Digital Commons Network^™

Effect Of Different Collegiate Sports On Cortical Bone In The Tibia, L. A. Weidauer, M. M. Eilers, T. L. Binkley, M. D. Vukovich, B. L. Specker

Health and Nutritional Sciences Faculty Publications

Objectives: The purpose of this study was to determine the effect of sports participation on cortical bone in the tibia. Methods: 53 female collegiate athletes (25 cross-country, 16 soccer, and 12 volleyball) and 20 inactive controls had the left distal 20% tibia scanned by pQCT. Cortical volumetric BMD (vBMD) was measured within the cortical shell at the anterior, posterior, medial, and lateral regions and standard deviations were calculated. Results: Total vBMD was greater in the control group (1161±5 mg/mm3) than each of the sports (p<0.05). Soccer players (1147±5 mg/mm3) had greater vBMD than volleyball players (1136±7 mg/mm3) (p<0.05), but similar to cross-country runners (1145±5 mg/mm3). Cortical thickness was greatest in soccer players (4.1±0.1 mm), while cross-country and control subjects (3.8±0.1 mm) had greater thickness than volleyball players (3.4±0.1 mm)(p<0.05). Periosteal circumference was greater in volleyball players (71±1.4 mm) than soccer, cross-country, and control subjects (68±0.9, 69±0.8, and 66±1 mm, respectively; all, p<0.05). vBMD variation within the cortical shell was greater among control subjects (70±6 mg/cm3) than each of the athlete groups, with soccer players having lower variation than cross country runners (within-in person SD 36±6 mg/cm3 and 54±5 mg/cm3 respectively; p<0.05). Conclusion: These results indicate bone geometry and distribution within the cortical shell of the tibia …

Research Profile: Dr.Boriana Marintcheva And Protein Synthesis, Andrew C. Holman

Bridgewater Review

No abstract provided.

Phosphorylation Of Vasodilator-Stimulated Phosphoprotein Ser239 Suppresses Filopodia And Invadopodia In Colon Cancer., David S Zuzga, Joshua Pelta-Heller, Peng Li, Alessandro Bombonati, Scott A Waldman, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In colorectal cancer, the antitumorigenic guanylyl cyclase C (GCC) signalome is defective reflecting ligand deprivation from downregulation of endogenous hormone expression. Although the proximal intracellular mediators of that signal transduction system, including cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), are well characterized, the functional significance of its distal effectors remain vague. Dysregulation of ligand-dependent GCC signaling through vasodilator-stimulated phosphoprotein (VASP), an actin-binding protein implicated in membrane protrusion dynamics, drastically reduced cGMP-dependent VASP phosphorylation levels in colorectal tumors from patients. Restoration of cGMP-dependent VASP phosphorylation by GCC agonists suppressed the number and length of locomotory (filopodia) and invasive (invadopodia) …

Role Of The Pituitary-Adrenal Axis In G-Csf Therapy After Neonatal Hypoxia-Ischemia, Melissa Stephanie Charles

Loma Linda University Electronic Theses, Dissertations & Projects

Several reports indicate that the activity of the hypothalamic-pituitary-adrenal axis (HPA) as measured by the increased level of adrenocorticotropic hormone (ACTH), and corticosterone is increased after a brain insult. These hormones are the effectors secreted respectively by the pituitary and adrenal glands. It has been shown that the down-regulation of corticosterone levels can improve detrimental outcomes associated with ischemic brain injuries. Neonatal hypoxia-ischemia (HI) is a devastating perinatal event with a grim prognosis and limited therapeutic strategies. In recent studies, granulocyte-colony stimulating factor (G-CSF) has shown promise in neonatal HI investigations by improving neuromotor function and reducing apoptosis in the …

Mechanism Of Lmx1b-Regulated Limb Dorsalization, Jennifer Feenstra

Loma Linda University Electronic Theses, Dissertations & Projects

Lmx1b, a LIM homeodomain transcription factor is necessary for limb, kidney, eye, and central nervous system development. Lmx1b knockout (KO) mice display; abnormal limb dorsalization with distal ventral-ventral limbs, nephropathy, ocular malformations, loss of dopaminergic/serotonergic neurons, and reduced cerebellum and tectum formation. The developmental mechanisms utilized by Lmx1b remain largely unknown; to investigate downstream targets, we have used the limb as a model because of its accessibility and striking Lmx1b KO phenotype. To identify candidate genes, we compared gene arrays from Lmx1b KO and wildtype mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified …

Analysis Of Minocycline As A Radioprotectant, Shalini Mehrotra

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to radiation is increasing in a variety of settings including space exploration, diagnostic medical procedures and radiotherapy. Cells of the hematopoietic system, such as white blood cells (WBC), are especially sensitive to radiation and their decline can result in Acute Radiation Syndrome (ARS). Radiotherapy is often used for cancers of the central nervous system (CNS), but includes the risk for normal tissue damage, often leading to cognitive impairment. The literature suggests that tetracyclines can be radioprotectors of the hematopoietic system with potential utility in radiation emergencies and anticancer radiotherapy. Minocycline, a semisynthetic tetracycline derivative, has anti-inflammatory, free radical scavenging, …

Kinetically Controlled Synthesis Of Triblock Copolymer Stabilized Gold Nanoparticles, Theodore Saleem Sabir

Loma Linda University Electronic Theses, Dissertations & Projects

Concerns for the environmental and economic impact of organic solvents in gold nanoparticle synthesis have motivated the search for more environmentally benign alternatives. One viable approach is the synthesis of AuNPs from tetrachloroauric(III) acid (HAuCl4) using triblock copolymers (TBPs). However, a major challenge of using TBPs is the heterogeneous nature of the formed nanocrystals. Establishing control over AuNP size and shape requires a detailed mechanistic understanding of precursor reduction and nanoparticle growth. By using mixtures of TBPs (L31 and F68), a more flexible method to tune AuNP size and shape is demonstrated. This is achieved by adjusting the TBP/Au(III) ratio …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; …

Metabolic Reconstruction For Metagenomic Data And Its Application To The Human Microbiome, Sahar Abubucker, Nicola Segata, Johannes Goll, Alyxandria M. Schubert, Jacques Izard, Brandi L. Cantarel, Beltran Rodriguez-Mueller, Jeremy Zucker, Mathangi Thiagarajan, Bernard Henrissat, Owen White, Scott T. Scott, Barbara Methé, Patrick D. Schloss, Dirk Gever, Makedonka Mitreva, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities’ metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as …

Malignant Peripheral Nerve Sheath Tumor (Mpnst): An Overview With Emphasis On Pathology, Imaging And Management Strategies, Timothy C. Beer

Department of Neurosurgery Faculty Papers

Presentation: 20 slides

MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires …

Glutathione-Mediated Neuroprotection Against Methylmercury Neurotoxicity In Cortical Culture Is Dependent On Mrp1, Travis Rush, Xiaoqian Liu, Andrew B. Nowakowski, David H. Petering, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture. MeHg (5 μM) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures. Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6 h. This oxidative stress was prevented by the presence of either GSHME or …

Roles Of Resveratrol And Genistein In Invasion And Metastasis Of Breast Cancer, Brittany Wolfe

College of Science and Health Theses and Dissertations

Breast cancer is a cellular disease characterized by the exploitation of several cellular and molecular mechanisms involved in cell proliferation, apoptosis, motility, and invasion. Effective treatment is available for non-invasive breast cancer at diagnosis, leading to a very high survival rate compared to the low survival rate for those where the breast cancer has spread. Thus, identifying effective therapies and preventative agents is imperative to successfully treat breast cancer. Since diet compromises a large component of the risk factors for breast cancer, it would be beneficial to examine dietary compounds that could potentially play a beneficial role in inhibiting cancer …

Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates Igf-I-Induced Cell Motility And Invasion Of Urothelial Carcinoma Cells, Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonio Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in …

Perk-Dependent Repression Of Mir-106b-25 Cluster Is Required For Er Stress-Induced Apoptosis., S. Gupta, D. E. Read, A. Deepti, K. Cawley, A. Gupta, D. Oommen, T. Verfaillie, S. Matus, Mary A. Smith, Justin L. Mott, P. Agostinis, C. Hetz, A. Samali

Journal Articles: Biochemistry & Molecular Biology

Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of …

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane

Theses and Dissertations

Mitf and Otx transcription factors have been identified as essential to the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific role in the RPE developmental pathway have not been clearly defined. The role of the two Mitf transcription factors (Mitfa and Mitfb) and two Otx transcription factors (Otx1a and Otx2) in zebrafish RPE development was explored in these experiments. The loss of Mitf activity in mitfa, mitfb, or double mitf null mutant fish lines had no effect on RPE pigmentation or development. The loss of Otx2 activity through morpholino knockdown produced a …

Inhibition Of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations And Ca2+ Dysregulation In Aged Rats, Diana M. Sama, Hafiz Mohmmad Abdul, Jennifer L. Furman, Irina A. Artiushin, David E. Szymkowski, Stephen W. Scheff, Christopher M. Norris

Graduate Center for Gerontology Faculty Publications

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits …

The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas

Theses and Dissertations

The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system (CNS) and in the periphery. Positive allosteric modulators (PAMs) of the α7 increase the response to an agonist and are divided into two types depending on whether they also decrease desensitization of the receptor (type II) or not (type I). Therefore, this study aims to investigate whether the enhancement of endogenous α7 nAChR function will result in a beneficial effect in nociceptive, inflammatory and chronic neuropathic pain models. While NS1738 and PNU-120596 were not active to reduce acute thermal pain, measured by hot-plate and tail-flick …

Cdo Patterns The Musculature Of The Esophagus And Is Required For Esophageal Motility In Mice, Anthony I. Romera, Jagmohan Singhb, Satish Rattan, Robert S. Krauss

Department of Medicine Faculty Papers

Introduction:

Cdo is a multifunctional cell surface co-receptor that promotes Hedgehog signaling during rostroventral midline development and cadherin-mediated signaling during skeletal myogenesis. We report here novel roles for Cdo in patterning of the murine esophageal musculature and esophageal motility disorders such as achalasia.

Effect Of Age And Vaccination On Extent And Spread Of Chlamydia Pneumoniae Infection In C57bl/6 Mice, Taylor Eddens, Sarah Beaudoin, Amanda Steinberger, Christopher Scott Little, Dawn Shell, Benjamin Wizel, Brian J. Balin Phd, Kerin L. Fresa-Dillon

PCOM Scholarly Works

BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen for humans. Infection by C. pneumoniae may be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotes C. pneumoniae respiratory infection and extra-respiratory spread in BALB/c mice.

FINDINGS: Aged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection by Chlamydia pneumoniae when compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting against C. …

Scavenger Receptor Cd36 Expression Contributes To Adipose Tissue Inflammation And Cell Death In Diet-Induced Obesity, Lei Cai, Zhen Wang, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.

EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.

RESULTS: Compared to WT …

Polyamidoamine Dendrimer Nanoparticle Cytotoxicity, Oxidative Stress, Caspase Activation And Infammatory Response: Experimental Observation And Numerical Simulation, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

Mechanisms underlying the in vitro cytotoxicity of Polyamidoamine nano-dendrimers in human keratinocytes are explored. Previous studies demonstrated a systematic, dendrimer-generation-dependent cytotoxicity, oxidative stress, and genotoxicity. The emerging picture is of dendrimer endocytosis, endosomal rupture and subsequent mitochondrial attack and cell death. To understand the underlying mechanisms, the evolution of reactive oxygen species, intracellular glutathione, caspase activation, mitochondrial membrane potential decay, and inflammatory responses have been examined. Early-stage responses are associated with endosomal encapsulation, later-stage with mitochondrial attack. In all cases, the magnitude and evolution of responses depend on dendrimer generation and dose. The early-stage response is modelled using a rate …

Reduction Of Na/K-Atpase Potentiates Marinobufagenin-Induced Cardiac Dysfunction And Myocyte Apoptosis, Changxuan Liu, Yan Bai, Yiliang Chen, Yu Wang, Yoann Sottejeau, Lijun Liu, Xiaomei Li, Jerry B. Lingrel, Deepak Malhorta, Christopher Cooper, Joseph I. Shapiro M.D., Zi-Jian Xie, Jiang Tian

Biochemistry and Microbiology

Background: Na/K-ATPase decrease has been reported in patients with heart failure and is related to cardiac dysfunction.

Results: Reducing Na/K-ATPase activates caspase 9 and induces cardiac dilation when treated with marinobufagenin.

Conclusion: Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac myocyte apoptosis.

Significance: Decreased Na/K-ATPase content together with increased cardiotonic steroids levels is a novel mechanism that may account for cardiac dysfunction.

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …

Generating Induced Pluripotent Stem Cells From Human Fibroblast Utilizing Controlled Expression Of Transcription Factors, Ju-Sung Song

Honors Scholar Theses

Human Embryonic stem cells (hESCs) represent a pluripotent cell population derived from the inner cell mass (ICM) of the blastocyst stage of the developing embryo. Ethical concerns have been raised regarding the derivation process, as the procedure ultimately results in the destruction of the embryos. Recently, alternative approach has been devised that encompasses reprogramming of terminally differentiated cells into an hESC-like state. This process relies on the over-expression of four pluripotency-associated factors, and successfully reprogrammed cells are termed induced pluripotent stem cells (iPSCs). These cells hold great promise for the use in future cell-based therapeutics such as evaluating drug induced …

Effects Of Burn Injury On Biological Ethanol And Ethyl Glucuronide Concentrations, Trista Haupt Wright

Electronic Theses and Dissertations

Alcohol is the most abused drug in the United States and most frequently performed assay in forensic laboratories. Alcohol is routinely present in biological specimens from fatal residential fires and forensic toxicologists must interpret if these individuals are impaired by determination of their blood alcohol concentrations on post-incineration blood collected at autopsy. There is no known data available to confirm or refute blood alcohol concentrations and impairment in fire-related deaths. Ethyl glucuronide (EtG), a non-volatile minor ethanol metabolite, may provide a better biomarker for ethanol consumption prior to burn injury. The literature does not address the possibility that ethanol or …

Synaptic And Intrinsic Activation Of Gabaergic Neurons In The Cardiorespiratory Brainstem Network, Julie G. Frank, David Mendelowitz

Pharmacology and Physiology Faculty Publications

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson

Theses and Dissertations

Radiation therapy is a widely used tool in cancer therapy and is frequently offered as the first line of treatment for cancers of the breast. While radiotherapy is often initially effective in killing tumor cells or suppressing their growth, there are factors that confer tumor cell resistance to irradiation. Development of resistance may lead to disease recurrence despite the use of surgery, chemotherapy and radiation therapy. A primary goal of the studies in Dr. Gewirtz’s laboratory is to develop strategies to overcome resistance to radiation (and chemotherapy) in breast cancer, with the ultimate goal of preventing or attenuating disease recurrence. …

A Mathematical Model For Dengue Fever In A Virgin Environment, Jason K. Bowman

Senior Honors Projects

Dengue is a mosquito-borne viral infection found in tropical and subtropical regions around the world. The disease was named in 1779 and the first recorded epidemic of it occurred simultaneously on three continents within the following decade. Dengue is characterized by flu-like symptoms and, while its symptoms are generally reported as quite unpleasant, is rarely fatal. However, in some cases patients can contract a more serious form of the disease, known as Dengue Hemorrhagic Fever, which is far more dangerous. The World Health Organization estimates that today over 2.5 billion people are at risk for Dengue (over 40% of the …

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …