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Genetics and immune therapy

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https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#1
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#2
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29328507/genetics-of-immune-mediated-inflammatory-diseases
#3
REVIEW
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29326244/gene-therapy-comes-of-age
#4
REVIEW
Cynthia E Dunbar, Katherine A High, J Keith Joung, Donald B Kohn, Keiya Ozawa, Michel Sadelain
After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29325489/creating-effective-biocontainment-facilities-and-maintenance-protocols-for-raising-specific-pathogen-free-severe-combined-immunodeficient-scid-pigs
#5
Ellis J Powell, Sara Charley, Adeline N Boettcher, Lisa Varley, Justin Brown, Martine Schroyen, Malavika K Adur, Susan Dekkers, Dean Isaacson, Mary Sauer, Joan Cunnick, N Matthew Ellinwood, Jason W Ross, Jack Cm Dekkers, Christopher K Tuggle
Severe combined immunodeficiency (SCID) is defined by the lack of an adaptive immune system. Mutations causing SCID are found naturally in humans, mice, horses, dogs, and recently in pigs, with the serendipitous discovery of the Iowa State University SCID pigs. As research models, SCID animals are naturally tolerant of xenotransplantation and offer valuable insight into research areas such as regenerative medicine, cancer therapy, as well as immune cell signaling mechanisms. Large-animal biomedical models, particularly pigs, are increasingly essential to advance the efficacy and safety of novel regenerative therapies on human disease...
January 1, 2018: Laboratory Animals
https://www.readbyqxmd.com/read/29324309/the-promising-future-of-ventricular-restraint-therapy-for-the-management-of-end-stage-heart-failure
#6
REVIEW
Muhammad Naveed, Imran Shair Mohammad, Li Xue, Sara Khan, Wang Gang, Yanfang Cao, Yijie Cheng, Xingxing Cui, Chen DingDing, Yu Feng, Wang Zhijie, Zhou Xiaohui
Complicated pathophysiological syndrome associated with irregular functioning of the heart leading to insufficient blood supply to the organs is linked to congestive heart failure (CHF) which is the leading cause of death in developed countries. Numerous factors can add to heart failure (HF) pathogenesis, including myocardial infarction (MI), genetic factors, coronary artery disease (CAD), ischemia or hypertension. Presently, most of the therapies against CHF cause modest symptom relief but incapable of giving significant recovery for long-term survival outcomes...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29321330/glycosyl-phosphatidylinositol-anchored-anti-hiv-env-single-chain-variable-fragments-interfere-with-hiv-1-env-processing-and-viral-infectivity
#7
Anisha Misra, Emile Gleeson, Weiming Wang, Chaobaihui Ye, Paul Zhou, Jason T Kimata
In previous studies, we demonstrated that single-chain variable fragments (scFv) from anti-HIV Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphitidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with infectivity of newly produced virions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29316814/biology-of-the-adrenal-gland-cortex-obviates-effective-use-of-adeno-associated-virus-vectors-to-treat-hereditary-adrenal-disorders
#8
Sandra Markmann, Bishnu P De, Jasmine Reid, Clarisse Jose, Jonathan B Rosenberg, Philip Leopold, Stephen M Kaminsky, Dolan Sondhi, Odelya E Pagovich, Ronald G Crystal
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder occurring in 1:10,000-1:20,000 live births. In >95% of the cases, CAH results from mutations in the CYP21A2 gene, encoding the adrenal steroid enzyme 21-hydroxylase (21OH). Cardinal phenotypic features of CAH include genital ambiguity and sexual precocity, and in severe cases, neonatal salt loss and death. Current standard of care consists of life-long oral steroid replacement to reverse the cortisol deficiency. Although significant advances in the treatment of CAH have been made, the burden of a life-long therapeutic intervention is not ideal for quality of life...
January 9, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29314863/bacterial-derived-neutrophilic-inflammation-drives-lung-remodeling-in-a-mouse-model-of-copd
#9
Bradley W Richmond, Rui-Hong Du, Wei Han, John T Benjamin, Riet van der Meer, Linda Gleaves, Marshall Guo, Austin McKissack, Yongqin Zhang, Dong-Sheng Cheng, Vasiliy V Polosukhin, Timothy S Blackwell
Loss of secretory immunoglobulin A (SIgA) is common in the small airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease pathogenesis. Using mice that lack SIgA in the airways due to genetic deficiency of polymeric immunoglobulin receptor (pIgR-/- mice), we investigated the role of neutrophils in driving the fibrotic small airway wall remodeling and emphysema that develops spontaneously in these mice. By flow cytometry, we found an increase in the percentage of neutrophils among CD45+ cells in the lungs, as well as an increase in total neutrophils, in pIgR-/- mice compared to wild-type (WT) controls...
January 9, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29313952/how-to-consider-rare-genetic-variants-in-personalized-drug-therapy
#10
Volker M Lauschke, Magnus Ingelman-Sundberg
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME)...
January 5, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29313812/pathogenic-commonalities-between-spinal-muscular-atrophy-and-amyotrophic-lateral-sclerosis-converging-roads-to-therapeutic-development
#11
REVIEW
Melissa Bowerman, Lyndsay M Murrray, Frédérique Scamps, Bernard L Schneider, Rashmi Kothary, Cédric Raoul
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motoneuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72)...
December 4, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29298609/interferon-%C3%AE-promotes-neuronal-repair-by-transplanted-neural-stem-cells-in-ischemic-rats
#12
Guilong Zhang, Xiaoyuan Guo, Lukui Chen, Bingqian Li, Bin Gu, Hong Wang, Guojian Wu, Jun Kong, Wanghao Chen, Yongbo Yu
Ischemic stroke represents the leading cause of adult neurological disability, with no effective therapeutic strategy. Stem cell transplantation promises a new promising for treating stroke, via cell replacement and cytokines paracrine. However, due to the effect of hostile immune microenvironment, the survival and differentiation of stem cells is limited in vivo. Furthermore, the delayed inflammatory response to stroke induced secondary neurological injury. IFN-γ as pro-inflammatory cytokine has the potential to protect stem cell population during inflammatory response, as well stimulates neurogenesis of stem cells...
January 3, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29296917/checkpoint-blockade-in-hodgkin-and-non-hodgkin-lymphoma
#13
REVIEW
Reid W Merryman, Philippe Armand, Kyle T Wright, Scott J Rodig
Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284308/fighting-cancer-with-viruses-oncolytic-virus-therapy-in-china
#14
Ding Wei, Jing Xu, Xinyuan Liu, Zhi-Nan Chen, Huijie Bian
Oncolytic virus has the special property with selective infection of tumor cells, leading to oncolysis of cancer cells and minimal toxicity to normal tissues, which is administrated in cancer therapy called oncolytic virotherapy. As a biological agent, oncolytic virus could induce tumor cell lysis, local immunological reaction, and enhance systemic anti-tumor immunity. These immune stimulatory properties of oncolytic virus will provide enormous benefits to override cancer. Nowadays, a great variety of oncolytic viruses including genetically engineered and natural viruses have shown promise in preclinical models and clinical studies...
December 28, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29279259/change-in-gut-microbiota-for-eczema-implications-for-novel-therapeutic-strategies
#15
REVIEW
Y Kang, Y Cai, W Pan
Eczema is one of the most common inflammatory diseases, often constituting a lifelong burden for afflicted individuals. The complex interaction of host genetic and multiple environmental factors contribute to its pathogenesis. A relationship between maladjustment of gut microbiota and eczema has been brought into the light of day in most previous studies. In eczema preclinical models, specific intestinal microbial species have been demonstrated to prohibit or dwindle immune responsiveness, indicating that these strains among commensal gut bacteria may exert either a morbific or phylactic function in eczema progression...
December 23, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29278892/tauopathies-mechanisms-and-therapeutic-strategies
#16
Chen-Chen Tan, Xiao-Yan Zhang, Lan Tan, Jin-Tai Yu
Tauopathies are morphologically, biochemically, and clinically heterogeneous neurodegenerative diseases defined by the accumulation of abnormal tau proteins in the brain. There is no effective method to prevent and reverse the tauopathies, but this gloomy picture has been changed by recent research advances. Evidences from genetic studies, experimental animal models, and molecular and cell biology have shed light on the main mechanisms of the diseases. The development of radiology and biochemistry, especially the development of PET imaging, will provide important biomarkers for the clinical diagnosis and treatment...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29278509/gut-microbiota-and-obesity-implications-for-fecal-microbiota-transplantation-therapy
#17
REVIEW
Yongbo Kang, Yue Cai
Obesity is a major public health issue as it is causally associated with several chronic disorders, including type-2 diabetes, cerebrovascular disease (CVD), and cancer. In the United States and other countries worldwide, the obesity epidemic has drastically impacted the status of health of millions as well as healthcare costs. Aside from poor diet, hygiene, and genetics, there are many other factors thought to play an important role in the emergence of obesity. Nowadays, accumulating evidence is elucidating the relation of dysbiosis of intestinal bacteria with obesity and metabolic disorders...
July 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29275471/oncolytic-virotherapy-and-the-tumor-microenvironment
#18
Sara E Berkey, Steve H Thorne, David L Bartlett
Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using "targeted and armed" viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the immune system-such as cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29259601/preclinical-development-and-production-of-virus-like-particles-as-vaccine-candidates-for-hepatitis-c
#19
REVIEW
Makutiro Ghislain Masavuli, Danushka K Wijesundara, Joseph Torresi, Eric J Gowans, Branka Grubor-Bauk
Hepatitis C Virus (HCV) infects 2% of the world's population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29259248/aav-vector-meditated-expression-of-hla-g-reduces-injury-induced-corneal-vascularization-immune-cell-infiltration-and-fibrosis
#20
Matthew L Hirsch, Laura M Conatser, Sara M Smith, Jacklyn H Salmon, Jerry Wu, Nicholas E Buglak, Rich Davis, Brian C Gilger
Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated...
December 19, 2017: Scientific Reports
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