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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28917219/reuma-pt-contribution-to-the-knowledge-of-immune-mediated-systemic-rheumatic-diseases
#1
Maria José Santos, Helena Canhão, Ana Filipa Mourão, Filipa Oliveira Ramos, Cristina Ponte, Cátia Duarte, Anabela Barcelos, Fernando Martins, José António Melo Gomes
Patient registries are key instruments aimed at a better understanding of the natural history of diseases, at assessing the effectiveness of therapeutic interventions, as well as identifying rare events or outcomes that are not captured in clinical trials. However, the potential of registries goes far beyond these aspects. For example, registries promote the standardization of clinical practice, can also provide information on domains that are not routinely collected in clinical practice and can support decision-making...
September 14, 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28915150/tics-and-tourette-a-clinical-pathophysiological-and-etiological-review
#2
Russell C Dale
PURPOSE OF REVIEW: Describe developments in the etiological understanding of Tourette syndrome. RECENT FINDINGS: Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors...
September 14, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28914372/the-role-of-gut-microbiota-in-the-pathogenesis-of-rheumatic-diseases
#3
Danli Zhong, Chanyuan Wu, Xiaofeng Zeng, Qian Wang
Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses...
September 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28910969/polymorphisms-of-immunoglobulin-receptors-and-the-effects-on-clinical-outcome-in-cancer-immunotherapy-and-other-immune-diseases-a-general-review
#4
Tomonori Kaifu, Akira Nakamura
Receptors for the Fc domain of immunoglobulins [Fc receptors (FcRs)] are essential for the maintenance of antibody-mediated immune responses. FcRs consist of activating- and inhibitory-type receptors that regulate adequate thresholds for various immune cells. In particular, polymorphisms and/or gene copy-number variations of FcRs for IgG (FcγRs) are closely associated with the development of inflammatory disorders, including autoimmune diseases. Recent evidence has implicated polymorphisms of FcRs in the efficacy of monoclonal antibody (mAb)-mediated therapy...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28904067/whole-genome-sequencing-reveals-breast-cancers-with-mismatch-repair-deficiency
#5
Helen Davies, Sandro Morganella, Colin A Purdie, Se Jin Jang, Elin Borgen, Hege Russnes, Dominik Glodzik, Xueqing Zou, Alain Viari, Andrea L Richardson, Anne-Lise Børresen-Dale, Alastair Thompson, Jorunn E Eyfjord, Gu Kong, Michael R Stratton, Serena Nik-Zainal
Mismatch repair (MMR)-deficient cancers have been discovered to be highly responsive to immune therapies such as PD-1 checkpoint blockade, making their definition in patients, where they may be relatively rare, paramount for treatment decisions. In this study, we utilized patterns of mutagenesis known as mutational signatures, which are imprints of the mutagenic processes associated with MMR deficiency, to identify MMR-deficient breast tumors from a whole-genome sequencing dataset comprising a cohort of 640 patients...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903061/lymphatic-drainage-system-of-the-brain-a-novel-target-for-intervention-of-neurological-diseases
#6
REVIEW
Bao-Liang Sun, Li-Hua Wang, Tuo Yang, Lei-Lei Mao, Jing-Yi Sun, Ming-Feng Yang, Hui Yuan, Robert A Colvin, Xiao-Yi Yang
The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes...
September 10, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28901966/mouse-models-of-inflammatory-bowel-disease-for-investigating-mucosal-immunity-in-the-intestine
#7
Giorgos Bamias, Kristen O Arseneau, Fabio Cominelli
PURPOSE OF REVIEW: Currently several mouse models are considered representative of inflammatory bowel disease (IBD). This review presents recent developments regarding the role of animal models of intestinal inflammation as research tools in IBD. RECENT FINDINGS: Preclinical studies in animal models of intestinal inflammation have generated novel findings in several areas of IBD research. The combination of chemical and genetically engineered models have revealed protective or harmful roles for various components of the innate immune system in response to acute injury and repair mechanisms for the intestinal mucosa...
September 8, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28899854/non-classical-fcgr2c-haplotype-is-associated-with-protection-from-red-blood-cell-allo-immunization-in-sickle-cell-disease
#8
Sanne M Meinderts, Joep W R Sins, Karin Fijnvandraat, Sietse Q Nagelkerke, Judy Geissler, Michael W Tanck, Christine Bruggeman, Bart J Biemond, Anita W Rijneveld, Jean-Louis H Kerkhoffs, Sadaf Pakdaman, Anoosha Habibi, Robin van Bruggen, Taco W Kuijpers, France Pirenne, Timo K van den Berg
Red blood cell (RBC) transfusions are of vital importance in patients with sickle cell disease (SCD). However, a major complication of transfusion therapy is allo-immunization. The low-affinity Fc gamma receptors (FcγRs), expressed on immune cells, are important regulators of antibody responses. Genetic variation in FCGR genes has been associated with various auto- and allo-immune diseases. The aim of this study was to evaluate the association between genetic variation of FCGR and RBC allo-immunization in SCD...
September 12, 2017: Blood
https://www.readbyqxmd.com/read/28895957/atopic-dermatitis-addressing-allergy-infection-itch-and-complementary-therapies
#9
Jusleen Ahluwalia, Dawn Marie Davis, Sharon Jacob, Andrea Waldman, Peter Y Ong, Stuart Cohen, Adam Friedman, Peter Lio, Nathan Jetter, Jeffrey Bienstock, Jennifer LeBovidge, Jonathan Spergel, Luz Fonacier
Atopic dermatitis (AD) is a complex condition that results from the dynamic interplay between genetic predisposition, skin barrier defects, environmental factors, and a dysfunctional immune system. As a result, AD can be complicated by irritant and allergic contact dermatitis and imbalances in the skin microbiome, which can subsequently exacerbate the severity and complicate the course of preexisting atopic disease. Itch is an important symptom of AD, as it plays a large role in the quality of life of patients and their families...
September 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28895849/opening-marrow-niches-in-patients-undergoing-autologous-hematopoietic-stem-cell-gene-therapy
#10
REVIEW
Morton J Cowan, Christopher C Dvorak, Janel Long-Boyle
Successful gene therapy for genetic disorders requires marrow niches to be opened to varying degrees to engraft gene-corrected hematopoietic stem cells (HSC). For example, in severe combined immunodeficiency, relatively limited chimerism is necessary for both T- and B-cell immune reconstitution, whereas for inborn errors of metabolism maximal donor chimerism is the goal. Currently, alkylating chemotherapy is used for this purpose. Significant pharmacokinetic variability exists in drug clearance in children less than 12 years old...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28893280/eradication-of-hiv-1-latent-reservoirs-through-therapeutic-vaccination
#11
REVIEW
Joshua Pankrac, Katja Klein, Jamie F S Mann
Despite the significant success of combination anti-retroviral therapy to reduce HIV viremia and save lives, HIV-1 infection remains a lifelong infection that must be appropriately managed. Advances in the understanding of the HIV infection process and insights from vaccine development in other biomedical fields such as cancer, imaging, and genetic engineering have fueled rapid advancements in HIV cure research. In the last few years, several studies have focused on the development of "Kick and Kill" therapies to reverse HIV latency and kick start viral translational activity...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#12
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28892752/graphene-quantum-dots-suppress-proinflammatory-t-cell-responses-via-autophagy-dependent-induction-of-tolerogenic-dendritic-cells
#13
Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells...
August 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/28891129/gastric-cancer-basic-aspects
#14
REVIEW
Silvia Molina-Castro, Joana Pereira-Marques, Ceu Figueiredo, Jose C Machado, Christine Varon
Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy...
September 2017: Helicobacter
https://www.readbyqxmd.com/read/28890729/clinical-application-of-a-cancer-genomic-profiling-assay-to-guide-precision-medicine-decisions
#15
Cheryl Eifert, Angeliki Pantazi, Ruobai Sun, Jia Xu, Pablo Cingolani, Joerg Heyer, Meaghan Russell, Maria Lvova, Jennifer Ring, Julie Y Tse, Stephen Lyle, Alexei Protopopov
AIM: Develop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies. MATERIALS & METHODS: The performance of the CANCERPLEX(®) assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines. RESULTS: The maximum sensitivity of the assay is 99.5% and its accuracy is virtually 100% for detecting somatic alterations with an allele fraction of as low as 10%...
July 2017: Personalized Medicine
https://www.readbyqxmd.com/read/28889481/a-review-of-the-biologic-and-clinical-significance-of-genetic-mutations-in-angioimmunoblastic-t-cell-lymphoma
#16
REVIEW
Kota Fukumoto, Tran B Nguyen, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients...
September 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28889387/orthotopic-mouse-models-of-urothelial-cancer
#17
Wolfgang Jäger, Igor Moskalev, Peter Raven, Akihiro Goriki, Samir Bidnur, Peter C Black
Orthotopic mouse models of urothelial cancer are essential for testing novel therapies and molecular manipulations of cell lines in vivo. These models are either established by orthotopic inoculation of human (xenograft models) or murine tumor cells (syngeneic models) in immunocompromised or immune competent mice. Current techniques rely on inoculation by intravesical instillation or direct injection into the bladder wall. Alternative models include the induction of murine bladder tumors by chemical carcinogens (BBN) or genetic engineering (GEM)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28888210/antibody-cytokine-fusion-proteins-for-improving-efficacy-and-safety-of-cancer-therapy
#18
REVIEW
Zahra Valedkarimi, Hadi Nasiri, Leili Aghebati-Maleki, Jafar Majidi
Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules...
September 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28882929/rhob-blockade-selectively-inhibits-autoantibody-production-in-autoimmune-models-of-rheumatoid-arthritis-and-lupus
#19
Laura Mandik-Nayak, James B DuHadaway, Jennifer Mulgrew, Elizabeth Pigott, Kaylend Manley, Summer Sedano, George C Prendergast, Lisa D Laury-Kleintop
During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells favoring the production of pathogenic versus non-pathogenic autoantibodies. However, there is limited knowledge concerning how this pivotal step occurs. Here we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical model of inflammatory arthritis...
September 7, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28881745/whole-tumor-rna-sequencing-and-deconvolution-reveal-a-clinically-prognostic-pten-pi3k-regulated-glioma-transcriptional-signature
#20
Yuan Pan, Erin C Bush, Joseph A Toonen, Yu Ma, Anne C Solga, Peter A Sims, David H Gutmann
The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue...
August 8, 2017: Oncotarget
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