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PubMed1978

Telangiectatic osteosarcoma.

Of the 242 cases of osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968 only one was found to represent telangiectatic osteosarcoma. Another case was recently diagnosed in our department. The characteristic morphologic features of these neoplasms were anaplastic stroma, high mitotic activity, osteoid-formation, widely anastomosing blood spaces, and alkaline phosphatase activity. The experience gathered indicates that telangiectatic osteosarcoma constitutes a histopathologic variant of genuine osteosarcoma with a serious prognosis, necessitating the same kind of treatment as for the genuine tumour.

Adolescent↗
PubMed1981

Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma.

The effects of immunotherapy with irradiated tumour cells and BCG were studied in non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 X 10(6) irradiated tumour cells each 1 to 3 weeks before administration of 1 X 10(6) living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P less than 0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-week intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast to the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere.

Alkaline Phosphatase↗
PubMed2005

Tumor volume change after chemotheraphy as a predictive factor of disease free survival for osteosarcoma.

Change in tumor volume after chemotherapy appears to have a prognostic significance for the outcome of osteosarcoma. A newly developed volume measurement method based on three-dimensional summation with a proved reproducibility was utilized to measure osteosarcoma tumor volume. This retrospective analysis included 38 patients with biopsy- proven, nonsurface, skeletal high-grade osteosarcoma. The treatment was started by using three cycles of preoperative chemotherapy with cisplastin (100 mg/m2) and adriamycin (30 mg/m2). The tumor volume was measured before and after preoperative chemotherapy using three-dimensional magnetic resonance image measurement. The percentage of tumor necrosis was assessed by pathologic exam. After three cycle of postoperative chemotherapy, the patients were followed up at regular interval. For the 23 good responder patients, the mean survival time was 73.2 months (95% confidence interval 61.9-84.5 months), and for the 15 poor responder patients, the mean survival time was 50.8 months (95% confidence interval 38.6-63.1 months) (p<0.05). For the 14 patients with increased tumor volume after chemotherapy, the mean survival time was 47.5 months (range: 36.3-58.6 months) and for the 24 patients with stable or decreased tumor volume, the mean survival time was 74.3 months (range: 63.79-84.88 months) (p<0.05). Among the various factors, histopathologic response and tumor volume change after chemotherapy predicted disease free survival (p<0.05). Change in the tumor volume that was measured with a reproducible method and the histopathologic response after chemotherapy were the important predictors of disease free survival for osteosarcoma patients.

Antibiotics, Antineoplastic↗
PubMed2000

Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.

Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. The present study investigates magnetic liposomes designed to act as anticancer drug carriers, which can be effectively delivered to solid tumors via intravenous administration. Magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method, and an in vivo study was carried out to assess the magnetic targeting of these liposomes to hamster osteosarcoma. The average diameter of liposomes thus prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. After the hamsters had received an intravenous administration of either magnetic ADR liposomes or ADR solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor, liver, lung, heart, and kidney were determined at designated time intervals. Administration of magnetic ADR liposomes under magnetic force using a permanent magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold higher maximum ADR concentration in the tumor than did administration of ADR solution. The former administration modality induced an increase in ADR concentration in the liver and lung and a decrease in the heart compared with concentrations produced by the latter. The present results indicated that intravenously administered magnetic ADR liposomes can be used to effectively deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a common site of metastases for osteosarcoma. Our results also suggest that this new treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, can improve the clinical chemotherapy of solid tumors.

Animals↗
PubMed2007

Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells.

Previous studies have shown that oridonin, a diterpenoid isolated from Rabdosia rubescens, was able to inhibit proliferation and induce apoptosis in several cell types. But the mechanisms remain poorly understood. In this study, we investigated the apoptosis-inducing effect and mechanisms of action of oridonin in human osteosarcoma cells. Our results demonstrated that oridonin induced concentration- and time-dependent suppression of proliferation and activation of apoptosis in U2OS, MG63 and SaOS-2 osteosarcoma cell lines. Oridonin induced the release of cytochrome c accompanied by activation of caspase-9, caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). These events were all inhibited by z-VAD-fmk, a universal inhibitor of caspases. Oridonin treatment dephosphorylated constitutively active AKT, FOXO transcription factor, and glycogen synthase kinase 3 (GSK3). In addition, oridonin decreased the phosphorylation of ERK and increased the phosphorylation of p38 MAPK and JNK. Furthermore, oridonin treatment down-regulated the expression of the inhibitor of apoptosis protein(IAP) in osteosarcoma cells. All together, our results suggested that oridonin is able to inactivate Akt and ERK and activate p38 MAPK and JNK signalling pathways in osteosarcoma cells causing the suppression of proliferation and induction of mitochondria- and caspase-dependent apoptosis.

Antineoplastic Agents↗
PubMedDate not supplied

Primary osteosarcoma distal to the antebrachiocarpal and tarsocrural joints in nine dogs (1980-1992).

The medical records of nine dogs with primary osteosarcoma distal to the antebrachiocarpal or tarsocrural joint were reviewed. Eight of the nine dogs were treated with surgical removal of the primary tumor; seven received adjuvant chemotherapy; and one dog was treated with chemotherapy alone. Median survival of dogs in this series was 466 days. Six of the nine dogs died of causes attributable to osteosarcoma, and both skeletal and pulmonary metastases occurred. Survival of dogs with osteosarcoma distal to the antebrachiocarpal or tarsocrural joint was somewhat longer than survival of dogs with osteosarcoma of more common appendicular sites. However, these are aggressive tumors with a high potential for metastasis.

Animals↗
PubMed1988

Controversies in the treatment of osteosarcoma.

In my opinion, it is clear that improving the initial disease-free survival is the key to improving the cure rates for patients with osteosarcoma. However, until new drugs with marked activity against osteosarcoma are developed, significant improvements in disease-free survival are unlikely. Almost all patients with newly-diagnosed osteosarcoma will receive preoperative chemotherapy which is followed by a definitive surgical (limb-sparing or amputation) procedure and additional postoperative chemotherapy. The impact of limb-sparing surgery on the incidence of pulmonary metastases and long-term disease-free survival must be assessed carefully in continuing and future trials. It is conceivable that limb-sparing surgery may be contraindicated in certain situations. The cure rate after the development of metastatic disease must be assessed, although I fear that it will be quite low. Lastly, and possibly most importantly, the assessment of biological variables such as tumour ploidy, enzyme content, and so on, should be undertaken in an effort to promote a better understanding of osteosarcoma.

Bone Neoplasms↗
PubMed2006

Radiation-associated extraskeletal osteosarcoma of the chest wall.

Radiation-associated sarcoma is a rare but potential complication of radiation therapy. Most reported cases of osteosarcoma of the chest wall following radiation therapy for breast cancer arise from the chest wall skeletal structures. In contrast, few cases of extraskeletal osteosarcomas have been reported. We report a rare example of an extraskeletal osteosarcoma involving the pectoralis major muscle occurring after radiation therapy for breast cancer. Extraskeletal osteosarcomas are rare soft tissue tumors with a high rate of local recurrence and a poor prognosis.

Biomarkers, Tumor↗
PubMed2004

[A case of osteosarcoma in pelvic bone following radiation therapy for prostate cancer].

A case of osteosarcoma in pelvic bone following radiation therapy for prostate cancer is reported. A 74-year-old patient was diagnosed with prostate cancer 10 years ago and started on the endocrine therapy with LH-RH agonist. He had no apparent distant metastasis, and received radiation therapy 8 years ago. He has complained of low back pain since several months ago. A high uptake on bone scintigram and osteolytic and osteoblastic damages on CT were noted in pubic bone and sacrum. The PSA level was less than 0.2 ng/ml. Pathohistological diagnosis by biopsy of the pubic bone was chondroblastic type osteosarcoma, showing an atypical cell proliferation with osteoid. Immunostaining for nonepithelial marker vimentin was positive. He underwent heavy ion radiation therapy for osteosarcoma at the National Institute of Radiological Sciences. Osteosarcoma is one of the rare delayed complications after radiation therapy and requires biopsy for correct diagnosis.

Aged↗
PubMed2002

[Juxtacortical osteosarcoma of tibia from a medieval cemetery of Budapest].

Juxtacortical osteosarcoma occurred on the right tibia and fibula of a 20-22 years old man found in a medieval period cemetery of Budapest. MACROSCOPIC DESCRIPTION: The tumor is located circumferentially on the midshaft of the tibia and fibula and appears cone-shaped. The lesion measured 160 mm in length and 3-5 mm in height. The surface of the tumor is irregular, rough, in some areas shows spicules. These spicules averaged 2-4 mm in length and 1-2 mm in diameter. The anterior and medial surface of the tibia is completely covered by osseous tumor. RADIOGRAPHY: The X-ray study demonstrates the medullary involvement, with mixed osteolytic and osteoblastic areas. Tumor infiltration of the cortex is also apparent as irregular rarefication and lytic lesions. In some areas a "sunburst" picture could be seen. The X-ray picture is characteristic for juxtacortical osteosarcoma. MICROSCOPIC EXAMINATION: stereomicroscopy of specimens shows a sponge-like structure of the surface. The cortical bone is completely destroyed and deep cavities are seen between spiculous and gyrificated neoplastic bone. The spiculae are varied in length and thickness. Irregular bulky bone trabeculae demonstrating uncontrolled neoplastic reaction could be detected. By light microscopic examination severe destruction, osteolytic lesions are seen both in the cortical bone and in the cancellous bone in the peripheral parts of the tumors. Within the neoplastic bone only few remnants of the primary (normal) bone structure could be demonstrated. No reparative reactions were seen next to the osteolysis, the collagen fibers and lamellas are destroyed. Beside the destruction of original bone larger structures composed of irregular newly built nepotistic bone trabeculae can be detected. The newly formed trabeculae (spiculae) contain a tumorous ground substance (probably osteoid tissue) with few collagen fibers, and these areas are covered with a thin bony lamella. In some areas the neoplastic structures are in intimate contact with the original cancellous bone remnants. IMMUNOHISTOCHEMISTRY: Both the osteosarcoma and chondrosarcoma show osteoid and bone neoformation while in the chondrosarcoma type II collagen could also detected. By immunohistochemical reactions no type II and III collagen, only type I collagen reaction was positive. This means that no cartilaginous tissues were present in the tumor. Scanning electron microscopy of these specimens shows sponge-like structures. The tumor reveals irregular trabecular and spicular texture,the spicules are various in diameter and in some spiculae rounded deposits attached to the surface. In our case we found typical radiological and histological picture of the juxtacortical osteosarcoma.

Bone Neoplasms↗
PubMedDate not supplied

Multifocal osteosarcoma: an unusual presentation.

PURPOSE: Report the unusual presentation, clinical course, and cytogenetic abnormalities in a child with multifocal osteosarcoma. PATIENTS AND METHODS: A 10-year-old boy had multifocal osteosarcoma involving the entire skeleton, pleura, bone marrow, and lungs. He had marked anemia, thrombocytopenia, and severe hypocalcemia at diagnosis. RESULTS: Despite aggressive chemotherapy, he died from progressive disease 1 month after diagnosis. Cytogenetic analysis of tumor cells within the pleural fluid showed multiple chromosomal abnormalities with amplification of the c-myc oncogene. CONCLUSION: Multifocal osteosarcoma should be considered in the differential diagnosis of a child with pancytopenia and multiple bone lesions. Amplification of the c-myc oncogene may have had a significant role in the pathogenesis, etiology, and rapid progression of this patient's multifocal disease. Additional studies will be needed to determine the biologic significance of c-myc amplification in multifocal osteosarcoma.

Child↗
PubMed1999

Mechanisms of methotrexate resistance in osteosarcoma.

High-dose methotrexate is a major component of current protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resistance include decreased transport through the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade osteosarcoma. RFC and DHFR mRNA expression were studied by semiquantitative reverse transcription-PCR. The RFC and DHFR genes were studied for deletions and amplification by Southern blot. Thirteen of 20 (65%) osteosarcoma samples were found to have decreased RFC expression at the time of initial biopsy. At definitive surgery and relapse, 10 of 22 (45%) were found to have decreased RFC expression. Seventeen of 26 (65%) samples with a poor response to chemotherapy had decreased RFC expression, whereas 5 of 14 (36%) samples with a good response had a decrease (P = 0.03). None of the samples had an RFC gene deletion. Two of 20 samples (10%) showed increased DHFR expression at initial biopsy. The frequency of increased DHFR expression was significantly higher in metastatic or recurrent tumors (62%, P = 0.014). None of the samples showed evidence of DHFR gene amplification. The high frequency of decreased RFC expression in the biopsy material suggests that impaired transport of methotrexate is a common mechanism of intrinsic resistance in osteosarcoma. Increased DHFR expression in the pulmonary metastases may be a mechanism of acquired methotrexate resistance or a difference between primary and metastatic lesions.

Adolescent↗
PubMed1999

High-activity samarium-153-EDTMP therapy in unresectable osteosarcoma.

Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. We applied high-activity Sm-153-EDTMP therapy within a multimodal therapy concept to improve local control of an unresectable osteosarcoma with poor response to initial polychemotherapy. A 21-year-old woman with an extended, unresectable pelvic osteosarcoma and multiple pulmonary metastases was treated with high-activity of Sm-153- EDTMP (150 MBq/kg BW, total 8.1 GBq). Afterwards external radiotherapy of the primary tumor site was performed and polychemotherapy was continued, followed by autologous peripheral blood stem cell reinfusion. Within 48 h after Sm-153-EDTMP application the patient had complete pain relief. After three weeks the response was documented by 3-phase Tc-99m-MDP bone scintigraphy (primary tumor and metastases: decreased tracer uptake), whole-body F-18-FDG-PET (primary tumor and metastases: diminution of glucose metabolism) and thoracic CT (metastases: reduction of size). The present case warrants further evaluation of feasibility and efficacy of this multimodal therapy combination of high-activity Sm-153-EDTMP therapy, external radiation, polychemotherapy and stem cell support for unresectable osteosarcomas.

Adult↗
PubMed1999

Prognostic significance of DNA image cytophotometry for osteosarcoma.

OBJECTIVE: To investigate the prognostic significance of DNA image cytophotometric data. STUDY DESIGN: Twenty-six osteosarcomas in patients without lung metastases were investigated for several cytophotometric data. In 24 cases, these data were correlated with the clinical course of the patients to assess the prognostic value of nuclear DNA content in osteosarcomas. RESULTS: Of all osteosarcomas, 96% showed aneuploid DNA content. Patients with tumors having a 2c deviation index (2cDI) of 12.00, DNA malignancy grade (DNA-MG) of 2.0, a mean DNA content (MDC) of 4.95 c, DNA index (DI) of 1.75 or mean nuclear area (MNA) of 130 microns 2 had a significantly lower overall survival rate as compared to those with lower values (P < .05). CONCLUSION: Image cytophotometric features, such as 2cDI, DNA-MG, MDC, DI and MNA, are of prognostic value in patients with osteosarcoma and free of lung metastases.

Adolescent↗
PubMed1976

Immunogenicity of virus-induced rat osteosarcoma.

The immunogenicity of a virus-induced rat osteosarcoma was studied utilizing the lymphocyte microcytotoxicity test. Intratibial injection of murine sarcoma virus (Moloney) resulted in the development of palpable tumors at the injection site which on histopathological examination appeared to be osteosarcomas. In 73 per cent of animals injected these tumors progressed and metastasized to the lungs. Lymphocytes from these "progressor" animals demonstrated an ability to kill osteosarcoma cells in vitro (as quantitated in the microcytotoxicity test) while serum from these animals abrogated or blocked the cell-mediated cytotoxicity. In the remaining animals the tumors either failed to develop or regressed spontaneously. Lymphocytes from these "regressor" animals also demonstrated cytolytic activity against osteosarcoma cells in vitro, but serum failed to block the lymphocyte-mediated cytolysis. Both regressor and progressor groups demonstrated humoral cytotoxic antibodies to tumor antigen on the basis of the ability of their serum to kill tumor cells in vitro.

Animals↗
PubMed1997

[Image analysis of cell nuclear morphology and DNA content in osteosarcoma of the jaws].

The measurement of nuclear morphology and quantitative analysis of nuclear DNA content were made by Interactive Image Analysis System in 47 osteosarcomas of the jaws. The results showed that with a decreased degree of differentiation, the cell nuclei of osteoblastic and chondroblastic osteosarcomas came to be large and irregular, those of fibroblastic osteosarcomas, however, to be small and round. It was revealed that high-grade osteosarcomas had increased amounts of DNA and that the mean of DNA content, proportion of hyperploid cells and tumor ploidy were found to be of important prognostic value.

Cell Nucleus↗
PubMed2000

Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis.

To investigate the clinical significance of vascular endothelial growth factor (VEGF) in osteosarcoma, we immunohistochemically stained biopsy specimens of 27 primary osteosarcomas using an antibody against VEGF and evaluated the correlation between the expression of VEGF and local density of CD34-positive microvessels, clinicopathological variables, and survival of patients. VEGF staining was positive in 17 tumors (63.0%) in which the density of CD34-positive microvessels was significantly higher than that in VEGF-negative 10 tumors (P < 0.05). In terms of clinicopathological variables, there was no correlation between the expression of VEGF and histological subtype, stage, or response to neoadjuvant chemotherapy, or, strikingly, to the development of pulmonary metastasis (89% of VEGF-positive tumors versus 10% of VEGF-negative tumors; P < 0.0003). Moreover, patients with a VEGF-positive tumor were poorer in both disease-free survival (P < 0.001) and overall survival (P < 0.03) compared to those with a VEGF-negative tumor. These findings strongly suggest that VEGF expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy and also provide the basis for a therapeutic strategy targeting angiogeneic property of osteosarcoma.

Adolescent↗
PubMed1999

Long-term survival of patients with mandibular osteosarcoma.

Osteosarcoma generally has a poor prognosis. Osteosarcoma of the mandible is rare and may have a less aggressive course. Three patients with osteosarcoma of the mandible were treated during the past 19 years at National Taiwan University Hospital. All were women, with an average age of 49 years. The patients were treated with radical excision of the tumor, with either pre- or postoperative radiotherapy. None of the patients received chemotherapy. Reconstruction with iliac osteocutaneous free flap, fibular osteoseptocutaneous free flap, or Leibinger reconstruction plate was performed to repair the facial defects resulting from tumor resection or radiation-induced necrosis. The three patients were alive and without evidence of recurrence at the time of writing, with follow-up periods ranging from 7 to 18 years. All had acceptable facial contour and satisfactory oromandibular function after reconstruction. These results support the effectiveness of wide resection with radiotherapy for treatment of mandibular osteosarcoma. With the availability of microsurgical reconstruction and biocompatible reconstruction plates, we advocate extensive ablation of this tumor. Long-term survival, good functional recovery, and acceptable facial contour can be expected.

Adult↗