ABSTRACT
BACKGROUND: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α. AIMS: To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy. METHODS: In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies. RESULTS: A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%, and that of TNF-α decreased from 54.5 to 36.2%. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P = 0.001, respectively). CONCLUSIONS: These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Colitis, Ulcerative/drug therapy , Gene Expression Regulation/drug effects , Intracellular Signaling Peptides and Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis, Ulcerative/metabolism , Female , Humans , Infliximab , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Tumor Necrosis Factor-alpha/genetics , Young AdultABSTRACT
BACKGROUND/AIMS: Our aim was to assess the long-term data regarding efficacy and safety of infliximab (IFX) treatment for refractory Crohn's disease (CD) patients in our tertiary teaching hospital. METHODS: We have retrospectively analyzed the medical records of 89 CD patients who underwent IFX treatment between March 2003 and February 2011 at Kyung Hee University Hospital (Seoul, Korea). The primary outcome measurements were the rates of initial clinical response (CR) at 10 weeks after the 1st IFX infusion and sustained CR at the end of the follow-up. Overall adverse events related to IFX treatment were also evaluated. RESULTS: The mean (SD) follow-up period of eligible 80 patients was 33.7 (21.9) months. A total of 77 patients (96%) showed initial clinical response, but 8 patients showed loss of response to IFX during the follow-up. Finally, 59 patients (59/77, 76.6%) showed sustained CR at the end of the study. Logistic regression analyses showed that an initial CR at 10 weeks was the independent predictor associated with sustained CR (OR 22.286, 95% CI 2.742-132.717, p=0.001). Overall adverse events reported in 18 patients (18/80, 23.3%), including 3 serious infection (pulmonary tuberculosis and herpes zoster). CONCLUSIONS: Treatment with IFX was efficacious and relatively safe for refractory CD patients in Korea. An initial CR at 10 weeks was significantly associated with sustained CR.
