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1.
J Bone Miner Res ; 32(8): 1716-1726, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28425622

RESUMO

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH)2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus metabolism. This study demonstrates critical roles of neurofibromin in osteocytes for osteoid mineralization. © 2017 American Society for Bone and Mineral Research.


Assuntos
Neoplasias Ósseas , Fatores de Crescimento de Fibroblastos/metabolismo , Neurofibromina 1/deficiência , Osteócitos , Osteoma Osteoide , Osteomalacia , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Humanos , Camundongos , Camundongos Knockout , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Osteócitos/metabolismo , Osteócitos/patologia , Osteoma Osteoide/genética , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patologia , Osteomalacia/genética , Osteomalacia/metabolismo , Osteomalacia/patologia
2.
Hum Pathol ; 58: 24-34, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27498059

RESUMO

Sclerostin (SOST) is an extracellular Wnt signaling antagonist which negatively regulates bone mass. Despite this, the expression and function of SOST in skeletal tumors remain poorly described. Here, we first describe the immunohistochemical staining pattern of SOST across benign and malignant skeletal tumors with bone or cartilage matrix (n=68 primary tumors). Next, relative SOST expression was compared to markers of Wnt signaling activity and osteogenic differentiation across human osteosarcoma (OS) cell lines (n=7 cell lines examined). Results showed immunohistochemical detection of SOST in most bone-forming tumors (90.2%; 46/51) and all cartilage-forming tumors (100%; 17/17). Among OSs, variable intensity and distribution of SOST expression were observed, which highly correlated with the presence and degree of neoplastic bone. Patchy SOST expression was observed in cartilage-forming tumors, which did not distinguish between benign and malignant tumors or correlate with regional morphologic characteristics. Finally, SOST expression varied widely between OS cell lines, with more than 97-fold variation. Among OS cell lines, SOST expression positively correlated with the marker of osteogenic differentiation alkaline phosphatase and did not correlate well with markers of Wnt/ß-catenin signaling activity. In summary, SOST is frequently expressed in skeletal bone- and cartilage-forming tumors. The strong spatial correlation with bone formation and the in vitro expression patterns are in line with the known functions of SOST in nonneoplastic bone, as a feedback inhibitor on osteogenic differentiation. With anti-SOST as a potential therapy for osteoporosis in the near future, its basic biologic and phenotypic consequences in skeletal tumors should not be overlooked.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias de Tecido Ósseo/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Fosfatase Alcalina/metabolismo , Biópsia , Neoplasias Ósseas/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Condroma/metabolismo , Condroma/patologia , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Neoplasias de Tecido Ósseo/patologia , Osteoblastoma/metabolismo , Osteoblastoma/patologia , Osteogênese , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Estudos Retrospectivos , Via de Sinalização Wnt
4.
J Clin Pathol ; 66(9): 768-74, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23814261

RESUMO

AIMS: Osteoid osteoma and osteoblastoma have, in the past, been variously regarded as both similar and distinct entities. Currently, WHO classifies these tumours separately. We compared archetypal cases to identify novel histomorphological and immunohistochemical features attempting to clarify their mutual relationship. METHODS AND RESULTS: 10 osteoid osteomas and 20 osteoblastomas (10 spinal and 10 non-spinal) were retrieved and reviewed clinically, radiologically and histologically. Immunohistochemistry was performed for: desmin, SMA, neurofilament, S100, vimentin, PGP9.5, GFAP, EMA, caldesmon, CD34, broad-spectrum cytokeratins, claudin-1. We identified features, common to both osteoid osteoma and osteoblastoma, namely, areas of lesional non-osteoblastic stroma and the presence of scattered, large cells with smudged/degenerate nuclei. Immunohistochemically, we confirmed the innervated status of osteoid osteomas, and found that osteoblastomas were similarly innervated. The non-osteoblastic lesional stroma was distinctive owing to expression of EMA and NSE by the mesenchymal spindle cells and expression of desmin, PGP9.5 and S100 by the scattered, large cells with 'smudged' nuclei. CONCLUSIONS: Both osteoid osteoma and osteoblastoma are innervated bone-forming lesions which share novel histomorphological and immunohistochemical features supporting the view that separate classification is unjustified, and we offer a pathogenetic explanation for their apparent clinical and radiological variance.


Assuntos
Neoplasias Ósseas/patologia , Osteoblastoma/patologia , Osteoma Osteoide/patologia , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Osteoblastoma/metabolismo , Osteoma Osteoide/metabolismo
5.
Histopathology ; 63(1): 36-49, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23701429

RESUMO

AIMS: Diagnosing osteosarcoma can be challenging, as osteoid deposition is often limited in extent, and hyalinized stroma may closely mimic osteoid. SATB2 is a nuclear protein that plays a critical role in osteoblast lineage commitment. The aim of this study was to examine SATB2 expression in osteosarcomas and other bone and soft tissue tumours, to evaluate its diagnostic utility. METHODS AND RESULTS: Whole sections of 215 tumours were evaluated, including 52 osteosarcomas (43 of skeletal origin; nine extraskeletal), 86 other bone tumours, and 77 other soft tissue tumours. All skeletal osteosarcomas, osteoblastomas, osteoid osteomas, and fibrous dysplasias, eight (89%) extraskeletal osteosarcomas, five (83%) giant cell tumours and three (50%) chondromyxoid fibromas showed nuclear immunoreactivity for SATB2. Staining in other bone and soft tissue tumours was predominantly limited to areas of heterologous osteoblastic differentiation. Focal weak staining was identified in one (9%) unclassified pleomorphic sarcoma and one (13%) monophasic synovial sarcoma. SATB2 was negative in all soft tissue tumours with prominent sclerotic stromal collagen. CONCLUSIONS: SATB2 is a marker of osteoblastic differentiation in benign and malignant mesenchymal tumours. Although SATB2 is not specific for osteosarcoma, it has the potential to be a useful adjunct in some settings, particularly in the distinction between hyalinized collagen and osteoid.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/metabolismo , Diferenciação Celular , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Osteoblastos/patologia , Neoplasias de Tecidos Moles/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , Osteoblastoma/metabolismo , Osteoblastoma/patologia , Osteoblastos/metabolismo , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Sarcoma Sinovial/metabolismo , Sarcoma Sinovial/patologia , Neoplasias de Tecidos Moles/patologia , Fatores de Transcrição/genética
6.
Pathology ; 44(4): 325-30, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22531343

RESUMO

AIMS: Syndecan-4 (SDC4) and fibronectin (FN), which belong to the cell adhesion molecules, have been reported to correlate with tumour growth and invasion in various carcinomas. We aimed to investigate the prognostic value of these molecules in osteosarcoma. METHODS: Using immunohistochemistry, we compared the expression of these molecules in high grade osteosarcoma to low grade central osteosarcoma, osteoid osteoma and normal bone. Further, the expression of SDC4 and FN were analysed with prognostic factors of high grade osteosarcoma. RESULTS: In high grade osteosarcoma, SDC4 was expressed in 50 of the 65 samples; of these, 32 of 65 showed strong expression profiles. FN was expressed in 46 of 65 samples, and 29 of 65 had evidence of strong expression of this molecule. SDC4 and FN expression were increased in high grade osteosarcoma as compared to other tissues. Strong SDC4 expression was associated with the occurrence of distant metastasis and a large tumour size, and strong FN expression was associated with the occurrence of distant metastasis. Strong expression of SDC4 or FN was associated with significantly shorter overall survival, respectively. CONCLUSIONS: [corrected] Increased expression of SDC4 and FN may be underlying molecular alteration of osteosarcoma which accounts for more aggressive clinical behaviour.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/diagnóstico , Fibronectinas/metabolismo , Osteossarcoma/secundário , Sindecana-4/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Criança , Feminino , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Osteoma Osteoide/metabolismo , Osteoma Osteoide/mortalidade , Osteoma Osteoide/patologia , Osteossarcoma/metabolismo , Osteossarcoma/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
7.
Osteoporos Int ; 23(5): 1645-50, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21681611

RESUMO

Osteocalcin is a hormone secreted by osteoblasts, which regulates energy metabolism by increasing ß-cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. This has been demonstrated in mice, but to date, the evidence implicating osteocalcin in the regulation of energy metabolism in humans are indirect. To address this question more directly, we asked whether a benign osteoblastic tumor, such as osteoma osteoid in young adults, may secrete osteocalcin. The study was designed to assess the effect of surgical resection of osteoid osteoma on osteocalcin and blood glucose levels in comparison with patients undergoing knee surgery and healthy volunteers. Blood collections were performed the day of surgery and the following morning after overnight fasting. Patients and controls were recruited in the orthopedic surgery department of New York Presbiterian Hospital, NY-USA and Hospices Civils de Lyon, France. Seven young males were included in the study: two had osteoid osteoma, two underwent knee surgery, and three were healthy volunteers. After resection of the osteoid osteomas, we observed a decrease of osteocalcin by 62% and 30% from the initial levels. Simultaneously, blood glucose increased respectively by 32% and 15%. Bone turnover markers were not affected. This case study shows for the first time that osteocalcin in humans affects blood glucose level. This study also suggests that ostoid osteoma may be considered, at least in part, as an osteocalcinoma.


Assuntos
Glicemia/metabolismo , Neoplasias Ósseas/sangue , Osteoma Osteoide/sangue , Adulto , Biomarcadores/sangue , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/cirurgia , Humanos , Resistência à Insulina/fisiologia , Masculino , Osteocalcina/sangue , Osteocalcina/metabolismo , Osteocalcina/fisiologia , Osteoma Osteoide/metabolismo , Osteoma Osteoide/cirurgia , Período Pós-Operatório , Adulto Jovem
8.
Zhonghua Zhong Liu Za Zhi ; 32(8): 586-9, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21122409

RESUMO

OBJECTIVE: To evaluate the expression of N-cadherin and ß-catenin protein and their relationship with clinicopathological characteristics of osteosarcoma. METHODS: The expressions of N-cadherin and ß-catenin at protein level were detected by immunohistochemical staining in 54 cases of osteosarcoma, 11 cases of osteoid osteoma, 7 cases of osteoblastoma and 8 cases of newly formed bone in nonmalignant bone diseases. The relationship between the two indexes and clinicopathological characteristics of osteosarcoma was analyzed. RESULTS: In newly formed bone, osteoblastoma, osteoid osteoma and osteosarcoma, the positive expression rate of N-cadherin protein was 75.0%, 71.4%, 63.6% and 35.2%, respectively. The positive expression rate of N-cadherin protein in osteosarcoma was significantly lower than that in osteoid osteoma, osteoblastoma and newly formed bone in nonmalignant bone diseases (P = 0.035). The positive expression rate of N-cadherin protein in osteosarcoma cases with pulmonary metastasis was lower than that in cases without (21.7% vs. 56.3%, P = 0.027). The positive expression rate of N-cadherin protein in osteosarcoma cases died in two years was lower than that in cases lived for more than two years (18.2% vs. 50.0%, P = 0.024). In newly formed bone, osteoblastoma, osteoid osteoma and osteosarcoma, the aberrant expression rate of ß-catenin protein was 12.5%, 28.6%, 27.3% and 66.7%, respectively. The aberrant expression rate of ß-catenin protein in osteosarcoma was significantly higher than that in osteoid osteoma, osteoblastoma and newly formed bone (P = 0.002). Aberrant expression rate of ß-catenin in osteosarcoma cases with pulmonary metastasis was higher than that without (82.6% vs. 43.8%, P = 0.011). An inverse correlation was found between the aberrant expression of ß-catenin and N-cadherin expression in osteosarcoma(r = -0.302, P = 0.027). CONCLUSION: The positive expression rate of N-cadherin is decreased in osteosarcoma while aberrant expression rate of ß-catenin increased. The expression of N-cadherin protein is closely correlated with the metastasis and prognosis of osteosarcoma, but the expression of ß-catenin protein is merely correlated with the metastasis of osteosarcoma.


Assuntos
Neoplasias Ósseas/metabolismo , Caderinas/metabolismo , Neoplasias Pulmonares/metabolismo , Osteossarcoma/metabolismo , beta Catenina/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Osteoblastoma/metabolismo , Osteoma Osteoide/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/secundário , Osteossarcoma/cirurgia , Taxa de Sobrevida , Adulto Jovem
9.
Hum Pathol ; 41(12): 1788-93, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21078438

RESUMO

Recent progress in skeletal molecular biology has led to the clarification of the transcriptional mechanisms of chondroblastic and osteoblastic lineage differentiation. Three master transcription factors-Sox9, Runx2, and Osterix-were shown to play an essential role in determining the skeletal progenitor cells' fate. The present study evaluates the expression of these factors in 4 types of benign bone tumors-chondromyxoid fibroma, chondroblastoma, osteoid osteoma, and osteoblastoma-using immunohistochemistry and tissue microarrays. Osteoid osteoma and osteoblastoma showed strong nuclear expression of Osterix and Runx2. In contrast, only a few chondroblastomas showed positive nuclear expression of Osterix. Strong nuclear expression of Sox9 was detected in all chondroblastomas, whereas nearly half of the osteoblastomas showed focal weak cytoplasmic expression of Sox9.


Assuntos
Neoplasias Ósseas/genética , Cartilagem/crescimento & desenvolvimento , Redes Reguladoras de Genes , Neoplasias de Tecido Conjuntivo/genética , Osteogênese/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Neoplasias Ósseas/patologia , Cartilagem/patologia , Criança , Condroblastoma/genética , Condroblastoma/metabolismo , Condroblastoma/patologia , Condroma/genética , Condroma/metabolismo , Condroma/patologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Fibroma/genética , Fibroma/metabolismo , Fibroma/patologia , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/metabolismo , Neoplasias de Tecido Conjuntivo/patologia , Osteoblastoma/genética , Osteoblastoma/metabolismo , Osteoblastoma/patologia , Osteoma Osteoide/genética , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patologia , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Fator de Transcrição Sp7 , Células-Tronco/metabolismo , Células-Tronco/patologia , Análise Serial de Tecidos , Fatores de Transcrição/metabolismo , Adulto Jovem
10.
Clin Nucl Med ; 32(8): 628-30, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17667437

RESUMO

Osteoid osteoma is a common skeletal neoplasm with distinctive histologic abnormalities that consist of a central core of vascular osteoid tissue and a peripheral sclerotic zone. We report a case of intense F-18 FDG uptake in the nidus of cortical osteoid osteoma of the distal metaphysis of the right tibia.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Fluordesoxiglucose F18 , Osteoma Osteoide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tíbia/diagnóstico por imagem , Tíbia/metabolismo , Adulto , Neoplasias Ósseas/metabolismo , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Osteoma Osteoide/metabolismo , Compostos Radiofarmacêuticos/farmacocinética
11.
Clin Nucl Med ; 28(8): 696-8, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12897666

RESUMO

The authors present a case of pathologically proved osteoid osteoma that was visualized randomly on an I-131 whole-body scan. Search of the medical literature did not reveal any mention of radioactive iodine uptake by osteoid osteomas. Therefore, the authors concluded that this pathology must be included in the differential diagnostic list of positive findings on I-131 scans.


Assuntos
Radioisótopos do Iodo , Osso Nasal/diagnóstico por imagem , Osso Nasal/patologia , Neoplasias Nasais/diagnóstico por imagem , Neoplasias Nasais/patologia , Osteoma Osteoide/diagnóstico por imagem , Osteoma Osteoide/patologia , Idoso , Diagnóstico Diferencial , Humanos , Achados Incidentais , Radioisótopos do Iodo/farmacocinética , Masculino , Osso Nasal/metabolismo , Neoplasias Nasais/metabolismo , Osteoma Osteoide/metabolismo , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Contagem Corporal Total
12.
J Orthop Res ; 20(1): 159-62, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11853083

RESUMO

Osteoid osteoma is a benign bone forming neoplasm that is characterized by its small size (less than 2 cm), self-limited growth, and the tendency to cause extensive reactive changes in the adjacent tissue. The lesion classically presents with severe pain at night that is dramatically relieved by NSAIDs. The tumor has been shown to express very high levels of prostaglandins, particularly PGE2 and PGI2. The high local levels of these prostaglandins are presumed to be the cause of the intense pain seen in patients with this lesion. One generally accepted form of treatment is the prolonged use of NSAIDs. Since the cyclooxygenases are thought to be the source of these prostaglandins, and the central target of NSAIDs, we evaluated the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in osteoid osteoma tissues from patients following surgery. In the 12 specimens examined we found that the tumor osteoblasts had strong immunohistochemical staining for COX-2, while the staining in the surrounding host osteoblasts in the reactive bone was scant. Significant COX-1 staining was also detected in both tumor and host osteoblasts. For comparison we examined the COX expression in human fracture callus, fibrous dysplasia, osteoblastoma, osteofibrous dysplasia, and myositis ossificans. With the exception of fracture callus, very limited amounts of COX-2 could be detected in these tissues. Taken together, we conclude that the increased production of prostaglandins by osteoid osteomas implicates that COX-2 is one of the mediators of this condition. These findings suggest that the newly selective COX-2 inhibitors could be used to more safely treat osteoid osteomas.


Assuntos
Neoplasias Ósseas/metabolismo , Isoenzimas/biossíntese , Osteoma Osteoide/metabolismo , Prostaglandina-Endoperóxido Sintases/biossíntese , Calo Ósseo/metabolismo , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Humanos , Imuno-Histoquímica , Isoenzimas/análise , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/análise
13.
Mod Pathol ; 11(2): 175-80, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9504688

RESUMO

Osteoid osteomas are benign bone-forming tumors that despite their small size (<2.0 cm) characteristically produce severe nocturnal bone pain that is relieved by aspirin. This typical clinical presentation is virtually unique among bone tumors. Histologically, osteoid osteomas are circumscribed nodules of woven bone and osteoid with prominent osteoblastic rimming (the nidus), surrounded by thickened cortical and trabecular bone and loose fibrovascular tissue (the reactive zone). Prostaglandins mediate the pain of osteoid osteomas, but there have been few studies of their innervation. We investigated 34 osteoid osteomas using a streptavidin immunohistochemical technique and a panel of antibodies to neural and neural-associated antigens (phosphorylated neurofilament, neurofilament, and S-100 protein). Whenever possible, sections of the nidus and the reactive zone were stained. As controls, we stained other bone tumors that can be painful, including 10 osteoblastomas, 5 osteosarcomas, 6 giant cell tumors, 4 chondroblastomas, 3 aneurysmal bone cysts, and 6 cases of fibrous dysplasia. Twenty-five osteoid osteomas contained phosphorylated neurofilament-, neurofilament-, and/or S-100-positive nerve fibers in the reactive zone around the nidus and/or in the nidus. The nerve fibers were larger and more abundant in the reactive zone than in the nidus, and they were occasionally visible on hematoxylin- and eosin-stained slides on retrospective review. The smaller nerve fibers within the nidi were never identified, even after extensive review of those slides. In the nine cases in which nerve fibers were not identified, the sampled tissue consisted only of nidus. None of the control "bone tumors" contained detectable nerve fibers within their substance or in the adjacent peripheral bone. The nerve supply of osteoid osteoma seems unique among bone tumors, and it might serve as a marker in diagnostically difficult cases.


Assuntos
Neoplasias Ósseas/patologia , Osso e Ossos/inervação , Osteoma Osteoide/patologia , Nervos Periféricos/patologia , Neoplasias Ósseas/metabolismo , Humanos , Técnicas Imunoenzimáticas , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Proteínas de Neurofilamentos/metabolismo , Osteoma Osteoide/metabolismo , Nervos Periféricos/metabolismo , Estudos Retrospectivos , Proteínas S100/metabolismo
14.
Ital J Orthop Traumatol ; 18(1): 63-9, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1399536

RESUMO

The joint is a relatively rare localization for osteoid osteoma. The location of the tumor and the concomitant synovitis-explain the peculiarity of the clinical features, which makes differential diagnosis with inflammatory diseases of the joint difficult. The authors report the results of three cases of intra-articular osteoid osteoma in which it was possible to determine the levels of prostaglandin (PGE2) and prostacyclin (PGI2), which are synthesized by the tumoral tissue. The increased production of these substances, which can reach up to 70 times their production in normal tissue, explain both the character of the pain and the origin of the synovitis which is so commonly found in this kind of tumor. The results of this study confirm the ability of the neoplastic tissue to produce high quantities of mediators of inflammation and enable the authors to formulate a theory as to the pathogenesis of the concomitant reactive synovitis observed in cases of intra-articular osteoid osteoma.


Assuntos
Dinoprostona/biossíntese , Epoprostenol/biossíntese , Artropatias/metabolismo , Osteoma Osteoide/metabolismo , 6-Cetoprostaglandina F1 alfa/análogos & derivados , 6-Cetoprostaglandina F1 alfa/urina , Osso e Ossos/metabolismo , Humanos , Osteoma Osteoide/complicações , Sinovite/etiologia
15.
Eicosanoids ; 4(3): 165-7, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1772689

RESUMO

Osteoid osteoma is a benign osteoid-forming tumor of the bone characterized by pain which is relieved by nonsteroidal anti-inflammatory drugs. Very high levels of prostaglandins have been found in the lesion. In nine patients with osteoid osteoma, prostaglandin E2 (PGE2) and prostacyclin (PGI2) synthesis in explants from the nidus incubated in vitro yielded 947.3 +/- 482.6 (mean +/- SD) and 340.2 +/- 178.1 pg/mg of wet tissue respectively, values 32 and 49 times higher than in fragments of normal bone. In eight patients the excretion rate of the major urinary metabolite of PGI2, i.e. 2,3-dinor-6-keto-PGF1 alpha, was nearly double the control value (499 +/- 93 vs 257 +/- 117 pg/mg of creatinine; mean +/- SD). In six of them, from whom urine was collected 1 month after surgery, urinary 2,3-dinor-6-keto-PGF1 alpha decreased significantly (P less than 0.01) from 487 +/- 100 to 229 +/- 52 pg/mg creatinine. Urinary 6-keto-PGF1 alpha, largely a reflection of intrarenal PGI2 synthesis, was comparable to the control group (4.6 +/- 0.9 vs 4.5 +/- 1.0 ng/h, respectively) and remained unchanged after operation. These results suggest an enhanced PGI2 biosynthesis in vivo in patients with osteoid osteoma. This abnormality of arachidonate metabolism is consistent with enhanced biosynthetic capacity of the tumor in vitro, and is reversible upon its removal.


Assuntos
Neoplasias Ósseas/metabolismo , Dinoprostona/biossíntese , Epoprostenol/biossíntese , Osteoma Osteoide/metabolismo , 6-Cetoprostaglandina F1 alfa/análogos & derivados , 6-Cetoprostaglandina F1 alfa/urina , Adolescente , Adulto , Osso e Ossos/metabolismo , Feminino , Humanos , Masculino
16.
Mol Endocrinol ; 4(2): 184-90, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2329998

RESUMO

The effects of recombinant human interleukin-1 alpha (IL-1) on procollagen gene expression were examined in the clonal mouse osteoblastic cell line MC3T3-E1. Cells were grown in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum and 50 micrograms/ml ascorbic acid. Collagen synthesis was assessed as [3H]proline incorporation into collagenase-digestible protein (CDP). Procollagen mRNA levels were determined by Northern blot analysis using a 32P-labeled alpha 1(I) cDNA. Transcription rates were determined by nuclear run-off assay. IL-1 at 1-1000 pg/ml caused a concentration-dependent inhibition of CDP, which was maximally reduced by 75-80%, and a parallel reduction of procollagen alpha 1(I) mRNA levels. The effects of IL-1 were mimicked by the tumor promoter phorbol 12-myristate 13-acetate (PMA) at 1-100 nM, which inhibited CDP and reduced procollagen alpha 1(I) mRNA levels to a similar extent. The effects of IL-1 and PMA were independent of prostaglandin production, since indomethacin did not alter the inhibitory effect of either agent on CDP. Neither IL-1 (up to 10 ng/ml) nor PMA (100 nM) affected adenylate cyclase activity, while forskolin (10 microM), PTH (10 nM) and prostaglandin E2 (1 microM) stimulated adenylate cyclase activity 3- to 5-fold. However, forskolin (10 microM) and (Bu)2cAMP (100 microM) failed to alter CDP or procollagen alpha 1(I) mRNA levels. IL-1 (1 ng/ml) and PMA (100 nM) reduced transcription of the alpha 1(I) procollagen gene by 70% and 80%, respectively, while alpha 2(I) transcription was decreased by 59% and 53%. Neither IL-1 nor PMA affected transcription of the beta-actin or beta-tubulin genes.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Colágeno/biossíntese , Interleucina-1/farmacologia , Osteoma Osteoide/patologia , Ésteres de Forbol/farmacologia , Animais , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Camundongos , Osteoma Osteoide/metabolismo , Osteoma Osteoide/fisiopatologia , Pró-Colágeno/genética , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/fisiologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologia
17.
Histol Histopathol ; 4(2): 123-8, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2562462

RESUMO

A case of malignant Müllerian mixed tumor of the uterus, exhibiting a histology of heterologous osteosarcomatous differentiation, is presented. Special emphasis is placed on the characteristic immunohistochemical reactivity of the tumor tissue in comparison with that of normal uterine tissue in the proliferative phase. Keratin, cytokeratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (HCG) were found only in the carcinomatous element. However, neuron specific enolase (NSE), S-100 protein (S 100) and vimentin were identified in almost all tumor tissue elements. Desmin and actin were not stained in any elements. Myoglobin was only detected weakly in the squamous carcinomatous element. Undifferentiated cell element, composed of small, round, spindle, or polygonal cells showed positive reactions to NSE and S 100, but not to any other antibodies. As compared to the reactivities of the normal proliferative endometrium, the glandular epithelial cells were positive with NSE, S 100, vimentin and CEA, but the stromal cells were only positive with vimentin. Such a multitudinous and concomitant expression of antigenicity to the different tumor elements indicates a close relationship to its mesodermal Müllerian origin, and NSE, S 100 and vimentin might be most adequate indicators of these types of tumors.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Uterinas/patologia , Útero/ultraestrutura , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patologia , Inclusão em Parafina , Sarcoma/metabolismo , Sarcoma/patologia , Fixação de Tecidos , Útero/fisiologia
18.
Mod Pathol ; 1(2): 129-31, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3266336

RESUMO

Osteoid osteomas are characterized clinically by a pattern of nocturnal pain which is exquisitely sensitive to salicylates. Etiology for the pain has been ascribed by previous investigators to the presence of nonmyelinated nerve fibers or to the effect of prostaglandins. In an effort to corroborate the potential role of prostaglandins in mediating the pain associated with this tumor, we have determined the concentration of prostaglandins E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 utilizing radioimmunoassay of extracts of homogenated tumor tissue. Results were compared with similar extracts of normal bone and a variety of other osseous tumors. The increased concentrations of prostaglandin E2 found in cases of osteoid osteoma and osteoblastoma confirm studies of explants of these tumors previously recorded in the literature.


Assuntos
Osteoma Osteoide/metabolismo , Prostaglandinas/biossíntese , Neoplasias Ósseas/análise , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/análise , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Condroblastoma/análise , Condroblastoma/metabolismo , Condroblastoma/patologia , Displasia Fibrosa Óssea/metabolismo , Displasia Fibrosa Óssea/patologia , Tumores de Células Gigantes/análise , Tumores de Células Gigantes/metabolismo , Tumores de Células Gigantes/patologia , Histiocitose de Células de Langerhans/metabolismo , Histiocitose de Células de Langerhans/patologia , Humanos , Osteoma Osteoide/análise , Osteoma Osteoide/patologia , Osteossarcoma/análise , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Dor/etiologia , Prostaglandinas/análise
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