Diseases Commons^™

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Jessica L Fairley, Dylan Hansen, Laura Ross, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Jennifer Walker, Lauren V Host, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

Videolaryngoscopy Versus Direct Laryngoscopy For Tracheal Intubation In Neonates, Krithika Lingappan, Nicole Neveln, Jennifer L Arnold, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Establishment of a secure airway is a critical part of neonatal resuscitation in the delivery room and the neonatal intensive care unit. Videolaryngoscopy has the potential to facilitate successful endotracheal intubation, and decrease adverse consequences of a delay in airway stabilization. Videolaryngoscopy may enhance visualization of the glottis and intubation success in neonates. This is an update of a review first published in 2015, and updated in 2018.

OBJECTIVES: To determine the effectiveness and safety of videolaryngoscopy compared to direct laryngoscopy in decreasing the time and attempts required for endotracheal intubation and increasing the success rate on first intubation …

Meqtl Mapping In The Genoa Study Reveals Genetic Determinants Of Dna Methylation In African Americans, Lulu Shang, Wei Zhao, Yi Zhe Wang, Zheng Li, Jerome J Choi, Minjung Kho, Thomas H Mosley, Sharon L R Kardia, Jennifer A Smith, Xiang Zhou

Faculty, Staff and Student Publications

Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs …

3-Phosphoinositide-Dependent Kinase 1 Drives Acquired Resistance To Osimertinib, Ismail M Meraz, Mourad Majidi, Bingliang Fang, Feng Meng, Lihui Gao, Ruping Shao, Renduo Song, Feng Li, Yonathan Lissanu, Huiqin Chen, Min Jin Ha, Qi Wang, Jing Wang, Elizabeth Shpall, Sung Yun Jung, Franziska Haderk, Philippe Gui, Jonathan Wesley Riess, Victor Olivas, Trever G Bivona, Jack A Roth

Faculty, Staff and Students Publications

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of …

Preclinical Investigations Of The Efficacy Of The Glutaminase Inhibitor Cb-839 Alone And In Combinations In Chronic Lymphocytic Leukemia, Natalia Timofeeva, Mary L Ayres, Natalia Baran, Janice M Santiago-O'Farrill, Gamze Bildik, Zhen Lu, Marina Konopleva, Varsha Gandhi

Faculty, Staff and Student Publications

INTRODUCTION: Chronic lymphocytic leukemia (CLL) cells are metabolically flexible and adapt to modern anticancer treatments. Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) inhibitors have been widely used to treat CLL, but CLL cells become resistant to these treatments over time. CB-839 is a small-molecule glutaminase-1 (GLS-1) inhibitor that impairs glutamine use, disrupts downstream energy metabolism, and impedes the elimination of reactive oxygen species.

METHODS: To investigate the

RESULTS: We found that CB-839 caused dose-dependent decreases in GLS-1 activity and glutathione synthesis. CB-839-treated cells also showed increased mitochondrial superoxide metabolism and impaired energy metabolism, which were reflected in decreases in …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho

School of Graduate Studies Faculty Publications

Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration-and time-dependent in both assays, since the lowest concentration …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Genetic Influences On The Response To Neuromodulation In Craving Behaviors, Carly J. Haring

Honors Thesis

Obesity and eating disorders are highly prevalent in the United States. People who suffer from obesity and/or eating disorders face serious health consequences and even death. Current treatments are not effective as recovery rates are low, so there is a dire need for an effective treatment for obesity and eating disorders. There have been studies investigating the use of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) as a means of treatment for these people. While findings show promise, there is much variability. The goal of this study is to further prior …

Center Based Cardiac Rehabilitation Outcomes Associated With Covid-19 Pandemic: A Retrospective Comparative Cohort Study, Haley Williams, Kayla Woodworth

Doctor of Nursing Practice Projects: College of Nursing

Background: Traditional cardiac rehabilitation (CR) is a multidisciplinary, multifaceted program for cardiac patients. Throughout the Covid-19 pandemic, health care, including center-based CR (CBCR) programs, were closed to in-person sessions. Even with the return to CBCR participation, patient outcomes may have been affected by this disruption in care. The goal of this study was to determine if CR participation outcomes differed before and after CBCR program closure due to Covid-19.

Methods: A retrospective comparative cohort design was used to examine CR participant outcome data before and after the Covid-19 pandemic. Convenience sampling of CR participants at a large, urban …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

Cystic Duct Morphology And Heister Valves: A Cadaveric Study, Cierra R. Goerish

Theses & Dissertations

Continued occurrence of cholelithiasis, gallstones, commonly results in cholecystectomy, removal of the gallbladder. Having a comprehensive anatomical, histological, and physiological knowledge of the biliary apparatus is imperative in clinical medicine today. Additionally, the functionality of cystic duct (CD) Heister valves (HV) has been speculatory since being reported in 1732. This study summarizes the morphology, orientation, and variability of the gross biliary system and provides data to help justify HV functionality.

Cadaveric dissection was utilized for gross observation and analysis of the biliary system. The angulation of the CD was found primarily as an acute angle; however, obtuse angulation could be …

Home-Based Tdcs For Apathy In Alzheimer’S Disease: A Protocol For A Randomized Double-Blinded Controlled Pilot Study, Antonio L Teixeira, Laís Bhering Martins, Thiago Macedo E Cordeiro, Lijin Jose, Robert Suchting, Holly M Holmes, Ron Acierno, Hyochol Ahn

Faculty, Staff and Student Publications

BACKGROUND: Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Brash Syndrome Case Report And Brief Review, Kelly Schuitema

Rowan-Virtua Research Day

BRASH syndrome is an acronym that stands for bradycardia, renal failure, AV node blocker, shock and hyperkalemia. The syndrome is precipitated by synergism from AV nodal blocking agents and hyperkalemia. The combination of the AV nodal blockade and renal failure leads to a cycle of severe bradycardia and hyperkalemia. We will discuss a case of BRASH syndrome with a 68 year old female who presented with generalized weakness and was found to be hypotensive, bradycardia, in acute renal failure with hyperkalemia likely related to metoprolol and amlodipine use.

Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, …

Maldi-Tof Ms Based Proteomic Fingerprinting Of Total Serum Plasma For Somatic Pain Syndromes, Isaiah Pinkerton, Venkateswar Venkataraman

Rowan-Virtua Research Day

There are racial and ethnic disparities regarding pain management within the United States, and that disproportionately affects women of color. There is also a fundamental lack of information regarding the biological mechanism by which pain sensitization and perception occurs, and how it could be affected by both neurologic and somatic pain syndromes.

Methods: Research was performed on principal electronic scientific databases including Google Scholar, PubMed, and Embase with search terms “MALDI-TOF”, “ESI-MS”, “Pain”, and “Biomarkers”, as well as other modifiers to narrow the literature search.

Results: Studies on comparison between MALDI-TOF and other traditional analysis platforms, including Electrospray Ionization (ESI-MS), …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

Is There A Role For Plant-Based “Meat” In Cardiovascular Disease Prevention?, Aziza Jadallah, Usmaan Al-Shehab, Adam Friedman

Rowan-Virtua Research Day

Diet is an established risk factor for cardiovascular disease. The American Heart Association recommends following a whole-food, minimally processed diet emphasizing fruit and vegetables to reduce cardiovascular mortality. Recently, processed plant-based meat substitutes, such as Beyond Meat® and Impossible™ foods have become easily accessible to consumers and are advertised as a healthful addition to a plant-based diet. However, these products are highly processed and contain high amounts of saturated fat and sodium. The purpose of this research is to investigate the effect of processed plant-based meat diets on adverse cardiovascular events compared to animal-based meat diets and minimally processed healthful …

The Role Of Food Accessibility In Weight Loss In A Rat Model Of Parkinson’S Disease, Anjali Kikkisetti, Nicole Charles, Francois Gould

Rowan-Virtua Research Day

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. The goal of this project was to understand whether the weight loss seen with Parkinson’s disease was due to the lack of being able to access the food because of the food placement or because of inability to chew the food due to degeneration of muscles required for chewing food. Both treatment groups, Adjusted Diet and Unadjusted Diet, lost weight after injections started, whereas control weights were stable throughout the experiment. There is no statistically significant difference in weight loss between adjusted and unadjusted …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Human Airway Mucociliary Tissue Cultures Chronically Exposed To E-Cigarette Vapors Exhibit Altered Cell Populations And Increased Secretion Of Immunomodulatory Cytokines, Vanessa Pizutelli, Vincent Manna, Shannon Dwyer, Salvatore Caradonna

Rowan-Virtua Research Day

Vape-pens or electronic cigarettes (e-cigarettes) are handheld battery powered devices that use a vape-liquid to produce a vapor that is inhaled by the user. The active ingredients in commercial vape-liquids are commonly nicotine, tetrahydrocannabinol or cannabidiol. A consequence of the rise in e-cigarette usage was the 2019 emergence of a vaping-induced respiratory disease denoted ‘e-cigarette or vaping use-associated lung injury’ (EVALI). One of the suspected causes of EVALI is Vitamin E Acetate (VEA), which was found to be a diluent in certain illicit tetrahydrocannabinol vape-pens, whereas nicotine is commonly diluted in equal parts propylene glycol and vegetable glycerin (PG:VG). The …

A 5-Year Clinical Course Of Phenocopy Syndrome Of Behavioral Variant Frontotemporal Dementia: Case Report And Literature Review, Joseph Melillo, Keyur Patel, Christian White

Rowan-Virtua Research Day

Frontotemporal dementia is a neurocognitive disease which affects language, behavior, or executive functioning. This disease includes a spectrum of presentations which includes multiple variants. The phenocopy syndrome of behavioral variant frontotemporal dementia is one which mimics the behavioral variant of frontotemporal dementia. Patients with this condition show a decline in personality, social conduct and cognitive ability but often display no signs of neurological imaging and exhibit slow progression. This case focuses on a now 70-year-old male who has shown signs of behavioral changes with a slowly progressive clinical course and minimal findings on PET scan, but moderate changes seen on …

Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville

Rowan-Virtua Research Day

PMPS is defined as chronic neuropathic pain following breast cancer procedures in the ipsilateral arm, chest wall, axilla or shoulder.1-3 Approximately 20 to 50% of post mastectomy patients suffer from Post Mastectomy Pain Syndrome (PMPS).1 With more than 3.8 million breast cancer survivors, due to advances in treatment, there is increased importance in findings ways to better manage the quality of life of breast cancer survivors.1,4 Ketamine induces analgesic effects through its non-competitive antagonism of NDMA receptors.5 Low doses of ketamine infusion (20–30 mg x h−1) have been shown to produce analgesia in neuropathic pain states with benefits lasting up …

Aneurysmal Subarachnoid Hemorrhage In Pregnancy: National Trends Of Treatment, Predictors, And Outcomes, Kasra Khatibi, Hamidreza Saber, Smit Patel, Lucido Luciano Ponce Mejia, Naoki Kaneko, Viktor Szeder, May Nour, Reza Jahan, Satoshi Tateshima, Geoffrey Colby, Gary Duckwiler, Yalda Afshar

School of Medicine Faculty Publications

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) is a rare event associated with significant pregnancy-associated maternal and neonatal morbidity and mortality. The optimal treatment strategy and clinical outcome of aSAH in pregnancy remains unclear. We aimed to investigate the treatment utilizations and outcomes of aSAH in pregnant people. Methods Using the 2010-2018 National Inpatient Sample, we identified all birth hospitalizations of women between ages of 18 to 45 associated with subarachnoid hemorrhage and aneurysm treatment were included. Multivariate analyses were used to evaluate the effect of pregnancy state, mode of treatment of aneurysms, severity of subarachnoid hemorrhage on mortality and discharge destination …

Functional Characterization Of Age-Dependent P16 Epimutation Reveals Biological Drivers And Therapeutic Targets For Colorectal Cancer, Li Yang, Xiaomin Chen, Christy Lee, Jiejun Shi, Emily B Lawrence, Lanjing Zhang, Yumei Li, Nan Gao, Sung Yun Jung, Chad J Creighton, Jingyi Jessica Li, Ya Cui, Sumimasa Arimura, Yunping Lei, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: Methylation of the p16 promoter resulting in epigenetic gene silencing-known as p16 epimutation-is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis.

METHODS: We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA …

Using Cancer Proteomics Data To Identify Gene Candidates For Therapeutic Targeting, Diana Monsivais, Sydney E Parks, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. When recently surveying proteomic correlates of tumor grade across multiple cancer types, we identified specific protein kinases having a functional impact on uterine endometrial cancer cells. This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients. Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer …

Glynac (Glycine And N-Acetylcysteine) Supplementation In Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation And Neurotrophic Factors To Reverse Age-Associated Cognitive Decline: Implications For Improving Brain Health In Aging, Premranjan Kumar, Ob W Osahon, Rajagopal V Sekhar

Faculty, Staff and Students Publications

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we …

Impact Of Clonal Plasma Cells In Autografts On Outcomes In High-Risk Multiple Myeloma Patients, Oren Pasvolsky, Denái R Milton, Mikael Rauf, Sassine Ghanem, Adeel Masood, Ali H Mohamedi, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Katy Rezvani, Richard Champlin, Elizabeth J Shpall, Pei Lin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC- in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC- (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p < 0.001). Median progression free survival (PFS) and overall survival (OS) were (12.8 vs. 32.1 months) and (36.4 vs. 81.2 months) in the CPC + and CPC- groups, respectively (both p < 0.001). Also in the subset of patients with MRD-negative ≥VGPR prior to autoHCT, those with CPC + autografts had inferior PFS (HR 4.21, p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.

In Vitro Characterization Of A Novel Murine Model Of Cancerous Progression, Steven D. Scahill, Kelly Jean Sherman, Jessie J. Guidry, Whitney Walkowski, Theresa Nguyen, Durwood B. Ray, David H. Jones, Harry J. Gould, Dennis Paul

School of Graduate Studies Faculty Publications

To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high …