Medicine and Health Sciences Commons^™

Feature-Guided Deep Radiomics For Glioblastoma Patient Survival Prediction, Zeina A. Shboul, Mahbubul Alam, Lasitha Vidyaratne, Linmin Pei, Mohamed I. Elbakary, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Glioblastoma is recognized as World Health Organization (WHO) grade IV glioma with an aggressive growth pattern. The current clinical practice in diagnosis and prognosis of Glioblastoma using MRI involves multiple steps including manual tumor sizing. Accurate identification and segmentation of multiple abnormal tissues within tumor volume in MRI is essential for precise survival prediction. Manual tumor and abnormal tissue detection and sizing are tedious, and subject to inter-observer variability. Consequently, this work proposes a fully automated MRI-based glioblastoma and abnormal tissue segmentation, and survival prediction framework. The framework includes radiomics feature-guided deep neural network methods for tumor tissue segmentation; followed …

The Children's Oncology Group: Organizational Structure, Membership, And Institutional Characteristics., Janice S. Withycombe, Todd A. Alonzo, Michele A. Wilkins-Sanchez, Maxine Hetherington, Peter C. Adamson, Wendy Landier

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Children's Oncology Group (COG) is the only organization within the National Cancer Institute's National Clinical Trials Network dedicated exclusively to pediatric cancer research. The purpose of this article is to provide an overview of COG's organizational structure, to characterize its institutional and individual membership, and to summarize enrollments onto COG clinical trials.

METHOD: Data from 2013 to 2015 were compiled from sources internal (Network Operations, Statistics and Data Center, Chair's Office) and external (American Hospital Association, American Nurses Credentialing Center) to COG, to present a comprehensive overview of COG's structure, individual and institutional membership, and group operations.

RESULTS: …

Embolus Prevention: Anticoagulant Therapy In Comparison To Watchman's Procedure In Patients With Atrial Fibrillation, Erik Fladmo

Physician Assistant Scholarly Project Posters

• Atrial fibrillation or A-fib is a common cardiac disease that occurs as individuals get older.

• A risk factor of atrial fibrillation is blood clot formation and dislodgement or ‘embolus’ in the left atrium.

• Current treatment methods to prevent clot formation include anticoagulants, as well as a left atrial appendage closure device, The Watchman’s device is the only FDA approved left atrial appendage closure device.

• Study results confirm the rising efficacy and cost effectiveness of Watchman’s device versus long term anticoagulant therapy as well as their adverse effects regarding placement and post procedure; however further randomized control …

Comparing Screening And Treatment Of Bacterial Vaginosis And Pregnancy Outcomes, Stephanie Severson

Physician Assistant Scholarly Project Posters

• Evidence shows that bacterial vaginosis (BV) can lead to poor perinatal outcomes.

• The goal of this project is to answer the question of which pregnant patients should be screened for BV and does identification and treatment of BV during pregnancy improve perinatal outcomes.

• Due to variability in a multitude of factors, a generalized recommendation is difficult to make. Lack of recommendations are largely due to harm of treatment in those who were misdiagnosed.

• The development of polymerase chain reaction (PCR) has the capability to reduce misdiagnosis.

• Newer studies have shown benefit of early screening and …

Comparison Of Pharmacologic Treatments For Postmenopausal Osteoporosis, Kaitlyn Wirtz

Physician Assistant Scholarly Project Posters

• The prevalence of osteoporosis in the United States in adults > 50 years of age is “more than 10 million people overall and 33 million have low bone mineral density (BMD) at the hip” (DynaMed Plus, 2018).

• To combat postmenopausal osteoporosis, two treatment options include bisphosphonates and the anti-receptor activator of nuclear factor kappa β ligand (RANKL) agent (denosumab).

• The purpose of this scholarly project is to determine if there is a statistical significance regarding safety, efficacy, and preference between bisphosphonates and denosumab.

• Three databases were searched: PubMed, CINAHL, and Cochrane Database of Systematic Reviews. Topics researched …

Case–Control Research Study Of Auto-Brewery Syndrome, Barbara Jean Cordell, Anup Kanodia, Gregory K. Miller

Faculty Publications

Background: Auto-brewery syndrome (ABS), also known as Gut Fermentation Syndrome and Endogenous Ethanol Fermentation, is afflicting people worldwide, but little is known about ABS patients’ demographics, health history, lifestyle factors, and diet.

Method: We conducted a broad-based case–control survey study on 52 patients known to have a diagnosis of ABS and their household members. The research compares the symptomatic group (N ¼ 28) to the asymptomatic group (N ¼ 18) regarding lifestyle and health, diet, and medical history.

Results: With a response rate of 88% and using rank-sum tests, the data demonstrate that patients with ABS have …

Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy

Biological Sciences Faculty Publications

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific …

Host Factors Against Plant Viruses, Hernan García-Ruiz

Department of Plant Pathology: Faculty Publications

Plant virus genome replication and movement is dependent on host resources and factors. However, plants respond to virus infection through several mechanisms, such as autophagy, ubiquitination, mRNA decay and gene silencing, that target viral components. Viral factors work in synchrony with pro-viral host factors during the infection cycle and are targeted by antiviral responses. Accordingly, establishment of virus infection is genetically determined by the availability of the pro-viral factors necessary for genome replication and movement, and by the balance between plant defence and viral suppression of defence responses. Sequential requirement of pro-viral factors and the antagonistic activity of antiviral factors …

Comparative Assessment Of Methicillin Resistant Staphylococcus Aureus Diagnostic Assays For Use In Resource-Limited Settings, A. Ayebare, Lisa M. Bebell, Joel Bazira, S. Ttendo, V. Katawera, David Bangsberg, Mark J. Siedner, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: The rise of methicillin-resistant Staphylococcus aureus(MRSA) is a global health concern. Paucity of data on MRSA carriage prevalence and diagnostic methods in resource-limited settings hampers efforts to define the problem and plan an appropriate response. Additionally, high variability in cost and logistical characteristics of MRSA screening methods may impede infection control efforts. We compared the performance of locally-available chromogenic agar BD CHROMagar MRSA II and two PCR-based assays (Hain GenoQuick MRSA and Cepheid Xpert SA Complete) for the detection of asymptomatic MRSA carriage in nasal swabs.

Results: During 2015, we enrolled 500 patients from five hospital …

Evaluation Of Cross-Reactivity To Taenia Hydatigena And Echinococcus Granulosus In The Enzyme-Linked Immunoelectrotransfer Blot Assay For The Diagnosis Of Porcine Cysticercosis, Lucho Gomez-Puerta, Ana Vargas-Calla, Yesenia Castillo, Maria Teresa Lopez-Urbina, Pierre Dorny, Hector H. Garcia, Armando E. Gonzalez, Seth E. O'Neal

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background:

Taenia solium is an important zoonotic parasite that infects humans as definitive host (taeniasis) and pigs as intermediate host (cysticercosis). Serological diagnosis of porcine cysticercosis is limited to antigen detection using ELISA, which is known to cross-react with other Taenia species, and antibody detection using the lentil-lectin glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP EITB), which has not been adequately evaluated for cross-reactivity to other parasites. Field studies suggest that the GP50 diagnostic band of the LLGP EITB may crossreact to Taenia hydatigena, a common non-zoonotic parasitic infection of pigs. The objective of this study was to evaluate the specificity of …

Art Adherence And Viral Suppression Are High Among Most Non-Pregnant Individuals With Early-Stage, Asymptomatic Hiv Infection: An Observational Study From Uganda And South Africa, Jessica E. Haberer, Bosco M. Bwana, Catherine Orrell, Stephen Asiimwe, Gideon Amanyire, Nicholas Musinguzi, Mark J. Siedner, Lynn T. Matthews, Alexander Tsai, Ingrid T. Katz, Kathleen Bell, Annet Kembabazi, Stephen Mugisha, Victoria Kibirige, Anna Cross, Nicola Kelly, Bethany Hedt-Gauthie, David R. Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction

The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support.

Methods

From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 < 200 cells/μL). Socio‐behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically.

Results

Adherence data were available for 869 participants: 322 (37%) early/non‐pregnant, …

Timing Of Antiretroviral Therapy And Systemic Inflammation In Sub-Saharan Africa: Results From The Meta Longitudinal Cohort Study, Mark J. Siedner, Bosco M. Bwana, Stephen Asiimwe, Gideon Amanyire, Nicholas Musinguzi, Jose R. Castillo-Mancilla, Russell P. Tracy, Ingrid T. Katz, David Bangsberg, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/μL) or late-stage disease (CD4 T-cell count <200/ μL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in latestage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

Feasibility Of A Point-Of-Care Test Based On Quantum Dots With A Mobile Phone Reader For Detection Of Antibody Responses, Chan Lee, John Noh, Seth E. O’Neal, Armando E. Gonzalez, Hector H. Garcia, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects …

Implementation Of Stroke Pathways To Reduce Length Of Stay, Cost, Readmissions, And Mortality, Jayme Strauss, Daniel Hartnett, Jenny Ductant, Peter De Armas, Albert Fernandez, Andrew Waisbrot, Amy Starosciak, Felipe De Los Rios La Rosa

All Publications

No abstract provided.

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Predictors And Health Outcomes Of Treatment-Resistant Depression Among Adults With Chronic Non-Cancer Pain Conditions And Major Depressive Disorder, Drishti Shah

Graduate Theses, Dissertations, and Problem Reports (ETD)

Understanding major depressive disorder (MDD) as a comorbidity in patients with chronic non-cancer pain conditions (CNPC) is of importance because of the high prevalence and well documented bi-directional relationship between MDD and pain. Furthermore, presence of CNPC among adults with MDD often reduces benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. Treatment-resistant depression (TRD) commonly defined as insufficient response to multiple antidepressant trials, often worsens depression and pain symptoms and can amplify the clinical and economic burden among adults with CNPC and MDD. Additionally, long-term opioid therapy (LTOT) may be prescribed at a higher rate to adults …

Åstrand-Rhyming And Ymca: A Compare And Contrast Literature Review Of Two Submaximal Cycle Ergometer Tests, Sean Roberts

Williams Honors College, Honors Research Projects

In the world of exercise prescription there are two major protocols that are used to test an individual’s aerobic capacity at a submaximal intensity using a stationary bicycle. These protocols require participants to exercise at a constant work rate until a specified hear rate is reached. Data can then be analyzed to determine the participant’s aerobic capacity. The objective of this literature review is to look at these two tests – the Åstrand-Rhyming cycle ergometer test (ARCET) and the YMCA cycle ergometer test – and determine if one is better than the other for different populations and which one an …

Investigating Iron Metabolism In Subarachnoid Hemorrhage Patients, Alexander A. Maynard, Gardenia Pacheco

Williams Honors College, Honors Research Projects

Subarachnoid hemorrhage (SAH) is a stroke characterized by bleeding into the subarachnoid space of the brain, typically resulting in high mortality rate.⁸ Delayed cerebral ischemia (DCI), characterized by vasospasms induced arterial constriction, occurs in roughly one third of the surviving patients.²⁰ The development of DCI and neurodegeneration could be linked to metabolic pathology that occurs after SAH, specifically iron induced changes in redox status. The oxidized environment induced by iron has the potential to functionally affect the ferroxidase ceruloplasmin (Cp), which is linked to neurodegeneration.¹⁵ Global LC-MS based metabolomics data revealed alterations in metabolism in the CSF …

Evaluating Sex Related Differences In The Osteocyte Lacunar Canalicular Network Across The Lifespan: A Confocal Laser Scanning Microscopy Approach, Gina Tubo

Williams Honors College, Honors Research Projects

Bone is a dynamic tissue with the ability to remodel itself. This capability is facilitated via communication mechanisms through the osteocyte-lacunar-canalicular (LCN) network. Osteocytes are bone cells housed in small, hollow spaces called lacunae. Lacunae are linked by canals called canaliculi. A diminished network can lead to the inability to form bone following breakdown. A decrease in osteocyte-LCN density has been shown to correlate with aging (Ashique et al. 2017). This decline leads to the development of osteoporosis. Osteoporosis preferentially affects women. Prior studies have shown that women older than 50 are four times more likely to be osteoporotic when …

The Relationship Between Physical Activity And Cardiorespiratory Fitness Among People Living With Human Immunodeficiency Virus Throughout The Life Span, Allison R. Webel, Joseph Perazzo, J. Craig Phillips, Kathleen M. Nokes, Cynthia Rentrope, Rebecca Schnall, Rita Musanti, Kimberly Adams Tufts, Elizabeth Sefcik, Mary Jane Hamilton, Carmen Portillo, Puangtip Chaiphibalsarisdi, Penelope Orton, Liana Davis, Carol Dawson Rose

Ellmer School of Nursing Faculty Publications

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are at an increased risk for developing cardiovascular disease (CVD). Physical activity and cardiorespiratory fitness in PLHIV are poorly understood.

OBJECTIVE: The aims of this study were to describe physical activity and cardiorespiratory fitness by sex and age and to examine the association between physical activity and cardiorespiratory fitness in PLHIV, controlling for covariates.

METHODS: Seven hundred two PLHIV participated in a cross-sectional study and completed validated measures of self-reported physical activity (7-day Physical Activity Recall) and cardiorespiratory fitness (6-minute walk test). Participants were recruited from 7 diverse sites in the United …

The Effect Of Extensible And Non-Extensible Lumbar Belts On Trunk Postural Balance In Subjects With Low Back Pain And Healthy Controls, Ali Shahvarpour, Richard Preuss, Christian Larivière

Études primaires

Background

Previous findings suggest that wearing a lumbar belt may benefit some patients with low back pain; however, the mechanisms of action are not yet fully understood.

Research question

The effect of wearing two flexible (extensible and non-extensible) lumbar belts on trunk postural control was investigated during an unstable sitting task.

Methods

Healthy subjects and subjects with LBP sat on a wobbling chair, with and without the lumbar belts. Chair rotation was measured in the sagittal and frontal planes, and 10 linear and nonlinear measures of balance were computed to assess the quantity (3 measures) and quality (7 measures) of …

Scientometric Analysis And Literature Research Growth Of Lupus During 2010-2017, Mohamed Idhris, Manuelraj Peter, Abdurahiman Pattukuthu, Spurgeon Anandraj Samuel

Library Philosophy and Practice (e-journal)

Abstract:

The paper analyses the growth pattern of Lupus disease literature during 2010-2017. The data downloaded from web of science database, further interpreted and analyzed for the study purpose. Total number of publications has been identified as 38750 records. The distribution of publications based on the year of production, country wise productivity, document type of the publications, Major subject categories, Authors whose contribution is in the maximum level were studied. The study reveals a progressive increase on LUPUS research during 2010-2017. The year 2016 contributed highest number of publications. United States is the top contributor during 2010-2017. PETRI M is …

Synthesis And Biological Evaluation Of 2,4-Diaminopyrimidine-5-Carbonitrile And N-(2-Amino-5-Cyanopyrimidin-4-Yl)Benzamide Derivatives As Egfr Inhibitors, Pathan Sultan Ismail, Irfan Khan, Vivek Kumar Kashyap, Ved Prakash Verma, Monika Shukla, Anupam Dhasmana, Shashi Pandey, Girdhar Pal Singh, Shahnawaz Khan, Jaybir Singh

School of Medicine Publications

A series of 2,4-diaminopyrimidine-5-carbonitrile and N-(2-amino-5-cyanopyrimidin-4-yl) benzamide derivatives (5–14) were synthesized and their chemical structures were confirmed by 1 H, 13C NMR and mass spectral data. Anticancer activity of all the synthesized compounds were evaluated for in vitro cytotoxic activity against a panel of four human cancer cell lines i.e., human breast (MCF-7,), cervical cancer (C33A), oral (KB) and prostrate (DU-145). All the examined compounds, demonstrated potent to moderate anticancer activity. Among all the synthesized compounds, 6 and 11 were exhibited more potent activity. Docking studies for 6 and 11 into EGFR active site was carried out to investigate their …

Molecular Mechanism Of Cancer Susceptibility Associated With Fok1 Single Nucleotide Polymorphism Of Vdr In Relation To Breast Cancer, Sana Raza, Anupam Dhasmana, Madan Lal Brahma Bhatt, Mohtashim Lohani, Jamal M. Arif

School of Medicine Publications

Breast cancer is the leading cause of death among women worldwide. It is a multi-factorial disease caused by genetic and environmental factors. Vitamin D has been hypothesized to lower the risk of breast cancer via the nuclear vitamin D receptor (VDR). Genetic variants of these vitamin D metabolizing genes may alter the bioavailability of vitamin D, and hence modulate the risk of breast cancer. Materials and Methods: The distribution of Fok1 VDR gene (rs2228570) polymorphism and its association with breast cancer was analysed in a case–control study based on 125 breast cancer patients and 125 healthy females from North Indian …

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O₂^-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O₂^- with no evident changes in hydrogen peroxide (H₂O₂), peroxynitrite (ONOO^-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …

Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …

Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …