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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28339063/viral-and-host-factors-associated-with-outcomes-of-hepatitis-c-virus-infection-review
#1
Zehui Yan, Yuming Wang
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338065/prospects-for-combining-targeted-and-conventional-cancer-therapy-with-immunotherapy
#2
REVIEW
Philip Gotwals, Scott Cameron, Daniela Cipolletta, Viviana Cremasco, Adam Crystal, Becker Hewes, Britta Mueller, Sonia Quaratino, Catherine Sabatos-Peyton, Lilli Petruzzelli, Jeffrey A Engelman, Glenn Dranoff
Over the past 25 years, research in cancer therapeutics has largely focused on two distinct lines of enquiry. In one approach, efforts to understand the underlying cell-autonomous, genetic drivers of tumorigenesis have led to the development of clinically important targeted agents that result in profound, but often not durable, tumour responses in genetically defined patient populations. In the second parallel approach, exploration of the mechanisms of protective tumour immunity has provided several therapeutic strategies - most notably the 'immune checkpoint' antibodies that reverse the negative regulators of T cell function - that accomplish durable clinical responses in subsets of patients with various tumour types...
March 24, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28334154/ethical-issues-of-crispr-technology-and-gene-editing-through-the-lens-of-solidarity
#3
John J Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A E Zwart, Ruth Chadwick
Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients...
February 23, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28331526/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#4
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#5
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28327183/modeling-multi-mutation-and-drug-resistance-analysis-of-some-case-studies
#6
Mitra Shojania Feizabadi
BACKGROUND: Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. Different genetic alterations occur when tumor cells divide. Among new generations of tumor cells, some may express intrinsic resistance to a specific chemotherapeutic agent. Also, some tumor cells may carry a gene that can develop resistance induced by the therapeutic drug. The methods by which the therapeutic approaches need to be revised in the occurrence of drug induced resistance is still being explored...
March 21, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28326304/hiv-diagnosis-and-treatment-through-advanced-technologies
#7
REVIEW
Hafiza Fizzah Zulfiqar, Aneeqa Javed, Sumbal, Bakht Afroze, Qurban Ali, Khadija Akbar, Tariq Nadeem, Muhammad Adeel Rana, Zaheer Ahmad Nazar, Idrees Ahmad Nasir, Tayyab Husnain
Human immunodeficiency virus (HIV) is the chief contributor to global burden of disease. In 2010, HIV was the fifth leading cause of disability-adjusted life years in people of all ages and leading cause for people aged 30-44 years. It is classified as a member of the family Retroviridae and genus Lentivirus based on the biological, morphological, and genetic properties. It infects different cells of the immune system, such as CD4+ T cells (T-helper cells), dendritic cells, and macrophages. HIV has two subtypes: HIV-1 and HIV-2...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28325288/retroviral-replicating-vector-delivery-of-mir-pdl1-inhibits-immune-checkpoint-pdl1-and-enhances-immune-responses-in%C3%A2-vitro
#8
Amy H Lin, Christopher G Twitty, Ryan Burnett, Andrew Hofacre, Leah A Mitchell, Fernando Lopez Espinoza, Harry E Gruber, Douglas J Jolly
Tumor cells express a number of immunosuppressive molecules that can suppress anti-tumor immune responses. Efficient delivery of small interfering RNAs to treat a wide range of diseases including cancers remains a challenge. Retroviral replicating vectors (RRV) can be used to stably and selectively introduce genetic material into cancer cells. Here, we designed RRV to express shRNA (RRV-shPDL1) or microRNA30-derived shRNA (RRV-miRPDL1) using Pol II or Pol III promoters to downregulate PDL1 in human cancer cells...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28322583/interplay-between-genetic-and-epigenetic-mechanisms-in-rheumatoid-arthritis
#9
Mojca Frank-Bertoncelj, Kerstin Klein, Steffen Gay
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28320483/human-and-feline-adipose-derived-mesenchymal-stem-cells-have-comparable-phenotype-immunomodulatory-functions-and-transcriptome
#10
Kaitlin C Clark, Fernando A Fierro, Emily Mills Ko, Naomi J Walker, Boaz Arzi, Clifford G Tepper, Heather Dahlenburg, Andrew Cicchetto, Amir Kol, Lyndsey Marsh, William J Murphy, Nasim Fazel, Dori L Borjesson
BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28320417/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#11
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
March 20, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28320170/evaluating-the-association-of-allergies-with-multiple-sclerosis-susceptibility-risk-and-disease-activity-in-a-pediatric-population
#12
Theresa Bourne, Michael Waltz, T C Casper, K Kavak, G Aaen, A Belman, L Benson, M Candee, T Chitnis, J Graves, B Greenberg, M Gorman, Y Harris, L Krupp, T Lotze, S Mar, J Ness, C Olsen, S Roalstad, M Rodriguez, J Rose, J Rubin, T Schreiner, J M Tillema, I Kahn, A Waldman, L Barcellos, E Waubant, B Weinstock-Guttman
BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319174/simultaneous-induction-of-graves-hyperthyroidism-and-graves-ophthalmopathy-by-tshr-genetic-immunization-in-balb-c-mice
#13
Nan Xia, Xiaozhen Ye, Xiaohao Hu, Shiyu Song, Hui Xu, Mengyuan Niu, Hongwei Wang, Jian Wang
BACKGROUND: Graves' disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves' disease (GD) in concert with Graves' Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized...
2017: PloS One
https://www.readbyqxmd.com/read/28314733/genetics-implicate-common-mechanisms-in-autism-and-schizophrenia-synaptic-activity-and-immunity
#14
REVIEW
Xiaoming Liu, Zhengwei Li, Conghai Fan, Dongli Zhang, Jiao Chen
The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk...
March 17, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#15
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#16
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28303495/genetic-landscape-and-classification-of-peripheral-t-cell-lymphomas
#17
REVIEW
Rosalind F Sandell, Rebecca L Boddicker, Andrew L Feldman
PURPOSE OF REVIEW: Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification. RECENT FINDINGS: Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28301970/disclosing-the-parameters-leading-to-high-productivity-of-retroviral-producer-cells-lines-evaluating-random-vs-targeted-integration
#18
Vanessa Sofia Bandeira, Hélio A Tomás, Evren Alici, Manuel J C T Carrondo, Ana Sofia Coroadinha
Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T- and NK- cells to be used in immune-cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using Gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GalV pseudotyped gammaretroviral vector productivity in stable producer cells using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination)...
March 16, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28299457/current-trends-of-human-infections-and-antibiotic-resistance-of-the-genus-shewanella
#19
REVIEW
K Yousfi, S Bekal, V Usongo, A Touati
Shewanella spp. are commonly known as environmental bacteria and are most frequently isolated from aquatic areas. Currently, diseases syndromes and multidrug resistance have increasingly been reported in the genus Shewanella. Some species are associated with various infections, such as skin and soft tissue infections, as well as bacteremia. Generally, these bacteria are opportunistic and mostly affect people with an impaired immune system. This genus is also a probable vehicle and progenitor of antibiotic resistance genes...
March 15, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28296915/genetic-variation-in-the-vitamin-d-pathway-cyp2r1-gene-predicts-sustained-hbeag-seroconversion-in-chronic-hepatitis-b-patients-treated-with-pegylated-interferon-a-multicenter-study
#20
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjareon, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supot Tantipanichtheerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpajit, Yong Poovorawan, Piyawat Komolmit
Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients...
2017: PloS One
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