Effect of an hdm-2 antagonist peptide inhibitor on cell cycle progression in p53-deficient H1299 human lung carcinoma cells.

The hdm-2 oncogene is overexpressed in several types of malignancies including osteosarcomas, soft tissue sarcomas and gliomas and hdm-2 has been associated with accelerated tumor formation in both hereditary and sporadic cancers. Among the other key binding partners, hdm-2 forms a complex with the tumor suppressor p53, resulting in a rapid proteasome-mediated degradation of the p53 protein. This positions the hdm-2-p53 complex as an attractive target for the development of anticancer therapy and recently the first small molecule hdm-2 antagonist has been reported.

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand mRNA expression in patients with rheumatoid arthritis and healthy controls.

Objective: To further understand the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANK-L) in rheumatoid arthritis (RA), we studied the levels of RANK-L and OPG mRNA in peripheral blood mononuclear cells (PBMC) and synovial tissue of patients with RA and controls.

Methods: RANK-L and OPG mRNA levels were measured in PBMC and CD4+/CD8+ T cell subsets of patients with chronic RA, osteoarthritis (OA), and healthy controls, using quantitative real-time polymerase chain reaction. OPG and RANK-L mRNA levels were measured in paired blood and synovial tissue samples of patients with early, untreated RA at 2 timepoints with an interval of 16 weeks.

Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis: effects of treatment with cyclosporin A (Neoral).

Objective: To study T cell receptor (TCR) repertoire changes in synovial membrane over a 16 week period in patients with early rheumatoid arthritis (RA); and to study the influence of cyclosporin A (CSA) on TCR repertoire in a subgroup of these patients.

Methods: Synovial tissue biopsies and paired blood samples were obtained from 12 patients with early RA at 2 time points. Seven patients were treated with CSA (Neoral-Sandimmun, 3 mg/kg/day) and 5 patients with placebo for 16 weeks.

The autoimmune pathogenesis of rheumatoid arthritis: role of autoreactive T cells and new immunotherapies.

Objectives: To review the role of T lymphocytes in the pathogenesis of rheumatoid arthritis (RA) and discuss the relevance of the components of the trimolecular complex (synovial T cells, autoantigens, and antigen presenting cells) in the pathogenic autoimmune response in RA.

Methods: Currently available experimental data are combined into a hypothetical pathway that may explain some of the events in the RA process. The literature regarding the potential therapeutic strategies that interfere with specific components of the trimolecular complex and other mediators are discussed briefly.

Skewed T-cell receptor variable gene usage in the synovium of early and chronic rheumatoid arthritis patients and persistence of clonally expanded T cells in a chronic patient.

Objective: Autoreactive T cells may contribute to the pathogenesis of rheumatoid arthritis (RA). We studied the T-cell receptor (TCR) V-gene repertoire in the blood and synovium of early and chronic RA patients using polymerase chain reaction-enzyme-linked immunosorbent assay to evaluate possible differences between these patient groups.

Results: Over-represented TCR V genes were observed in the synovium, but not in the blood of all RA patients (n = 38).