Search PubMed⌕ Search

Biomedical subjects

Daisuke Goto

Publications and source records attributed to Daisuke Goto.

38 records · Page 3Linked to original sources

[Adalimumab].

Recently, the anti-tumor necrosis factor(TNF)-alpha treatments for RA are successful in alleviating the discomforts associated with swollen, painful joints. Adalimumab(D2E7) is the first fully human anti-TNF-alpha monoclonal antibody(IgG1). Therefore, it has low immunogenicity and possibly greater therapeutic potential compared with other anti-TNF-alpha antibodies. This is administered subcutaneously at a dose of 1 mg/kg biweekly. The combined therapy with methotrexate(MTX) is efficacious to the patients who receive MTX alone and are insufficient to control symptoms of RA. The therapeutic effects become evident within 24 hours to one week after administration and reached maximum effect after one to two weeks. In adalimumab recipient, radiographic progression is also controlled and serum levels of matrix metalloproteinase-1(MMP-1) and MMP-3 decrease. For patients with RA, the treatment of adalimumab will set a new standard for symptom control and joint protection.

Adalimumab↗

c-myc is a downstream target of the Smad pathway.

c-Myc is one of the most potent regulators of cell cycle progression in higher eukaryotes. Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-beta (TGF-beta) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-myc promoter. This element is a complex of the TGF-beta1 inhibitory element (TIE) originally identified in the transin/stromelysin promoter and an E2F site responsible for transcriptional activation of the c-myc promoter. Smad3 and E2F-4 directly bound to the element (TIE/E2F), and substitution of two nucleotides in TIE/E2F impaired binding of both Smad3 and E2F-4 as well as serum-induced activation and TGF-beta-induced suppression of the c-myc promoter activity. Smads bound TIE/E2F within 1 h after stimulation with TGF-beta, before the suppression of c-myc transcription, whereas binding of p130 to TIE/E2F became augmented later than 12 h. TGF-beta signaling did not compete with E2F-4 for binding to TIE/E2F, but reduced p300 co-immunoprecipitating with E2F-4. Therefore, TGF-beta signaling may suppress c-myc promoter activity by dissociating p300 from E2F-4.

Animals↗