Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance.

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 Dis

authors

Kis E,Nagy T,Jani M,Molnár E,Jánossy J,Ujhellyi O,Német K,Herédi-Szabó K,Krajcsi P

doi

10.1136/ard.2007.086264

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

1201-7

issue

7

eissn

0003-4967

issn

1468-2060

pii

ard.2007.086264

journal_volume

68

pub_type

杂志文章
  • A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

    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

    authors: Villeneuve E,Nam JL,Bell MJ,Deighton CM,Felson DT,Hazes JM,McInnes IB,Silman AJ,Solomon DH,Thompson AE,White PH,Bykerk VP,Emery P

    更新日期:2013-01-01 00:00:00

  • Periodontal disease in patients with ankylosing spondylitis.

    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

    authors: Pischon N,Pischon T,Gülmez E,Kröger J,Purucker P,Kleber BM,Landau H,Jost-Brinkmann PG,Schlattmann P,Zernicke J,Burmester GR,Bernimoulin JP,Buttgereit F,Detert J

    更新日期:2010-01-01 00:00:00

  • Clinical and radiological features of osteonecrosis in systemic lupus erythematosus.

    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

    authors: Griffiths ID,Maini RN,Scott JT

    更新日期:1979-10-01 00:00:00

  • Morphological evidence that activated polymorphs circulate in the peripheral blood of patients with rheumatoid arthritis.

    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

    authors: McCarthy DA,Bernhagen J,Taylor MJ,Hamblin AS,James I,Thompson PW,Perry JD

    更新日期:1992-01-01 00:00:00

  • Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities.

    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

    authors: Ioan-Facsinay A,el-Bannoudi H,Scherer HU,van der Woude D,Ménard HA,Lora M,Trouw LA,Huizinga TW,Toes RE

    更新日期:2011-01-01 00:00:00

  • Association between beta2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope.

    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

    authors: Malysheva O,Pierer M,Wagner U,Wahle M,Wagner U,Baerwald CG

    更新日期:2008-12-01 00:00:00

  • No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19.

    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

    authors: Bengtsson A,Widell A,Elmstâhl S,Sturfelt G

    更新日期:2000-01-01 00:00:00

  • Detection, scoring and volume assessment of bone erosions by ultrasonography in rheumatoid arthritis: comparison with CT.

    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

    authors: Døhn UM,Terslev L,Szkudlarek M,Hansen MS,Hetland ML,Hansen A,Madsen OR,Hasselquist M,Møller J,Ostergaard M

    更新日期:2013-04-01 00:00:00

  • Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study.

    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

    authors: Hoff M,Kvien TK,Kälvesten J,Elden A,Haugeberg G

    更新日期:2009-07-01 00:00:00

  • Terminal complement component deficiencies and rheumatic disease: development of a rheumatic syndrome and anticomplementary activity in a patient with complete C6 deficiency.

    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

    authors: Wisnieski JJ,Naff GB,Pensky J,Sorin SB

    更新日期:1985-10-01 00:00:00

  • Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes.

    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

    authors: Hurst NP,Bell AL,Nuki G

    更新日期:1986-01-01 00:00:00

  • Clinical significance of worsening versus stable preradiographic MRI lesions in a cohort study of persons at higher risk for knee osteoarthritis.

    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

    authors: Sharma L,Nevitt M,Hochberg M,Guermazi A,Roemer FW,Crema M,Eaton C,Jackson R,Kwoh K,Cauley J,Almagor O,Chmiel JS

    更新日期:2016-09-01 00:00:00

  • Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling.

    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

    authors: Zhao YP,Liu B,Tian QY,Wei JL,Richbourgh B,Liu CJ

    更新日期:2015-12-01 00:00:00

  • Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts.

    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

    authors: Volkmann ER,Tashkin DP,Sim M,Li N,Goldmuntz E,Keyes-Elstein L,Pinckney A,Furst DE,Clements PJ,Khanna D,Steen V,Schraufnagel DE,Arami S,Hsu V,Roth MD,Elashoff RM,Sullivan KM,SLS I and SLS II study groups.

    更新日期:2019-01-01 00:00:00

  • Subacute bacterial endocarditis in a patient with ankylosing spondylitis.

    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

    authors: Hoppmann RA,Wise CM,Challa VR,Peacock JE

    更新日期:1988-05-01 00:00:00

  • Associations of obesity with modifiable risk factors for the development of cardiovascular disease in patients with rheumatoid arthritis.

    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

    authors: Stavropoulos-Kalinoglou A,Metsios GS,Panoulas VF,Douglas KM,Nevill AM,Jamurtas AZ,Kita M,Koutedakis Y,Kitas GD

    更新日期:2009-02-01 00:00:00

  • Disease related use of the internet in chronically ill adults: current and expected use.

    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

    authors: van Lankveld WG,Derks AM,van den Hoogen FH

    更新日期:2006-01-01 00:00:00

  • Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT).

    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

    authors: Reginster JY,Dudler J,Blicharski T,Pavelka K

    更新日期:2017-09-01 00:00:00

  • Reproducibility along a 10 cm vertical visual analogue scale.

    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

    authors: Dixon JS,Bird HA

    更新日期:1981-02-01 00:00:00

  • Native type II collagen-induced arthritis in the rat. I. Incidence and humoral response to collagen.

    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

    authors: Morgan K,Clague RB,Shaw MJ,Holt PJ

    更新日期:1980-06-01 00:00:00

  • Early abnormalities of pisiform and triquetrum in rheumatoid arthritis.

    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

    authors: Resnick D

    更新日期:1976-02-01 00:00:00

  • Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement.

    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

    authors: Showalter K,Spiera R,Magro C,Agius P,Martyanov V,Franks JM,Sharma R,Geiger H,Wood TA,Zhang Y,Hale CR,Finik J,Whitfield ML,Orange DE,Gordon JK

    更新日期:2021-02-01 00:00:00

  • Matching prevalence of peripheral arthritis and acute anterior uveitis in individuals with ankylosing spondylitis.

    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

    authors: Maksymowych WP,Chou CT,Russell AS

    更新日期:1995-02-01 00:00:00

  • High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis receiving treatment with soluble tumour necrosis factor alpha receptor (etanercept).

    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

    authors: Hau M,Kneitz C,Tony HP,Keberle M,Jahns R,Jenett M

    更新日期:2002-01-01 00:00:00

  • The relationship between longitudinal serum leptin measures and measures of magnetic resonance imaging-assessed knee joint damage in a population of mid-life women.

    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

    authors: Karvonen-Gutierrez CA,Harlow SD,Jacobson J,Mancuso P,Jiang Y

    更新日期:2014-05-01 00:00:00

  • Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade.

    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

    authors: Tong W,Zeng Y,Chow DHK,Yeung W,Xu J,Deng Y,Chen S,Zhao H,Zhang X,Ho KK,Qin L,Mak KK

    更新日期:2019-04-01 00:00:00

  • 2019 EULAR recommendations for the generic core competences of health professionals in rheumatology.

    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

    authors: Edelaar L,Nikiphorou E,Fragoulis GE,Iagnocco A,Haines C,Bakkers M,Barbosa L,Cikes N,Ndosi M,Primdahl J,Prior Y,Pchelnikova P,Ritschl V,Schäfer VS,Smucrova H,Storrønning I,Testa M,Wiek D,Vliet Vlieland TPM

    更新日期:2020-01-01 00:00:00

  • Parasympathetic failure does not contribute to ocular dryness in primary Sjögren's syndrome.

    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

    authors: Barendregt PJ,van Den Meiracker AH,Markusse HM,Tulen JH,Boomsma F,van Der Heijde GL,Veld AJ

    更新日期:1999-12-01 00:00:00

  • Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study.

    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

    authors: Harboe E,Tjensvoll AB,Maroni S,Gøransson LG,Greve OJ,Beyer MK,Herigstad A,Kvaløy JT,Omdal R

    更新日期:2009-10-01 00:00:00

  • Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

    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

    authors: Jokinen I,Poikonen K,Möttönen T,Hannonen P,Oka M,Ilonen J,Surcel HM,Karttunen R,Arvilommi H

    更新日期:1990-07-01 00:00:00