Overcoming multidrug resistance (MDR) is an urgent issue to improve the prognosis of osteosarcoma patients. In this study, we undertook to clarify the effect of photodynamic therapy (PDT) with acridine orange (AO) on the MDR mouse osteosarcoma (MOS/ADR1) cell line, by comparing the outcome with the effect on a chemosensitive osteosarcoma (MOS) cell line. Cultured cells of MOS and MOS/ADR1 cell lines were exposed to AO at various concentrations for various times, followed by long-or short-term (10 or 1 min) illumination with blue light (466.5 nm) for excitation. Key words: Multidrug resistance -Osteosarcoma -Acridine orange -Photodynamic therapyThere is no doubt that chemotherapy is the most important treatment for improving the prognosis of patients with osteosarcoma. However, about 30% of these patients have been found to be resistant to chemotherapy.1-3) Therefore, overcoming multidrug resistance (MDR) is an urgent issue in the management of osteosarcomas. There have been many studies conducted on the modification of MDR in various tumor cell lines, [4][5][6][7][8][9][10] but none is clinically applicable at present. Recently, we have found that photodynamic therapy (PDT) with acridine orange (AO) has a strong cytocidal effect on a chemosensitive mouse osteosarcoma cell line. We conducted the present study to clarify the effect of PDT with AO (AO-PDT) on an MDR mouse osteosarcoma cell line, in comparison with the effect on the chemosensitive cell line. MATERIALS AND METHODS AO-PDT with mouse osteosarcoma cellsThe MDR mouse osteosarcoma cell line (MOS/ADR1) 11) was used in this study. This cell line was established from a radiationinduced mouse osteosarcoma cell line (MOS) 12) by single cell culture after exposure to six-pulsed, stepwise increments of doxorubicin (DOX) concentration ranging from 0.01 to 1 µg/ml. The MOS cells were chemosensitive to most anticancer agents, but the MOS/ADR1 cells showed a classical MDR phenotype with overexpression of P-glycoprotein; they were resistant to DOX, vincristine, vinblastine, etoposide, mitomycin C, and actinomycin D. 11)DOX binding assay demonstrated that more than 90% of the MOS/ADR1 cells were negative for nuclear DOX fluorescence. 11)We cultured 2×10 5 MOS/ADR1 cells and MOS cells in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal calf serum (FCS) at 37°C under a 5% CO 2 atmosphere, using 6-well plates. At 24 h, in a preconfluent cell growth condition, the medium of the wells was replaced with 0.025, 0.05, 0.1, 1.0, or 2.0 µg/ml AO containing DMEM. After 15-min exposure to AO, 1400 lx blue light selected through an interference filter (466.5 nm) from a 150-W halogen lamp source (Nikon Fibertrans 2; Nikon, Tokyo) was employed to illuminate the cell surface, to excite AO bound to the cells, using a double fiber tube system (PDT with AO: AO-PDT). This blue light has low energy and does not generate heat. In the continuous AO exposure study, after illumination for 10 min, both tumor cell groups were further cultured in an AO-containing medium. In the fl...

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Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

We report on an 11-year-old girl who developed steroid-resistant nephrotic syndrome (NS) at the onset of systemic lupus erythematosus (SLE), and clinical and renal histological findings suggested that her NS would be associated with SLE-related podocytopathy. Although initial treatment with intravenous pulse methylprednisolone was ineffective, following treatment with cyclosporine and an angiotensin receptor blocker was effective for her nephrotic proteinuria. She had developed posterior reversible encephalopathy syndrome (PRES), and mycophenolate mofetil (MMF) was started instead of cyclosporine. At present, 45 months after the onset, she is in remission of both NS and SLE. This case indicates that NS associated with SLE-related podocytopathy should be included in the spectrum of glomerulopathy accompanying SLE, also in the pediatric population.

These results showed that in normal articular cartilages most chondrocytes are in the G0 phase, while some became 4c polyploid cells, and that these G0-phase chondrocytes had a potential to proliferate under diseased conditions.