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

Osteosarcoma is one of the most common pediatric cancers. Accurate imaging of osteosarcoma is important for proper clinical staging of the disease and monitoring of the tumor's response to therapy. The MYC oncogene has been commonly implicated in the pathogenesis of human osteosarcoma. Previously, we have described a conditional transgenic mouse model of MYC-induced osteosarcoma. These tumors are highly invasive and are frequently associated with pulmonary metastases. In our model, upon MYC inactivation osteosarcomas lose their neoplastic properties, undergo proliferative arrest and differentiate into mature bone. We reasoned that we could use our model system to develop noninvasive imaging modalities to interrogate the consequences of MYC inactivation on tumor cell biology in situ. We performed positron emission tomography (PET) combining the use of both (18)F-fluorodeoxyglucose ((18)FDG) and (18)F-flouride ((18)F) to detect metabolic activity and bone mineralization/remodeling. We found that upon MYC inactivation, tumors exhibited a slight reduction in uptake of (18)FDG and a significant increase in the uptake of (18)F along with associated histological changes. Thus, these cells have apparently lost their neoplastic properties based upon both examination of their histology and biologic activity. However, these tumors continue to accumulate (18)FDG at levels significantly elevated compared to normal bone. Therefore, PET can be used to distinguish normal bone cells from tumors that have undergone differentiation upon oncogene inactivation. In addition, we found that (18)F is a highly sensitive tracer for detection of pulmonary metastasis. Collectively, we conclude that combined modality PET/CT imaging incorporating both (18)FDG and (18)F is a highly sensitive means to non-invasively measure osteosarcoma growth and the therapeutic response, as well as to detect tumor cells that have undergone differentiation upon oncogene inactivation.
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PMID:(18)F and (18)FDG PET imaging of osteosarcoma to non-invasively monitor in situ changes in cellular proliferation and bone differentiation upon MYC inactivation. 1898 8

Osteosarcoma is the most common bone sarcoma, which mainly affects adolescents and young adults. Although the combination of modern surgery and systemic chemotherapy has improved osteosarcoma treatment dramatically, no substantial change in survival has been seen over the past 20 years. Therefore, novel therapeutic strategies for osteosarcoma are required if the 35% of patients with fatal metastases are to be successfully treated. Recently, osteoclasts have drawn attention as a therapeutic target in various bone disorders including osteosarcoma. The osteoclast is the sole cell that resorbs bone and is central in pathologic situations, where bone destruction is intricately involved. Osteosarcoma cells are of the osteoblastic lineage, the latter of which is characterized by cells secreting the osteoclast-inducing factor, receptor activator of nuclear factor-kappaB ligand. Hence, osteosarcoma is a better candidate for osteoclast-targeted therapy than other primary and metastatic bone tumors. The rapid progress on the molecular mechanism regulating osteoclast has propelled a development of new therapeutic approaches. In this review article, we present the prospects of osteoclast-targeted therapy as a novel treatment strategy for osteosarcoma. Receptor activator of nuclear factor-kappaB-Fc, osteoprotegerin, bisphosphonates, and Src inhibitor are shown as positive candidates and can control various aspects of osteoclast function. This review article will attempt to discuss these issues in term.
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PMID:Novel therapeutic strategy for osteosarcoma targeting osteoclast differentiation, bone-resorbing activity, and apoptosis pathway. 1900 31

Osteosarcoma (OS) is a highly malignant primary skeletal tumor with a striking tendency to rapidly destroy the surrounding bone and metastasize, since metastases are frequently present at clinical onset. The basis for the aggressiveness of this tumor is largely unknown. However, recent studies in in vivo models indicate that the anti-osteolytic drugs, bisphosphonates, can inhibit the tumor local expansion and the formation of metastases. We further investigated the association between the presence of active osteoclasts and the aggressiveness of OS. We evaluated the presence of osteoclasts and the mRNA of different osteoclast-related genes in tumor biopsies from 16 OS patients and in three OS cell lines and the serum levels of bone resorption markers in the same series and in 28 other patients. Tumor-associated osteoclasts were found in 63 and 75% of cases by histological and mRNA analysis. Among different serum markers, only MMP-9 was significantly higher in OS cases (p=0.0001), whereas TRACP 5b was significantly higher in metastatic patients compared to nonmetastatic patients (p=0.0509). Serum TRACP 5b was significantly correlated to serum NTX (p<0.0001) and cathepsin K mRNA in tumor tissues (p=0.0153). In 8 patients we also analyzed TRACP 5b serum level at follow-up and we verified a significant decrease of TRACP 5b after primary tumor removal (p=0.0117). In conclusion, tumor-infiltrating osteoclasts are frequently found in OS and increased serum TRACP 5b levels and the presence of active osteoclast at primary sites were positively associated with tumor aggressiveness.
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PMID:Increased osteoclast activity is associated with aggressiveness of osteosarcoma. 1902 Jul 56

Osteosarcoma (OS) is a class of cancer originating from bone, mainly afflicting children or young adults. It is the second highest cause of cancer-related death in these age groups, mainly due to development of often fatal metastasis, usually in the lungs. Survival for these patients is poor despite the aggressive use of surgery, chemotherapy, and/or radiotherapy. Thus, new effective drugs and other forms of therapy are needed. This article reviews the biology and the state of the art management of OS. New experimental drugs and potential therapies targeting molecular pathways of OS are also discussed.
Cancer Metastasis Rev 2009 Jun
PMID:Osteosarcoma treatment: state of the art. 1921 8

Osteosarcoma is the most common primary malignancy of bone in children and young adults. There is a paucity of tumorigenic and highly metastatic human osteosarcoma cell lines that have not been further transformed by exogenous means. Here we establish and characterize a highly metastatic human osteosarcoma cell line that is derived from a poorly metastatic MG63 line through serial passage in nude mice via intratibial injections. The occasional pulmonary metastases developed from MG63 were harvested and repassaged in mice until a highly metastatic subline (MG63.2) was established. The parental MG63 and highly metastatic MG63.2 cells were further characterized in vitro and in vivo. MG63.2 cells demonstrated increased cell migration and invasion compared to the parental MG63 cells. Conversely, cell adhesion was significantly greater in MG63 cells when compared to the MG63.2 cells. MG63.2 cells grew at a slightly slower rate than that of the parental cells. When injected into nude mice, MG63.2 cells had a greater than 200-fold increase in developing pulmonary metastases compared to the parental MG63 cells. MG63.2 cells also formed larger primary tumors when compared to the parental MG63 cells. Further analysis revealed that ezrin expression was up-regulated in the metastatic MG63.2 cells. Interestingly, expressions of MMP-2 and MMP-9 were down-regulated, and expression of TIMP-2 was up-regulated in the MG63.2 cells. Taken together, we have established and characterized a highly metastatic human osteosarcoma cell line that should serve as a valuable tool for future investigations on the pathogenesis, metastasis, and potential treatments of human osteosarcoma.
Clin Exp Metastasis 2009
PMID:Establishment and characterization of a new highly metastatic human osteosarcoma cell line. 1936 54

Osteosarcoma is the most common malignant primary bone tumor in childhood. Despite multiagent chemotherapy and aggressive surgical resection, 30% of patients with localized disease and 80% of patients with metastatic disease at diagnosis will relapse. Survival for these patients has remained unchanged over the past 20 years. A number of novel agents in various stages of development hold promise for improving therapy for patients with osteosarcoma. This article will focus on novel therapeutic approaches, including agents targeting signal-transduction pathways, inhibitors of the tumor microenvironment and immunomodulatory agents, as well as overcoming resistance mechanisms and the use of novel delivery mechanisms.
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PMID:Novel therapeutic agents for osteosarcoma. 1937 4

Osteosarcoma, the most common bone sarcoma, affects approximately 560 children and adolescents annually in the United States. The incidence of new diagnoses peaks in the second decade of life. Twenty percent of patients present with clinically detectable metastases, with micrometastases presumed to be present in many of the remaining patients. Treatment typically includes preoperative chemotherapy, surgical resection, and postoperative chemotherapy. Limb-salvage procedures with wide surgical margins are the mainstay of surgical intervention. Advances in chemotherapy protocols have led to a 5-year survival rate of 60% to 78%. Among the goals of future treatment regimens are improved chemotherapeutic agents with higher specificity and lower toxicity.
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PMID:Osteosarcoma. 1965 33

Osteosarcoma is one of the most common primary malignant bone tumours in childhood, mainly affecting the metaphysis of long extremity bones. In rare cases, patients present at time of diagnosis with multiple bone lesions, sometimes in the absence of pulmonary metastases. The pathology pattern of these multifocal osteosarcomas occurring with a rare incidence of 0.5-4% is not yet clear, and in spite of investigations in diagnosis and therapy, the prognosis is still poor. We report two cases of multifocal synchronous osteosarcoma. The age of both children at the time of tumour detection was 14 years. A synchronous or metachronous occurrence of multiple bone lesions, initially in the absence of pulmonary metastases was seen. In both cases, treatment consisted of neoadjuvant chemotherapy, oncologic surgery and adjuvant chemotherapy. Tumour response to chemotherapy was good in one patient, and poor in the other case. In both patients initial R0-resection of the tumours was performed. The disease-free time was 1 year before detection of pulmonary metastases or relapse. By the combination of chemotherapy and aggressive surgery the prognosis in multifocal osteosarcoma has been improved over the last years. Nevertheless, the survival time is still short and seems to be correlated with the initial histological tumour response to chemotherapy.
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PMID:Multifocal osteosarcoma in childhood. 1971 Nov 59

Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.
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PMID:Three-dimensional alginate spheroid culture system of murine osteosarcoma. 1978 12

Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. In spite of successful control of the primary tumor, death from lung metastasis occurs in more than a third of patients. To investigate the efficacy of zoledronic acid (ZOL) on the development, progression and metastatic spread of OS, we used a rat model of OS, with features of the disease similar to human patients, including spontaneous metastasis to lungs. Rat OS cells were inoculated into the tibial marrow cavity of syngeneic rats. OS development was associated with osteolysis mixed with new bone formation, adjacent to the periosteum and extended into the surrounding soft tissue. Metastatic foci in the lungs formed 3-4 weeks postcancer cell transplantation. Treatment with a clinically relevant dose of ZOL was initiated 1 week after tumors were established and continued once weekly or as a single dose. ZOL preserved the integrity of both trabecular and cortical bone and reduced tumor-induced bone formation. However, the overall tumor burden at the primary site was not reduced because of the persistent growth of cancer cells in the extramedullary space, which was not affected by ZOL treatment. ZOL treatment failed to prevent the metastatic spread of OS to the lungs. These findings suggest that ZOL as a single agent protects against OS-induced bone destruction but lacks efficacy against pulmonary metastases in this rat model. ZOL may have potential value as an adjuvant therapy in patients with established OS.
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PMID:Zoledronic acid protects against osteosarcoma-induced bone destruction but lacks efficacy against pulmonary metastases in a syngeneic rat model. 1992 13


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