Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.
The goal of this study was to investigate the utility of inpatient rehabilitation in eleven recipients that underwent adult-to-adult living-donor liver transplantation (LDLT) using the Functional Independence Measure (FIM) scale. Following transplantation, muscle atrophy was noted in all patients and was worse in the lower limbs. Joint stiffness was also noted in the four limbs, especially in the upper limbs. Assessment with the FIM scale demonstrated low motor scores (mean 16) and low cognitive scores (mean 20) before rehabilitation.Of the six patients that received intensive rehabilitation and were discharged from our institution, inpatient rehabilitation resulted in improvement in joint stiffness but not in muscle atrophy. Of the six patients discharged, final FIM motor scores had improved markedly (mean 61), and the mean postoperative admission period and the mean rehabilitation period were 163 days and 59 days, respectively. However, of the five patients that died from postoperative complications, final FIM motor scores showed no improvement (mean 14). These results suggest that transplant recipients that do not experience critical complications do benefit from inpatient rehabilitation. However, improvements in functional outcome occur over a long time course, and we advocate initiating rehabilitation before LDLT or hospital admission. (Jpn J Rehabil Med 2004; 41: 859-867) Yasunari HIOKI et al
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