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Pathobiome Driven Gut Inflammation In Pakistani Children With Environmental Enteric Dysfunction, Najeeha Talat Iqbal, Sana Syed, Furqan Kabir, Zehra Jamil, Tauseef Akhund, Shahida Qureshi, Jie Liu, Jennie Ma Z, Shan Guleria, Andrew Gewirtz, Christopher Duggan P, Molly Hughes A, Kamran Sadiq, Asad Ali

Department of Paediatrics and Child Health

Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children <5 years of age in low- and middle-income countries. Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p<0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter [β (SE) 7751.2 (2608.5), p = 0.003] and ETEC LT [β (SE) 7089.2 (3015.04), p = 0.019] was associated with increase in MPO. Giardia was associated with increase in Reg1b [β (SE) 72.189 (26.394), p = 0.006] and antiflic IgA[β (SE) 0.054 (0.021), p = 0.0091]. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stunting

Anti-Pd-1 Monoclonal Antibody Medi0680 In A Phase I Study Of Patients With Advanced Solid Malignancies., Aung Naing, Jeffrey Infante, Sanjay Goel, Howard Burris, Chelsea Black, Shannon Marshall, Ikbel Achour, Susannah Barbee, Rena May, Chris Morehouse, Kristen Pollizzi, Xuyang Song, Keith Steele, Nairouz Elgeioushi, Farzana Walcott, Joyson Karakunnel, Patricia Lorusso, Amy Weise, Joseph Eder, Brendan Curti, Michael Oberst

Articles, Abstracts, and Reports

BACKGROUND: The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies.

METHODS: MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics.

RESULTS: Fifty-eight patients were treated. Median age was 62.5 …

Mice Exposed To Combined Chronic Low-Dose Irradiation And Modeled Microgravity Develop Long-Term Neurological Sequelae, Amber M. Paul, Eliah G. Overbey, William A. Da Silveira, Candice G.T. Tahimic, Sigrid S. Reinsch, Nathaniel Szewczyk, Seta Stanbouly, Charles Wang, Jonathan M. Galazka, Xiao Wen Mao

Publications

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single …

Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan

LSU Doctoral Dissertations

Breast cancer is the most diagnosed cancer in women under 60 and the second most diagnosed cancer in women over 60. While treatments for localized breast cancer are quite successful with high survival rates at 99%, advanced breast cancer remains hard to treat with a nearly 75% decrease in survival. Current treatments are inefficient at treating advanced stages of breast cancer, and thus, new therapies are sorely needed to address the complexity of advanced stage breast cancer. The ideal therapy would be capable of systemic administration, targets cancer cells and spares normal tissue. Oncolytic adenovirus is an ideal therapeutic vector …

Predicting Premature Birth Risk With Cfrna, Jason Lin, Jonathan Marin, John Santerre

SMU Data Science Review

Identifying which genes are early indicators for preterm births using cell-free ribonucleic acid (cfRNA) from non-invasive blood tests provided by pregnant women can improve prenatal care. Currently, there are no medical tests for early detection of preterm birth risk in routine checkups for pregnant women. Recent studies have shown potential genes that can predict preterm birth. Machine learning techniques are utilized to see if the Area Under the Curve (AUC) can be improved upon when evaluating the prediction accuracy for chosen genes sequences and concentrations. Using cell-free RNA data from non-invasive blood tests in conjunction with machine learning, we improve …

Efficacy And Safety Of Intravenous Golimumab Plus Methotrexate In Patients With Rheumatoid Arthritis Aged < 65 Years And Those ≥ 65 Years Of Age., John Tesser, Shelly Kafka, Raphael J. Dehoratius, Stephen Xu, Elizabeth C Hsia, Anthony Turkiewicz

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged < 65 years and those ≥ 65 years who were enrolled in the GO-FURTHER study.

METHODS: In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, patients with active RA were randomized to intravenous (IV) golimumab 2 mg/kg + MTX or placebo + MTX at weeks 0 and 4, then every 8 weeks thereafter (with crossover to golimumab at week 16 [early escape] or week 24 [per-protocol]). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology (ACR) 20/50/70 response criteria. Efficacy and adverse events (AEs) were monitored through 2 years. …

Editorial: Cancer Ecosystems., Ubaldo E. Martinez-Outshoorn, Mireia Bartrons, Ramon Bartrons

Department of Medical Oncology Faculty Papers

No abstract provided.

First-In-Human Study Of Tk-Positive Oncolytic Vaccinia Virus Delivered By Adipose Stromal Vascular Fraction Cells., Boris R Minev, Elliot Lander, John F Feller, Mark Berman, Bernadette M Greenwood, Ivelina Minev, Antonio F Santidrian, Duong Nguyen, Dobrin Draganov, Mehmet O Killinc, Anna Vyalkova, Santosh Kesari, Edward Mcclay, Gabriel Carabulea, Francesco M Marincola, Lisa H Butterfield, Aladar A Szalay

Articles, Abstracts, and Reports

BACKGROUND: ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).

METHODS: Twenty-four patients with solid tumors and two patients with AML participated in this open-label, non-randomized dose-escalation trial. All patients were treated with SVF derived from autologous fat and incubated for …

Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo

School of Medicine Faculty Publications

The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Burden Of Disease In Pediatric Patients With Hypophosphatasia: Results From The Hpp Impact Patient Survey And The Hpp Outcomes Study Telephone Interview., Eric T. Rush, Scott Moseley, Anna Petryk

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hypophosphatasia (HPP) is a rare, inherited, metabolic bone disease caused by deficient tissue-non-specific isoenzyme of alkaline phosphatase activity that manifests as a broad range of signs/symptoms, including bone mineralization defects and systemic complications. The burden of disease is poorly characterized, particularly in children. This study aimed to characterize the patient-reported burden of disease among children with HPP using two survey instruments: the HPP Impact Patient Survey (HIPS) and the HPP Outcomes Study Telephone interview (HOST).

METHODS: Between September 2009 and June 2011, pediatric patients (aged younger than 18 years) with HPP were recruited to participate in the study via …

Response Of Human Small Intestinal Epithelium To Fractionated Irradiation: Dynamical Modeling Approach, Francis A. Cucinotta, Olga A. Smirnova

Health Physics and Diagnostic Sciences Faculty Research

A biologically motivated mathematical model of the dynamics of the small intestinal epithelium in humans treated with fractionated radiotherapy has been developed and is further investigated here. This model, originating from our previous work, is implemented as a system of nonlinear ordinary differential equations, in which the variables and parameters have a clear biological meaning. The model also includes, as input, the key parameters of fractionated irradiation. The modeling results on the dynamical response of the human normal small intestinal epithelium to fractionated radiation therapy regimens were in agreement with the corresponding empirical data, which, in turn, demonstrates the capability …

Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of …

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …

Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer

Department of Orthopaedic Surgery Faculty Papers

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such …

Infertility In Muslim Refugees: A Review Of The Literature, Simone N. Reaves, Fern R. Hauck

Journal of Refugee & Global Health

Many couples worldwide are affected by infertility, which is defined as an inability to conceive after at least one year of regular unprotected sexual intercourse. Many Muslim and Middle Eastern societies place a high societal value on having children and therefore, couples who are unable to conceive for various reasons often find themselves feeling stigmatized and socially isolated. Muslim refugees living in the United States face additional challenges and barriers to care due to their refugee status. This review is a synthesis of existing literature that 1) identifies Islamic viewpoints on infertility and assistive reproductive technology (ART), 2) explores the …

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …

Rig-I-Like Receptors Direct Inflammatory Macrophage Polarization Against West Nile Virus Infection., Amy E. L. Stone, Richard Green, Courtney Wilkins, Emily A. Hemann, Michael Gale Jr.

College of Osteopathic Medicine (TUN) Publications and Research

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 …

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

Advances In Management Of Neuropsychiatric Syndromes In Neurodegenerative Diseases, Jeffrey Cummings, Aaron Ritter, Kasia Rothenberg

School of Medicine Faculty Research

Purpose of Review Neuropsychiatric syndromes (NPS) are common in neurodegenerative disorders (NDD). This review describes the role of NPS in the diagnosis of NDD, criteria for the diagnosis of NPS, management of NPS, and agents in clinical trials for NPS. Recent Findings NPS play an increasingly important role in the diagnosis of NDD. Consensus diagnostic criteria have evolved for psychosis, depression, agitation, and apathy in NDD. With one exception—pimavanserin is approved for the treatment of hallucinations and delusions in Parkinson’s disease—there are no drugs approved by the FDA for treatment of NPS in NDD. Trials show that atypical antipsychotics reduce …

Non-Thermal Plasma-Induced Immunogenic Cell Death In Cancer: A Topical Review., Marian Khalili, Lynsey Daniels, Abraham Lin, Fred C. Krebs, Adam E. Snook, Sander Bekeschus, Wilbur B. Bowne, Vandana Miller

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational …

Electromechanical Dyssynchrony And Clinically Silent Ventricular Dysfunction In Young Subjects With Ventricular Pacing For Congenital And Early Acquired Av Block, Daniel Forsha, David G. Gamboa, Niels Risum, Andrea Kropf, Christoph P. Hornik, Piers Barker, Joseph Kisslo, Ronald J. Kanter

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Single site ventricular pacing can result in electromechanical dyssynchrony and LV dysfunction. A classic pattern by strain echocardiography pattern analysis has been defined that specifically identifies electromechanical dyssynchrony that leads to LV dysfunction in other populations. Our purpose is to evaluate for the presence of the classic pattern and an association with LV dysfunction in asymptomatic young subjects with chronic pacing.

Methods: Inclusion criteria of non-surgical 2nd or 3rd degree AV block, normal cardiac anatomy, chronic ventricular pacing (> 95% of beats) and a quality 4-chamber apical image were met by 24 retrospective and 10 prospectively enrolled subjects. Global …

Helicobacter Pylori Pathophysiology, Alisha Smith

Nursing Student Class Projects (Formerly MSN)

Abstract

This poster provides current research evidence on Helicobacter Pylori pathophysiology, treatment guidelines, and the potential etiology of associated disorders. The purpose is to provide a detailed overview of the functional changes within the intestinal cells caused by the microorganism. Furthermore, explaining of the mechanism and clinical manifestations of symptoms. The research focuses on risk factors, transmission, diagnostic evaluation, and the implications for nursing care. The best-available evidence offers concrete data examining the detrimental effects of the immune and inflammatory response stimulated by H. pylori. A description of the functional structures of H. pylori and its’ ability to survive. …

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting …

Leaving Against Medical Advice From In-Patients Departments Rate, Reasons And Predicting Risk Factors For Re-Visiting Hospital Retrospective Cohort From A Tertiary Care Hospital, Obada Hasan, Muhammad Adil Samad, Hamza Khan, Maryam Sarfraz, Shahryar Noordin, Tashfeen Ahmad, Gul Nowshad

Section of Orthopaedic Surgery

Background: Approximately 1% to 2% of hospitalized patients get discharged or leave from the hospital against medical advice and up to 26% in some centers. They have higher readmission rate and risk of complications than patients who receive complete care. In this study we aimed to determine the rate of leave against medical advice (LAMA) and reasons for the same across different in-patient departments of a tertiary care hospital.
Methods: Retrospective cohort study on patients admitted in all departments at our institute over a 1-year period. All patients who were admitted to an in-patient ward at the hospital and who …

A Phenomenological Investigation Of Women’S Infertility And Miscarriage Grief Experiences, Tristan Mcbain

Dissertations

Infertility and miscarriage are reproductive losses that often produce grief reactions in affected women. This phenomenological study investigated the grief experiences of infertility and miscarriage through the ambiguous loss and disenfranchised grief frameworks in order to better understand both the obscurity of reproductive loss and how the resulting grief may be invalidated.

Sixteen women volunteered to participate in this study and each fell into one of the following three categories: women affected by infertility without miscarriage (4); women affected by miscarriage without infertility (4); and women affected by infertility and miscarriage (8). A phenomenological hermeneutic approach was utilized to uncover …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Appropriate Therapeutic Drug Monitoring Of Biologic Agents For Patients With Inflammatory Bowel Diseases., Konstantinos Papamichael, Adam S. Cheifetz, Gil Y. Melmed, Peter M. Irving, Niels Vande Casteele, Patricia L. Kozuch, Laura E. Raffals, Leonard Baidoo, Brian Bressler, Shane M. Devlin, Jennifer Jones, Gilaad G. Kaplan, Miles P. Sparrow, Fernando S Velayos, Thomas Ullman, Corey A. Siegel

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD.

METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) …

Characterizing The Role Of Extracellular Matrix In Non-Small Cell Lung Carcinoma Metastasis Using A 3d Microenvironment Mimetic In-Vitro Culture System., Douglas John Owulaku Saforo

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer related death in the United States and worldwide. Five-year survival rates for non-small cell lung carcinoma patients have not improved in decades, and a majority of patients succumb to metastasis. Identification of therapeutic targets for metastatic disease is essential for the development of novel therapies. However, current 2-dimensional (2D) in vitro models are not reflective of the tumor microenvironment (TME) and are inadequate in identifying therapeutic targets. We adapted a 3-dimensional (3D) extracellular matrix (ECM) in vitro model to a hypoxic incubator to approximate physiological hypoxia of the TME in a microenvironment …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …