ABSTRACT
Objective: To investigate the efficacy and safety of high-dose recombinant human interleukin-2 (rhIL-2) in treatment of patients with advanced melanoma. Methods: Twenty Chinese patients with advanced melanoma were planned to be enrolled to receive high-dose rhIL-2 treatment. The overall response rare (ORR), progression-free survival (PFS), overall survival (OS) and incidence of toxicity were evaluated. Results: Fourteen patients were enrolled, of them twelve could be evaluated. One patient achieved partial response (PR), and the maintaining duration of response was 43.0 months; three patients achieved stable disease (SD); 8 patients achieved progressive disease (PD). The median PFS was 56.0±7.6 d, and the median OS was 11.0±2.6 months. The incidence rate of grade III-IV toxicity was 40.3%, mainly manifested as gastrointestinal reaction, fever and cardiovascular reaction. Conclusion: The efficacy of high-dose rhIL-2 for Chinese patients with advanced melanoma is not as good as those previously reported in studies abroad, with high incidence rate of adverse effects. The patients can get long response duration as rhIL-2 worked. It is necessary to perform further studies on how to make choice of administration dose and select potential patients who will benefit from the treatment. Copyright© 2011 by TUMOR.
ABSTRACT
<p><b>BACKGROUND</b>p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA).</p><p><b>METHODS</b>Human FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ, retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured.</p><p><b>RESULTS</b>IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes.</p><p><b>CONCLUSION</b>p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.</p>