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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#1
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#2
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28714919/overcoming-oncogenic-mediated-tumor-immunity-in-prostate-cancer
#3
REVIEW
Geoffrey Bryant, Lin Wang, David J Mulholland
Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially responsive to immune-based strategies and that the clinical stage, pathological grade and underlying genetic landscape may be important criteria in identifying tumors that respond to immune therapies...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#4
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28713390/hematopoietic-stem-cell-transplantation-in-an-infant-with-immunodeficiency-centromeric-instability-and-facial-anomaly-syndrome
#5
Katharina L Gössling, Cyrill Schipp, Ute Fischer, Florian Babor, Gerhard Koch, Friedhelm R Schuster, Jutta Dietzel-Dahmen, Dagmar Wieczorek, Arndt Borkhardt, Roland Meisel, Michaela Kuhlen
Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713086/intensifying-approach-to-the-therapy-of-patients-with-constellation-of-the-diseases-chronic-obstructive-pulmonary-disease-and-osteoarthritis
#6
Vyacheslav N Zhdan, Maksim М Potyazhenko, Galina S Khaymenova, Nadezhda N Lyulka, Tatyana V Dubrovinskaya, Igor V Ivanitsky
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of 21st century. About 210 million people all over the world are suffering with COPD, and annually 3 million people die of it. Under the influence of different factors, such as smoking, air prolusion, evaporation of chemicals, poisoning effect of chemical firings, inflammation processes take place in lungs, and if it is prolonged and take place simultaneously with morphological changes in the lungs, it it provide the de4velopment of the systemic inflammation process...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28711137/genomics-biology-and%C3%A2-human-illness-advances-in-the-monogenic-autoinflammatory-diseases
#7
REVIEW
Hirotsugu Oda, Daniel L Kastner
The monogenic autoinflammatory diseases are a group of illnesses with prominent rheumatic manifestations that are characterized by genetically determined recurrent sterile inflammation and are thus inborn errors of innate immunity. Molecular targeted therapies against inflammatory cytokines, such as interleukin 1 and tumor necrosis factor, and intracellular cytokine signaling pathways have proved effective in many cases. Emerging next-generation sequencing technologies have accelerated the identification of previously unreported genes causing autoinflammatory diseases...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28709006/compartmental-hbv-evolution-and-replication-in-liver-and-extrahepatic-sites-after-nucleos-tide-analogue-therapy-in-chronic-hepatitis-b-carriers
#8
Shan Gao, Zhong-Ping Duan, Yu Chen, Frank van der Meer, Samuel S Lee, Carla Osiowy, Guido van Marle, Carla S Coffin
BACKGROUND: Hepatitis B virus (HBV) variants are associated with nucleos/tide analogue (NA) response and liver disease but it is unknown whether NA influences extrahepatic HBV persistence. OBJECTIVES: To investigate HBV replication and genetic evolution in hepatic and extrahepatic sites of chronic hepatitis B (CHB) before and after NA therapy. STUDY DESIGN: A total of 13 paired plasma, peripheral blood mononuclear cells (PBMC), were collected from chronic HBV carriers at baseline and after a median 53 weeks NA therapy as well as liver biopsy (N=7 baseline, N=5 follow-up)...
July 5, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28703313/mesenchymal-stem-cells-a-new-platform-for-targeting-suicide-genes-in-cancer
#9
REVIEW
Rana Moradian Tehrani, Javad Verdi, Mahdi Noureddini, Rasoul Salehi, Reza Salarinia, Meysam Mosalaei, Miganosh Simonian, Behrang Alani, Moosa Rahimi Ghiasi, Mahmoud Reza Jaafari, Hamid Reza Mirzaei, Hamed Mirzaie
One of the important strategies for the treatment of cancer is gene therapy which has the potential to exclusively eradicate malignant cells, without any damage to the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step gene therapy approach, where a suicide gene is directed to tumor cells. The gene encodes an enzyme that expressed intracellularly where it is able to convert a prodrug into cytotoxic metabolites. Various delivery systems have been developed to achieve the appropriate levels of tumor restricted expression of chemotherapeutic drugs...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28700415/the-role-of-monogenic-disease-in-children-with-very-early-onset-inflammatory-bowel-disease
#10
Judith R Kelsen, Robert N Baldassano
PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions...
July 11, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28695412/-basis-for-the-treatment-of-eczematous-diseases-in-otorhinolaryngology
#11
REVIEW
R Fölster-Holst, A Sperl, T Albrecht, L Klimek
According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. In otorhinolaryngology, delayed allergic hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis, auricle and ear canal eczema as well as perioral eczema belong to the most common forms of contact dermatitis in ENT patients...
July 10, 2017: HNO
https://www.readbyqxmd.com/read/28694805/primary-immunodeficiency-diseases-in-highly-consanguineous-populations-from-middle-east-and-north-africa-epidemiology-diagnosis-and-care
#12
REVIEW
Hamoud Al-Mousa, Bandar Al-Saud
Middle East and North Africa region (MENA) populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28693973/rationally-combining-immunotherapies-to-improve-efficacy-of-immune-checkpoint-blockade-in-solid-tumors
#13
REVIEW
Floris Dammeijer, Sai Ping Lau, Casper H J van Eijck, Sjoerd H van der Burg, Joachim G J V Aerts
With the widespread application of immune checkpoint blocking antibodies (ICBs) for the treatment of advanced cancer, immunotherapy has proven to be capable of yielding unparalleled clinical results. However, despite the initial success of ICB-treatment, still a minority of patients experience durable responses to ICB therapy. A plethora of mechanisms underlie ICB resistance ranging from low immunogenicity, inadequate generation or recruitment of tumor-specific T cells or local suppression by stromal cells to acquired genetic alterations leading to immune escape...
June 28, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28685247/vitiligo-focus-on-clinical-aspects-immunopathogenesis-and-therapy
#14
REVIEW
Katia Boniface, Julien Seneschal, Mauro Picardo, Alain Taïeb
Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants...
July 6, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28682226/la-g%C3%A3-n%C3%A3-tique-de-l%C3%A2-h%C3%A3-te-influe-sur-les-%C3%A3-cosyst%C3%A3-mes-microbiens-par-l%C3%A2-interm%C3%A3-diaire-du-syst%C3%A3-me-immunitaire-de-l%C3%A2-h%C3%A3-te
#15
Hela El Kafsy, Guy Gorochov, Martin Larsen
Genetic evolution of multicellular organisms occurred as a response to environmental challenges, in particular competition for nutrients, climatic change, physical and chemical stressors and pathogens. However organism fitness depends on both the efficiency of its defences and its capacities for benefiting from its symbiotic organisms. Indeed microbes not only engender pathogenies, but enable efficient uptake of host non-self biodegradable nutriments. Furthermore, microbes play an important role in the development of host immunity...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28681086/effect-of-low-level-laser-treated-mesenchymal-stem-cells-on-myocardial-infarction
#16
Zaynab H El Gammal, Amr M Zaher, Nagwa El-Badri
Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation...
July 6, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28674983/multiple-sclerosis-basic-and-clinical
#17
Katherine Buzzard, Wing Hei Chan, Trevor Kilpatrick, Simon Murray
Multiple sclerosis (MS) is the most common neurodegenerative disease affecting young adults in our community. It is a complex disease influenced by gender, genetic and environmental factors. MS is a chronic inflammatory disease of the central nervous system caused by aberrant immune activation resulting in damage to myelin sheaths within the brain and spinal cord and axonal loss. The demyelinating insult initially impairs the speed and efficiency of nerve cell function. In the majority of cases, this is followed by an innate endogenous repair response that can restore the myelin sheath and nerve cell function to relatively normal levels...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28671573/histone-deacetylase-inhibitors-as-anticancer-drugs
#18
REVIEW
Tomas Eckschlager, Johana Plch, Marie Stiborova, Jan Hrabeta
Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#19
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28668320/engineering-natural-killer-cells-for-cancer-immunotherapy
#20
REVIEW
Katayoun Rezvani, Rayne Rouce, Enli Liu, Elizabeth Shpall
The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification...
June 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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