Citations

Background: An uncontrolled pilot study demonstrated that daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for the treatment of active ulcerative colitis. Methods: A randomised, double blind, placebo controlled trial was conducted to evaluate the efficacy of daclizumab induction therapy in patients with active ulcerative colitis. A total of 159 patients with moderate ulcerative colitis were randomised to receive induction therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was induction of remission at week 8. Remission was defined as a Mayo score of 0 on both endoscopy and rectal bleeding components and a score of 0 or 1 on stool frequency and physician’s global assessment components. Response was defined as a decrease from baseline in the Mayo score of at least 3 points. Results: Two per cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with 10% of those who received placebo. Response occurred at week 8 in 25% of patients receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated. The most frequently reported adverse events in daclizumab treated patients compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia (10.7%). Conclusion: Patients with moderate ulcerative colitis who are treated with daclizumab are not more likely to be in remission or response at eight weeks than patients treated with placebo.

Abstract PURPOSE: We analyzed the expression of genes to identify reliable molecular markers in the diagnosis and progression of prostate cancer. EXPERIMENTAL DESIGN: Gene expression profiling was done using HG-U133 set microarrays in 32 prostate cancer and 8 benign tissues of patients with cancer. Expression levels of 11 genes were selected for quantitative real-time PCR evaluation in 52 prostate cancer and 20 benign tissues. Further, to assess transcriptional inactivation, we analyzed the promoter methylation of genes by quantitative methylation-specific PCR in 62 tumor and 36 benign tissues. RESULTS: Our results showed a significant down-regulation in the mRNA expression levels of PRIMA1, TU3A, PDLIM4, FLJ14084, SVIL, SORBS1, C21orf63, and KIAA1210 and up-regulation of FABP5, SOX4, and MLP in prostate cancer tissues by TaqMan real-time PCR. Quantitative methylation-specific PCR of PDLIM4, SVIL, PRIMA1, GSTP1, and PTGS2 detected prostate carcinoma with a sensitivity of 94.7%, 75.4%, 47.4%, 89.5%, and 87.7%, and a specificity of 90.5%, 75%, 54.2%, 95.8%, and 90.2%, respectively. Using this panel of methylation markers in combination, we were able to distinguish between prostate cancer and adjacent benign tissues with sensitivities and specificities of about 90% to 100%. Our data provide evidence of transcriptional repression of the putative tumor suppressor gene PDLIM4 by hypermethylation. CONCLUSIONS: Our analysis revealed differential expression of eight down-regulated and three up-regulated genes, implicating their role in prostate cancer development and progression. We further showed that the hypermethylation of PDLIM4 gene could be used as a sensitive molecular tool in detection of prostate tumorigenesis.