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2017

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Ablation Of Adipose-Ho-1 Expression Increases White Fat Over Beige Fat Through Inhibition Of Mitochondrial Fusion And Of Pgc1alpha In Female Mice, S Singh, I Grant, A Meissner, A Kappas, Nader Abraham Aug 2017

Ablation Of Adipose-Ho-1 Expression Increases White Fat Over Beige Fat Through Inhibition Of Mitochondrial Fusion And Of Pgc1alpha In Female Mice, S Singh, I Grant, A Meissner, A Kappas, Nader Abraham

NYMC Faculty Publications

Background Hmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction. Methods We investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO activity was inhibited. Adiposity, signaling proteins, fasting glucose and oxygen consumption were determined and compared to adipocyte cultures with depressed levels of both HO-1/HO-2. Results …


Application Of Open-Access Databases To Determine Functional Connectivity Between Resveratrol-Binding Protein Qr2 And Colorectal Carcinoma, Barbara B. Doonan, Evelien Schaafsma, John T. Pinto, Joseph M. Wu, Tze-Chen Hsieh Aug 2017

Application Of Open-Access Databases To Determine Functional Connectivity Between Resveratrol-Binding Protein Qr2 And Colorectal Carcinoma, Barbara B. Doonan, Evelien Schaafsma, John T. Pinto, Joseph M. Wu, Tze-Chen Hsieh

NYMC Faculty Publications

Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies …


Two Distinct Mechanisms Govern Rpos-Mediated Repression Of Tick-Phase Genes During Mammalian Host Adaptation By Borrelia Burgdorferi, The Lyme Disease Spirochete, A Grove, Dionysios Liveris, Radha Iyer, Mary Petzke, J Rudman, M Caimano, J Radolf, Ira Schwartz Aug 2017

Two Distinct Mechanisms Govern Rpos-Mediated Repression Of Tick-Phase Genes During Mammalian Host Adaptation By Borrelia Burgdorferi, The Lyme Disease Spirochete, A Grove, Dionysios Liveris, Radha Iyer, Mary Petzke, J Rudman, M Caimano, J Radolf, Ira Schwartz

NYMC Faculty Publications

The alternative sigma factor RpoS plays a key role modulating gene expression in Borrelia burgdorferi, the Lyme disease spirochete, by transcribing mammalian host-phase genes and repressing sigma(70)-dependent genes required within the arthropod vector. To identify cis regulatory elements involved in RpoS-dependent repression, we analyzed green fluorescent protein (GFP) transcriptional reporters containing portions of the upstream regions of the prototypical tick-phase genes ospAB, the glp operon, and bba74 As RpoS-mediated repression occurs only following mammalian host adaptation, strains containing the reporters were grown in dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats. Wild-type spirochetes harboring ospAB- and glp-gfp …


Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas Aug 2017

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.


Ablation Of Long-Standing Persistent Atrial Fibrillation, B Mody, A Raza, Jason T. Jacobson, Sei Iwai, Daniel Frenkel, Rhadames Rojas, Wilbert Aronow Aug 2017

Ablation Of Long-Standing Persistent Atrial Fibrillation, B Mody, A Raza, Jason T. Jacobson, Sei Iwai, Daniel Frenkel, Rhadames Rojas, Wilbert Aronow

NYMC Faculty Publications

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in the clinical setting affecting nearly 6 million people in United States and the numbers are only expected to rise as the population continues to age. Broadly it is classified into paroxysmal, persistent and longstanding persistent AF. Electrical, structural and autonomic remodeling are some of the diverse pathophysiological mechanisms that contribute to the persistence of AF. Our review article emphasizes particularly on long standing persistent atrial fibrillation (LSPAF) aspect of the disease which poses a great challenge for electrophysiologists. While pulmonary vein isolation (PVI) has been established as a successful ablation …


Metabolic Differentiation Of Early Lyme Disease From Southern Tick-Associated Rash Illness (Stari), C Molins, L Ashton, Gary Wormser, B Andre, A Hess, J Belisle Aug 2017

Metabolic Differentiation Of Early Lyme Disease From Southern Tick-Associated Rash Illness (Stari), C Molins, L Ashton, Gary Wormser, B Andre, A Hess, J Belisle

NYMC Faculty Publications

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early …


The Role Of Calcium In Regulation Of Glial Cell Line Derived Neurotrophic Factor By Skeletal Muscle Cells, Alicia M. Boynton Aug 2017

The Role Of Calcium In Regulation Of Glial Cell Line Derived Neurotrophic Factor By Skeletal Muscle Cells, Alicia M. Boynton

Masters Theses

Glial cell line-derived neurotrophic factor (GDNF) is an important signaling molecule for the somatic motor nervous system. GDNF protein is produced and secreted by skeletal muscle cells and helps maintain motor neuron innervation at the neuromuscular junction. Treatment with exogenous GDNF prevents denervation which is characteristic of aging and neurodegenerative disease. The therapeutic potential of GDNF cannot be fully explored without understanding the mechanisms by which GDNF protein production is regulated. The primary objective of this study was to determine the role of calcium in regulating GDNF protein expression by skeletal muscle cells. Skeletal muscle cells (C2C12) were grown in …


Nutritional, Endocrine, And Social Influences On Reproductive Physiology At The Origins Of Social Behavior, Karen M. Kapheim Aug 2017

Nutritional, Endocrine, And Social Influences On Reproductive Physiology At The Origins Of Social Behavior, Karen M. Kapheim

Biology Faculty Publications

Understanding the evolutionary origins of social behavior in insects requires understanding the physiological basis for reproductive plasticity. Solitary bees and wasps or those living in small, flexible societies will be key to understanding how conserved pathways have evolved to give rise to reproductive castes. Nutrient-sensing and endocrine pathways are decoupled from reproduction in some life stages of social insects. Heterochrony, particularly as it is related to diapause physiology, may be an important mechanism by which this decoupling occurs. Additional research is needed to understand how these pathways became sensitive to cues from the social environment. Future research targeting species with …


A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib Aug 2017

A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib

Articles, Abstracts, and Reports

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in …


August 2017 News Releases, University Of Montana--Missoula. Office Of University Relations Aug 2017

August 2017 News Releases, University Of Montana--Missoula. Office Of University Relations

University of Montana News Releases, 1928, 1956-present

No abstract provided.


The Relationship Between Microbiota, Diet, And Energy Production In The Alpaca, Courtney Carroll Aug 2017

The Relationship Between Microbiota, Diet, And Energy Production In The Alpaca, Courtney Carroll

Theses and Dissertations

The alpaca is a small South American camelid (SAC) that is an important production animal in Peru, especially among the highly impoverished communities of the high Andes, and raised for its fiber and meat. Alpacas are highly reliant on the microbes within their digestive tracts to digest the plant material they consume; volatile fatty acids (VFAs) are released as a byproduct of this microbial fermentation and used as a major source of energy by the alpaca. To explore optimal parameters for alpaca microbiome analysis, performed 16S rRNA gene surveys on alpaca C1 and fecal samples that had been extracted using …


Mirna Expression Changes In Arsenic-Induced Skin Cancer In Vitro And In Vivo., Laila Al-Eryani Aug 2017

Mirna Expression Changes In Arsenic-Induced Skin Cancer In Vitro And In Vivo., Laila Al-Eryani

Electronic Theses and Dissertations

Arsenic is a naturally prevalent metalloid. Chronic arsenic ingestion through drinking water causes skin cancer. Arsenic-induced cancer mechanisms are not well defined. Epigenetic changes, including microRNA expression changes, might be playing a role. This dissertation investigates the impact of miRNA expression changes in arsenic-induced skin cancer. MiRNA expression was measure and compared using 3 different techniques, RTq-PCR, hybridization arrays and RNA-sequencing. MiRNAs differential expression in skin lesions was phenotype- and stage-related. Immortalized human keratinocytes (HaCaT) were transformed by chronic low arsenite exposure serving as a model for arsenic-induced skin carcinogenesis. Early changes in miRNAs and target mRNAs contribute to arsenic-induced …


Trigger Warnings: From Panic To Data, Francesca Laguardia, Venezia Michalsen, Holly Rider-Milkovich Aug 2017

Trigger Warnings: From Panic To Data, Francesca Laguardia, Venezia Michalsen, Holly Rider-Milkovich

Journal of Legal Education

No abstract provided.


Clemson Commencement Program, August 2017, Clemson University Aug 2017

Clemson Commencement Program, August 2017, Clemson University

Clemson Commencement Programs

No abstract provided.


Exploring The Relationship Between Physical Activity And Executive Function In Early Childhood Populations: An Investigation Of Maternal Encouragement Of Activity, Lauren P. Driggers-Jones Aug 2017

Exploring The Relationship Between Physical Activity And Executive Function In Early Childhood Populations: An Investigation Of Maternal Encouragement Of Activity, Lauren P. Driggers-Jones

Electronic Theses and Dissertations

Researchers have found positive associations between physical activity and executive function in adolescence and adulthood. However, research in early childhood has revealed only negative relationships. In the present study, I explored whether maternal encouragement of physical activity might moderate this relationship in very young children. Using video recordings from an archival dataset, eight maternal encouragement measures were derived from mother-child free play sessions. Although it was expected that maternal encouragement of child activity would broadly play a moderating role in the relationship between children’s physical activity and their executive function, only maternal questions seemed to moderate this relationship. One explanation …


A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock Aug 2017

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to …


Experiences And Perceptions Of Human Vulnerability To Climate Change In Calakmul, Mexico, Lisa Green Aug 2017

Experiences And Perceptions Of Human Vulnerability To Climate Change In Calakmul, Mexico, Lisa Green

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

This report explores how residents of Calakmul, Mexico perceive and experience their own vulnerability to climate change, and how these perceptions and experiences are differentiated among communities, households, and individuals. Fifty-five semi-structured interviews in 2013 and 45 follow-up interviews in 2016 provide data on familiarity with climate change and perceived effects of climate-related stressors on livelihood activities, health, and experiences of hunger. We found that coping responses to the effects of climate change often require cash inputs, and communities are differentiated in their experiences of vulnerability, based in part on their access to wage labor and importantly governmental support.


Mormons And Youtube, Ryan Reeder Aug 2017

Mormons And Youtube, Ryan Reeder

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

As the internet’s second-most trafficked site, behind only Google in both the United States and globally, and with 600,000 hours of content uploaded and one billion hours viewed daily by more than one billion monthly users, YouTube’s reach and scope is vast. Growing out of a need to better facilitate the production and distribution of online video, YouTube was able to become dominant through a combination of factors including the implementation of innovative features, an ability to capitalize on popular videos hosted on its site, and good timing in managing to become a key component of the social media revolution. …


The Evolution Of Natriuretic Peptide Augmentation In Management Of Heart Failure And The Role Of Sacubitril/Valsartan, Srikanth Yandrapalli, Wilbert Aronow, P Mondal, D Chabbott Aug 2017

The Evolution Of Natriuretic Peptide Augmentation In Management Of Heart Failure And The Role Of Sacubitril/Valsartan, Srikanth Yandrapalli, Wilbert Aronow, P Mondal, D Chabbott

NYMC Faculty Publications

Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, …


Investigation Of Ammonia And Nitrate Removal From Municipal Wastewater Using Biowish, Emily Holland Aug 2017

Investigation Of Ammonia And Nitrate Removal From Municipal Wastewater Using Biowish, Emily Holland

Master's Theses

This research entails investigation of ammonia, nitrate, and nitrite removal from wastewater using a proprietary blend of bacteria known as BiOWiSHTM. The degradation rates of ammonia, nitrate, and nitrite for Aqua were determined using wastewater at the San Luis Obispo Water Resource Recovery Facility (SLO WRRF). Laboratory and field experiments were conducted to test how Aqua compared with natural bacteria for removal of nitrogen compounds. Preliminary data suggested that Aqua performed nitrate removal best in SLO WRRF wastewater at the secondary clarifier. Aqua could perform anoxic and aerobic denitrification in secondary clarifier wastewater. In mineral media, Aqua removed …


Potential Of Ozone And Hydroxyl Radicals To Degrade Emerging Organic Contaminants, Lisa Elaine Vance Aug 2017

Potential Of Ozone And Hydroxyl Radicals To Degrade Emerging Organic Contaminants, Lisa Elaine Vance

Master's Theses

Advanced water treatment processes are necessary for the treatment of emerging organic contaminants. Traditional treatment processes do not filter or treat these contaminants causing humans and animals to come into contact and ingest them, both causing illness. Advanced oxidation processes are a good alternative method, but are cost and time intensive.

Previous research on ozone and hydroxyl radicals leads to the conclusion that they might be a vial option for advanced water treatment processes. To test the effects of ozone and hydroxyl radicals on the destruction of algae, ozonated phosphate buffer was mixed with Anabaena and modified BG11 culture media …


The Good Behavior Game: Effects On And Maintenance Of Behavior In Middle-School Classrooms Using Class Dojo, Komila Dadakhodjaeva Aug 2017

The Good Behavior Game: Effects On And Maintenance Of Behavior In Middle-School Classrooms Using Class Dojo, Komila Dadakhodjaeva

Dissertations

Classroom management is one of the key components for successful instruction and affects both instructors and learners. Although most frequent discipline strategies in schools involve punitive actions, research suggests that using positive statements to teach and reinforce desirable behaviors is more appropriate and effective. A form of a group-oriented contingency that focuses on desirable behaviors is a positive variation of the Good Behavior Game (GBG). The GBG has been used widely in its original form, focusing on undesirable behaviors, and more research is needed on its positive version. Another strategy that can be used within classrooms is Class Dojo, a …


Automated Arduino Based Temperature Control And Resistance Change Reading System For Gas Sensors, Hohite Fetene Aug 2017

Automated Arduino Based Temperature Control And Resistance Change Reading System For Gas Sensors, Hohite Fetene

All Theses

Semiconductor gas sensors detect gases by a chemical reaction that takes place when the gas is in contact with the sensor and sensitivity is affected by operating temperature and humidity. The accurate control of gas sensor’s operating temperature is a fundamental aspect that determines the sensitivity and selectivity of gas sensors. A variety of gas sensors are developed so far, and each has different working temperature requirement ranging from 200°C - 400°C for functioning at the finest. This research mainly focuses on the package design criteria of semiconductor gas sensor substrate being developed by Arizona State University. To maximize the …


Prolonged Growth Hormone/Insulin/Insulin-Like Growth Factor Nutrient Response Signaling Pathway As A Silent Killer Of Stem Cells And A Culprit In Aging, Mariusz Ratajczak, Andrzej Bartke, Zbigniew Darzynkiewicz Aug 2017

Prolonged Growth Hormone/Insulin/Insulin-Like Growth Factor Nutrient Response Signaling Pathway As A Silent Killer Of Stem Cells And A Culprit In Aging, Mariusz Ratajczak, Andrzej Bartke, Zbigniew Darzynkiewicz

NYMC Faculty Publications

The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem …


Inhibitory Control And Its Relation To Personality/Temperament, Executive Function, And The Brain, Sarah Mailander Dyer Aug 2017

Inhibitory Control And Its Relation To Personality/Temperament, Executive Function, And The Brain, Sarah Mailander Dyer

Dissertations

Inhibitory control, described as the ability to suppress one response in favor of a goal-directed response, is thought to play an important role in the development of emotional regulation as well as various forms of psychopathology, including ADHD. Up until very recently, inhibitory control has been researched within two completely separate fields of study: temperament and neuropsychology. In the temperament/personality literature, inhibitory control is a major component of the overarching temperament/personality factor of Effortful Control/Conscientiousness. In the field of neuropsychology, inhibitory control is considered one aspect of executive function. Further complicating the current understanding of inhibitory control is the complexity …


Optogenetic Interrogation Of Primary Visual Cortex And Its Impact On Neural Coding And Behavior, Ariana R. Andrei Aug 2017

Optogenetic Interrogation Of Primary Visual Cortex And Its Impact On Neural Coding And Behavior, Ariana R. Andrei

Dissertations and Theses (Open Access)

Understanding the mechanism by which the brain transforms simple sensory inputs into rich perceptual experiences is one of the great mysteries of systems neuroscience. Undoubtedly this involves the activity of large populations of interconnected neurons, but while the responses of individual neurons to a variety of sensory stimuli have been well-characterized, how populations of such neurons organize their activity to create our sensory perceptions is almost entirely unknown. To investigate this complex circuitry requires the ability to causally manipulate the activity of neural populations and monitor the resultant effects. Here we focus on primary visual cortex (V1), which has been …


Involvement Of The Receptor For Advanced Glycation End Products (Rage) In Progression Of Pancreatic Cancer, Nancy Azizian Ms Aug 2017

Involvement Of The Receptor For Advanced Glycation End Products (Rage) In Progression Of Pancreatic Cancer, Nancy Azizian Ms

Dissertations and Theses (Open Access)

Oncogenic KRAS is central to several cancer types including pancreatic ductal adenocarcinoma (PDAC), but has been determined to be “undruggable”. Recent studies have indicated that oncogenic KRAS is not constitutively active but relies on a feed-forward stimulatory mechanism involving inflammation. In the current study we investigated the mechanisms by which, the receptor for advanced glycation end products (RAGE) affects and maintains KRAS activity. We observed that RAGE levels were elevated and there was a shift in the levels of specific isoforms upon inflammation in pancreatic cells and PDAC. Furthermore, RAGE agonists were found to increase Ras activity and downstream signaling …


The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng Aug 2017

The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths due to conventional therapy resistance and metastatic disease, therefore understanding the mechanisms governing these biological functions is vital for improving patient survival. Approximately 30% of patients with the adenocarcinoma histologic subset of lung cancer possess an activating KRAS mutation, characterized by a lack of response to chemotherapies with a poor overall 5-year survival rate. Despite the mutational frequency, KRAS remains a challenge to pharmacologically inhibit and current drugs undergoing clinical trials that target specific downstream effector proteins of KRAS, such as MEK inhibitors, have failed to produce significant clinical benefits. Previous …


Contrasting Effects Of An Mdm2 Functional Polymorphism On Tumor Phenotypes, Guadalupe J. Ortiz Iv Aug 2017

Contrasting Effects Of An Mdm2 Functional Polymorphism On Tumor Phenotypes, Guadalupe J. Ortiz Iv

Dissertations and Theses (Open Access)

Cancer predisposition by the cooperation of genetic variants, such as single nucleotide polymorphisms (SNPs), may be of much greater significance to public health than previously appreciated. Functional polymorphisms are genetic variants that alter gene function. Meta-analyses associate many functional polymorphisms with cancer risk. The MDM2 SNP309G allele is a cancer-associated functional polymorphism positioned in the MDM2 P2 promoter that enhances transcription factor SP1 binding, resulting in elevated levels of MDM2 concomitant with decreased p53 tumor-suppressor activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP on …


Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz Aug 2017

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …