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)

Dynamic enhanced magnetic resonance imaging has been used to assess tumor angiogenesis in osteosarcoma. Vascular endothelial growth factor has been shown to correlate with pulmonary metastasis and a poor prognosis in osteosarcoma. The purpose of this investigation was to determine whether vascular endothelial growth factor expression in osteosarcoma correlates with vascular permeability detected by dynamic enhanced magnetic resonance imaging and to explore the role of dynamic enhanced magnetic resonance imaging as a noninvasive means of assessing tumor angiogenic activity. Fifty-five osteosarcoma patients with osteosarcoma enrolled in a treatment protocol that included dynamic enhanced magnetic resonance imaging. In 15 patients, tumor tissues were available for vascular endothelial growth factor immunohistochemical studies. A two-compartment model used the exchange rate constants (kep) between the plasma and tumor compartments to quantify vascular permeability during dynamic magnetic resonance imaging studies. Immunohistochemical staining for vascular endothelial growth factor was graded according to the intensity and number of positively stained cells. Vascular endothelial growth factor-positive tumors showed higher mean vascular permeability when compared with vascular endothelial growth factor-negative tumors. Vascular permeability also correlated with increasing vascular endothelial growth factor expression. The preliminary results in this study show an association between vascular endothelial growth factor and dynamic MR signal enhancement in osteosarcoma. Dynamic enhanced magnetic resonance imaging should be investigated as a means to prognosticate osteosarcoma patients with osteosarcoma according to their tumor angiogenic activity.
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PMID:VEGF expression in osteosarcoma correlates with vascular permeability by dynamic MRI. 1534 48

Developmentally regulated endothelial cell locus 1 (Del1) is a new angiogenic molecules expressed specifically in early embryonic endothelial cells. We investigated the relationship between Del1 and tumor cell-derived vascular endothelial growth factor (VEGF). Dunn osteosarcoma cells and high- and low-metastatic murine sarcoma cells did not express Del1. However, the expression of Del1 was observed in these primary tumor tissues and the pulmonary metastatic tissues after subcutaneous inoculation in vivo. Every tumor cell-conditioned medium containing VEGF induced the expression of Del1 in murine lung microvascular endothelial (MLE) cells, although control MLE cells did not express Del1. The anti-mouse VEGF monoclonal antibody inhibited the induction of the Del1 expression. In addition, mouse recombinant interleukin-1alpha and tumor necrosis factor-alpha also induced Del1 in MLE cells. Del1 may play an important role in tumor angiogenesis through the effects of tumor-derived factors including VEGF.
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PMID:Expression of developmentally regulated endothelial cell locus 1 was induced by tumor-derived factors including VEGF. 1596 46

Pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that loss of PEDF is involved in angiogenic eye diseases such as proliferative diabetic retinopathy. Angiogenesis is required for tumor growth and progression as well. We, along with others, have recently found that PEDF could inhibit growth of melanoma and hepatocellular carcinoma in nude mice through its anti-angiogenic effects on tumor endothelial cells. However, the possibility of the direct effect of PEDF on tumor cells has remained. In this study, we investigated the effects of PEDF on growth and vascular endothelial growth factor (VEGF) expression in MG63 human cultured osteosarcoma cells. PEDF decreased viable cell number as well as DNA synthesis in MG63 cells in a dose-dependent manner. Furthermore, PEDF was found to increase caspase-3/7 activity and to subsequently induce apoptotic cell death in MG63 cells. PEDF also inhibited VEGF expression in MG63 cells at both mRNA and protein levels. Our present study provides novel beneficial aspects of PEDF on osteosarcoma cells; one is induction of apoptotic cell death of tumor cells, and the other is the suppression of VEGF expression, which would lead to inhibition of tumor angiogenesis. PEDF therefore might be a promising therapeutic agent for treatment of patients with osteosarcoma.
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PMID:Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. 1598 68

Vascular endothelial growth factor (VEGF) mediates tumor angiogenesis, growth, and metastasis. Murine models of metastatic tumors in which green fluorescent protein (GFP) expression is driven by the VEGF promoter can be imaged both intravitally and externally and thus offer many possibilities for real-time studies of tumor angiogenesis, metastasis, and treatment in vivo. In our defined-flora animal facility, an 11-month-old female transgenic mouse with a C3H background (VEGF(P)-GFP/C3H) developed a spontaneous tumor that expressed GFP under the control of VEGF. Necropsy and histopathologic examination revealed an osteosarcoma with lung metastases. Fresh tumor fragments were transplanted successfully into other VEGF(P)-GFP/C3H transgenic mice. During the first five generations, the tumor "take rate" was 100% (25 of 25 animals), with a latent period of 8 days and an average tumor volume of 1500 mm3 at 36 days. Transplanted tumors have maintained their original histopathologic characteristics and metastatic behavior. In addition, the tumor grows in wild-type C3H mice with an 83% take rate (10 of 12 animals) and as monolayer cells in vitro. GFP was expressed strongly in tumor tissue, lung metastatic foci, and cultured tumor cells. Real-time growth of tumors grown in dorsal skin chambers in C3H mice could be visualized using GFP fluorescence. In addition, GFP fluorescence of metastatic lesions in lungs of C3H mice was clearly visible by multiphoton laser scanning microscopy. This in vitro and in vivo transplantable and metastatic osteosarcoma (Os-P0107) is an attractive model for further study of tumor pathophysiology and treatment efficiency affecting VEGF expression.
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PMID:Green fluorescent protein (GFP)-expressing tumor model derived from a spontaneous osteosarcoma in a vascular endothelial growth factor (VEGF)-GFP transgenic mouse. 1608 71

Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.
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PMID:Low-dose methotrexate inhibits lung metastasis and lengthens survival in rat osteosarcoma. 1647 26

The growth and dissemination of sarcomas depends on angiogenesis. A number of measurable markers related to tumor angiogenesis have been studied in patients with sarcoma. The available literature related to markers of angiogenesis and clinical features in patients with sarcoma was reviewed. Clinical features of interest included tumor size, tumor grade, tumor stage, presence of metastatic disease, and prognosis. In patients with soft-tissue sarcomas, tumor vascular endothelial growth factor (VEGF) expression correlates with stage, grade, and prognosis. Circulating VEGF levels also correlate with tumor grade. High circulating angiopoietin-2 levels are associated with increased tumor size in soft-tissue sarcoma. For patients with osteosarcoma, tumor VEGF expression correlates with outcome. Elevated tumor and circulating VEGF levels are associated with the development of lung metastases in osteosarcoma. Patients with Ewing sarcoma have increased circulating VEGF levels compared with controls. Angiogenesis markers correlate with important clinical features in patients with sarcomas ranging from soft-tissue sarcomas to bone sarcomas. Markers of angiogenesis may serve an important role in predicting a particular patient's clinical course and in identifying patients for possible antiangiogenic therapy. Cancer 2007 (c) 2006 American Cancer Society.
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PMID:Markers of angiogenesis and clinical features in patients with sarcoma. 1726 25

The rapid development of an osteosarcoma, after surgical resection of an osteochondroma, has not been yet reported. We present here the case of a 12-year-old girl that had, in less than 2 months, an osteosarcoma at the initial site of a treated osteochondroma. Comparative Genomic Hybridization analyses showed that the 2 tumors were genetically distinct, suggesting a distant, if any, relationship. The possible implication of a deregulated tissue homeostasis caused by the surgical intervention is discussed. Proangiogenic factors involved in the tissue healing could be the triggering factor favoring tumor angiogenesis and explaining the very rapid progression of the tumor.
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PMID:Rapid development of an osteosarcoma after surgical resection of an osteochondroma. 1771 63

Antiangiogenic therapy for the treatment of cancer and other neovascular diseases is desired to be selective for pathological angiogenesis and lymphangiogenesis. Macrophage colony-stimulating factor (M-CSF), a cytokine required for the differentiation of monocyte lineage cells, promotes the formation of high-density vessel networks in tumors and therefore possesses therapeutic potential as an M-CSF inhibitor. However, the physiological role of M-CSF in vascular and lymphatic development, as well as the precise mechanisms underlying the antiangiogenic effects of M-CSF inhibition, remains unclear. Moreover, therapeutic potential of M-CSF inhibition in other neovascular diseases has not yet been evaluated. We used osteopetrotic (op/op) mice to demonstrate that M-CSF deficiency reduces the abundance of LYVE-1(+) and LYVE1(-) macrophages, resulting in defects in vascular and lymphatic development. In ischemic retinopathy, M-CSF was required for pathological neovascularization but was not required for the recovery of normal vasculature. In mouse osteosarcoma, M-CSF inhibition effectively suppressed tumor angiogenesis and lymphangiogenesis, and it disorganized extracellular matrices. In contrast to VEGF blockade, interruption of M-CSF inhibition did not promote rapid vascular regrowth. Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF-targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer.
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PMID:M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. 1939 55

Clinical studies over the past several years have reported that metastasis-free survival times in humans and dogs with osteosarcoma are significantly increased in patients that develop chronic bacterial osteomyelitis at their surgical site. However, the immunological mechanism by which osteomyelitis may suppress tumor growth has not been investigated. Therefore, we used a mouse model of osteomyelitis to assess the effects of bone infection on innate immunity and tumor growth. A chronic Staphylococcal osteomyelitis model was established in C3H mice and the effects of infection on tumor growth of syngeneic DLM8 osteosarcoma were assessed. The effects of infection on tumor angiogenesis and innate immunity, including NK cell and monocyte responses, were assessed. We found that osteomyelitis significantly inhibited the growth of tumors in mice, and that the effect was independent of the infecting bacterial type, tumor type, or mouse strain. Depletion of NK cells or monocytes reversed the antitumor activity elicited by infection. Moreover, infected mice had a significant increase in circulating monocytes and numbers of tumor associated macrophages. Infection suppressed tumor angiogenesis but did not affect the numbers of circulating endothelial cells. Therefore, we concluded that chronic localized bacterial infection could elicit significant systemic antitumor activity dependent on NK cells and macrophages.
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PMID:Chronic bacterial osteomyelitis suppression of tumor growth requires innate immune responses. 1970 48

Major advances have been achieved in the treatment of osteosarcoma with the discovery of several chemotherapeutic agents that were active in the disease. These agents comprise high-dose methotrexate with leucovorin rescue, Adriamycin, cisplatin, ifosfamide and cyclophosphamide. The agents were integrated into various regimens and administered in an effort to destroy silent pulmonary micrometastases which are considered to be present in at least 80% of patients at the time of diagnosis. Their efficacy in achieving this goal was realized and their use was further extended to the application of preoperative (neoadjuvant) chemotherapy to destroy the primary tumor and achieve safe surgical resections. Disease free survival was escalated from <20% prior to the introduction of effective chemotherapy to 55-75% and overall survival to 85%. Further, the opportunity to perform limb salvage was expanded to 80% of patients. Of interest also was an attempt in one series to treat the primary tumor exclusively with chemotherapy, and abrogation of surgery. Adding to these advances, varieties of subsequently discovered agents are currently undergoing investigations in patients who have relapsed and/or failed conventional therapy. The agents include Gemcitabine, Docetaxel, novel antifolate compounds, and a liposome formulation of adriamycin (Doxil). A biological agent, muramyl tripeptide phosphatidyl ethanolamine (MTPPE) was also recently investigated in a 2x2 factorial design to determine its efficacy in combination with chemotherapy (methotrexate, cisplatin, Adriamycin and ifosfamide).In circumstances where the tumor was considered inoperable, chemotherapy and radiotherapy were advocated for local control. High dose methotrexate, Adriamycin and cisplatin and Gemcitabine interact with radiation therapy and potentiate its therapeutic effect. This combination is also particularly useful in palliation. Occasionally, the combination of radiation and chemotherapy may render a tumor suitable for surgical ablation. Samarium153, a radio active agent, is also used as palliative therapy for bone metastases.However, despite the advances achieved with the multidisciplinary application of chemotherapy, radiotherapy and surgical ablation of the primary tumor over the past 3(1/2) decades, the improved cure rate reported initially has not altered. Particularly vexing is the problem of rescuing patients who develop pulmonary metastases after receiving seemingly effective multidisciplinary treatment. Approximately 15-25% of such patients only are rendered free of disease with the reintroduction of chemotherapy and resection of metastases. Extrapulmonary metastases and multifocal osteosarcoma also constitute a major problem. The arsenal of available agents to treat such patients has not made any substantial impact in improving their survival. New chemotherapeutic agents are urgently required to improve treatment and outcome. Additional strategies to be considered are targeted tumor therapy, anti tumor angiogenesis, biotherapy and therapy based upon molecular profiles. This communication outlines sequential discoveries in the chemotherapeutic research of osteosarcoma in the United States of America. It also describes the principles regulating the therapeutic application of the regimens and considers the impact of their results on the conduct in the design of future investigations and treatment.
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PMID:Osteosarcoma: review of the past, impact on the future. The American experience. 2021 94


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