Digital Commons Network^™

Erosive Arthritis And Hepatic Granuloma Formation Induced By Peptidoglycan Polysaccharide In Rats Is Aggravated By Prasugrel Treatment., Analia E Garcia, Mario C Rico, Elisabetta Liverani, Raul A Dela Cadena, Paul F. Bray, Satya P Kunapuli

Cardeza Foundation for Hematologic Research

Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with …

Support For A Smoke-Free Bylaw In Parks And On Beaches, Chizimuzo T.C. Okoli, Ann Pederson, Wendy Rice

Nursing Faculty Publications

BACKGROUND: In September 2010, Vancouver, Canada enacted a smoke-free bylaw in parks and on beaches.

OBJECTIVE: To examine demographic and attitudinal factors associated with the public opinion on Vancouver's outdoor smoke-free bylaw.

METHODS: From 496 randomly selected Vancouver residents, information on demographics, smoking status, and opinions and support for or opposition to the smoke-free bylaw were obtained by telephone surveys.

RESULTS: Approximately 84.2% of the sample endorsed the legislation; a greater proportion of non-smokers supported the bylaw than smokers (88.6% vs. 52.0%). In multivariate analysis, demographic variables significantly associated with supporting the smoke-free bylaw were being female, having completed community …

Dna Methylation Analysis Reveals Distinct Methylation Signatures In Pediatric Germ Cell Tumors, James F. Amatruda, Julie A. Ross, Brock Christensen, Nicholas J. Fustino, Kenneth S. Chen, Anthony J. Hooten, Heather Nelson, Jacquelyn K. Kuriger, Dinesh Rakheja, A. Lindsay Frazier, Jenny N. Poynter

Dartmouth Scholarship

Background: Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. Methods: We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and …

Systematic Examination Of Infant Size And Growth Metrics As Risk Factors For Overweight In Young Adulthood, Andrew O. Odegaard, Audrey C. Choh, Ramzi W. Nahhas, Bradford Towne, Stefan A. Czerwinski, Ellen W. Demerath

Population and Public Health Sciences Faculty Publications

Objective:To systematically examine infant size and growth, according to the 2006 WHO infant growth standards, as risk factors for overweight status in young adulthood in a historical cohort. Specifically, to assess: Whether accounting for length (weight-for-length) provides a different picture of risk than weight-for-age, intervals of rapid growth in both weight-for-age and weight-for-length metrics, and what particular target ages for infant size and intervals of rapid growth associate most strongly with overweight as a young adult.Patients/Methods:Data analysis of 422 appropriate for gestational age white singleton infants enrolled in the Fels Longitudinal Study. Odds ratios (OR) for overweight and obesity in …

Operative Management Of Partial-Thickness Tears Of The Proximal Hamstring Muscles In Athletes., Karl F Bowman, Steven B. Cohen, James P Bradley

Rothman Institute Papers

BACKGROUND: Partial tears of the hamstring muscle origin represent a challenging clinical problem to the patient and orthopaedic surgeon. Although nonoperative treatment is frequently met with limited success, there is a paucity of data on the efficacy of surgical management for partial proximal hamstring tears in the active and athletic population.

PURPOSE: To evaluate the results of an anatomic repair for partial tears of the hamstring muscle origin in athletes.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: The records of 17 patients with partial tears of the proximal hamstring origin were reviewed after institutional review board approval was …

B Cell Response And Hemagglutinin Stalk-Reactive Antibody Production In Different Age Cohorts Following 2009 H1n1 Influenza Virus Vaccination, Mark Y. Sangster, Jane Baer, Felix W. Santiago, Theresa T. Fitzgerald, Natalia A. Ilyushina

Dartmouth Scholarship

The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior ex- posure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated dif- ferences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) …

Prevalence And Patterns Of Sexting Among Ethnic Minority Urban High School Students, Melissa Fleschler Peskin, Christine M Markham, Robert C Addy, Ross Shegog, Melanie Thiel, Susan R Tortolero

Faculty, Staff and Student Publications

Although sexting among U.S. youth has received much popular media attention, there are only limited data on its prevalence among ethnic minority youth. This study, therefore, specifically examined the prevalence and patterns of sexting (sending and/or receiving a nude or semi-nude picture/video or a sexual text-only message) among a sample of black and Hispanic youth. Data from 1,034 tenth graders from a large, urban school district in southeast Texas were used to calculate the prevalence of sexting by gender-race/ethnicity. Overlap among sexting behaviors was also examined. Electronic surveys were administered via an audio-computer-assisted self-interview on laptop computers. Prevalence estimates were …

Echocardiographic Methods, Quality Review, And Measurement Accuracy In A Randomized Multicenter Clinical Trial Of Marfan Syndrome., Elif Seda Selamet Tierney, Jami C. Levine, Shan Chen, Timothy J. Bradley, Gail D. Pearson, Steven D. Colan, Lynn A. Sleeper, M Jay Campbell, Meryl S. Cohen, Julie De Backer, Lin T. Guey, Haleh Heydarian, Wyman W. Lai, Mark B. Lewin, Edward Marcus, Christopher R. Mart, Ricardo H. Pignatelli, Beth F. Printz, Angela M. Sharkey, Girish S. Shirali, Shubhika Srivastava, Ronald V. Lacro, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Background: The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement.

Methods: Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the …

Ensemble-Based Methods For Forecasting Census In Hospital Units, Devin C. Koestler, Hernando Ombao, Jesse Bender

Dartmouth Scholarship

The ability to accurately forecast census counts in hospital departments has considerable implications for hospital resource allocation. In recent years several different methods have been proposed forecasting census counts, however many of these approaches do not use available patient-specific information. In this paper we present an ensemble-based methodology for forecasting the census under a framework that simultaneously incorporates both (i) arrival trends over time and (ii) patient-specific baseline and time-varying information. The proposed model for predicting census has three components, namely: current census count, number of daily arrivals and number of daily departures. To model the number of daily arrivals, …

Significant Sequelae After Bacterial Meningitis In Niger: A Cohort Study, Jean-François Jusot, Zilahatou Tohon, Abdoul Aziz Yazi, Jean-Marc Collard

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Beside high mortality, acute bacterial meningitis may lead to a high frequency of neuropsychological sequelae. The Sahelian countries belonging to the meningitis belt experience approximately 50% of the meningitis cases occurring in the world. Studies in Africa have shown that N. meningitidis could cause hearing loss in up to 30% of the cases, exceeding sometimes measles. The situation is similar in Niger which experiences yearly meningitis epidemics and where rehabilitation wards are rare and hearing aids remain unaffordable. The aim of this study was to estimate the frequency of neuropsychological sequelae after acute bacterial meningitis in four of the …

Pilot Comparative Effectiveness Study Of Surface Perturbation Treadmill Training To Prevent Falls In Older Adults, Jon D. Lurie, Alexandra B. Zagaria, Dawna M. Pidgeon, Judith L. Forman, Kevin Spratt

Dartmouth Scholarship

Falls are the leading cause of fatal and non-fatal injuries among older adults. Exercise programs appear to reduce fall risk, but the optimal type, frequency, and duration of exercise is unknown. External perturbations such as tripping and slipping are a major contributor to falls, and task-specific perturbation training to enhance dynamic stability has emerged as a promising approach to modifying fall risk. The purpose of this pilot study was 1) to determine the feasibility of conducting a large pragmatic randomized trial comparing a multidimensional exercise program inclusive of the surface perturbation treadmill training (SPTT) to multidimensional exercise alone (Standard PT); …

Grotesque Drag Queens And Toxic Matriarchs: Motherhood And The Subversive Female Body In Disney Animated Films, Allison Footit

Master's Theses

No abstract provided.

Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another. Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial orrelation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Beyond The Stated Function: Showcasing, Through Everyday Objects, Social Obstacles Imposed On Qatari Female Youth, Kazem Esra

Theses and Dissertations

This critical design project showcases obstacles that the Qatari culture and society impose on their female youth, hindering them from becoming independent individuals. It critiques the society and its social pressures. The project stimulates people to think by challenging their assumptions and perceptions, specifically social perception and judgment, family authority, and gender favoritism. This is achieved through hybridized accessories that are embedded with a meta-meaning that arouses curiosity, invites questions, and stimulates thoughts. Through the design of these appealing, high quality, and functionally viable everyday accessories, the project aims to communicate the social and cultural forces which impede Qatari female …

Reinforcing Effects Of Compounds Lacking Intrinsic Efficacy At Α1 Subunit-Containing Gabaa Receptor Subtypes In Midazolam- But Not Cocaine-Experienced Rhesus Monkeys., Nina M Shinday, Eileen K Sawyer, Bradford D Fischer, Donna M Platt, Stephanie C Licata, John R Atack, Gerard R Dawson, David S Reynolds, James K Rowlett

Cooper Medical School of Rowan University Departmental Research

Benzodiazepines are prescribed widely but their utility is limited by unwanted side effects, including abuse potential. The mechanisms underlying the abuse-related effects of benzodiazepines are not well understood, although α1 subunit-containing GABAA receptors have been proposed to have a critical role. Here, we examine the reinforcing effects of several compounds that vary with respect to intrinsic efficacy at α2, α3, and α5 subunit-containing GABAA receptors but lack efficacy at α1 subunit-containing GABAA receptors ('α1-sparing compounds'): MRK-623 (functional selectivity for α2/α3 subunit-containing receptors), TPA023B (functional selectivity for α2/α3/α5 subunit-containing receptors), and TP003 (functional selectivity for α3 subunit-containing receptors). The reinforcing effects …

The Mathematics Self-Efficacy Of Rural Central Appalachian Undergraduate Females., Lisa J. Music

Electronic Theses and Dissertations

This dissertation study was a two-part investigation with a sample of undergraduate students from three community and technical colleges and one university in the state of Kentucky. The purpose of this study was to investigate the factors that contribute to the mathematics self-efficacy of rural Central Appalachian undergraduate females. Two subscales of the Fennema-Sherman Mathematics Attitude Scale, the Confidence in Learning Mathematics and the Effectance Motivation Scale in Mathematics, were used to identify potential interview subjects. The 596 subjects, including 360 females and 236 males, also completed a questionnaire designed to determine their classification as being from rural Central Appalachia, …

Common Peroneal Nerve Palsy Following Total Hip Arthroplasty: Prognostic Factors For Recovery., Jai Hyung Park, Bryan Hozack, Peter Kim, Robert Norton, Steven Mandel, Camilo Restrepo, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Common peroneal nerve palsy, although rare, is a serious complication of total hip arthroplasty. Although several publications have dealt with the risk factors for peroneal nerve palsy, there is little literature regarding the time it takes for the nerve to recover and the factors that influence its recovery. The purpose of this study was to elucidate the clinical course of this injury and identify prognostic factors for recovery.

METHODS: From January 2000 to December 2007, 7969 primary and 1601 revision total hip arthroplasties were performed at our institution. Common peroneal nerve palsy developed following thirty-one (0.32%) of these procedures. …

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Department of Surgery Faculty Papers

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …

State-By-State Variation In Emergency Versus Elective Colon Resections: Room For Improvement., Augustine C. Obirieze, Mehreen Kisat, Caitlin W. Hicks, Tolulope A. Oyetunji, Eric B. Schneider, Darrell J. Gaskin, Elliott R. Haut, David T. Efron, Edward E. Cornwell, Adil H. Haider

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Compared with elective surgical procedures, emergency procedures are associated with higher cost, morbidity, and mortality. This study seeks to investigate potential state-by-state variations in the incidence of emergent versus elective colon resections.

METHODS: A retrospective analysis of all adult patients (aged ≥18 years) included in the Nationwide Inpatient Sample from 2005 to 2009 who underwent hemicolectomy (right or left) or sigmoidectomy was conducted. Discharge-level weights were applied, and generalized linear models were used to assess the odds of a patient undergoing emergent versus elective colon surgery nationally and for each state after adjusting for patient and hospital factors. Odds …

A Phenomenological Study Of Mid-Career Female Student Affairs Administrators' Experiences Navigating The Career Labyrinth Including Obstacles In Catholic Higher Education, Michele Starzyk

Department of Educational Administration: Dissertations, Theses, and Student Research

While the role of women in the Catholic Church has been a topic of much discussion, there has also been a call for the Church to partner with the laity. However, women who choose to work in Catholic co-educational, male sponsored higher education institutions may find a gendered organizational culture to embrace. Little research has been done in regards to the experience women have navigating the career labyrinth at mid-career while employed at Catholic institutions.

This study attempted to answer the grand tour question of what meaning do mid-career female student affairs professionals make of navigating the career labyrinth, including …

A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual diseases such as Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent …

Functional And Quality-Of-Life Outcomes In Geriatric Patients With Type-Ii Dens Fracture., Alexander R Vaccaro, Christopher K Kepler, Branko Kopjar, Jens Chapman, Christopher Shaffrey, Paul Arnold, Ziya Gokaslan, Darrel Brodke, John France, Mark Dekutoski, Rick Sasso, S Tim Yoon, Christopher Bono, James Harrop, Michael G Fehlings

Rothman Institute Papers

BACKGROUND: Dens fractures are relatively common in the elderly. The treatment of Type-II dens fractures remains controversial. The aim of this multicenter prospective cohort study was to compare outcomes (assessed with use of validated clinical measures) and complications of nonsurgical and surgical treatment of Type-II dens fractures in patients sixty-five years of age or older.

METHODS: One hundred and fifty-nine patients with a Type-II dens fracture were enrolled in a multicenter prospective study. Subjects were treated either surgically (n = 101) or nonsurgically (n = 58) as determined by the treatment preferences of the treating physicians and the patients. The …

Voices Raised, Issue 40, University Of Dayton. Women's Center

Women’s Center Newsletter

Included in this issue: Merit and Modesty: The Miryam Award; Sleep; Remembering Friendship; Women and Equal Pay Day; Dedication to a Department and a Community; Inspiring Women in Unexpected Places; What Can You Do With a WGS Major or Minor?; Creative Chameleon: The Lovely Lauren; Tradition vs. Truth: Rediscovered Destiny; (Un)equal pay for women; The Changing Roles of American Women .

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Cultural Diversity And Views On Alzheimer Disease In Older African Americans., Barry W. Rovner, Robin J. Casten, Lynn F. Harris

Department of Psychiatry and Human Behavior Faculty Papers

Cultural constructs prevalent in older African Americans may influence their risk perceptions and knowledge of Alzheimer disease (AD). To examine this issue, we administered 3 sociocultural scales, the AD Knowledge Scale, and a Risk Perception questionnaire to 271 older African Americans who were recruited from a large community senior center and local churches. Higher Present Time Orientation was significantly related to perceptions of having little control over risks to health (P=0.004), God's Will in determining AD (P=0.001), and lower AD knowledge (P

Nutrition Intervention To Decrease Symptoms In Patients With Advanced Heart Failure, Terry A. Lennie, Debra K. Moser, Martha J. Biddle, Darlene Welsh, Geza G. Bruckner, D. Travis Thomas, Mary Kay Rayens, Alison L. Bailey

Nursing Faculty Publications

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, …

Derivation Of Multivariate Syndromic Outcome Metrics For Consistent Testing Across Multiple Models Of Cervical Spinal Cord Injury In Rats, Adam R. Ferguson, Karen-Amanda Irvine, John C. Gensel, Jessica L. Nielson, Amity Lin, Johnathan Ly, Mark R. Segal, Rajiv R. Ratan, Jacqueline C. Bresnahan, Michael S. Beattie

Physiology Faculty Publications

Spinal cord injury (SCI) and other neurological disorders involve complex biological and functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental models represents a significant challenge for translating findings across research projects and presents a substantial hurdle for translation of novel therapies to humans. In the present work we demonstrate a novel 'syndromic' information-processing approach for capitalizing on heterogeneous data from diverse preclinical models of SCI to discover translational outcomes for therapeutic testing. We first built a large, detailed repository of preclinical outcome data from 10 years of basic …

Using Online Adverts To Increase The Uptake Of Cervical Screening Amongst "Real Eastenders": An Opportunistic Controlled Trial., Ray B. Jones, Mar Soler-Lopez, Daniel Zahra, Judith Shankleman, Esther Trenchard-Mabere

School of Nursing and Midwifery

BACKGROUND: Cervical screening uptake has increased as a result of occurrences of cervical cancer in TV 'soap operas' and in real life celebrities such as Jade Goody. Media analysis at the time of Jade Goody's death suggested the NHS did not take sufficient advantage of this opportunity to improve cervical screening rates. Google AdWords has been used to recruit and raise awareness of health but we were not aware of its use to supplement media events. METHODS: This was an opportunistic service evaluation to accompany a cervical cancer storyline in Eastenders (a TV 'soap opera'). We ran an AdWords campaign …

Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou

Toxicology and Cancer Biology Faculty Publications

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing …