scholarly journals Good response to methotrexate is associated with a decrease in the gene expression of the drug transporter ABCG2 in patients with rheumatoid arthritis

2020 ◽  
Author(s):  
Satoshi Muto ◽  
Nana Minamitani ◽  
Takehisa Ogura ◽  
Arata Nakajima ◽  
Koichi Nakagawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Clinical Response ◽  
Characteristic Curve ◽  
Rate Of Change ◽  
Gene Expression Level ◽  
Expression Level ◽  
Drug Transporter ◽  
Cancer Resistance ◽  
Abcg2 Gene

Abstract Background Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). We previously performed a cross-sectional, observational study and reported an association between the gene expression level of the drug transporter ABCG2/BCRP (breast cancer resistance protein) and RA disease control in patients receiving MTX. Methods We designed a prospective study in two medical centers in Japan to confirm the association of ABCG2 gene expression level with the clinical response to MTX in MTX-naive patients with RA. The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. Results Based on the clinical response at 12 weeks after the initiation of MTX, a total of 24 patients were classified into the good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of baseline gene expression levels for the prediction of the EULAR good response at week 12 showed a significant association with ABCG2 alone, and the rate of baseline expression of ABCG2 mRNA above the cut-off value determined by a receiver operating characteristic curve was higher in good responders than in non-good responders (p = 0.012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% versus +41% from baseline, respectively; p = 0.011). The ABCG2 gene expression level did not correlate with DAS28 at baseline or at week 12, and neither did the rate of change in ABCG2 gene expression level. Conclusions We have confirmed the association between the gene expression level of the drug transporter ABCG2 and the clinical response to MTX in patients with RA.

scholarly journals Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients

Reumatismo ◽  
2020 ◽  
Vol 72 (2) ◽  
pp. 93-102
Author(s):  
N.A.G. Gaafar ◽  
M. Aslani ◽  
Z. Aghazadeh ◽  
S.S. Mortazavi-Jahromi ◽  
A. Razavi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Conventional Therapy ◽  
Gene Expression Level ◽  
Expression Level ◽  
Control Group ◽  
Healthy Controls ◽  
Signal Transducer ◽  
Mannuronic Acid ◽  
Significant Difference

Rheumatoid arthritis (RA), a form of inflammatory arthritis, is a chronic joint disease characterized by pain and inflammation that affects 0.5% to 1% of the population worldwide. The safety, efficacy, tolerability, and potency of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been reported by several in vitro studies, experimental models and clinical trials phase I/II and III in ankylosing spondylitis and rheumatoid arthritis (RA) patients This research is designed to study the therapeutic efficacy of oral administration of mannuronic acid in RA patients who had inadequate response to conventional drugs and to assess the effect of this drug on gene expression of the signal transducer and activator of transcription (STATs) protein (STAT1, STAT3, STAT4, and STAT6). The study has included 15 RA patients who had an insufficient response to the conventional therapy. The oral dose of mannuronic acid was 1000mg divided into two 500 mg doses per day for 3 months as an addition to conventional therapy. There were 15 healthy volunteer in the control group. Blood samples were collected from both groups, once from healthy controls and twice from RA patients before and after treatment by M2000. The peripheral blood mononuclear cells (PBMCs) were isolated to assess the gene expression level of STAT1, STAT3, STAT4, and STAT6 using the real-time PCR method. Results obtained in this study demonstrated a significant difference in the gene expression level of STAT1 between healthy controls and patients before treatment as well as a significant reduction in RA patients after treatment compared with the level before treatment. In addition, the gene expression level of STAT3 and STAT4 showed a significant reduction in RA patients after treatment compared to patients before treatment, while there was no significant difference between RA patients before treatment and the healthy control group for both molecules. On the other hand, there was no change in the gene expression level of STAT6 among all groups. The outcomes of this study confirmed that β-D-mannuronic acid (M2000) has the ability to control the levels of STAT1, STAT3 and STAT4 in RA patients, and might be beneficial in the management and therapy of RA.

The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients

2020 ◽  
Vol 17 (5) ◽  
pp. 704-710
Author(s):  
Nada A.G. Gaafar ◽  
Mona Aslani ◽  
Zahra Aghazadeh ◽  
Alireza Razavi ◽  
Abbas Mirshafiey
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Oral Administration ◽  
Therapeutic Efficacy ◽  
Gene Expression Level ◽  
Expression Level ◽  
Mannuronic Acid ◽  
Significant Difference ◽  
Before And After ◽  
Immunosuppressive Property

Background: Rheumatoid Arthritis (RA) is a complex disease involving an unknown number of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately 1% of the population worldwide. The safety and therapeutic efficacy of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to phase I/11 and 111 in Rheumatoid Arthritis (RA) patients. Objective: In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000 on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase (TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis. Methods: The study has included 15 RA patients who had an insufficient response to the conventional drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15 healthy participants considered as control. Blood samples have been collected from both groups once from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method. Results: The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients after treatment with M2000 compared to before treatment. On the other hand, the gene expression level of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared to before treatment, but there was no significant difference between the group of RA patients before treatment and the control group. Vice versa to other molecules, there was no significant difference in the level of TIMP1 in compression with RA patients before and after treatment. Conclusion: our findings proved that the β -D- mannuronic acid) as a novel NSAID with immunosuppressive property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2 molecules in RA patients.

The investigation of CD36 scavenger receptor and MSR1 scavenger receptor gene expression level in patients with atherosclerosis

2010 ◽  
Vol 27 ◽  
pp. S66
Author(s):  
M. Piechota ◽  
A. Banaszewska ◽  
E. Guzniczak ◽  
G. Rosinski ◽  
T. Siminiak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Scavenger Receptor ◽  
Gene Expression Level ◽  
Expression Level ◽  
Receptor Gene Expression

The impact of gene-body H3K36me3 patterns on gene expression level changes in chronic myelogenous leukemia

Gene ◽  
2021 ◽  
pp. 145862
Author(s):  
Lu-Qiang Zhang ◽  
Jun-Jie Liu ◽  
Li Liu ◽  
Guo-Liang Fan ◽  
Yan-Nan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Gene Expression Level ◽  
Expression Level ◽  
Gene Body ◽  
The Impact

scholarly journals Elevated Lipocalin-2 Can Indicate the Vascular Inflammation in Patients with Ischemic Stroke

2019 ◽  
Author(s):  
Rajnics P ◽  
◽  
Kellner A ◽  
Nagy F ◽  
Alföldi V ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Stroke ◽  
Gene Expression Level ◽  
Expression Level ◽  
Neutrophil Granulocytes ◽  
Lipocalin 2 ◽  
Relative Gene Expression ◽  
Thrombotic Risk ◽  
Relative Gene ◽  
Relative Gene Expression Level

Purpose: Elevated level of Lipocalin-2 (LCN2), a new acute phase adipokine, was described after ischemic stroke. A number of researchers feel as though that LCN2 originated from the infiltrating neutrophils and other cells in brain after stroke. Others measured elevated LCN2 expression in arteriosclerotic plaque. Therefore we have investigated LCN2 relative gene expression level of blood neutrophil granulocytes in patients with ischemic stroke to assess if elevated LCN2 is the cause or consequence of ischemic stroke. Methods: Laboratory and anamnestic data were collected, which could have a role in development of thrombo-embolic events in patients with ischemic stroke. RNA based method was used to evaluate the relative gene expression level of LCN2. We calculated Odds Ratio (OR) and Confidence Interval (CI) for the association between LCN2 and ischemic stroke. Results: 34 samples were available for evaluation. The LCN 2 relative gene expression level was decreased in 12 cases. In this group, 91% of patients have Atrial Fibrillation (AF) at the time of hospitalisation. The mean LCN2 relative gene expression value was 64.25% (ranges: 34%-115%) in patients with AF. It was significantly lower than in patients with normal sinus rhythm (409.2%; ranges: 127%-1127%; p=0.0003). The elevated LCN2 relative gene expression level significantly (p=0.012) increases the risk of stroke (OR: 12.6) independently from other factors. Conclusions: High LCN2 expression level seems to have strong positive predictive value on ischemic stroke, and may be useful in thrombotic risk stratification of plaque vulnerability in these patients.

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