Cytokines are believed to be involved in a “vicious circle” of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In th...Cytokines are believed to be involved in a “vicious circle” of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose（30 μg/m L） iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.展开更多
Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-6...Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. Methods In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo （n=95） or T-614 at 50 mg （n=93） or 25 mg （n=92） daily. Active disease was defined by 4 of the following 5 criteria： 〉5 tender joints, 〉3 swollen joints, morning stiffness lasting for 〉60 minutes, and Westergren erythrocyte sedimentation rate （ESR） 〉28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology （ACR） response rate using the intent-to-treat population. Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo （P〈0.0001）, and the 50 mg/d dose compared to the 25 mg/d dose （P〈0.05） when using the ACR response analyses after 24 weeks. ESR and c-reactive protein （CRP） were significantly different in the treatment groups after 24 weeks. The incidence of adverse events （AEs） was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase （sALT）, skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. Conclusion T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81372852 and 81202095)
文摘Cytokines are believed to be involved in a “vicious circle” of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose（30 μg/m L） iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
文摘Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. Methods In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo （n=95） or T-614 at 50 mg （n=93） or 25 mg （n=92） daily. Active disease was defined by 4 of the following 5 criteria： 〉5 tender joints, 〉3 swollen joints, morning stiffness lasting for 〉60 minutes, and Westergren erythrocyte sedimentation rate （ESR） 〉28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology （ACR） response rate using the intent-to-treat population. Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo （P〈0.0001）, and the 50 mg/d dose compared to the 25 mg/d dose （P〈0.05） when using the ACR response analyses after 24 weeks. ESR and c-reactive protein （CRP） were significantly different in the treatment groups after 24 weeks. The incidence of adverse events （AEs） was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase （sALT）, skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. Conclusion T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.
