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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/28331226/the-histone-deacetylase-inhibitor-givinostat-itf2357-exhibits-potent-anti-tumor-activity-against-crlf2-rearranged-bcp-all
#1
A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K Davis, G Gaipa, S Izraeli, L H Meyer, G P Nolan, A Biondi, G Te Kronnie, C Palmi, G Cazzaniga
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert antineoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations...
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28296761/polymorphisms-and-pharmacogenomics-for-the-toxicity-of-methotrexate-monotherapy-in-patients-with-rheumatoid-arthritis-a-systematic-review-and-meta-analysis
#2
Qi Qiu, Jing Huang, Yang Lin, Xiaoming Shu, Huizheng Fan, Zhihua Tu, Youwen Zhou, Cheng Xiao
BACKGROUND: Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28294321/artesunate-inhibits-rankl-induced-osteoclastogenesis-and-bone-resorption-in-vitro-and-prevents-lps-induced-bone-loss-in-vivo
#3
Cheng-Ming Wei, Qian Liu, Fang-Ming Song, Xi-Xi Lin, Yi-Ji Su, Jiake Xu, Lin Huang, Shao-Hui Zong, Jin-Min Zhao
Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs)...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28286757/effect-of-tumor-necrosis-factor-inhibitor-therapy-on-osteoclasts-precursors-in-rheumatoid-arthritis
#4
Inês P Perpétuo, Joana Caetano-Lopes, Ana Maria Rodrigues, Raquel Campanilho-Marques, Cristina Ponte, Helena Canhão, Mari Ainola, João E Fonseca
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28258822/intra-articular-lentivirus-mediated-gene-therapy-targeting-cracm1-for-the-treatment-of-collagen-induced-arthritis
#5
Shuang Liu, Takeshi Kiyoi, Erika Takemasa, Kazutaka Maeyama
Abnormal store-operated calcium uptake has been observed in peripheral T lymphocytes of rheumatoid arthritis (RA) patients, and sustained intracellular calcium signalling is known to mediate the functions of many types of immune cells. Thus, it is hypothesized that regulating calcium entry through CRACM1 (the pore-forming subunit of calcium release-activated calcium (CRAC) channels; also known as ORAI1) may be beneficial for the management of RA. Localized CRACM1 knockdown in the joints and draining lymph nodes (DLNs) of mice with collagen-induced arthritis (CIA) was achieved via lentiviral-based delivery of shRNA targeting mouse CRACM1...
February 11, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28207896/rna-seq-analysis-of-chikungunya-virus-infection-and-identification-of-granzyme-a-as-a-major-promoter-of-arthritic-inflammation
#6
Jane A C Wilson, Natalie A Prow, Wayne A Schroder, Jonathan J Ellis, Helen E Cumming, Linden J Gearing, Yee Suan Poo, Adam Taylor, Paul J Hertzog, Francesca Di Giallonardo, Linda Hueston, Roger Le Grand, Bing Tang, Thuy T Le, Joy Gardner, Suresh Mahalingam, Pierre Roques, Phillip I Bird, Andreas Suhrbier
Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28129106/a-synthetic-mammalian-therapeutic-gene-circuit-for-sensing-and-suppressing-inflammation
#7
Anže Smole, Duško Lainšček, Urban Bezeljak, Simon Horvat, Roman Jerala
Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a "thresholder" to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28121199/functional-analysis-of-choline-transporters-in-rheumatoid-arthritis-synovial-fibroblasts
#8
Masayuki Seki, Yuiko Kawai, Chikanao Ishii, Tsuyoshi Yamanaka, Masato Odawara, Masato Inazu
OBJECTIVES: In this study, we examined the functional characteristics of choline uptake and sought to identify the transporters in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: The expression of choline transporters was evaluated by quantitative real-time PCR, western blotting, and immunocytochemistry. Time course, Na(+)-dependency, and kinetics of [(3)H]choline uptake were investigated. Effects of cationic drugs on the uptake of [(3)H]choline, cell viability, and caspase-3/7 activity were also examined...
February 1, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28115015/early-changes-in-gene-expression-and-inflammatory-proteins-in-systemic-juvenile-idiopathic-arthritis-patients-on-canakinumab-therapy
#9
Arndt H Brachat, Alexei A Grom, Nico Wulffraat, Hermine I Brunner, Pierre Quartier, Riva Brik, Liza McCann, Huri Ozdogan, Lidia Rutkowska-Sak, Rayfel Schneider, Valeria Gerloni, Liora Harel, Maria Terreri, Kristin Houghton, Rik Joos, Daniel Kingsbury, Jorge M Lopez-Benitez, Stephan Bek, Martin Schumacher, Marie-Anne Valentin, Hermann Gram, Ken Abrams, Alberto Martini, Daniel J Lovell, Nanguneri R Nirmala, Nicolino Ruperto
BACKGROUND: Canakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). METHODS: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA)...
January 23, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28107378/polymorphisms-in-stat4-ptpn2-psors1c1-and-traf3ip2-genes-are-associated-with-the-response-to-tnf-inhibitors-in-patients-with-rheumatoid-arthritis
#10
Paola Conigliaro, Cinzia Ciccacci, Cristina Politi, Paola Triggianese, Sara Rufini, Barbara Kroegler, Carlo Perricone, Andrea Latini, Giuseppe Novelli, Paola Borgiani, Roberto Perricone
OBJECTIVE: Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients...
2017: PloS One
https://www.readbyqxmd.com/read/28058501/-cytokine-neutralization-at-specific-cellular-source-a%C3%A2-new-therapeutic-paradigm-german-version
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
March 2017: 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
#19
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
#20
Patricia Ruiz-Limón, Rafaela Ortega, Ivan Arias de la Rosa, Maria Del Carmen Abalos-Aguilera, Carlos Perez-Sanchez, Yolanda Jimenez-Gomez, Esther Peralbo-Santaella, Pilar Font, Desiree Ruiz-Vilches, Gustavo Ferrin, Eduardo Collantes-Estevez, Alejandro Escudero-Contreras, Chary López-Pedrera, Nuria 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
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