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PubMed1991

Intracortical osteosarcoma. A case report.

Intracortical osteosarcoma (IO) is the rarest form of osteosarcoma. A 19-year-old man had one of these lesions in the upper diaphysis of the femur. Microscopically, IO was a well-differentiated osteosarcoma with an osteoblastic histologic pattern. The typical location in the diaphysis and the peculiar histologic and roentgenographic findings with intracortical origin clearly separate this entity from conventional osteosarcomas as well as periosteal and parosteal osteosarcomas. IO are lytic neoplasms confined to the cortex of the diaphysis with a benign roentgenographic appearance, but are included in the differential diagnosis of benign tumors.

Adult↗
PubMed1990

Frequency and structure of p53 rearrangements in human osteosarcoma.

Osteosarcoma is the most frequent childhood bone cancer (Tebbi, C. K., and Gaeta, J. Pediatr. Ann., 17:285-300, 1988). Using Southern blot mapping, we found that 11 of 60 (18%) osteosarcomas had altered restriction patterns of the p53 gene and that six of these had loss of the other p53 allele. In contrast, no alteration of the p53 gene was detected in 50 samples from other types of sarcomas. Fifty % of osteosarcoma cell lines (4 of 8) also had gross rearrangements of one p53 allele with loss of the second allele, and these had no detectable p53 mRNA. Osteosarcoma cell lines with no detectable alteration of the p53 gene contained abundant p53 transcripts. Taken together, data show that human osteosarcomas can have rearrangements of the p53 gene; these rearrangements may cause loss of normal constraints on cellular growth.

Cell Line↗
PubMed1989

Establishment of a cell line producing bone morphogenetic protein from a human osteosarcoma.

A human osteosarcoma cell line was established from a biopsy specimen from a 13-year-old girl. The osteosarcoma tissue was maintained in athymic nude mice (Balb C nu/nu) by serial transplantation for three years. The tumor was excised from a host mouse and digested with collagenase. The isolated cells were cultured by 98 passages in 14 months, and clones of osteosarcoma cells were obtained by limiting dilution. A clone named human osteosarcoma cell 6 (H-OS-6) that showed the osteoblastic phenotypes of productions of bone morphogenetic protein (BMP) and alkaline phosphatase and a response to human parathyroid hormone (h-PTH 1-34) was selected. The morphology of its chromosomes indicated its human origin. This human osteosarcoma cell line is unique in producing BMP under in vitro conditions.

Adolescent↗
PubMed1989

Retroviral particles in radionuclide-induced murine osteosarcomas: mouse strain-related differences.

Twenty-six osteosarcomas from strain NMRI mice and twenty-six osteosarcomas from (C3H x 101)F1 hybrid mice were investigated by electron microscopy for the presence of retroviral particles. The bone tumors had been induced by the incorporation of the short-lived bone-seeking radionuclides 224Ra, 223Ra, or 227Th. All of the 26 osteosarcomas from NMRI mice contained retrovirus-like intracisternal type A particles in varying quantities. No type C retrovirus particles could be detected. In contrast, most of the 26 osteosarcomas from (C3H x 101)F1 mice contained budding, immature, and mature type C virus particles predominantly in large quantities. Intracisternal type A particles were also present in all tumors from these mice, but were found only occasionally after extensive search. The mouse strain-related differences in the presence of intracisternal type A particles and type C virus particles in the bone tumors do not provide evidence of an etiological relation of these particles to radionuclide-induced osteosarcomagenesis. Some of the mature type C virus particles observed in osteosarcoma tissue from the hybrid mice were atypical in structure and size. Such pleomorphic particles are probably associated with the spontaneous osteomagenesis which occurs in untreated old (C3H x 101)F1 mice.

Animals↗
PubMed1979

Typical and atypical osteosarcomas: a clinicopathologic study of sixty-two cases.

Of 62 cases of histologically confirmed osteosarcomas, 50 long bone cases aged under 30 years were grouped as "typical" osteosarcoma, and the other 4 long bone cases and 8 short and flat bone cases were grouped as "atypical" osteosarcoma. Gross and microscopic findings of the lesions, postmortem findings, and survival of the patients were compared between the two groups. Small round cell-type tumor cells and relatively well-differentiated foci resembling osteoblastoma were more often found in the atypical than in the typical osteosarcomas. Although patterns of metastasis were not very different between the two groups, 2 of 6 autopsied short and flat bone cases showed no metastasis. Five-year survival rates of both groups were similar, each about 25%. Six patients of the typical and only one of the atypical osteosarcomas are alive without recurrence more than 6 years after amputation.

Adolescent↗
PubMed1988

[Osteosarcoma. A new diagnostic approach in presurgical loco-regional staging].

The value of Magnetic Resonance (MR) imaging was examined in the anatomical staging of bone osteosarcomas. Eleven patients were studied--8 central and 3 parosteal osteosarcomas. The accuracy of MR imaging was compared to that of plain film, scintigraphy, CT, and angiography. MR imaging was superior to both CT and radionuclide scanning in defining intramedullary extension and in showing skip metastases. Cortical erosion in central osteosarcomas was demonstrated by MR imaging, CT, and plain film; in 1 case of parosteal osteosarcoma MR imaging was superior to CT in showing cortical penetration. In two cases MR imaging did not accurately demonstrate the relationship of the tumor to the major vessels; only angiography showed vascular involvement. MR imaging was useful in delineating extraosseous extension. The importance is stressed of a correct use of MR imaging towards an accurate diagnosis. In fact, intramedullary extension and skip metastases were better demonstrated on T1-weighted images with large fields, while T2-weighted images and small fields were needed for the best overall evaluation of extraosseous involvement. In conclusion, MR imaging should be used for preoperative staging of osteosarcomas in those cases where diagnosis was made on the basis of clinical, radiographic, and bioptic findings.

Adolescent↗
PubMed1986

[Surgery and adjuvant chemotherapy of osteosarcoma].

The primary site of metastasis of osteosarcoma is the lung. In the past, even if the primary lesion was completely removed by radical surgery, more than 90% of patients of died pulmonary metastasis with in one to two years. Control of osteosarcoma therefore depends upon the prevention and treatment of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin and high-dose methotrexate with Leucovorin rescue, dramatically improved the prognosis of osteosarcoma. In the past where systemic chemotherapy was not available, the five-year survival rate was around 19%. The majority of patients developed bilateral pulmonary metastasis within one year after onset, and died. These patients exhibited numerous micro-metastases as well. In patients receiving surgical adjuvant chemotherapy with current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, a single metastasis appearing after the termination of treatment, or early and multiple, appearing resistant to treatment. Surgery is indicated in the former situation while some therapeutic system must be devised for the latter. Recently, preoperative chemotherapy for limb-saving is given to patients with osteosarcoma of the extremities (NSH-3, 4, 5). The adjuvant of chemotherapy proved to be of great significance for improving the survival rate of osteosarcoma and for achieving limb salvage.

Adolescent↗
PubMed1986

Monoclonal antibodies to human osteosarcoma-associated antigen(s).

Monoclonal antibodies (MoAbs) against human osteosarcoma cells were obtained by the production and cloning of hybrids resulting from the fusion of mouse myeloma cells P3 X 63Ag8.653 with spleen cells from partially purified, osteosarcoma-associated antigen (OSAA)-immunized BALB/c mice. OSAAs were isolated from the spent culture medium of a human osteosarcoma cell line (TE-85). Five hybrid clones were established and designated as OSA1, OSA2, OSA3, OSA4, and OSA5. OSA1 and OSA2 had similar activity. All 5 MoAbs reacted strongly with most osteosarcoma cell lines and with all osteosarcoma tissues tested but not with 10 tumor cell lines and 2 tumor tissues from other cancers. OSA3, OSA4, and OSA5 cross-reacted with a fibrosarcoma cell line, a colon cell line, and fibrosarcoma, respectively, as well as with a melanoma cell line. None of the MoAbs were reactive with activated normal human peripheral blood mononuclear cells (PBMC). Immunoprecipitation of membrane protein isolated from LM cells and TE-85 cells with the MoAbs OSA1 and OSA2 conjugated with Staphylococcus aureus yielded a molecule with molecular weight of approximately 92,000. No detectable membrane protein was precipitated when 125I-labeled membrane protein from pooled activated human PBMC and tumor cells of other histologic types were used in the immunoprecipitation.

Animals↗
PubMed1980

A study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas.

Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle-cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas were detected 1--2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas.

Animals↗
PubMed1984

Dedifferentiated parosteal osteosarcoma.

Parosteal osteosarcoma is an uncommon malignant tumor of bone, and in a review of Mayo Clinic records we identified eleven cases of so-called dedifferentiated parosteal osteosarcoma. Ten of the eleven patients had had a long history of treatment for multiple recurrences of the tumor as a low-grade parosteal osteosarcoma and then for a definite recurrence as a high-grade undifferentiated osteosarcoma. The prognosis in this group of patients was similar to that in patients with conventional osteosarcoma.

Adolescent↗
PubMed1981

[Experimental studies on ascites tumor of human osteosarcoma in nude mice (author's transl)].

Six human osteosarcomas were transplanted subcutaneously in the back of nude mice and three of the six were found to be serially transplantable. Two of three transplantable solid tumors were called DOS tumor and KOS tumor. The 4th generation of DOS tumor and the 1st generation of KOS tumor grew to invade the peritoneum and tumor cells were spilt spontaneously into the abdominal cavity. These two cases were transformed to ascites tumor, called DOS-NM ascites tumor and KOS-NM ascites tumor. They were found to be serially transplantable by an intraperitoneal injection of free tumor cells (10-20 x 10(5) cells). DOS-NM and KOS-NM ascites tumor cells were analysed to have human karyotype and alkaline phosphatase activity. Ascites tumor cells were studied under light and electron microscopes. A large number of elongated and ballooned mitochondria were characteristically seen in the cytoplasm of two ascites tumor cells by electron microscope. Development of rough surfaced endoplasmic reticulum and Golgi's apparatus was poor, and no production of collagen fiber was seen in these materials. There is no report referring to ascites tumor of human osteosarcoma, therefore ascites tumor of osteosarcoma was made deliberately and the following results were obtained. 1) Several blocks of DOS tumor were implanted intraperitoneally into 5 nude mice, and only solid tumors grew in the abdominal cavity without ascites. 2) Minced DOS tumor was implanted subcutaneously close to the peritoneum and 2 out of 6 nude mice developed ascites tumor. 3) Cell suspension of DOS tumor was injected intraperitoneally and 3 out of 4 nude mice developed ascites tumors. As mentioned above, human osteosarcoma was successfully induced to ascites tumor (DOS-NM), which was established earlier compared with solid tumor (DOS). Characteristics of human osteosarcoma are easily examined with ascites tumor and in vivo screening test of anticancer drugs can be quantitatively done. Therefore ascites tumor is considered to be a valuable experimental model.

Adult↗
PubMed1982

Osteosarcomas in BALB/c female mice.

Osteosarcomas were found in 16 of 24,192 (0.066%) BALB/c female mice, 14 were in 21,816 (0.064%) 2-acetylaminofluorene-treated mice, and two were in 2,376 (0.084%) untreated controls. The osteosarcomas were classified into osteoblastic, fibroblastic, and mixed types. Seven of the osteosarcomas metastasized to the lungs. The osteosarcomas in control and 2-acetylaminofluorene-treated mice showed little or no difference in the incidence, type, size, or site of origin, indicating that 2-acetylaminofluorene did not affect the development of osteosarcomas in BALB/c female mice.U

2-Acetylaminofluorene↗
PubMed1982

[A study on the treatment of pulmonary metastatic osteosarcoma].

The primary site of metastasis of osteosarcoma is the lung. Even if a primary lesion was completely removed by radical surgery, more than 90% of the patients died of pulmonary metastasis in one to two years in the past. A control of osteosarcoma depends upon the prevention and treatment of its pulmonary metastasis. An introduction of chemotherapy consisting mainly of adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. We analyzed the clinical data, and gross as well as histopathologic post mortem findings, in 161 cases without chemotherapy and 42 cases with systemic adjuvant chemotherapy. Based on these analysis, we tried to clarify the nature of pulmonary metastasis of osteosarcoma and to evaluate its response to treatment from a standpoint of clinical pathology, hoping that this would yield a clue to future treatment of osteosarcoma.

Antineoplastic Agents↗
PubMedDate not supplied

Current aspects of the pathology of osteosarcoma.

Since the introduction of standardized chemotherapy protocols of osteosarcoma a lot of new aspects in prognosis and curability of these have best developed. Current subclassification which divided osteosarcoma into a conventional type and eleven important recognizable varieties is one of the reason for this success. Cytological grading also serves as a good indicator for the prognosis and is an important criterion for application of adjuvant chemotherapy. Several structure proteins of the extracellular matrix have gained importance in making the diagnosis of an osteosarcoma. Immunohistochemically and biochemically evaluations could show that different collagenous-proteins can be useful for the differential diagnosis of bone tumors. The integration of molecular pathologic methods into the structural morphologic findings will be helpfull in the identification of mutated structure proteins. Oncogenes and tumor suppressor genes are of major importance for the tumorigenesis of osteosarcoma. The prognostic significance of the inactivation of p53 and RBI gene remains to be elucidated. Resistance to chemotherapy is the major mechanism responsible for the failure of osteosarcoma treatment. The main cause for this failure is multidrug resistance, which is often related to a plasma membrane protein, the P-glycoprotein. Immunohistologic investigations of P-glycoprotein are not sufficient to demonstrate the possible association between overexpression of this protein and tumor progression.

Bone Neoplasms↗
PubMed1995

The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit.

The c-MET oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor (HGF), a cytokine that stimulates the invasive growth of normal and neoplastic cells. The Met/HGF receptor is expressed by epithelial cells and its ligand by cells of mesenchymal origin. Receptor-ligand interaction occurs via a paracrine circuit. We studied the expression of the Met/HGF receptor and of its ligand in mesenchymal human tumours by examining 39 clinical samples of bone tumours. The Met/HGF receptor was not detectable in the majority of bone tumours, as expected from their mesenchymal origin. Notably, the receptor was overexpressed in 60% of the osteosarcomas examined. In 12 osteosarcoma cell lines the Met/HGF receptor was overexpressed, phosphorylated by HGF stimulation and fully functional. HGF was detected in two out of seven clinical specimens of osteosarcoma. The ligand and the receptor are co-expressed in two clonal osteosarcoma cell lines. In these lines the Met/HGF receptor was constitutively phosphorylated; phosphorylation was suppressed by suramin treatment, a known blocker of autocrine loops. These data suggest that activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.

Bone Neoplasms↗
PubMed1995

In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral protein.

Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), was conjugated to TP-3 to produce an immunotoxin highly active against osteosarcoma. After 48 h no viable human OHS osteosarcoma cells were present in cultures containing TP-3-PAP as demonstrated by the absence of [3H]thymidine uptake into DNA. Furthermore, clonogenic assays indicated > 3.9 log kill of OHS at 18 h. The IC50 of TP-3-PAP against OHS was 3.5 +/- 1.0 (SD) x 10(-12) M. TP-3 mAb without PAP had no effect on OHS proliferation; PAP alone had no effect on OHS growth unless concentrations > 1000 pM were used. When TP-3-PAP (1.25 micrograms-10.0 micrograms) was given i.p. q.d. on days 3-5 after tumor inoculation, a dose-dependent reduction of the number of lung metastases was observed (P < 0.001). These results indicate that the TP-3-PAP immunotoxin may be useful in the treatment of osteosarcoma and some soft tissue sarcomas.

Animals↗
PubMed1994

Periosteal sunburst spiculation in osteosarcoma. A possible role for bone morphogenetic protein.

Periosteal sunburst spiculation is a peculiar radiographic feature of osteosarcoma, and it represents a reactive ossification resulting from the action of normal osteoblasts rather than tumor cells. Because bone morphogenetic protein is known to be a potent inducer of ectopic bone formation, the authors hypothesized that bone morphogenetic protein may be involved in the pathogenesis of such reactive bone formation in osteosarcoma. Chinese hamster ovary cells transfected with the bone morphogenetic protein-4 gene were injected into the femurs of athymic nude mice to form experimental bone tumors producing bone morphogenetic protein. Two weeks after intramedullary injection, new bone formation was observed radiographically and histologically within the extraosseous portions of the tumors. This showed a close resemblance to sunburst spiculation in human osteosarcomas. In contrast, the control nontransformed Chinese hamster ovary tumors showed no extraosseous bone formation. Because the induced bone was composed of multiple parallel spicules similar to those found in human bone morphogenetic protein-producing osteosarcomas, these findings suggest that periosteal sunburst spiculation may be the result of bone morphogenetic protein production by osteosarcoma cells.

Animals↗
PubMed1994

[Expression of the p53 protein in human osteosarcoma].

The expression of the p53 tumor suppressor gene protein was analyzed in 35 resected osteosarcomas, 5 resected osteochondromas, and in 2 human osteosarcoma cell lines by immunohistochemistry and flow cytometry. An abnormality in the expression of the p53 protein was found in 10(29%) of the 35 osteosarcomas. An overexpression of the p53 protein showed no correlation with the clinicopathological features, but the p53 protein staining pattern showed a tendency to be correlated with aggressive growth and the metastatic potential. Diffusely-stained tumors had a worse prognosis than those focally-stained. The relationship between the expression of p53 protein and the cell cycle was examined by flow cytometry. The maximum overexpression of p53 protein was detected in the cells at the S phase. These results indicated that the nuclear accumulation of the p53 protein, especially the staining pattern, was a potentially useful prognostic factor for osteosarcoma. However our study did not show any clear correlation between either the growth pattern or the morphological type of osteosarcoma and the immunohistochemical results for the p53 protein.

Adolescent↗