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PubMed1984

[Adjuvant chemotherapy for osteosarcoma in Japan--past, present and future].

The therapeutic results for osteosarcoma were very discouraging before 1970 in Japan despite many modes of treatment. In 1960, Miki introduced the regional perfusion technique into the treatment of osteosarcoma, and in 1963, Akaboshi pioneered the intraarterial infusion technique. By these methods, a five-year survival rate about 30% was achieved during the period from 1971 to 1976. In Japan, the five-year disease-free survival rate will soon exceed 50% thanks to intensive multi-drug adjuvant chemotherapy, considering the therapeutic results of 117 cases of JOOG treated during 6 years from 1975 to 1980 and 114 cases included in the Group Study of Osteosarcoma treated during 8 years from 1973 to 1981. In most cases, ablative surgery must still be considered the standard method of treatment. However, the importance of preoperative adjuvant chemotherapy is emphasized because limb-saving operations have become an increasingly common feature in the management of osteosarcoma as a result of the recent advances achieved by intensive multi-drug adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1980

Experimental osteosarcoma in the mouse, induced by Moloney's murine sarcoma virus.

The writers report an experimental trial on the mouse, consisting in the induction of osteosarcoma by inoculation of Moloney's murine sarcoma virus (MSV-M) into the proximal metaphysis of the tibia. This experiment was conducted on 90 BALB/c female mice aged twenty-one days and of mean weight 12.8 g. One group of animals was also given immunodepressive drugs. The tumour developed in 100 per cent of cases, producing metastases in some of the animals and resulting in death in three cases. The radiographic changes were initially osteolytic followed later by new bone formation. The histological examinations confirmed that the tumour was of an osteosarcomatous nature. Cells characteristic of rhabdomyosarcoma were observed in the soft tissues surrounding the bone. The skeletal metastases had the characteristics of osteosarcoma, while those in the lymph glands and lungs had those of an undifferentiated sarcoma. The writers also took into consideration a series of previous trial performed at the Institute of Clinical Orthopaedics of the University of Milan, involving a total of 740 mice, in arriving at their final conclusion that MSV-M induces, in the mouse, an osteosarcoma similar to spontaneous osteosarcoma in man, capable of producing osteoid tissue, of giving rise to metastases, and of causing the death of the animal.

Animals↗
PubMed1982

Biochemical stability of a bone-inducing substance from murine osteosarcoma.

Devitalized cultured cells of a murine osteosarcoma preserved strong osteogenic activity even after incubation in neutral and acidic buffer at 37 degrees for six days. This observation suggested that an osteosarcoma-derived osteogenic factor was considerably stable to endogenous proteases, or that osteosarcomas do not synthesize enzymes for degradation of the osteogenic factor. EDTA decalcification or extraction of the osteosarcoma at 37 degrees for six days had no apparent effect on the osteogenic factor. Disulfide-bond reducing agents (2-mercaptoethanol and dithiothreitol) completely inactivated the osteogenic activity and in the presence of guanidine HCl, the loss of activity was irreversible by reoxidation. There findings support the view that disulfide-bonds in the molecular structure of the osteogenic factor are essential for the biological activity.

Animals↗
PubMed1982

Electron microscopy of bone tumors--osteosarcoma, chondrosarcoma, giant cell tumor of bone.

Six cases of osteosarcoma, 5 cases of chondrosarcoma, and 6 cases of giant cell tumor of bone were studied by electron microscopy. The cells comprising osteosarcoma were basically osteoblasts and in addition to them, malignant chondrocytes, myofibroblasts and undifferentiated cells. The ratio of number of these cells were variable according to the portions designated microscopically as osteoblastic, chondroblastic and fibroblastic. Previous ultrastructural studies on osteosarcoma have scarcely revealed the presence of myofibroblasts. It is likely that osteosarcoma arises from undifferentiated mesenchymal cells capable of differentiating into various cells such as osteoblasts, chondroblasts, and fibroblasts; especially capable of differentiating into osteoblasts. On the other hand, chondrosarcoma was composed of the cells in the series of maturation from undifferentiated cells to chondrocytes. In high-grade malignant cases, glycogen particles and rough endoplasmic reticulum became less conspicuous, and occasionally malignant multinucleated cells were seen. In one case, endoplasmic reticular inclusions which were thought to be viral nucleocapsid by some authors were found. They, however, seemed to be formed by condensation of intracisternal granular material secreted by the rough endoplasmic reticulum. The cells comprising giant cell tumor of bone were multinucleated giant cells and stromal cells classified into four types. In a malignant case, giant cells showed no remarkable morphological change while stromal cells underwent an atypical change. This finding suggests that the mononuclear stromal cells are the principal tumor cells and the establishment of histological grading should mainly depend on the atypism of stromal cells. The tumor is likely to originate from undifferentiated mesenchymal cells which have the tendency of histiocytic and fibroblastic differentiation. The morphogenesis of multinucleated giant cells is not clarified in this study. Although the possibility that stromal cells are the origin of giant cells is still remained, it could also be speculated that giant cells are somehow related to immune response to the tumor having macrophage-related origin.

Adolescent↗
PubMed1995

[Radiologic features of osteosarcoma of the jaw].

Osteosarcoma of the jaw differs from that in other sites because it is less aggressive, rarely metastasizes and appears later in life. The literature lacking a systematic treatise on the radiologic features of this disease, the authors decided to collect the case histories of 9 patients, 5 men and 4 women, 24 to 48 years old, suffering from osteosarcoma of the jaw. Both conventional radiography and CT were used to examine all patients. The accurate study of radiologic findings made it possible to establish 3 basic lesion patterns. The first and very rare one, is characterized by the total absence of neoplastic tissue ossification processes; in this case, the radiologic diagnosis is extremely difficult, even with CT support. The second and more common pattern exhibits evident tumor neo-ossification, the most representative cases present several bone lamellae radiating from the lesion, with a sunburst-like appearance. The disease can be diagnosed with conventional radiography alone, especially in the most advanced cases; CT permits the identification of early forms, missed with conventional methods. The third pattern is characterized by amorphous lesion ossification: there are small areas of structureless ossification and a patchy appearance, separated by non-ossified neoplastic tissue. CT shows tumor ossification missed at conventional radiography. Finally, the authors observed an extremely rare case of parosteal sarcoma of the jaw, considered a variety of osteosarcoma by some pathologists. The lesion presented uniform neo-ossification which was highly sclerotic and separated from cortical bone by a thin layer of radiolucent tissue: both findings were clearly visible with CT. In conclusion, the systemic use of CT has led to a marked improvement in the radiologic diagnosis of osteosarcoma of the jaw.

Adult↗
PubMed1995

In vitro chemosensitivity assay for human osteosarcoma using tumor xenografts.

The authors have established an in vitro chemosensitivity assay for human osteosarcoma. To overcome the difficulty of maintaining primary osteosarcoma cells in culture, biopsy or surgical specimens were transplanted directly into athymic nude mice and early generation xenografts were used for in vitro scintillation assay. These xenografts enabled a large number of viable tumor cells to be obtained even from small biopsy specimens. As a result, this system afforded a workable assay in 21 (62%) of 34 osteosarcomas tested and enabled the assay of numerous drugs at 4 different concentrations. Reproducibility of the assay can be checked by using serially transplanted xenografts. Retrospectively, the in vitro results were compared with the histologic response of the resected tumor in 18 patients who had received preoperative chemotherapy. The true positive rate, true negative rate, and predictive accuracy were 40%, 100%, and 66.7%, respectively. The authors suggest that this system provides a valid tool to determine which drugs are ineffective in individual osteosarcoma patients and thus may allow more efficient therapy.

Animals↗
PubMed1993

Osteosarcoma with epithelioid features. An immunohistochemical study.

We report a case of osteosarcoma with coexpression of epithelial and mesenchymal markers immunohistochemically of the second lumbar vertebra in a 49-year-old man. Histologically, the tumor largely showed typical patterns of osteosarcoma with lacelike osteoid deposition and chondroblastic and fibroblastic areas. Immunoreactivity for osteocalcin (human bone gamma-carboxyglutamic acid-containing protein) was demonstrated in most of these tumor cells. Both primary and recurrent tumors contained areas that were composed of epithelioid cells with an alveolar pattern and a trabecular arrangement that resembled carcinoma. Some of the epithelioid cells gave positive reactions for cytokeratin and epithelial membrane antigen. On extensive examination, no other site of malignancy was detected. There have been a few reports of osteosarcomas with epithelioid cells, but to our knowledge, the immunohistochemical properties of this type of tumor have not been reported previously. This is an unusual case of osteosarcoma with epithelioid features.

Humans↗
PubMed1994

[Periosteal osteosarcoma of the jaw. Apropos of 2 cases].

The authors report two cases of periosteal osteosarcoma of the jaws, a tumour which is one of the two variants of juxtacortical osteosarcoma. Periosteal osteosarcoma involving the jaw bones is extremely rare. Because of its chondroblastic differentiation, sometimes predominant, this tumour may pose some problems of differential diagnosis with chondrosarcoma or pleomorphic adenoma: immunochemistry may be necessary. This localization does not change the clinical, radiologic, histologic and prognostic features of periosteal osteosarcoma.

Aged↗
PubMed1994

Plasminogen activators and their inhibitor in osteosarcomas and other bone tumors.

The concentrations of the plasminogen activators u-PA and t-PA as well as the inhibitor PAI-1 were studied immunohistochemically in 35 osteosarcoma specimens compared to 15 Ewing's sarcomas and various other bone lesions. The immunoreactivities of plasminogen activators in osteosarcoma specimens were significantly higher than PAI-1. Biochemically in cell cultures and immunohistochemically in the pathological specimens of the osteosarcomas u-PA was the dominant antigen, all factors showing a generally strong reactivity. Here a relation to the malignancy and invasivity of the tumors could be seen, which was comparable to the results in other tumors. This correlation, however, could not be detected in Ewing's sarcomas. On the whole low immunoreactivity of all enzymes, and of u-PA in particular, could be seen. In comparison in some benign lesions (fibrous dysplasias, aneurysmal bone cysts) the immunohistochemical reactions were distinctly stronger. Dominant antigens did not exist in Ewing's sarcomas. In all mesenchymal tumors studied the immunohistochemical localisation and concentration of the antigens showed a definite correlation with their histological differentiation. Chondroblastic differentiations in different tumors (chondrosarcomas, enchondromas, chondroblastic osteosarcomas) or chondroid parts were always negative for both activators and the inhibitor, especially in their central parts. Here, the biological malignancy was not decisive for the result.

Bone Neoplasms↗
PubMed1994

[p53 antioncogene abnormal in osteosarcoma].

Immunohistochemical evaluation of 24 osteosarcoma using an anti-p53 protein monoclonal antibody (Moab p53-12) showed strong positive reaction in the nuclei of tumor cells in 14 osteosarcoma (58.3%). Many studies have proved that this overexpression of p53 protein in tumor cells is associated with mutation of the p53 gene. Contrast study with DNA flow cytometry made on osteosarcoma showed that most of the p53 strongly positive tumors have higher DNA Index value than negative or slightly positive ones, though no statistically difference existed between two groups. Southern blot hybridization of p53 gene was also made in osteosarcomas. 5 of 20 cases (20%) had the structural changes of p53 gene. 3 of them were part or whole deletion of the gene. 2 of them had the extra-band, indicating the rearrangement of the gene.

Adolescent↗
PubMed1994

[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity].

We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.

Adolescent↗
PubMed1993

Distribution of immune effector cells within an experimental osteosarcoma of the nude rat.

In vivo studies on osteosarcoma are limited by the relative low incidence of this tumor in man. Therefore, there is a high dependence on a reliable experimental tumor model. In previous studies, a transplantable osteosarcoma of the athymic nude rat was established. In the present study the content and pattern of distribution of immune effector cells within this osteosarcoma were investigated by immunohistochemistry, and were related to histomorphologic findings. The absence of T-like cells within the tumor of 1- to 2-month-old athymic nude rats was shown using the T-lymphocyte-specific monoclonal antibody OX-19. In contrast, OX-6-positive cells, representing B lymphocytes and macrophages, were distributed throughout the whole tumor with a discrete accumulation at the borderline between the peripheral proliferative tumor tissue and the central necrotic area. Using the macrophage-specific monoclonal antibody ED1 we found the accumulation of mononuclear cells to consist mainly of macrophages. The distribution of these macrophages was closely related to histomorphologic tumor characteristics: the major proportion was found in the proliferative peripheral part of the tumor with highest macrophage content at the border to the central necrosis. As the measurement of tumor necrosis in osteosarcoma plays an important role in the judgement of therapeutic response, this distinct delimitation of tumor necrosis by macrophages could be helpful in the evaluation of therapeutic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Inactivation of human osteosarcoma cells in vitro by 211At-TP-3 monoclonal antibody: comparison with astatine-211-labeled bovine serum albumin, free astatine-211 and external-beam X rays.

The potential usefulness of alpha-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) 211At-TP-3 of different specific activities, (b) 211At-labeled bovine serum albumin (BSA), (c) free 211At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, 211At-BSA or free 211At. The D0's were lower for free 211At than for 211At-BSA. The survival curves for 211At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to 211At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to 211At-TP-3 treatment was the antigen expression. Cell inactivation after 211At-TP-3 treatment increased substantially with increasing specific activity of the 211At-TP-3. At high specific activities, the cytotoxic effect of 211At-TP-3 was significantly higher than that of 211At-BSA. In conclusion, 211At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma.

Antibodies, Monoclonal↗
PubMed1994

[A case of parosteal osteosarcoma at the cranial vault].

A rare case of parosteal osteosarcoma of the cranial vault has been reported. A 32-year-old male was admitted complaining of a hard scalp mass at the left temporoparietal region for several years. On admission he showed no neurological abnormalities. The craniogram, CT and MRI revealed a calcifying mass attached by a small stalk to the skull, and a radiolucent cleft between the tumor and the skull. On operation, the tumor proved to be hard, and it existed between the temporal muscle and the periosteum. A small tumoral attachment existed at the parietal region. The tumor was detached from the skull and the surrounding cranial bone was removed. The histological diagnosis was parosteal osteosarcoma. There have been only 12 cases of parosteal osteosarcoma of the skull reported. The pathological, neuroradiological findings and treatment of parosteal osteosarcoma were the main topics of discussion. This disease should be considered as one of the possible etiologies when a patient with a tumor of the skull is encountered.

Adult↗
PubMed1994

An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis in hamsters.

Animal models of osteosarcoma with spontaneous pulmonary metastasis which retain metastatic capacity and osteoid formation after serial passages have been reported infrequently. In this communication we describe some biological features of a transplantable osteosarcoma, Os515, induced by BK-virus in Syrian golden hamsters. The subcutaneously transplanted tumours in 2-week-old animals grew progressively until death, with a mean survival time of 32 days. Distant metastases occurred only in the lungs in all animals. The histological appearance was osteosarcoma of osteoblastic type. Enzyme-histochemical staining showed alkaline phosphatase activity in many cells and beta-glucuronidase activity in few cells. Tumours transplanted intramuscularly in the hind limbs were amputated radically at 5 or 11 days. A small number of animals died from lung metastases without local relapse during the observation period of 140 days after grafting. All the control hamsters bearing unamputated tumours died much earlier. Necropsy revealed large metastatic nodules in the lungs of limb-amputated animals and small diffuse nodules in the lungs of untreated control animals. The development of lung metastases was monitored by soft X-ray without sacrificing the animals. This model will be useful in studies of mechanisms of metastasis and for the experimental treatment of osteosarcoma.

Animals↗
PubMed1994

Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma cells.

Interrelationships between nuclear architecture and gene expression were examined by comparing the representation of nuclear matrix proteins in ROS 17/2.8 rat and MG-63 human osteosarcoma cells with those in normal diploid osteoblasts. The tumor-derived cells coexpress genes which are expressed in a sequential and mutually exclusive manner during the progressive stages of osteoblast differentiation. In osteosarcoma cells two-dimensional electrophoretic analysis indicates a composite representation of nuclear matrix proteins characteristic of both the proliferative and postproliferative periods of osteoblast phenotype development. In addition, nuclear matrix proteins unique to the tumor cells and the absence of nuclear matrix proteins found only in normal diploid osteoblasts are observed. Tumor-specific nuclear matrix proteins include those expressed in a proliferation-dependent and independent manner. There is a parallel relationship between nuclear matrix proteins and the expression of cell growth and tissue-specific genes during osteoblast differentiation and in osteosarcoma cells where the developmental sequence of gene expression has been abrogated. Nuclear matrix proteins therefore provide markers reflecting defined periods of bone cell differentiation and phenotypic characteristics of an osteosarcoma.

Animals↗
PubMed1993

[Immunohistochemical localization of bone Gla protein and osteonectin in normal human bone and cartilage tissues, and in osteosarcomas and chondrosarcomas].

The immunohistochemical localization of bone Gla protein (BGP) and osteonectin (ON) was investigated in normal human bone and cartilage tissues, and in osteosarcomas and chondrosarcomas with their respective antibodies. In normal bone and heterotopic ossification tissues, BGP and ON were detected in preosteoblasts, osteoblasts and young osteocytes, the reaction of which was strongest in osteoblasts. They were also demonstrated in most osteosarcomas, and their reaction was stronger in osteosarcomas with higher differentiation. These observations suggested that BGP and ON were related to the formation of normal and tumoral osteoid. In contrast, the localization of ON in normal cartilage and chondrosarcoma tissues was markedly different from that of BGP in these tissues. In normal growth cartilage, ON reacted with chondrocytes in hypertrophic and calcifying zone and matrix in calcifying zone, whereas BGP did not react. ON was also demonstrated in the cytoplasm and calcifying portion of most chondrosarcomas. These findings indicated that ON plays an important role in calcification of normal and tumoral cartilage tissues. BGP was detected in poorly differentiated and dedifferentiated chondrosarcomas. Thus, these antibodies are expected to be useful for studying calcification of human bone and cartilage and for the diagnosis of human osteosarcomas and chondrosarcomas.

Adolescent↗
PubMed1993

Evaluation of single-agent chemotherapy for treatment of clinically evident osteosarcoma metastases in dogs: 45 cases (1987-1991).

A study was undertaken to determine the effect chemotherapy had when used to treat 45 dogs with measurable metastatic osteosarcoma. The primary tumor was histologically confirmed as an osteosarcoma in each case. Thirty-nine dogs had the primary tumor surgically removed. Twenty-four of these dogs were treated adjunctively with cisplatin (70 mg/m2 of body surface, IV, q 3 weeks; median 2 doses, range 1 to 6 doses) prior to the onset of metastasis. The remaining 6 dogs from which the primary tumor was not surgically removed were diagnosed as having metastatic osteosarcoma in addition to the primary tumor on initial examination. The median time from initial examination until the development of metastatic disease was 115 days (range, 27 to 1,199 days). The location of the metastatic disease was lungs (31 dogs), bone (3 dogs), soft tissue (1 dog), and multiple sites including lungs, bone, and soft tissue sites (10 dogs). The metastatic lesions were confirmed by pretreatment biopsy (n = 8) or cytologic evaluation (n = 2) in 10 cases and at necropsy in 27 cases. The remaining 8 cases were diagnosed radiographically as multiple metastatic lesions in the lungs consistent with metastatic osteosarcoma. The metastatic disease was treated with cisplatin in 31 dogs (70 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 4 doses), doxorubicin in 11 dogs (30 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 3 doses), and mitoxantrone in 3 dogs (5 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 3 doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗