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PubMedDate not supplied

[Nuclear medicine prediction of histologic tumor response of osteosarcoma].

The prediction of histologic tumor response to preoperative chemotherapy was assessed by quantitative scintigraphic follow-up examinations of 54 osteosarcomas. Tumor/non-tumor scintimetry using 99mTc labeled diphosphonates allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (accuracy = 83%) at the half-way stage of preoperative chemotherapy evaluating only those tumors which showed convergent changes of tumor/non-tumor ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc MDP plasma clearance predicted the histologic tumor response to chemotherapy in 12 of 13 tumors (accuracy = 92%) after completion and in all 11 cases (accuracy = 100%) at the half-way stage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Immune complex formation and complement changes in osteosarcoma patients treated with high-dose methotrexate].

Patients with osteosarcoma frequently have elevated immune complex levels, which are correlated with disease activity and tumor volume. During treatment with high-dose methotrexate (MTX) some patients develop specific immune complexes containing MTX. These patients suffered from anaphylactic reactions. To study the influence of MTX on immune complex formation we looked for polyethyleneglycol (PEG) precipitable and C3b-binding immune complexes in the sera of 10 children with osteosarcoma during treatment according to the COSS 80 protocol. Sera were obtained before, 24, 48 and 72 hours after MTX-infusion. Furthermore we analysed changes of the complement system in the same way. The minority of the patients developed PEG-precipitable immune complexes. C3b-binding IgG complexes were observed at the beginning and at the end of treatment. High levels of immune complexes at the end of chemotherapy were correlated with a poorer prognosis. There was no relationship between MTX-infusion and immune complex formation. No significant changes of the complement system during MTX-infusion were found. The complement analysis were of no prognostic value concerning the osteosarcoma.

Adolescent↗
PubMedDate not supplied

[Fluorescence cytophotometric DNA studies of Ewing and osteosarcomas].

The single-cell fluorescence cytometric data presented in this study basing on measurements on 6 osseous Ewing's-Sarcoma and 17 classical osteosarcoma are showing a mirrorlike behaviour to cytological and histological appearance. The cellular monotony in Ewing's-Sarcoma and the polymorphic appearance of osteosarcoma are represented by typical aneuploid DNA-histograms. Ewing's-Sarcoma histogram's show a large peak between the diploid and tetraploid region and little deviation to the octoploid value. The conventional osteosarcomas are characterised by a very polyploid and changeable DNA-histogram with variable blocks and peaks and deviation up to 34c. Special trends in the subtypes are remarkable, but depend on further investigations. DNA-measurements support objectivization of histological appearance on the one hand and the controlling of therapeutical responses on the other hand.

Adolescent↗
PubMed1985

[Comparison of x-ray and histological findings in osteosarcomas following preoperative chemotherapy].

Since the introduction of pre-operative chemotherapy, osteosarcomas have shown a more favourable prognosis. Reaction of the tumour due to chemotherapy is judged pre-operative primarily by radiology (plain films, angiography, CT, scintigraphy). There is little evidence concerning the radiological appearances after pre-operative chemotherapy and morphological changes, particularly in respect of tumour regression. Specific radiological changes were therefore compared with pathological findings following chemotherapy and operation in 17 patients with osteosarcomas. Tumours were examined which showed radiological evidence of intra-and extra-osseous sclerosis or lysis and which still were classified as vital tumour tissue. Tumour planes were reconstructed from large histological sections of the operative specimen and compared with the radiological appearances. Sclerosis was found to be due to reactive new bone formation or to mineralisation of the osteosarcomatous tissue. Lysis correlated with persistent vital tumour, or in connective tissue. Nine out of ten cases, regarded as vital on radiological evidence, showed vital tumour cells on histological section. Lyses and scleroses were not reliable indications of the pre-operative state of the osteosarcoma following chemotherapy. On the other hand, combined qualitative radiological criteria for assessing tumour vitality, proved to be helpful.

Adolescent↗
PubMed1986

The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity.

We conducted a randomized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high-grade osteosarcoma of the extremity, as compared with concurrent controls. After undergoing definitive surgery, 36 patients were randomly assigned to adjuvant chemotherapy or to observation without adjuvant treatment. At two years the actuarial relapse-free survival was 17 percent in the control group, similar to that found in studies before 1970, and 66 percent in the adjuvant-chemotherapy group (P less than 0.001). Similar results were observed among 77 additional patients who declined to undergo randomization but who elected observation or chemotherapy. We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades, that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high-grade osteosarcoma, and that it should be given to all such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

A case of extraskeletal osteosarcoma with metastasis to the skin.

We present an 83-year-old woman with extraskeletal osteosarcoma (ESOS) of the breast who developed metastasis to the scalp. Skeletal osteosarcoma is the most common primary malignant neoplasm of the bone, predominantly occurring in the metaphysis of the long bones of adolescents and young adults. ESOS, in contrast, occurs primarily in the fifth and sixth decades of life, most commonly in the soft tissue of the thigh. Although the lung is overwhelmingly the most common site of metastasis for both skeletal osteosarcoma and ESOS, the skin is an uncommon metastatic site with only a few reported cases. Metastasis of ESOS to the skin is an exceedingly infrequent phenomenon, which may be a sign of widespread metastases foreboding a grim prognosis.

Aged↗
PubMed2001

Osteosarcoma metastatic to the mandible: a case report.

A case of osteosarcoma that metastasized to the mandibular ramus from the femur in a 36-year-old man is presented. The patient was referred to us for the diagnosis and treatment of swelling of the left cheek. Radiologic examination showed a radiolucent lesion containing radiopaque areas within the left mandibular ramus. The patient previously suffered from a femoral small cell osteosarcoma, which was resected 71 months before our first examination. After induction of general anesthesia, a unilateral mandibulectomy and a simultaneous reconstruction using a titanium plate and an artificial condyle were performed. The postoperative course was uneventful, with satisfactory facial appearance and jaw function. The histopathologic features of the mandibular tumor were identical to those of the femoral tumor. Thus the mandibular lesion was diagnosed as a metastatic small cell osteosarcoma. At 27 months after the operation there had been no recurrence.

Adult↗
PubMed2001

Ultrasound features of osteosarcoma of the mandible--a first report.

Ultrasound imaging is becoming widely used in the head and neck region as a first-line investigation to assess soft tissue swellings. Clinicians should be aware of the potential of diagnostic ultrasound to identify important signs of malignant disease involving bone. Involvement of the mandible by osteosarcoma is uncommon. A young adult patient presented with facial swelling and an apparently infected lower third molar extraction socket. Subtle signs were missed on dental radiographs. Diagnostic ultrasound investigation was pivotal in identifying sinister signs: namely, soft tissue mass associated with bone thinning, erosion, expansion, and the "sunray" appearance of the buccal cortex, which were suggestive of osteosarcoma. These findings enabled priority to be given to subsequent investigations using other modalities. We present a first report of the ultrasound features of osteosarcoma of the mandible and consider this to be a useful modality in an initial investigation.

Adult↗
PubMed2005

Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma cells.

Bone sialoprotein (BSP), a major protein in the extracellular matrix of bone, is expressed almost exclusively by bone cells and by cancer cells that have a propensity to metastasize to bone. Previous studies have shown that v-src stimulates basal transcription of bsp in osteosarcoma (ROS 17/2.8) cells by targeting the inverted CCAAT element (ICE) in the proximal promoter. To identify possible downstream effectors of Src we studied the effects of the proto-oncogene c-jun, which functions downstream of Src, on basal transcription of bsp using transient transfection assays. Increased expression of endogenous c-Jun induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and ectopic expression of c-Jun increased basal transcription of chimeric reporter constructs encompassing the proximal promoter by 1.5-3-fold in ROS 17/2.8 osteosarcoma cells, with more modest effects in a normal bone cell line, RBMC-D8. The effects of c-Jun were abrogated by mutations in the ICE box and by co-expression of dominant negative nuclear factor Y, subunit A (NF-YA). The increase in bsp transcription did not require phosphorylation of c-Jun and was not altered by trichostatin treatment or by ectopic expression of p300/CREB-binding protein (CBP) or mutated forms lacking histone acetyltransferase (HAT) activity. Similarly, ectopic expression of p300/CBP-associated factor (P/CAF), which transduces p300/CBP effects, or of HAT-defective P/CAF did not influence the c-jun effects. Surprisingly, E1A, which competes with P/CAF binding to p300/CBP, also stimulated BSP transcription through NF-Y independently of c-jun, p300/CBP, and P/CAF. Collectively, these studies show that c-Jun and E1A regulate basal transcription of bsp in osteosarcoma cells by recruiting the NF-Y transcriptional complex to the ICE box in a mechanism that is independent of p300/CBP and P/CAF HAT activities.

Animals↗
PubMed2000

Selective activation of the glucocorticoid receptor by steroid antagonists in human breast cancer and osteosarcoma cells.

Steroid hormones regulate the transcription of numerous genes via high affinity receptors that act in concert with chromatin remodeling complexes, coactivators and corepressors. We have compared the activities of a variety of glucocorticoid receptor (GR) antagonists in breast cancer and osteosarcoma cell lines engineered to stably maintain the mouse mammary tumor virus promoter. In both cell types, GR activation by dexamethasone occurs via the disruption of mouse mammary tumor virus chromatin structure and the recruitment of receptor coactivator proteins. However, when challenged with a variety of antagonists the GR displays differential ability to activate transcription within the two cell types. For the breast cancer cells, the antagonists fail to activate the promoter and do not promote the association of the GR with either remodeling or coactivator proteins. In contrast, in osteosarcoma cells, the antiglucocorticoids, RU486 and RU43044, exhibit partial agonist activity. The capacity of these antagonists to stimulate transcription in the osteosarcoma cells is reflected in the ability of the RU486-bound receptor to remodel chromatin and associate with chromatin-remodeling proteins. Similarly, the observation that the RU486-bound receptor does not fully activate transcription is consistent with its inability to recruit receptor coactivator proteins.

Animals↗
PubMed2001

Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases.

Between April 1990 and December 1994, we treated 24 patients with telangiectatic osteosarcoma (TO) of the extremities with neoadjuvant chemotherapy using 2 protocols. Surgery consisted of limb salvage in 21 patients and amputation or rotation plasty in 3. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 23 patients, of whom 12 had total necrosis. With a mean follow-up of 74 (60-96) months, 20 patients remained continuously free of disease and 4 relapsed with lung metastases. There were no local recurrences. Comparing these results to the ones achieved in 269 contemporary patients with conventional osteosarcoma of the extremities using the same protocols for chemotherapy, we found a significantly better histologic response to chemotherapy (96% vs 68% of good histologic response; p = 0.004) and disease-free survival (83% vs 55%; p = 0.01) in the TO group. We conclude that TO, once considered a lethal tumor, seems to be even more sensitive to chemotherapy than conventional osteosarcoma, and that most of these patients may be cured without amputation.

Adolescent↗
PubMed1999

Osteosarcoma of the scapula arising in osteogenesis imperfecta.

A case of osteosarcoma arising in the scapula of a 37 year old woman with severe congenital sporadic white sclera type osteogenesis imperfecta (OI) is presented. Osteosarcoma occurs as a sporadic rather than a related occurrence in patients with OI. A delay in the diagnosis of osteosarcoma may occur due to the similarity in symptomatology between the two conditions and because of the difficulty in differentiating between hyperplastic callus and tumor using conventional radiographic imaging techniques.

Adult↗
PubMedDate not supplied

Apoptosis induced by hyperthermia in Dunn osteosarcoma cell line in vitro.

The effect of hyperthermia at 43.5 degrees C for 1 h on Dunn osteosarcoma cells was studied. With sham-heated cells (37 degrees C, 1 h) as the control, the hyperthermia treated cells were divided into five groups. Time 0 group was the cells that were harvested immediately after heated at 43.5 degrees C for 1 h. Whereas time 3, 6, 12, and 24 h groups were the cells that were collected respectively after reincubation at 37 degrees C for the above different time periods. The appearance of hyperthermia-induced apoptosis of Dunn osteosarcoma cells was demonstrated to be time dependent. With the confocal microscopic study and TUNEL staining, the morphological characteristics of apoptosis, condensed nuclei and fragmented nuclei were obvious when reincubated at 37 degrees C for 6 h after hyperthermic treatment. This hyperthermia-induced apoptosis was further confirmed by flow cytometric analysis on DNA contents. The sub-G1 region that was proposed as a marker of apoptotic cells was most significantly elevated at 6 h after hyperthermic treatment and, thereafter, decreased to the levels of control values by 24 h, as the apoptotic cells underwent secondary necrosis and degraded to debris. The DNA strand breaks, considered as the key biochemical event of apoptosis, were detected by the TUNEL assay. This study indicated that hyperthermia (43.5 degrees C for 1 h) can induce apoptotic changes on osteosarcoma cells in vitro very rapidly (within 6 h after treatment), and its occurrence might not be detected if the samples are not taken at several early time points after hyperthermia.

Apoptosis↗
PubMedDate not supplied

Reversible downregulation of telomerase activity by hyperthermia in osteosarcoma cells.

Telomerase, a ribonucleoprotein enzyme, maintains telomere length and is expressed by the majority of malignant tumours, but not in normal tissue. Telomerase facilitates the division of tumour cells and its activity has been suggested as a prognostic indicator, but so far the regulation or modulation of telomerase activity has not been described. Hyperthermia has been shown to decrease tumour growth by inhibition of proliferation. Therefore, the effect of hyperthermia on telomerase activity in human osteosarcoma cells was studied. Telomerase activity was measured by the Telomeric Repeat Amplification Protocol (TRAP) assay in three different osteosarcoma cell lines subjected to hyperthermia (42.5 degrees C, 90 min) and in controls cultured under basal conditions (37 degrees C). Telomerase activity was strongly inhibited by hyperthermia and decreased in all cell lines tested after a recovery time of 2 h under basal conditions (37 degrees C) to an activity of approximately 85%, after 12 h approximately 60% and with lowest activity approximately 55% compared to activity of control cells. Telomerase activity then increased and reached the same, i.e. basal, level as before hyperthermia, after 112 h. These results show that hyperthermia results in a reversible downregulation of telomerase activity in osteosarcoma cells. This effect facilities studies on the regulation of telomerase activity and detailed information might lead to new therapeutic strategies.

Cell Division↗
PubMedDate not supplied

Squamous cell carcinoma of the tongue as a second malignancy in a patient previously treated for osteosarcoma.

A 15-year-old girl was diagnosed with osteosarcoma; limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 2 years. One year after completion of chemotherapy, the patient was readmitted for systemic recurrence. Amputation of the lower extremity and wedge resection of lung metastasis were performed followed by combination chemotherapy. Two years after cessation of chemotherapy, ulcer of the tongue was noted and cervical lymph nodes were detected by palpation. Biopsy of the lesion showed squamous cell carcinoma. The patient underwent a radical partial tongue resection and postoperative irradiation, followed by chemotherapy. Six years after treatment for the second malignancy, the patient remains well without evidence of disease. Squamous cell carcinoma of the tongue as a second malignancy after treatment of osteosarcoma is quite rare. Long-term follow-up, with particular attention to the head and neck, may be warranted in children treated for osteosarcoma.

Adolescent↗
PubMed2001

A rare tumor of craniofacial bones in children: a pediatric chondroblastic osteosarcoma case with diagnostic and therapeutic problems.

Osteosarcoma of the cranial facial region is uncommon and only rarely involves the ethmoid or sphenoid bones. The authors report on an unusual case of a 17-year-old male presenting with chondroblastic osteosarcoma of the maxillary, ethmoid, and sphenoid sinuses who remains well and disease-free at 46 months. He was treated with anterior craniofacial resection followed by postoperative radiotherapy to the sight of the primary tumor. He did not receive chemotherapy because of emerging hepatitis-B infection and vasculitis. The literature on extragnathic craniofacial osteosarcomas is reviewed with particular emphasis on treatment options of this rare tumor.

Adolescent↗
PubMedDate not supplied

Osteosarcoma as a second malignancy after treatment for neuroblastoma.

A 4-month old girl was diagnosed as having stage IV neuroblastoma of the right adrenal gland. Preoperative chemotherapy was given, followed by local surgical excision. Postoperatively, irradiation of the tumor bed and adjuvant chemotherapy was given for 11 months. Nine years after cessation of chemotherapy, the patient developed left hip-joint pain. Biopsy of the ischium showed chondroblastic osteosarcoma. Limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 14 months. Twenty-two months after treatment for the secondary osteosarcoma, the patient has been remained in disease-free condition without any evidence of relapse. A second osteosarcoma occurring outside the radiation field after treatment for neuroblastoma is quite rare. This unusual case emphasized the need for close monitoring for development of second malignant neoplasms in survivors of neuroblastoma even in the absence of a known predisposing factor, such as radiation therapy.

Combined Modality Therapy↗
PubMed2004

Identification of a transcriptionally inactive p53 mutant by functional analysis of separated alleles in yeasts (FASAY) in a child osteosarcoma tumor: a case report.

Tumor suppressor gene p53 is one of the most specific genetic alterations occurring in osteosarcoma pathogenesis. It is thought to be an early and key step in the tumorigenesis of osteosarcoma. However, whether the p53 status is a marker predictive of response to therapy and a marker of prognostic value remains controversial. The choice of p53 status detection method certainly account for discrepancies. The authors used a simple functional assay (functional analysis of separated alleles in yeast) on the tumor sample of an 8-year-old girl presenting with an osteosarcoma of the tibia. While making it possible to exclude the presence of a germline mutation, FASAY indicated the presence of a somatic p53 mutation lacking transcriptional activity on p21 and bax target genes. FASAY also strongly suggested a loss of heterozygosity p53, which was confirmed by cytogenetic analysis. Sequencing of cDNA extracted from yeast colonies containing mutated p53 identified a 213 stop mutation in exon 6. Despite these p53 alterations, the child is still in complete remission after a follow-up of 48 months.

Child↗