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)

Five-hundred and twenty-six patients with non-metastatic osteosarcoma of the extremities treated at Istituto Ortopedico Rizzoli from 1983 to 1995 with neoadjuvant chemotherapy and limb salvage, were retrospectively studied to evaluate the rate of local and systemic control. At a mean follow-up of 9.5 years (3-17), 320 patients remained continuously free of disease and 206 relapsed. The 5-year disease-free survival and overall survival were 64% and 70% respectively. In patients who relapsed, there were 31 local recurrences (6%). The rate of local failures was significantly higher in the 79 patients with inadequate surgical margins (marginal, intralesional, and contaminated margins) than in the 486 patients with wide surgical margins (2.6% vs. 25.0%; P<0.0001). Twenty-nine of the 31 patients (94%) with local recurrence also had metastases and died of the tumor. In comparison with patients who only had a systemic relapse, patients with local recurrences had a higher rate of metastases located in bones (41% vs. 7%; P<0.001), and a worse post-relapse outcome (5-year overall survival: 6% vs. 24%; P<0.04). We concluded that in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: i) limb salvages procedures do not compromise the outcome of patients, provided the achievement of adequate surgical margins; ii) local recurrences are a marker either of the inadequacy of local treatment or of the high local and systemic aggressiveness of the tumor.
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PMID:Local and systemic control for osteosarcoma of the extremity treated with neoadjuvant chemotherapy and limb salvage surgery: the Rizzoli experience. 1094 51

Sixty-one dogs with appendicular osteosarcoma were treated with amputation and chemotherapy of cisplatin and doxorubicin. Serum samples were obtained before and after treatment for determination of total alkaline phosphatase (TALP) activity as well as the activities of the constituent bone (BALP), liver (LALP), and corticosteroid-induced (CALP) isoenzymes. The relationship between alkaline phosphatase activities and survival was examined by Cox proportional hazards regression analysis and Kaplan-Meier log rank analysis. Mean activity of TALP, BALP, and LALP decreased significantly after treatment (P < .001). TALP and LALP activities before treatment were significantly correlated with survival (P = .006 and .001, respectively). The correlation between BALP activity before treatment and survival approached significance (P = .054). CALP activity and TALP, BALP, and LALP activities after treatment were not significantly correlated with survival. Dogs with normal pretreatment TALP and BALP activities survived significantly longer than dogs with increased pretreatment activities (P = .001 and .003, respectively). Median survival times for dogs with normal or increased TALP activities before treatment were 12.5 and 5.5 months, respectively; and median survival times for dogs with normal or increased BALP activities before treatment were 16.6 and 9.5 months, respectively. In the design of future clinical trials involving dogs with osteosarcoma, consideration should be given to stratifying the randomization according to alkaline phosphatase activity. In addition, alkaline phosphatase activity should be a factor considered by clinicians attempting to tailor the aggressiveness of adjuvant chemotherapy to the needs of individual patients or owners.
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PMID:Prognostic significance of serum alkaline phosphatase activity in canine appendicular osteosarcoma. 1111 Mar 79

Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was observed and correlated with aggressiveness in different neoplasms such as breast, prostate, blood and brain cancers, among others. To investigate whether telomerase activity is an index of aggressiveness in bone and soft tissue lesions of the extremities, 66 biopsy samples from our tissue bank were studied. These samples included 43 high-grade sarcomas, 9 aggressive benign tumors and 14 totally benign lesions. The samples were collected from patients homogeneously treated at the Rizzoli Orthopaedic Institute with a follow-up ranging from 4 to 11 years (median, 7 years). A non-radioactive polymerase chain reaction-based enzyme-linked immunosorbent assay was used for the study. All tumors investigated were positive for telomerase activity. Among benign lesions, only 2 aneurysmal bone cysts showed higher telomerase activity than the cut-off point, whereas all the other benign lesions had lower activity. Our results indicate that high levels of telomerase activity in bone and soft tissue lesions correlate with more aggressive clinical behavior in patients treated with surgery alone. An interesting inverse correlation between telomerase activity and occurrence of pulmonary metastasis was detected in osteosarcoma patients treated with chemotherapy. A parallel increase of telomerase activity and malignancy was observed in the adipose and cartilagineous tissue lesions. Our data suggest that telomerase activity could be considered a marker of tumor aggressiveness for bone and soft tissue lesions. The results obtained in osteosarcoma samples suggest that low levels of telomerase activity may be predictive of the prognosis and should influence the therapeutic protocol.
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PMID:Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness. 1130 48

The role of urokinase plasminogen activator (uPA) in osteosarcoma is poorly understood. We examined the importance of uPA, its receptor, uPAR, and its inhibitor, PAI-1, in our in vivo model of metastatic osteosarcoma. Rodent osteosarcoma cells (UMR 106-01) were inoculated into the tibia of athymic mice. Animals were sacrificed and autopsied at 4 days to 5 weeks after inoculation. Tibiae and lungs were excised, fixed, and examined histologically and by in situ hybridization. Osteosarcoma development was associated with tibial swelling and lameness, and radiographic changes included osteolysis and new bone formation. Lung metastases developed spontaneously. In the tibial tumors, uPAR mRNA was expressed early (4 days), whereas uPA and PAI-1 mRNA increased as the tumor invaded the surrounding tissue (3 weeks). There was also an increase in the mRNA expression of the osteoblast-related genes, alpha1(I) procollagen and osteopontin, but not matrix Gla protein. Lung metastases also expressed mRNA for the uPA system and the bone-related proteins. We have produced a model of metastatic osteosarcoma, which typifies the characteristics of the human tumor. Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and, in particular, indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma.
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PMID:The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model. 1141 May 3

In 560 patients with high-grade osteosarcoma of the extremity treated with 5 different protocols of neoadjuvant chemotherapy at a single institution between 1983 and 1995, the pre-treatment serum alkaline phosphatase (SAP) was examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. SAP was normal in 302 (54%) patients and high in 258 (46%). High levels of SAP was observed significantly and independently more frequently in male patients over 14-years-old, and in tumours larger than 150 ml and of osteoblastic subtypes. The 5-year event-free survival (EFS) and overall survival (OS) for all patients were respectively 60 and 68%. With multivariate analysis only two factors were independently correlated with the 5-year EFS: SAP levels (p=0.002) and the grade of chemotherapy-induced necrosis (p=0.0001). The authors conclude that in planning randomized clinical trials of neoadjuvant treatment for osteosarcoma, patients should be stratified according to SAP levels, and that when tailoring the aggressiveness of postoperative chemotherapy to the risk of relapse, in addition to the histologic response to preoperative treatment, the SAP levels should also be considered.
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PMID:Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute. 1174 77

The authors reviewed 43 children with high-grade sarcomas of bone and soft tissue who underwent surgery during the past 9 years. Twenty-six patients had osteosarcoma, 7 had Ewing sarcoma, and 10 had soft tissue sarcomas. Patients ranged in age from 4 months to 13 years. Mean follow-up period was 6 years. The feasibility of resection, results of local resection, and failure of local disease control were reviewed. Limb salvage was feasible in 81% of patients. Of the 35 patients undergoing limb salvage, margins were considered adequate in 88% and inadequate in 12%. Limb-sparing resection was not feasible in 19% of patients. Five patients (four with metastatic disease at presentation) did not undergo surgery and were given palliative care; three other patients underwent amputation. The decision of whether to proceed with limb salvage surgery must depend on the aggressiveness of the underlying tumor, its stage, the feasibility of obtaining tumor-free resection margins, and the response to neoadjuvant therapy.
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PMID:Scope and limitations of limb-sparing surgery in childhood sarcomas. 1185 40

Sarcomas account for less than 1% of all malignant neoplasms occurring in the head and neck in adults. These tumors exhibit variable growth and degrees of aggressiveness which are primarily dependent on histologic grade. The pattern of growth demonstrated by sarcomas is generally by local advancement with high-grade tumor exhibiting extensive involvement of adjacent visceral and neurovascular structures. Regional metastasis is uncommon. Etiologic considerations include the tumorigenic effects of prior external beam radiotherapy and the development of second malignancies in the form of sarcomas. The clinical presentation of these neoplasms is variable and dependent on subsite of involvement as well as the aggressiveness of tumor growth. Histologic diagnosis is frequently challenging, often requiring the aid of immunohistochemical staining techniques. Treatment is predominantly surgical, utilizing wide local excision where en-bloc resection is feasible. Radiotherapy, by means of external beam or implant, plays an important adjunctive role in management, especially for tumors where en-bloc resection with margin control is not possible. Chemotherapy regimens are available for soft tissue neoplasms and osteosarcoma and are primarily designed to improve local control. Survival is predicted on the incidence of local recurrence and risk of distant metastasis, both of which are influenced by tumor grade. Low-grade tumors exhibit improved survival over that of less differentiated tumors.
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PMID:Management of sarcomas of the head and neck in adults. 1245 15

Osteosarcoma is the most frequent primary high grade bone tumor, usually occurring in adolescents and children. The aim of the present study was to investigate parameters of bone turnover as urinary excretion of pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), serum osteocalcin (OC), and total alkaline phosphatase (AP) in patients with osteosarcoma. Thirty-five patients aged 7-22 (median age 14) with primary high-grade osteosarcoma of the extremity entered the study. A control population of age- and sex-matched healthy individuals was studied. Urinary excretion of Pyr, D-Pyr was measured on fasting urine specimens, corrected for creatine excretion (Ucr), and expressed as pM/microM UCr. At the same time as urine collection, blood samples were taken for measurement of AP and OC. In patients with osteosarcoma the urinary excretion of D-Pyr (74.5 +/- 41) was significantly higher (P = 0.005) than in controls (38.2 +/- 22.5). The serum level of OC was significantly lower (P < 0.001) in patients with osteosarcoma than in controls. Moreover, significantly (P = 0.03) higher excretion of D-Pyr (85.3 +/- 43) was found in patients who relapsed after surgical removal of the tumor and chemotherapeutic treatment compared with those (58.1 +/- 22) who remained continuously free of disease. The present study showed significant abnormalities of urinary excretion of pyridinium crosslinks and serum OC level in patients with osteosarcoma. The relation between urinary excretion of D-Pyr and biological tumor aggressiveness observed in the present study requires further investigation.
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PMID:Urinary excretion of pyridinium cross-links and serum osteocalcin levels in patients with primary high-grade osteosarcoma. 1450 46

A 40-year-old woman presented with a known case of osteogenic sarcoma of the right leg and underwent below-the-knee amputation. The preoperative workup was negative for distant metastases, and the patient was followed regularly. Two years later she developed dyspnea and chest pain. Computed tomography revealed diffuse left lung metastases with pleural involvement and nodular metastases in the right lung. Tc-99m methylene diphosphonate whole-body bone scanning revealed the amputated right leg with a clean stump but with widespread metastases in the right thigh involving soft tissue and bone, and the pelvis, left femur, and skull. In addition, diffuse left lung metastases involving both parietal pleura and lung parenchyma were seen. Tc-99m methylene diphosphonate uptake has been observed in the soft tissue and lungs in patients with osteogenic sarcoma but is rarely observed in practice with this degree of aggressiveness.
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PMID:Bone scan appearance in aggressive osteogenic sarcoma with pleural, lung, bone, and soft-tissue metastases. 1457 12

Alkaline phosphatases (ALPs) are a family of cell surface glycoproteins that catalyze the hydrolysis of phosphomonoesters with release of inorganic phosphate. Liver/bone/kidney (L/B/K) ALP participates in bone mineralization, but its other physiological and pathological functions remain obscure. In human osteosarcoma, an inverse relationship has been found between cellular L/B/K ALP expression and aggressiveness. To explore this relationship, we employed cDNA microarray technology to characterize and compare the gene expression profile of two U-2 OS osteosarcoma clones with high L/B/K ALP activity (U-2/ALP28 and U-2/ALP40) and one with contrasting characteristics (U-2/ALP23). We identified 79 differentially expressed genes (58 upregulated in U-2/ALP28 and U-2/ALP40 compared to U-2/ALP23). Using GenMAPP/MAPPFinder, we highlighted nine functional groups strictly related to high L/B/K ALP activity, including microtubule-based movement and cell adhesion groups, two functions well related to tumor invasiveness. Notably, cadherin 13 (CDH13) and caveolin 1 (CAV1) genes were upregulated in our cells. Since these two genes are involved in cell-cell adhesion and cell growth, their co-expression with L/B/K ALP could help explain the lower levels of malignancy found in osteosarcoma cells with high L/B/K ALP activity. Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/K ALP in bone tumors.
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PMID:Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene. 1505 Aug 98


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