Development of Evaluating Ways for the Efficacy of Anti-VEGF Biopharmaceuticals

BACKGROUND: Angiogenesis mediated by VEGF constitutes a new target for anti-cancer therapy which has explored through different ways of intervention aiming at the blocking of the tumoral angiogenesis. In the present study, we developed the assays by which efficacies of anti-VEGF inhibitor candidates are evaluated at the various levels. METHODS & RESULTS: First, we developed two sandwich ELISAs using coated anti-VEGF Ab and soluble Flt-1 receptor fusion protein (sFlt-1/Fc). As low as 200 pg/ml of hVEGF diluted in human sera was detectable by these assays. In addition, we found that VEGF inhibitors (2 microngram/ml of either anti-VEGF Ab or sFlt-1/Fc) completely block 5 ng/ml VEGF in these ELISAs. Subsequently, two bioassays, wound healing and HUVEC tube formation assays, revealed that anti-VEGF Ab (1 microngram/ml) & sFlt-1/Fc Ab (1 microngram/ml), or SU5416 (VEGFR tyrosine kinase inhibitor, 1 micronM) prevents the activity of VEGF (1~10 ng/ml). Finally, secretion of MMP-9 by VEGF-stimulated macrophages was abolished by treatment of anti-VEGF Ab (1 microngram/ml) in gelatin zymography. CONCLUSION: ELISAs together with bioassays developed in this study are appropriate for evaluation of the efficacy of inhibitors of VEGF.

The clinical characteristics of elderly onset rheumatoid arthritis / 대한내과학회지

BACKGROUND: Elderly-onset rheumatoid arthritis (EORA) is considered to be different from younger-onset rheumatoid arthritis (YORA) in clinical manifestations, laboratory indices, and in prognosis. However, the differences between these two diseases have not been clearly defined. The aim of this study was to more clearly define the clinical characteristics of EORA. METHODS: We retrospectively reviewed 50 EORA and 58 YORA patients who met the classification criteria established by the American College of Rheumatology (ACR). The two groups (EORA and YORA) were compared by three criteria. First, we considered the patterns of the joints involved and the presence of rheumatoid nodules. Second, we compared the disease activity indices and the level of auto-antibodies. Finally, we compared the use of medications. RESULTS: The mean age-of-onset and the women-to-men ratio in the EORA group was 66.2+/-5.5 years and 2.1:1, respectively. There was more large joint involvement seen in the EORA group. The titer of disease activity indices (ESR, CRP) and positive rate of auto-antibodies (rheumatoid factor, ANA, but not anti-CCP antibody) were also higher in the EORA group. We found no differences in the prescribed medications between the two groups. CONCLUSIONS: From these studies, we believe that EORA has higher disease activity indices at onset and greater joint involvement, along with higher titers of auto-antibodies as compared to YORA.