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https://www.readbyqxmd.com/read/29791011/a-pharmacokinetic-and-pharmacogenetic-analysis-of-osteosarcoma-patients-treated-with-high-dose-methotrexate-data-from-the-os2006-sarcoma-09-trial
#1
Gabrielle Lui, Jean-Marc Treluyer, Brice Fresneau, Sophie Piperno-Neumann, Nathalie Gaspar, Nadège Corradini, Jean-Claude Gentet, Perrine Marec Berard, Valérie Laurence, Pascale Schneider, Natacha Entz-Werle, Hélène Pacquement, Frédéric Millot, Sophie Taque, Claire Freycon, Cyril Lervat, Marie Cécile Le Deley, Céline Mahier Ait Oukhatar, Laurence Brugieres, Gwénaël Le Teuff, Naïm Bouazza
Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials...
May 23, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786138/association-of-different-immunosuppressive-medications-with-periodontal-condition-in-patients-with-rheumatoid-arthritis-results-from-a-cross-sectional-study
#2
Dirk Ziebolz, Annegret Rupprecht, Jan Schmickler, Laura Bothmann, Juliane Krämer, Daniel Patschan, Gerhard A Müller, Rainer F Mausberg, Jana Schmidt, Gerhard Schmalz, Susann Patschan
BACKGROUND: The aim of this cross-sectional study was to investigate clinical periodontal findings as well as prevalence of selected potentially periodontal pathogenic bacteria in patients with rheumatoid arthritis (RA) treated with different immunosuppressive rheumatic medications. METHODS: 168 patients with RA undergoing different immunosuppressive medications were included and divided into subgroups according to their medication, which was taken in the past six months, in detail I) non-steroidal anti-inflammatory drugs (NSAID) and glucocorticoids combined, and II-VII) different disease modifying anti-rheumatic drugs (DMARDs): II) Methotrexate (MTX), III) Leflunomide, IV) MTX and TNF-α antagonists combined, V) Interleukin-6 (IL-6) antagonist, VI) MTX and Rituximab combined, and VII) combination therapies of more than two of these DMARDs...
May 22, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29785434/integration-of-phospholipid-hyaluronic-acid-methotrexate-nanocarrier-assembly-and-amphiphilic-drug-drug-conjugate-for-synergistic-targeted-delivery-and-combinational-tumor-therapy
#3
Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29781586/treatment-algorithms-for-systemic-sclerosis-according-to-experts
#4
Andreu Fernández-Codina, Kyle M Walker, Janet E Pope
INTRODUCTION: Treatment for many aspects of systemic sclerosis (SSc) lacks agreement. OBJECTIVES: To generate SSc treatment algorithms endorsed by high percentage of SSc experts. METHODS: Experts from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research group (N=170) were asked whether they agreed with SSc algorithms (from 2012). Two consensus rounds refined agreement; 62 (36%), 54 (32%) and 48 (28%) experts completed surveys...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29780646/incorporating-cystatin-c-to-predict-methotrexate-elimination-in-patients-with-cns-lymphoma-and-suspicious-renal-function
#5
Jason N Barreto, Allison L McClanahan, Andrew D Rule, Carrie A Thompson, Erin Frazee
High-dose methotrexate (MTX; ≥1 g/m2 ) is a renally eliminated and nephrotoxic first-line therapy for central nervous system (CNS) lymphoma. Creatinine-based estimation of renal function is the recommended approach to dosing MTX in these cases, but nonrenal determinants of creatinine production and elimination in cancer patients such as malnutrition and cachexia lead to overestimation of glomerular filtration rate (GFR) by this method and a heightened risk for drug toxicity. Serum cystatin C is one of the first readily available, relatively inexpensive, endogenous biomarkers to emerge as a practical adjunct to creatinine for estimation of renal function for drug dosing...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29780382/extracellular-purine-metabolism-is-the-switchboard-of-immunosuppressive-macrophages-and-a-novel-target-to-treat-diseases-with-macrophage-imbalances
#6
Anna Ohradanova-Repic, Christian Machacek, Celine Charvet, Franck Lager, Delphine Le Roux, René Platzer, Vladimir Leksa, Goran Mitulovic, Thomas R Burkard, Gerhard J Zlabinger, Michael B Fischer, Vincent Feuillet, Gilles Renault, Stephan Blüml, Miroslav Benko, Miloslav Suchanek, Johannes B Huppa, Takami Matsuyama, Artur Cavaco-Paulo, Georges Bismuth, Hannes Stockinger
If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780139/methotrexate-associated-intravascular-large-b-cell-lymphoma-in-a-patient-with-rheumatoid-arthritis-a-very-rare-case
#7
Masao Hagihara, Toru Mese, Shin Ohara, Jian Hua, Shiro Ide, Morihiro Inoue
we herein report a rare case of methotrexate (MTX)-associated intravascular large B-cell lymphoma (IVLBCL) in a man with rheumatoid arthritis. Two episodes of a fever of unknown origin accompanied by elevated levels of serum lactate dehydrogenase and the soluble interleukin-2 receptor occurred within a year, so the patient was suspected of having an MTX-associated lymphoproliferative disorder. His clinical symptoms resolved after the cessation of MTX. However, after treatment with iguratimod, another disease-modified anti-rheumatic drug, markedly similar symptoms recurred, and random skin biopsies resulted in a diagnosis of IVLBCL...
May 18, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29780094/-the-treatment-of-patients-with-elderly-onset-rheumatoid-arthritis-at-niigata-rheumatic-center
#8
Chinatsu Takai, Daisuke Kobayashi, Satoshi Ito, Akira Murasawa, Yoko Wada, Ichiei Narita, Kiyoshi Nakazono
AIM: To investigate the clinical course of patients with elderly-onset rheumatoid arthritis (RA). METHODS: We compared the characteristics, and clinical course of 55 patients who developed RA at over 80 years of age (elderly-onset [EO] group) with 119 patients who developed RA at 40-59 years of age (non-elderly onset [non-EO] group). We also investigated the characteristics and clinical course of 19 patients who developed RA at over 80 and who received biological disease-modifying anti-rheumatic drugs (bDMARDs)...
2018: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
https://www.readbyqxmd.com/read/29779420/regression-of-atherosclerotic-plaques-of-cholesterol-fed-rabbits-by-combined-chemotherapy-with-paclitaxel-and-methotrexate-carried-in-lipid-core-nanoparticles
#9
Fernando L T Gomes, Raul C Maranhão, Elaine R Tavares, Priscila O Carvalho, Maria L Higuchi, Fernando R Mattos, Fabio G Pitta, Sergio A Hatab, Roberto Kalil-Filho, Carlos V Serrano
In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29778661/epigenetic-dysregulation-of-zeb1-is-involved-in-lmo2-promoted-t-cell-acute-lymphoblastic-leukaemia-leukaemogenesis
#10
Chao Wu, Jianjun Li, Chenchen Tian, Wen Shi, Huimin Jiang, Zhen Zhang, Hang Wang, Quansheng Zhang, Wei Sun, Peiqing Sun, Rong Xiang, Shuang Yang
T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29768710/improving-the-safety-of-high-dose-methotrexate-for-children-with-hematologic-cancers-in-settings-without-access-to-mtx-levels-using-extended-hydration-and-additional-leucovorin
#11
Kalthi Vaishnavi, Deepak Bansal, Amita Trehan, Richa Jain, Savita Verma Attri
BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively...
May 16, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29761789/ph-and-redox-responsive-nanoparticles-composed-of-charge-reversible-pullulan-based-shells-and-disulfide-containing-poly-%C3%AE-amino-ester-cores-for-co-delivery-of-gene-and-chemotherapeutic-agent
#12
Sipei Zhang, Dan Wang, Yating Li, Ling Li, Hongli Chen, Qingqing Xiong, Yuan-Yuan Liu, Yingsong Wang
A novel pH- and redox-responsive nanoparticle system was designed based on charge-reversible pullulan derivative (CAPL) and disulfide-containing poly(β-amino ester) (ssPBAE) for the co-delivery of gene and chemotherapeutic agent targeting hepatoma. The end-alkene groups of ssPBAE were reacted with diethylenetriamine to form amino-modified ssPBAE (NH-ssPBAE). Methotrexate (MTX), a chemotherapy agent, was then conjugated to NH-ssPBAE via amide bond to obtain a polymeric prodrug ssPBAE-MTX. ssPBAE-MTX exhibited a good capability for condensing genes including plasmid DNA (pDNA) and tetramethyl rhodamine-labeled DNA (TAMRA-DNA), and almost completely condensed pDNA at the weight ratio of 5/1 to form spherical nanocomplexes with an uniform size...
May 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29761420/long-term-radiographic-and-patient-reported-outcomes-in-patients-with-rheumatoid-arthritis-treated-with-tofacitinib-oral-start-and-oral-scan-post-hoc-analyses
#13
Vibeke Strand, Arthur Kavanaugh, Alan J Kivitz, Désirée van der Heijde, Kenneth Kwok, Ermeg Akylbekova, Arif Soonasra, Mark Snyder, Carol Connell, Eustratios Bananis, Josef S Smolen
INTRODUCTION: Here we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function. METHODS: This was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX...
May 14, 2018: Rheumatology and Therapy
https://www.readbyqxmd.com/read/29760159/inadequate-response-to-treat-to-target-methotrexate-therapy-in-patients-with-new-onset-rheumatoid-arthritis-development-and-validation-of-clinical-predictors
#14
Xavier M Teitsma, Johannes W G Jacobs, Paco M J Welsing, Pascal H P de Jong, Johanna M W Hazes, Angelique E A M Weel, Attila Pethö-Schramm, Michelle E A Borm, Jacob M van Laar, Floris P J G Lafeber, Johannes W J Bijlsma
OBJECTIVE: To identify and validate clinical baseline predictors associated with inadequate response (IR) to methotrexate (MTX) therapy in newly diagnosed patients with rheumatoid arthritis (RA). METHODS: In U-Act-Early, 108 disease-modifying antirheumatic drug (DMARD)-naive patients with RA were randomised to initiate MTX therapy and treated to target until sustained remission (disease activity score assessing 28 joints (DAS28) <2.6 with four or less swollen joints for ≥24 weeks) was achieved...
May 14, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29757046/biologic-treatment-of-recalcitrant-pediatric-psoriasis-a-case-series-from-a-tertiary-medical-center
#15
Ayelet Ollech, Alex Zvulunov, Lev Pavlovsky, Emmilia Hodak, Dan Ben Amitai
BACKGROUND: There is a paucity of data on the use of biologic therapy in recalcitrant pediatric psoriasis. The current study presents pediatric psoriasis cases treated with biologic agents in a tertiary referral center. METHODS: In this retrospective case series, data was collected on all patients ≤ 18 years old with severe psoriasis treated with biological therapy from 2010 through 2016 in a tertiary children's hospital. We included demographic data, previous systemic treatments, reason for discontinuation or switch to other systemic treatments, efficacy and side effects...
May 14, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29753054/psoriatic-patients-with-chronic-viral-hepatitis-do-not-have-an-increased-risk-of-liver-cirrhosis-despite-long-term-methotrexate-use-real-world-data-from-a-nationwide-cohort-study-in-taiwan
#16
Kuo-Tung Tang, Yi-Ming Chen, Shih-Ni Chang, Ching-Heng Lin, Der-Yuan Chen
BACKGROUND: Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. OBJECTIVE: We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. METHODS: This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010...
May 9, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29752115/core-shell-structure-of-fe-3-o-4-mtx-ldh-au-nps-for-cancer-therapy
#17
Xiu-Fen Zhao, Wei-Yuan Wang, Xiao-Dong Li, Shu-Ping Li, Fu-Gui Song
Nearly monodispersed magnetic Fe3 O4 @MTX-LDH/Au nanoparticles (NPs) containing the anticancer agent of methotrexate (MTX) were prepared via a coprecipitation-electrostatic interaction strategy. Firstly, layered double hydroxide (LDH) materials were deposited over the surface of Fe3 O4 NPs by the coprecipitation method. Secondly, Au NPs were successfully conjugated onto the surface of LDH through electrostatic interaction. Herein, MTX was used both as the agent for surface modification and the anticancer drug for chemotherapy...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29746672/two-years-of-sarilumab-in-patients-with-rheumatoid-arthritis-and-an-inadequate-response-to-mtx-safety-efficacy-and-radiographic-outcomes
#18
Mark C Genovese, Janet van Adelsberg, Chunpeng Fan, Neil M H Graham, Hubert van Hoogstraten, Janie Parrino, Erin K Mangan, Alberto Spindler, Tom W J Huizinga, Désirée van der Heijde
Objectives: To examine 2-year safety, efficacy and radiographic outcomes of sarilumab in adults with RA and inadequate response to MTX (MTX-IR). Methods: In the randomized, placebo-controlled MOBILITY trial, MTX-IR patients received subcutaneous sarilumab (150 or 200 mg) or placebo every 2 weeks (q2w) plus MTX for up to 1 year. Upon study completion, patients could enrol in the open-label, long-term extension study (EXTEND, NCT011046652), in which all patients received sarilumab 200 mg q2w plus MTX...
May 9, 2018: Rheumatology
https://www.readbyqxmd.com/read/29745884/type-iv-collagen-metabolism-is-associated-with-disease-activity-radiographic-progression-and-response-to-tocilizumab-in-rheumatoid-arthritis
#19
Natasja Stæhr Gudmann, Peter Junker, Pernille Juhl, Christian Schneider Thudium, Anne Sofie Siebuhr, Inger Byrjalsen, Morten Asser Karsdal, Anne Christine Bay-Jensen
OBJECTIVES: The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular matrix of the synovial lining layer. We aimed to investigate the association of type IV collagen turnover with RA disease activity, response to IL-6 inhibition and radiographic progression...
May 8, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29745729/anti-proliferate-and-apoptosis-triggering-potential-of-methotrexate-transferrin-conjugate-encapsulated-plga-nanoparticles-with-enhanced-cellular-uptake-by-high-affinity-folate-receptors
#20
Ankush Parmar, Atul Jain, Shivani Uppal, S K Mehta, Khuswinder Kaur, Bhupinder Singh, Rajat Sandhir, Shweta Sharma
The objective of the present study is to enhance the permeation of bioactive molecules across highly lipophilic insurmountable blood brain barrier (BBB) using folic acid (FA) functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FA-PNPs) coated with non-ionic surfactant, Polysorbate 80 (P80 ). The developed Mtx-Tf loaded folic acid anchored PNPs formulation depicted particle size, zeta potential and entrapment efficiency of 109 ± 2.3 nm, -9.38 ± 0.9 mV and 71.0 ± 0.6%, respectively...
May 10, 2018: Artificial Cells, Nanomedicine, and Biotechnology
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