Medicine and Health Sciences Commons^™

Contraceptive Provision To Adolescent Females Prescribed Teratogenic Medications., Stephani L. Stancil, Melissa K. Miller, Holley Briggs, Daryl Lynch, Kathy Goggin, Gregory Kearns

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population.

METHODS: A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic …

Whole-Genome Sequencing And Disability In The Nicu: Exploring Practical And Ethical Challenges., Michael J. Deem

Manuscripts, Articles, Book Chapters and Other Papers

Clinical whole-genome sequencing (WGS) promises to deliver faster diagnoses and lead to better management of care in the NICU. However,several disability rights advocates have expressed concern that clinical use of genetic technologies may reinforce and perpetuate stigmatization of and discrimination against disabled persons in medical and social contexts. There is growing need, then, for clinicians and bioethicists to consider how the clinical use of WGS in the newborn period might exacerbate such harms to persons with disabilities. This article explores ways to extend these concerns to clinical WGS in neonatal care. By considering these perspectives during the early phases of …

Interrelationships In The Variability Of Root Canal Anatomy Among The Permanent Teeth: A Full-Mouth Approach By Cone-Beam Ct., Paul Monsarrat, Bertrand Arcaute, Ove A. Peters, Elisabeth Maury, Norbert Telmon, Marie Georgelin-Gurgel, Delphine Maret

All Dugoni School of Dentistry Faculty Articles

OBJECTIVES: In endodontic practice, clinicians should be aware of possible root canal anatomic variations. The aim of this study was to assess using CBCT acquisitions regarding whether one root canal anatomy of a tooth is associated with a specific anatomy of another tooth.

METHODS: A total of 106 CBCT acquisitions were obtained using a CBCT scanner with 200μm voxel size. Numbers of roots and canals of the entire dentition were described. Bivariate analyses and logistic regressions were conducted to explore root canal anatomy on one tooth according to age, gender, jaw, side and the others teeth. Multiple correspondence analysis (MCA) …

Placental Epigenetics In Children’S Environmental Health, Carmen Marsit

Dartmouth Scholarship

There is a growing interest in understanding the mechanisms that drive the developmental origins of health and disease, and the role of epigenetic regulation has risen to the forefront of these studies. In particular, the placenta may be a model organ to consider as a mediator of the impact of the environment on developmental programming of children's health, as this organ plays a critical role in directing development and regulating the fetal environment. Several recent studies have begun to examine how environmental toxicant exposures can impact the placental epigenome, focusing on studies of DNA methylation and microRNA expression. This review …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Identification And Use Of Frailty Indicators From Text To Examine Associations With Clinical Outcomes Among Patients With Heart Failure., Yijun Shao, April F Mohanty, Ali Ahmed, Charlene R Weir, Bruce E Bray, Rashmee U Shah, Douglas Redd, Qing Zeng-Treitler

Clinical Research and Leadership Faculty Publications

Frailty is an important health outcomes indicator and valuable for guiding healthcare decisions in older adults, but is rarely collected in a quantitative, systematic fashion in routine healthcare. Using a cohort of 12,000 Veterans with heart failure, we investigated the feasibility of topic modeling to identify frailty topics in clinical notes. Topics were generated through unsupervised learning and then manually reviewed by an expert. A total of 53 frailty topics were identified from 100,000 notes. We further examined associations of frailty with age-, sex-, and Charlson Comorbidity Index-adjusted 1-year hospitalizations and mortality (composite outcome) using logistic regression. Frailty (≤ 4 …

Hematologic Outcomes After Total Splenectomy And Partial Splenectomy For Congenital Hemolytic Anemia., Brian R Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M Heeney, C Jason Smithers, Rebeccah L Brown, Theodosia Kalfa, Jacob C Langer, Michaela Cada, Keith T Oldham, J Paul Scott, Mukta Sharma, Andrew M Davidoff, Kerri Nottage, Kathryn Bernabe, David B Wilson, Sanjeev Dutta, Bertil Glader, Shelley E Crary, Melvin S Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Henry E Rice, Splenectomy In Congenital Hemolytic Anemia Consortium, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD).

Methods: The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy.

Results: The analysis included 130 children, with 62.3% (n=81) undergoing TS. For children with HS, all …

Introduction To Bioethics Special Supplement V: Ethical Issues In Genomic Testing Of Children., John D. Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Next-generation genome sequencing of children is one of the most promising and most challenging new technologies in pediatrics. On the one hand, it offers the hope that we will be able to diagnose rare conditions that were previously impossible to diagnose, which, in turn, might lead to new treatments. On the other hand, the technology for sequencing presents daunting problems of interpretation. It is problematic to conduct the research necessary to characterize the pathogenicity of those variants at the same time that we are using them to guide the clinical care of children who have complex medical problems. It is …

The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies. Whole-exome or whole-genome sequencing allows diagnoses in many patients who have complex phenotypes and unusual clinical presentations. As genomic and exomic testing expands in both the research and clinical settings, pediatricians will need to understand the technology of next-generation sequencing and the complexity of interpreting genomic variants relevant to patient phenotypic features. This article briefly explains the technology by which genomes are sequenced and discusses some of the complexity related to interpreting genomic variants. We conclude with some thoughts on the clinical applications of such testing.

Slug Bug: Quality Improvement With Orchestrated Testing Leads To Nicu Clabsi Reduction., Anthony J. Piazza, Beverly Brozanski, Lloyd Provost, Theresa R. Grover, John Chuo, Joan R. Smith, Teresa Mingrone, Susan Moran, Lorna Morelli, Isabella Zaniletti, Eugenia K. Pallotto

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices.

METHODS: Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 …

Can Office Blood Pressure Readings Predict Masked Hypertension?, Mark M. Mitsnefes, Chris Pierce, Joseph Flynn, Joshua Samuels, Janis Dionne, Susan Furth, Bradley A. Warady, Ckid Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP).

METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles …

Please Do Whatever It Takes To End Our Daughter's Suffering!, Stéphan Clément De Cléty, Marie Friedel, A A Eduard Verhagen, John D. Lantos, Brian S. Carter

Manuscripts, Articles, Book Chapters and Other Papers

What is the best way to care for a child with severe neurologic impairment who seems to be dying and is in intractable pain? Can we give sedation as we remove life support? Is it ethically permissible to hasten death? In the United States, 5 states have legalized assisted suicide (although only for competent adults). In Belgium and the Netherlands, euthanasia is legal for children under some circumstances. We present a case in which parents and doctors face difficult decisions about palliative care. Experts from Belgium, the Netherlands, and the United States then discuss how they would respond to such …

Early Adverse Experiences And Health: The Transition To College, Kelly B. Filipkowski, Kristin E. Heron, Joshua M. Smyth

Psychology Faculty Publications

Objective: This study cross-sectionally and prospectively examined the impact of adversity experienced prior to college on the health and well-being of students adjusting to their first college semester. Methods: Two-hundred sixteen (216) first-year students completed measures of adverse life experiences, perceived stress, physical symptoms, and health-related behaviors during the first 2 weeks of college entry and again at the end of the first semester. Results: Reported adversity prior to college predicted greater perceived stress and physical symptoms at college entry and an increase in physical symptoms over the semester; perceived stress mediated the prospective changes. Early adversity …

Nutritional Status And Tuberculosis Risk In Adult And Pediatric Household Contacts, Omowunmi Aibana, Xeno Acharya, Chuan-Chin Huang, Mercedes C Becerra, Jerome T Galea, Silvia S Chiang, Carmen Contreras, Roger Calderon, Rosa Yataco, Gustavo E Velásquez, Karen Tintaya, Judith Jimenez, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children.

METHODS AND FINDINGS: We conducted a prospective cohort study among household contacts of pulmonary TB cases in Lima, Peru. We determined body mass index at baseline and followed participants for one year for TB infection and disease. We used …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Identification Of A Novel Gene On 10q221 Causing Autosomal Dominant Retinitis Pigmentosa (Adrp), Stephen P Daiger, Lori S Sullivan, Sara J Bowne, Daniel C Koboldt, Susan H Blanton, Dianna K Wheaton, Cheryl E Avery, Elizabeth D Cadena, Robert K Koenekoop, Robert S Fulton, Richard K Wilson, George M Weinstock, Richard A Lewis, David G Birch

Faculty, Staff and Students Publications

Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.0 at 0 % recombination in a six-generation family with autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked RP genes were excluded in the family by a combination of methods. Whole-exome next-generation sequencing revealed a missense mutation in hexokinase 1, HK1 c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members. One severely-affected male is homozygous for this region by linkage analysis and has two copies of the mutation. No other potential mutations were detected in the linkage region nor were …

Tissue Restricted Splice Junctions Originate Not Only From Tissue-Specific Gene Loci, But Gene Loci With A Broad Pattern Of Expression, Matthew S. Hestand, Zheng Zeng, Stephen J. Coleman, Jinze Liu, James N. Macleod

Maxwell H. Gluck Equine Research Center Faculty Publications

Cellular mechanisms that achieve protein diversity in eukaryotes are multifaceted, including transcriptional components such as RNA splicing. Through alternative splicing, a single protein-coding gene can generate multiple mRNA transcripts and protein isoforms, some of which are tissue-specific. We have conducted qualitative and quantitative analyses of the Bodymap 2.0 messenger RNA-sequencing data from 16 human tissue samples and identified 209,363 splice junctions. Of these, 22,231 (10.6%) were not previously annotated and 21,650 (10.3%) were expressed in a tissue-restricted pattern. Tissue-restricted alternative splicing was found to be widespread, with approximately 65% of expressed multi-exon genes containing at least one tissue-specific splice junction. …

Atp-Site Binding Inhibitor Effectively Targets Mtorc1 And Mtorc2 Complexes In Glioblastoma, Jayson Neil, Craig Shannon, Avinash Mohan, Dimitri Laurent, Raj Murali, Meena Jhanwar-Uniyal

NYMC Faculty Publications

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding …

Framework For Hyperspectral Image Processing And Quantification For Cancer Detection During Animal Tumor Surgery, Guolan Lu, Dongsheng Wang, Xulei Qin, Luma Halig, Susan Muller, Hongzheng Zhang, Amy Chen, Brian W. Pogue, Zhuo G. Chen

Dartmouth Scholarship

Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, …

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

The Happy Older Latinos Are Active (Hola) Health Promotion And Prevention Study: Study Protocol For A Pilot Randomized Controlled Trial, Daniel E. Jimenez, Charles F. Reynolds, Margarita Alegría, Philip Harvey, Stephen Bartels

Dartmouth Scholarship

Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at-risk Latinos.

Methods/Design: HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). …

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L C Luban, Joseph M Devaney, Anthony D Sandler

Genomics and Precision Medicine Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Leveraging Global Gene Expression Patterns To Predict Expression Of Unmeasured Genes, James Rudd, René A. Zelaya, Eugene Demidenko, Ellen L. Goode, Casey S. Greene S. Greene, Jennifer A. Doherty

Dartmouth Scholarship

BackgroundLarge collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes.

The Visual Priming Of Motion-Defined 3d Objects, Xiong Jiang, Yang Jiang, Raja Parasuraman

Behavioral Science Faculty Publications

The perception of a stimulus can be influenced by previous perceptual experience, a phenomenon known as perceptual priming. However, there has been limited investigation on perceptual priming of shape perception of three-dimensional object structures defined by moving dots. Here we examined the perceptual priming of a 3D object shape defined purely by motion-in-depth cues (i.e., Shape-From-Motion, SFM) using a classic prime-target paradigm. The results from the first two experiments revealed a significant increase in accuracy when a "cloudy" SFM stimulus (whose object structure was difficult to recognize due to the presence of strong noise) was preceded by an unambiguous SFM …

Isosorbide Mononitrate In Heart Failure With Preserved Ejection Fraction., Margaret M. Redfield, Kevin J. Anstrom, James A. Levine, Gabe A. Koepp, Barry A. Borlaug, Horng H. Chen, Martin M. Lewinter, Susan M. Joseph, Sanjiv J. Shah, Marc J. Semigran, G. Michael Felker, Robert T. Cole, Gordon R. Reeves, Ryan J. Tedford, W.H. Wilson Tang, Steven E. Mcnulty, Eric J. Velazquez, Monica R Shah, Eugene Braunwald

Division of Cardiology Faculty Papers

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.

METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer …

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

‘Much Clearer With Pictures’: Using Community-Based Participatory Research To Design And Test A Picture Option Grid For Underserved Patients With Breast Cancer, Marie-Anne Durand, Shama Alam, Stuart W. Grande, Glyn Elwyn

Dartmouth Scholarship

Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer.

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …