Biomedical subjects

K Kusuzaki

Publications and source records attributed to K Kusuzaki.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Oral administration of 1 alpha hydroxyvitamin D3 inhibits tumor growth and metastasis of a murine osteosarcoma model.

We studied the effect of oral administration of 1 alpha hydroxyvitamin D3 (1-D3) on the growth and metastatic ability of Dunn murine osteosarcoma model. A solution of 1-D3 or vehicle alone was administered daily for 2 weeks to tumor-bearing mice using an esophageal tube and tumor size was serially monitored. In 1-D3-treated mice, the growth of Dunn osteosarcoma was significantly suppressed in a dose-dependent manner. Histologically, tumor cells in the control mice proliferated in marginal regions of the tumor with wide central necrosis, whereas in the 1-D3-treated mice, tumor cells were distributed as scattered islands among extensive necrotic tissue. The mean tumor necrosis area was 55.7% in the control tumors and 94.6% in 1-D3-treated tumors (p < 0.001). There were no substantial differences in the cytofluorometric cell cycle distribution or the histological mitotic index between control and 1-D3-treated tumors. When 1-D3 was administered to mice from 2 days before to 2 weeks after transplantation of the tumor, there were significantly fewer metastatic foci in the lungs in 1-D3-treated mice than in control mice. We also tested the effect of coadministration of 1-D3 and doxorubicin on the growth of Dunn osteosarcoma and found that these two drugs act additively to suppress tumor growth. These results indicated that 1-D3 given orally inhibits tumor growth and metastases in a Dunn osteosarcoma model. Although the mechanism remains unknown, oral administration of 1-D3 might be promising as a new method of treating human osteosarcoma.

Administration, Oral↗

PubMedDate not supplied

Relationship between histologic grade and cytofluorometric cellular DNA and RNA content in primary bone tumors.

The diagnosis and grading of bone tumors remains a challenging problem. We studied the relationship between histologic grade and cytofluorometric cellular DNA and RNA content in 108 primary bone tumors. The data included DNA ploidy, mean DNA content (MDC), S-phase fraction (SPF), mean RNA content (MRC) and RNA/DNA ratio (RDR; MRC/MDC) which represents the RNA content normalized for the DNA content. Benign tumors had a diploid stem line with low MDC (mean; 1.04), low SPF (0.9), high MRC (2.41) and high RDR (2.31). Giant cell tumors of bone, which are locally aggressive benign tumors, showed diploidy with relatively higher MDC (1.07, p < 0.01) and SPF (2.6, p < 0.01) and lower MRC (1.81, p < 0.01) and RDR (1.69, p < 0.01). Similar results were obtained in low-grade sarcomas. In high-grade sarcomas, the data depended on the histologic findings. Pleomorphic sarcomas such as osteosarcomas revealed aneuploidy with remarkably higher MDC (1.70 in osteosarcomas, p < 0.01) and SPF (6.5, p < 0.01), but lower RDR (1.70, p < 0.01). In contrast, small cell sarcomas, such as Ewing's sarcomas, showed diploidy with low MDC (1.11 in Ewing's sarcomas, N.S.) and SPF (2.5, p < 0.01) and extremely low RDR (1.34, p < 0.01). The RDR value was higher in well-differentiated tumors than in primitive tumors, rendering it useful in grading bone tumors with a diploid stem line. By combining the RDR value with the MDC value, 96% of diploid sarcomas could be distinguished from benign tumors. These results indicate that cellular DNA and RNA content analysis may be of value in assessing the malignant potential of diploid as well as aneuploid bone sarcomas.

Bone Neoplasms↗

PubMedDate not supplied

Eleven cases of intraosseous lipoma of the calcaneus.

Intraosseous lipomas are rare benign primary bone tumors, with an incidence of one per thousand bone tumors. We studied eleven cases of intraosseous lipoma of the calcaneus. All the patients received radiographic examinations and MRI with T1-and T2-weighted images with Gd-DTPA enhancement. Seven patients received tumor curettage. Plain radiographs demonstrated that all of the lesions showed clear osteolysis surrounded by a sclerotic margin in the central body of the calcaneus. MRI revealed that all the lesions had demarcated homogenous high signal intensity lesions on both T1- and T2-weighted images, which strongly suggested adipose tissue. In 5 cases, the center of the lesion showed low signal intensity lesions on T1-weighted images, suggesting the existence of central necrosis or cyst formation. After excising the tumors of 7 patients, there was no local tumor recurrence. Surgical intervention was considered unnecessary in all cases after the diagnosis of an intraosseous lipoma was determined by MRI.

Adolescent↗

PubMedDate not supplied

Avoidance of doxorubicin resistance in osteosarcoma cells using a new quinoline derivative, MS-209.

P-glycoprotein (Pgp), a membrane drug efflux pump, is thought to be responsible for the observed drug resistance in osteosarcoma. We have recently developed Pgp-positive, multidrug resistant (MDR) murine osteosarcoma cell lines, which may be suitable models for the study of drug resistance in osteosarcoma. In this study, we investigated the effect of a newly synthesized quinoline compound, MS-209, on the reversal of doxorubicin (DOX) resistance in these cell lines. Three different types of resistance modifying agents (RMAs) as well as MS-209 were studied. These included the calcium channel blocker verapamil, and the immunosuppressive agents cyclosporin A and FK506. The reversal effects of the RMAs on DOX resistance were assessed by the MTT assay. In the absence of RMAs, the MDR osteosarcoma cells were 20-fold more resistant to DOX than the parental cells. When MS-209 was added at a final concentration of 0.1 to 3 microM to the MDR cells, 3-to 74-fold sensitization was observed. A complete reversal (37-fold sensitization) of the resistance was obtained at 1 microM MS-209. This concentration of MS-209 was 3-, 8- and 28-fold more effective than the same concentration of FK506, verapamil and cyclosporin A, respectively. These results indicate that MS-209 may be a more effective RMA, and that DOX resistance in osteosarcoma cells could be reversed by comparatively low doses of MS-209.

Antineoplastic Agents↗