Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is a fatal disease. Neoadjuvant chemotherapy combined with irradiation treatment provide a better survival. In the Faculty of Medicine, Ramathibodi Hospital, the overall 9 year survival probability was 55 per cent among 130 cases of more than Enneking stage II osteosarcoma. Between 15 cases of bony metastases, there were 2 cases which were classified as multifoci osteosarcoma or osteosarcomatosis. These two cases developed second bone disease, 32 and 38 months after initial diagnosis and survived for 84 and 88 months with one patient also developing pulmonary metastasis. Both of them are still alive and in very good health.
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PMID:7 year-survival of 2 cases of multicentric or metastatic osteosarcoma. 973 34

Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases, including a rare large bone-forming retroperitoneal metastasis, is described. Despite the extensive extrapulmonary metastases, the patient did not develop pulmonary metastases in the 4 years following initial presentation of the primary tumour.
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PMID:Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement. 1065 67

Primary bone tumors represent about 7% of paediatric malignancies. Osteosarcoma and Ewing's tumor are the most frequent ones, however they are rare in facial bones. Mandibular localization is slightly more frequent and of better prognosis than maxillary one. Until 1995 there were only about 70 cases reported in the medical literature, mainly in the oncological or dental periodics. Our material consists of two children with Ewing's tumor of the mandible and one patient with osteosarcoma. The diagnosis was based on histopathological or cytological studies. The combined treatment--chemotherapy and radiotherapy--was performed in two patients with Ewing's tumor. The recommended resection of the mandible including the tumor mass has not been performed. No facial asymmetry is seen after termination of the radiotherapy. The boy with osteosarcoma underwent primary mandibular partial resection; a two-year chemotherapy was introduced only when metastases in the regional lymph nodes occurred (BLM, CTX, ACT-D, ADM, CDDP). The mandible was reconstructed surgically in 5 years after termination of radiotherapy and the anatomical relationship in the masticatory organ was restored. All children are now in good condition under our long-term observation. We present these cases of mandibular tumors regarding their rare occurrence and positive results of the introduced treatment.
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PMID:[Malignant tumors of mandible in children]. 1073 62

Osteosarcoma is the most frequent malignant bone tumor, mainly occurring in the second and third decade of life. Diagnosis is limited to clinical symptoms, radiology and histology, but so far no diagnostic laboratory tests are available. Heat shock proteins (hsp), highly conserved proteins performing vital intracellular chaperoning functions and preventing cells from death, have been shown to be involved in tumor immunity. We analyzed 75 sera from 23 patients with high-grade osteosarcoma, 8 patients with chondrosarcoma, 10 patients with Ewing's sarcoma, 5 patients with soft tissue sarcoma, 11 patients with benign bone tumors at the time of diagnosis and from 18 healthy controls with an indirect one-site enzyme linked immunosorbent assay (ELISA) for the presence of anti-hsp60 and 70 antibodies. In these assays 10/23 osteosarcoma patients (43%) had anti-hsp60 antibodies with a mean +/- S.D. titer of 0.382 +/- 0.243 U/ml. Only one of the 18 healthy controls (1/18, 5.6%; titer 0.22 U/ml), two of the Ewing's sarcoma patients (2/10, 20%; titer 0.2 +/- 0.09 U/ml), two of the patients with a benign bone tumor (2/11, 18%; titer 0.22 +/- 0.16 U/ml) and one of the chondrosarcoma patients (1/8, 12.5%; titer 0.14 U/ml) were positive, whereas all others, including all soft tissue sarcomas were negative throughout. Anti-hsp60 antibodies in patients with osteosarcoma are therefore significantly increased (p < 0.05). 19/23 (83%) of osteosarcoma biopsy specimens expressed hsp60 immunohistochemically and all specimens from patients with a positive anti-hsp60 serum titer expressed hsp60. The level of the anti-hsp60 antibodies did not correlate with clinical parameters such as response to preoperative chemotherapy, duration of symptoms, age, gender, tumor size, serum alkaline-phosphatase levels and metastases. Although no difference in anti-hsp70 antibodies could be observed between sera from patients and healthy controls, a positive correlation was found for the presence of anti-hsp70 serum antibodies and lung metastases at the time of diagnosis in osteosarcoma patients. These data suggest an increase of anti-hsp60 antibodies at the time of first diagnosis of osteosarcoma. These findings should therefore give rise to further investigations on a group of new markers for the diagnosis of osteosarcoma.
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PMID:Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma. 1077 93

Limb salvage of large segmental and osteoarticular defects after tumor resection has become the standard of care for most patients with musculoskeletal tumors because overall survival is the same when compared with that seen in amputation patients. This study examines limb salvage for the surgical management of large segmental defects in terms of local recurrence, complications, and functional outcome in both primary and metastatic lesions. We retrospectively identified 32 patients with benign or malignant tumors of bone who underwent resection and limb salvage reconstruction by means of a custom or modular metal implant between 1985 and 1995. The most common tumor sites were the proximal femur (41%), distal femur (37.5%), and proximal humerus (12.5%). Primary bone lesions accounted for 18 patients (56%); metastatic disease accounted for 14 patients (44%). Osteosarcoma (n = 11) and chondrosarcoma (n = 3) were the most frequent primary tumors. The overall limb salvage rate (91%) was high, yet complications (28%) were common. Except for 3 patients who underwent amputation after prosthetic failure, all surviving patients were independent with or without assistive devices at latest follow-up. In patients with advanced metastatic disease, average survival was 7.6 months. No cases of aseptic loosening or implant breakage were observed in patients followed up for 2 years or more. Treatment after tumor resection with a limb salvage prosthetic reconstruction has shown good functional outcomes with an acceptable complication rate. This modality, therefore, offers patients a more favorable functional outcome with a more energy-efficient gait when compared with limb amputation.
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PMID:Segmental limb reconstruction after tumor resection. 1092 2

Osteosarcoma cells are useful for investigating bone metabolism as malignant counterpart of osteoblasts. In hematogenous metastases of osteosarcoma cells, the cells need to adjust to various changes in pericellular environment. The changes in pericellular environment may change intracellular environment and consequently the secretion of matrix metalloproteinases (MMPs) which destroy extracellular matrices. In this report, a new cell line, KOS-1, derived from human osteoblastic osteosarcoma was established, and we assumed various culture conditions containing ingredients of the extracellular matrix to make a comparative study on MMPs detected from the culture supernatants. A wide spectrum of MMPs, including MMP-1 and -3 which were increased in the presence of interleukin 1 beta, was detected in this cell line. Production of MMP-1, the enzyme which decomposes types I, II, III and X collagen, by the cells, was increased in the presence of type I collagen. MMP-3 (stromelysin-1) which degrades types III and IV collagen, laminin, fibronectin, proteoglycan, etc. was produced more abundantly in the presence of type IV collagen. MMP-2 (72-kd type IV collagenase/gelatinase A) activity was found to be increased in the presence of gelatin and type IV collagen. The MMPs production in cultured osteosarcoma cells was changed depending on the culture conditions. This indicates that the same osteosarocma cells produce different amounts and kinds of enzymes involved in local infiltration and remote metastases and increase the production of the enzymes most required under a specific environment.
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PMID:Establishment of an osteoblastic osteosarcoma cell line and effects of cell culture conditions on secretion of matrix metalloproteinases from the cultured osteosarcoma cells. 1094 49

Matrix degrading enzymes released upon autocrine and/or paracrine induction exert a key role in modulating tumor cell behavior. Osteosarcoma is a highly metastatic cancer, with a redundancy of autocrine loops. Here we report that human osteosarcoma cells express a wide array of chemokine receptors and respond to chemokine activation with the release of N-acetyl-beta-D-glucosaminidase and gelatinase/collagenase activity. Of the two cell lines studied, the osteoblast-like MG-63 showed a higher responsivity compared to the less differentiated HOS. This suggests that chemokine modulation of matrix degrading enzymes requires the maintaining of the osteoblastic phenotype and of signaling pathways which occur in normal tissue.
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PMID:Human osteosarcoma cells release matrix degrading enzymes in response to chemokine activation. 1111 33

Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.
Clin Exp Metastasis 2000
PMID:Antioxidants inhibit TNFalpha-induced motility and invasion of human osteosarcoma cells: possible involvement of NFkappaB activation. 1123 87

Osteosarcomas are malignant tumors arising from skeletal tissue and occur most frequently during childhood and adolescence. Osteosarcoma was once fatal in more than 80% of patients who presented with apparently localized disease. Chemotherapy, better surgical techniques, and improved staging methods now allow most patients to be treated with limb-sparing surgery and to be cured of their disease. However, many patients still die of metastatic disease and new approaches are still needed. The lung is the most frequent metastatic site and is treated with chemotherapy and surgical resections. Multiple resections for repeated recurrences that are limited to the lung are not uncommon but are limited by the amount of lung tissue that can be removed and become futile as recurrences become more frequent. Although a main component of initial therapy, chemotherapy has not been shown to be of benefit for recurrent disease. Direct introduction of therapeutic genes into malignant cells in vivo may provide effective treatment of solid tumors. The proposed study will use the adenoviral vector Ad-OC-E1a (OCaP1), which contains a murine osteocalcin (OC) promoter to regulate the production of the adenoviral E1a protein to allow for restricted viral replication and subsequent lysis of tumor cells. The OC promoter is developmentally regulated, with peak expression in the neonate. It functions primarily in osteoblasts found in growing bone and is highly expressed in osteogenic sarcomas. Because adenovirus is quickly cleared by normal tissues, especially the liver, systemic administration has been problematic. Although bioavailability would be decreased following exposure to the liver, the OcaP1 construct should not be hepatotoxic due to OC-restricted tissue expression of the Ela protein. Metastatic disease to the lung is a major problem and often is the cause of death for patients with osteogenic sarcoma. Treatment of pulmonary metastases could potentially be accomplished using intravenously administered OcaP1 since the material would pass through the lung prior to reaching the systemic circulation. In animal models using OC expressing tumors, OCaP1 has been effective at reducing lung metastases following intravenous injection. This protocol is a phase I/II investigational study of bolus intravenous injections of Ad-OC-E1a for the treatment of chemotherapy-refractory osteogenic sarcoma that has metastasized to the lungs. Initially patients will receive one injection of 1 x 10(10), 1 X 10(11), 1 X 10(12), or 5 x 10(12) viral particles of Ad-OC-E1a using a standard Phase I dose escalation design that studies 3 to 6 patients per dose group. After safety has been established in the first part of the trial, we will evaluate the anti-tumor activity of OCaP1. Because the matrix associated with osteogenic sarcoma may not change despite tumor necrosis, radiographic evaluation alone has not been considered sufficient to evaluate response in this disease. Histologic criteria that assess the amount of necrosis have been shown to have prognostic significance and are a key component of the anti-tumor response assessment. Therefore, the anti-tumor assessments will be carried out in patients for whom resection of their pulmonary metastases is clinically indicated. These patients will receive one injection of OCaP1 and 28 to 42 days later undergo their planned pulmonary resection. Responses will be graded using radiographic and histologic objective response criteria that are considered standard for osteogenic sarcoma. A total of 14 to 25 patients, depending upon whether objective anti-tumor responses occur, will be studied in this part of the protocol.
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PMID:A phase I/II dose escalation and activity study of intravenous injections of OCaP1 for subjects with refractory osteosarcoma metastatic to lung. 1152 47

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


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