Digital Commons Network^™

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …

Modelling The Impact Of Improving Screening And Treatment Of Chronic Hepatitis C Virus Infection On Future Hepatocellular Carcinoma Rates And Liver-Related Mortality., Matthew E. Cramp, William M. Rosenberg, Steven D. Ryder, Sarah Blach, Julie Parkes

Peninsula Medical School

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated …

Clinical And Biochemical Function Of Polymorphic Nr0b1 Ggaa-Microsatellites In Ewing Sarcoma: A Report From The Children's Oncology Group., Michael J. Monument, Kirsten M. Johnson, Elizabeth Mcilvaine, Lisa Abegglen, W. Scott Watkins, Lynn B. Jorde, Richard B. Womer, Natalie Beeler, Laura Monovich, Elizabeth R. Lawlor, Julia A. Bridge, Joshua D. Schiffman, Mark D Krailo, R. Lor Randall, Stephen L. Lessnick

Journal Articles: Pathology and Microbiology

BACKGROUND: The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite.

OBJECTIVES: Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes.

RESULTS: A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed …

Diagnosis-Specific Readmission Risk Prediction Using Electronic Health Data: A Retrospective Cohort Study, Courtney Hebert, Chaitanya Shivade, Randi Foraker, Jared Wasserman, Caryn Roth, Hagop Mekhjan, Stanley Lemeshow, Peter Embi

Dartmouth Scholarship

Background: Readmissions after hospital discharge are a common occurrence and are costly for both hospitals and patients. Previous attempts to create universal risk prediction models for readmission have not met with success. In this study we leveraged a comprehensive electronic health record to create readmission-risk models that were institution- and patient- specific in an attempt to improve our ability to predict readmission. Methods: This is a retrospective cohort study performed at a large midwestern tertiary care medical center. All patients with a primary discharge diagnosis of congestive heart failure, acute myocardial infarction or pneumonia over a two-year time period were …

Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (Hmsc) Express Sialyl Lewis X And Actively Adhere To Arterial Endothelium In A Chick Embryo Model System, Harris E. Mcferrin, Scott D. Olson, Miriam V. Gutschow, Julie A. Semon, Deborah E. Sullivan, Darwin J. Prockop

Biological Sciences Faculty Research & Creative Works

Background: There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing.

Methods: Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In Vivo experiments were performed to determine …

Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis

College of Science & Mathematics Departmental Research

OBJECTIVES: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group.

PARTICIPANTS: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation.

OUTCOME MEASURES: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods. Self-reported negative affect was also assessed before and after …

Pulmonary Ventilation Defects In Older Never-Smokers, Khadija Sheikh, Gregory A Paulin, Sarah Svenningsen, Miranda Kirby, Nigel A M Paterson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Hyperpolarized (3)He MRI previously revealed spatially persistent ventilation defects in healthy, older compared with healthy, younger never-smokers. To understand better the physiological consequences and potential relevance of (3)He MRI ventilation defects, we evaluated (3)He-MRI ventilation-defect percent (VDP) and the effect of deep inspiration (DI) and salbutamol on VDP in older never-smokers. To identify the potential determinants of ventilation defects in these subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise test (CPET) measurements, as well as occupational and second-hand smoke exposure. Fifty-two never-smokers (71 ± 6 yr) with no history of chronic respiratory disease were evaluated. During a single visit, …

Rules And Values: A Coordinated Regulatory And Educational Approach To The Public Health Crises Of Chronic Pain And Addiction, Joanna G. Katzman, George D. Comerci, Michael Landen, Larry Loring, Steven M. Jenkusky, Sanjeev Arora, Summers Kalishman, Lisa Marr, Chris Camarata, Daniel Duhigg, Jennifer Dillow, Eugene Koshkin, Denise E. Taylor, Cynthia M A Geppert

Project ECHO Bibliography

Chronic pain and opioid addiction are 2 pressing public health problems, and prescribing clinicians often lack the skills necessary to manage these conditions. Our study sought to address the benefits of a coalition of an academic medical center pain faculty and government agencies in addressing the high unintentional overdose death rates in New Mexico. New Mexico's 2012-2013 mandated chronic pain and addiction education programs studied more than 1000 clinicians. Positive changes were noted in precourse and postcourse surveys of knowledge, self-efficacy, and attitudes. Controlled substance dispensing data from the New Mexico Board of Pharmacy also demonstrated safer prescribing. The total …

Eccentric Muscle Challenge Shows Osteopontin Polymorphism Modulation Of Muscle Damage., Whitney L. Barfield, Kitipong Uaesoontrachoon, Chung-Sheih Wu, Stephen Lin, Yue Chen, Paul C. Wang, Yasmine Kanaan, Vernon Bond, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitroreporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric …

Breach Of Tolerance: Primary Biliary Cirrhosis., Lifeng Wang, Fu-Sheng Wang, Christopher Chang, M Eric Gershwin

Department of Medical Genetics Faculty Papers

In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play …

Obesity And Mortality: Are The Risks Declining? Evidence From Multiple Prospective Studies In The United States., Tapan S. Mehta, Kevin R. Fontaine, Scott W. Keith, Sripal S. Bangalore, Gustavo De Los Campos, Alfred Bartolucci, Nicholas M. Pajewski, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

We evaluated whether the obesity-associated years of life lost (YLL) have decreased over calendar time. We implemented a meta-analysis including only studies with two or more serial body mass index (BMI) assessments at different calendar years. For each BMI category (normal weight: BMI 18.5 to <25 >[reference]; overweight: BMI 25 to60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and increased by 0.63 years for grade 2-3 obesity (P = 0.63). Among women aged ≤60, YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P < 0.001) for grade 2-3 obesity. In women aged >60, YLL for grade 1 obesity decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2-3 obesity. Grade 1 obesity's association with decreased longevity has reduced for older Caucasian men. For Caucasian women, there is evidence of a decline in the obesity YLL association across all ages.

Cardioprotection By Controlling Hyperamylinemia In A "Humanized" Diabetic Rat Model, Sanda Despa, Savita Sharma, Todd R. Harris, Hua Dong, Ning Li, Nipavan Chiamvimonvat, Heinrich Taegtmeyer, Kenneth B. Margulies, Bruce D. Hammock, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart.

METHODS AND RESULTS: By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP …

Reduction In Overall Occurrences Of Ischemic Events With Vorapaxar: Results From Tracer, Harvey D. White, Zhen Huang, Pierluigi Tricoci, Frans Van De Werf, Lars Wallentin, Yuliya Lokhnygina, David J. Moliterno, Philip E. Aylward, Kenneth W. Mahaffey, Paul W. Armstrong

Internal Medicine Faculty Publications

BACKGROUND: Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.

METHODS AND RESULTS: TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar …

Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy. Our objective was to determine any associations between risk factors for sleep-related deaths at different ages.

METHODS: A cross-sectional study of sleep-related infant deaths from 24 states during 2004-2012 contained in the National Center for the Review and Prevention of Child Deaths Case Reporting System, a database of death reports from state child death review teams. The main exposure was age, divided into younger (0-3 months) and older …

Neurotrophic Factor Gdnf Promotes Survival Of Salivary Stem Cells, Nan (Tori) Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le

All Dugoni School of Dentistry Faculty Articles

Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland …

Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu

Markey Cancer Center Faculty Publications

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC …

Intravitreal Triamcinolone Acetonide Injection For Macular Edema Due To Central Retinal Vein Occlusion Persisting Despite Multiple Intravitreal Bevacizumab Injections., Rayan A Alshareef, Sunir Garg, Jason Hsu, James Vander, Carl Park, Marc J Spirn

Wills Eye Hospital Papers

PURPOSE: To evaluate the response to intravitreal triamcinolone acetonide for macular edema persisting or recurring despite multiple intravitreal bevacizumab (IVB) treatments for central retinal vein occlusion (CRVO).

METHODS: Retrospective interventional case series of 21 eyes with CRVO from 21 patients who were diagnosed with persistent or recurrent macular edema secondary to CRVO and treated with 0.1mL (4mg) intravitreal triamcinolone acetonide (IVTA) after initial treatment with 3 or more IVB injections. Anatomic and visual responses were the study primary outcomes.

RESULTS: Mean logarithm of the minimum angle of resolution visual acuity was 1.19 (20/316) immediately before IVTA injection, and improved to …

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

The In-Hospital Consultation Today: Whom Does It Best Serve?, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Use Of Oversized Injectable Valves In Growing Children For Total Repair Of Right Ventricular Outflow Tract Anomalies (Preliminary Results), Luca Deorsola, Pietro Angelo Abbruzzese

The Texas Heart Institute Journal

Right ventricular outflow tract surgery was originally confined to transannular patching, in the belief that pulmonary regurgitation was well tolerated. Because follow-up evaluations revealed the deleterious effects of pulmonary regurgitation, surgery today aims to spare or replace the valve. Available replacement devices have short lifetimes, considering growth mismatch in children. We hypothesize that oversizing the right infundibulum anticipates growth and that a squeezed prosthesis can complete the expansion process.

The No-React® Injectable BioPulmonic Valve is designed for right infundibular surgery in adults, and hundreds of implants have shown promising results. We used this device for surgery in babies, with the …

Abdominal Fat Suspension Device For Maintaining Normal Cardiorespiratory Function In Patients Undergoing Conscious Sedation During Surgery: A Feasibility Study, Norman F Truong, Joanna C Nathan, Daeun Yoon, Gabriel Ochoa, Marisa Prevost, Sehyun Yun, Z Maria Oden, Mehdi Razavi

The Texas Heart Institute Journal

Obese patients undergoing conscious-sedation surgery have increased perioperative morbidity because their excess abdominal tissue limits diaphragmatic excursion. We describe a simple device that might help attenuate this risk. We created a noninvasive suction device for abdominal suspension. By lifting the burden of excess weight, this device should decrease respiratory effort. To test the feasibility of excess weight removal in relieving cardiac stress, we tested 22 supine, healthy, normal-weight subjects by measuring their heart rates with and without a 13-kg tissue model on their abdomen to simulate excess weight. There was no significant difference in blood oxygen saturation before and after …

Right Ventricular Outflow Tract Obstruction Caused By Double-Chambered Right Ventricle Presenting In Adulthood, John Kokotsakis, Efthymia G Rouska, Leanne Harling, Hutan Ashrafian, Vania Anagnostakou, Christos Charitos, Thanos Athanasiou

The Texas Heart Institute Journal

Congenital heart diseases that cause obstruction of the right ventricular outflow tract are often difficult to diagnose. We report the case of a 49-year-old man who presented with long-standing shortness of breath on exertion. Imaging revealed right ventricular outflow tract obstruction caused by a double-chambered right ventricle, and he was referred for surgical correction. This case emphasizes both the detailed perioperative evaluation that is needed when diagnosing adults who present with manifestations of congenital heart disease and a method of successful surgical correction that resulted in symptom resolution.

Making A Decision About Trial Participation: The Feasibility Of Measuring Deliberation During The Informed Consent Process For Clinical Trials, Katie Gillies, Glyn Elwyn, Jonathan Cook

Dartmouth Scholarship

Background:

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of ‘informed-ness’ is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making.

Methods:

Potential trial participants who were approached regarding participation in …

Novel Role Of Pancreatic Differentiation 2 In Facilitating Self-Renewal And Drug Resistance Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Satyanarayana Rachagani, P Dey, Apar Kishor Ganti, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.

METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.

RESULTS: A …

Association Of Trauma Exposure With Proinflammatory Activity: A Transdiagnostic Meta-Analysis., M Tursich, R W J Neufeld, P A Frewen, S Harricharan, J L Kibler, S G Rhind, R A Lanius

Faculty Articles

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. …

Cell Type-Dependent Rna Recombination Frequency In The Japanese Encephalitis Virus, Wei-Wei Chiang, Chingkai Chuang, Mei Chao, Wei-June Chen

Plant Pathology Faculty Publications

Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially …

Three-Dimensional Carotid Ultrasound Plaque Texture Predicts Vascular Events, Arna Van Engelen, Thapat Wannarong, Grace Parraga, Wiro J Niessen, Aaron Fenster, J David Spence, Marleen De Bruijne

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Carotid ultrasound atherosclerosis measurements, including those of the arterial wall and plaque, provide a way to monitor patients at risk of vascular events. Our objective was to examine carotid ultrasound plaque texture measurements and the change in carotid plaque texture during 1 year in patients at risk of events and to compare these with measurements of plaque volume and other risk factors as predictors of vascular events.

METHODS: We evaluated 298 patients with carotid atherosclerosis using 3-dimensional (3D) ultrasound at baseline and after 1 year and measured carotid plaque volume and 376 measures of plaque texture. Patients …

Visual Speech Perception In Foveal And Extrafoveal Vision: Further Implications For Divisions In Hemispheric Projections, Timothy R. Jordan, Mercedes Sheen, Lily Abedipour, Kevin B. Paterson

All Works

When observing a talking face, it has often been argued that visual speech to the left and right of fixation may produce differences in performance due to divided projections to the two cerebral hemispheres. However, while it seems likely that such a division in hemispheric projections exists for areas away from fixation, the nature and existence of a functional division in visual speech perception at the foveal midline remains to be determined. We investigated this issue by presenting visual speech in matched hemiface displays to the left and right of a central fixation point, either exactly abutting the foveal midline …

Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng

CALS Publications

Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein …

Stag2 Promotes Error Correction In Mitosis By Regulating Kinetochore–Microtubule Attachments, Marianna Kleyman, Lilian Kabeche, Duane A. Compton

Dartmouth Scholarship

Mutations in the STAG2 gene are present in ∼20% of tumors from different tissues of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss-of-function mutations are usually aneuploid and display elevated frequencies of lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of chromosomal instability (CIN) arising from persistent errors in kinetochore-microtubule (kMT) attachment. To determine whether the loss of STAG2 increases the rate of formation of kMT attachment errors or decreases the rate of their correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does not impair bipolar spindle formation or delay mitotic progression. Instead, …