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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28549776/methylome-and-transcriptome-profiling-in-myasthenia-gravis-monozygotic-twins
#1
Shimrat Mamrut, Nili Avidan, Frédérique Truffault, Elsebeth Staun-Ram, Tarek Sharshar, Bruno Eymard, Mélinée Frenkian, Jiri Pitha, Marc de Baets, Laurent Servais, Sonia Berrih-Aknin, Ariel Miller
OBJECTIVE: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. METHODS: The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples...
May 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#2
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#3
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#4
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28546563/microbiota-in-t-cell-homeostasis-and-inflammatory-diseases
#5
REVIEW
Naeun Lee, Wan-Uk Kim
The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#6
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537236/-allelic-variants-of-immune-response-genes-in-children-with-infectious-complications-during-the-treatment-of-acute-leukemia
#7
M A Avdonina, I S Abramov, Y I Ammour, T V Nasedkina
Infectious complications that arise during the treatment of children with acute leukemia with chemotherapeutic agents at high doses represent a serious problem in oncohematology. To find genetic conditions that may lead to the development of postchemotherapy infections, the genomes of 12 children with acute leukemia who had severe infectious complications during therapy were examined. At the same time, the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28536352/designing-the-sniper-improving-targeted-human-cytolytic-fusion-proteins-for-anti-cancer-therapy-via-molecular-simulation
#8
REVIEW
Anna Bochicchio, Sandra Jordaan, Valeria Losasso, Shivan Chetty, Rodrigo Casasnovas Perera, Emiliano Ippoliti, Stefan Barth, Paolo Carloni
Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv) specifically binding to e.g., tumor associated antigens (TAAs). After internalization and translocation of the enzyme from endocytosed endosomes, the human enzymes introduced into the cytosol are efficiently inducing apoptosis...
February 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28531117/immunobiology-of-newcastle-disease-virus-and-its-use-for-prophylactic-vaccination-in-poultry-and-as-adjuvant-for-therapeutic-vaccination-in-cancer-patients
#9
REVIEW
Volker Schirrmacher
Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastledisease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#10
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529524/antithyroid-drug-therapy-for-graves-disease-and-implications-for-recurrence
#11
REVIEW
Jia Liu, Jing Fu, Yuan Xu, Guang Wang
Graves' disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28524624/pulmonary-arterial-hypertension-progress-in-understanding-the-disease-and-prioritizing-strategies-for-drug-development
#12
REVIEW
P Ghataorhe, C J Rhodes, L Harbaum, M Attard, J Wharton, M R Wilkins
Pulmonary arterial hypertension (PAH), at one time a largely overlooked disease, is now the subject of intense study in many academic and biotech groups. The availability of new treatments has increased awareness of the condition. This in turn has driven a change in the demographics of PAH, with an increase in the mean age at diagnosis. The diagnosis of PAH in more elderly patients has highlighted the need for careful phenotyping of patients and for further studies to understand how best to manage pulmonary hypertension associated with, for example, left heart disease...
May 19, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28522905/strategies-used-by-helicobacter-pylori-to-establish-persistent-infection
#13
REVIEW
Amin Talebi Bezmin Abadi
Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host's entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522341/systemic-and-ocular-fluid-compounds-as-potential-biomarkers-in-age-related-macular-degeneration
#14
REVIEW
Eveline Kersten, Constantin C Paun, Rosa L Schellevis, Carel B Hoyng, Cécile Delcourt, Imre Lengyel, Tunde Peto, Marius Ueffing, Caroline C W Klaver, Sascha Dammeier, Anneke I den Hollander, Eiko K de Jong
Biomarkers can help unravel mechanisms of disease and identify new targets for therapy. They can also be useful in clinical practice for monitoring disease progression, evaluation of treatment efficacy and risk assessment in multifactorial diseases, such as age-related macular degeneration (AMD). AMD is a highly prevalent progressive retinal disorder for which multiple genetic and environmental risk factors have been described, but the exact etiology is not yet fully understood. Many compounds have been evaluated for their association with AMD...
May 15, 2017: Survey of Ophthalmology
https://www.readbyqxmd.com/read/28515940/nivolumab-induced-autoimmune-diabetes-mellitus-presenting-as-diabetic-ketoacidosis-in-a-patient-with-metastatic-lung-cancer
#15
James Luke Godwin, Shuchie Jaggi, Imali Sirisena, Pankaj Sharda, Ajay D Rao, Ranee Mehra, Colleen Veloski
BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28508256/the-role-of-micronutrients-in-alopecia-areata-a-review
#16
REVIEW
Jordan M Thompson, Mehwish A Mirza, Min Kyung Park, Abrar A Qureshi, Eunyoung Cho
Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune-mediated attack of the hair follicle. As with other immune-mediated diseases, a complex interplay between environment and genetics is thought to lead to the development of AA. Deficiency of micronutrients such as vitamins and minerals may represent a modifiable risk factor associated with development of AA. Given the role of these micronutrients in normal hair follicle development and in immune cell function, a growing number of investigations have sought to determine whether serum levels of these nutrients might differ in AA patients, and whether supplementation of these nutrients might represent a therapeutic option for AA...
May 15, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28507801/the-novel-negative-checkpoint-regulator-vista-is-expressed-in-gastric-carcinoma-and-associated-with-pd-l1-pd-1-a-future-perspective-for-a-combined-gastric-cancer-therapy
#17
Christine Böger, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD-1 is a promising new cancer treatment option, which was efficient in murine tumor models and is currently tested in first phase I studies. Here, we analyzed the VISTA expression in a large and well-characterized gastric cancer (GC) cohort on 464 therapy-naive GC samples and 14 corresponding liver metastases using immunohistochemistry. Staining results were correlated with clinico-pathological characteristics, genetic alterations and survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506464/recruited-monocytes-and-type-2-immunity-promote-lung-regeneration-following-pneumonectomy
#18
Andrew J Lechner, Ian H Driver, Jinwoo Lee, Carmen M Conroy, Abigail Nagle, Richard M Locksley, Jason R Rock
To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes...
May 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28505128/a-proposal-for-a-study-on-treatment-selection-and-lifestyle-recommendations-in-chronic-inflammatory-diseases-a-danish-multidisciplinary-collaboration-on-prognostic-factors-and-personalised-medicine
#19
Vibeke Andersen, Uffe Holmskov, Signe Bek Sørensen, Mohamad Jawhara, Karina W Andersen, Anette Bygum, Lone Hvid, Jakob Grauslund, Jimmi Wied, Henning Glerup, Ulrich Fredberg, Jan Alexander Villadsen, Søren Geill Kjær, Jan Fallingborg, Seyed A G R Moghadd, Torben Knudsen, Jacob Brodersen, Jesper Frøjk, Jens F Dahlerup, Ole Haagen Nielsen, Robin Christensen, Anders Bo Bojesen, Grith Lykke Sorensen, Steffen Thiel, Nils J Færgeman, Ivan Brandslund, Allan Stensballe, Erik Berg Schmidt, Andre Franke, David Ellinghaus, Philip Rosenstiel, Jeroen Raes, Berit Heitmann, Mette Boye, Charlotte Lindgaard Nielsen, Lars Werner, Jens Kjeldsen, Torkell Ellingsen
Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome...
May 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28501851/implementing-liquid-biopsies-into-clinical-decision-making-for-cancer-immunotherapy
#20
REVIEW
Dagmar Quandt, Hans D Zucht, Arno Amann, Anne Wulf-Goldenberg, Carl Borrebaeck, Michael Cannarile, Diether Lambrechts, Herbert Oberacher, James Garrett, Tapan Nayak, Michael Kazinski, Charles Massie, Heidi Schwarzenbach, Michele Maio, Robert Prins, Björn Wendik, Richard Hockett, Daniel Enderle, Mikkel Noerholm, Hans Hendriks, Heinz Zwierzina, Barbara Seliger
During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies...
April 24, 2017: Oncotarget
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