Digital Commons Network^™

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin

Paediatrics Publications

Background

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS’s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx …

Surgical Technique For Developing A Rabbit Model Of Congenital Diaphragmatic Hernia And Tracheal Occlusion, M. Mudri, S. A. Smith, C. Vander Tuin, J. Davidson, T. R.H. Regnault, A. Bütter

Paediatrics Publications

The surgical model of congenital diaphragmatic hernia (CDH) has been utilized in exploring treatments and innovative therapies, such as tracheal occlusion (TO). The rabbit is an excellent surgical model compared to others due to lower cost, ease of care, short gestational period, and large litter size. This model is also ideal in studying lung hypoplasia of CDH because rabbit lung development is most similar to humans as alveolarization begins prior to birth and continues post-natally. However, the surgical technique in creating a rabbit model of CDH is quite difficult and information is lacking on how to establish this model. Therefore, …

Sensitivity Of Single Organ Versus Multiorgan Point-Of-Care Ultrasound Compared To Computed Tomography Pulmonary Angiography In Detecting Pulmonary Embolism In Adult Patients, Jessica Stangenes

Theses and Graduate Projects

Background: Pulmonary embolism (PE) is a serious and potentially life-threatening complication of venous thromboembolism and its diagnosis remains a challenge. The current gold standard to confirm diagnosis of PE is multi-row computed tomography pulmonary angiography (CTPA) but has limitations and alternative imaging modalities are being investigated. Point-of-care ultrasound (POCUS) has been applied in the diagnostic process in PE but whether it can safely replace the gold standard is of question.

Methods: A literature review was conducted to evaluate the sensitivity of single versus multiorgan point-of-care ultrasound (POCUS) compared to CTPA in detecting PE in adult patients.

Discussion: Several prospective observational …

Antibiotic Resistance Of Streptococcus Pneumoniae In The United States And Latin American Countries: Contributing Factors And Potential Solutions, Brian Sherman

Theses and Graduate Projects

Antibiotics have been heralded as one of the greatest contributions to modern medicine.

While antibiotics have been documented throughout many parts of the world, it was the discovery of penicillin in 1928 that marked the modern era of medicine.1 An antibiotic is a natural, semi-synthetic, or synthetic compound that interferes with the growth of, or results in the death of a microorganism, specifically bacteria.2 These medications are used to treat or prevent infection of humans or animals. With the advent of antibiotics, many infections that would cause significant morbidity and mortality were greatly reduced. The 1930s-1960s is regarded as the …

Use Of Intraarticular Injections Of Platelet-Rich Plasma In The Treatment Of Knee Osteoarthritis: A Review Article, Naveed Baloch, Obada Hasan, Zain Baig, Umme-E-Hani Abdullah, Mohammad Atif, Hiroshi Ohuchi

Section of Orthopaedic Surgery

Osteoarthritis is one of the most common degenerative conditions affecting knee joint. As our understanding in the disease pathogenesis is evolving, so do the treatment modalities. One of the postulated mechanisms suggests the production of inflammatory cytokines secondary to repeated micro trauma than in turn lead to cartilage damage overtime. Cartilage being avascular structure has limited potential for repair. Based on this, recent studies have been focusing on stimulating cartilage-healing process by growth factors. This is where platelet-rich plasma comes in to light. Literature is showing promising results of platelet-rich plasma in treating knee osteoarthritis. In this review we have …

The Effects Of Matrix Metalloproteinase-9 On Cx3cl1 Shedding And Axon Retraction, Lauren A. Dobrie

Honors Undergraduate Theses

Spinal cord injury (SCI) often leads to irreversible damage, and permanent paralysis inferior to the injury is common (Leibinger et al., 2013). Injury to the spinal cord occurs in two phases. In the first phase, components of the spinal cord are subject to mechanical trauma causing direct damage. In the second phase, damage spreads from the area of injury through molecular processes. Several studies have linked M1 "pro-inflammatory" macrophages to exacerbation of damage by inducing dieback of dystrophic axons, but not healthy axons, through direct cellular contact. Several studies have identified the presence of macrophage subtypes at specific time. A …

Effects Of A Plant-Based Vegan Diet On The Risk Of Cancer: An Integrative Review Of The Literature, Chelsie M. Silavent

Honors Undergraduate Theses

Cancer, an aggressive chronic disease, impacts the lives of millions of people every day. There are numerous proposed triggers related to the diagnosis and much remains to be learned about the causes. Associated with this disease's variability is the challenge to identify a single causative agent that lead to its prevention. Specific topics that need additional evidence relate to environmental factors and lifestyle behaviors in the development, treatment and, in some instances, even suppression of disease progression. Specifically, a diet that excludes animal-based products but consists of a variety of fruits and vegetables (i.e., plant-based vegan diet) is reported to …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis., Sean J O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A S Reyes, Jon Gorky, Rajanikanth Vadigepalli, Elisabeth J Van Bockstaele, James S Schwaber

Articles, Abstracts, and Reports

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably

Identification Of Candidate Mirna Biomarkers For Glaucoma, Allyson Hindle, Robrecht Thoonen, Jessica V. Jasien, Robert M. H. Grange, Krishna Amin, Jasen Wise, Mineo Ozaki, Robert Ritch, Rajeev Malhotra, Emmanuel S. Buys

Life Sciences Faculty Research

Purpose: Glaucoma, a leading cause of blindness worldwide, often remains undetected until irreversible vision loss has occurred. Treatments focus on lowering intraocular pressure (IOP), the only modifiable and readily measurable risk factor. However, IOP can vary and does not always predict disease progression. MicroRNAs (miRNAs) are promising biomarkers. They are abundant and stable in biological fluids, including plasma and aqueous humor (AqH). We aimed to identify differentially expressed miRNAs in AqH and plasma from glaucoma, exfoliation syndrome (XFS), and control subjects. Methods: Plasma and AqH from two ethnic cohorts were harvested from glaucoma or XFS (often associated with glaucoma, n …

Minimal Information For Studies Of Extracellular Vesicles 2018 (Misev2018): A Position Statement Of The International Society For Extracellular Vesicles And Update Of The Misev2014 Guidelines, Clotilde Théry, Kenneth W. Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D. Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K. Atkiin-Smith, D. Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N. Bauer, Amy A. Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Abderrahim Benmoussa, Anna C. Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfrid Boireau, Antonella Bongiovanni, Francesc E. Borràs, Steffi Bosch, Chantal M. Boulanger, Xandra Breakefield, Andrew M. Breglio, Meadhbh Á. Brennan, David R. Brigstock, Alain Brisson, Marike L.D. Broekman, Jacqueline F. Bromberg, Paulina Bryl-Górecka, Shilpa Buch, Amy H. Buck, Dylan Burger, Sara Busatto, Dominik Buschmann, Benedetta Bussolati, Edit I. Buzás, James Bryan Byrd, Giovanni Camussi, David R.F. Carter, Sarah Caruso, Lawrence W. Chamley, Yu-Ting Chang, Chichen Chen, Shuai Chen, Lesley Cheng, Andrew R. Chin, Aled Clayton, Stefano P. Clerici, Alex Cocks, Emanuele Cocucci, Robert J. Coffey, Anabela Cordeiro-Da-Silva, Yvonne Couch, Frank A.W. Coumans, Beth Coyle, Rossella Crescitelli, Miria Ferreira Criado, Crislyn D’ Souza-Schorey, Saumya Das, Amrita Datta Chaudhuri, Paola De Candia, Eliezer F. De Santana Junior, Olivier De Wever, Hernando A. Del Portillo, Tanguy Demaret, Sarah Deville, Andrew Devitt, Bert Dhondt, Dolores Di Vizio, Lothar C. Dieterich, Vincenza Dolo, Ana Paula Dominguez Rubio, Massimo Dominici, Mauricio R. Dourado, Tom A.P Driedonks, Filipe V. Duarte, Heather M. Duncan, Ramon M. Eichenberger, Karin Ekström, Samir El Andaloussi, Celine Elie-Caille, Uta Erdbrügger, Juan M. Falcón-Pérez, Farah Fatima, Jason E. Fish, Miguel Flores-Bellver, András Försönits, Annie Frelet-Barrand, Fabia Fricke, Gregor Fuhrmann, Susanne Gabrielsson, Ana Gámez-Valero, Chris Gardiner, Kathrin Gärtner, Raphael Gaudin, Yong Song Gho, Bernd Giebel, Caroline Gilbert, Mario Gimona, Ilaria Giusti, Deborah C.I. Goberdhan, André Görgens, Sharon M. Gorski, David W. Greening, Julia Christina Gross, Alice Gualerzi, Gopal N. Gupta, Dakota Gustafson, Aase Handberg, Reka A. Haraszti, Paul Harrison, Hargita Hegyesi, An Hendrix, Andrew F. Hill, Fred H. Hochberg, Karl F. Hoffmann, Beth Holder, Harry Holthofer, Baharak Hosseinkhani, Guoku Hu, Yiyao Huang, Veronica Huber, Stuart Hunt, Ahmed Gamal-Eldin Ibrahim, Tsuneya Ikezu, Jameel M. Inal, Mustafa Isin, Alena Ivanova, Hannah K. Jackson, Soren Jacobsen, Steven M. Jay, Muthuvel Jayachandran, Guido Jenster, Lanzhou Jiang, Suzanne M. Johnson, Jennifer C. Jones, Ambrose Jong, Tijana Jovanovic-Talisman, Stephanie Jung, Raghu Kalluri, Shin-Ichi Kano, Sukhbir Kaur, Yumi Kawamura, Evan T. Keller, Delaram Khamari, Elena Khomyakova, Anastasia Khvorova, Peter Kierulf, Kwang Pyo Kim, Thomas Kislinger, Mikael Klingeborn, David J. Klinke Ii, Miroslaw Kornek, Maja M. Kosanović, Árpád Ferenc Kovács, Eva-Maria Krämer-Albers, Susanne Krasemann, Mirja Krause, Igor V. Kurochkin, Gina D. Kusuma, Sören Kuypers, Saara Laitinen, Scott M. Langevin, Lucia R. Languino, Joanne Lannigan, Cecilia Lässer, Louise C. Laurent, Gregory Lavieu, Elisa Lázaro-Ibáñez, Soazig Le Lay, Myung-Shin Lee, Yi Xin Fiona Lee, Debora S. Lemos, Metka Lenassi, Aleksandra Leszczynska, Isaac T.S. Li, Ke Liao, Sten F. Libregts, Erzsebet Ligeti, Rebecca Lim, Sai Kiang Lim, Aija Linē, Karen Linnemannstöns, Alicia Llorente, Catherine A. Lombard, Magdalena J. Lorenowicz, Ákos M. Lörincz, Jan Lötvall, Jason Lovett, Michelle C. Lowry, Xavier Loyer, Quan Lu, Barbara Lukomska, Taral R. Lunavat, Sybren L.N. Maas, Harmeet Malhi, Antonio Marcilla, Jacopo Mariani, Javier Mariscal, Elena S. Martens-Uzunova, Lorena Martin-Jaular, M. Carmen Martinez, Vilma Regina Martins, Mathilde Mathieu, Suresh Mathivanan, Marco Maugeri, Lynda K. Mcginnis, Mark J. Mcvey, David G. Meckes, Jr., Katie L. Meehan, Inge Mertens, Valentina R. Minciacchi, Andreas Möller, Malene Møller Jørgensen, Aizea Morales-Kastresana, Jess Morhayim, François Mullier, Maurizio Muraca, Luca Musante, Veronika Mussack, Dillon C. Muth, Kathryn H. Myburgh, Tanbir Najrana, Muhammad Nawaz, Irina Nazarenko, Peter Nejsum, Christian Neri, Tommaso Neri, Rienk Nieuwland, Leonardo Nimrichter, John P. Nolan, Esther N.M. Nolte-’ T Hoen, Nicole Noren Hooten, Lorraine O’Driscoll, Tina O’Grady, Ana O’Loghlen, Takahiro Ochiya, Martin Olivier, Alberto Ortiz, Luis A. Ortiz, Xabier Osteikoetxea, Ole Ostegaard, Matias Ostrowski, Jaesung Park, D. Michiel Pegtel, Hector Peinado, Francesca Perut, Michael W. Pfaffl, Donald G. Phinney, Bartijn C.H. Pieters, Ryan C. Pink, David S. Pisetsky, Elke Pogge Von Strandmann, Iva Polakovicova, Ivan K.H. Poon, Bonita H. Powell, Ilaria Prada, Lynn Pulliam, Peter Quesenberry, Annalisa Radeghieri, Robert L. Raffai, Stefania Raimondo, Janusz Rak, Marcel I. Ramirez, Graça Raposo, Morsi S. Rayyan, Neta Regev-Rudzki, Fran L. Ricklefs, Paul D. Robbins, David D. Roberts, Silvia C. Rodrigues, Eva Rohde, Sophie Rome, Kasper M.A. Rouschop, Aurelia Rughetti, Ashley E. Russell, Paula Saá, Susmita Sahoo, Edison Salas-Huenuleo, Catherine Sánchez, Julie A. Saugstad, Meike J. Saul, Raymond M. Schiffelers, Raphael Schneider, Tine Hiorth Schøyen, Aaron Scott, Eriomina Shahaj, Shivani Sharma, Olga Shatnyeva, Faezeh Shekari, Ganesh Vilas Shelke, Ashok K. Shetty, Kiyotaka Shiba, Pia R-M Siljander, Andreia M. Silva, Agata Skowronek, Orman L. Snyder Ii, Rodrigo Pedro Soares, Barbara W. Sódar, Carolina Soekmadji, Javier Sotillo, Philip D. Stahl, Willem Stoorvogel, Shannon L. Stott, Erwin F. Strasser, Simon Swift, Hidetoshi Tahara, Muneesh Tewari, Kate Timms, Swasti Tiwari, Rochelle Tixeira, Mercedes Tkach, Wei Seong Toh, Richard Tomasini, Ana Claudia Torrecilhas, Juan Pablo Tosar, Vasilis Toxavidis, Lorena Urbanelli, Pieter Vader, Bas W.M. Van Balkom, Susanne G. Van Der Grein, Jan Van Deun, Martijn J.C. Van Herwijnen, Kendall Van Keuren-Jensen, Guillaume Van Niel, Martin E. Van Royen, Andre J. Van Wijnen, M. Helena Vasconcelos, Ivan J. Vechetti Jr., Tiago D. Veit, Laura J. Vella, Émilie Velot, Frederik J. Verweij, Beate Vestad, Jose L. Viñas, Tamás Visnovitz, Krisztina V. Vukman, Jessica Wahlgren, Dionysios C. Watson, Marca H.M. Wauben, Alissa Weaver, Jason P. Webber, Viktoria Weber, Ann M. Wehman, Daniel J. Weiss, Joshua A. Welsh, Sebastian Wendt, Asa M. Wheelock, Zoltán Wiener, Leonie Witte, Joy Wolfram, Angeliki Xagorari, Patricia Xander, Jing Xu, Xiaomei Yan, María Yáñez-Mó, Hang Yin, Yuana Yuana, Valentina Zappulli, Jana Zarubova, Vytautas Žėkas, Jian-Ye Zhang, Zezhou Zhao, Lei Zheng, Alexander R. Zheutlin, Antje M. Zickler, Pascale Zimmermann, Angela M. Zivkovic, Davide Zocco, Ewa K. Zuba-Surma

Department of Cancer Biology Faculty Papers

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines …

Lipid-Polymer Hybrid Nanoparticles As A Next-Generation Drug Delivery Platform: State Of The Art, Emerging Technologies, And Perspectives., Anubhab Mukherjee, Ariana K Waters, Pranav Kalyan, Achal Singh Achrol, Santosh Kesari, Venkata Yenugonda

Articles, Abstracts, and Reports

Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways …

Serum Amyloid A And Janus Kinase 2 In A Mouse Model Of Diabetic Kidney Disease., Brad P Dieter, Rick L Meek, Robert J Anderberg, Sheryl K Cooney, Jen L Bergin, Hongyu Zhang, Viji Nair, Matthias Kretzler, Frank C Brosius, Katherine Tuttle

Articles, Abstracts, and Reports

BACKGROUND: Serum amyloid A (SAA), a potent inflammatory mediator, and Janus kinase 2 (JAK2), an intracellular signaling kinase, are increased by diabetes. The aims were to elucidate: 1) a JAK2-mediated pathway for increased SAA in the kidneys of diabetic mice; 2) a JAK2-SAA pathway for inflammation in podocytes.

METHODS: Akita diabetic mice (129S6) with podocyte JAK2 overexpression and angiotensin II infusion (4 weeks) were given a JAK1,2 inhibitor (LY03103801, 3 mg/kg/day orally for the last two weeks). Kidneys were immunostained for SAA isoform 3 (SAA3). SAA3 knockout and control mouse podocytes were exposed to advanced glycation end products (AGE) or …

Lipophagy And Alcohol-Induced Fatty Liver, Li Yang, Changqing Yang, Paul G. Thomes, Kusum K. Kharbanda, Carol A. Casey, Mark A. Mcniven, Terrence M. Donohue

Journal Articles: Internal Medicine

This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our …

Prophylactic Treatment Of Hyperbaric Oxygen Treatment Mitigates Inflammatory Response Via Mitochondria Transfer, Trenton Lippert, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.

Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Four decades of preclinical research demonstrating survival, functional integration, and behavioral effects of transplanted stem cells in experimental stroke models have provided ample scientific basis for initiating limited clinical trials of stem cell therapy in stroke patients. Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as …

Microrna-133a And Myocardial Infarction, Yi Xiao, Jiling Zhao, Julian P. Tuazon, Cesar V. Borlongan, Guolong Yu

Neurosurgery and Brain Repair Faculty Publications

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is …

A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart

Neurosurgery and Brain Repair Faculty Publications

The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances …

Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low

Neurosurgery and Brain Repair Faculty Publications

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that …

Alkylaminophenol Induces G1/S Phase Cell Cycle Arrest In Glioblastoma Cells Through P53 And Cyclin-Dependent Kinase Signaling Pathway., Phuong Doan, Aliyu Musa, Nuno R Candeias, Frank Emmert-Streib, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC

Reverting Immune Suppression To Enhance Cancer Immunotherapy., Bella S Guerrouahen, Cristina Maccalli, Chiara Cugno, Sergio Rutella, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8

Subcellular Compartmentalization Of Pkm2 Identifies Anti-Pkm2 Therapy Response In Vitro And In Vivo Mouse Model Of Human Non-Small-Cell Lung Cancer., Akiko Suzuki, Sachin Puri, Pamela Leland, Ankit Puri, Tarsem Moudgil, Bernard A Fox, Raj K Puri, Bharat H Joshi

Articles, Abstracts, and Reports

Pyruvate kinase M2 (PKM2) is an alternatively spliced variant, which mediates the conversion of glucose to lactate in cancer cells under normoxic conditions, known as the Warburg effect. Previously, we demonstrated that PKM2 is one of 97 genes that are overexpressed in non-small-cell lung cancer (NSCLC) cell lines. Herein, we demonstrate a novel role of subcellular PKM2 expression as a biomarker of therapeutic response after targeting this gene by shRNA or small molecule inhibitor (SMI) of PKM2 enzyme activity in vitro and in vivo. We examined two established lung cancer cell lines, nine patients derived NSCLC and three normal lung …

Kiaa1549-Braf Expression Establishes A Permissive Tumor Microenvironment Through Nfκb-Mediated Ccl2 Production, Ran Chen, Chanel Keoni, Christopher A. Waker, Robert M. Lober, Robert M. Lober, Yihsien Chen, David H. Gutmann

Pediatrics Faculty Publications

KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production …

Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna

Open Access Theses & Dissertations

Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …

Nutrition Manual For Nsu Student Athletes, Kaitlyn Flaskerud, Katie Emerson, Stephanie Fonesca, Angel Marquez, Alejandra Velandia, Marilyn Gordon

Faculty Articles

No abstract provided.

Gutting The Brain Of Inflammation: A Key Role Of Gut Microbiome In Human Umbilical Cord Blood Plasma Therapy In Parkinson's Disease Model, Jea-Young Lee, Julian P. Tuazon, Jared Ehrhart, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Current therapies for Parkinson's disease (PD), including L-3,4-dihydroxyphenylalanine (L-DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem/progenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft-mediated secretion of growth factors, anti-inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non-cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB-derived plasma into the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rat model of PD. …

Retrospective Case Series Of Traumatic Brain Injury And Post-Traumatic Stress Disorder Treated With Hyperbaric Oxygen Therapy, R. Douglas Shytle, David J. Eve, Soel-Hee Kim, Allan Spiegel, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Returning veterans are frequently diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Considering a recent case-controlled study of hyperbaric oxygen therapy (HBOT) reporting a reduction in suicidal ideation, we investigated retrospectively three veterans with chronic TBI/PTSD symptoms who were treated with multiple rounds of HBOT with neurophysiological testing performed before and after treatment. Improvements were detected on parameters within neurocognitive domains, including reductions in suicide-related symptoms. These findings independently confirm that HBOT may be effective in treating specific symptoms of TBI/PTSD that are not currently addressed with existing therapeutic approaches.

Administration Of Rctrp9 Attenuates Neuronal Apoptosis Through Adipor1/Pi3k/Akt Signaling Pathway After Ich In Mice, Lianhua Zhao, John H. Zhang, Prativa Sherchan, Paul R. Krafft, Wei Zhao, Sa Wang, Shengpan Chen, Zaiyu Guo, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were …

Pathophysiology Of Ganglioside Gm1 In Ischemic Stroke: Ganglioside Gm1: A Critical Review, Wenchao Zhang, Paul R. Krafft, Tianlong Wang, John H. Zhang, Li Li, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be …

Safety, Pharmacodynamics, And Potential Benefit Of Omaveloxolone In Friedreich Ataxia, David R. Lynch, Jennifer Farmer, Lauren Hauser, Ian A. Blair, Qing Qing Wang, Clementina Mesaros, Nathaniel Snyder, Sylvia Boesch, Melanie Chin, Martin B. Delatycki, Paola Giunti, Angela Goldsberry, Chad Hoyle, Michael G. Mcbride, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S. H. Subramony, George R. Wilmot, Theresa A. Zesiewicz, Colin Meyer

Neurology Faculty Publications

Objective Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435).

Methods Sixty-nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5–300 mg/day.

Results Omaveloxolone was well tolerated, and adverse …

Folic Acid Intake, Fetal Brain Growth, And Maternal Smoking In Pregnancy: A Randomized Controlled Trial, Korede K. Yusuf, Hamisu M. Salihu, Roneé Wilson, Alfred K. Mbah, William Sappenfield, Karen Bruder, Usman J. Wudil, Muktar H. Aliyu

Obstetrics & Gynecology Faculty Publications

Background: Folic acid supplementation during pregnancy plays an important role in fetal growth and development. To our knowledge, no experimental study has examined the effect of folic acid on fetal brain growth in women who smoke cigarettes during pregnancy. Objectives: The aim of this study was to investigate the efficacy of higher-dose compared with standard-dose folic acid supplementation on prenatal fetal brain growth, measured by head circumference, brain weight, and brain-body weight ratio (BBR). Design: In this randomly assigned, double-blind, controlled clinical trial, we recruited 345 smoking pregnant women attending a community health center in Tampa, FL between 2010 and …