Vilnius University Life Sciences Center. Annual Report 2019
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(TPZ) Prodrugs for the Management of Hypoxic Solid Tumors by Sindhuja
Evaluation of bioreductively-activated Tirapazamine (TPZ) prodrugs for the management of hypoxic solid tumors by Sindhuja Pattabhi Raman A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Cancer Sciences Department of Oncology University of Alberta © Sindhuja Pattabhi Raman, 2019 Abstract Solid tumors often have large areas with low levels of oxygen (termed hypoxic regions), which are associated with poor prognosis and treatment response. Tirapazamine (TPZ), a hypoxia targeting anticancer drug, started as a promising candidate to deal with this issue. However, it was withdrawn from the clinic due to severe neurotoxic side effects and poor target delivery. Hypoxic cells overexpress glucose transporters (GLUT) - a key feature during hypoxic tumor progression. Our project aims at conjugating TPZ with glucose to exploit the upregulated GLUTs for its delivery, and thereby facilitate the therapeutic management of hypoxic tumors. We hypothesized that glucose-conjugated TPZ (G6-TPZ) would be selectively recruited to these receptors, facilitating its entrapment in poorly oxygenated cells only, with minimal damage to their oxygenated counterparts. However, our results reveal that the addition of the glucose moiety to TPZ was counterproductive since G6-TPZ displayed selective hypoxic cytotoxicity only at very high concentrations of the compound. We speculate that the reduced cytotoxicity of G6-TPZ might be due to the fact that the compound was not taken up by the cells. In order to monitor the cellular uptake of TPZ, we developed a click chemistry-based approach by incorporating an azido (N3) group to our parent compound (N3-TPZ). We observed that the azido-conjugated TPZ was highly hypoxia selective and the compound successfully tracks cellular hypoxia. -
Phages for Phage Therapy: Isolation, Characterization, and Host Range Breadth
pharmaceuticals Review Phages for Phage Therapy: Isolation, Characterization, and Host Range Breadth Paul Hyman Department of Biology/Toxicology, Ashland University, 401 College Ave., Ashland, OH 44805, USA; [email protected]; Tel.: +1-419-207-6309 Received: 28 December 2018; Accepted: 4 March 2019; Published: 11 March 2019 Abstract: For a bacteriophage to be useful for phage therapy it must be both isolated from the environment and shown to have certain characteristics beyond just killing strains of the target bacterial pathogen. These include desirable characteristics such as a relatively broad host range and a lack of other characteristics such as carrying toxin genes and the ability to form a lysogen. While phages are commonly isolated first and subsequently characterized, it is possible to alter isolation procedures to bias the isolation toward phages with desirable characteristics. Some of these variations are regularly used by some groups while others have only been shown in a few publications. In this review I will describe (1) isolation procedures and variations that are designed to isolate phages with broader host ranges, (2) characterization procedures used to show that a phage may have utility in phage therapy, including some of the limits of such characterization, and (3) results of a survey and discussion with phage researchers in industry and academia on the practice of characterization of phages. Keywords: phage therapy; bacteriophage isolation; host range; bacteriophage characterization; genome sequencing; enrichment culture 1. Introduction The isolation of bacteriophages for phage therapy is often presented as a fairly straightforward exercise of mixing a phage-containing sample with host bacteria, followed by a simple removal of bacterial debris by filtration and/or centrifugation the next day [1–3]. -
First Description of a Temperate Bacteriophage (Vb Fhim KIRK) of Francisella Hispaniensis Strain 3523
viruses Article First Description of a Temperate Bacteriophage (vB_FhiM_KIRK) of Francisella hispaniensis Strain 3523 Kristin Köppen 1,†, Grisna I. Prensa 1,†, Kerstin Rydzewski 1, Hana Tlapák 1, Gudrun Holland 2 and Klaus Heuner 1,* 1 Centre for Biological Threats and Special Pathogens, Cellular Interactions of Bacterial Pathogens, ZBS 2, Robert Koch Institute, 13353 Berlin, Germany; [email protected] (K.K.); [email protected] (G.I.P.); [email protected] (K.R.); [email protected] (H.T.) 2 Centre for Biological Threats and Special Pathogens, Advanced Light and Electron Microscopy, ZBS 4, Robert Koch Institute, D-13353 Berlin, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-30-18754-2226 † Both authors contributed equally to this work. Abstract: Here we present the characterization of a Francisella bacteriophage (vB_FhiM_KIRK) includ- ing the morphology, the genome sequence and the induction of the prophage. The prophage sequence (FhaGI-1) has previously been identified in F. hispaniensis strain 3523. UV radiation induced the prophage to assemble phage particles consisting of an icosahedral head (~52 nm in diameter), a tail of up to 97 nm in length and a mean width of 9 nm. The double stranded genome of vB_FhiM_KIRK contains 51 open reading frames and is 34,259 bp in length. The genotypic and phylogenetic analysis indicated that this phage seems to belong to the Myoviridae family of bacteriophages. Under the Citation: Köppen, K.; Prensa, G.I.; conditions tested here, host cell (Francisella hispaniensis 3523) lysis activity of KIRK was very low, and Rydzewski, K.; Tlapák, H.; Holland, the phage particles seem to be defective for infecting new bacterial cells. -
Method of Tumor Treatment
Europaisches Patentamt J European Patent Office 0 Publication number: 0 649 658 A1 Office europeen des brevets EUROPEAN PATENT APPLICATION 0 Application number: 94202693.1 mt . ci .6 :A61K 31/53 0 Date of filing: 19.09.94 0 Priority: 22.09.93 US 125609 Palo Alto, CA 94304-1850 (US) 0 Date of publication of application: 0 Inventor: Brown, Martin J. 26.04.95 Bulletin 95/17 c/o Sterling Winthrop, Inc., 90 Park Avenue 0 Designated Contracting States: New York 10016 (US) AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE 0 Representative: Le Guen, Gerard 0 Applicant: THE BOARD OF TRUSTEES OF THE CABINET LAVOIX LELAND STANFORD JUNIOR UNIVERSITY 2, place d'Estienne d'Orves 900 Welch Road, Suite 350 F-75441 Paris Cedex 09 (FR) 0 Method of tumor treatment. 0 The present invention provides methods for increasing the cytotoxicity of a chemotherapy agent towards a solid tumor, such tumor susceptible to treatment with the chemotherapy agent, comprising administering to a mammal having such a tumor, from about one half hour to about twenty-four hours prior to administering the chemotherapy agent, or from about one hour to about two hours after administering the chemotherapy agent, a cytotoxicity-enhancing amount of a compound of Formula I. The invention also provides kits for treatment of such tumors which comprise a chemotherapy agent and a cytotoxicity-enhancing amount of a 1,2,4-ben- zotriazine oxide as defined in Formula I. The present invention also provides the use of a compound of Formula I capable of exerting a cytotoxic- enhancing effect on a cancer tumor for the manufacture of a medicament, for the therapeutic administration to a mammal having such a tumour from about one half hour to about twenty-four hours prior to treatment of said tumor with a chemotherapy agent. -
Elucidating Viral Communities During a Phytoplankton Bloom on the West Antarctic Peninsula
fmicb-10-01014 May 10, 2019 Time: 14:46 # 1 ORIGINAL RESEARCH published: 14 May 2019 doi: 10.3389/fmicb.2019.01014 Elucidating Viral Communities During a Phytoplankton Bloom on the West Antarctic Peninsula Tomás Alarcón-Schumacher1,2†, Sergio Guajardo-Leiva1†, Josefa Antón3 and Beatriz Díez1,4* 1 Department of Molecular Genetics and Microbiology, Pontificia Universidad Católica de Chile, Santiago, Chile, 2 Max Planck Institute for Marine Microbiology, Bremen, Germany, 3 Department of Physiology, Genetics, and Microbiology, University of Alicante, Alicante, Spain, 4 Center for Climate and Resilience Research (CR2), University of Chile, Santiago, Chile In Antarctic coastal waters where nutrient limitations are low, viruses are expected to play a major role in the regulation of bloom events. Despite this, research in viral identification and dynamics is scarce, with limited information available for the Southern Ocean (SO). This study presents an integrative-omics approach, comparing variation in the viral and microbial active communities on two contrasting sample conditions from Edited by: a diatom-dominated phytoplankton bloom occurring in Chile Bay in the West Antarctic David Velazquez, Autonomous University of Madrid, Peninsula (WAP) in the summer of 2014. The known viral community, initially dominated Spain by Myoviridae family (∼82% of the total assigned reads), changed to become dominated Reviewed by: by Phycodnaviridae (∼90%), while viral activity was predominantly driven by dsDNA Carole Anne Llewellyn, ∼ ∼ Swansea University, United Kingdom members of the Phycodnaviridae ( 50%) and diatom infecting ssRNA viruses ( 38%), Márcio Silva de Souza, becoming more significant as chlorophyll a increased. A genomic and phylogenetic Fundação Universidade Federal do characterization allowed the identification of a new viral lineage within the Myoviridae Rio Grande, Brazil family. -
Pioneering Soil Viromics to Elucidate Viral Impacts on Soil Ecosystem Services
Pioneering Soil Viromics to Elucidate Viral Impacts on Soil Ecosystem Services DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Gareth Trubl Graduate Program in Microbiology The Ohio State University 2018 Dissertation Committee: Virginia Rich, Advisor Matthew Sullivan, Co-Advisor Kelly Wrighton Matthew Anderson Copyrighted by Gareth Trubl 2018 Abstract Permafrost contains 30–50% of global soil carbon (C) and is rapidly thawing. While the fate of this C is unknown, it will be shaped in part by microbes and their associated viruses, which modulate microbial activities via mortality and metabolic control. To date, viral research in soils has been outpaced by that in aquatic environments due to the technical challenges of accessing soil viruses, compounded by the dramatic physicochemical heterogeneity in soils. The Stordalen Mire long-term ecological field site in Arctic Sweden encompasses a mosaic of natural permafrost thaw stages, and has been well characterized biogeochemically and microbiologically, making it an ideal site to characterize the soil virosphere and its potential impacts on the C cycle. A viral resuspension protocol was developed to generate quantitatively- amplified dsDNA viromes. The protocol yielded ~108 virus-like particles (VLPs) g−1 of soil across three thaw-stage habitats, and seven resulting viromes yielded 53 vOTUs. Viral-specific bioinformatics methods were used to recover viral populations, define their gene content, connect them to other related viruses (globally) and potential hosts (locally). Only 15% of these vOTUs had genetic similarity to publicly available viruses in the RefSeq database, and ∼30% of the genes could be annotated, supporting the concept of soils as reservoirs of substantial undescribed viral genetic diversity. -
Characterization and Genomic Analyses of Two Newly Isolated
View metadata, citation and similar papers at core.ac.uk brought to you by CORE www.nature.com/scientificreportsprovided by Lirias OPEN Characterization and genomic analyses of two newly isolated Morganella phages define distant Received: 07 November 2016 Accepted: 09 March 2017 members among Tevenvirinae and Published: 07 April 2017 Autographivirinae subfamilies Hugo Oliveira1,*, Graça Pinto1,*, Ana Oliveira1, Jean-Paul Noben2, Hanne Hendrix3, Rob Lavigne3, Małgorzata Łobocka4,5, Andrew M. Kropinski6 & Joana Azeredo1 Morganella morganii is a common but frequent neglected environmental opportunistic pathogen which can cause deadly nosocomial infections. The increased number of multidrug-resistant M. morganii isolates motivates the search for alternative and effective antibacterials. We have isolated two novel obligatorily lytic M. morganii bacteriophages (vB_MmoM_MP1, vB_MmoP_MP2) and characterized them with respect to specificity, morphology, genome organization and phylogenetic relationships. MP1’s dsDNA genome consists of 163,095 bp and encodes 271 proteins, exhibiting low DNA (<40%) and protein (<70%) homology to other members of the Tevenvirinae. Its unique property is a >10 kb chromosomal inversion that encompass the baseplate assembly and head outer capsid synthesis genes when compared to other T-even bacteriophages. MP2 has a dsDNA molecule with 39,394 bp and encodes 55 proteins, presenting significant genomic (70%) and proteomic identity (86%) but only to Morganella bacteriophage MmP1. MP1 and MP2 are then novel members of Tevenvirinae and Autographivirinae, respectively, but differ significantly from other tailed bacteriophages of these subfamilies to warrant proposing new genera. Both bacteriophages together could propagate in 23 of 27 M. morganii clinical isolates of different origin and antibiotic resistance profiles, making them suitable for further studies on a development of bacteriophage cocktail for potential therapeutic applications. -
Theranostics Self-Accelerating H2O2-Responsive Plasmonic
Theranostics 2020, Vol. 10, Issue 19 8691 Ivyspring International Publisher Theranostics 2020; 10(19): 8691-8704. doi: 10.7150/thno.45392 Research Paper Self-accelerating H2O2-responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors Yao Tang1, Yuejia Ji1, Chenglin Yi2, Di Cheng1, Bin Wang1, Yun Fu1, Yufang Xu1, Xuhong Qian1, Yahya E. Choonara3, Viness Pillay3, Weiping Zhu1, Yunen Liu4 and Zhihong Nie2 1. State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. 2. State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China. 3. Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown 2193 Johannesburg, South Africa. 4. Department of Emergency Medicine, the General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Trauma PLA, Shenyang l10016, China. Corresponding author: E-mails: [email protected] (Z. Nie); [email protected] (Y. Liu); [email protected] (W. Zhu). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2020.02.27; Accepted: 2020.06.17; Published: 2020.07.09 Abstract Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. -
TESIS DOCTORAL Estudio Metagenómico De La Comunidad De
TESIS DOCTORAL Estudio metagenómico de la comunidad de virus y de su interacción con la microbiota en la cavidad bucal humana Marcos Parras Moltó Madrid, 2019 Estudio metagenómico de la comunidad de virus y de su interacción con la microbiota en la cavidad bucal humana Memoria presentada por Marcos Parras Moltó para optar al título de Doctor por la Universidad Autónoma de Madrid Esta Tesis se ha realizado en el Centro de Biología Molecular Severo Ochoa bajo la supervisión del Tutor y Director Alberto López Bueno, en el Programa de Doctorado en Biociencias Moleculares (RD 99/2011) Universidad Autónoma de Madrid Facultad de Ciencias Departamento de Biología Molecular Centro de Biología Molecular Severo Ochoa (CBMSO) Madrid, 2019 El Dr. Alberto López Bueno, Profesor Contratado Doctor en el Departamento de Biología Molecular de la Universidad Autónoma de Madrid (UAM) e investigador en el Centro de Biología Molecular Severo Ochoa (CBMSO): CERTIFICA: Haber dirigido y supervisado la Tesis Doctoral titulada "Estudio metagenómico de la comunidad de virus y de su interacción con la microbiota en la cavidad bucal humana” realizada por D. Marcos Parras Moltó, en el Programa de Doctorado en Biociencias Moleculares de la Universidad Autónoma de Madrid, por lo que autoriza la presentación de la misma. Madrid, a 23 de Abril de 2019, Alberto López Bueno La presente tesis doctoral ha sido posible gracias a la concesión de una “Ayuda para Contratos Predoctorales para la Formación de Doctores” convocatoria de 2013 (BES-2013-064773) asociada al proyecto SAF2012-38421 del Ministerio de Economía y Competitividad. Durante esta tesis se realizó una estancia de dos meses en el laboratorio del Catedrático Francisco Rodríguez Valera, director de grupo de investigación: Evolutionary Genomics Group de la Universidad Miguel Hernández de Elche (San Juan de Alicante), gracias a una “Ayuda a la Movilidad Predoctoral para la Realización de Estancias Breves en Centros de I+D” convocatoria de 2015 (EEBB-I-16-11876) concedida por el Ministerio de Economía y Competitividad. -
Genome Sequence Analysis of Cronobacter Phage PF-CE2 and Proposal of a New Species in the Escherichia Virus RB16 Genus
Genome Sequence Analysis of Cronobacter Phage PF-CE2 and Proposal of a New Species in the Escherichia Virus RB16 Genus Mengshi Xiao Ocean University of China Xinmiao Ren Ocean University of China Ying Yu Ocean University of China Han Sun Ocean University of China Haijin Mou ( [email protected] ) Ocean University of China https://orcid.org/0000-0003-3667-1562 Xiaodan Fu Ocean University of China Research Article Keywords: Cronobacter sakazakii, Escherichia virus, subsequent heterologous, PF-CE2 glycanase Posted Date: June 21st, 2021 DOI: https://doi.org/10.21203/rs.3.rs-258819/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract The genome of Cronobacter sakazakii M1 phage named PF-CE2 was characterized in this work. And a new species named Cronobacter virus PF-CE2, in the Escherichia virus RB16 genus of the subfamily Tevenvirinae of the family Myoviridae was established. The Gp190 gene of phage PF-CE2 was rst proposed to encode a bacteriophage-borne glycanase, which is capable of degrading fucose-containing exopolysaccharides produced by C. sakazakii M1. Further, the taxonomic status of eight additional phages was modied according to average nucleotide identity analysis. This nding provides a theoretical basis for subsequent heterologous expression of the phage PF-CE2 glycanase and provides an important reference for the preservation and sharing of these phages. Main Text Cronobacter sakazakii are facultative, anaerobic Gram-negative bacteria that exist widely in various foods and raw materials [1, 2]. In recent years, as a new foodborne pathogen, C. -
(12) Patent Application Publication (10) Pub. No.: US 2006/0216288 A1 Chang (43) Pub
US 20060216288A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0216288 A1 Chang (43) Pub. Date: Sep. 28, 2006 (54) COMBINATIONS FOR THE TREATMENT OF Publication Classification CANCER (51) Int. Cl. (75) Inventor: David Chang, Calabasas, CA (US) A 6LX 39/395 (2006.01) A6II 3/55 (2006.01) Correspondence Address: A6II 3 L/4545 (2006.01) SESS is 2-C A61K 31/4439 (2006.01) ONE AMGEN CENTERY DRIVE A6II 3/44 (2006.O1 ) THOUSAND OAKS, CA 91320-1799 (US) (52) U.S. Cl. ................... 424/143.1: 514/352: 514/210.2: (73) Assignee: Amgen Inc., Thousand Oaks, CA 514/318: 514/340; 514/217.04 (21) Appl. No.: 11/386,271 (22) Filed: Mar. 21, 2006 (57) ABSTRACT Related U.S. Application Data This invention is in the field of pharmaceutical agents and (60) Provisional application No. 60/664,381, filed on Mar. specifically relates to compounds, compositions, uses and 22, 2005. methods for treating cancer. Patent Application Publication Sep. 28, 2006 Sheet 1 of 5 US 2006/0216288A1 Figure 1 -- Vehicle X Compound B, 10 mpk 1800 -- Antibody A, 20 ug 1600 Compound B, 10 mpk+ 1400 Antibody A, 20 ug 1200 1000 800 600 p = 0.0003 1/10 1110 1/10 p < 0.0001 v v v v v v V 174. 22 27 32 37 42 47 Time (days) V Antibody A injection Patent Application Publication Sep. 28, 2006 Sheet 2 of 5 US 2006/0216288A1 Figure 2 -- Vehicle 1800 X Compound B, 75 mpk 1600 th- Antibody A, 500 u 1400 dy 9 1200 Compound B, 75 mpk+ Antibody A, 500 ug 1000 800 600 V Antibodyy A, ipp injectionin 400 200 p < 0.0001 st 0.9515 V. -
Ab Komplet 6.07.2018
CONTENTS 1. Welcome addresses 2 2. Introduction 3 3. Acknowledgements 10 4. General information 11 5. Scientific program 16 6. Abstracts – oral presentations 27 7. Abstracts – poster sessions 99 8. Participants 419 1 EMBO Workshop Viruses of Microbes 2018 09 – 13 July 2018 | Wrocław, Poland 1. WELCOME ADDRESSES Welcome to the Viruses of Microbes 2018 EMBO Workshop! We are happy to welcome you to Wrocław for the 5th meeting of the Viruses of Microbes series. This series was launched in the year 2010 in Paris, and was continued in Brussels (2012), Zurich (2014), and Liverpool (2016). This year our meeting is co-organized by two partner institutions: the University of Wrocław and the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences. The conference venue (University of Wrocław, Uniwersytecka 7-10, Building D) is located in the heart of Wrocław, within the old, historic part of the city. This creates an opportunity to experience the over 1000-year history of the city, combined with its current positive energy. The Viruses of Microbes community is constantly growing. More and more researchers are joining it, and they represent more and more countries worldwide. Our goal for this meeting was to create a true global platform for networking and exchanging ideas. We are most happy to welcome representatives of so many countries and continents. To accommodate the diversity and expertise of the scientists and practitioners gathered by VoM2018, the leading theme of this conference is “Biodiversity and Future Application”. With the help of your contribution, this theme was developed into a program covering a wide range of topics with the strongest practical aspect.