecules In The Placenta Of Patients With Gestational Diabetes Mellitus, Intrauterine Growth Restriction, Or Preeclampsia, Katherine Price, Brent Kimbler, Nekel Knowlton, Kelsey Hirschi, Paul Reynolds, Juan Arroyo

Student Works

The mechanistic target of rapamycin (mTOR) pathway is involved in placental growth and function during pregnancy. The mTOR pathway responds to nutrient availability and growth factors regulating protein transcription and cell growth. mTOR disruptions are associated with the development of obstetric complications which may result in adverse health outcomes for the mother and/or fetus. The purpose of this study is to identify the differing placental expression of various mTOR-associated proteins during normal gestation (Control), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Immunohistochemistry was used to stain human placenta for activated proteins (phospho; p)AKT, (p)ERK, (p)mTOR, (p)p70 …

Regulation Of Trophoblast Invasion By Pyruvate Kinase Isozyme M2 (Pkm2), Juan Mejia, Parker Hall, Kelsey Hirschi, Paul R. Reynolds, Juan Arroyo

Student Works

The Pyruvate kinase isozymes M2 (PKM2) protein is a metabolic enzyme that regulates the final step of glycolysis. This enzyme is present in highly proliferating cells such as those present in embryonic tissues, cancer and in the placental trophoblast. We recently studied PKM2 protein in the human placenta at term. Our results demonstrated upregulated placental PKM2 during preeclampsia (PE) where trophoblast invasion is decreased and hypoxia is present. Our objective was to determine the cytosolic and nuclear PKM2 expression pattern and determine PKM2 regulation of trophoblast cell invasion. Trophoblast cells were cultured in normoxic and hypoxic conditions and real time …

Combating Subclonal Evolution Of Resistant Cancer Phenotypes, Samuel W. Brady, Jasmine A. Mcquerry, Yi Qiao, Stephen Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, Brent S. Pedersen, Ryan H. Miller, Amanda Esch, Sara R. Selitsky, Joel S. Parker, Layla A. Anderson, Brian K. Dalley, Rachel E. Factor, Chakravarthy B. Reddy, Jonathan P. Boltax, Dean Li, Philip J. Moos, Joe W. Gray, Laura M. Heiser, Saundra S. Buys, Adam L. Cohen, W. Evan Johnson, Aaron R. Quinlan, Gabor Marth, Theresa L. Werner, Andrea H. Bild

Faculty Publications

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these …

Differentiation And Containment Of Derived Pancreatic Beta Cells, Caden Duffy, Alonzo Cook Ph.D.

Biomedical Engineering Western Regional Conference

Currently, the only permanent cure for Type 1 Diabetes is a pancreatic or islet transplant. With the shortage of donors, we are progressing research towards alternative therapies by differentiating induced pluripotent stem cells into derived pancreatic β-cells that can be transplanted and used as treatment for Type 1 Diabetes. We are investigating methods to increase the yield of fully derived, insulin producing pancreatic β-cells and are additionally researching the use of hydrophilized expanded polytetrafluoroethylene for use in cell containment devices. These devices could offer a future alternative for islet transplantation in human patients.

Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows

Biomedical Engineering Western Regional Conference

No abstract provided.

A Cloud-Based Workflow To Quantify Transcript-Expression Levels In Public Cancer Compendia, P J. Tatlow, Stephen R. Piccolo

Faculty Publications

Public compendia of sequencing data are now measured in petabytes. Accordingly, it is infeasible for researchers to transfer these data to local computers. Recently, the National Cancer Institute began exploring opportunities to work with molecular data in cloud-computing environments. With this approach, it becomes possible for scientists to take their tools to the data and thereby avoid large data transfers. It also becomes feasible to scale computing resources to the needs of a given analysis. We quantified transcript-expression levels for 12,307 RNA-Sequencing samples from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas. We used two cloud-based configurations and …

Insulin Treatment Increases Myocardial Ceramide Accumulation And Disrupts Cardiometabolic Function, Aimee Elizabeth Hodson

Theses and Dissertations

Prevalence of diabetes, especially type 2 diabetes mellitus (T2DM) is increasing worldwide. Millions of people are already affected by T2DM and estimates predict over half a billion people will likely be suffering from the disease by 2030. T2DM is associated with an increased risk of developing cardiovascular disease. Cardiovascular dysfunction is the leading cause of mortality among type 2 diabetics. Treatment for T2DM has changed over time. Though it was once known as insulin independent, a large portion of type 2 diabetics are now treated with insulin injections. However, type 2 diabetics treated with insulin are more likely to suffer …

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …

Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf

Theses and Dissertations

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to …

The Anatomy Of Porcine And Human Larynges: Structural Analysis And High Resolution Magnetic Resonance Imaging Of The Recurrent Laryngeal Nerve, Nena Lundgreen Mason

Theses and Dissertations

The recurrent laryngeal nerve (RLN) innervates all the intrinsic muscles of the larynx that are responsible for human vocalization and language. The RLN runs along the tracheoesophageal groove bilaterally and is often accidentally damaged or transected during head and neck surgical procedures. RLN palsy and vocal cord paralysis are the most common and serious post op complications of thyroid surgeries. Patients who suffer from RLN injury can develop unilateral or bilateral vocal fold paralysis (BVFP). Theoretically, selective reinnervation of the posterior cricoarytenoid muscle would be the best treatment for BVFP. The phrenic nerve has been shown in several studies to …

Iron As A Biomarker For Alzheimer’S Disease, Samual Barlow, Dr. Jonathan Wisco

Journal of Undergraduate Research

Alzheimer’s Disease (AD) is one of the highest causes of death in the United States. After the age of 65, the chance of getting Alzheimer’s doubles every five years. As the average lifespan of Americans increases, the importance of understanding AD and finding more efficient ways to treat it increases as well. The earlier AD is treated, the more effectively we are able to treat it. Non-heme iron (Fe) has been shown to spatially correlate with Abeta. Since Fe causes a signal dropout in susceptibility-weighted Magnetic Resonance Imaging (MRI), this imaging modality could possibly be used as a way to …

Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander

Theses and Dissertations

Preeclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes (GDM) increase the risk of maternal and fetal morbidity and mortality. The roles of Advanced Glycation End-products (AGEs) are already well documented concerning inflammation, hypoxia and oxidative stress. AGEs bind to its receptor, Receptor for Advanced Glycation End-products (RAGE), and activate an inflammatory pathway. This pathway alters the efficacy of invasive trophoblast cells and in the placenta and can result in placental dysfunction. We hypothesized that the placental dysfunction found in PE, IUGR, and GDM resulted from an over activation of the RAGE-mediated inflammatory pathway. Using human placental samples, we found …

The Effects Of Inhibiting Wnt Secretion And Activity On Cranial And Neural Development, Julie Louise Hulet

Theses and Dissertations

Wnt signaling has been shown to have several roles in the development of sensory neurons, particularly in the ophthalmic portion of the trigeminal nerve. Many of these studies have relied on the conclusion that Wnt is necessary but not sufficient for the induction and maintenance of the neural precursor cells that develop in the ophthalmic placode. Wnt had been inhibited in the ophthalmic placode using a dominant negative t-cell factor (TCF) and resulted in the loss of Pax3 expression (indicative of undifferentiated placode cells) in all targeted cells, suggesting a loss of specification/commitment of these cells to the sensory neuron …

Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts

Theses and Dissertations

Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide's harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration. Lung cells were exposed to cigarette smoke extract and heart cells were exposed to the lung-cell conditioned …

The Biology Of Claudin 6 (Cldn6) In The Developing Mouse Lung, Felix Ruben Jimenez Rondan

Theses and Dissertations

The tight junctions (TJ), which are located in the apical region between epithelial and endothelial cells, regulate the paracellular diffusion of ions and small molecules and play an important role in maintaining cell polarity, cell-cell integrity, and permeability. In the lung, epithelial cells are attached by TJ structures. They provide a permeable barrier and cell communication. The loss of barrier integrity, which is maintained by the expression of claudins (Cldn), results in cellular permibilization and leads to paracellular diffusion of solutes and harmful molecules. There are 27 known Cldn homologous members in mice and human. Cldn6 is mostly expressed in …

The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson

Theses and Dissertations

Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo …