We examined the survival prognosis of patients with osteosarcoma after orally administering the active form of vitamin D3, 1alpha (OH) D3 (alphaD3). The 29 patients, ranging in age from 9 to 58 years (mean, 19 years), with osteosarcoma were treated in our department between 1983 and 1995. The surgical stage was IIB in all patients. Among the 29 patients, alphaD3 was administered to 18 patients, and the remaining 11 patients served as controls. These patients underwent chemotherapy mainly with adriamycin and cisplatin, and wide tumor resection. In the alphaD3-treated group, the 5- or 10-year survival rate was 61.1%, while in the untreated group, the 5-year survival rate was 63.6%, and 10-year survival rate was 33.9%. Prognosis of the patients treated with alphaD3 tended to be better than that of untreated patients, but there was no significant difference in the survival rate between the groups (p=0.3823). The survival rate in the group treated with a total dose of alphaD3 more than 1,500 microg was also higher than that in the untreated group, but the difference was not significant (p=0.0740). Therefore, we concluded that alphaD3 at the dose used in this study was not effective in improving the prognosis of osteosarcoma patients.

Adolescent↗

PubMedDate not supplied

Extra-articular wide tumor resection and limb reconstruction in malignant bone tumors invading the knee joint.

We demonstrate our procedure of extra-articular wide tumor resection and its clinical outcome. The knee joint including the femorotibial, patellofemoral and the proximal tibiofibular joints was totally resected without any view of articular cartilage and synovium. The resected limb was reconstructed with endoprosthesis of the knee joint. The average score of the limb function evaluated by ISOLS criteria was 69.3% in all patients. The limb function of these patients was almost the same as that of the patients who received the intra-articular procedure. The procedure of extra-articular resection was theoretically necessary and clinically practical.

Arthroplasty, Replacement, Knee↗

PubMedDate not supplied

[A case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease].

We reported a case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease. A 56-year-old woman was admitted with asymmetrical patchy sensory and motor disturbance in the extremities. Muscle atrophy and weakness in the left palm and bilateral tibialis anterior muscles were also noted. Deep tendon reflexes were normal in all the extremities. Superficial and deep sensations were reduced in the hands and feet bilaterally, and the distribution of sensory loss was irregular. Her serum was positive for antinuclear antibody, rheumatoid factor, anti-RNP antibody, and anti-SS-A antibody. Serial electrophysiological studies suggested that the predominant process was axonal degeneration of the sensorimotor nerves. On sural nerve biopsy, there were no findings of vasculitis but severe axonal degeneration was observed. Thin-layer chromatography with immunostaining revealed anti-GM1 and -SGLPG antibodies. Treatment with corticosteroids was successful. In this case, the anti-GM1 antibody may have played a role in the pathogenesis of mononeuropathy multiplex associated with autoimmune disease.

Autoantibodies↗

PubMedDate not supplied

Two cases of secondary angiosarcoma arising from fibrous dysplasia.

Angiosarcoma associated with fibrous dysplasia is very rare. We have recently experienced two cases of angiosarcoma that secondarily arose from fibrous dysplasia. The first patient, a 55 year-old man, had noticed a deformity in the right upper arm since he was five years old. At the age of 25 years, polyostotic fibrous dysplasia was diagnosed by X-ray examination. The patient complained of swelling and pain around the left shoulder. The diaphysis of the humerus was mostly non-observable due to severe bone destruction by tumor invasion and there was a large soft tissue tumor. Biopsy examination revealed grade II or III hemangioendothelioma with typical histologic findings of fibrous dysplasia. After interscapulothoracic amputation for wide tumor resection, he died of DIC. Autopsy revealed multiple liver metastatic lesions of angiosarcoma. The second patient was a 66-year-old woman. She presented with a pathological fracture in the right tibia, due to an osteolytic lesion with cortical bone swelling and thinning. The histologic diagnosis was fibrous dysplasia without any sarcomatous changes. However, after a 3-time recurrence, angiosarcoma arose from the same lesion. She is now still alive with disease-free period of 6.5 years after amputation.

Aged↗

PubMedDate not supplied

Acquisition of multidrug resistance in osteosarcomas, analyzed by doxorubicin binding assay, and histologic response to chemotherapy.

BACKGROUND: The mechanism by which multidrug resistance is acquired in human osteosarcomas remains unclear. In this study, we analyzed the changes in doxorubicin (DOX) binding ability (%DB), showing chemosensitivity before and after chemotherapy with DOX and cisplatin (CDDP), and evaluated the histologic response of human osteosarcomas to chemotherapy. MATERIALS AND METHODS: Eight osteosarcomas were analyzed. %DB by the DOX binding assay was measured in fresh tumor tissues at biopsy and at resection after preoperative chemotherapy. The histologic response to chemotherapy was also evaluated. RESULTS: Changes in %DB before and after chemotherapy were classified into 4 patterns; A: high (> 80%) to low (< 80%), B: high to high, C: low to low, D: low to high. The two tumors, classified as type A and B were responders (> 90% necrosis), whereas the 6 tumors of type C and D were classified as non-responders (< 90% necrosis). Based on these data, we speculated that the fraction of cell populations with different chemosensitivities to DOX and CDDP varied and found that type B tumors have no population of resistant cells, whereas type C tumors have a large fraction of resistant cells. CONCLUSION: We concluded that osteosarcomas are composed of mixed cell populations with different chemosensitivities to anticancer agents and also that survival of multidrug resistant cell populations may be the most important mechanism in acquisition of multidrug resistance of osteosarcomas after chemotherapy.

Adolescent↗

PubMedDate not supplied

Case report: natural development of osteosarcoma from precancerous lesion.

We encountered a very rare case that suggested the natural development of osteosarcoma from a precancerous lesion. The patient presented with a huge osteosarcoma in the distal femur on the initial consultation to our hospital. He had undergone X-ray examination twice previously, due to a knee injury. The findings of the lesion detected by the first X-ray examination were similar to a fibrous cortical defect (FCD), differing from those of an osteosarcoma lesion detected by second and last X-ray examinations. We retrospectively estimated the growth rate of the FCD-like and osteosarcoma lesions and found that FCD-like lesion was not osteosarcoma, but might have been a precancerous lesion. We also speculated that this osteosarcoma lesion might have appeared 18 months before the patient consulted our hospital.

Accidental Falls↗

PubMedDate not supplied

Intracellular binding sites of acridine orange in living osteosarcoma cells.

There have been many reports concerning the intracellular binding sites of acridine orange (AO), although the actual localization of AO in living cells remains controversial. This study was undertaken to clarify the intracellular localization of AO in living mouse osteosarcoma cells by cytochemical staining. A mouse osteosarcoma cell line (MOS) was cultured and continuously exposed to 0.5 microgram/ml of AO. The intracellular localization and stainability of AO the living tumor cells was morphologically detected by a high resolution fluorescence microscope. To detect the intracellular microstructure, cytochemical staining with rhodamin 123 for mitochondria, acid phosphatase for lysosome, Sudan-black for fat vesicle and toluidine blue for glucosaminoglycan were performed using fixed cells. The results showed that both the nucleus and cytoplasm of tumor cells at 10 minutes after exposure to 0.5 microgram/ml of AO emitted green fluorescence, which was especially intense in the nucleolus, but not brilliant in the nucleus and was granular orange to red fluorescence in the perinuclear particles. This stainability of AO was different from that of rhodamin 123, Sudan-black or toluidine blue, but similar to that of acid phosphatase. Based on these results, we conclude that the green fluorescence may have derived from AO binding to double stranded RNA, not to DNA, and that orange fluorescence may have derived from aggregated AO binding to lysosome.

Acid Phosphatase↗

PubMedDate not supplied

Relationship between binuclear and multinuclear cells in giant cell tumor of bone.

Giant cell tumor of bone (GCT) consists of stromal and multinuclear type tumor cells. Although most people believe that the stromal cells are mononuclear, we recently found the existence of many binuclear cells among stromal cells using DNA cytofluorometric examination. This study, using 18 tumors of GCT was conducted to elucidate the cell biological significance of the binuclear cell, especially its relationship to multinuclear cell formation or tumor cell proliferation. The investigation was carried out by means of DNA-RNA cytofluorometry with acridine orange (AO) and histological method. Using fluorescence microscopic observation, we counted the numbers of both mononuclear and binuclear cells and calculated the index of % BNC, which expresses the frequency (percentage) of binuclear cells in a population of mononuclear and binuclear cells. The index of % S-G2 obtained by DNA-RNA cytofluorometry showed the frequency (percentage) of mononuclear cells in the S and G2 phases of the cell cycle. In the histological study, we counted the numbers of multinuclear giant cells with more than 3 nuclei in the cytoplasm and stromal cells including mononuclear and binuclear cells and calculated MNS/SC, which showed the percentage of multinuclear cells in the stromal cells in the microscopic field. Eight tumors showed a value of % BNC greater than 10% and 2 had a value of 40%. The index of % BNC significantly correlated with the average value of MNC/SC in all tumors. There was no significant correlation between % BNC and the average value of % S-G2, in 18 tumors although 4 tumors having a % BNC value greater than 20% showed a % S-G2 value greater than 12% in 18 tumors. These results revealed the presence of many binuclear cells among stromal cells of GCT and suggested that these binuclear cells might be formed in association with the active proliferation of mononuclear cells and closely relate to the formation of multinuclear giant cells.

Adolescent↗

PubMedDate not supplied

Binuclear cells induced by acridine orange in giant cell tumor of bone.

We have recently found the presence of many binuclear cells among isolated and smeared cells in giant cell tumor of the bone (GCT). These binuclear cells are possibly associated with the formation of multinuclear cells. Therefore, this study was undertaken to clarify the mechanism of binucleation in GCT, using primary culture cells exposed to acridine orange (AO) which is a fluorescent vital staining dye for the cytoplasm and nucleus and which inhibits mitosis. The cells were isolated from explants of fresh tumor materials obtained from two GCT patients (GCT1 and GCT2). These cells were cultured in Dulbecco's modified Eagle medium (DMEM) with 10% Fetal calf serum (FCS). After exposure to 0.5 microgram/ml AO, for 0, 6, 24, 48, 96 and 144 hours the following parameters were investigated: 1) cell growth rate (GR); 2) frequency of hyperdiploid cells (%HDC) by DNA cytofluorometry; 3) mitotic index (MI); 4) BrdU labeling index (LI); 5) frequency of binuclear cells (%BNC). Compared to the control cells which were cultured in AO-free medium, the GR of both GCT cells exposed to AO was remarkably inhibited. The MI was 0 from 24 to 144 hours. The %HDC was increased at 24 hours and was maintained high until 144 hours. The LI was temporarily increased at 6 hours, but was decreased at 48 hours. The %BNC was gradually increased. AO inhibited DNA synthesis and cell mitotic activity in cultured GCT cells and it finally caused inhibition of cell growth. However, the frequencies of G2 arrest cells and binuclear cells were increased. These results suggested that the binuclear cells in GCT may be formed from G2 arrest cells by amitotic nuclear division, but not by mitosis without cytoplasmic division, or by cell fusion.

Acid Phosphatase↗

PubMedDate not supplied

Fluorovisualization effect of acridine orange on mouse osteosarcoma.

If the localization of musculoskeletal sarcomas could be visualized during surgery, it would be possible to completely resect the tumor with minimum damage to normal tissues and the patients could retain a functional limb. Therefore, we conducted the present study to clarify the usefulness of acridine orange (AO) for fluorovisualization of tumors using a mouse osteosarcoma model. At 2 hours after injection of 10 mg/kg AO to mice inoculated with MOS mouse osteosarcoma cells, fluorovisualization of mouse osteosarcoma reached the maximum level. Even a 1-mm-diameter lesion of pulmonary metastasis was visualized. The results suggested that AO may be useful for specific fluorovisualization of human osteosarcomas during surgery.

Acridine Orange↗

PubMedDate not supplied

DNA cytofluorometric analysis of benign and malignant nerve sheath tumors.

The present study was undertaken to examine the ploidy patterns of benign and malignant nerve sheath tumors using PI-DNA cytofluorometry and to clarify the relationship between the ploidy patterns and pathological findings for these lesions. The benign nerve sheath tumors (schwannomas and neurofibromas) were found to be dipolid or to be euploid-polyploidization, with a few DNA synthetic cells. The number of polyploid cells increased with increase in the frequency of cells with large and atypical nuclei in histology, regardless of the natures of cellular arrangements. Malignant schwannomas were composed of many polyploid and aneuploid cells with DNA synthetic cells, indicating their active cell proliferation. Thus, benign nerve sheath tumors exhibited low-proliferative ploidy patterns that were clearly different from those of malignant nerve sheath tumors. As Takeshita has already stated, it is difficult to ascertain why some of the neurogenic tumors show euploid-polyploidization (19). Further investigations will be needed in this direction. Finally, it is clear from the results of this study that the cytofluorometric analysis mentioned above is useful for assessing malignancy and that it may be useful for predicting prognosis of nerve sheath tumors.

Adolescent↗

PubMedDate not supplied

Relationship between doxorubicin binding ability and tumor volume decrease after chemotherapy in adult malignant soft tissue tumors in the extremities.

We have previously reported that the doxorubicin (DOX) binding ability detected by the DOX (or adriamycin) binding assay closely correlated with the chemosensitivity of human osteosarcomas (1). We performed the present study to clarify the relationship between the DOX binding ability (%DB) and the histologic response, rate of decrease in tumor volume of malignant soft tissue tumors after preoperative chemotherapy and prognosis. Nine malignant soft tissue tumors (4 liposarcomas, 3 synovial sarcomas, one malignant fibrous histiocytoma (MFH) and one extraskeletal osteosarcoma (EOS)) which arose at the extremities of adult patients were analyzed by the DOX binding assay using freshly biopsied specimens. After preoperative chemotherapy including DOX or pirarubicin (THP), the rate of decrease in tumor volume was measured using magnetic resonance imaging, and the histologic response expressed as tumor necrosis to chemotherapy was also investigated. All the patients, apart for one, were continuously disease-free after treatment. One patient with EOS died of metastatic disease before surgery. The histologic response in 8 tumors without EOS was poor. The %DB of 5 tumors was greater than 80% (average: 95.90%), whereas that of 4 tumors was less than 80% (average: 38.33%). Although there was no correlation between the %DB and the histologic response, or prognosis, a significantly positive correlation was found between the %DB and the rate of decrease in tumor volume (r = 0.7455, p < 0.05). These results suggest that in malignant soft tissue tumors, the rate of decrease in tumor volume after chemotherapy might be a better indicator for chemosensitivity than the histologic response and also that the DOX binding ability might be a good predictor for chemosensitivity before chemotherapy.

Adult↗