Cell and Developmental Biology Commons^™

A Prospective Study To Validate The Functional Assessment Of Cancer Therapy (Fact) For Epidermal Growth Factor Receptor Inhibitor (Egfri)-Induced Dermatologic Toxicities Fact-Egfri 18 Questionnaire: Swog S1013, Siu Fun Wong, Joseph M. Unger, James L. Wade Iii, Lynne I. Wagner, Mario E. Lacouture, Keisha C. Humphries, Anna Moseley, Kathryn Arnold, Mario R. Velasco Jr., Justin D. Floyd, Benjamin T. Esparaz, Afsaneh Barzi, Heinz-Josef Lenz, Marianna Koczywas, Shaker Dakhil, Gary V. Burton, Michael J. Fisch, N. Lynn Henry, Dawn L. Hershman, Carol M. Moinpour

Pharmacy Faculty Articles and Research

Background

Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients’ health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status.

Methods

Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using …

Cellular Dynamics Of Double Fertilization And Early Embryogenesis In Flowering Plants, Ji Min Shin, Ling Yuan, Masaru Ohme-Takagi, Tomokazu Kawashima

Plant and Soil Sciences Faculty Publications

Flowering plants (angiosperms) perform a unique double fertilization in which two sperm cells fuse with two female gamete cells in the embryo sac to develop a seed. Furthermore, during land plant evolution, the mode of sexual reproduction has been modified dramatically from motile sperm in the early-diverging land plants, such as mosses and ferns as well as some gymnosperms (Ginkgo and cycads) to nonmotile sperm that are delivered to female gametes by the pollen tube in flowering plants. Recent studies have revealed the cellular dynamics and molecular mechanisms for the complex series of double fertilization processes and elucidated differences …

Insulin-Like Growth Factor 2 Mrna-Binding Protein 3 Modulates Aggressiveness Of Ewing Sarcoma By Regulating The Cd164-Cxcr4 Axis, Caterina Mancarella, Giulia Caldoni, Irene Ribolsi, Alessandro Parra, Maria Cristina Manara, Arthur M Mercurio, Andrea Morrione, Katia Scotlandi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ewing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of EWS progression. The aim of this study was to further define the …

Consideration Of Pannexin 1 Channels In Covid-19 Pathology And Treatment, Leigh Anne Swayne, Scott R. Johnstone, Chen Seng Ng, Juan C. Sanchez-Arias, Miranda E. Good, Silvia Penuela, Alexander W. Lohman, Abigail G. Wolpe, Victor E. Laubach, X. Michael Koval, Brant E. Isakson

Anatomy and Cell Biology Publications

Copyright © 2020 the American Physiological Society Pannexin 1 (PANX1) is a ubiquitously expressed, channel-forming protein found in a number of tissues throughout the body (e.g., lung, vasculature, liver, central nervous system, immune system) that is important in many key physiological and immune responses (18, 55). PANX1 channels passively flux ATP (predominantly), multiple metabolites, and likely other small anions (37, 39). PANX1 channels regulate inflammation and host responses to several pathogens, including viruses (36, 42, 53). While there is currently no evidence suggesting novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PANX1 directly interact, there is an urgent need …

Dissecting The Cellular Control Of Septin Organization In A Global Cereal Killer, Nawaraj Dulal

Graduate Theses and Dissertations

Rice blast disease, caused by the filamentous fungus Magnaporthe oryzae, destroys sufficient rice each year to feed 60 million people, and is a serious threat to global food security. A wheat-adapted lineage of M. oryzae now poses threat to global wheat production. Rice blast disease is currently controlled using limited fungicides, and the emergence of fungicide resistance within M. oryzae populations is a growing concern. There is a pressing need to identify new classes of fungicides to control the disease, which requires better understanding of the basic biology of the pathogen. To establish disease, M. oryzae forms a specialized dome …

Secretion Of Proteins And Antibody Fragments From Transiently Transfected Endothelial Progenitor Cells, Loree Heller, Reynald Thinard, Melanie Chevalier, Sezgi Arpag, Yu Jing, Ruth Greferath, Richard Heller, Claude Nicolau

Bioelectrics Publications

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood-brain barrier (BBB) breakdown. After intravenous or intra-arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti-beta-amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti-beta-amyloid Fab protein functions in beta-amyloid aggregate solubilization.

Introducing An Indigenous Non-Toxigenic Aspergillus Flavus Strain Isolated From Iraqi Corn Grains As A Bio-Control Agent To Reduce Aflatoxin Contamination In Corn Grains, Ali Almatakeez

Graduate Theses and Dissertations

Mycotoxin contamination of cereal crops, such as maize and sorghum, is a global concern because of the potential health effects on humans and animals. Although substantial research has been conducting regarding mycotoxin prevention and mitigation, little information is available about the association of mycotoxin-producing fungi with corn and sorghum grain in Iraq. Identifying and refining indigenous atoxigenic strains to reduce mycotoxin contamination of maize and sorghum has the potential to enhance the nutritional value of these grains while reducing economic losses. However, to our knowledge, this tactic has not yet been adopted by agricultural authorities and farmers in Iraq. To …

Phenotypic Switching Of Bacterial Cells In Extreme Environments, Sudip Nepal

Graduate Theses and Dissertations

A large number of terrestrial microbial lives thrive in extremes of environmental conditions, including extremes of pressure, temperature, salinity, pH, and a combination of them. For example, all the marine biomass thrive at high hydrostatic pressure depending on depth. The temperature in the ocean can be very high near the hydrothermal vents and salinity and pH depends on the composition of salt in the surrounding areas. On the surface, hot springs, lakes and geysers provide high temperature conditions, while many places are permafrost regions with subzero temperatures. There is an emerging body of work on the viability, genomics, and metagenomics …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans …

Palbociclib Treatment Alters Nucleotide Biosynthesis And Glutamine Dependency In A549 Cells, Lindsey R. Conroy, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Shesh N. Rai, Brian F. Clem

Neuroscience Faculty Publications

Background

Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown.

Methods

In …

Evaluating The Effects Of Fasting Conditions In Combination With Temozolomide For The Treatment Of Glioblastoma Multiforme, Joseph Duffy

All NMU Master's Theses

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of adult brain cancer. The standard of care for GBM is maximal surgical resection followed by adjuvant treatment with the chemotherapeutic agent temozolomide (TMZ) and radiotherapy. O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein involved in TMZ resistance. Known as the Warburg effect, cancer cells will preferentially oxidize glucose to lactate in glycolysis. This less effective pathway of energy production means cancer cells must uptake significantly greater amounts of glucose to sustain physiological needs. One method that directly targets the bioavailability of glucose is fasting. Among other adaptations, fasting lowers …

Inactivation Of Hippo And Cjun-N-Terminal Kinase (Jnk) Signaling Mitigate Fus Mediated Neurodegeneration In-Vivo, Ankita Sarkar, Abijeet Singh Mehta, Prajakta Deshpande, Madhuri Kango-Singh, Udai Bhan Pandey, Amit Singh

Biology Faculty Publications

Amyotrophic Lateral Sclerosis (ALS), a late-onset neurodegenerative disorder characterized by the loss of motor neurons in the central nervous system, has no known cure to-date. Disease causing mutations in human Fused in Sarcoma (FUS) leads to aggressive and juvenile onset of ALS. FUS is a well-conserved protein across different species, which plays a crucial role in regulating different aspects of RNA metabolism. Targeted misexpression of FUS in Drosophila model recapitulates several interesting phenotypes relevant to ALS including cytoplasmic mislocalization, defects at the neuromuscular junction and motor dysfunction. We screened for the genetic modifiers of human FUS-mediated neurodegenerative phenotype using molecularly …

Phenotypic Plasticity Of Japanese Medaka Gill In Response To Changing Salinities, Laura V. Ellis

Graduate Theses and Dissertations

Japanese medaka (Oryzais latipes) are euryhaline fish, meaning they are capable of surviving in a variety of salinities from fresh water to seawater. The ability to maintain an internal osmotic concentration stems from the phenotypic plasticity of the osmoregulatory organs, the gill, kidney, intestine, and integument. The gill is the main site of osmotic and ionic regulation in fish due to the three-dimensional structure, the direct contact with the outside environment, and the composition of the gill cells. Fish gills are multifunctional as they regulate water movement, acid/base exchange, nitrogenous waste excretion, and ion fluctuations. In freshwater environments, fish are …

Bioavailability And Modes Of Action Of Novel Metal Based Phenanthroline Drugs, Tadhg O’Leary

Doctoral

Metal-basedcompounds have been utilised as chemotherapeutic agents for the last four decades due to their well-documented and clinically relevant anti-tumour properties.Acquired resistance is a challenge for the clinical use of these compounds and there is a continuing need to search for potential new therapeutic agents. Herein, the potential of two metal-basedcompounds containing chelated1,10-phenanthroline (1,10-Phen), one manganese-based (CMPD 73)andonecopper-based (CMPD 74), to act as novel therapeutic agents is explored.CMPD 73 displayed high micromolar (IC50>100μM) cytotoxic properties againstvarious cell systems but interestingly displayed increased cytotoxicity against ovarian (A2780), lung (A549) and cisplatin resistant mesothelioma cells(IC5040-50μM). CMPD 74 was equally cytotoxic against …

Vesicular And Uncoated Rab1-Dependent Cargo Carriers Facilitate Er To Golgi Transport, Laura M. Westrate, Melissa J. Hoyer, Michael J. Nash, Gia K. Voeltz

University Faculty Publications and Creative Works

Secretory cargo is recognized, concentrated and trafficked from endoplasmic reticulum (ER) exit sites (ERES) to the Golgi. Cargo export from the ER begins when a series of highly conserved COPII coat proteins accumulate at the ER and regulate the formation of cargo-loaded COPII vesicles. In animal cells, capturing live de novo cargo trafficking past this point is challenging; it has been difficult to discriminate whether cargo is trafficked to the Golgi in a COPII-coated vesicle. Here, we describe a recently developed live-cell cargo export system that can be synchronously released from ERES to illustrate de novo trafficking in animal cells. …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

Biological And Proteomic Characterization Of Cornus Officinalis On Human 1.1b4 Pancreatic Β Cells: Exploring Use For T1d Interventional Application, Arielle E. Tawfik

USF Tampa Graduate Theses and Dissertations

Type 1 diabetes (T1D) is an autoimmune disease resulting in the loss of pancreatic β cells and subsequent loss of insulin production. Exogenous insulin coupled with continuous glucose monitoring is the only treatment for T1D. Therefore, novel interventional therapies are needed that can inhibit the autoimmune destruction and increase β cell proliferation and function. Based on initial in vitro studies, traditional Chinese medicine (TCM) extract, Cornus officinalis, may be able to serve in this function. CO has been used for 2 millennia for its glucose regulating potential and has shown efficacy in animal models but rarely studied in the context …

Proteomic Identification Reveals The Role Of Ciliary Extracellular‐Like Vesicle In Cardiovascular Function, Ashraf M. Mohieldin, Rajasekharreddy Pala, Rinzhin T. Sherpa, Madhawi Alanazi, Ashwaq Alanazi, Kiumars Shamloo, Amir Ahsan, Wissam A. Aboualaiwi, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)‐like characteristics. The ciliary extracellular‐like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo …

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 …

Gocats: A Tool For Categorizing Gene Ontology Into Subgraphs Of User-Defined Concepts, Eugene Waverly Hinderer Iii, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Gene Ontology is used extensively in scientific knowledgebases and repositories to organize a wealth of biological information. However, interpreting annotations derived from differential gene lists is often difficult without manually sorting into higher-order categories. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. We tested GOcats performance using subcellular location categories to mine annotations from GO-utilizing knowledgebases and evaluated their accuracy against immunohistochemistry datasets in the Human Protein Atlas (HPA). In comparison to term categorizations …