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ID PMID Title PublicationDate abstract
19258150 The minimal clinically important difference of the Michigan hand outcomes questionnaire. 2009 Mar PURPOSE: To determine the change in score required in various domains of the Michigan Hand Outcomes Questionnaire (MHQ) to indicate meaningful patient improvement, or the minimal clinically important difference (MCID), for 3 common hand conditions: rheumatoid arthritis (RA), carpal tunnel syndrome (CTS) and distal radius fracture (DRF). METHODS: The MHQ was administered to patients at 2 time points. Patient satisfaction was defined as a satisfaction score > or =80% of the standard deviation of that patient sample. The minimal change in score in specific MHQ domains that corresponded with patient satisfaction was determined using receiver operating characteristic curves. RESULTS: For CTS patients, MCIDs of 23, 13, and 8 were identified for the pain, function, and work domains, respectively. For RA patients, pain and function were also identified as having discriminative ability, with MCIDs of 11 and 13, respectively. An MCID of 3 was identified for the activities of daily living domain. For DRF patients, no MHQ domains showed discriminative ability because of the ceiling effect at the 3-month assessment period. CONCLUSIONS: Individual domains of the MHQ can be used to discriminate between patients who are satisfied and those who are not after either carpal tunnel release or silicone arthroplasty of the metacarpophalangeal joints for RA. Pain and function are the domains of the MHQ that are best able to discriminate between patients who are satisfied and those who are not. The identical function MCID for both RA patients and CTS patients, despite markedly different preoperative values, indicates that a standard amount of functional change may indicate patient satisfaction. High postoperative satisfaction, even only 3 months after surgery, prevented any domains from showing discriminative ability for the DRF patients.
19951408 A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken ty 2009 INTRODUCTION: Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. A 24-week, double-blind, double-dummy, randomized, methotrexate (MTX)-controlled study was conducted to evaluate the efficacy and safety of CCII in the treatment of rheumatoid arthritis (RA). METHODS: Five hundred three RA patients were included in the study. Patients received either 0.1 mg daily of CCII (n = 326) or 10 mg once a week of MTX (n = 177) for 24 weeks. Each patient was evaluated for pain, morning stiffness, tender joint count, swollen joint count, health assessment questionnaire (HAQ), assessments by investigator and patient, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) by using the standard tools at baseline (week 0) and at weeks 12 and 24. Additionally, rheumatoid factor (RF) was evaluated at weeks 0 and 24. Measurement of a battery of biochemical parameters in serum, hematological parameters, and urine analysis was performed to evaluate the safety of CCII. RESULTS: Four hundred fifty-four patients (94.43%) completed the 24-week follow-up. In both groups, there were decreases in pain, morning stiffness, tender joint count, swollen joint count, HAQ, and assessments by investigator and patient, and all differences were statistically significant. In the MTX group, ESR and CRP decreased. RF did not change in either group. At 24 weeks, 41.55% of patients in the CCII group and 57.86% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR-20) and 16.89% and 30.82%, respectively, met the ACR 50% improvement criteria (ACR-50). Both response rates for ACR-20 and ACR-50 in the CCII group were lower than those of the MTX group, and this difference was statistically significant (P < 0.05). The DAS28 (disease activity score using 28 joint counts) values of the two treatment groups were calculated, and there was a statistically significant difference between the two treatment groups (P < 0.05). Gastrointestinal complaints were common in both groups, but there were fewer and milder side effects in the CCII group than in the MTX group. The incidence of adverse events between the two groups was statistically significant (P < 0.05). CONCLUSIONS: CCII is effective in the treatment of RA and is safe for human consumption. CCII exerts its beneficial effects by controlling inflammatory responses through inducing oral tolerance in RA patients. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-00000093.
19338457 Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthriti 2009 Sep In rheumatoid arthritis (RA), synovial inflammation results in focal erosion of articular bone. Despite treatment attenuating inflammation, repair of erosions with adequate formation of new bone is uncommon in RA, suggesting that bone formation may be compromised at these sites. Dynamic bone histomorphometry was used in a murine model of RA to determine the impact of inflammation on osteoblast function within eroded arthritic bone. Bone formation rates at bone surfaces adjacent to inflammation were similar to those observed in nonarthritic bone; therefore, osteoblast activity is unlikely to compensate for the increased bone resorption at these sites. Within arthritic bone, the extent of actively mineralizing surface was reduced at bone surfaces adjacent to inflammation compared with bone surfaces adjacent to normal marrow. Consistent with the reduction in mineralized bone formation, there was a notable paucity of cells expressing the mid- to late stage osteoblast lineage marker alkaline phosphatase, despite a clear presence of cells expressing the early osteoblast lineage marker Runx2. In addition, several members of the Dickkopf and secreted Frizzled-related protein families of Wnt signaling antagonists were upregulated in arthritic synovial tissues, suggesting that inhibition of Wnt signaling could be one mechanism contributing to impaired osteoblast function within arthritic bone. Together, these data indicate that the presence of inflammation within arthritic bone impairs osteoblast capacity to form adequate mineralized bone, thus contributing to the net loss of bone and failure of bone repair at sites of focal bone erosion in RA.
19758225 Proliferation signal inhibitors for the treatment of refractory autoimmune rheumatic disea 2009 Sep Sirolimus and everolimus belong to the novel class of immunosuppressant agents known as proliferation signal inhibitors (PSIs). They act by preventing antigen-driven T cell proliferation. While PSIs are widely used in transplantation, there are few reports of PSI usage in the treatment of autoimmune rheumatic diseases. The author has presented a series in the APLAR 2006 conference. This report summarizes the clinical experience with PSIs in the treatment of resistant or relapsed rheumatic diseases where conventional immunosuppressive agents have failed. This is a retrospective review of patients with various autoimmune rheumatic diseases who had sirolimus and everolimus treatment from the rheumatological clinics of Changi Hospital or the Arthritis and Rheumatism Specialist Medical Centre. The period of review was from April 2006 to April 2008. A total of 46 patients were reviewed, 39 females and 7 males. The racial distribution was 33 Chinese, 7 Malays, and 6 Indians. Their disease conditions were as follows: 26 (57%) rheumatoid arthritis, 7 psoriatic arthritis, 4 systemic lupus erythematosus, 3 scleroderma, 2 anti-Jo-1 syndrome, 2 spondyloarthropathy, 1 MCTD, and 1 vasculitis. All patients had failed at least three DMARDs or immunosuppressants. Twenty-eight patients received sirolimus and 28 patients received everolimus. Overall positive response rate was 48.2%. Twenty-seven percent had adverse events. 20% had no response. 7% relapsed after initial response. PSIs, namely sirolimus and everolimus, are a novel class of immunosuppressants that can be added to the armamentarium of rheumatologists for the treatment of patients with refractory autoimmune rheumatic diseases.
20704620 Total hip arthroplasty in patients with chronic autoimmune inflammatory arthroplasties. 2010 Aug OBJECTIVE: Patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) often require total hip arthroplasties. We present a retrospective review of 32 total hip arthroplasties (THA) performed for patients with SLE, RA or AS from 2003 to 2008 in a tertiary hospital in Singapore. MATERIALS AND METHODS: A total of 323 THAs performed between January 2003 to December 2008 were traced and cases of arthroplasties performed for such patients were isolated. Pre- and post-operative range of motion, Harris hip score, limb length discrepancies and complications were studied. RESULTS: Twenty-six patients aged 24-66 years (mean 47 years) were reviewed, with two AS patients (7.7%), 16 RA patients (61.5%), seven SLE patients (26.9%) and one patient (3.8%) with both RA and SLE. Thirty-two THA operations were conducted with six patients requiring bilateral THAs. The average follow-up was 3.3 years. Mean Harris hip score for 25 patients (one excluded due to patient expiry 2 month post-surgery) improved from 41.3 to 86.53 (P < 0.05). Mean pre-operative hip flexion improved from 61.3 degrees (0-120) to 89.7 degrees (30-120) (P < 0.05). Seventeen cases had preoperative limb length discrepancies (median 1 cm) which were all corrected. There were no implants loosening, infective arthritis, dislocations or neurovascular injuries documented. CONCLUSION: Our series demonstrated the excellent outcome of THA for patients with chronic autoimmune arthropathies at the time of follow-up. Careful patient selection remains a priority as long-term outcomes for such patients of a significantly younger population is yet to be determined.
20096267 Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-kappaB activation. 2010 May 15 In this work, we aimed to build a 3D-model of NIK and to study the binding of pyrazolo[4,3-c]isoquinolines with a view to highlight the structural elements responsible for their inhibitory potency. However, in the course of this work, we unexpectedly found that the pyrazolo[4,3-c]isoquinolines initially reported as NIK inhibitors were neither inhibitors of this enzyme nor of the alternative NF-kappaB pathway, but were in fact inhibitors of another kinase, the TGF-beta activated kinase 1 (TAK1) which is involved in the classical NF-kappaB pathway.
20661690 Clinical value of 18F-fluorodeoxyglucose positron emission tomography in patients with con 2010 Jul Connective tissue diseases represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs other than the lung. (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is widely used in oncology but may also be valuable in patients with infections or inflammatory disease. The purpose of this article was to assess the clinical value of (18)F-FDG PET in patients with connective tissue disease. Our experience demonstrates that (18)F-FDG PET is a unique imaging technique for assessing the metabolic activity throughout the body in those with a connective tissue disease. The technique appears to be a promising imaging modality for detecting coexistent neoplastic diseases and other autoimmune disorders.
21618890 Histamine, immune cells and autoimmunity. 2010 Histamine is one ofthe most versatile biogenic amines with multiple roles during the immune response and in allergic disorders. With four distinct G protein-coupled receptors (H1R, HER, H3R and H4R), intracellular histamine binding sites (most likely members of the cytochrome P450 family) as well as a membrane transporter (Organic Cation Transporter; OCT3) expressed in various immunocompetent cells, it can entertain a complex network of interactions. These signaling pathways are expressed differentially, depending on the stage of differentiation or activation of target cells, thus adding a further degree of complexity to the system. For this reason, published data are sometimes conflicting and varying according to the particular cell type or responses analyzed and the experimental approaches used. On the other hand, histamine is generated by several cells during the immune response, not only through release of intracellular stores in mast cells or basophils in response to IgE-dependent or -independent stimuli, but also through neosynthesis catalyzed by histidine decarboxylase (HDC) in a number ofhematopoietic cells that secrete the amine immediately without prior storage. These features enable histamine to tune the fine balance between immunity and tolerance by affecting dendritic cells, immunoregulatory cells, T-cell polarization and cytokine production, making the way for new pharmacological strategies to control immune reactivity during immune disorders, such as autoimmunity.
20714814 Cell biology of osteoimmunology. 2010 Sep Osteoimmunology is defined as the research area focusing on the crosstalk between the immune system and the muskoskeletal system. After nearly a decade of research, we are now beginning to understand the basic principles of this crosstalk. It seems that almost all immune cells are capable of communicating with osteoblasts, osteoclasts, and their respective progenitors - and vice versa. Diseases that fall into the category of osteoimmunology including osteoporosis, rheumatoid arthritis, and periodontal disease are of particular significance considering their implications in quality of life, their increased incidence in the population, and socioeconomic issues. To better understand the underlying pathogenesis, the main pathways of the crosstalk between the immune system and the muskoskeletal system need to be uncovered. Our current understanding has already provided the scientific basis for the development of targeted therapies. However, the challenge of future studies is to further decipher this crosstalk at cellular and molecular levels.
19373466 Interstitial pneumonitis associated with infliximab therapy without methotrexate treatment 2009 Dec Tumor necrosis factor (TNF)-α inhibitors are increasingly being used to treat rheumatoid arthritis. Infliximab (INF) is a TNF-α inhibitor that is usually used in combination with methotrexate (MTX). Interstitial lung disease (ILD) during combination therapy has been attributed to MTX rather than INF. However, INF-associated ILD without combination with MTX has recently been reported. We describe herein a case of severe ILD secondary to INF without MTX therapy.
19953908 [Cytokine in synovial monocytic cells from rheumatoid arthritis patients]. 2009 Jul 21 OBJECTIVE: To evaluate the inhibitory effect of blockade of Rho kinase upon mediating the secretion of proinflammatory cytokine in monocytic cells from rheumatoid arthritis (RA) patients. METHODS: Synovial fluid (SF) monocytic cells and peripheral blood monocytes (PB) from active RA patients were treated with TNFalpha or LPS respectively in the presence or absence of a specific ROK inhibitor, Y27632. ROK activity was assessed by Western blot and cytokine secretion measured by ELISA. RESULTS: Elevated ROK activity was found in synovial fluid monocytic cells from active RA patients. ROK activity was correlated with DAS, an index of disease activity of RA patients. ROK inhibitor Y27632 reduced the secretion of TNFalpha, IL-1beta and IL-6 in RA SF monocytic cells, but had no effect upon the secretion of IL-10, an anti-inflammatory cytokine. CONCLUSION: The present study provides novel evidence that ROK mediates the secretion of proinflammatory cytokines in monocytic cells from RA synovial fluids, suggesting a critical role of ROK in macrophage-mediated synovial inflammation of RA. Thus inhibition of ROK may be a new therapeutic target for RA.
20231202 Single-joint outcome measures: preliminary validation of patient-reported outcomes and phy 2010 May OBJECTIVE: To assess the validity, responsiveness, and reliability of single-joint outcome measures for determining target joint (TJ) response in patients with inflammatory arthritis. METHODS: Patient-reported outcomes (PRO), consisting of responses to single questions about TJ global status on a 100-mm visual analog scale (VAS; TJ global score), function on a 100-mm VAS (TJ function score), and pain on a 5-point Likert scale (TJ pain score) were piloted in 66 inflammatory arthritis subjects in a phase 1/2 clinical study of an intraarticular gene transfer agent and compared to physical examination measures (TJ swelling, TJ tenderness) and validated function questionnaires (Disabilities of the Arm, Shoulder and Hand scale, Rheumatoid Arthritis Outcome Score, and the Health Assessment Questionnaire). Construct validity was assessed by evaluating the correlation between the single-joint outcome measures and validated function questionnaires using Spearman's rank correlation. Responsiveness or sensitivity to change was assessed through calculating effect size and standardized response means (SRM). Reliability of physical examination measures was assessed by determining interobserver agreement. RESULTS: The single-joint PRO were highly correlated with each other and correlated well with validated functional measures. The TJ global score exhibited modest effect size and modest SRM that correlated well with the patient's assessment of response on a 100-mm VAS. Physical examination measures exhibited high interrater reliability, but correlated less well with validated functional measures and the patient's assessment of response. CONCLUSION: Single-joint PRO, particularly the TJ global score, are simple to administer and demonstrate construct validity and responsiveness in patients with inflammatory arthritis. (ClinicalTrials.gov identifier NCT00126724).
19634927 Etoricoxib: a review of its use in the symptomatic treatment of osteoarthritis, rheumatoid 2009 Jul 30 Etoricoxib is a selective cyclo-oxygenase (COX)-2 inhibitor, approved in Europe for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis. Etoricoxib provided similar symptomatic relief to nonselective NSAIDs in patients with these conditions, and to celecoxib in patients with osteoarthritis. The drug was associated with fewer uncomplicated upper gastrointestinal (GI) adverse events than nonselective NSAIDs, and was noninferior to diclofenac in terms of the rate of thrombotic cardiovascular (CV) events. Etoricoxib may be considered as a treatment option for patients requiring NSAID therapy, particularly those at risk of upper GI events, after careful consideration of significant risk factors for CV events (including uncontrolled hypertension). As with all NSAIDs, the potential GI and CV risks of treatment with etoricoxib should be weighed against the potential benefits in individual patients, and it should be administered at the lowest effective dose for as short a duration as possible.
20873248 [Comparative evaluation of the safety and efficacy of etoricoxib and diclofenac on the upp 2010 The review gives and analyzes the data of a number of studies evaluating the safety and efficacy of nonsteroidal anti-inflammatory drugs on the upper gastrointestinal tract. Particular emphasis is laid on the results of the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) study program. The randomized MEDAL study has shown that etoricoxib has more benefits than diclofenac.
20527084 Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatin 2009 INTRODUCTION: In rheumatoid arthritis (RA), synovial fluid (SF)contains a large number of neutrophils that contribute to the inflammation and destruction of the joints. The SF also contains granulocyte-macrophage colony-stimulating factor (GM-CSF),which sustains viability of neutrophils and activates their functions. Using proteomic surveillance, we here tried to elucidate the effects of GM-CSF on neutrophils. METHODS: Neutrophils stimulated by GM-CSF were divided in to four subcellular fractions: cytosol, membrane/organelle, nuclei,and cytoskeleton. Then, proteins were extracted from each fraction and digested by trypsin. The produced peptides were detected using matrix-assisted laser desorption ionisation-time of-flight mass spectrometry (MALDI-TOF MS). RESULTS: We detected 33 peptide peaks whose expression was upregulated by more than 2.5-fold in GM-CSF stimulated neutrophils and identified 11 proteins out of the 33 peptides using MALDI-TOF/TOF MS analysis and protein database searches. One of the identified proteins was neutrophil gelatinase-associated lipocalin (NGAL). We confirmed that the level of NGAL in SF was significantly higher in patients with RA than in those with osteoarthritis. We next addressed possible roles of the increased NGAL in RA. We analysed proteome alteration of synoviocytes from patients with RA by treatment with NGAL in vitro. We found that, out of the detected protein spots (approximately 3,600 protein spots), the intensity of 21 protein spots increased by more than 1.5-fold and the intensity of 10 protein spots decreased by less than 1 to 1.5-fold as a result of the NGAL treatment. Among the 21 increased protein spots, we identified 9 proteins including transitional endoplasmic reticulum ATPase (TERA), cathepsin D, and transglutaminase 2 (TG2), which increased to 4.8-fold, 1.5-fold and 1.6-fold, respectively. Two-dimensional electrophoresis followed by western blot analysis confirmed the upregulation of TERA by the NGAL treatment and, moreover, the western blot analysis showed that the NGAL treatment changed the protein spots caused by post-translational modification of TERA.Furthermore, NGAL cancelled out the proliferative effects of fibroblast growth factor (FGF)-2 and epidermal growth factor(EGF) on chondrocytes from a patient with RA and proliferative effect of FGF-2 on chondrosarcoma cells.Conclusions Our results indicate that GM-CSF contributes to the pathogenesis of RA through upregulation of NGAL in neutrophils, followed by induction of TERA, cathepsin D and TG2 in synoviocytes. NGAL and the upregulated enzymes may therefore play an important role in RA.
19124087 A measles-derived peptide treats and vaccinates against adjuvant arthritis. 2009 Mar Measles vaccine and porcine myelin basic protein were both found to ameliorate or abolish the symptoms of adjuvant arthritis (AA) in Lewis rats whether inoculated at the time of adjuvant administration or after the onset of arthritis. These results are consistent with clinical observations that measles infection can sometimes cause remission of juvenile rheumatoid arthritis. The fact that measles virus proteins and myelin basic protein have significant regions of homology allowed peptides based on these regions to be synthesized. A twenty-amino acid sequence exhibits significant anti-arthritic activity when inoculated into rats with pre-existing AA and it also prevented onset of AA when a single dose was preinoculated three weeks prior to AA induction. These data suggest the possibility of developing novel therapeutic vaccines against some forms of arthritis.
19910301 Use of "spydergrams" to present and interpret SF-36 health-related quality of life data ac 2009 Dec The Medical Outcomes Study Short Form-36 (SF-36) is a generic measure of health-related quality of life (HRQOL), validated and cross-culturally translated, which has been extensively utilised in rheumatology. In randomised controlled trials and observational studies, SF-36 provides rich data regarding HRQOL; but as typically portrayed, patterns of disease and treatment-associated effects can be difficult to discern. "Spydergrams" offer a simplified means to visualise complex results across all domains of SF-36 in a single figure: depicting disease and population-specific patterns of decrements in HRQOL compared with age and gender-matched normative data, as well as providing a tool for interpreting complex treatment-associated or longitudinal changes. Utilising spydergrams as a standard format to illustrate and report changes in SF-36 across different rheumatic diseases can greatly facilitate analyses and interpretations of clinical trial results, as well as providing patients an accessible means to compare baseline scores and treatment-associated improvements with normative data from individuals without arthritis. Furthermore, SF-6D utility scores based on mean changes across all eight domains of SF-36 are suggested as a quantitative means of summarising changes illustrated by spydergrams, offering a universal metric for cost-effectiveness analyses of therapeutic interventions.
20850384 Down regulation of Fc and complement receptors on B cells in rheumatoid arthritis. 2010 Dec B cell tolerance is regulated by receptors that modulate B cell receptor signaling, such as Fc gamma receptor IIb (FcγRIIb; CD32b) and complement receptors (CR) 1 and 2. Deficiency in these receptors may contribute to autoimmunity. To address this we have investigated the receptor expression in healthy individuals in comparison with rheumatoid arthritis (RA) patients. In healthy subjects we found that women had overall lower FcγRIIb expression on B cells than men that significantly decreased with age. RA patients had fewer FcγRIIb, CR1 and CR2 positive B cells and decreased receptor expressions compared to healthy subjects. Further, the RA B cells displayed a significantly increased proliferative response when cultured with interleukin-2 in vitro. In summary, the dysregulated B cells in RA are associated with lower FcγRIIb, CR1 and CR2 levels. The reduced FcγRIIb expression on B cells in women may influence the increased frequency of autoimmunity in women.
19579138 Circulating TNFRI and TNFRII levels correlated with the disease activity score (DAS28) in 2009 OBJECTIVE: To measure levels of soluble tumour necrosis factor alpha (TNFalpha) receptor type I (sTNFRI) and type II (sTNFRII) in order to correlate them with C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score (DAS28) in RA patients. METHODS: We recruited 41 RA patients classified according to American College of Rheumatology (ACR) criteria and 38 healthy subjects (HS). sTNFRI and sTNFRII were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Clinical activity in RA patients was evaluated using the Disease Activity Score using 28 joint counts (DAS28). The statistical analysis was realized using SPSS version 10.0. RESULTS: Soluble TNFRI and TNFRII levels were higher in RA patients (p = 0.04 and 0.001, respectively) than HS. Serum levels of sTNFRI correlated with sTNFRII (r = 0.699, p < 0.0001). sTNFRII correlated with DAS28 (r = 0.375, p = 0.017), RF (r = 0.505, p = 0.004), and ESR (r = 0.323, p = 0.042). CONCLUSION: The increased levels of both sTNFRI and sTNFRII suggest a secondary event related to the inflammatory state observed in RA, whereas the correlation of sTNFRII with RF, ESR, and DAS28 reflects the preferential TNFRII shedding induced by TNFalpha. sTNFRII may be useful as an additional inflammatory marker in RA.
19664474 Inhibition of HIF-1alpha activity by BP-1 ameliorates adjuvant induced arthritis in rats. 2009 Sep 18 Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1alpha. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1alpha, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.