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The GIRs were higher than the PIRs in Japanese junior soccer players. A lower overall PIR suggested that players in the U-12 age group practiced under appropriate conditions. However, the higher GIR in this age category needs to be decreased.

Ras gene mutations occur in 30% to 40% of patients with multiple myeloma (MM), and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore, we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7-aminoactinomycin D (7AAD) showed that R115777 induced apoptosis of 2 of 3 myeloma cell lines at a concentration of 1.0 ؋ 10 ؊8 M. R115777 appears to be a potent inducer of apoptosis, and its effects depend on the status of Ras mutation in cloned myeloma cells but not on IntroductionMultiple myeloma (MM) is a malignancy of B cells characterized by the monoclonal proliferation of malignant plasma cells and osteolytic bone destruction. Several chemotherapeutic regimens have been used to improve the survival of patients with MM. Although high-dose melphalan supported by autologous stem cell transplantation (auto-SCT) has improved the survival of patients with MM, many patients were found to relapse during a long follow-up period. 1,2 Allogeneic stem cell transplantation (allo-SCT) is possibly the only genuinely curative therapy for MM, and a graft-versus-myeloma effect by immunocompetent donor lymphocytes has been demonstrated but the treatment-related mortality is high. 3,4 Recently, nonmyeloablative SCT has been reported to provide a stable engraftment of allogeneic stem cells and tolerable toxicity in patients with MM, but a longer follow-up period is necessary to evaluate late mortality. 5,6 Therefore, there is an obvious need for new therapeutic strategies.Ras proteins are prototypical G proteins that have been shown to play a key role in signal transduction, cell proliferation, and malignant transformation. Ligand-stimulated activation of the cell-surface receptor, receptor-associated tyrosine kinase, or agonist mediated through G protein-coupled receptors results in the activation of Ras protein. The Ras gene family consists of 3 functional genes, H-Ras, N-Ras, and K-Ras. Activating point mutations in all 3 Ras genes have been detected in a wide variety of human malignancies and are one of the most common alternations in hematologic malignancies. [7][8][9] In MM, Ras gene activation is observed in 30% to 40% of cases and one of the most frequent point mutations. [10][11][12][13] Although Ras protein undergoes several steps of posttranslational modification, farnesylation is the first and most important step for its membrane localization and cell-transforming activity. Thus, farnesyltransferase (FTase) is a very attractive target for the development of anticancer agents. R115777 (Zarnestra, Johnson & Johnson, Raritan, NJ), a potent and selective farnesy...