Magnetic Resonance Imaging of Bilateral Hands Is More Optimal Than MRI of Unilateral Hands for Rheumatoid Arthritis.

OBJECTIVE: To explore the advantages of magnetic resonance imaging (MRI) of bilateral hands in rheumatoid arthritis (RA). METHODS: Consecutive patients with active RA were recruited for clinical assessments, radiographs, and MRI of bilateral hands. Bilateral hands were scanned simultaneously on 3.0 T whole-body MRI system and were scored on synovitis, osteitis, and bone erosion according to the RA MRI scoring (RAMRIS) system. RESULTS: Among 120 patients included, wrist bones and metacarpophalangeal joint (MCPJ) 2 proximal showed bone erosion in early RA. The second to fifth metacarpal bases and the second to fourth MCPJ distal showed more bone erosion in mid-stage or late-stage RA. When MRI of dominant unilateral hand was analyzed, MRI synovitis and osteitis in 5% of wrists and 3 MRI features in 5-14% of MCPJ were misdiagnosed (McNemar test, all p < 0.05). There were 46% wrist synovitis, 29-52% MCPJ2-5 synovitis, 45% wrist osteitis, and 20%-34% MCPJ2-5 osteitis not detected by joint tenderness and/or swelling. When the clinically more severe hand was selected for MRI of unilateral hand according to physical examination, MRI synovitis in 5% of wrists and 3 MRI features in 7-15% of MCPJ were misdiagnosed (all p < 0.05). Scatter plots and linear regression analyses were used to illustrate RAMRIS between dominant or selected hand (Y values) and nondominant or nonselected hand (X values). All linear models were markedly different from a Y = X linear model, indicating the dominant or clinically more severe hand could not represent the contralateral hand to evaluate RAMRIS. CONCLUSION: MRI of bilateral hands is more optimal than MRI of the unilateral hand in RA.

Concurrent blockade of the NF-kappaB and Akt pathways potently sensitizes cancer cells to chemotherapeutic-induced cytotoxicity.

Nuclear factor-kappaB (NF-kappaB) and Akt are two major cell survival pathways that are often constitutively activated and can be further stimulated by chemotherpeutics in cancer cells. Although individually targeting the NF-kappaB or Akt has been reported to sensitize caner therapy, the effectiveness of concurrent blocking these two pathways for chemosensitizing of cancer cells to genotoxic therapeutics has not been investigated. In the present study, we investigate the activation of the NF-kappaB and Akt pathways by two frontline anticancer drugs cisplatin and etopside in a variety of cancer cell lines. The effects of blocking these two survival pathways individually or concurrently on cisplatin- or etopside-induced cytotoxicity were detected. The results show that cisplatin and etopside activate both NF-kappaB and Akt in cancer cells. Blockade of either of these pathways with chemical inhibitors or siRNA moderately sensitized cancer cells to cisplatin- or etopside-induced cytotoxicity. Strikingly, much more effective potentiation of cytotoxicity to these anticancer drugs was achieved when NF-kappaB and Akt were concurrently blocked. These data suggest that NF-kappaB and Akt cooperatively attenuate therapeutic-induced cytotoxicity and concurrently blocking these pathways is an effective strategy for improving the anticancer efficacy of therapeutics.