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1/17. Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a.

    We report a 5-year-old girl with a large rapidly growing giant cell tumor of the mandible that recurred 2 months after the first surgical excision and 3 months after a second resection. An angiogenic protein, (bFGF), was abnormally elevated in her urine. The patient was treated with interferon alfa-2a for 1 year because this agent inhibits angiogenesis by suppressing bFGF overexpression in infantile hemangiomas and in other human tumors. During this time the bone tumor regressed and disappeared, the urinary bFGF fell to normal levels, and the mandible regenerated. She has remained tumor-free and has been off therapy for 3 years at this writing. This first successful use of interferon alfa-2a to treat a mandibular tumor in a child demonstrates: 1) low grade tumors that overexpress bFGF may respond to interferon alfa-2a, in a manner similar to life-threatening infantile hemangiomas; 2) antiangiogenic therapy, given without interruption for 1 year, was safe and effective in this patient; and 3) treatment may be continued for 1 year without the development of drug resistance.
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ranking = 1
keywords = bone
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2/17. Interferon alpha-2b at low doses as long-term antiangiogenic treatment of a metastatic intracranial hemangioendothelioma: a case report.

    We describe a case of intracranial haemangioendothelioma in a 20-year old female patient who presented severe neurological symptoms and relapsed after two surgical interventions. The patient was treated with low doses of recombinant interferon alpha-2b (1 MUI three times a week) after surgical resection which led to recovery of daily function and work activity. To our knowledge, this is the ninth patient reported with intracranial hemangioendothelioma, but the only one having diffuse and painful bone metastases resolved by treatment with interferon. After 30 months the patient is free from symptoms and recurrence. The effectiveness shown by recombinant interferon alpha-2b against vascular neoplasms prompted us to look for the possible biological basis of such a property.
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keywords = bone
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3/17. Epithelioid haemangioendothelioma of the sphenoid bone.

    The authors report a case of cranial EH occurred in the left sphenoid bone that was totally excised without transfusion. A 26-year-old woman presented with a 1-year history of progressing exophthalmos in the left eye. A cranial X-ray showed a mixed osteolytic and sclerotic expansile mass lesion in the left sphenoid bone. Neuroradiologic imaging study revealed a left temporosphenoidal extra-axial expansile mass lesion with heterogeneous enhancement after contrast enhancement associated with destruction and erosion of the temporal and sphenoid bones. The cerebral parenchyma and orbital contents were compressed without any sign of infiltration. Bone scan showed hot uptake in the left orbital region. Angiogram demonstrated marked neoplastic angiogenesis from the middle meningeal artery and other branches of left external carotid artery, for which preoperative embolisation was tried in vain. Cranio-orbito-zygomatic approach was undergone in two stages because of the patient's religious belief (patient was Jehovah's witness) and profuse bleeding during the first surgery. Two weeks after initial operation, second surgery was carried out with total excision of the residual mass in the left orbital ridge. Histopathological examination revealed typical epithelioid cell cords or nests in myxoid stroma with a positive immunoreactivity to factor viii-related antigen. The authors report an unusual case of EH involving sphenoid and temporal bone in a young woman. Preoperative embolisation is thought to be absolutely essential before removal. Because there is no convincing data to advise radiation/chemotherapy, total resection and close follow-up may be reasonable.
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keywords = bone
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4/17. Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries.

    Pathogenesis of in-stent restenosis remains poorly understood because information from human histopathologic studies is scarce. We used an improved saw-grinding and cutting method on methacrylate-embedded samples containing metal stents, which allows in situ hybridization and immunohistochemical analysis of in-stent restenosis. Twenty-one samples were collected 3 hours to 3 years after stenting from 6 patients aged 36 to 81 years. Except in very early samples collected within hours after the stent deployment, neovascularization was present in all segments studied. At advanced stages, extensive neovascularization was located mainly at the luminal side of the stent struts and was only rarely accompanied by inflammatory cells. The neovessels colocalized with vascular endothelial growth factor (VEGF)-A mRNA and protein expression as well as with iron deposits and oxidation-specific epitopes, which imply the presence of chronic oxidative stress. VEGF-A expression was detected in the same areas containing macrophages, endothelial cells, and, to a lesser extent, smooth muscle cells, which also showed platelet-derived growth factor-BB expression. We conclude that in-stent restenosis features neovascularization, VEGF-A and platelet-derived growth factor-BB expression, and iron deposition, which is most probably derived from microhemorrhages. These mechanisms may play an important role in the development of neointimal thickening and could provide useful targets for the prevention and treatment of in-stent restenosis.
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ranking = 127.93225765306
keywords = macrophage
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5/17. Is angiomatosis an intrinsic pathohistological feature of massive osteolysis? Report of an autopsy case and a review of the literature.

    We report here an autopsied patient who had died during the clinical course of massive osteolysis (MO), which is a rare chronic disease that begins insidiously and is characterized by progressive regional loss of bone. Since the original description by Gorham and Stout in 1955, vascular proliferation, e.g., hemangiomatosis, has been considered to be the characteristic feature related to the pathogenesis. However, no such vascular changes were observed in the present patient. It was also important to note that a significant number of cases of MO that showed no vascular proliferation have been described previously. Therefore, we consider that vascular proliferation is not always associated with the osteolysis in MO and that the increased vascularity, if any, may be one of the results of the disease rather than the cause.
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keywords = bone
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6/17. Spindle cell hemangioendothelioma exhibits the ultrastructural features of reactive vascular proliferation rather than of angiosarcoma.

    A patient with spindle cell hemangioendotheliomas was followed from 1964 to the present time, allowing the authors the opportunity to examine the lesions in the early, mature, and old phases. Organizing thrombi of different stages associated with slit-like vascular proliferation were always observed, whereas cavernous vascular spaces predominated as the lesions became older. Each spindle cell hemangioendothelioma initially developed relatively rapidly and was sometimes painful but then persisted as a silent nodule for decades. Transmission and scanning electron microscopic studies revealed that endothelial cells tended to digitate into the slit-like proliferating channels, became attached to other cells by means of tight junctions, and thus obstructed the channels at sites where thrombi developed repeatedly. The vascular spaces, ranging in nature from slit-like to cavernous, were outlined further by a relatively sparse mantle of ramified or dendritic interstitial cells that corresponded to spindle cells. Most of the cells appeared simply to be fibroblasts, but they developed the features of pericytes when they were close to the endothelial lining of well-developed vascular lumens. Large vascular spaces and phleboliths were surrounded by smooth muscle cells. Approximately 20% of the interstitial cells were dendritic macrophages characterized by phagocytic activity, presence of many lysosomes, and factor xiiia expression. The long and characteristic clinical course, the histologic evidence that thrombosis and its organization was continually occurring within the lesions, and the ultrastructural finding that spindle cell hemangioendotheliomas were composed of different microvascular segments from capillaries to veins, suggest that spindle cell hemangioendotheliomas may develop from a cycle of recanalization after thrombosis that occurs repeatedly because of the unique endothelial growth that was noted. This is in contrast with the previous conception that they were low-grade angiosarcomas.
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ranking = 127.93225765306
keywords = macrophage
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7/17. Transmission electron microscopic study of a subretinal choroidal neovascular membrane due to age-related macular degeneration.

    From a patient with age-related macular degeneration we studied ultrastructurally a disciform scar that was removed from an eye with a vitreous hemorrhage. In cross section, the scar was divided by a retinal pigment epithelial (RPE) cell layer. The choroidal side consisted of fibrovascular tissue with active neovascular buds and inflammatory cells, including macrophages attached to the RPE basement membrane. Apart from the RPE, no components of Bruch's membrane could be identified. The retinal side contained organizing hemorrhage and a collagenous matrix with fibroblastlike cells probably of RPE and choroidal origin. The anatomy and the clinical findings at surgery suggest that such scars lie on (rather than within) the inner collagenous layer of Bruch's membrane and contain two components divided by the original RPE layer. The choroidal side is fibrovascular, including active neovascularization, and the retinal side is fibrous and formed by metaplastic RPE cells and choroidal fibrovascular ingrowth.
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ranking = 127.93225765306
keywords = macrophage
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8/17. Trauma-associated growth of suspected dormant micrometastasis.

    BACKGROUND: Cancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release. CASE PRESENTATION: We describe a patient with non-small lung cancer who had a rapid tumor growth and recurrence at a minor trauma site of his skull bone. CONCLUSION: This case is an illustration of the phenomenon of tumor growth after trauma or surgery and its associated cellular mechanisms. This phenomenon deserves further investigation and study.
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ranking = 1
keywords = bone
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9/17. Histopathologic findings of retrieved specimens of vertebroplasty with polymethylmethacrylate cement: case control study.

    STUDY DESIGN: Case control study. OBJECTIVE: To investigate the histopathologic findings of 2 retrieved specimens from failed vertebroplasty with polymethylmethacrylate (PMMA) cement. SUMMARY OF BACKGROUND DATA: vertebroplasty using PMMA cement has been commonly used to treat debilitating back pain from compression fracture, angiomas, and metastatic cancer. However, there was concern about the unpredictable future results with PMMA cement. The histopathologic changes were rarely reported. methods: There were 2 PMMA augmented and 3 nonaugmented fractured vertebral bodies retrieved for histopathologic study. Between the 2 groups, we compared the findings of bone necrosis, foreign body reaction, fibrotic wall formation, and neovascularization. RESULTS: Bone necrosis was noted in the periphery of PMMA cement, which was surrounded by fibrotic tissues. In contrast, no fibrotic wall formation could be found in the nonaugmented control group. Foreign body reaction was only noted in PMMA augmented cases, and neovascularization was only noted in the control cases. CONCLUSION: PMMA cement might not be as bioinert as we considered. Therefore, the long-term safety of vertebroplasty should be further evaluated.
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ranking = 1
keywords = bone
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10/17. Angiogenetic factors and biochemical markers of bone metabolism in poems syndrome treated with high-dose therapy and autologous stem cell support.

    The cause of the polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes (POEMS) syndrome is currently unknown, but increased levels of vascular endothelial growth factor (VEGF) appear to play a pathogenetic role. Osteosclerotic bone lesions are a characteristic finding in POEMS, but there are no data about the specific role of various molecules that control bone remodeling in patients with POEMS. serum levels of angiogenic cytokines (VEGF, angiogenin, angiopoietin-2, and basic fibroblast growth factor) along with a series of bone remodeling indices (C-telopeptide of type I collagen, bone-alkaline phosphatase [bALP], osteocalcin [OC], soluble receptor activator of nuclear factor-kappaB ligand [RANKL], osteoprotegerin [OPG], and macrophage inflammatory protein-1alpha) were measured in 2 patients with POEMS before and after high-dose therapy (HDT) with autologous stem cell transplantation and in age- and sex-matched controls. Increased VEGF levels before HDT were reduced significantly after treatment, although levels of the other angiogenetic factors did not differ from that of controls and were less influenced by HDT. serum RANKL levels were increased before HDT, whereas OPG levels were within the levels of healthy controls, resulting in an abnormal soluble RANKL to OPG ratio. Levels of bone resorption markers (C-telopeptide of type I collagen) were very low or undetectable before HDT, although bALP and OC levels were similar to that of controls. After HDT, soluble RANKL levels decreased, OPG remained rather stable, bone resorption markers increased to levels of normal individuals, bALP levels were rather unchanged, and OC levels increased. Decreasing VEGF levels parallel clinical improvement, and the restoration of normal bone metabolism follows HDT.
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ranking = 138.93225765306
keywords = macrophage, bone
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