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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28812721/predicting-evolution
#1
Michael Lässig, Ville Mustonen, Aleksandra M Walczak
The face of evolutionary biology is changing: from reconstructing and analysing the past to predicting future evolutionary processes. Recent developments include prediction of reproducible patterns in parallel evolution experiments, forecasting the future of individual populations using data from their past, and controlled manipulation of evolutionary dynamics. Here we undertake a synthesis of central concepts for evolutionary predictions, based on examples of microbial and viral systems, cancer cell populations, and immune receptor repertoires...
February 21, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28811194/immunogenetic-studies-of-the-hepatitis-c-virus-infection-in-an-era-of-pan-genotype-antiviral-therapies-effective-treatment-is-coming
#2
Joel Henrique Ellwanger, Valéria de Lima Kaminski, Jacqueline Maria Valverde-Villegas, Daniel Simon, Vagner Ricardo Lunge, José Artur Bogo Chies
What are the factors that influence human hepatitis C virus (HCV) infection, hepatitis status establishment, and disease progression? Firstly, one has to consider the genetic background of the host and HCV genotypes. The immunogenetic host profile will reflect how each infected individual deals with infection. Secondly, there are environmental factors that drive susceptibility or resistance to certain viral strains. These will dictate (I) the susceptibility to infection; (II) whether or not an infected person will promote viral clearance; (III) the immune response and the response profile to therapy; and (IV) whether and how long it would take to the development of HCV-associated diseases, as well as their severity...
August 12, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28810029/celiac-disease-and-nonceliac-gluten-sensitivity-a-review
#3
Maureen M Leonard, Anna Sapone, Carlo Catassi, Alessio Fasano
Importance: The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Observations: Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial)...
August 15, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28806273/the-changing-landscape-of-gene-editing-in-hematopoietic-stem-cells-a-step-towards-cas9-clinical-translation
#4
Daniel P Dever, Matthew H Porteus
PURPOSE OF REVIEW: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#5
REVIEW
Anuradha Ratna, Pranoti Mandrekar
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms...
August 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28805207/periodontal-diseases
#6
REVIEW
Denis F Kinane, Panagiota G Stathopoulou, Panos N Papapanou
Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease...
June 22, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28803390/cancer-clonal-theory-immune-escape-and-their-evolving-roles-in-cancer-multi-agent-therapeutics
#7
REVIEW
Jonathan L Messerschmidt, Prianka Bhattacharya, Gerald L Messerschmidt
PURPOSE OF REVIEW: The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus...
August 12, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28802906/pathways-towards-indolent-b-cell-lymphoma-etiology-and-therapeutic-strategies
#8
REVIEW
Michiel van den Brand, Blanca Scheijen, Corine J Hess, J Han Jm van Krieken, Patricia J T A Groenen
Although patients with indolent B-cell lymphomas have a relatively good survival rate, conventional chemotherapy is not curative. Disease courses are typically characterized by multiple relapses and progressively shorter response duration with subsequent lines of therapy. There has been an explosion of innovative targeted agents in the past years. This review discusses current knowledge on the etiology of indolent B-cell lymphomas with respect to the role of micro-organisms, auto-immune diseases, and deregulated pathways caused by mutations...
August 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#9
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28798244/atypical-haemolytic-uremic-syndrome-ahus-and-membranoproliferative-glomerulonephritis-mpgn-different-diseases-or-a-spectrum-of-complement-mediated-glomerular-diseases
#10
Ghada A Ankawi, William F Clark
Historically, patients with kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway have been grouped into clinical syndromes, C3 glomerulopathy (C3GN/DDD) and thrombotic microangiopathy (TMA), specifically atypical haemolytic uremic syndrome (aHUS). Recent data suggested that these diseases share a common pathophysiology and that patients can transition between glomerulopathies in this spectrum. Histopathologically, the main difference cited is the immunofluorescence (IF) findings, with C3 predominance in C3 glomerulopathy (compared with immunoglobulins and complements in immune complex-mediated membranoproliferative glomerulonephritis (MPGN)) and negative IF in TMA...
August 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28796964/can-minimal-residual-disease-determination-in-acute-myeloid-leukemia-be-used-in-clinical-practice
#11
Marlise R Luskin, Richard M Stone
In acute myeloid leukemia (AML) that is in complete remission, minimal residual disease (MRD) is presumed to be present, though not morphologically evident. Advances in diagnostics now permit the detection and quantification of MRD in AML by several techniques. The level of MRD after induction and consolidation therapy correlates with disease sensitivity to chemotherapy and has greater power to predict long-term survival than patient and disease characteristics that are available at diagnosis, including genetic information...
August 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28793015/virulence-factors-and-genetic-variability-of-vaginal-candida-albicans-isolates-from-hiv-infected-women-in-the-post-highly-active-antiretroviral-era
#12
Pâmela Cristina Mastellaro Delvas Zanni, Patrícia de Souza Bonfim-Mendonça, Melyssa Negri, Sandra Sayuri Nakamura, Lucélia Donatti, Terezinha Inez Estivalet Svidzinski, Márcia Edilaine Lopes Consolaro
Vulvovaginal candidiasis (VVC) in HIV-infected (HIV+) women is a serious public health problem. However, little is known about the virulence mechanisms of vaginal Candida albicans from HIV+ women in the post-highly active antiretroviral therapy (HAART) era. Here, we report a comparative analysis of the expression of key virulence factors and genetic variability of 26 vaginal C. albicans strains isolated from HIV+ women undergoing HAART and 18 from HIV-uninfected (HIV-) women. In general, we observed that C...
2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28792537/isolation-and-functional-characterization-of-hepatitis-b-virus-specific-t-cell-receptors-as-new-tools-for-experimental-and-clinical-use
#13
Karin Wisskirchen, Kai Metzger, Sophia Schreiber, Theresa Asen, Luise Weigand, Christina Dargel, Klaus Witter, Elisa Kieback, Martin F Sprinzl, Wolfgang Uckert, Matthias Schiemann, Dirk H Busch, Angela M Krackhardt, Ulrike Protzer
T-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricted, hepatitis B virus (HBV)-specific T cells from patients with acute or resolved HBV infection. We isolated 11 envelope- or core-specific TCRs and evaluated them in comprehensive functional analyses. T cells were genetically modified by retroviral transduction to express HBV-specific TCRs...
2017: PloS One
https://www.readbyqxmd.com/read/28792504/common-gene-network-signature-of-different-neurological-disorders-and-their-potential-implications-to-neuroaids
#14
Vidya Sagar, S Pilakka-Kanthikeel, Paola C Martinez, V S R Atluri, M Nair
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28783698/maintenance-of-macrophage-transcriptional-programs-and-intestinal-homeostasis-by-epigenetic-reader-sp140
#15
Stuti Mehta, D Alexander Cronkite, Megha Basavappa, Tahnee L Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A Morrison, Jose D Pagan, Robert M Anthony, Pierre Tonnerre, Georg M Lauer, James C Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J Xavier, Terry K Means, Kate L Jeffrey
Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28771673/activity-of-lenalidomide-in-mantle-cell-lymphoma-can-be-explained-by-nk-cell-mediated-cytotoxicity
#16
Patrick R Hagner, Hsiling Chiu, Maria Ortiz, Benedetta Apollonio, Maria Wang, Suzana Couto, Michelle F Waldman, Erin Flynt, Alan G Ramsay, Matthew Trotter, Anita K Gandhi, Rajesh Chopra, Anjan Thakurta
Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC-5013-MCL-002 trial (NCT00875667) comparing single-agent lenalidomide versus investigator's choice single-agent therapy and validated our findings in pre-clinical models of MCL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#17
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#18
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28765517/the-hedgehog-gli-pathway-in-embryonic-development-and-cancer-implications-for-pulmonary-oncology-therapy
#19
REVIEW
Armas López Leonel, Zúñiga Joaquín, Arrieta Oscar, Ávila-Moreno Federico
Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies.Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28763790/platelets-subvert-t-cell-immunity-against-cancer-via-garp-tgf%C3%AE-axis
#20
Saleh Rachidi, Alessandra Metelli, Brian Riesenberg, Bill X Wu, Michelle H Nelson, Caroline Wallace, Chrystal M Paulos, Mark P Rubinstein, Elizabeth Garrett-Mayer, Mirko Hennig, Daniel W Bearden, Yi Yang, Bei Liu, Zihai Li
Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. We show that genetic targeting of platelets enhances adoptive T cell therapy of cancer. An unbiased biochemical and structural biology approach established transforming growth factor β (TGFβ) and lactate as major platelet-derived soluble factors to obliterate CD4(+) and CD8(+) T cell functions...
May 5, 2017: Science Immunology
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