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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/28058501/-cytokine-neutralization-at-specific-cellular-source-a%C3%A2-new-therapeutic-paradigm-german-version
#1
A A Kruglov, S A Nedospasov
BACKGROUND: Currently, treatment of autoimmune diseases is based on manipulation of general control mechanisms, including those mediated by immunoregulatory cytokines. This approach is non-curative and may cause unwanted side effects due to numerous beneficial and non-redundant functions of a particular cytokine. METHODS: Techniques of reverse genetics, such as conditional gene targeting, were employed to uncover the contributions of two proinflammatory and immunomodulatory cytokines, tumour necrosis factor (TNF) and interleukin 6 (IL-6), in various disease states...
January 5, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28048692/mo-fg-207b-01-thorax-lung
#2
H Aerts
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048031/mo-fg-207b-02-breast
#3
H Li
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047352/mo-fg-207b-03-brain
#4
P Tiwari
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046682/mo-fg-207b-04-respond-to-therapy
#5
W Lu
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046637/mo-fg-207b-00-state-of-the-art-in-radiomics-in-radiology-and-radiation-oncology
#6
Maryellen Giger, Joseph Deasy
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28040706/familial-mediterranean-fever-associated-diseases-in-children
#7
Z Birsin Özçakar, Nilgün Çakar, Nermin Uncu, Banu Acar Çelikel, Fatoş Yalçınkaya
BACKGROUND: MEditerranean FeVer (MEFV) gene encodes for the pyrin protein and a mutated pyrin is associated with a prolonged or augmented inflammation. Hence, various diseases were reported to be associated with familial Mediterranean fever (FMF) or carriers of MEFV mutations. However, systematic evaluation of all associated diseases in children with FMF has not been done previously. AIM: The aim of this study was to investigate the frequency and type of FMF-associated diseases in children...
December 30, 2016: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28039611/alternative-new-mesenchymal-stem-cell-source-exerts-tumor-tropism-through-alcam-and-n-cadherin-via-regulation-of-microrna-192-and-218
#8
Ran Kim, Sang In Park, Chang Youn Lee, Jihyun Lee, Pilseog Kim, Sekyung Oh, Hojin Lee, Min Young Lee, Jongmin Kim, Yong-An Chung, Ki-Chul Hwang, Lee-So Maeng, Woochul Chang
Gliomas are the most common type of malignant primary brain tumors. Some treatments of gliomas exist, but they are rarely curative. Mesenchymal stem cells (MSCs) are emerging as potential modes of targeted cancer therapy owing to their capacity for homing toward tumor sites. It has been proposed that MSCs derived from various sources, such as bone marrow, adipose tissue and umbilical cord blood, can be used as cell-based therapy for brain tumors. Here, MSCs obtained from the synovial fluid of osteoarthritis or rheumatoid arthritis patients were investigated as therapeutic candidates...
December 30, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28028154/analysis-of-haematological-changes-in-tofacitinib-treated-patients-with-rheumatoid-arthritis-across-phase-3-and-long-term-extension-studies
#9
Hendrik Schulze-Koops, Vibeke Strand, Chudy Nduaka, Ryan DeMasi, Gene Wallenstein, Kenneth Kwok, Lisy Wang
OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. METHODS: Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration...
January 2017: Rheumatology
https://www.readbyqxmd.com/read/28027930/tocilizumab-improves-the-proatherothrombotic-profile-of-rheumatoid-arthritis-patients-modulating-endothelial-dysfunction-netosis-and-inflammation
#10
P Ruiz-Limón, R Ortega, I Arias de la Rosa, M C Abalos-Aguilera, C Perez Sanchez, Y Jimenez Gomez, E Peralbo-Santaella, P Font, D Ruiz-Vilches, G Ferrin, E Collantes-Estevez, A Escudero, C H López Pedrera, N Barbarroja
Tocilizumab (TCZ) is an effective treatment for rheumatoid arthritis (RA). However, the changes that occurred after TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet. A total of 20 RA patients received 162 mg per week subcutaneous TCZ for 6 months. Endothelial function was measured through postocclusive hyperemia using Laser Doppler. Oxidative stress markers in monocytes and neutrophils were analyzed by flow cytometry...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28002318/brahma-related-gene-1-induces-apoptosis-in-a-p53-dependent-manner-in-human-rheumatoid-fibroblast-like-synoviocyte-mh7a
#11
Hongli Hou, Weipeng Xing, Wuyin Li
Blocked apoptosis and aggressive inflammatory responses occur in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) patients. Although Brahma-related gene 1 (BRG1) is considered as a tumor suppressor, few research covers its role in RA. This study aims to reveal effects and potential mechanisms of BRG1 in human FLS cell line MH7A.BRG1 expression in MH7A cells was altered by transfection of overexpression vectors or short hairpin RNAs (shRNAs). Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry after transfection...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27988396/total-sesquiterpene-lactones-prepared-from-inula-helenium-l-has-potentials-in-prevention-and-therapy-of-rheumatoid-arthritis
#12
Shuang Gao, Qun Wang, Xin-Hui Tian, Hui-Liang Li, Yun-Heng Shen, Xi-Ke Xu, Guo-Zhen Wu, Zhen-Lin Hu, Wei-Dong Zhang
BACKGROUNDS: Inula helenium L. is an herb with anti-inflammatory properties. Sesquiterpene lactones (SLs), mainly alantolactone (AL) and isoalantolactone (IAL), are considered as its active ingredients. However, the anti-inflammatory effects of SL-containing extracts of I. helenium have not been explored. Here we prepared total SLs from I. helenium (TSL-IHL), analyzed its chemical constituents, and performed cellular and animal studies to evaluate its anti-inflammatory activities. MATERIALS AND METHODS: The chemical profile of TSL-IHL was analyzed by HPLC-UV...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27960219/an-mri-evaluation-of-patients-who-underwent-treatment-with-a-cell-mediated-gene-therapy-for-degenerative-knee-arthritis-a-phase-iia-clinical-trial
#13
Jung Jong Cho, Saara Totterman, Randa K Elmallah, Tae Won Kim, Bumsup Lee, Michael A Mont
Multiple therapies have been developed to slow down the progression of knee osteoarthritis (OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming growth factor-β1. Using magnetic resonance imaging (MRI), we evaluated patients who underwent treatment with this injection in a Phase II study and assessed structural changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal, as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial inflammation...
December 13, 2016: Journal of Knee Surgery
https://www.readbyqxmd.com/read/27958380/influence-of-il6r-gene-polymorphisms-in-the-effectiveness-to-treatment-with-tocilizumab-in-rheumatoid-arthritis
#14
M Maldonado-Montoro, M Cañadas-Garre, A González-Utrilla, M Ángel Calleja-Hernández
In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27912794/a-genetic-risk-score-composed-of-rheumatoid-arthritis-risk-alleles-hla-drb1-haplotypes-and-response-to-tnfi-therapy-results-from-a-swedish-cohort-study
#15
Xia Jiang, Johan Askling, Saedis Saevarsdottir, Leonid Padyukov, Lars Alfredsson, Sebastien Viatte, Thomas Frisell
BACKGROUND: To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27910765/gene-therapy-for-rheumatoid-arthritis
#16
Shuang Liu, Kazutaka Maeyama
With the aim of controlling disease relapse and bone deformation of individual joints, the application of gene therapy in rheumatoid arthritis (RA) has slowly progressed on a trial-and-error basis. Several new therapeutic targets have been identified in preclinical studies in animal models, although a limited number of gene-based clinical trials have been conducted. In this article, we summarize the status of gene therapy for RA by addressing issues related to innovating drug development. More disease- and target-specific preclinical tests are required to overcome the insufficient information regarding pharmacokinetics and toxicokinetics, which are related to safety issues in the field of RA gene therapy...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27906774/lessons-from-characterization-and-treatment-of-the-autoinflammatory-syndromes
#17
Ivona Aksentijevich, Michael F McDermott
PURPOSE OF REVIEW: The list of genes associated with systemic inflammatory diseases has been steadily growing because of the explosion of new genomic technologies. Significant advances in the past year have deepened our understanding of the molecular mechanisms linked to inflammation and elucidated insights on the efficacy of specific therapies for these and related conditions. We review the molecular pathogenesis of four recently characterized monogenic autoinflammatory diseases: haploinsufficiency of A20, otulipenia, a severe form of pyrin-associated disease, and a monogenic form of systemic juvenile idiopathic arthritis...
November 30, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27885916/atic-missense-variant-affects-response-to-methotrexate-treatment-in-rheumatoid-arthritis-patients
#18
Mateusz Kurzawski, Damian Malinowski, Natalia Szarmach, Anna Nowak, Aleksandra Goryniak, Andrzej Pawlik, Marek Droździk
AIM: The study was aimed at investigation of several gene variants of folate pathway enzymes for their potential association with methotrexate (MTX) treatment response in patients with rheumatoid arthritis. PATIENTS & METHODS: Four hundred and twenty two Caucasian patients were classified as good or poor responders, and subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes. RESULTS: No significant differences were observed in case of DHFR and FGPS SNPs...
December 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27870898/functional-tissue-analysis-reveals-successful-cryopreservation-of-human-osteoarthritic-synovium
#19
Mathijs G A Broeren, Marieke de Vries, Miranda B Bennink, Peter L E M van Lent, Peter M van der Kraan, Marije I Koenders, Rogier M Thurlings, Fons A J van de Loo
Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use...
2016: PloS One
https://www.readbyqxmd.com/read/27849614/epipolymorphisms-associated-with-the-clinical-outcome-of-autoimmune-arthritis-affect-cd4-t-cell-activation-pathways
#20
Roberto Spreafico, Maura Rossetti, John W Whitaker, Wei Wang, Daniel J Lovell, Salvatore Albani
Multifactorial diseases, including autoimmune juvenile idiopathic arthritis (JIA), result from a complex interplay between genetics and environment. Epigenetic mechanisms are believed to integrate such gene-environment interactions, fine-tuning gene expression, and possibly contributing to immune system dysregulation. Although anti-TNF therapy has strongly increased JIA remission rates, it is not curative and up to 80% of patients flare upon treatment withdrawal. Thus, a crucial unmet medical and scientific need is to understand the immunological mechanisms associated with remission or flare to inform clinical decisions...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
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