Abstract:
BACKGROUND:Earlier publications have suggested a possible role for the efflux transporter breast cancer resistance protein (BCRP) in acquired resistance to disease-modifying antirheumatic drugs (DMARDs) such as leflunomide and its metabolite A771726 (teriflunomide). However, there is no direct evidence that BCRP interacts with these drugs. OBJECTIVES:To characterise the interaction between BCRP transporter and leflunomide and its active metabolite A771726, with emphasis on the nature of the interaction (substrate or inhibitor) and the kinetic characterisation of the interactions. METHODS:Different in vitro membrane-based methods (ATPase and vesicular transport assay) using BCRP-HAM-Sf9 membrane preparations and cellular assays (Hoechst assay and cytotoxicity assay) were performed on PLB985-BCRP and HEK293-BCRP cell lines overexpressing BCRP. RESULTS:In all assays used, an interaction between the investigated drugs and BCRP was detected. In the vesicular transport assay, both leflunomide and its metabolite inhibited BCRP-mediated methotrexate transport. Both compounds are likely substrates of BCRP as shown by the vanadate-sensitive ATPase assay. In line with the membrane assays, leflunomide and A771726 inhibited BCRP-mediated Hoechst efflux from PLB985-BCRP cells. In the cytotoxicity assay, overexpression of BCRP conferred 20.6-fold and 7.5-fold resistance to HEK293 cells against leflunomide and A771726, respectively. The resistance could be reversed by Ko134, a specific inhibitor of BCRP. CONCLUSION:Based on these results, BCRP could play an important role in the resistance to leflunomide and A771726 via interactions with these drugs. BCRP may also mediate drug-drug interactions when leflunomide is administered with other BCRP substrate drugs such as methotrexate.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Kis E,Nagy T,Jani M,Molnár E,Jánossy J,Ujhellyi O,Német K,Herédi-Szabó K,Krajcsi Pdoi
10.1136/ard.2007.086264subject
Has Abstractpub_date
2009-07-01 00:00:00pages
1201-7issue
7eissn
0003-4967issn
1468-2060pii
ard.2007.086264journal_volume
68pub_type
杂志文章abstract:BACKGROUND:Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE:To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Agains...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2011-201063
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with infl...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.097212
更新日期:2010-01-01 00:00:00
abstract::Symptomatic osteonecrosis occurred in 8 out of 68 patients with systemic lupus erythematosus. Multiple joints were involved in 3 patients, and weight-bearing joints were most frequently affected. Osteonecrosis tended to occur early in the disease, and the patients had all received corticosteroids. Symptoms tended to o...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.38.5.413
更新日期:1979-10-01 00:00:00
abstract::Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients ...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/ard.51.1.13
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:Anti-citrullinated protein antibodies (ACPA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or proteins as antige...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2010.131102
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:In the present work, the frequency of inherited polymorphisms of the beta2 adrenergic receptor (beta2AR) gene and their association with rheumatoid arthritis (RA) as well as human leukocyte antigen (HLA)-DRB1 alleles was examined. METHODS:An allele-specific polymerase chain reaction was used to determine the...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.083782
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVES:Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual se...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.59.1.64
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVES:To determine the accuracy of ultrasonography (US) for bone erosion detection in different areas of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints with multislice CT as the reference method. Second, to establish the necessary bone volume loss on CT for US to reliably detect it as an erosion, and f...
journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章
doi:10.1136/annrheumdis-2011-201114
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. METHODS:768 patients (537 fulfilled...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/ard.2008.091264
更新日期:2009-07-01 00:00:00
abstract::Hereditary deficiencies of early complement components have usually been associated with the development of rheumatic diseases like systemic lupus erythematosus (SLE), while terminal component deficiency is well known to predispose to recurrent neisserial infection. In contrast, only recently have patients been report...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.10.716
更新日期:1985-10-01 00:00:00
abstract::The capacity of monocytes from patients with rheumatoid arthritis to generate superoxide anion in vitro after stimulation with serum treated zymosan (STZ) or IgG treated zymosan (IgTZ) was studied before and during therapy with penicillamine (n = 9) or sodium aurothiomalate (AuTM) (n = 12). Significant increases in ra...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.1.37
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12-48 month MRI lesion status worsening is associated with 12-48 month incident radiographic osteoarthritis (obje...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208129
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVE:Progranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-205779
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:To assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II. METHODS:SLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II rando...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,随机对照试验
doi:10.1136/annrheumdis-2018-213708
更新日期:2019-01-01 00:00:00
abstract::A 57 year old white man with aortic insufficiency and previously undiagnosed ankylosing spondylitis, who developed subacute bacterial endocarditis (SBE), is described. Emergency aortic valve replacement was necessary, and the aortic valve pathology showed diffusely fibrosed and thickened valve leaflets with bacterial ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.47.5.423
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVES:To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS:BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.095596
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:To determine discrepancies in patients' current use and expected future use of the internet for different functions. METHOD:A short questionnaire was developed to assess patients' current use of the internet for three functions: "seeking information", "mutual support", and "care provider contact". This quest...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2004.035006
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVES:Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. METHODS:A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/annrheumdis-2016-210860
更新日期:2017-09-01 00:00:00
abstract::Reproducibility along a vertical 10 cm visual analogue scale (VAS) was investigated. Eight normal volunteers attempted to duplicate a set of marked VAS. There was a tendency to estimate too high on the scale, and reproducibility was found to be variable along its length. This indicates that the error involved in the u...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.1.87
更新日期:1981-02-01 00:00:00
abstract::An acute inflammatory arthritis has been induced in 76% of rats injected intradermally with native bovine type II collagen emulsified in Freund's complete (CFA) or incomplete (ICFA) adjuvant. The arthritis became chronic in 14 out of 31 rats, and ear and tail lesions were noted in some rats. No arthritis was induced b...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.3.285
更新日期:1980-06-01 00:00:00
abstract::Erosions on the triquetrum and pisiform are frequent in early rheumatoid arthritis and occur characteristically at 3 sites. (a) A shallow erosion on the proximal medial triquetral "bare" area is related to synovial proliferation at the margin of the radiocarpal cavity, although compressive forces from an adjacent long...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.35.1.46
更新日期:1976-02-01 00:00:00
abstract:OBJECTIVE:We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma). METHODS:Fifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of glob...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2020-217840
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVE:To study the association between the occurrence of peripheral arthritis and of acute anterior uveitis during the course of ankylosing spondylitis (AS). METHODS:Retrospective clinical follow up by both chart review and direct patient interview was performed on 271 individuals comprised of 222 local white and ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.2.128
更新日期:1995-02-01 00:00:00
abstract:OBJECTIVE:High resolution ultrasound (HRUS) was used to investigate the effects of tumour necrosis factor alpha (TNFalpha) blockade on pannus formation and vascularisation of small finger joints in patients with active rheumatoid arthritis (RA). METHODS:Five patients with active RA were treated with etanercept, a solu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.61.1.55
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Serum leptin measures are associated with radiographic knee osteoarthritis, but no studies have examined leptin levels with respect to different measures of knee joint damage from MRI. METHODS:Participants in the Michigan Study of Women's Health Across the Nation underwent bilateral knee MRIs ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-202685
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVES:Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional r...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2018-214200
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND/OBJECTIVES:To maintain and optimise the quality of care provided by health professionals in rheumatology (HPRs), adequate educational offerings are needed. This task force (TF) aimed to develop evidence-based recommendations for the generic core competences of HPRs, with specific reference to nurses, physica...
journal_title:Annals of the rheumatic diseases
pub_type: 共识发展会议,指南,杂志文章
doi:10.1136/annrheumdis-2019-215803
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:To investigate the sympathetic and parasympathetic cardiovascular function in primary Sjögren's syndrome (SS) and to investigate the possible relation with ocular dryness. METHODS:41 (40 women) patients with primary SS, mean age 50 years (range 20-80) with a mean disease duration of eight years (range 1-30),...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.58.12.746
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVES:To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. METHODS:A population-based study was conducte...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2008.098301
更新日期:2009-10-01 00:00:00
abstract::Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired cont...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.49.7.507
更新日期:1990-07-01 00:00:00