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Il-4 Signaling Drives A Unique Arginase+/Il-1Β+ Microglia Phenotype And Recruits Macrophages To The Inflammatory Cns: Consequences Of Age-Related Deficits In Il-4rα After Traumatic Spinal Cord Injury, Ashley M. Fenn, Jodie C.E. Hall, John C. Gensel, Phillip G. Popovich, Jonathan P. Godbout Jun 2014

Il-4 Signaling Drives A Unique Arginase+/Il-1Β+ Microglia Phenotype And Recruits Macrophages To The Inflammatory Cns: Consequences Of Age-Related Deficits In Il-4rα After Traumatic Spinal Cord Injury, Ashley M. Fenn, Jodie C.E. Hall, John C. Gensel, Phillip G. Popovich, Jonathan P. Godbout

Spinal Cord and Brain Injury Research Center Faculty Publications

Alternative activation of microglia/macrophages (M2a) by interleukin (IL)-4 is purported to support intrinsic growth and repair processes after CNS injury. Nonetheless, alternative activation of microglia is poorly understood in vivo, particularly in the context of inflammation, injury, and aging. Here, we show that aged mice (18-19 months) had reduced functional recovery after spinal cord injury (SCI) associated with impaired induction of IL-4 receptor α (IL-4Rα) on microglia. The failure to successfully promote an IL-4/IL-4Rα response in aged mice resulted in attenuated arginase (M2a associated), IL-1β, and chemokine ligand 2 (CCL2) expression, and diminished recruitment of IL-4Rα+ macrophages to …


A Central Role For Carbon-Overflow Pathways In The Modulation Of Bacterial Cell Death., Vinai Chittezham Thomas, Marat Sadykov, Sujata S. Chaudhari, Joselyn Jones, Jennifer L. Endres, Todd J. Widhelm, Jong-Sam Ahn, Randeep S. Jawa, Matthew C. Zimmerman, Kenneth W. Bayles Jun 2014

A Central Role For Carbon-Overflow Pathways In The Modulation Of Bacterial Cell Death., Vinai Chittezham Thomas, Marat Sadykov, Sujata S. Chaudhari, Joselyn Jones, Jennifer L. Endres, Todd J. Widhelm, Jong-Sam Ahn, Randeep S. Jawa, Matthew C. Zimmerman, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux …


Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder Jun 2014

Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder

Dartmouth Scholarship

Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these …


What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Han Jo Kim, Alexander Vaccaro, Md, Phd, Jeffrey C Wang Jun 2014

What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Han Jo Kim, Alexander Vaccaro, Md, Phd, Jeffrey C Wang

Rothman Institute Papers

No abstract provided.


Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535, Roberto Gedaly, Roberto Galuppo, Michael F. Daily, Malay B. Shah, Erin Colleen Maynard, Changguo Chen, Xiping Zhang, Karyn A. Esser, Donald A. Cohen, B. Mark Evers, Jieyun Jiang, Brett T. Spear Jun 2014

Targeting The Wnt/Β-Catenin Signaling Pathway In Liver Cancer Stem Cells And Hepatocellular Carcinoma Cell Lines With Fh535, Roberto Gedaly, Roberto Galuppo, Michael F. Daily, Malay B. Shah, Erin Colleen Maynard, Changguo Chen, Xiping Zhang, Karyn A. Esser, Donald A. Cohen, B. Mark Evers, Jieyun Jiang, Brett T. Spear

Surgery Faculty Publications

Activation of the Wnt/β-catenin pathway has been observed in at least 1/3 of hepatocellular carcinomas (HCC), and a significant number of these have mutations in the β-catenin gene. Therefore, effective inhibition of this pathway could provide a novel method to treat HCC. The purposed of this study was to determine whether FH535, which was previously shown to block the β-catenin pathway, could inhibit β-catenin activation of target genes and inhibit proliferation of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using β-catenin responsive reporter genes, our data indicates that FH535 can inhibit target gene activation by endogenous and exogenously …


The Tumor Suppressive Role Of Camk2n1 In Castration-Resistant Prostate Cancer., Tao Wang, Zhuo Liu, Shuiming Guo, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Shaohua Xu, Liping Wang, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen Jun 2014

The Tumor Suppressive Role Of Camk2n1 In Castration-Resistant Prostate Cancer., Tao Wang, Zhuo Liu, Shuiming Guo, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Shaohua Xu, Liping Wang, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen

Department of Cancer Biology Faculty Papers

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell …


Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy Jun 2014

Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APPΔNL/ΔNLx PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small …


Targeting Cancer Metabolism With Ketosis And Hyperbaric Oxygen, Angela M. Poff Jun 2014

Targeting Cancer Metabolism With Ketosis And Hyperbaric Oxygen, Angela M. Poff

USF Tampa Graduate Theses and Dissertations

Cancer cells exhibit an abnormal metabolic phenotype characterized by glycolysis and lactate fermentation in the presence of oxygen, a phenomenon known as the Warburg effect. This dysregulated metabolism plays an important role in every aspect of cancer progression, from tumorigenesis to invasion and metastasis. The Warburg effect is a common phenotype shared by most, if not all, cancer types. It is especially prominent in metastatic tumors, which are notoriously resistant to treatment and responsible for the majority of cancer-related deaths. Thus, metabolic therapies which target the Warburg effect could offer novel therapeutic options for most cancer patients, including those with …


Acute Sterol O-Acyltransferase 2 (Soat2) Knockdown Rapidly Mobilizes Hepatic Cholesterol For Fecal Excretion, Stephanie M. Marshall, Anthony D Gromovsky, Kathryn L. Kelley, Matthew A. Davis, Martha D. Wilson, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Lawrence L. Rudel, J. Mark Brown, Ryan E. Temel Jun 2014

Acute Sterol O-Acyltransferase 2 (Soat2) Knockdown Rapidly Mobilizes Hepatic Cholesterol For Fecal Excretion, Stephanie M. Marshall, Anthony D Gromovsky, Kathryn L. Kelley, Matthew A. Davis, Martha D. Wilson, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Lawrence L. Rudel, J. Mark Brown, Ryan E. Temel

Saha Cardiovascular Research Center Faculty Publications

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting …


Characterization Of Methylene Diphenyl Diisocyanate Protein Conjugates, Morgen Mhike Jun 2014

Characterization Of Methylene Diphenyl Diisocyanate Protein Conjugates, Morgen Mhike

Dissertations and Theses

Diisocyanates (dNCO) such as methylene diphenyl diisocyanate (MDI) are used primarily as cross-linking agents in the production of polyurethane products such as paints, elastomers, coatings and adhesives, and are the most frequently reported cause of chemically induced immunologic sensitization and occupational asthma (OA). Immune mediated hypersensitivity reactions to dNCOs include allergic rhinitis, asthma, hypersensitivity pneumonitis and allergic contact dermatitis.

There is currently no simple diagnosis for the identification of dNCO asthma due to the variability of symptoms and uncertainty regarding the underlying mechanisms. Immunological sensitization due to dNCO exposure is traditionally thought to require initial conjugation of the dNCO to …


Advances In Neurovascular Treatments., Robert M Starke, Stephen J Monteith, Nohra Chalouhi, Dale Ding, Ricky Medel, David Hasan, Aaron S Dumont Jun 2014

Advances In Neurovascular Treatments., Robert M Starke, Stephen J Monteith, Nohra Chalouhi, Dale Ding, Ricky Medel, David Hasan, Aaron S Dumont

Department of Neurosurgery Faculty Papers

No abstract provided.


Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan Jun 2014

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …


Vulnerability Of The Ventral Language Network In Children With Focal Epilepsy, Louise J. Croft, Torsten Baldeweg, Leigh Sepeta, Lauren Zimmaro, Madison M. Berl, William D. Gaillard Jun 2014

Vulnerability Of The Ventral Language Network In Children With Focal Epilepsy, Louise J. Croft, Torsten Baldeweg, Leigh Sepeta, Lauren Zimmaro, Madison M. Berl, William D. Gaillard

Neurology Faculty Publications

Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4–12 years, 24 females) and children with focal epilepsy (n = 21, 5–12 years, nine females) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. …


Mir-221/222 Promotes S-Phase Entry And Cellular Migration In Control Of Basal-Like Breast Cancer., Yuan Li, Chunli Liang, Haizhong Ma, Qian Zhao, Ying Lu, Zhendong Xiang, Li Li, Jie Qin, Yihan Chen, William C Cho, Richard G Pestell, Li Liang, Zuoren Yu Jun 2014

Mir-221/222 Promotes S-Phase Entry And Cellular Migration In Control Of Basal-Like Breast Cancer., Yuan Li, Chunli Liang, Haizhong Ma, Qian Zhao, Ying Lu, Zhendong Xiang, Li Li, Jie Qin, Yihan Chen, William C Cho, Richard G Pestell, Li Liang, Zuoren Yu

Department of Cancer Biology Faculty Papers

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both …


Resveratrol And Cancer: Focus On In Vivo Evidence, Lindsay G. Carter, John A. D'Orazio, Kevin J. Pearson Jun 2014

Resveratrol And Cancer: Focus On In Vivo Evidence, Lindsay G. Carter, John A. D'Orazio, Kevin J. Pearson

Graduate Center for Nutritional Sciences Faculty Publications

Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, …


Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio Jun 2014

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …


Oncolytic Tanapoxvirus Expressing Flic Causes Regression Of Human Colorectal Cancer Xenografts In Nude Mice, Steven J. Conrad Jun 2014

Oncolytic Tanapoxvirus Expressing Flic Causes Regression Of Human Colorectal Cancer Xenografts In Nude Mice, Steven J. Conrad

Dissertations

Cancers of the colon and rectum are a significant cause of morbidity and mortality worldwide and existing therapies often perform poorly for individuals afflicted with advanced stage disease. Oncolytic virotherapy is an emerging therapeutic modality which shows great promise for addressing this serious medical need. Herein we describe the in vivo testing of recombinant variants of the tanapoxvirus (TPV), a virus endemic to equatorial Africa which causes a mild and self-limiting disease in humans. Recombinant tanapoxviruses were made deleted for the 66R gene, the 2L gene, or both. Some of the recombinants were armed with mouse chemotactic protein 1 (m …


Correlational Studies Of Organophosphate Levels And Endocrine Disruption, Immunomodulation, And Altered Glucose Homeostasis In A Human Population Study, Carrie Mckean Jun 2014

Correlational Studies Of Organophosphate Levels And Endocrine Disruption, Immunomodulation, And Altered Glucose Homeostasis In A Human Population Study, Carrie Mckean

Dissertations

Organophosphate (OP) pesticides have become the most widely used insecticides since the removal of organochlorine pesticides (“Ch4 Organophosphate Insecticides.pdf,” n.d.) and are generally the most toxic of all pesticides to vertebrates (Soltaninejad & Abdollahi, 2009). As a result, ongoing research has been aimed at further understanding potential health effects from exposure.

The aim of this dissertation research project is to investigate and characterize correlations of OP body burden with human health effects. This research involves an investigation into three pertinent areas concerning OP exposure: thyroid disruption, altered hematology biomarkers, and alterations of glucose homeostasis. Data under investigation come exclusively from …


Cystic Echinococcoses In Mongolia: Molecular Identification, Serology And Risk Factors, Akira Ito, Temuulen Dorjsuren, Anu Davaasuren, Tetsuya Yanagida, Yasuhito Sako, Kazuhiro Nakaya, Minoru Nakao, Oyun-Erdene Bat-Ochir, Tsendjav Ayushkhuu, Narantuya Bazarragchaa, Nyamkhuu Gonchigsengee, Tiaoying Li, Gurbadam Agvaandaram, Abmed Davaajav, Chinchuluun Boldbaatar, Gantigmaa Chuluunbaatar Jun 2014

Cystic Echinococcoses In Mongolia: Molecular Identification, Serology And Risk Factors, Akira Ito, Temuulen Dorjsuren, Anu Davaasuren, Tetsuya Yanagida, Yasuhito Sako, Kazuhiro Nakaya, Minoru Nakao, Oyun-Erdene Bat-Ochir, Tsendjav Ayushkhuu, Narantuya Bazarragchaa, Nyamkhuu Gonchigsengee, Tiaoying Li, Gurbadam Agvaandaram, Abmed Davaajav, Chinchuluun Boldbaatar, Gantigmaa Chuluunbaatar

Harold W. Manter Laboratory of Parasitology: Library Materials

Abstract

Background

Cystic echinococcosis (CE) is a globally distributed cestode zoonosis that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.) is the major causative agent of CE worldwide, recent molecular epidemiological studies have revealed that E. canadensis is common in countries where camels are present. One such country is Mongolia.

Methodology/Principal Findings

Forty-three human hepatic CE cases that were confirmed histopathologically at the National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by analysis of mitochondrial cox1 gene as being caused by either E. canadensis (n = 31, 72.1%) or E. granulosus s.s. ( …


Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri Jun 2014

Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Section of Gastroenterology

We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different groups …


Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger Jun 2014

Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger

Department of Medicine Faculty Papers

No abstract provided.


Azd8931, An Equipotent, Reversible Inhibitor Of Signaling By Epidermal Growth Factor Receptor (Egfr), Her2, And Her3: Preclinical Activity In Her2 Non-Amplified Inflammatory Breast Cancer Models., Zhaomei Mu, Teresa Klinowska, Xiaoshen Dong, Emily Foster, Chris Womack, Sandra V Fernandez, Massimo Cristofanilli May 2014

Azd8931, An Equipotent, Reversible Inhibitor Of Signaling By Epidermal Growth Factor Receptor (Egfr), Her2, And Her3: Preclinical Activity In Her2 Non-Amplified Inflammatory Breast Cancer Models., Zhaomei Mu, Teresa Klinowska, Xiaoshen Dong, Emily Foster, Chris Womack, Sandra V Fernandez, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Epidermal growth factor receptor (EGFR) overexpression has been associated with prognostic and predictive value in inflammatory breast cancer (IBC). Epidermal growth factor receptor 2 (HER2) overexpression is observed at a higher rate in IBC compared with noninflammatory breast cancer. Current clinically available anti-HER2 therapies are effective only in patients with HER2 amplified breast cancer, including IBC. AZD8931 is a novel small-molecule equipotent inhibitor of EGFR, HER2, and HER3 signaling. In this study, we investigated the antitumor activity of AZD8931 alone or in combination with paclitaxel using preclinical models of EGFR-overexpressed and HER2 non-amplified IBC cells.

METHODS: Two IBC cell …


Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore May 2014

Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, …


Withanolides, Probes And Binding Targets And Methods Of Use Thereof, Royce Mohan, Paola Bargagna-Mohan, Kyung Bo Kim May 2014

Withanolides, Probes And Binding Targets And Methods Of Use Thereof, Royce Mohan, Paola Bargagna-Mohan, Kyung Bo Kim

Ophthalmology and Visual Science Faculty Patents

Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics …


Controlling Cytomegalovirus: Helping The Immune System Take The Lead, Patrick J. Hanley, Catherine M. Bollard May 2014

Controlling Cytomegalovirus: Helping The Immune System Take The Lead, Patrick J. Hanley, Catherine M. Bollard

Pediatrics Faculty Publications

Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of …


Ultraviolet Radiation, Aging And The Skin: Prevention Of Damage By Topical Camp Manipulation, Alexandra Amaro-Ortiz, Betty Yan, John A. D’Orazio May 2014

Ultraviolet Radiation, Aging And The Skin: Prevention Of Damage By Topical Camp Manipulation, Alexandra Amaro-Ortiz, Betty Yan, John A. D’Orazio

Markey Cancer Center Faculty Publications

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. …


Human Antimicrobial Peptides And Proteins, Guangshun Wang May 2014

Human Antimicrobial Peptides And Proteins, Guangshun Wang

Journal Articles: Pathology and Microbiology

As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids …


Activation Of C-Met And Upregulation Of Cd44 Expression Are Associated With The Metastatic Phenotype In The Colorectal Cancer Liver Metastasis Model, Victoria Allison Elliott, Piotr G. Rychahou, Yekaterina Y. Zaytseva, B. Mark Evers May 2014

Activation Of C-Met And Upregulation Of Cd44 Expression Are Associated With The Metastatic Phenotype In The Colorectal Cancer Liver Metastasis Model, Victoria Allison Elliott, Piotr G. Rychahou, Yekaterina Y. Zaytseva, B. Mark Evers

Markey Cancer Center Faculty Publications

Background

Liver metastasis is the most common cause of death in patients with colorectal cancer. Despite extensive research into the biology of cancer progression, the molecular mechanisms that drive colorectal cancer metastasis are not well characterized.

Methods

HT29 LM1, HT29 LM2, HT29 LM3 cell lines were derived from the human colorectal cancer cell line HT29 following multiple rounds of in vivo selection in immunodeficient mice.

Results

CD44 expression, a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesions, and cancer cells adhesion to endothelial cells was increased in all in vivo selected cell lines, with maximum CD44 expression and cancer cells …


The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo May 2014

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …


Wai-Kwan Alfred Yung, Md, Oral History Interview, May 7, 2014, Wai-Kwan Alfred Yung Md, Tacey A. Rosolowski Phd May 2014

Wai-Kwan Alfred Yung, Md, Oral History Interview, May 7, 2014, Wai-Kwan Alfred Yung Md, Tacey A. Rosolowski Phd

Interview Sessions

Major Topics Coveted:

  • History of Neuro-Oncology services and research at MD Anderson
  • History of the Department of Neuro-Oncology
  • The Brain Tumor Center: collaborative relationships and shared resources with Neuro-Oncology, Neuro-Surgery, Neuro-Pathology, neuro-imaging and other support fields