Drugs Dimethyl Fumarate Research Articles

HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells.

We recently reported that pretreatment of IL-2 activated human natural killer (NK) cells with the drugs dimethyl fumarate (DMF) and monomethyl fumarate (MMF) upregulated the expression of surface chemokine receptor CCR10. Ligands for CCR10, namely CCL27 and CCL28, induced the chemotaxis of these cells. Here, we performed a bioinformatics analysis to see which chemokines might be expressed by the human HCT-116 colorectal cancer cells. We observed that, in addition to CCL27 and CCL28, HCT-116 colorectal cancer cells profoundly express CXCL16 which binds CXCR6. Consequently, NK92 cells were treated with DMF and MMF for 24h to investigate in vitro chemotaxis towards CXCL16, CCL27, and CCL28. Furthermore, supernatants collected from HCT-116 cells after 24 or 48h incubation induced the chemotaxis of NK92 cells. Similar to their effects on human IL-2-activated NK cells, MMF and DMF enhanced the expression of CCR10 and CXCR6 in NK92 cells. Neutralizing anti-CXCL16 or anti-CCL28 inhibited the chemotactic effects of 24 and 48 supernatants, whereas anti-CCL27 only inhibited the 48h supernatant activity, suggesting that 24h supernatant contains CXCL16 and CCL28, whereas HCT-116 secretes all three chemokines after 48h in vitro cultures. CXCL16, CCL27, and CCL28, as well as the supernatants collected from HCT-116, induced the mobilization of (Ca)2+ in NK92 cells. Cross-desensitization experiments confirmed the results of the chemotaxis experiments. Finally, incubation of NK92 cells with HCT-116 induced the lysis of the tumor cells. In summary, these results might have important implications in directing the anti-tumor effectors NK cells towards tumor growth sites.

Interferon beta-1a for multiple sclerosis: old drug, new clothes

The development of new drugs for treatment of relapsing-remitting multiple sclerosis has been extremely successful. The oral drugs dimethylfumarate and teriflunomide and the monoclonal antibody alemtuzumab have enlarged the therapeutic armamentarium, which is presently composed of ten approved drugs. 1 Wingerchuk DM Carter JL Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014; 89: 225-240 Summary Full Text Full Text PDF PubMed Scopus (301) Google Scholar , 2 Oh J Calabresi PA Emerging injectable therapies for multiple sclerosis. Lancet Neurol. 2013; 12: 1115-1126 Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar In The Lancet Neurology, Peter Calabresi and colleagues report the 48-week results of a phase 3 trial (ADVANCE) 3 Calabresi P Kieseier BC Douglas LA et al. Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014; (published online May 1.)http://dx.doi.org/10.1016/S1474-4422(14)70068-7 PubMed Google Scholar of an old drug in a new formulation: pegylated interferon beta-1a. Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind studyAfter 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Full-Text PDF

Advance in new oral drugs for multiple sclerosis

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system and represents one of the most common causes of chronic neurologic disability. Until recently, major treatments have relied on agents by injection which can induce injection ⁃related adverse events. The parenteral route of administration may affect the compliance with therapy in multiple sclerosis. Therefore, there is a need for the development of oral agents. The research of five oral drugs (cladribine, fingolimod, teriflunomide, laquinimod and dimethyl fumarate), is carrying out in Phase Ⅲ study. In this article, we review the undergoing clinical trials of these five oral agents. DOI：10.3969/j.issn.1672⁃6731.2012.02.011