No abstract

Acridine orange (AO) has unique biological actions enabling tumor visualization (fluorovisualization) and a strong cytocidal effect (photodynamic therapy: AO-PDT) under illumination with blue light. Accordingly, in this study, we attempted to develop a new surgical technique for total tumor cell elimination using these photodynamic reactions with AO in a mouse osteosarcoma model. The results showed that local tumor recurrence was significantly inhibited (23%) in the group treated with curettage under fluorovisualization and AO-PDT, compared to that (80%) in the control group treated with curettage alone under ordinary light. Therefore, we concluded that the combination of curettage under fluorovisualization and AO-PDT may be useful for total tumor cell elimination with minimum damage to normal tissue in musculoskeletal sarcomas.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was used for the measurement of relative proteoglycan depletion of articular cartilage in the patellofemoral (PF) joint following a proprietary protocol, which was compared with the X-ray images, proton density weighted MR images (PDWI) and arthroscopic findings. The study examined 30 knees. The ages ranged from 16 to 74 (average 40.3) years. The Gd-DTPA(2-)containing contrast medium was used in a single dose. The subjects were made to exercise the knee joint for 10 min; and MR images were taken 2 h after intravenous injection of contrast medium. T1-calculated images were produced and the region of interest (ROI) was set as follows. (1) ROI1: entire articular cartilage in a slice through the center of the patella. (2) ROI2: low signal region in T1-calculated images, which were set in a blind fashion by two observers. (3) ROI3: articular cartilage on one side that includes ROI2 where low signal region were detected (medial or lateral). ROI3 was set to examine the contrast of ROI2 with surrounding articular cartilage. The average T1 values of ROI1 was 393.5+/-33.6 ms for radiographic grade 0 and 361.3+/-11.1 ms for grade I, which showed a significant difference (P=0.036). The T1 value of ROI2 was 351.6+/-28.2 ms for grade I, 361.9+/-38.3 ms for grade II, 362.1+/-67.7 ms for grade III, and 297.8+/-54.1 ms for grade IV according to arthroscopic Outerbridge classification. All cases, that demonstrated decrease of T1 values on dGEMRIC (ROI2), showed abnormal arthroscopic or direct viewing findings. The ratio (ROI3/ROI2) in cases of only slight damage classified as Outerbridge grade I (6 cases) was an average of 1.04+/-0.02 and was 1.0 or greater in all cases, thereby indicating well-defined contrast with the surrounding cartilage. The diagnosis of damage in articular cartilage was possible in all 16 cases with radiographic K-L grade I on dGEMRIC, while the intensity changes were not found in 10 of 16 cases on PDWI. The dGEMRIC with a single-dose would be useful on a diagnosis of the area demonstrating early relative proteoglycan depletion in the articular cartilage of the PF joint prior to any discernible changes in the subchondral bone on X-ray images and exceeds to plain MR images for examining deterioration of articular cartilage.

Clinical results of our reconstruction technique for anterior cruciate ligament using the double bundle, i.e., the combination of bone-tendon-bone (BTB) from the patellar tendon and semitendinosus tendon (ST), were evaluated. BTB was fixed in the tunnels produced on the isometric points on the tibia and femur, and ST, on the tibial tunnel through the same route as BTB. Throughout the observation period, no patients developed pain, limited range of motion, and/or instability of the operated knee. All patients were able to return to previous sports activities within 12 months. No apparent changes occurred on the reconstructed ligament. In 4 of 14 patients, knee stability was quantitatively examined, and a good result was obtained. The double bundle was found to be a useful method for patients who require physiologically more durable reconstruction.

A recent study of multidrug resistance (MDR) 1 gene transfected osteosarcoma cells found a cause-effect relationship between increased expression of P-glycoprotein (P-gp) and a low aggressive phenotype. However, several experimental and clinical studies have observed contradictory findings in that P-gp expression has been associated with tumour progression. In the present study, we characterized P-gp-positive and P-gp-negative single-cell clones of a murine osteosarcoma, to further investigate the relationship between P-gp expression and changes in cell phenotype. Although these clones were all selected by doxorubicin (DOX) exposure, they were heterogeneous with respect to MDR1 gene expression. The P-gp-positive clones revealed MDR phenotype, whereas the P-gp-negative clones showed no resistance to drugs. Morphological and functional analysis showed that both the P-gp-positive and P-gp-negative clones were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase, an increase in well-organized actin stress fibres and enhanced osteogenic activity. Moreover, these subclones all displayed a decrease in malignant potential such as oncogenic activity, tumour growth rate and metastatic ability, regardless of their P-gp status. These results indicate that the observed osteoblastic differentiation and less aggressive phenotype in DOX-selected osteosarcoma cells may not only be explained by the direct effect of P-gp, and accordingly, consideration of the effect of DOX, as well as P-gp, appears to be important. © 2000 Cancer Research Campaign