Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comprehensive multidisciplinary approach has transformed osteosarcoma from a disease with a modest long-term survival to one in which at least two-thirds of patients will be cured. Surgery remains the vital modality for treating the primary tumor, whereas adjuvant chemotherapy plays an essential role in the control of subclinical metastatic disease. Complete surgical excision of the primary tumor remains an essential element of treatment. For many patients, a combination of advances in surgical technique, improved imaging modalities to accurately document tumor extent, and the effect of neoadjuvant chemotherapy has made limb salvage procedures a safe alternative to amputation. In some patients for whom complete surgical excision is impossible, the addition of radiation therapy may allow local tumor control. The most effective chemotherapy agents currently in use include high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide/etoposide. The optimal schedule of therapy is still being investigated, as is the role of dose intensification. Unfortunately, some groups of patients remain at high risk of eventual relapse. Those whose tumors show relatively low degrees of necrosis after administration of chemotherapy have poorer survival than patients with more chemotherapy-responsive tumors. Similarly, patients who present with overt metastatic disease (particularly bone metastases), as well as patients with tumors that recur after treatment, continue to have an unsatisfactory outcome. These groups, in particular, may benefit from future investigations into novel agents, such as biological response modifiers, antiangiogenesis factors, and growth receptor modulation.
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PMID:Current treatment of osteosarcoma. 1133 87

Bisphosphonates (BPs), such as pamidronate and clodronate, are an important class of drugs for the treatment of bone diseases. It is widely recognized that they inhibit bone resorption by suppressing the action of osteoclasts through antagonizing the mevalonate pathway, thereby reducing osteolytic bone metastases derived from different cancers, i.e. breast carcinoma and multiple myeloma. In contrast, the effects of BPs on primary bone tumors is an issue still to be resolved. Therefore, a systematic approach was set up to test the hypothesis that BPs could act directly on osteosarcoma cells. The effects of pamidronate and clodronate on seven osteosarcoma cell lines (HOS, MG-63, OST, SaOS-2, SJSA-1, U(2)OS and ZK-58) were studied. Pamidronate inhibited cell growth in a time- and dose-dependent manner, and decreased proliferation for up to 73% at 50 microM after 72 h, whereas its monophosphonate analog 3-aminopropyl phosphonate did not reduce cell viability at concentrations up to 2 mM. Clodronate showed less inhibitory effects (maximally 38% reduction at 1 mM after 72 h). Importantly, cell growth of fibroblasts was only very weakly affected by treatment with pamidronate. These results suggest that pamidronate may be a useful agent for the treatment of patients with osteosarcoma.
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PMID:The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro. 1139 74

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment. The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of "primary" and "secondary" lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metastases from a monocentric tumor.
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PMID:Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases. 1145 Aug 92

Long term outcome and prognosis factors of patients with metastatic osteosarcoma were evaluated on 29 observations from 3 centres reviewed retrospectively. Twenty-nine patients less than 18 years old were treated from 1990 to 1998. Only 29 of these patients had received similar treatments associating chemotherapy and surgery, adapted according to histological and clinical response to treatment, as recommended by the SFOP. Overall survival at five years was 26%, and disease free survival 14%. Eight patients are alive, four in first complete remission (CR) and four in second CR. Three of the four patients alive in first CR had bone metastases at diagnosis. On univariate analysis, factors predicting survival are: the numbers of organs affected by metastatic lesions, the number of lung nodules and the type of surgery. This is, to our knowledge, the first report of long term survivors with bone metastases at diagnosis. Metastatic osteosarcoma prognosis remain poor. A randomised study would help to define the best possible treatment for this disease.
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PMID:[Metastatic osteosarcoma: prognosis factors and treatment]. 1174 7

The treatment of osteosarcoma requires a multidisciplinary approach involving the family physician, orthopedic oncologist, medical oncologist, radiologist and pathologist. Osteosarcoma is a mesenchymally derived, high-grade bone sarcoma. It is the third most common malignancy in children and adolescents. The most frequent sites of origin are the distal femur, proximal tibia and proximal humerus. Patients typically present with pain, swelling, localized enlargement of the extremity and, occasionally, pathologic fracture. Most patients present with localized disease. Radiographs commonly demonstrate a mixed sclerotic and lytic lesion arising in the metaphyseal region of the involved bone. Computed tomography and bone scanning are recommended to detect pulmonary and bone metastases, respectively. Before 1970, osteosarcomas were treated with amputation. Survival was poor: 80 percent of patients died from metastatic disease. With the development of induction and adjuvant chemotherapy protocols, advances in surgical techniques and improvements in radiologic staging studies, 90 to 95 percent of patients with osteosarcoma can now be treated with limb-sparing resection and reconstruction. Long-term survival and cure rates have increased to between 60 and 80 percent in patients with localized disease.
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PMID:Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. 1192 89

Bone sialoprotein (BSP) is a major noncollagenous protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite. Recent studies have shown that BSP is also expressed by osteotropic cancers suggesting BSP might play a role in the pathogenesis of bone metastases. The present study investigates regulation of BSP transcription in rat osteosarcoma ROS 17/2.8 cells by flavonoids: genistein (an inhibitor of protein tyrosine kinases), daidzein (an inactive compound of genistein), flavone, and flavanone. Genistein, daidzein, and flavone (50 microM) increased steady state levels of BSP mRNA about 1.7-fold at 12 h. From transient transfection assays using various sized BSP promoter-luciferase constructs, genistein increased luciferase activities within 12 h. Constructs including the promoter sequence nucleotides (nts) -116 to -43 (pLUC3) were found to enhance transcriptional activity approximately 2.6-fold in ROS 17/2.8 cells treated with genistein (50 microM). Daidzein, flavone, and flavanone (50 microM) also increased luciferase activities. In contrast, the tyrosine kinase inhibitors, herbimycin A and lavendustin A, which do not have a flavonoid structure, did not stimulate BSP transcription. Transcriptional stimulation by genistein was almost completely abrogated in a construct that included 2 bp mutations in the inverted CCAAT box. A monoclonal antibody against NF-YA, a CCAAT box-binding transcription factor, inhibited formation of DNA-NF-Y protein complex in gel shift assays formed by nuclear extracts of ROS 17/2.8 cells. These data suggest that the inverted CCAAT box is required for flavonoid-induced BSP expression and that the stimulatory action is dependent on the flavone structure and does not involve an inhibitory action on protein tyrosine kinase.
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PMID:Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. 1211 14

Bony metastases in patients with osteosarcoma are unusual and normally appear late in the course of the disease. We report our experience with eight such patients, four with solitary and four with multiple metastases. Those with solitary metastases were treated as new tumours with neoadjuvant chemotherapy and surgery. Three remain alive with no evidence of disease at 5, 7 and 8 years follow-up respectively. Histology and response to neoadjuvant chemotherapy was similar in both the primary and metastatic lesions and is a predictive factor of outcome. Those with multiple metastases were treated by palliative measures, and none survived. We conclude that resection of solitary metastases from osteosarcoma after neoadjuvant chemotherapy can be curative.
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PMID:Bone metastases from osteosarcoma. 1270 Sep 38

Starting from our previous finding that 99mTc(V) dimercaptosuccinic acid (99mTc(V)-DMSA), a useful agent for the localization of osteosarcoma and bone metastases, loses its bone affinity when one ester group is introduced into the complex we studied the impact of esterification in more detail. This paper reports on the evaluation of various ester complexes of 99mTc(V)-DMSA in rats and tumour-bearing nude mice with regard to their tumour retention and improvement of the tumour to tissue ratios. The distribution patterns of the complexes [99mTcO(DMSA)2]- (A), [99mTcO(DMSA/DMSEt)]- (B) and [99mTcO(DMSEt)2]- (C) are gradually changed with the number of ester groups in the anionic complex. However, the asymmetric diester complex [99mTcO(DMSA/DMSEt2)]- (D) is very slowly cleared, especially from the blood of nude mice. Moreover, this complex differs significantly from the symmetrical complex C in its elimination behaviour from the liver and kidneys. The tumour uptake is maintained with complexes that contain one or two non-hydrolysable ester functions. Preliminary biodistribution studies of the monoethyl and diethyl ester complexes B, C and D in comparison with A in tumour-bearing nude mice showed similar uptake into the human squamous cell carcinoma (FaDu) as well as into the human colonic cell carcinoma (HT29) of nude mice. The low bone accumulation of B, C and D results in excellent tumour-to-bone ratios, e.g., approx. 3:1 for the ester complex B compared to approx. 1:2 for complex A. Differences were observed in the accumulation and elimination behaviour of the complexes A and B in various bone structures of rats. The age-dependent uptake of A and B was compared in long bone (femur) and in cranial bone of rats. The results suggest that 99mTc(V)-DMSA complexes that contain a functional ester, and their 188Re analogues, may be superior to 99mTc(V)/188Re(V)-DMSA in diagnostic and therapeutic nuclear medicine.
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PMID:Novel tumortropic ester derivatives of 99mTc(V) mesodimercapto succinic acid with low affinity for bone tissue. 1456 72

To investigate somatostatin receptors (SSTRs) in primary or metastatic high-grade osteosarcoma, 18 patients (12 without metastases, 4 with synchronous lung, and 2 with metachronous bone metastases) underwent SSTR scintigraphy. After intravenous (i.v.) injection of 200-250 MPq of 111In-pentreotide, images were recorded at 4 and 24 hours. All patients underwent 99mTc-methylene diphosphonate (MDP) bone scan (BS). Scans were interpreted both with qualitative evaluation and with semiquantitative image processing, by means of tumor-to-background ratio modification over time. Primary tumor: SSTR scintigraphy was positive in 12 (75%) patients: 10 (83%) of the 12 nonmetastatic patients, and 2 (50%) of those with synchronous metastases. Metastases: SSTR scintigraphy was positive only in one (17%) of the six patients with metastatic disease. No relation was found between SSTR scintigraphy results and gender, histologic subtype, site, and size of the tumor. After primary chemotherapy, 15 patients underwent surgery of primary tumor; a good histologic response was found in 7 (64%) of the 11 patients with positive SSTR scintigraphy versus 1 (25%) of the 4 patients with negative SSTR scintigraphy. High-grade osteosarcoma exhibits somatostatin receptors, usually detectable in the primary tumor, but not in the metastatic lesions. The different expression of somatostatin receptors observed in primary and metastatic lesions, and in patients with tumors having different chemosensitivity, could indicate a possible relation between somatostatin receptors and biological behavior of the tumor.
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PMID:Somatostatin receptor (SSTR) scintigraphy in patients with osteosarcoma. 1462 33

The article shows differential diagnosis of giant sell tumor of bone with bone cystae, displasia fibrosis, chondroblastoma, osteosarcoma, chondrosarcoma, plasmocitoma, enchondroma and bone metastases. The main methods of diagnosis is morphological investigation of biopsy material.
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PMID:[Differential diagnosis of giant cell tumors]. 1496 8


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