A multicentre Phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic Castration Resistant Prostate Cancer (mCRPC), suitable for treatment with a taxane.

开始日期2019-08-21

申办/合作机构-

NCT04028388 / Completed临床2期

A Multicentre Phase 2b Trial to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC), Suitable for Treatment With a Taxane

This is a multicenter phase 2b study to evaluate the efficacy and tolerability of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer, suitable for treatment with a taxane.

开始日期2019-07-17

申办/合作机构

Modra Pharmaceuticals BV

100 项与 Tubulin x HIV-1 pol 相关的临床结果

登录后查看更多信息

100 项与 Tubulin x HIV-1 pol 相关的转化医学

登录后查看更多信息

0 项与 Tubulin x HIV-1 pol 相关的专利（医药）

登录后查看更多信息

项与 Tubulin x HIV-1 pol 相关的文献（医药）

2011-06-01·Connective Tissue Research4区 · 医学

Cyclic mechanical stretch downregulates IL-1β-induced COX-2 expression and PGE₂production in rheumatoid arthritis fibroblast-like synoviocytes

4区 · 医学

Article

作者: Lv, Yonggang ; Yan, Yan ; Singh, Gurinder K. ; You, Xin ; Li, Xian ; Zhang, Feifei ; Yang, Li ; Zhou, Wei ; Liu, Wanqian ; Wang, Ping

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are one of the primary sources of inflammatory cytokines, including prostaglandins (PGs) and matrix metalloproteinases (MMPs) in joints that are detrimental to the bone, cartilage, and the surrounding tissue. Many studies, in recent years, have shown that physiotherapies play a beneficial effect on the maintenance of joint homeostasis in RA; however, the underlying mechanisms involved are still not fully elucidated. This study was performed to investigate cellular mechanism of mechanical strain-mediated actions in RA-FLS. RA-FLS were grown on collagen-coated silicone membranes and were exposed to 6% cyclic mechanical stretch at a frequency of 0.5 Hz for different times in the presence/absence of IL-1β. Real-time PCR and western blotting were used to detect the mRNA and protein level of cyclooxygenase-2 (COX-2) and MMP-1. The production of prostaglandin E(2) (PGE(2)) was quantified by ELISA method. Our results showed that 6% cyclic mechanical stretch significantly inhibited IL-1β-induced MMP-1 (gene) and COX-2 (gene and protein) expression at 15, 40, and 80 min. It also downregulated the IL-1β-induced production of PGE(2). Further investigation of nuclear factor kappa B (NF-κB) signal pathway-related effectors IκB-α and IκB-β revealed that 6% cyclic stretch inhibited their IL-1β-induced degradation in cytoplasm as well as reversed their gene transcription levels. Our data suggest that gentle level of cyclic mechanical stretch exerts a protective effect on RA-FLS as it downregulates the level of MMP-1 protease, COX-2, and proinflammatory PGE(2). The underlying mechanism appears to be, in part, executed through NF-κB and its upstream effectors.