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Genetics and immune therapy

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https://www.readbyqxmd.com/read/28443381/pharmacological-management-of-narcolepsy-with-and-without-cataplexy
#1
Ulf Kallweit, Claudio L Bassetti
Introduction Narcolepsy is an orphan neurological disease and presents with sleep- wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28441138/employing-rna-viruses-to-fight-cancer-novel-insights-into-oncolytic-virotherapy
#2
Dörthe Masemann, Yvonne Boergeling, Stephan Ludwig
Within the last decades, viruses that specifically target tumor cells have emerged as novel therapeutic agents against cancer. These viruses do not only act via their cell-lytic properties, but also harbor immunostimulatory features to re-direct the tumor-microenvironment and stimulate tumor-directed immune responses. Furthermore, oncolytic viruses are considered to be superior to classical cancer therapies due to higher selectivity towards tumor cell destruction and, consequently, less collateral damage of non-transformed healthy tissue...
April 25, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28440027/the-crispr-cas9-system-their-delivery-in-vivo-and-ex-vivo-applications-and-clinical-development-by-startups
#3
REVIEW
Minjung Song
The CRISPR/Cas9 gene editing system was originally derived from the prokaryotic adaptive immune system mediated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas). The system has been successfully applied to genome editing in eukaryotes and has contributed to remarkable advances in the life sciences, in areas ranging from agriculture to genetic disease therapies. For efficient editing and extending the influence of this system, proper delivery of its components is crucial...
April 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28432221/biological-considerations-of-plasma-derived-and-recombinant-factor-viii-immunogenicity
#4
Jesse Lai, Christine Hough, Julie Tarrant, David Lillicrap
In hemophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the formation of FVIII neutralizing antibodies, also known as inhibitors, in 25-30% of patients. This adverse event is associated with a significant increase in morbidity and economic burden, thus highlighting the need to identify methods to limit FVIII immunogenicity. Inhibitor development is regulated by a complex balance of genetic factors, such as FVIII genotype, and environmental variables, such as coexistent inflammation...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431620/role-of-inflammatory-molecules-in-the-alzheimer-s-disease-progression-and-diagnosis
#5
REVIEW
Eva Bagyinszky, Vo Van Giau, Kyuhwan Shim, Kyoungho Suk, Seong Soo A An, SangYun Kim
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#6
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#7
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28425954/inherited-variation-in-vitamin-d-genes-and-type-1-diabetes-predisposition
#8
REVIEW
Marissa Penna-Martinez, Klaus Badenhoop
The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials...
April 20, 2017: Genes
https://www.readbyqxmd.com/read/28425754/immunotherapy-and-targeted-therapy-in-brain-metastases-emerging-options-in-precision-medicine
#9
Tyler Lazaro, Priscilla K Brastianos
Brain metastases (BM) continue to represent an unmet clinical need in oncology. Immunotherapy and targeted therapy hold great promise in the treatment of BM. Emerging data are confirming the activity of these agents in patients with BM. Genomic studies have confirmed that clinically actionable mutations are present in BM and they can be used in clinical studies to link targeted therapies with their genetic targets. Furthermore, as molecular signatures associated with sensitivity and resistance to immunotherapies are developed, we will better be able to select BM patients who will most benefit from these therapies...
April 2017: CNS Oncology
https://www.readbyqxmd.com/read/28414303/development-of-potent-class-ii-transactivator-gene-delivery-systems-capable-of-inducing-de-novo-mhc-ii-expression-in-human-cells-in-vitro-and-ex-vivo
#10
M de Lucena Palma, P Duangkhae, B Douradinha, I F T Viana, P O Rigato, R Dhalia, R B Mailliard, S M Barratt-Boyes, E J M do Nascimento, T M Oshiro, A J da Silva Duarte, E T de A Marques
Class II Transactivator (CIITA) induces transcription of MHC II genes and can potentially be used to improve genetic immunotherapies by converting non-immune cells into cells capable of presenting antigens to CD4(+) T cells. However, CIITA expression is tightly controlled and it remains unclear whether distinct non-immune cells differ in this transactivator regulation. Here we describe the development of gene delivery systems capable of promoting the efficient CIITA expression in non-immune cell lines and in primary human cells of an ex vivo skin explant model...
April 17, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28414152/rituximab-for-immunologic-renal-disease-what-the-nephrologist-needs-to-know
#11
REVIEW
Andreas Kronbichler, Martin Windpessl, Herwig Pieringer, David R W Jayne
Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used in immune-mediated renal diseases. While licensed in the induction treatment of ANCA-associated vasculitis, it represents one of the most commonly prescribed off-label drugs. Much of the information regarding its safety has been drawn from experience in hematology and rheumatology. Ample evidence illustrates the safety of RTX, however, rare but serious adverse events have emerged that include progressive multifocal leucoencephalopathy and hepatitis B reactivation...
April 13, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28407685/extra-pancreatic-invasion-induces-lipolytic-and-fibrotic-changes-in-the-adipose-microenvironment-with-released-fatty-acids-enhancing-the-invasiveness-of-pancreatic-cancer-cells
#12
Takashi Okumura, Kenoki Ohuchida, Masafumi Sada, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Chika Iwamoto, Daisuke Miura, Yusuke Mizuuchi, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405519/the-interleukin-il-1r1-pathway-is-a-critical-negative-regulator-of-pymt-mediated-mammary-tumorigenesis-and-pulmonary-metastasis
#13
Maryse Dagenais, Jeremy Dupaul-Chicoine, Todd Douglas, Claudia Champagne, Alexandre Morizot, Maya Saleh
Breast cancer is the most common cancer in women and the second leading cause of female cancer-related deaths worldwide. Inflammation is an established hallmark of tumorigenesis and an important determinant of tumor outcome and response to therapy. With advances in cancer immunotherapy, there is an urgent need to dissect the contribution of specific immune effectors in cancer development. Here, we genetically investigated the role of the Interleukin-1 (IL-1) receptor 1 (IL-1R1) pathway in breast cancer tumorigenesis and metastasis using the MMTV-PyMT mouse model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405501/pdl1-expression-is-a-poor-prognosis-factor-in-soft-tissue-sarcomas
#14
François Bertucci, Pascal Finetti, Delphine Perrot, Agnès Leroux, Françoise Collin, Axel Le Cesne, Jean-Michel Coindre, Jean-Yves Blay, Daniel Birnbaum, Emilie Mamessier
Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405194/modeling-natural-killer-cell-targeted-immunotherapies
#15
REVIEW
Silvia Lopez-Lastra, James P Di Santo
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of diseases. However, mouse models do not reproduce the genetic and molecular complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis and tumor immunobiology provide one means to bridge the interspecies gap. Natural killer cells are the founding member of the innate lymphoid cell family...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#16
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404115/advances-in-primary-sclerosing-cholangitis
#17
REVIEW
Jennifer L Horsley-Silva, Elizabeth J Carey, Keith D Lindor
Primary sclerosing cholangitis is a chronic, progressive cholangiopathy that frequently affects men and is associated with inflammatory bowel disease. Although the cause of the disease is still debated, a genetic association and link to immune-mediated disease triggered by environmental factors are thought to contribute. The disease can present as isolated imaging abnormalities, biochemical changes, cholangiocarcinoma, or end-stage complications such as cirrhosis. Symptoms of primary sclerosing cholangitis include fatigue, jaundice, pruritus, or steatorrhoea...
September 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28404070/pathophysiology-of-irritable-bowel-syndrome
#18
REVIEW
Gerald J Holtmann, Alexander C Ford, Nicholas J Talley
Traditionally, irritable bowel syndrome has been considered to be a disorder with no known underlying structural or biochemical explanation, but this concept is likely to be outdated. In this Review we challenge the widely accepted view that irritable bowel syndrome is an unexplained brain-gut disorder. There is epidemiological evidence that, in a major subset of patients, gastrointestinal symptoms arise first and only later do incident mood disorders occur. Additionally, possible mechanisms for gut-brain dysfunction have been identified, suggesting primary gut disturbances might be the underlying cause in a subgroup...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28401658/kreuth-iv-european-consensus-proposals-for-treatment-of-haemophilia-with-coagulation-factor-concentrates
#19
P L F Giangrande, F Peyvandi, B O'Mahony, M-E Behr-Gross, A Hilger, W Schramm, P M Mannucci
INTRODUCTION: This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the 'Kreuth IV' meeting in May 2016. AIM: The objective of the meeting was for experts in the field of haemophilia from across Europe to draft resolutions regarding current issues relating to the treatment of haemophilia. RESULTS: Hospitals providing clinical care for people with haemophilia and related disorders are strongly recommended to seek formal designation as either European Haemophilia Treatment Centres (EHTC) or European Haemophilia Comprehensive Care Centres (EHCCC)...
April 12, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28399486/determination-of-cytokine-levels-in-multiple-sclerosis-patients-and-their-relevance-with-patients-response-to-cinnovex
#20
Mohammad Taheri, Soudeh Ghafouri-Fard, Ghasem Solgi, Arezou Sayad, Mehrdokht Mazdeh, Mir Davood Omrani
Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervous system (CNS) with several environmental and genetic factors participating in its development and disease course. Interferon (IFN)-β therapy is considered as the first line treatment in this disorder. The present study enrolled 231 relapsing-remitting MS patients who were diagnosed as IFN-β responders (n=146) and non-responders (n=85). Serum cytokine levels were analyzed by commercially available ELISA kits in distinct groups based on HLA-A, -B and -DRB1 alleles...
April 8, 2017: Cytokine
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