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1.
Carcinogenesis ; 41(7): 904-908, 2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-32556091

RESUMEN

DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7-59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18-3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82-3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54-2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.


Asunto(s)
Proteína BRCA1/genética , Reparación del ADN/genética , Neoplasias de Tejido Óseo/genética , Neoplasias de la Próstata/genética , Adulto , Anciano , Biomarcadores de Tumor , Progresión de la Enfermedad , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Clasificación del Tumor , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Neoplasias de Tejido Óseo/patología , Neoplasias de Tejido Óseo/secundario , Neoplasias de la Próstata/patología
2.
Clin Orthop Relat Res ; 478(11): 2505-2519, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32510187

RESUMEN

BACKGROUND: Reconstruction of defects after resection of malignant bone tumors with liquid nitrogen-sterilized recycled autografts is an alternative to bone allografts and endoprostheses in resource-constrained environments. Most studies reporting favorable outcomes with liquid nitrogen-sterilized autografts for bone reconstruction are geographically restricted to a few countries, and the technical challenges of routinely using liquid nitrogen intraoperatively, especially when using the pedicle freezing technique, has not been documented. QUESTIONS/PURPOSES: (1) What are the technical challenges of liquid nitrogen sterilization of bone tumors for inexperienced surgeons? (2) What are the complications associated with the procedure? METHODS: Between May 2017 and October 2019, 88 patients underwent limb salvage procedures for malignant bone tumors of the extremities at our institution. An endoprosthesis was used for reconstruction of the defect following resection in 45% (40 of 88) of these patients, mostly in adults (median age 21 years; range 9 to 68). In the remaining 55% (48 of 88) of patients undergoing biological reconstruction, liquid nitrogen-sterilized autograft was used in 90% (43 of 48), extracorporeal irradiation-sterilized autograft was used in 4% (2 of 48) and allograft was used in 6% (3 of 48). Of the 43 patients receiving liquid nitrogen-sterilized autograft, 5% (2 of 43) were excluded due to loss to follow-up and the remaining 95% (41 of 43) were included for the analysis. Liquid nitrogen-sterilized autograft was the preferred method of reconstruction at our institution during the study period, unless the patient had an indication for prosthesis reconstruction; extracorporeal irradiation-sterilized autograft was used due to resource constraints with liquid nitrogen and allograft was used when patients insisted.All surgical procedures were performed by the same team of trained orthopaedic oncology surgeons. The medical records of the included 41 patients were retrieved using an institutional database search in this retrospective study, and all were used to ascertain technical challenges associated with the operations as well as early (within 3 weeks of the index procedure) and late complications (those occurring 3 weeks or more after surgery). The technical challenges were defined as follows: the quantity of liquid nitrogen to be used; arranging, storing and handling of liquid nitrogen in the operating room, type and size of the container to be used for sterilization, the positioning of the container during pedicle freezing, level of fibular osteotomy for pedicle freezing of tibia, soft tissue protection, limb rotation during pedicle freezing, managing tourniquet time, and any other intraoperative factors with the use of liquid nitrogen for sterilizing the autograft. As our experience with the technique gradually grew, the answers to the above-mentioned factors were determined. Considering the removal of autograft as the endpoint of interest, survival of the autograft was determined by Kaplan-Meier analysis.The median (range) patient age was 14 years (2 to 49), and 54% (22 of 41) were males. Osteosarcoma was the most common diagnosis (68%, [28 of 41]) followed by Ewing's sarcoma (20%, [8 of 41]). On presentation, 27% of patients (11 of 41) had radiological evidence of pulmonary metastasis. Tumors were seen frequently around the knee (39% [16 of 41] proximal tibia and 22% [9 of 41] distal femur). Before resection 85% (35 of 41) underwent neoadjuvant chemotherapy. Sixty-six percent (27 of 41) underwent pedicle-freezing and the remaining 34% (14 of 41) underwent free-freezing of the tumor segment of the bone. The median (range) duration of surgery was 280 minutes (210 to 510). The patients were followed up for a median (range) duration of 21 months (5 to 30); two patients were lost to follow-up. RESULTS: With gradual experience using liquid nitrogen-sterilization over time at our institution, we determined that the following factors helped us in performing liquid nitrogen-sterilization more efficiently. For every operation 15 L to 20 L of unsterilized liquid nitrogen was arranged, 1 or 2 days before the procedure, and stored in industrial-grade cryocylinders in the operating complex. During the procedure, the operating surgeons wore additional plastic aprons under the surgical gowns, surgical goggles, and rubber boots. The staff managing the liquid nitrogen in the operating room wore thermal protective gloves. For most of the pedicle freezing procedures, we used a cylindrical stainless-steel container that was 30 cm in height and 15 cm in diameter, with a narrow opening. The container was kept on a separate moveable cart that was placed next to the operating table at a slightly lower level, and it was wrapped in multiple cotton rolls, plastic sheets, surgical sheets, and a crepe bandage. For pedicle freezing of the tibia, we performed the fibular osteotomy at least 5 cm away from the planned surgical margin, roughly around the axis of rotation of the limb. The soft tissue at the base of the delivered bone segment was dissected for at least 5 cm beyond the planned surgical margin of bone, and was protected with multiple layers of cotton rolls, plastic drapes, a single roll of Esmarch and crepe bandage. The tumor segment was externally rotated during pedicle freezing for all anatomic sites (proximal tibia, distal tibia, proximal humerus, and proximal femur). The tourniquet was inflated just before pedicle freezing to prevent tumor dissemination and not before the initial incision in all pedicle freezing procedures.Thirty-nine percent of patients (16 of 41) experienced complications associated with the procedures, and 15% (6 of 41) underwent revision surgery. Early complications (occurring within 3 weeks of the index procedure) were skin necrosis in four of 16 patients, intraoperative fracture in one of 16, superficial infection in one of 16, and neurapraxia in one of 16 patients. Late complications (occurring 3 weeks or more after surgery) were resorption of the recycled bone in four of 16 patients, nonunion of the osteotomy site in two of 12, delayed union of the osteotomy site in one of 16, collapse of the recycled bone in one of 16, and local recurrence in 1 of 16 patients. Kaplan-Meier survivorship free from removal of autograft at 2 years after surgery was 92% (95% confidence interval 89 to 96). CONCLUSION: Liquid nitrogen-sterilization is an alternative technique that requires some training and experience for the surgeon to become proficient in treating primary malignant bone tumors. Because it is widely available, it may be an option worth exploring in resource-constrained environments, where allografts and endoprostheses cannot be procured. The methods we developed to address the technical challenges will require more study and experience, but we believe these observations will aid others who may wish to use and evaluate liquid nitrogen sterilization of extremity bone sarcomas. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Asunto(s)
Autoinjertos , Neoplasias de Tejido Óseo/cirugía , Nitrógeno , Procedimientos de Cirugía Plástica , Esterilización/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Extremidades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Tejido Óseo/patología , Estudios Retrospectivos , Adulto Joven
4.
J Cell Physiol ; 229(12): 2049-56, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24812032

RESUMEN

Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma.


Asunto(s)
Subunidad alfa 3 del Factor de Unión al Sitio Principal/biosíntesis , Neoplasias de Tejido Óseo/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteína Proto-Oncogénica c-fli-1/metabolismo , Proteína EWS de Unión a ARN/metabolismo , Sarcoma de Ewing/genética , Diferenciación Celular/genética , Línea Celular Tumoral , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias de Tejido Óseo/patología , Proteínas de Fusión Oncogénica/genética , Proteína Proto-Oncogénica c-fli-1/genética , Proteína EWS de Unión a ARN/genética , Sarcoma de Ewing/patología
5.
Semin Musculoskelet Radiol ; 18(3): 280-99, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24896744

RESUMEN

Spinal tumors consist of a large spectrum of various histologic entities. Multiple spinal lesions frequently represent known metastatic disease or lymphoproliferative disease. In solitary lesions primary neoplasms of the spine should be considered. Primary spinal tumors may arise from the spinal cord, the surrounding leptomeninges, or the extradural soft tissues and bony structures. A wide variety of benign neoplasms can involve the spine including enostosis, osteoid osteoma, osteoblastoma, aneurysmal bone cyst, giant cell tumor, and osteochondroma. Common malignant primary neoplasms are chordoma, chondrosarcoma, Ewing sarcoma or primitive neuroectodermal tumor, and osteosarcoma. Although plain radiographs may be useful to characterize some spinal lesions, magnetic resonance imaging is indispensable to determine the extension and the relationship with the spinal canal and nerve roots, and thus determine the plan of management. In this article we review the characteristic imaging features of extradural spinal lesions.


Asunto(s)
Neoplasias de la Columna Vertebral/patología , Enfermedades Óseas/patología , Condrosarcoma/patología , Cordoma/patología , Diagnóstico por Imagen , Hemangioma/patología , Histiocitosis de Células de Langerhans/patología , Humanos , Neoplasias de Tejido Óseo/patología , Tumores Neuroectodérmicos Primitivos/patología
6.
Sci Rep ; 10(1): 21319, 2020 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-33288803

RESUMEN

The distal femur is the predominant site for benign bone tumours and a common site for fracture following tumour removal or cementation. However, the lack of conclusive assessment criterion for post-operative fracture risk and appropriate devices for cement augmentation are serious concerns. Hence, a validated biomechanical tool was developed to assess bone strength, depending on the size and location of artificially created tumorous defects in the distal femora. The mechanics of the bone-cement interface was investigated to determine the main causes of reconstruction failure. Based on quantitative-CT images, non-linear and heterogeneous finite element (FE) models of human cadaveric distal femora with simulated tumourous defects were created and validated using in vitro mechanical tests from 14 cadaveric samples. Statistical analyses demonstrated a strong linear relationship (R2 = 0.95, slope = 1.12) with no significant difference between bone strengths predicted by in silico analyses and in vitro tests (P = 0.174). FE analyses showed little reduction in bone strength until the defect was 35% or more of epiphyseal volume, and reduction in bone strength was less pronounced for laterally located defects than medial side defects. Moreover, the proximal end of the cortical window and the most interior wall of the bone-cement interface were the most vulnerable sites for reconstruction failure.


Asunto(s)
Legrado , Fémur/patología , Fémur/cirugía , Neoplasias de Tejido Óseo/patología , Neoplasias de Tejido Óseo/cirugía , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Humanos , Medición de Riesgo
7.
Acta Radiol ; 50(5): 531-42, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19353343

RESUMEN

Calvarial lesions are frequently identified in radiological studies. A wide variety of neoplasms and non-neoplastic lesions can involve the calvarium, and their imaging appearances vary according to their pathologic features. These lesions are usually asymptomatic but may manifest as a lump with or without associated pain. Clinical information, including the age of patient, is an important factor in the diagnostic process. In this paper, we illustrate the value of cross-sectional imaging techniques by computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating these lesions. We also review the literature and discuss the specific imaging characteristics of the most common calvarial lesions in order to provide information that can guide radiological diagnosis or limit differential diagnosis.


Asunto(s)
Hemangioma/diagnóstico , Imagen por Resonancia Magnética/métodos , Neoplasias de Tejido Óseo/diagnóstico , Neoplasias Craneales/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Hemangioma/diagnóstico por imagen , Hemangioma/patología , Humanos , Neoplasias de Tejido Óseo/diagnóstico por imagen , Neoplasias de Tejido Óseo/patología , Noruega , Cráneo/diagnóstico por imagen , Cráneo/patología , Neoplasias Craneales/diagnóstico por imagen , Neoplasias Craneales/patología
8.
Pathol Res Pract ; 203(9): 633-40, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17728073

RESUMEN

Heterotopic ossification (HO) within tissues involved by a pathologic process is a well-recognized phenomenon. It is most frequently observed in atherosclerotic plaques, in soft tissue around joints, and in the central nervous system. Less frequently, carcinomas and some benign neoplasms will undergo heterotopic ossification. We performed a retrospective review of our experience with HO over a 10-year period to determine the frequency and tissue site distribution of heterotopic ossification. A computerized review of surgical pathology records of approximately 126,000 reports revealed 85 cases in which heterotopic ossification, ectopic bone or metaplastic bone was specifically mentioned in the surgical pathology diagnosis. Twenty-two cases were neoplasms of non-osseous tissues, and 63 cases were non-neoplastic lesions. Immunohistochemical staining for bone morphogenic proteins (BMP) 1, 4, and 6 was performed. Fourteen cases showed staining for BMP-1, 22 cases showed staining for BMP-4, and five cases showed weak staining for BMP-6. HO is a relatively infrequent finding and is more commonly seen in degenerative and reparative conditions than in neoplasms.


Asunto(s)
Artritis/patología , Aterosclerosis/patología , Proteínas Morfogenéticas Óseas/análisis , Neoplasias de Tejido Óseo/patología , Osificación Heterotópica/patología , Artritis/metabolismo , Aterosclerosis/metabolismo , Proteína Morfogenética Ósea 1 , Proteína Morfogenética Ósea 4 , Proteína Morfogenética Ósea 6 , Humanos , Metaloendopeptidasas/análisis , Necrosis , Neoplasias de Tejido Óseo/química , Osificación Heterotópica/metabolismo , Estudios Retrospectivos , Membrana Sinovial/química , Membrana Sinovial/patología
9.
Pathol Res Pract ; 203(6): 473-7, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17537587

RESUMEN

Extraskeletal osteosarcoma (EOS) is a highly aggressive and exceedingly rare mesenchymal tumor. Due to the rare nature of the disease, the diagnosis can be difficult and is often confirmed only after diagnostic laparotomy and histopathology. We describe the clinical history, radiologic and histomorphologic presentation, and clinical management of a 61-year-old patient who presented with abdominal pain. Abdominal ultrasound and computerized tomography (CT) scan revealed a calcified intra-abdominal mass. Following an explorative laparotomy, histology showed a large extraosseous osteosarcoma of the small bowel mesentery. Therapy according to the Cooperative Sarcoma Study-96 (COSS-96) was commenced. Diagnosis, management, and outcome in the context of the current literature are discussed. To our knowledge, this is the first description of an extraosseous osteosarcomas in the small bowel mesentery in the literature.


Asunto(s)
Calcinosis/diagnóstico , Neoplasias Intestinales/diagnóstico , Neoplasias de Tejido Óseo/diagnóstico , Osteosarcoma/diagnóstico , Neoplasias Peritoneales/diagnóstico , Calcinosis/patología , Calcinosis/terapia , Terapia Combinada , Diagnóstico Diferencial , Resultado Fatal , Humanos , Neoplasias Intestinales/patología , Neoplasias Intestinales/terapia , Intestino Delgado/patología , Masculino , Mesenterio/patología , Persona de Mediana Edad , Neoplasias de Tejido Óseo/patología , Neoplasias de Tejido Óseo/terapia , Osteosarcoma/patología , Osteosarcoma/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Tomografía Computarizada por Rayos X
11.
Pathology ; 49(5): 506-513, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28688724

RESUMEN

PD-1 and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the Unites States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently expanded the use of immunotherapy for metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and lipoma were used as control and benign counterparts. Western blot was performed to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines. Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD-1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue, skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the presence of PD-1 protein in all four sarcoma cell lines. Overall, our results showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while PD-L1 was negative. Whether these data are an indication for effectiveness of immunotherapy in the management of malignant bone and soft tissue sarcomas remains to be elucidated.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias de Tejido Óseo/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Sarcoma/metabolismo , Antígeno B7-H1/genética , Línea Celular Tumoral , Condrosarcoma/metabolismo , Condrosarcoma/patología , Femenino , Humanos , Liposarcoma/metabolismo , Liposarcoma/patología , Masculino , Neoplasias de Tejido Óseo/patología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Receptor de Muerte Celular Programada 1/genética , Rabdomiosarcoma/metabolismo , Rabdomiosarcoma/patología , Sarcoma/patología , Análisis de Matrices Tisulares
12.
Mol Cancer Res ; 15(12): 1714-1721, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28860121

RESUMEN

Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT) are rate-limiting enzymes in the NAD+ synthesis pathway. Chondrosarcoma is a malignant cartilage forming bone tumor, in which mutations altering isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) activity have been identified as potential driver mutations. Vulnerability for NAD+ depletion has been reported for IDH1/2-mutant cells. Here, the potency of NAMPT inhibitors as a treatment of chondrosarcoma was explored. Eleven chondrosarcoma cell lines were treated with NAMPT inhibitors, in which the effect on cell viability, colony formation, and 3D collagen invasion was assessed. The expression level of NAMPT and NAPRT transcripts in chondrosarcoma cells was determined by qRT-PCR. Methylation of the NAPRT promoter was evaluated using a previously published dataset of genome-wide methylation. In addition, a methylation dataset was used to determine methylation of the NAPRT promoter in 20 IDH1/2-mutated cartilage tumors. Chondrosarcoma cells showed a dose-dependent decrease in cell viability, 3D collagen invasion, and colony formation upon treatment with NAMPT inhibitors, in which nearly half of the cell lines demonstrated absolute IC50s in the low nanomolar range. Increasing IC50s correlated to increasing NAPRT expression levels and decreasing NAPRT promoter methylation. No correlation between IDH1/2 mutation status and sensitivity for NAMPT inhibitors was observed. Strikingly, higher methylation of the NAPRT promoter was observed in high-grade versus low-grade chondrosarcomas. In conclusion, this study identified NAMPT as a potential target for treatment of chondrosarcoma.Implications: Chondrosarcoma patients, especially those of high histologic grade with lower expression and hypermethylation of NAPRT, may benefit from inhibition of the NAD synthesis pathway. Mol Cancer Res; 15(12); 1714-21. ©2017 AACR.


Asunto(s)
Condrosarcoma/genética , Citocinas/genética , Isocitrato Deshidrogenasa/genética , Neoplasias de Tejido Óseo/genética , Nicotinamida Fosforribosiltransferasa/genética , Pentosiltransferasa/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/patología , Citocinas/antagonistas & inhibidores , Inhibidores Enzimáticos/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Mutación , NAD/antagonistas & inhibidores , NAD/biosíntesis , NAD/genética , Invasividad Neoplásica/genética , Neoplasias de Tejido Óseo/tratamiento farmacológico , Neoplasias de Tejido Óseo/patología , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Pentosiltransferasa/antagonistas & inhibidores , Regiones Promotoras Genéticas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
13.
Hum Pathol ; 58: 24-34, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27498059

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Neoplasias Óseas/metabolismo , Neoplasias de Tejido Óseo/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Fosfatasa Alcalina/metabolismo , Biopsia , Neoplasias Óseas/patología , Diferenciación Celular , Línea Celular Tumoral , Condroma/metabolismo , Condroma/patología , Condrosarcoma/metabolismo , Condrosarcoma/patología , Marcadores Genéticos , Humanos , Inmunohistoquímica , Neoplasias de Tejido Óseo/patología , Osteoblastoma/metabolismo , Osteoblastoma/patología , Osteogénesis , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Estudios Retrospectivos , Vía de Señalización Wnt
14.
Radiol Clin North Am ; 36(6): 1241-59, xii, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9884700

RESUMEN

Fibro-osseous and cartilaginous lesions of the orbit and facial region share overlapping clinical, radiologic, and pathologic features that may lead to diagnostic confusion and possible misdiagnosis. The value of imaging studies in the histopathologic diagnosis of these lesions cannot be overemphasized. The histopathologic diagnosis of such lesions should not be rendered in the absence of radiographic correlation.


Asunto(s)
Imagen por Resonancia Magnética , Enfermedades Orbitales/diagnóstico , Neoplasias Orbitales/diagnóstico , Tomografía Computarizada por Rayos X , Enfermedades de los Cartílagos/diagnóstico , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/patología , Diagnóstico Diferencial , Displasia Fibrosa Ósea/diagnóstico , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Ósea/patología , Tumor Óseo de Células Gigantes/diagnóstico , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Tumor Óseo de Células Gigantes/patología , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/diagnóstico por imagen , Granuloma de Células Gigantes/patología , Humanos , Neoplasias de Tejido Óseo/diagnóstico , Neoplasias de Tejido Óseo/diagnóstico por imagen , Neoplasias de Tejido Óseo/patología , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/diagnóstico por imagen , Neoplasias de Tejido Conjuntivo/patología , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/patología , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/patología
15.
Top Magn Reson Imaging ; 13(4): 219-29, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12409690

RESUMEN

A benign bone lesion may have a typical appearance on plain radiographs. This is the case with benign cortical defects and osteochondroma. With most other lesions, cross-sectional imaging is needed to complete the study of the tumor. The nidus of osteoid osteoma is well demonstrated on computed tomography, but magnetic resonance imaging also will show the nidus in most cases. Magnetic resonance imaging is considered the modality of choice for evaluation of other benign musculoskeletal lesions because it is highly sensitive to changes in the signal intensity of bone marrow and adjacent soft tissues. It provides useful information for diagnosis of the lesion as in primary or secondary aneurysmal bone cyst, chondroblastoma, osteoblastoma, fibrous dysplasia, and osteofibrous dysplasia, and it helps differentiate these lesions from osteomyelitis, Langerhans' cell histiocytosis, and stress fracture. Bone scanning is most useful for depicting multiple silent lesions as may be seen in multiple osteochondromatosis, nonossifying fibromas, and polyostotic fibrous dysplasia.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Neoplasias de Tejido Óseo/diagnóstico , Adolescente , Quistes Óseos Aneurismáticos/diagnóstico , Quistes Óseos Aneurismáticos/patología , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Displasia Fibrosa Ósea/diagnóstico , Displasia Fibrosa Ósea/patología , Humanos , Lactante , Masculino , Neoplasias de Tejido Óseo/patología
16.
Pathol Res Pract ; 195(11): 753-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10605695

RESUMEN

To assess the role and status of telomerase activity in benign bone tumors and tumor-like lesions, we performed telomerase assays in four giant cell tumors of bone, four fibrous dysplasias, three osteochondromas, three aneurysmal bone cysts, two osteoblastomas, one juvenile bone cyst and one myositis ossificans. A very sensitive non-radioactive TRAP assay was applied. Low level activity was detected in 7 of 18 tumor samples (38.9%), and high level activity was not detected in any of the cases. Telomerase activity was observed in all patients with osteochondromas, in two of the three aneurysmal bone cysts, in one of the four giant cell tumors of bone and in one of the four fibrous dysplasias, but not in osteoblastomas, juvenile bone cyst and myositis ossificans. Although the origin of this enzyme is still unclear, it might play a role in precancerous immortalization of benign bone tumors. Other possible reasons explaining the occurrence of telomerase activity, such as migrating lymphocytes or contamination of immortalized non-tumor cells, should not be ruled out. Telomerase activity, however, does exist in those samples having no malignant phenotype, for which reason telomerase assays are not always useful for the clinical and diagnostic approach in benign bone tumors. Determination of the telomerase status in benign lesions may contribute to a better understanding of the regulation mechanism of telomerase activity during progression of bone tumors.


Asunto(s)
Neoplasias Óseas/enzimología , Neoplasias de Tejido Óseo/enzimología , Telomerasa/metabolismo , Adolescente , Adulto , Quistes Óseos Aneurismáticos/enzimología , Quistes Óseos Aneurismáticos/genética , Quistes Óseos Aneurismáticos/patología , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular , Niño , Femenino , Displasia Fibrosa Ósea/enzimología , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/patología , Tumor Óseo de Células Gigantes/enzimología , Tumor Óseo de Células Gigantes/genética , Tumor Óseo de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Miositis Osificante/enzimología , Miositis Osificante/genética , Miositis Osificante/patología , Neoplasias de Tejido Óseo/genética , Neoplasias de Tejido Óseo/patología , Osteocondroma/enzimología , Osteocondroma/genética , Osteocondroma/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
17.
J Formos Med Assoc ; 98(3): 218-21, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10365544

RESUMEN

Dense calcification and psammomatous bodies are common in spinal meningioma, but are rarely reported in osteogenic meningioma. We present a 73-year-old woman with an extramedullary, intradural tumor located at the T5 vertebra. The tumor showed mixed intensity and heterogeneous enhancement on the T1-weighted image and hypointensity on the T2-weighted image, and was situated near the spinal nerve root. The tumor's initial symptom was myelopathy, as is usual with spinal meningioma. We successfully removed the tumor under microscopy and found it to be separated from the vertebral column by the epidural space. The symptoms and signs improved gradually after the operation. Because the pathologic examination revealed areas of lamellar bone with bone marrow in the transitional meningioma, and because these were not related to the psammomatous bodies, osteogenic meningioma was diagnosed. Metaplasia of arachnoid cells is considered to be the putative etiology of osteogenic meningioma.


Asunto(s)
Meningioma/patología , Neoplasias de Tejido Óseo/patología , Anciano , Femenino , Humanos , Meningioma/cirugía , Neoplasias de Tejido Óseo/cirugía
18.
J Am Osteopath Assoc ; 96(7): 419-21, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8758875

RESUMEN

Metaplastic breast carcinoma, a rare entity, accounts for only about 0.02% of all breast carcinomas. It involves the transformation of mammary neoplasms into osteoid and chondroid substances. Because of the relatively small patient population and the limited number of controlled studies, there is confusion regarding its classification and staging. Its histogenesis is unknown. The authors describe a 65-year-old woman with findings consistent with metaplastic breast carcinoma. Theories as to etiology and prognosis as well as treatment are discussed.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Adenoescamoso/patología , Carcinoma/patología , Neoplasias de Tejido Óseo/patología , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Carcinoma/cirugía , Carcinoma Adenoescamoso/cirugía , Femenino , Humanos , Mamografía , Mastectomía Radical , Metaplasia/patología , Neoplasias de Tejido Óseo/cirugía , Pronóstico
19.
Clin Podiatr Med Surg ; 10(4): 683-715, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8221546

RESUMEN

Topics discussed in this article include osteogenic sarcoma, osteoid osteoma, osteoblastoma, chondrosarcoma, chondromyxoid fibroma, chondroblastoma, chondroma, Ollier's disease, Maffucci's syndrome, osteochondroma, hereditary multiple exostoses, unicameral bone cyst, fibrous dysplasia, Albright's syndrome, nonossifying fibroma, giant cell tumor, Ewing's sarcoma, and metastasis. Numerous radiographs, CT scans, MR images, arteriograms, and photomicrographs supplement the text.


Asunto(s)
Neoplasias Óseas/diagnóstico , Enfermedades del Pie/diagnóstico , Neoplasias Óseas/patología , Diagnóstico Diferencial , Enfermedades del Pie/patología , Humanos , Neoplasias de Tejido Óseo/diagnóstico , Neoplasias de Tejido Óseo/patología , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/patología
20.
Artículo en Francés | MEDLINE | ID: mdl-8159840

RESUMEN

Twelve patients presenting with a bone tumor were operated on using autoclaved bone autografts for reconstruction following carcinologic resection. According to the Enneking grading system, 6 were high malignancy tumors (3 osteosarcomas and 3 grade 2 chondrosarcomas), 4 were low grade tumors (1 paraosteal sarcoma, 1 chondrosarcoma, 1 secondary chondrosarcoma, 1 liposarcoma). One was a metastasis from a kidney tumor. The last patient had a femoral osteoid osteoma. Six local recurrences were responsible for 4 reoperations: 2 disarticulations and 2 iterative resections. With a 1-6 years range of follow-up (average follow-up 2.5 years), osseointegration of autoclaved grafts was studied. Fusion at the host/graft junction was roentgenographically observed. In three cases, proximal resorption of the humeral graft occurred. Five biopsies were obtained during reoperation after 1 year, which showed partial revascularization of autoclaved bone autografts. The authors conclude that autoclaved tumoral bone grafts, are reliable and discuss indications. They point out the main contraindication, represented by chemosensitive bone tumors, in which conservation of the removed tumor is necessary to quantify the response to chemotherapy.


Asunto(s)
Neoplasias Óseas/cirugía , Trasplante Óseo/métodos , Neoplasias de Tejido Óseo/cirugía , Adolescente , Adulto , Neoplasias Óseas/patología , Condrosarcoma/patología , Condrosarcoma/cirugía , Femenino , Estudios de Seguimiento , Calor , Humanos , Liposarcoma/patología , Liposarcoma/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de Tejido Óseo/patología , Oseointegración , Osteosarcoma/patología , Osteosarcoma/cirugía , Conservación de Tejido/métodos , Trasplante Autólogo
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