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Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?
International Journal of Molecular Sciences Review Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level? Rola El Sayed 1 , Yolla Haibe 2, Ghid Amhaz 2, Youssef Bouferraa 2 and Ali Shamseddine 2,* 1 Global Health Institute, American University of Beirut, Beirut 11-0236, Lebanon; [email protected] 2 Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, Lebanon; [email protected] (Y.H.); [email protected] (G.A.); [email protected] (Y.B.) * Correspondence: [email protected]; Tel.: +961-1-350-000 (ext. 5390) Abstract: Immunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors de- veloping innate or acquired resistance to checkpoint inhibition. Certain “hot” or “immune-sensitive” tumors become “cold” or “immune-resistant”, with resultant tumor growth and disease progres- sion. Multiple factors are at play both at the cellular and host levels. The tumor microenvironment (TME) contributes the most to immune-resistance, with nutrient deficiency, hypoxia, acidity and different secreted inflammatory markers, all contributing to modulation of immune-metabolism and reprogramming of immune cells towards pro- or anti-inflammatory phenotypes. Both the tumor and surrounding immune cells require high amounts of glucose, amino acids and fatty acids to fulfill their energy demands. Thus, both compete over one pool of nutrients that falls short on needs, obliging cells to resort to alternative adaptive metabolic mechanisms that take part in shaping their inflammatory phenotypes. Aerobic or anaerobic glycolysis, oxidative phosphorylation, tryptophan catabolism, glutaminolysis, fatty acid synthesis or fatty acid oxidation, etc. -
Modulating the Immune System Through Nanotechnology
Modulating the immune system through nanotechnology Tamara G. Dacobaa,b*, Ana Oliveraa,b*, Dolores Torresb, José Crecente- Campoa,b#, María José Alonsoa,b## aCenter for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain. bDepartment of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus Vida, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain. *These authors contributed equally to this work. #Corresponding author e-mail address: [email protected] ##Corresponding author e-mail address: [email protected] 1 Abstract Nowadays, nanotechnology-based modulation of the immune system is presented as a cutting-edge strategy, which may lead to significant improvements in the treatment of severe diseases. In particular, efforts have been focused on the development of nanotechnology- based vaccines, which could be used for immunization or generation of tolerance. In this review, we highlight how different immune responses can be elicited by tuning nanosystems properties. In addition, we discuss specific formulation approaches designed for the development of anti-infectious and anti-autoimmune vaccines, as well as those intended to prevent the formation of antibodies against biologicals. Graphical abstract Keywords: nanotechnology; immune system; tolerance; stimulation; autoimmune disease; vaccine Highlights - Nanocarriers can be designed to target specific immune cells - Nanovaccines may help fighting diseases that are elusive to traditional vaccines - Nanocarriers can bias the immune response from humoral to cellular - Autoimmune disease treatments can be improved with nanotechnology-based approaches - The use of nanocarriers may help to avoid ADAs formation against biotherapeutics 2 1. Introduction The modulation of the immune system is the base of new and promising therapies for some of the most prevalent and/or severe diseases of our time, such as cancer, HIV, and diabetes. -
List of Union Reference Dates A
Active substance name (INN) EU DLP BfArM / BAH DLP yearly PSUR 6-month-PSUR yearly PSUR bis DLP (List of Union PSUR Submission Reference Dates and Frequency (List of Union Frequency of Reference Dates and submission of Periodic Frequency of submission of Safety Update Reports, Periodic Safety Update 30 Nov. 2012) Reports, 30 Nov. -
An Active Immunotherapy Combined with First-Line Weekly Paclitaxel In
An active immunotherapy combined with first-line weekly paclitaxel in metastatic breast cancer: first results of IMP321 (LAG-3Ig) as an antigen presenting cell activator in the AIPAC phase IIb trial Frédéric Triebel, CSO/CMO Precision: Breast Cancer March 7-8, 2017 Boston, MA. 1 ASX:PRR; NASDAQ:PBMD Notice: Forward Looking Statements The purpose of the presentation is to provide an update of the business of Prima BioMed Ltd ACN 009 237 889 (ASX:PRR; NASDAQ:PBMD). These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Accordingly, these slides and the information they contain should be read in conjunction with past and future announcements made by Prima BioMed and should not be relied upon as an independent source of information. Please refer to the Company's website and/or the Company’s filings to the ASX and SEC for further information. The views expressed in this presentation contain information derived from publicly available sources that have not been independently verified. No representation or warranty is made as to the accuracy, completeness or reliability of the information. Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside Prima BioMed’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this presentation include known and unknown risks. -
In February 2013, Glaxosmithkline (GSK) Announced a Commitment To
In February 2013, GlaxoSmithKline (GSK) announced a commitment to further clinical transparency through the public disclosure of GSK Clinical Study Reports (CSRs) on the GSK Clinical Study Register. The following guiding principles have been applied to the disclosure: Information will be excluded in order to protect the privacy of patients and all named persons associated with the study Patient data listings will be completely removed* to protect patient privacy. Anonymized data from each patient may be made available subject to an approved research proposal. For further information please see the Patient Level Data section of the GSK Clincal Study Register. Aggregate data will be included; with any direct reference to individual patients excluded *Complete removal of patient data listings may mean that page numbers are no longer consecutively numbered CONFIDENTIAL GM2004/00056/00GM2004/00056/00 SAM40040SAM40040 The GlaxoSmithKline group of companies A twenty-four week, randomised, double-dummy, double-blind, parallel group study to compare the occurrence of exacerbations between SERETIDE DISKUS 50/250µg 1 inhalation bd and formoterol/budesonide Breath-Actuated Dry Powder Inhaler 4.5/160µg 2 inhalations bd in subjects with moderate to severe asthma. Clinical Study Report for Study SAM40040 (Development Phase IV) Document Number: GM2004/00056/00 Compound Number: CCI18781/ GR33343 Investigational Product: SERETIDE Generic Drug Name: salmeterol/fluticasone propionate combination Indication Studied: Asthma Initiation Date: 26 Nov 2001 Completion Date: 13 Jan 2003 Early Termination Date: N/A Date of Report: August 2004 Sponsor Signatory: (and Medical Officer) Vice President European Clinical Respiratory Medicines Development Centre This study was performed in compliance with Good Clinical Practices including the archiving of essential documents. -
Moderní Antihistaminika V Léčbě Alergie – Současné Trendy V Symptomatické Terapii Alergických Onemocnění
100 Hlavní téma Moderní antihistaminika v léčbě alergie – současné trendy v symptomatické terapii alergických onemocnění Jaroslava Braunová, Mojmír Račanský Oddělení alergologie a klinické imunologie FNOL, Ústav imunologie UP Olomouc Alergická onemocnění jsou problémem současné medicíny. Nejde o pouhé projevy sezónní rýmy, s nimiž se do jisté míry setkal snad každý, ale také o závažné stavy, jako je anafylakticky šok a exacerbace bronchiálního astmatu. Nezanedbatelnou kapitolu tvoří problematika různých kožních projevů přecitlivělosti. Vždy však působí postiženému značné nepříjemnosti. Spolu s rostoucí incidencí těchto alergolo- gických diagnóz pochopitelně stoupá i poptávka po jejich účinné léčbě. Za kauzální léčbu považujeme alergenovou imunoterapii (AIT). Ta však není indikována pro všechny pacienty a všechny alergologické diagnózy. Vyžaduje vysokou compliance ze strany nemocného, přesné určení spouštěče alergické reakce u daného pacienta a existenci dostupného standardizovaného alergenu. Symptomatická terapie antihistaminiky představuje jednu ze zásadních možností ovlivnění rozvoje alergické reakce přímo na periferním histaminovém receptoru H1. Klíčová slova: alergie, symptomatická terapie, antihistaminika, alergický zánět. Modern antihistamines in treating allergies: current trends in symptomatic therapy of allergic conditions Allergic diseases are a serious problem in modern medicine. It is not only a question of pollinosis, but also of other allergic diseases such as bronchial asthma, atopic dermatitis, urticaria, angioedema or -
Molecular Advances in Pediatric Low-Grade Gliomas As a Model
Published OnlineFirst July 23, 2013; DOI: 10.1158/1078-0432.CCR-13-0662 Clinical Cancer CCR New Strategies Research New Strategies in Pediatric Gliomas: Molecular Advances in Pediatric Low-Grade Gliomas as a Model Eric Raabe1, Mark W. Kieran2, and Kenneth J. Cohen1 Abstract Pediatric low-grade gliomas (pLGG) account for more brain tumors in children than any other histologic subtype. While surgery, chemotherapy and radiation remain the mainstay of upfront treatment, recent advances in molecular interrogation of pLGG have shown a small number of recurring genetic mutations in these tumors that might be exploited therapeutically. Notable findings include abnormalities in the RAS/ MAP kinase pathway such as NF-1 loss or BRAF activation and mTOR activation. Recent identification of activating re-arrangements in c-MYB and MYBL1 in pediatric diffuse astrocytoma also provide candidates for therapeutic intervention. Targeting these molecularly identified pathways may allow for improved outcomes for patients as pediatric oncology moves into the era of biology-driven medicine. Clin Cancer Res; 19(17); 4553–8. Ó2013 AACR. Disclosure of Potential Conflicts of Interest M.W. Kieran is a consultant/advisory board member of Boehringer-Ingelheim, Incyte, Merck, Novartis, and Sanofi. No potential conflicts of interest were disclosed by the other authors. CME Staff Planners' Disclosures The members of the planning committee have no real or apparent conflict of interest to disclose. Learning Objective(s) Upon completion of this activity, the participant should have a better understanding of the molecular pathways that are active in pediatric low-grade gliomas and the biologic rationale underlying novel therapeutic strategies for children with these tumors. -
Obecná Alergologie, Alergie - Pojem
12.02.2017 Obecná alergologie, Alergie - pojem (alergie, „nealergie“, alergeny, léčba neadekvátní reakce imunitního systému typu zánětu alergií a alergické stavy) na jinak neškodnou cizorodou látku (alergen), má s přihlédnutím k dětskému věku objektivní i subjektivní složku: - objektivně jsou známky poškození některých orgánů (sliznice nosu, spojivky, kůže, bronchy, ..) - subjektivně jsou nepříjemně vnímané poruchy funkce takto postižených orgánů Alergik = pacient s klinickými příznaky reakce přecitlivosti navozené imunolog.mechanismy. MUDr.Jiří NEVRLKA Poliklinika Zahradníkova 2/8 BRNO ambulance pro alergologii a klinickou imunologii Alergie pozitivita v testech na alergeny !! Alergie - pojem Alergie - pojem imunopatologické reakce „nepravé alergie a pseudoalergie“ časný typ Reakce I.typu - mediovaná protilátkami IgE, • IgE non dependentní alergie (pozdní typ) - vyjádřena u osob s atopickou reaktivitou Alergolog - reakce nezprostředkovaná IgE, ale Ag-specif.T-lymfocyty - nejčastější typ alergie (alergie v užším smyslu) navazující na IgE mechanismus .. např. potraviny, alergie na lepek - inhalační alergie, alergie hmyzí jed, anafylaxe, (atopická dermatitida).. dominantní mechanismus .. např. kontaktní alergeny, léky, celiakie Reakce II.typu - mediovaná non IgE protilátkami - cytotoxické protilátky, např. transfuzní reakce x blokující protilátky, např. • Zkřížená reaktivita: myastenia gravis x stimulační protilátky, např. Graves-Basedowova choroba - reakce na antigeny strukturálně podobné reálnému alergenu Reakce III.typu – mediovaná -
Anti-Depressant-Like Effect of Curculigoside Isolated from Curculigo Orchioides Gaertn Root
Wang et al Tropical Journal of Pharmaceutical Research October 2016; 15 (10): 2165-2172 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v15i10.15 Original Research Article Anti-depressant-like effect of curculigoside isolated from Curculigo orchioides Gaertn root Jing Wang1*, Xiao-Li Zhao2 and Lan Gao3 1Neurology Department, Shanxi Provincial People’s Hospital, Taiyuan 030012, 2Neurology Department, The First Hospital of Xi’an City, Xi’an 710002, Shanxi, 3Beijing Huilongguan Hospital, Beijing 100096, China *For correspondence: Email: [email protected]; Tel/Fax: +86-0351-4960171 Received: 5 March 2016 Revised accepted: 9 September 2016 Abstract Purpose: To investigate the anti-depressant-like activity of curculigoside from Curculigo orchioides Gaertn and its underlying mechanism(s). Methods: Antidepressant-like activity was determined in mice through forced swimming test (FST), tail suspending test (TST), and open field test (OFT). Mechanism of action was investigated by measuring levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) in chronic mild stress (CMS) rats using high-performance liquid chromatography-electron capture detector (HPLC-ECD). Western blotting was used to investigate the effect of curculigoside on the expression of brain-derived neurotrophic factor (BDNF) protein in rats. Results: In FST and TST, treatment of mice with curculigoside (10, 20, 40 mg/kg, p.o.) significantly reduced immobility time, which was, however, unaffected by locomotor activity when assessed in the OFT. The treatment led to significant increases in DA, NE and 5-HT, and up-regulation of BDNF protein expression in the hippocampus of the CMS rats. -
Immunosuppressant Ingredients, Immunostimulant Ingredients
Immunosuppressant Ingredients, Immunostimulant Ingredients Immunosuppressant Ingredients Immunosuppressant ingredients are chemical and medicinal agents used for the suppression and regulation of immune responses. Pharmacologically speaking, these agents have varied mecha- nisms of action, such as regulation of inflammatory gene expression, suppression of lymphocyte signal transduction, neutralization of cytokine activity, and inhibition lymphocyte proliferation by agent-induced cytotoxicity. Common agents include glucocorticoids, alkylating agents, metabolic antagonists, calcineurin inhibitors, T-cell suppressive agents, and cytokine inhibitors. 5-Aminosalicylic Acid 25g / 500g [A0317] 5-Aminosalicylic acid (5-ASA) is commonly used as a gastrointestinal anti-inflammatory agent. It has in vitro and in vivo pharmacologic effects that decrease leukotriene production, scavenge for free radicals, and inhibits leukocyte chemotaxis et al. Azathioprine 5g / 25g [A2069] Azathioprine is a prodrug of 6-mercaptopurine (6-MP), which inhibits the synthesis of purine ribonucleotides and DNA/RNA. Cyclophosphamide Monohydrate 5g / 25g [C2236] Cyclophosphamide is an antitumor alkylating reagent involved in the cross-linking of tumor cell DNA. Cyclosporin A 100mg / 1g [C2408] Cyclosporin A is a cyclic polypeptide immunosuppressant. It inhibits the activity of T-lymphocytes, and the phosphatase activity of calcineurin. Dimethyl Fumarate 25g / 500g [F0069] Dimethyl fumarate has neuroprotective and immunomodulating effects. Fingolimod Hydrochloride 200mg / 1g [F1018] Fingolimod (FTY720) is an immunomodulatory agent. It is an agonist at sphingosine 1-phosphate (S1P) receptors, and inhibits lymphocyte emigra- tion from lymphoid organs. Iguratimod 25mg / 250mg [I0945] Iguratimod (T-614) is an agent with anti-inflammatory and immunomodulatory activities. Its activity functions by the inhibiting production of immune globulin and inflammatory cytokines such as TNF-α, IL-1β and IL-6, and used as a disease modifying anti-rheumatic drug (DMARD). -
Azelastine Hydrochloride
568 Antihistamines been withdrawn from the market in most countries because of the Preparations treatment of non-allergic rhinitis in adults and children risk of adverse effects. USP 31: Azatadine Maleate Tablets. aged 12 years and over. The dose is 2 sprays into each Astemizole has been given in an oral dose of 10 mg once daily, Proprietary Preparations (details are given in Part 3) nostril twice daily. In the treatment of conjunctivitis, or 5 mg daily in children aged 6 to 12 years. These doses must Austral.: Zadine; Canad.: Optimine; Hong Kong: Zadine†; Malaysia: azelastine is licensed in the UK for the treatment of not be exceeded because of the risk of cardiac arrhythmias with Zadine†; Mex.: Idulamine†; NZ: Zadine†; Singapore: Zadine†; Spain: seasonal allergic conjunctivitis in adults and children higher doses. Lergocil. aged 4 years and over and for the treatment of perenni- The active metabolite of astemizole, tecastemizole (norastemi- Multi-ingredient: Braz.: Cedrin; Canad.: Trinalin; Mex.: Trinalin†; al allergic conjunctivitis in adults and children aged 12 zole) has been investigated for the treatment of allergic rhinitis. Spain: Atiramin; Idulanex; USA: Rynatan†; Trinalin†. years and over. In the USA, it is licensed for the treat- Preparations ment of allergic conjunctivitis in adults and children USP 31: Astemizole Tablets. aged 3 years and over. Regardless of the age and indi- Azelastine Hydrochloride cation, a 0.05% solution is instilled into each eye twice Proprietary Preparations (details are given in Part 3) (BANM, USAN, rINNM) daily; this may be increased to four times daily in se- Arg.: Alermizol†; Astezol†; Cezane†; Mudantil†; Cz.: Hismanal†; Gr.: Mibiron†; Tulipe-R†; Tyrenol†; Waruzol†; India: Astizole; Stemiz†; Mex.: A-5610 (azelastine or azelastine hydrochloride); Atselastiinihy- vere conditions. -
Feline Infectious Peritonitis Treatment
Addie: Feline infectious peritonitis treatment www.catvirus.com Feline infectious peritonitis (FIP) treatment Diane D. Addie PhD, BVMS, MRCVS www.catvirus.com 22 Feb 2018 IMPORTANT NOTICE Prior to even considering treatment for feline infectious peritonitis (FIP) you absolutely MUST ensure that the cat really does have FIP. At time of writing, FIP treatment is mainly immunosuppressive and immunosuppression of a cat with an infection other than FIP will kill the cat. Do a FCoV antibody test: provided the test is sensitive enough, a negative result will rule out FIP. Addie et al, 2015 You can find out which FCoV antibody tests are recommended (and which ones are useless) at www.catvirus.com/FCoVantibody.htm. A major differential of FIP is toxoplasmosis: run a toxoplasma antibody test in at-risk cats, for example those with access to outdoors or who are fed butcher meat. However a positive FCoV antibody test does NOT confirm FIP. PREVENTION IS BETTER THAN CURE It is my hope that by the time you have listened to this webinar you will have understood the complexity of the disease that is FIP. In many other diseases, the destruction of the invading pathogen, by antivirals or antibiotics, results in the cure of the patient, but FIP is a disease involving the very complex immune response of the cat. If we don’t completely understand the pathogenesis of FIP how can we hope to fix it? And the disease isn’t a fixed target, it changes, the pathology changes throughout the infection. FIP is slightly different in every individual so treatment needs to be tailored to that individual patient: it is not a case of one size fits all.