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Sample records for well-differentiated extraskeletal osteosarcoma

  1. Extraskeletal osteosarcoma arising in myositis ossificans

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    Konishi, Eiichi [Div. of Anatomic Pathology, Kyoto Prefectural University of Medicine (Japan); Kusuzaki, Katsuyuki; Murata, Hiroaki [Dept. of Orthopedic Surgery, Kyoto Prefectural University of Medicine (Japan); Tsuchihashi, Yasunari [Hospital Department of Pathology, Kyoto Prefectural University of Medicine (Japan); Beabout, J.W. [Dept. of Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, MN (United States); Unni, K.K. [Division of Anatomic Pathology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905 (United States); Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States)

    2001-01-01

    A 53-year-old woman had extraskeletal osteosarcoma that developed from a soft tissue bony mass present on the volar aspect of the left wrist for 4 years. Initially, the bony mass was soft and movable, but during the first year it became hard and fixed. The patient had no history of trauma. Because the lesion did not grow or cause any symptoms, the patient did not come to the hospital until 4 years after she first noticed the lesion. Radiologically, the bony mass had features characteristic of mature myositis ossificans, showing ''eggshell'' ossification. A nonmineralized soft tissue mass occurred between the surface of the radius and the bony shell. Histologically, a high-grade osteosarcoma was present between the surface of the radius and the well-differentiated bone tissue, which included fatty and hematopoietic marrow. All the findings indicated that our patient had an extremely rare case of malignant transformation of myositis ossificans. (orig.)

  2. Extraskeletal osteosarcoma arising in myositis ossificans

    International Nuclear Information System (INIS)

    Konishi, Eiichi; Kusuzaki, Katsuyuki; Murata, Hiroaki; Tsuchihashi, Yasunari; Beabout, J.W.; Unni, K.K.

    2001-01-01

    A 53-year-old woman had extraskeletal osteosarcoma that developed from a soft tissue bony mass present on the volar aspect of the left wrist for 4 years. Initially, the bony mass was soft and movable, but during the first year it became hard and fixed. The patient had no history of trauma. Because the lesion did not grow or cause any symptoms, the patient did not come to the hospital until 4 years after she first noticed the lesion. Radiologically, the bony mass had features characteristic of mature myositis ossificans, showing ''eggshell'' ossification. A nonmineralized soft tissue mass occurred between the surface of the radius and the bony shell. Histologically, a high-grade osteosarcoma was present between the surface of the radius and the well-differentiated bone tissue, which included fatty and hematopoietic marrow. All the findings indicated that our patient had an extremely rare case of malignant transformation of myositis ossificans. (orig.)

  3. A low-grade extraskeletal osteosarcoma

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    Okada, Kyoji; Ito, Hiroki; Miyakoshi, Naohisa; Itoi, Eiji [Department of Orthopedic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Sageshima, Masato [Department of Clinical Pathology, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543 (Japan); Nishida, Jun [Department of Orthopedic Surgery, Iwate Medical School, 19-1 Uchimaru, Morioka 020-8505 (Japan)

    2003-03-01

    The case of a 35-year-old woman with low-grade extraskeletal osteosarcoma of the left leg is presented. Radiographs showed peripheral ossification of the lesion, suggesting myositis ossificans. Most of the tumor was composed of cartilage, and the cellularity and cell atypia of the proliferating chondrocytes were mild to moderate. In the periphery, bone formation with a relatively clear margin and proliferation of spindle cells with minimal nuclear atypia were observed. The average percentage of cells positive for MIB-1 was 9.0%. A diagnosis of low-grade extraskeletal osteosarcoma was made on the basis of these histologic findings. The clinical course 47 months after a wide excision was uneventful. (orig.)

  4. Mesenteric extraskeletal osteosarcoma with telangiectatic features: a case report

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    Choi Chan

    2007-05-01

    Full Text Available Abstract Background Extraskeletal osteosarcoma is a rare malignant mesenchymal tumor, with a predominant occurrence in the extremities. Only two cases of mesenteric extraskeletal osteosarcoma have been documented. We describe an unusual case of extraskeletal osteosarcoma with telangiectatic features occurring in the mesentery. Case presentation A 67-year-old male presented with blood-tinged stool of 1-month's duration. On colonoscopy, a solid mass was detected protruding from the colon wall. Computed tomography showed a 15 × 9.7 cm heterogeneously enhancing mass, with mottled calcification and a cystic portion, occupying the left upper quadrant of the abdominal cavity. Curative resection of the tumor was performed, and the excised tumor was composed of large multilocular cysts containing old hematomas and necrotic debris. The histology revealed an osteosarcoma showing osteoid formation and blood-filled spaces lined with atypical cells. Despite postoperative chemotherapy, he developed a recurrent peritoneal mass and multiple lung metastases 3 months postoperatively. Conclusion Given the rarity of cases of mesenteric extraskeletal osteosarcoma, its biologic behavior at this location remains to be determined. However, extraskeletal osteosarcoma with telangiectatic features is an uncommon entity to be recognized because of the possible fatal outcome related to the tumors.

  5. Primary mesenteric extraskeletal osteosarcoma in the pelvic cavity

    International Nuclear Information System (INIS)

    Choudur, H.N.; Munk, P.L.; Ryan, A.G.M.J.; Nielson, T.O.

    2005-01-01

    A middle-aged man was being investigated for constipation. Abdominal radiographs incidentally revealed a large, densely calcified, rounded mass within the pelvic cavity. A CT scan was performed followed by surgical excision with a differential diagnosis of calcified hematoma and an enlarged calcified lymph nodal mass. Histopathological investigation revealed a primary mesenteric extraskeletal osteosarcoma. To the best of our knowledge, a primary extraskeletal osteosarcoma arising from the mesentery has not been described previously in the English literature. The radiological features and differential diagnosis are discussed. (orig.)

  6. Primary mesenteric extraskeletal osteosarcoma in the pelvic cavity

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    Choudur, H.N.; Munk, P.L.; Ryan, A.G.M.J. [Vancouver General Hospital, Department of Radiology, Vancouver, BC (Canada); Nielson, T.O. [Vancouver General Hospital, Department of Pathology, Vancouver, BC (Canada)

    2005-10-01

    A middle-aged man was being investigated for constipation. Abdominal radiographs incidentally revealed a large, densely calcified, rounded mass within the pelvic cavity. A CT scan was performed followed by surgical excision with a differential diagnosis of calcified hematoma and an enlarged calcified lymph nodal mass. Histopathological investigation revealed a primary mesenteric extraskeletal osteosarcoma. To the best of our knowledge, a primary extraskeletal osteosarcoma arising from the mesentery has not been described previously in the English literature. The radiological features and differential diagnosis are discussed. (orig.)

  7. Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma

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    Sheila Thampi

    2014-01-01

    Full Text Available Background. Extraskeletal osteosarcoma (ESOS is a rare subtype of osteosarcoma. We investigated patient characteristics, overall survival, and prognostic factors in ESOS. Methods. We identified cases of high-grade osteosarcoma with known tissue of origin in the Surveillance, Epidemiology, and End Results database from 1973 to 2009. Demographics were compared using univariate tests. Overall survival was compared with log-rank tests and multivariate analysis using Cox proportional hazards methods. Results. 256/4,173 (6% patients with high-grade osteosarcoma had ESOS. Patients with ESOS were older, were more likely to have an axial tumor and regional lymph node involvement, and were female. Multivariate analysis showed ESOS to be favorable after controlling for stage, age, tumor site, gender, and year of diagnosis [hazard ratio 0.75 (95% CI 0.62 to 0.90; p=0.002]. There was an interaction between age and tissue of origin such that older patients with ESOS had superior outcomes compared to older patients with skeletal osteosarcoma. Adverse prognostic factors in ESOS included metastatic disease, larger tumor size, older age, and axial tumor site. Conclusion. Patients with ESOS have distinct clinical features but similar prognostic factors compared to skeletal osteosarcoma. Older patients with ESOS have superior outcomes compared to older patients with skeletal osteosarcoma.

  8. Extraskeletal Osteosarcoma of the Thigh: An Autopsy Case Report

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    Akihito Nagano

    2009-01-01

    Full Text Available We report a case of extraskeletal osteosarcoma (ESOS and autopsy findings. A 35-year-old man presented with an ossified tumor in the right thigh and lung metastasis. The lung tumors continued to develop despite multiagent chemotherapy and caused death within 8 months. Autopsy revealed many secondary lesions in the lungs, especially in the left lung. Histopathologically, the primary tumor and one of the secondary tumors showed proliferation of spindle-shaped tumor cells focally forming lace-like osteoid material. Therefore, we made a definite diagnosis of ESOS.

  9. Small cell extraskeletal osteosarcoma: a rare case report

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    Neelam Sood

    2014-01-01

    Full Text Available Extraskeletal osteosarcoma is a rare malignant mesenchymal neoplasm and its small cell variant is one among the rarest variant. This article describes a 60-year-old woman presenting with a large, lobulated, painful mass in left thigh with associated history of trauma since 18 months. Her magnetic resonance imaging showed a variegated mixed intensity lesion with associated cystic degeneration, necrosis and matrix arborizing nearby muscles. Fine needle aspiration cytology showed a small cell lesion with very scant osteoid. Tumor was excised and histopathological diagnosis was small cell osteosarcoma involving adjacent muscles and fat with sparing of lymph nodes. The aim of this article is to present the clinical, radiological, cyto-histological and immunohistochemical features of this extremely rare lesion.

  10. Canine spirocercosis-associated extraskeletal osteosarcoma with central nervous system metastasis

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    Paolo Pazzi

    2013-04-01

    Full Text Available A five-year-old male Boerboel presented for examination, collapsed for an unknown period of time. On clinical examination, multifocal subcutaneous masses and enlarged prescapular lymph nodes as well as neurological deficits that suggested a multifocal neurological syndrome were found. Fine needle aspirates of the prescapular lymph nodes revealed cells suggestive of osteosarcoma. Radiographs showed foci of mineralisation within the soft tissue masses as well as diffuse pulmonary metastasis and a caudodorsal mediastinal mass believed to be a Spirocerca lupi nodule. Computed tomography imaging, necropsy and histopathology confirmed S. lupi oesophageal neoplastic transformation (extraskeletal osteosarcoma, believed to be the primary lesion, and the majority of secondary metastasis to the brain, spine, heart, multiple muscular groups and abdominal organs. This is the first known report of extraskeletal osteosarcoma metastasis to the brain and spinal cord in a dog.

  11. Extraskeletal osteosarcoma in the neck. A case report and review of the literature; Osteosarcoma extra-esqueletico na regiao cervical. Revisao de literatura e relato de caso clinico

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    Lima, Jose Jorge Gomes; Silva, Fabio Luis da [Santa Casa de Misericordia, Piracicaba, SP (Brazil). Centro de Tomografia Computadorizada; Manzi, Flavio Ricardo [Pontificia Univ. Catolica de Minas Gerais, Belo Horizonte, MG (Brazil). Radiologia Odontologica; Baptista, Mauricio Zuccollotto [Santa Casa de Misericordia, Piracicaba, SP (Brazil). Inst. de Oncologia Clinica

    2002-10-01

    Extra skeletal osteosarcoma is a rare neoplasm characterized by the formation of a malignant osteoid. This condition is usually described in patients aged greater than expected for other intraosseous osteosarcomas, and the thigh is the most common site. We report a clinical case of a 19-year-old female patient and review the literature. The patient present with a mass in the right side of the neck and paraesthesia of the upper limbs. The mass corresponded to an extraskeletal osteosarcoma. We discuss the clinical findings, image findings (conventional radiographs, computed tomography, magnetic resonance imaging), histopathology results and differential diagnosis of this condition. (author)

  12. Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature.

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    Sabatier, Renaud; Bouvier, Corinne; de Pinieux, Gonzague; Sarran, Anthony; Brenot-Rossi, Isabelle; Pedeutour, Florence; Chetaille, Bruno; Viens, Patrice; Weiller, Pierre-Jean; Bertucci, François

    2010-11-24

    Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare. We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of MDM2 and CDK4 oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms. We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.

  13. Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

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    Chetaille Bruno

    2010-11-01

    Full Text Available Abstract Background Low-grade extraskeletal osteosarcomas (ESOS are extremely rare. Case presentation We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of MDM2 and CDK4 oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms. Conclusion We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.

  14. Osteossarcoma extra-esquelético primário da região frontal Extraskeletal primary osteosarcoma of the frontal region

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    M.A. Lima

    1998-03-01

    Full Text Available OBJETIVO: Osteossarcoma extra-esquelético (OSEE primário de partes moles da cabeça é raro e não há, ao que nos parece, relato dele originando na região frontal. MÉTODOS: Homem de 78 anos, italiano, com história de tumoração em partes moles de região frontal há um mês. Tomografia computadorizada mostrou massa de densidade irregular ocupando tecido celular subcutâneo e fáscia. Nenhum tumor ósseo foi encontrado. A tumoração foi completamente ressecada, media 0,8x0,6x0,5cm, e a superfície de corte era sólida. Diagnosticou-se osteossarcoma osteoblástico extra-esquelético. A neoplasia recorreu quatro meses após o diagnóstico e foi novamente ressecado. O paciente foi submetido também a radioterapia de baixa penetração, e nove meses depois da primeira biópsia tinha sintomas em decorrência da infiltração neoplásica na base do crânio. O óbito ocorreu dez meses após a primeira biópsia. CONCLUSÃO: Os autores descrevem o primeiro caso de OSEE da região frontal sem uma condição preexistente ou história de irradiação.BACKGROUND: Extraskeletal osteosarcoma (ESOS in the head as a primary site has seldom been re-ported and none in the frontal region. METHODS: A 78-year-old Italian man presented with one month history of a frontal soft tissue mass. A CT scan showed a mass of uneven density occupying the subcutaneous soft tissue and involving fascial planes. No primary bone tumor was found. The entire mass was excised. The mass was solid measuring 0.8 x 0.6 x 0.5cm. Extraskeletal osteoblastic osteosarcoma was diagnosed by ligh microscopy. The tumor recurred four months after the diagnosis. The tumor was again ressected. The patient was also submitted to low penetration radiation therapy. Nine months after the first biopsy the patient had symptoms due to infiltration to the base of the cranium. He died 10 months after the first biopsy. CONCLUSIONS: The first case with ESOS of the frontal region without a pre

  15. Primary renal osteosarcoma: A case report

    African Journals Online (AJOL)

    C. Ahomadégbé

    Primitive renal osteosarcoma is a rare sarcoma of the kidney with only 27 cases reported in the literature. Its histogenesis .... low-grade extraskeletal osteosarcoma. Skeletal ... et al. Primary Ewing's sarcoma/primitive neuroectodermal tumor of.

  16. Osteossarcoma extra-esquelético na região cervical: revisão da literatura e relato de caso clínico Extraskeletal osteosarcoma in the neck: a case report and review of the literature

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    José Jorge Gomes Lima

    2002-10-01

    Full Text Available O osteossarcoma extra-esquelético é uma neoplasia rara caracterizada pela produção de osteóide "maligno". Esta condição tem sido descrita em faixa etária acima da esperada para o osteossarcoma ósseo, e a coxa é o local de predileção. Realizamos revisão da literatura e descrevemos o caso clínico de uma paciente de 19 anos de idade com história de massa na região cervical direita associada a parestesia dos membros superiores, a qual foi diagnosticada como portadora de osteossarcoma extra-esquelético. Enfatizamos as características clínicas, os aspectos das imagens em diversos métodos empregados (exames radiográficos convencionais, tomografia computadorizada, exame por ressonância magnética, análise histopatológica e os principais diagnósticos diferenciais desta afecção.Extraskeletal osteosarcoma is a rare neoplasm characterized by the formation of a malignant osteoid. This condition is usually described in patients aged greater than expected for other intraosseous osteosarcomas, and the thigh is the most common site. We report a clinical case of a 19-year-old female patient and review the literature. The patient presented with a mass in the right side of the neck and paresthesia of the upper limbs. The mass corresponded to an extraskeletal osteosarcoma. We discuss the clinical findings, image findings (conventional radiographs, computed tomography, magnetic resonance imaging, histopathology results and differential diagnosis of this condition.

  17. Cutaneous osteosarcoma arising from a burn scar

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    Lee, Min A.; Yi, Jaehyuck [Kyungpook National University, Department of Radiology, College of Medicine, Daegu (Korea, Republic of); Kyungpook National University Hospital, Department of Radiology, Daegu (Korea, Republic of); Chae, Jong Min [Kyungpook National University, Department of Pathology, College of Medicine, Daegu (Korea, Republic of)

    2017-04-15

    Tumors that develop in old burn scars are usually squamous cell carcinomas. Sarcomas have also been reported, albeit rarely. To our knowledge, there has been only one case report of an extraskeletal osteosarcoma arising in a prior burn scar reported in the English-language literature, mainly discussing the clinicopathological features. Herein, we present a case of cutaneous osteosarcoma visualized as a mineralized soft-tissue mass arising from the scar associated with a previous skin burn over the back. This seems to be the first report describing the imaging features of a cutaneous osteosarcoma from an old burn scar. (orig.)

  18. Well differentiated endocrine carcinomas of the pancreas

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    Čolović Radoje

    2011-01-01

    Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

  19. Extraskeletal effects of vitamin D

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    Maurizio Rossini

    2011-04-01

    Full Text Available In the last years we observed an increasing number of publications about the vitamin D, due to its recognised therapeutic actions and to the widespread hypovitaminosis D. In addition to the well known skeletal benefits, vitamin D can have multiple effects on other tissues.Muscular apparatus: hypovitaminosis D is associated with myopathy, sarcopenia, muscular strength reduction and increased risk of falls. The vitamin D supplementation increases the muscle functionality indexes. Cardiovascular system: low levels of vitamin D are related to increased levels of cardiovascular risk factors, heart failure, stroke, and cardiovascular mortality, while a good vitamin D status is associated with a decreased incidence of cardiovascular diseases. Diabetes and metabolic syndrome: a good vitamin D status is related to a decreased incidence of type 2 diabetes and metabolic syndrome; a vitamin D supplementation in the early childhood reduces (nearly 30% the risk of having type 1 diabetes. Cancer: vitamin D deficit is associated with breast, colorectal cancer and melanoma relapses. Low and high levels of 25-hydroxy-vitamin D (25(OHD are related to a higher neoplastic mortality. Infectious diseases: hypovitaminosis D is associated with higher incidence of upper respiratory tract infections and worse interferon response in chronic hepatitis C. Vitamin D supplementation decreases the risk of having type A influence. Rheumatic diseases: in rheumatoid arthritis low serum levels of vitamin D metabolites are related to a higher disease activity, while a good vitamin D status is associated with a higher probability of remission or response to therapy and a lower degree of disability. Neurologic diseases: associations between vitamin D deficit and risk of multiple sclerosis, depression, cognitive deficits, and Parkinson’s disease have been reported.There is evidence of the extraskeletal effects of vitamin D, but most derive from observational studies: clinical trials

  20. A large extraskeletal osteochondroma of the foot.

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    Estil, Jose Carlos C; Yeo, Eui-Dong; Kim, Hak Jun; Cho, Won Tae; Lee, Jeong-Ju

    2013-01-01

    Osteochondromas are very common benign tumors composed of cartilage and bone. They are usually found at the end of the growth plate of long bones, most often at the area of the joints, and are contiguous with the medullary cavity. Extraskeletal osteochondromas, the same as their namesake, are composed of cartilage and bone. However, unlike typical osteochondromas, extraskeletal osteochondromas are not contiguous with bone, as their name implies. They usually arise from the synovial tissue and tendon sheaths. Although rare, extraskeletal osteochondromas have been reported to occur within the knee and around the hip; however, they are more commonly reported to occur in the hands and feet. When found in the hands or feet, these new growths are often very small and only occasionally symptomatic. We present the case of a 49-year-old female who had a slow-growing mass of 4 years' duration, located on the plantar aspect of her left foot. The mass was slowly becoming more palpable as it increased in size and was progressively causing pain and discomfort during ambulation. Imaging studies revealed an ossified mass bearing no connection to any other structure on the plantar aspect of her foot. An excision biopsy was performed, and the easily dissectible mass, although much larger than its usual presentation, proved to be an extraskeletal osteochondroma. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Recurrent parosteal osteosarcoma of the talus in a 2-year-old child

    International Nuclear Information System (INIS)

    Jee, W.H.; Choe Bo-Young; Choi, K.H.; Shinn Kyung-Sub; Ok In-Young; Kim Jung-Man; Choi Yeong-Jin

    1998-01-01

    Parosteal osteosarcoma is an uncommon, low-grade malignant bone tumor and is found in an older age group than conventional osteosarcoma. We present a talar parosteal osteosarcoma that recurred twice in a 2-year-old child. To our knowledge, this is the youngest patient reported with a parosteal osteosarcoma. The talus is an unusual site for parosteal osteosarcoma. Inadequate resection due to a diagnosis of juxtacortical chondroma resulted in recurrence of the tumor. The age of the patient, the thick cartilaginous cap, and well-differentiated trabecular bone all contributed to the critical erroneous diagnosis. (orig.)

  2. Curious case of extraskeletal myxoid chondrosarcoma

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    Sushilkumar Satish Gupta

    2017-01-01

    Full Text Available Extraskeletal myxoid chondrosarcomas (EMC are a rare entity of soft tissue tumors that have slow growth with metastatic potential. We discuss here a case of EMC presenting with right upper extremity pain and hemoptysis. Computed tomography scans chest showed diffuse metastatic numerous lung nodules bilaterally. Biopsy confirmed the diagnosis of the tumor. Chemotherapy was a bigger challenge for our patient due to sparse research and data in the literature about the disease.

  3. OSTEOSARCOMA IN AFRICAN HEDGEHOGS (ATELERIX ALBIVENTRIS): FIVE CASES.

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    Reyes-Matute, Alonso; Méndez-Bernal, Adriana; Ramos-Garduño, Liliana-Aurora

    2017-06-01

    Osteosarcomas are unusual neoplasms in African hedgehogs ( Atelerix albiventris ) and have been reported in extraskeletal and skeletal locations, including mandible, ribs, and vertebra. Five hedgehogs with osteosarcoma submitted to the Pathology Department at Facultad de Medicina Veterinaria y Zootecnia, National Autonomous University of Mexico are reported. In two cases, the neoplasm arose from the skull; one case arose from the ribs with associated compression of the thoracic and abdominal cavity, and another case involved the vertebrae. In the last case, the neoplasm arose from the scapula. Histologic lesions were similar in all cases and consisted of well-demarcated nodules in which neoplastic cells were arranged in sheets of polyhedral to spindle-shaped cells with interspersed areas of necrosis. Numerous trabeculae of osteoid were present throughout the tumors. No metastases were detected. The predominant histologic pattern was osteoblastic, but a telangiectatic-like pattern was observed in the vertebral osteosarcoma. Electron microscopy was performed in two cases, and malignant osteoblasts had features consistent with descriptions in other species, including deposits of hydroxyapatite in osteoid. According to these cases and previously published data, axial osteosarcomas are more frequent in contrast to appendicular osteosarcomas in African hedgehogs, and metastases are rare.

  4. Osteosarcoma Overview.

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    Lindsey, Brock A; Markel, Justin E; Kleinerman, Eugenie S

    2017-06-01

    Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial. Noninvasive diagnostic methods include serum markers like alkaline phosphatase and a growing variety of imaging techniques including X-ray, computed tomography, magnetic resonance imaging, and positron emission as well as combinations thereof. Still, biopsy and microscopic examination are required to confirm the diagnosis and carry additional prognostic implications such as subtype classification and histological response to neoadjuvant chemotherapy. The current standard of care combines surgical and chemotherapeutic techniques, with a multitude of experimental biologics and small molecules currently in development and some in clinical trial phases. In this review, in addition to summarizing the current understanding of OS etiology, diagnostic methods, and the current standard of care, our group describes various experimental therapeutics and provides evidence to encourage a potential paradigm shift toward the introduction of immunomodulation, which may offer a more comprehensive approach to battling cancer pleomorphism.

  5. MRI features of extraskeletal myxoid chondrosarcoma

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    Tateishi, Ukihide; Arai, Yasuaki [National Cancer Center Hospital, Division of Diagnostic Radiology, Tokyo (Japan); Hasegawa, Tadashi [Sapporo Medical University School of Medicine, Department of Clinical Pathology, Sapporo (Japan); Nojima, Takayuki [Kanazawa Medical University, Department of Pathology, Ishikawa (Japan); Takegami, Tsutomu [Kanazawa Medical University, Medical Research Institute, Ishikawa (Japan)

    2006-01-01

    To describe the MRI features of extraskeletal myxoid chondrosarcoma in comparison with clinicopathologic findings. The study comprised 12 male subjects and seven female subjects with a mean age of 53 years (range 16-76 years). MRI findings, evaluated by two radiologists with agreement by consensus, were compared for histopathologic features. The tumor size ranged from 2.0 cm to 20.0 cm (mean 8.9 cm). Fusion gene transcripts could be detected in 13 (68%) of the 19 cases: EWS-CHN in nine cases, TAF2N-CHN in three, and TFG-TCH in one. There were six fusion-negative cases. Signal characteristics on T1-weighted and T2-weighted MR images were non-specific with regard to each cytogenetic variant. Peripheral enhancement was seen more frequently in tumors with the EWS-CHN variant than in those with other cytogenetic variants. The characteristic pattern of enhancement corresponded to the presence of fibrous septa and peripheral areas of high cellularity within lobules, by correlation with pathologic findings. All cases with TAF2N-CHN or TFG-TCH variants showed invasion of extracompartmental structure, bone, or vessels. Extraskeletal myxoid chondrosarcoma is an uncommon soft-tissue malignancy that may be recognized by MRI features of multi-lobular soft-tissue mass often invading extracompartmental, bony, and vascular structures. (orig.)

  6. Extra-skeletal Ewing's sarcoma of the nasal fossa.

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    Lane, S; Ironside, J W

    1990-07-01

    Extraskeletal Ewing's sarcoma is rarely found arising in the head and neck region. An unusual case arising in the nasal fossa in a young child is reported and the differential diagnosis, pathology and treatment discussed.

  7. Minireview: Vitamin D: Is There a Role in Extraskeletal Health?

    OpenAIRE

    Christakos, Sylvia; DeLuca, Hector F.

    2011-01-01

    In recent years, vitamin D has received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries together with the identification of extraskeletal vitamin D receptor-mediated actions, suggesting unexpected benefits of vitamin D in health and diseases. Although there is increased awareness of the importance of vitamin D, the role of vitamin D in extraskeletal health has been a matter of debate. In this review, we will summarize what is known and indi...

  8. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

    OpenAIRE

    Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

    2013-01-01

    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

  9. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

    Science.gov (United States)

    Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

    2013-06-21

    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

  10. Innate immunity in osteosarcoma

    NARCIS (Netherlands)

    Buddingh, Emilie Pauline

    2014-01-01

    High-grade osteosarcoma is a malignant bone tumor with the highest incidence in young patients. In chapter 2, we studied MSCs of osteosarcoma patients and found downregulation of HCLS1 in osteosarcoma patient derived MSCs as compared to healthy donor derived MSCs. Despite almost two years in

  11. Bone scintigraphy for metastasis detection in canine osteosarcoma

    International Nuclear Information System (INIS)

    Forrest, L.J.; Thrall, D.E.

    1994-01-01

    The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma

  12. [Jaw osteosarcomas].

    Science.gov (United States)

    Steve, M; Ernenwein, D; Chaine, A; Bertolus, C; Goudot, P; Ruhin-Poncet, B

    2011-11-01

    Osteosarcoma (OS) is the most frequent bone malignant tumor. It is usually found on long bones, 5 to 10% are located on jaws, accounting for 0.5 to 1% of all facial tumors. There is little published data which concerns only few patients. Our aim was to study retrospectively cases of facial bone OS in adults, and to compare our results with published data to suggest an optimal management scheme. Thirty-three patients were managed for an OS, from January 1997 to January 2007. Fourteen patients with a maxillary and mandibular OS, treated in first-intention in our unit, were included. The following data were analyzed: age; personal history; circumstance of discovery; clinical, functional, and physical signs; loco-regional extension and metastasis radiological investigation. The histological slides were systematically reviewed. The protocol, therapeutic outcome, and follow-up were studied. The mean age at diagnosis was 43. Swelling was the most frequent functional sign. The mean delay before management was 3.4 months. The most frequent radiological presentation was a lytic and hyperdense image. The diagnosis was suggested after CT scan in 57.1% of cases. The biopsy was correlated to the anatomopathological analysis in 78.6% of cases. The most common treatment was surgical exeresis completed by chemotherapy. The 5-year survival rate was 50%. Jaw OS are specific because of their localization and specific bone ultrastructure. Their management remains controversial: should they be managed like limb OS or treated more specifically? Neoadjuvant chemotherapy, even if it delays exeresis for 3 months, seems to stop the growth or reduce the tumor. An early anatomopathological analysis of the surgical piece determines adjuvant therapy. The negative prognostic factors are: maxillary localization because of limited exeresis margins, tumoral size, and osteoblastic sub-type. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Extraskeletal ewing sarcoma of cervical epidural region: cases report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong [Our Lady of Mercy Hospital, Inchon (Korea, Republic of)

    2003-01-01

    Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors.

  14. Extraskeletal ewing sarcoma of cervical epidural region: cases report

    International Nuclear Information System (INIS)

    Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong

    2003-01-01

    Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors

  15. Osteosarcoma associated with hyperparathyroidism

    International Nuclear Information System (INIS)

    Jutte, Paul C.; Rosso, Renato; Paolis, Massimiliano de; Errani, Costatino; Pasini, Elisabetta; Campanacci, Laura; Bacci, Gaetano; Bertoni, Franco; Mercuri, Mario

    2004-01-01

    The fourth case in the literature is presented of a patient with the rare association of hyperparathyroidism and osteosarcoma. A 56-year-old woman presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis was brown tumor. Histology, however, revealed osteosarcoma, and the patient was treated accordingly. The experimental induction of osteosarcoma by parathormone in rodent studies makes this finding alarming, considering the increasing use of parathormone in the treatment of osteoporosis. The mechanism by which osteosarcoma is induced in humans cannot be explained based on current knowledge of mechanisms of action of parathyroid hormone. (orig.)

  16. THE EXTRASKELETAL ACTIONS OF VITAMIN D--MYTHS AND FACTS.

    Science.gov (United States)

    Sebaaly, Amer; Bachour, Falah; Bayoud, Wael; Adib, Gemma; Bedran, Farid; Daher, Clea; Maalouf, Ghassan

    2015-01-01

    Vitamin D is well known for its effects on bone metabolism, calcium and phosphorus homeostasis. Recently, a worldwide focus has been made on the extraskeletal effects of this liposoluble vitamin. The New York Times even called it the "wonder drug". Vitamin D is a liposoluble vitamin and acts via an intracellular receptor. This article reviews the extra-skeletal effects of vitamin D focusing on cardiovascular effects, regulation of glucose, antitumoral properties, and effect on the immune system and the skeletal muscle and attempts to offer possible molecular explanations to these effects.

  17. Giant gastric lipoma mimicking well-differentiated liposarcoma ...

    African Journals Online (AJOL)

    Diagnosis of a well-differentiated liposarcoma was suspected and molecular cytogenetic analyses showed no MDM2 nor CDK4 gene amplification on fluorescent in situ hybridization. The diagnosis of lipoma was made. Twelve months following surgery, the patient is doing well. Pan African Medical Journal 2012; 13:16 ...

  18. Recurrences in well-differentiated cancer of Thyroid

    International Nuclear Information System (INIS)

    Cadena Enrique

    2000-01-01

    The paper analyzes epidemic data on the relapses as well as of the advantages of the complementary handling of the well differentiated carcinoma of thyroid, the diagnostic methods are commented and the treatment of the same ones, the article includes topics like epidemiology, prevention, recurrences detection, recurrences handling and clinical case

  19. The MRI findings of well-differentiated liposarcoma

    International Nuclear Information System (INIS)

    Odagiri, Haruki; Yakushiji, Toshitake; Sato, Hiroo; Yorimitsu, Shigeta; Oka, Kiyoshi; Uezono, Keiji; Mizuta, Hiroshi

    2008-01-01

    The purpose of this study was to evaluate the MRI findings of well-differentiated liposarcoma. Ten well-differentiated liposarcomas surgically excised with histologic diagnosis were included in this study. The subjects consisted of five men and five women, with an average age of 62.5 years (range: 43-79 years). Six cases occurred in the thigh, two in the forearm, one in the shoulder, and one in the chest wall. Thickened septa (generally ≥2 mm) of low T1 signal and high T2 signal, and prominent area of enhancement were suspicious for well-differentiated liposarcoma. So we checked these lesions and compared with the pathologic findings of these lesions. Thick septa and prominent area of enhancement were identified in all cases except one case who could not use Gadolinium. Pathologically, these lesions were composed of a relatively mature adipocytic proliferation in which, in contrast to benign lipoma, significant variation in cell size is easily appreciable. So we consider that thick septa and prominent area of enhancement are evidently suspicious lesions for well-differentiated liposarcoma. (author)

  20. Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib

    Directory of Open Access Journals (Sweden)

    Stacchiotti Silvia

    2012-10-01

    Full Text Available Abstract Background Extraskeletal myxoid chondrosarcoma (EMCS is a rare soft tissue sarcoma of uncertain differentiation, characterized in most cases by a translocation that results in the fusion protein EWSR1-CHN (the latter even called NR4A3 or TEC. EMCS is marked by >40% incidence of metastases in spite of its indolent behaviour. It is generally resistant to conventional chemotherapy, and, to the best of our knowledge, no data have been reported to date about the activity of tirosin-kinase inhibitor (TKI in this tumor. We report on two consecutive patients carrying an advanced EMCS treated with sunitinib. Methods Since July 2011, 2 patients with progressive pretreated metastatic EMCS (Patient1: woman, 58 years, PS1; Patient2: man, 63 years, PS1 have been treated with continuous SM 37.5 mg/day, on an individual use basis. Both patients are evaluable for response. In both cases diagnosis was confirmed by the presence of the typical EWSR1-CHN translocation. Results Both patients are still on treatment (11 and 8 months. Patient 1 got a RECIST response after 4 months from starting sunitinib, together with a complete response by PET. An interval progression was observed after stopping sunitinib for toxicity (abscess around previous femoral fixation, but response was restored after restarting sunitinib. Patient 2 had an initial tumor disease stabilization detected by CT scan at 3 months. Sunitinib was increased to 50 mg/day, with evidence of a dimensional response 3 months later. Conclusions Sunitinib showed antitumor activity in 2 patients with advanced EMCS. Further studies are needed to confirm these preliminary results.

  1. Imaging in primary osteosarcomas

    International Nuclear Information System (INIS)

    Davies, A.M.

    1998-01-01

    Osteosarcoma is the most common primary malignant bone tumour with the exception of myeloma. The majority of osteosarcoma cases arise within bone and are called conventional osteosarcoma. Intraosseous variants include telangiectatic, small-cell, low-grade intraosseous and cortical osteosarcoma. Less than 10% of osteosarcomas arise on the surface of bone and are subdivided into periosteal, high-grade surface and parosteal varieties. The imaging features of these subtypes of osteosarcoma are described and the impact on diagnosis highlighted. Using material from over 750 osteosarcomas treated at the author's centre, this article reviews the role of imaging in the management of this condition. Detection still relies principally on the conventional radiograph with bone scintigraphy and MR imaging useful in occult tumours. Establishing the radiological diagnosis depends on careful analysis of the radiographs, with particular attention paid to the nature and extent of bone destruction, periosteal new bone formation and matrix mineralization. The prudent radiologist will be wary of those bone conditions, such as stress fractures and osteomyelitis, which are frequently mistaken for osteosarcoma. Appropriate surgical staging requires MR imaging of the primary tumour to show the bony and soft tissue extent of the lesion and to confirm/exclude skip metastases and local lymph-node involvement. Staging should also include bone scintigraphy to confirm/exclude multiple lesions and chest CT to confirm/exclude pulmonary metastases. Following definitive surgery, imaging is used in the follow-up to monitor potential local recurrence and the development of pulmonary or osseous metastases. (orig.) [de

  2. Osteosarcoma associated with hyperparathyroidism

    NARCIS (Netherlands)

    Jutte, PC; Rosso, R; de Paolis, M; Errani, C; Pasini, E; Campanacci, L; Bacci, G; Bertoni, F; Mercuri, M

    The fourth case in the literature is presented of a patient with the rare association of hyperparathyroidism and osteosarcoma. A 56-year-old woman presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis was brown tumor. Histology, however, revealed osteosarcoma, and the

  3. Pulmonary extraskeletal myxoid chondrosarcoma: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Ricardo Balanzá, MD

    2016-01-01

    Conclusion: EMC is an intermediate-grade neoplasm, characterized by a long clinical course with high potential for local recurrence and distant metastasis. Treatment for EMC is surgical and non-surgical treatment is reserved for recurrence or metastatic disease. Pulmonary extraskeletal myxoid chondrosarcoma is a rare neoplasm with only isolated case reports found in the literature.

  4. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of breast

    Directory of Open Access Journals (Sweden)

    Smita Srivastava

    2016-01-01

    Full Text Available Extraskeletal Ewing's sarcoma (EES is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year-old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography–computed tomography.

  5. Recurrences in well-differentiated cancer of thyroid

    International Nuclear Information System (INIS)

    Cadena, Enrique

    2000-01-01

    The thyroid carcinoma is a frequent illness that can reach until 60% of the total of patients assisted in the head and neck consultation. Most of the carcinomas are well differentiated and they can be of the papillar (CPT) or follicular (CFT) type. El basic treatment is surgical and the procedure class impacts in the survival free of illness. The patients that are not managed with complementary treatments to the surgery, like they are the suppression and the iodine therapy, they have bigger possibility of local and regional relapse. In this article epidemic data they are analyzed on the relapses as well as of the advantages of the complementary handling of the well-differentiated carcinoma of thyroid (CBT), additionally, the methods diagnoses are commented for detection of the relapses and the treatment of the same ones. A case managed in the Cancerology National Institute, it discuss finally (INC) with recurrent illness for CPT

  6. Unusual manifestations of well-differentiated thyroid cancer: case reports

    International Nuclear Information System (INIS)

    Jesus, E.M.; Barrenechea, E.A.

    2004-01-01

    Purpose: To present two unusual cases of well-differentiated thyroid carcinomas Methods:Data gathering thru medical records, diagnostic examinations and laboratory results. Well-differentiated thyroid cancer (WDTC) are among the most common type of all thyroid cancers. These case reports were done because of the fact that both cases showed unusual presentations clinically. The first case had a histopathologic report of papillary cancer of the thyroid with some of the typical features of WDTC but within a month's time from the near-total thyroidectomy procedure, there was progression of the neck enlargement, compression symptoms and eventually stridor. I-131 total body scan showed only a small focus of residual neck tissues in the neck with no distant metastasis. Tracheostomy was done and another debulking of the multiple nodules which showed papillary cancer again this time with some anaplastic cells. The second case is a follicular WDTC who also underwent total thyroidectomy after presenting symptoms of soft tissue metastasis at the left buttocks which turned out to be follicular in origin. After total thyroidectomy, I-131 total body scan showed multiple skeleta/soft tissue metastases. These cases are presented to keep in mind that well-differentiated thyroid cancer may not be all the time slow growing and that it should not be taken for granted in terms of treatment. (authors)

  7. Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

    Science.gov (United States)

    Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

    2011-01-01

    Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

  8. Primary extra-skeletal Ewing's sarcoma mimicking a disc protrusion.

    Science.gov (United States)

    Ruelle, A; Boccardo, M

    1987-07-01

    One of the rarest cases of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In the literature only eleven cases of such an extra-skeletal Ewing's sarcoma have been described. The authors report an additional case presenting as a disc protrusion in a young male. The authors include some diagnostic, prognostic and nosologic remarks about this condition.

  9. Prognostic factors in well-differentiated carcinoma of the thyroid

    International Nuclear Information System (INIS)

    Rao, R.S.; Parikh, H.K.

    1999-01-01

    The choice of treatment for a well-differentiated carcinoma (WDC) of the thyroid has remained controversial for several decades. This is unfortunate because WDC occurs in the young, particularly in women, and is compatible with several years of survival. A retrospective analysis of 417 cases of WDC of the thyroid treated by definitive surgery at the Tata Memorial Hospital for the 15-year period (1970 to 1985) form the basis of the conclusion drawn in the present report. These include cases that were referred primarily and those who underwent revision or completion thyroidectomy at the hospital after being treated elsewhere. All relevant data of the cases with WDC, including histopathology slides, were reviewed by an experienced pathologist

  10. Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Bae Geun; Han, Yoon Hee; Lee, Byung Hoon; Kim, Su Young; Hwang, Yoon Joon; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee [Inje University, School of Medicine, Goyang (Korea, Republic of)

    2007-12-15

    The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. It represents approximately 1% of all chondrosarcomas and it carries a poor prognosis. It can occur in extraskeletal locations and mainly in the soft tissues of the orbit, the cranial and spinal meningeal coverings and the lower limbs. To the best of our knowledge, there has been no reported case of primary extraskeletal mesenchymal chondrosarcoma of the pancreas. Only two instances of metastatic chondrosarcomas in the pancreas have been reported in the literature. We report here on a case of primary mesenchymal chondrosarcoma arising from the pancreas in a 41-year-old man. In summary, we present here a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. Radiologically, it manifested as a necrotic soft tissue mass with chondroid calcifications.

  11. Osteosarcoma models : understanding complex disease

    NARCIS (Netherlands)

    Mohseny, Alexander Behzad

    2012-01-01

    A mesenchymal stem cell (MSC) based osteosarcoma model was established. The model provided evidence for a MSC origin of osteosarcoma. Normal MSCs transformed spontaneously to osteosarcoma-like cells which was always accompanied by genomic instability and loss of the Cdkn2a locus. Accordingly loss of

  12. Paraosteal (juxtacortical)osteosarcoma. Report of clinical-pathological case in a dog

    International Nuclear Information System (INIS)

    Sanchez Pacheco, A. Alejandro; Rangel Rodriguez, Ignacio Carlos; Aburto Martinez, Enrique M.; Martinez Flores, Melina; Paniagua Garcia, Jazmin; Miranda Monroy, N. Fernando

    1999-01-01

    Parosteal osteosarcoma is a primary bone tumor on the osseous surface, and is typically composed by well differentiated but malignant fibrous, osseous and cartilaginous tissue. This tumor occurred in a male, 8 year old German Shepherd dog which was diagnosed by fine needle biopsy and X-rays and confirmed by a histhological study [es

  13. Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

    Science.gov (United States)

    Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

    2018-03-01

    Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

  14. Osteosarcoma (Osteogenic sarcoma

    Directory of Open Access Journals (Sweden)

    Picci Piero

    2007-01-01

    Full Text Available Abstract Osteosarcoma is a primary malignant tumour of the skeleton characterised by the direct formation of immature bone or osteoid tissue by the tumour cells. The classic osteosarcoma is a rare (0.2% of all malignant tumours highly malignant tumour, with an estimated incidence of 3 cases/million population/year. Osteosarcoma arises predominantly in the long bones and rarely in the soft tissues. The age at presentation ranges from 10 to 25 years of age. Plain radiographs, computed tomography, magnetic resonance imaging, angiography and dynamic bone scintigraphy are used for diagnosis, evaluation the extent of tumour involvement and decision of the type of operation and, if necessary, the type of reconstruction. Years ago, all patients with osteosarcoma were treated by amputation but the cure rate was under 10% and almost all patients died within a year from diagnosis. Today, for localised osteosarcoma at onset (80% of cases treated in specialized bone tumour centres with pre- and postoperative chemotherapy associated with surgery, the percentage of patients cured varies between 60% and 70%. Surgery is conservative (limb salvage in more than 90% of patients. Prognosis is more severe (cure rate about 30% for tumours located in the axial skeleton and in patients with metastasis at onset.

  15. Well-Differentiated Thyroid Cancer: The Philippine General Hospital Experience

    Directory of Open Access Journals (Sweden)

    Tom Edward N. Lo

    2016-03-01

    Full Text Available BackgroundWell-differentiated thyroid cancer (WDTC is the most common form of thyroid malignancy. While it is typically associated with good prognosis, it may exhibit higher recurrence and mortality rates in selected groups, particularly Filipinos. This paper aims to describe the experience of a Philippine Hospital in managing patients with differentiated thyroid cancer.MethodsWe performed a retrospective cohort study of 723 patients with WDTC (649 papillary and 79 follicular, evaluating the clinicopathologic profiles, ultrasound features, management received, tumor recurrence, and eventual outcome over a mean follow-up period of 5 years.ResultsThe mean age at diagnosis was 44±13 years (range, 18 to 82, with a majority of cases occurring in the younger age group (<45 years. Most tumors were between 2 and 4 cm in size. The majority of papillary thyroid cancers (PTCs, 63.2% and follicular thyroid cancers (FTCs, 54.4% initially presented as stage 1, with a greater proportion of FTC cases (12.7% vs. 3.7% presenting with distant metastases. Nodal metastases at presentation were more frequent among patients with PTC (29.9% vs. 7.6%. A majority of cases were treated by complete thyroidectomy, followed by radioactive iodine therapy and thyroid stimulating hormone suppression, resulting in a disease-free state. Excluding patients with distant metastases at presentation, the recurrence rates for papillary and FTC were 30.1% and 18.8%, respectively.ConclusionOverall, PTC among Filipinos was associated with a more aggressive and recurrent behavior. FTC among Filipinos appeared to behave similarly with other racial groups.

  16. Imaging appearance of well-differentiated liposarcomas with myxoid stroma.

    Science.gov (United States)

    Morag, Yoav; Yablon, Corrie; Brigido, Monica Kalume; Jacobson, Jon; Lucas, David

    2018-04-16

    Describe the imaging appearance of well-differentiated liposarcoma with myxoid stroma (WDLMS) and correlate with histopathology. A keyword search of the institution medical records was performed from 1 January 2000 to 30 June 2017. The histopathology slides of cases identified in this fashion were then reviewed by a pathologist. Additional cases were prospectively collected from extramural referrals and tumor boards. Diagnostic imaging studies of pathologically proven cases of WDLMS were then reviewed in consensus and correlated with pathology. Ten cases of pathologically proven WDLMS were identified (7 men, 3 women, ages 26-81). Tumor location included the retroperitoneum (n = 5), thigh (n = 4), and the shin (n = 1). Nine patients had macroscopic fat on imaging. The nonlipomatous components had a variable appearance, including septal, nodular, and lacelike patterns. Two cases included two distinct areas that were predominantly myxoid or lipomatous ("bi-morphic"). One tumor had no macroscopic fat on imaging. On CT, the nonlipomatous nodular components were hypodense/had hypodense areas. On MRI, the nodular components had intermediate/bright T2W signal. Interval nonlipomatous nodular growth was identified in 3 cases. WDLMS may present on imaging as a mass with variable morphology and amounts of nonlipomatous components. Histopathological diagnosis of WDLMS is challenging and imaging correlation may be helpful, as this tumor may have ≥50% fatty volume, may have a myxoid nodular component or bi-morphic appearance, or may be located in the retroperitoneum, features that are unusual for myxoid liposarcoma. WDLMS with a nodular component cannot be distinguished from dedifferentiated liposarcoma based on imaging alone.

  17. Radioiodine Treatment of Well-Differentiated thyroid cancer in children

    International Nuclear Information System (INIS)

    Barrenechea, E.

    2007-01-01

    Full text: Well-differentiated thyroid cancer (DTCA) in children is quite different from the adult- onset disease in that they are more aggressive at the time of diagnosis and with metastases and has a higher risk for recurrence. Some studies claim it to be less lethal and hence treatment protocols may be different from that of the adult. This study was made to analyze the need for RAI therapy as one of the cornerstone of treatment aside from surgery and thyroid hormone suppression as well as to determine the behavior of WDTCA in children. Results: The incidence of DTCA is varied and ranges from 1-10% in several published series. In the Philippines where thyroid cancer in adults ranks 5th in mortality for both sexes, the incidence is likewise very low, around 0.5-1% for ages 18 years and below in a ten year study. It was predominantly a female population (74%) as compared to the males (26%). Fifteen cases were reviewed and included as most were given RAI (87%). Most presented as a solitary nodule and with lymph node metastases. Thirteen cases were papillary in nature and only two cases were follicular. The incidence of nodal metastases was 53% while lung metastases were seen in 20% of cases. Of the 13 cases that underwent RAI therapy, three cases of lung metastases needed repeat therapy. In the cases with lymph node metastases, 2 cases also had recurrence and which necessitated repeat RAI therapy. The two cases that did not get RAI therapy had progressive disease on follow- up after 5 and 7 years respectively from surgery. Discussion: Primary treatment for DTC should consist of surgery, radioiodine ablation and thyroid hormone suppression. We must rely on pediatric outcome studies and the high frequency of multifocal intrathyroidal disease, loco- regional spread and extra cervical metastases often seen as initial presentations of this particular group. The more advanced disease at diagnosis for children, propensity for recurrence as well as the greater radioiodine

  18. Extraskeletal mesenchymal chondrosarcoma of the carotid space: A case report

    International Nuclear Information System (INIS)

    Huh, Sun; Hong, Hyun Sook; Kwak, Jeong Ja; Park, Ji Sang; Jeong, Sun Hye

    2015-01-01

    Chondrosarcoma is a commonly encountered malignant cartilaginous tumor. However, only 1% of chondrosarcomas arise in the extraskeletal region. The pathologic types of this tumor include mesenchymal, myxoid, and low grade. A mesenchymal chondrosarcoma is a rare, highly malignant cartilaginous tumor that is rarely encountered, and it shows similar imaging features to other malignant soft-tissue tumors. Here, we report a mesenchymal chondrosarcoma presenting as a palpable mass in the neck, arising in the carotid space, which is also known as the retrostyloid parapharyngeal space.

  19. Extraskeletal mesenchymal chondrosarcoma of the carotid space: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Sun; Hong, Hyun Sook; Kwak, Jeong Ja; Park, Ji Sang; Jeong, Sun Hye [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2015-05-15

    Chondrosarcoma is a commonly encountered malignant cartilaginous tumor. However, only 1% of chondrosarcomas arise in the extraskeletal region. The pathologic types of this tumor include mesenchymal, myxoid, and low grade. A mesenchymal chondrosarcoma is a rare, highly malignant cartilaginous tumor that is rarely encountered, and it shows similar imaging features to other malignant soft-tissue tumors. Here, we report a mesenchymal chondrosarcoma presenting as a palpable mass in the neck, arising in the carotid space, which is also known as the retrostyloid parapharyngeal space.

  20. Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

    Science.gov (United States)

    Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

    2015-04-01

    Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

    OpenAIRE

    Bhagyalakshmi Atla; B Satya Vara Prasad; K Satya Sri; Geeta Vandana

    2011-01-01

    Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the li...

  2. Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

    Directory of Open Access Journals (Sweden)

    Bhagyalakshmi Atla

    2011-01-01

    Full Text Available Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the literature.

  3. Periosteal osteosarcoma: A case report

    Directory of Open Access Journals (Sweden)

    Errol U. Hutagalung

    2003-09-01

    Full Text Available Periosteal osteosarcoma is a rare type of malignant bone neoplasm, with predominantly cartilaginous component and arising on the bone surface. Reports of the case in the literature were rare. Last case was reported by Mayo Clinic in 1999. We report a case of periosteal osteosarcoma in a 17-year-old male, who was treated surgically with a limb salvage procedure, neoadjuvant and adjuvant chemotherapy were also given to the patient. There was no local recurrence and lung metastases up to 14 months after surgery. (Med J Indones 2003; 12: 166-70 Keywords: osteosarcoma, periosteal osteosarcoma, limb salvage

  4. Epiphyseal osteoblastoma-like osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Bonar, S.F. [Douglass Hanly Moir Pathology, 95 Epping Road, North Ryde, NSW 2113 (Australia); McCarthy, S.; Stalley, P.; Schatz, J.; Soper, J.; Scolyer, R. [Departments of Pathology, Radiology and Orthopaedic Surgery, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050 (Australia); Barrett, I. [Department of Orthopaedic Surgery, The Children' s Hospital, Westmead, NSW 2145 (Australia)

    2004-01-01

    Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma occurring in this instance in a highly unusual location: the lateral femoral condyle of a 13-year-old girl. The radiological features were non-aggressive and, although slightly unusual, were most suggestive of chondroblastoma. (orig.)

  5. Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

    International Nuclear Information System (INIS)

    Ehara, Shigeru; Nishida, Jun; Shiraishi, Hideo; Yoshioka, Hiroshi; Okada, Kyoji; Sumiya, Hisashi; Takano, Hideyuki

    2007-01-01

    The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

  6. Primary extraskeletal mesenchymal chondrosarcoma arising from the iliac vein

    Directory of Open Access Journals (Sweden)

    Hua Zhang

    2017-10-01

    Full Text Available The iliac vein is an extremely rare site for mesenchymal chondrosarcoma, and patients with primary extraskeletal mesenchymal chondrosarcoma arising from a vein always suffer a very poor prognosis. We report a case of a 45-year-old female who presented with a 5-month history of left leg edema in 2015. Contrast-enhanced computed tomography showed a large mass in the left iliac vein with scattered calcifications. Wide-margin resection was performed, and histopathologic and immunohistochemical analyses confirmed the presence of intraluminal mesenchymal chondrosarcoma with local invasion out of the vein wall. Due to poor patient compliance, postoperative neoadjuvant chemotherapy and radiotherapy were not started, and a bone scan performed 16 weeks postoperatively showed multiple bone metastases. The patient died on the twenty-fourth postoperative week.

  7. Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ehara, Shigeru [Iwate Medical University School of Medicine, Department of Radiology, Morioka (Japan); Nishida, Jun; Shiraishi, Hideo [Iwate Medical University School of Medicine, Department of Orthopedic Surgery, Iwate (Japan); Yoshioka, Hiroshi [University of Tsukuba School of Medicine, Department of Radiology, Tsukuba (Japan); Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Okada, Kyoji [Akita University School of Medicine, Department of Orthopedic Surgery, Akita (Japan); Sumiya, Hisashi [Kanazawa University School of Medicine, Department of Nuclear Medicine, Kanazawa (Japan); Yawata Medical Center, Komatsu (Japan); Takano, Hideyuki [Chiba Cancer Center, Division of Diagnostic Imaging, Chiba (Japan)

    2007-09-15

    The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

  8. Extra-skeletal Ewing's sarcoma of the submandibular gland.

    Science.gov (United States)

    Agir, Hakan; Brasch, Helen D; Tan, Swee T

    2007-01-01

    Extra-skeletal Ewing's sarcoma (EES) is an uncommon malignancy, especially in the head and neck region that may arise in various extra-osseous tissues. We report a 22-year-old male with an EES of the submandibular gland, which to the best of our knowledge, has not been described previously. The patient who underwent combined treatment with surgical resection and chemo-irradiation was disease free for 22 months but succumbed to multi-organ metastases 14 months later. This case highlights the combined diagnostic role of immunohistochemical, cytogenetic and radiological evaluation of EES. EES is an aggressive cancer that requires multidisciplinary management with wide surgical excision and adjunctive chemo-irradiation for the best outcome.

  9. Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.

    Science.gov (United States)

    Mertens, Michelle; Haenen, Filip W N; Siozopoulou, Vasiliki; Van Cleemput, Marc

    2017-06-01

    Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison with Ewing's sarcoma of bone and usually manifests in young patients. However, even in older patients, one must consider the diagnosis. In this case, we describe a 52-year-old woman diagnosed with EES, mimicking as adenocarcinoma of the sigmoid. The tumor was not visualized by a multi-slice spiral computed tomography of the abdomen and pelvis with intravenous contrast, and eventually the diagnosis was made by positive immunohistochemical staining for CD99 and by molecular testing for EWSR1 translocation. This combination of the patient's age and the localization of the tumor mimicking an adenocarcinoma of the sigmoid has never been described before.

  10. Radiological evaluation of the response to chemotherapy for osteosarcoma

    International Nuclear Information System (INIS)

    Miwa, Shinji; Taki, Junichi; Yamamoto, Norio

    2011-01-01

    Sixty-one patients with osteosarcoma were examined by radiographs, angiograms, MRI, 201 Tl and 99m Tc-methoxyisobutyl-isonitrile (MIBI) scintigram to evaluate their response to preoperative chemotherapy. All patients were classified as either responders or non-responder according based on the imaging findings. The radiographs were evaluated according to the degree of sclerotic change and cortical recovery, and the angiograms were evaluated according to the degree of vascular change. MR images were evaluated according to the rate of extraskeletal mass reduction. The 201 Tl and 99m Tc-MIBI scans were evaluated by the percentage reduction of the uptake ratio. All patients were evaluated on the basis of a pathological examination of the resected specimens. We also devised a combined radiological scoring system according to the predictive power of each type of diagnostic image and investigated the correlation between the radiological evaluation and the pathological evaluation. Sensitivity, specificity, and accuracy were 81.0%, 19.0%, and 60.3%, respectively for the radiographs; 77.1%, 20.0%, and 60.0%, respectively, for angiograms; 82.1%, 69.0%, and 75.4%, respectively for MRI; 81.5%, 68.0%, and 75.0%, respectively, for 201 Tl scans; 76.7%, 70.6%, and 74.5% for 99m Tc-MIBI scans; and 88.9%, 84.0%, and 86.9%, respectively, for the combined radiological evaluation. (author)

  11. Adjuvant chemotherapy for osteosarcoma.

    Science.gov (United States)

    Eilber, F R; Rosen, G

    1989-08-01

    From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at

  12. BNCT of canine osteosarcoma

    International Nuclear Information System (INIS)

    Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.

    2006-01-01

    A dog was diagnosed with osteosarcoma (8x6x5cm) in the right wing of ilium by radiography, radionuclide scintigraphy and histological study of biopsy material. The treatment plan was as follows: γ-therapy in combination with chemotherapy; prevention of hematogenous pulmonary metastases by the transfusion of 130 ml of allogenic marrow from a healthy donor; administration of 11.4g 10 B-boronphenylalanine into the right iliac artery; resection of the right iliac wing with the osteosarcoma lesion; neutron irradiation (MEPhI Reactor) of the bone fragment (dose on healthy osteocytes - 15±4 Gy (W), on tumor - 50±9 Gy (W); reimplantation and fixation of the fragment; three courses of adjuvant chemotherapy. The doses were determined in full-scale calculations of the reactor radiation fields with a model of the bone under the code RADUGA. The 10 B concentration (μg/g) in the bone was: normal tissue - 9±3, tumor - 28±5. In 24 hours post operation the dog was able to walk using the treated limb, and 6 months later it moved freely. The patient has been under observation for 30 months. The results of the research demonstrate complete cure. The use of similar treatment plans improves the therapeutic efficiency of BNCT. (author)

  13. Osteoblastic and fibroblastic multicentric osteosarcoma.

    Science.gov (United States)

    Cabello, Raúl Romero; Sánchez, Carlos J; Padilla, Marco A Duran; Navarro, José M De la Garza; Feregrino, Raul Romero; Vázquez, Avissai Alcántara; González, Mercedes Hernández; Feregrino, Rodrigo Romero

    2011-11-21

    Bone sarcomas are uncommon tumours, of which osteosarcoma is the least rare, as well as the third most common malignant tumour in childhood, appearing usually between the 10 and 20 years of age. The case the authors present in this work is of a patient suffering from a long-standing condition encompassing skin and soft tissue lesions. After multiple medical treatments, the patient was diagnosed with squamous osteosarcoma, which required aggressive surgical management and chemotherapy.

  14. Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, N.; Joyama, S.; Araki, N. [Osaka Medical Center for Cancer and Cardiovascular Disease, Department of Orthopedic Surgery, Osaka (Japan); Ueda, T.; Yoshikawa, H. [Osaka University Graduate School of Medicine, Department of Orthopedic Surgery, Osaka (Japan); Beppu, Y. [National Cancer Center Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Tatezaki, S. [Chiba Cancer Center Hospital, Department of Orthopedic Surgery, Chiba (Japan); Matsumoto, S. [Cancer Institute Hospital, Japanese Foundation for Cancer Research Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Nakanishi, K. [Osaka Seamen' s Insurance Hospital, Department of Radiology, Osaka (Japan); Tomita, Y. [Osaka University Graduate School of Medicine, Department of Pathology, Osaka (Japan)

    2005-12-01

    Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor. We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features. Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study. Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor. (orig.)

  15. Paravertebral Well-Differentiated Liposarcoma with Low-Grade Osteosarcomatous Component: Case Report with 11-Year Follow-Up, Radiological, Pathological, and Genetic Data, and Literature Review

    Directory of Open Access Journals (Sweden)

    Nicolas Macagno

    2017-01-01

    Full Text Available Despite being one of the most frequent soft-tissue sarcomas, well-differentiated liposarcoma has never been reported near the spine. The authors present the case of a 67-year-old man with progressive history of back pain. Physical examination revealed a mass located within the right paravertebral muscles. MR and CT imaging showed a heavily ossified central mass surrounded by a peripheral fatty component. No connection with the underlying bone was detected on imagery and during surgery. After surgical resection, histopathological examination revealed a tumor harboring combined features of well-differentiated liposarcoma and low-grade osteosarcoma. Tumor cells displayed overexpression of MDM2, CDK4, and P16 by immunohistochemistry and CGH revealed amplification of 12q13-15 as the only genetic imbalance. MDM2 FISH analysis was performed but was inconclusive. The pathological, immunohistochemical, and genetic features, the differential diagnoses, and the therapeutic management of this unusual tumor are discussed. No complementary treatment was performed initially. Following first treatment, two recurrences occurred 6 and 9 years later, both displaying histological features similar to the first occurrence. Radiotherapy was started after the second recurrence. Follow-up shows no evidence of disease 11 years after initial diagnosis. This case was unusual due to the paravertebral location of the tumor and its divergent differentiation.

  16. Extraskeletal Ewing's Sarcoma: insight into a ten years follow-up.

    Science.gov (United States)

    Zitelli, A; Manfredelli, S; Brunotti, G; Marcantonio, M; Pontone, S; Angelici, A

    2013-01-01

    Extraskeletal Ewing's sarcoma is a rare malignant soft tissue tumor, classified within the Ewing's Sarcoma Family Tumors. While the classical Ewing's Sarcoma affects mainly the bone during youth, the Extraskeletal histotype differs for age incidence, primary location and prognosis. Peak incidence and typical location are during adolescence and in the extremities respectively. We report a 30 year old woman case with a positive outcome after ten years from first diagnosis of Extraskeletal Ewing's sarcoma. Treatment was achieved through surgical resection plus adjuvant chemoradiotherapy derived from EW93 and IRS III trials. Conclusion. Our report represents an unusual case due to age of presentation, neoplasm location and long survival reached. In last decades several trials results demonstrated that long survival could be achieved by combined surgery and adjuvant multi-drug treatment.

  17. Case report 393: Extraskeletal chondroma of the soft tissue of the wrist

    Energy Technology Data Exchange (ETDEWEB)

    Perri, G.; Tripi, D.

    1986-10-01

    An interesting case of extraskeletal intra-articular chondroma is described. The radiological appearance was that of a soft tissue mass of the wrist on the ulnar side, together with osteopenia and erosions of the pisiform and triquetrum bones. No calcification was noted. The most likely diagnosis was pigmented villonodular synovitis; synovial osteochondromatosis was also considered. However, at operation a single cartilaginous intra-articular nodule, firmly attached to the synovium, proved to be an extraskeletal chondroma. The authors offer speculative theories about the origins of such lesions and describe the various radiological and pathological features of a chondroma of soft tissues.

  18. Case report 393: Extraskeletal chondroma of the soft tissue of the wrist

    International Nuclear Information System (INIS)

    Perri, G.; Tripi, D.

    1986-01-01

    An interesting case of extraskeletal intra-articular chondroma is described. The radiological appearance was that of a soft tissue mass of the wrist on the ulnar side, together with osteopenia and erosions of the pisiform and triquetrum bones. No calcification was noted. The most likely diagnosis was pigmented villonodular synovitis; synovial osteochondromatosis was also considered. However, at operation a single cartilaginous intra-articular nodule, firmly attached to the synovium, proved to be an extraskeletal chondroma. The authors offer speculative theories about the origins of such lesions and describe the various radiological and pathological features of a chondroma of soft tissues. (orig.)

  19. Evaluation of radiation therapy for advanced well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Tatsuno, Ikuo; Tada, Akira; Choto, Shuichi; Takanaka, Tsuyoshi

    1987-01-01

    Eighty-two patients with advanced well-differentiated thyroid carcinoma were treated. Sixty-six patients survived for more than 10 years and 10-year-survival rate was 80.5 %. Multidisciplinary treatment, consisting of surgery, radioiodine, external irradiation and TSH suppression was studied. We emphasized that radioiodine treatment after thyroid-ectomy was unique and an ideal therapeutic model for locally advanced, distant metastatic and recurrent cases as far as radioiodine was accumulated on thyroid cancer tissue. External irradiation was sometimes effective for the remnant thyroid carcinoma and metastases. Occassionally, well-differentiated thyroid carcinoma showed good response to TSH suppression therapy using thyroid hormone. The significance of conversion of well-differentiated carcinoma of thyroid to anaplastic carcinoma was noticed. We recognized that radiation therapy was effective for advanced well-differentiated thyroid carcinoma in multidisciplinary treatment. (author)

  20. Evaluation of radiation therapy for advanced well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuno, Ikuo; Tada, Akira; Choto, Shuichi; Takanaka, Tsuyoshi

    1987-02-01

    Eighty-two patients with advanced well-differentiated thyroid carcinoma were treated. Sixty-six patients survived for more than 10 years and 10-year-survival rate was 80.5 %. Multidisciplinary treatment, consisting of surgery, radioiodine, external irradiation and TSH suppression was studied. We emphasized that radioiodine treatment after thyroid-ectomy was unique and an ideal therapeutic model for locally advanced, distant metastatic and recurrent cases as far as radioiodine was accumulated on thyroid cancer tissue. External irradiation was sometimes effective for the remnant thyroid carcinoma and metastases. Occassionally, well-differentiated thyroid carcinoma showed good response to TSH suppression therapy using thyroid hormone. The significance of conversion of well-differentiated carcinoma of thyroid to anaplastic carcinoma was noticed. We recognized that radiation therapy was effective for advanced well-differentiated thyroid carcinoma in multidisciplinary treatment.

  1. Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.

    Science.gov (United States)

    Hernando-Cubero, Jorge; Sanz-Moncasi, Pilar; Hernández-García, Alba; Pajares-Bernard, Isabel; Martínez-Trufero, Javier

    2016-10-01

    The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin ® ) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second-line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69-year-old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9×8×7-cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second-line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m 2 as a 24-h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months) progression-free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to

  2. Chondroblastic osteosarcoma mimicking periapical abscess.

    Science.gov (United States)

    Yamamoto-Silva, Fernanda Paula; Silva, Brunno Santos de Freitas; Batista, Aline Carvalho; Mendonça, Elismauro Francisco de; Pinto-Júnior, Décio Dos Santos; Estrela, Carlos

    2017-01-01

    The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

  3. The role of imaging in the evaluation of extraskeletal Ewing's sarcoma

    African Journals Online (AJOL)

    Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing's sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing's sarcoma (ESS). Computed tomography (CT) scanning and magnetic resonance imaging (MRI) features of Ewing's sarcoma are non-specific, and a ...

  4. Renal bone disease and extraskeletal calcification during dialysis and after transplantation

    International Nuclear Information System (INIS)

    Graaf, P. de.

    1980-01-01

    The author reports 10 studies concerning the diagnosis of renal osteodystrophy and extraskeletal calcification in patients on maintenance hemodialysis as well as some aspects of persistent hyperparathyroidism after renal transplantation. The majority of the studies focus on the value of bone scintigraphy with Tc-99m HEDP in the diagnosis of these disorders. (Auth.)

  5. CASE SERIES The role of imaging in the evaluation of extraskeletal ...

    African Journals Online (AJOL)

    muscle group and extended to insinuate into the spinal canal, displacing and compressing the thecal sac to the left (Fig. 3). The role of imaging in the evaluation of extraskeletal Ewing's sarcoma. P Barnardt, F Roux. Division of Clinical Oncology, Department of Medical Imaging and Clinical Oncology, Stellenbosch University.

  6. Small-cell osteosarcoma

    International Nuclear Information System (INIS)

    Edeiken, J.; Raymond, A.K.; Ayala, A.G.; Benjamin, R.S.; Murray, J.A.; Carrasco, H.C.

    1987-01-01

    Small-cell osteosarcoma, a subtype of osteogenic sarcoma, consists of sheets of round cells that produce an osteoid matrix. It may be confused with Ewing sarcoma if the osteoid matrix is not included in the biopsy. The distinctive radiographic features of an osteoblastic tumor and a pattern of permeative destruction will confirm the histologic diagnosis or indicate the true nature if tumor osteoid is not included in the histological sections. We add 13 patients to the 32 previously reported in the literature. Fourteen (31%) of the 45 are living and well, though three have been followed for only 2 months. The treatments have been so varied that a statistically significant evaluation cannot be developed. The radiographic features are not distinctive, but the diagnosis may be suggested when a tumor has osteoblastic features in the metaphysis and extends well down into the shaft with a pattern of permeative destruction. The radiographic features are especially important when limited biopsies reveal only sheets of round cells, thus suggesting Ewing sarcoma. The presence of an osteoid-producing tumor as evident by osteoblastic new bone formation will lead to the correct diagnosis. (orig.)

  7. Osteosarcoma: Evolution of Treatment Paradigms

    Directory of Open Access Journals (Sweden)

    Norman Jaffe

    2013-01-01

    Full Text Available This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success.

  8. Chondroblastic osteosarcoma mimicking periapical abscess

    Directory of Open Access Journals (Sweden)

    Fernanda Paula YAMAMOTO-SILVA

    Full Text Available Abstract Lesions of non-endodontic origin may mimic periapical abscess. Osteosarcoma is a rare malignant lesion. Case report The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Conclusions Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

  9. Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

    DEFF Research Database (Denmark)

    Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque

    2017-01-01

    Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. ...

  10. Transplantation of canine osteosarcoma into nude mice

    International Nuclear Information System (INIS)

    Shifrine, M.; Taylor, N.; Holloway, G.; Arnstein, P.R.; Chrisp, C.; Pool, R.; Whaley, C.

    1975-01-01

    Osteosarcomas from dogs were inoculated subcutaneously into mice. Sixty days later six mice had tumors that gradually increased in size. All tumors were undifferentiated sarcomas. Karyotypes of osteosarcomas grown in tissue culture and of tumors from mice inoculated with the culture were similar with two marker chromosomes. It was thus shown that radioinduced osteosarcomas can be cultivated in tissue culture while retaining their marker chromosomes and malignancy

  11. Multicentric extraskeletal myxoid chondrosarcoma of uterine adnexa in a young female: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Surbhi Goyal

    2012-01-01

    Full Text Available Extraskeletal myxoid chondrosarcoma is a rare soft-tissue sarcoma, mostly occurring in the proximal extremities and limb girdle. Majority of the patients are in fifth and sixth decades of life with male preponderance. We report here a case of primary extraskeletal myxoid chondrosarcoma of the uterine adnexa involving the broad ligament and fallopian tube synchronously without any evidence of uterine/ovarian involvement in a young multiparous female of 27 years. After the histopathological diagnosis, re-excision of the tumor bed with wide local margins was recommended. Since the tumor has an aggressive course, with propensity for late recurrence and metastases to lungs, the patient must be considered for long-term follow-up.

  12. Extraskeletal aneurysmal bone cyst: Report of a case and review of the literature.

    Science.gov (United States)

    Lopez, Liurka V; Rodriguez, Michael G; Siegal, Gene P; Wei, Shi

    2017-11-01

    Aneurysmal bone cyst (ABC) is an expansile cystic lesion that may affect any bone of the skeleton. Although exceedingly rare, lesions with histomorphologic characteristics of an ABC have reportedly originated within soft tissue. Extraskeletal ABC may mimic a variety of benign and malignant lesions and can be confused with other more common or rare giant cell-rich tumors of soft tissue, especially myositis ossificans. Clinical, radiological and histologic correlation is crucial in reaching the correct diagnosis. Cytogenetic and/or molecular genetic analysis is a useful adjunct in diagnosing these exquisitely rare lesions. Here we report a case of an ABC arising in an extraskeletal site and provide a comprehensive review of literature on this rare entity. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. SPIO-Enhanced MRI Findings of Well-Differentiated Hepatocellular Carcinomas: Correlation with MDCT Findings

    International Nuclear Information System (INIS)

    Kim, Seong Hyun; Lee, Won Jae; Lim, Hyo K.; Park, Cheol Keun

    2009-01-01

    This study was designed to assess superparamagnetic iron oxide (SPIO)-enhanced MRI findings of well-differentiated hepatocellular carcinomas (HCCs) correlated with their multidetector-row CT (MDCT) findings. Seventy-two patients with 84 pathologically proven well-differentiated HCCs underwent triple-phase MDCT and SPIO-enhanced MRI at a magnetic field strength of 1.5 Tesla (n = 49) and 3.0 Tesla (n = 23). Two radiologists in consensus retrospectively reviewed the CT and MR images for attenuation value and the signal intensity of each tumor. The proportion of hyperintense HCCs as depicted on SPIO-enhanced T2- or T2*-weighted images were compared in terms of tumor size ( 1 cm), five CT attenuation patterns based on arterial and equilibrium phases and magnetic field strength, by the use of univariate and multivariate analyses. Seventy-eight (93%) and 71 (85%) HCCs were identified by CT and on SPIO-enhanced T2- and T2*-weighted images, respectively. For the CT attenuation pattern, one (14%) of seven isodense-isodense, four (67%) of six hypodense- hypodense, four (80%) of five isodense-hypodense, 14 (88%) of 16 hyperdense- isodense and 48 (96%) of 50 hyperdense-hypodense HCCs were hyperintense (Cochran-Armitage test for trend, p 0.05). Most well-differentiated HCCs show hyperintensity on SPIOenhanced MRI, although the lesions show various CT attenuation patterns. The CT attenuation pattern is the main factor that affects the proportion of hyperintense well-differentiated HCCs as depicted on SPIO-enhanced MRI

  14. Well-differentiated papillary mesothelioma of tunica vaginalis testis of unknown malignant potential: Sonographic appearance.

    Science.gov (United States)

    Ko, K W S; Tse, K S; Shek, K W; Hau, M N; Ting, S H

    2017-10-09

    Paratesticular mesothelioma is a rare differential diagnosis in the presence of scrotal hydrocele. A 17-year-old boy presented with a 3-year history of progressive hydrocele. Sonography revealed a large left paratesticular mass within the hydrocele. Serum tumor markers were negative. Left hydrocelectomy was performed and pathological analysis of the epididymal mass revealed a well-differentiated papillary mesothelioma. We discuss the sonographic and pathological findings of this rare neoplasm. © 2017 Wiley Periodicals, Inc.

  15. Incidental finding of multiple well-differentiated papillary mesotheliomas in peritoneum

    DEFF Research Database (Denmark)

    Jakobsen, Mark; Engvad, Birte; Jensen, Thor

    2016-01-01

    We present a case of multiple well-differentiated papillary mesotheliomas (WDPM) in the peritoneum found incidentally in a 63-year-old man with urothelial carcinoma of the bladder. When multiple tumors are seen, malignant mesothelioma should be excluded by histopathological examination as this ma...... with a good prognosis. Great care is needed when diagnosing mesothelial proliferations, given the crucial nature of a benign vs malignant diagnosis. No standardized treatment has yet been established....

  16. Manipulation of Cell Physiology Enables Gene Silencing in Well-differentiated Airway Epithelia

    Directory of Open Access Journals (Sweden)

    Sateesh Krishnamurthy

    2012-01-01

    Full Text Available The application of RNA interference-based gene silencing to the airway surface epithelium holds great promise to manipulate host and pathogen gene expression for therapeutic purposes. However, well-differentiated airway epithelia display significant barriers to double-stranded small-interfering RNA (siRNA delivery despite testing varied classes of nonviral reagents. In well-differentiated primary pig airway epithelia (PAE or human airway epithelia (HAE grown at the air–liquid interface (ALI, the delivery of a Dicer-substrate small-interfering RNA (DsiRNA duplex against hypoxanthine–guanine phosphoribosyltransferase (HPRT with several nonviral reagents showed minimal uptake and no knockdown of the target. In contrast, poorly differentiated cells (2–5-day post-seeding exhibited significant oligonucleotide internalization and target knockdown. This finding suggested that during differentiation, the barrier properties of the epithelium are modified to an extent that impedes oligonucleotide uptake. We used two methods to overcome this inefficiency. First, we tested the impact of epidermal growth factor (EGF, a known enhancer of macropinocytosis. Treatment of the cells with EGF improved oligonucleotide uptake resulting in significant but modest levels of target knockdown. Secondly, we used the connectivity map (Cmap database to correlate gene expression changes during small molecule treatments on various cells types with genes that change upon mucociliary differentiation. Several different drug classes were identified from this correlative assessment. Well-differentiated epithelia treated with DsiRNAs and LY294002, a PI3K inhibitor, significantly improved gene silencing and concomitantly reduced target protein levels. These novel findings reveal that well-differentiated airway epithelia, normally resistant to siRNA delivery, can be pretreated with small molecules to improve uptake of synthetic oligonucleotide and RNA interference (RNAi responses.

  17. [Extra-skeletal Ewing's sarcoma. A case report with detailed review of the literature].

    Science.gov (United States)

    Auge, B; Pusel, J

    1990-01-01

    Extra-skeletal Ewing's Sarcoma (EES): a clinico-pathological entity described in 1975 by L. Angervall and F.M. Enzinger. This article reports a new case in which the primary was localized in the right forearm and metastasized to the left lung fourteen years later. A detailed review of the literature emphasized similarities and differences between osseous and extra-osseous Ewing's Sarcoma.

  18. In vitro cultivation of canine osteosarcoma

    International Nuclear Information System (INIS)

    Shifrine, M.; Taylor, N.J.; Holloway, G.L.; DeRock, E.

    1975-01-01

    Radioinduced osteosarcomas were grown in tissue culture; this provides a source of tumor-specific antigen for assaying antibodies directed against the osteosarcoma. Studies were conducted on cell-mediated immunity of 226 Ra-exposed dogs and the correlation of the immune response with radioinduced osteogenesis

  19. Proteomic Technologies for the Study of Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Stephanie D. Byrum

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary bone cancer of children and is established during stages of rapid bone growth. The disease is a consequence of immature osteoblast differentiation, which gives way to a rapidly synthesized incompletely mineralized and disorganized bone matrix. The mechanism of osteosarcoma tumorogenesis is poorly understood, and few proteomic studies have been used to interrogate the disease thus far. Accordingly, these studies have identified proteins that have been known to be associated with other malignancies, rather than being osteosarcoma specific. In this paper, we focus on the growing list of available state-of-the-art proteomic technologies and their specific application to the discovery of novel osteosarcoma diagnostic and therapeutic targets. The current signaling markers/pathways associated with primary and metastatic osteosarcoma that have been identified by early-stage proteomic technologies thus far are also described.

  20. Bifocal sclerosing osteosarcoma: unusual presentation and course

    International Nuclear Information System (INIS)

    Abramovici, L.; Steiner, G.C.; Rosenberg, Z.; Kenan, S.

    1998-01-01

    Multifocal osteosarcoma is uncommon. Long-term survival of an incompletely treated case is exceptional. We report an unusual case of bifocal sclerosing osteosarcoma in a 38-year-old women that involved the left ilium and right proximal femur. The femoral lesion was resected. The tumor in the left ilium was not treated. She did not receive chemotherapy and has been free of metastases for 7 years. Recently, growth of the pelvic osteosarcoma has resulted in vascular compression and edema of the lower extremity. The patient's alkaline phosphatase has been elevated throughout. The tumor was HMB-45 positive, which has not been previously reported in osteosarcoma. The pathogenesis of multifocal osteosarcoma is discussed. (orig.)

  1. Pleiotropic effects of bisphosphonates on osteosarcoma.

    Science.gov (United States)

    Ohba, Tetsuro; Cates, Justin M M; Cole, Heather A; Slosky, David A; Haro, Hirotaka; Ichikawa, Jiro; Ando, Takashi; Schwartz, Herbert S; Schoenecker, Jonathan G

    2014-06-01

    Osteosarcoma is the most common primary malignant tumor of bone and accounts for half of all primary skeletal malignancies in children and teenagers. The prognosis for patients who fail or progress on first-line chemotherapy protocols is poor, therefore, additional adjuvant therapeutic strategies are needed. A recent feasibility study has demonstrated that the nitrogen-containing bisphosphonate zoledronic acid (ZOL) can be combined safely with conventional chemotherapy. However, the pharmacodynamics of bisphosphonate therapy is not well characterized. Osteosarcoma is a highly angiogenic tumor. Recent reports of the anti-angiogenic effects of bisphosphonates prompted us to determine whether nitrogen-containing bisphosphonate (ZOL and alendronate) treatment attenuates osteosarcoma growth by inhibition of osteoclast activity, tumor-mediated angiogenesis, or direct inhibitory effects on osteosarcoma. Here, we demonstrate that bisphosphonates directly inhibit VEGFR2 expression in endothelial cells, as well as endothelial cell proliferation and migration. Additionally, bisphosphonates also decrease VEGF-A expression in osteosarcoma (K7M3) cells, resulting in reduced stimulation of endothelial cell migration in co-culture assays. ZOL also decreases VEGFR1 expression in aggressive osteosarcoma cell lines (K7M3, 143B) and induces apoptosis of these cells, but has negligible effects on less aggressive osteosarcoma cell lines (K12 and TE85). In vivo ZOL treatment results in significant reduction in osteosarcoma-initiated angiogenesis and tumor growth in a murine model of osteosarcoma. In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells. Published by Elsevier Inc.

  2. Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

    Science.gov (United States)

    Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

    2015-07-01

    To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

  3. Maternal and obstetrical outcome in 35 cases of well-differentiated thyroid carcinoma during pregnancy

    DEFF Research Database (Denmark)

    Boucek, Jan; de Haan, Jorine; Halaska, Michael J

    2018-01-01

    of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes. STUDY DESIGN: This is an international cohort study. METHODS: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration...... of the trimester at the time of surgery. However, the potential negative effects of thyroid surgery early in pregnancy demand management of these patients in an experienced multidisciplinary team to provide the best possible care for these patients and their unborn babies. LEVEL OF EVIDENCE: 4 Laryngoscope, 2017....

  4. Primary Well Differentiated Breast Liposarcoma with Divergent Cartilagenous Differentiation: A Case Report

    Directory of Open Access Journals (Sweden)

    Ammar Cherkess Al-Rikabi

    2013-03-01

    Full Text Available Primary liposarcomas of the female and male breasts are very rare. Heterologous differentiation in adipocytic tumors is also an exceedingly rare phenomenon, which is occasionally reported in the literature. We describe the case of a 22 year-old female who presented with a relatively large left breast mass which was clinically diagnosed as a case of giant fibroadenoma, but histologically showed a well differentiated liposarcoma with evidence of extensive chondroid differentiation. The mammographic and radiological features are presented and correlated with the histopathological appearances together with literature review and comparison with similar reported cases.

  5. Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.

    Science.gov (United States)

    Saha, Aniruddha; Mandal, Palash Kumar; Manna, Anupam; Khan, Kalyan; Pal, Subrata

    2018-01-01

    Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.

  6. Rare Cause of Dysphagy: Giant Polypoid Esophageal Well-Differentiated Liposarcoma

    Directory of Open Access Journals (Sweden)

    Ladislav Mica

    2007-06-01

    Full Text Available Liposarcoma represents one of the most frequent (10–20% malignant mesenchymal tumors in the adult, affecting mostly the soft tissue of extremities, the trunk or the retroperitoneum. This tumor type occurs exceptionally rarely in the gastrointestinal tract with only few cases described in the literature. In this case we present a 73-year-old male patient who was admitted due to loss of weight, anorexia and postprandial emesis with dysphagy. Gastrographin esophagography failed to make precise diagnostics. CT scan of the upper gastrointestinal tract revealed a large esophageal tumor filling out the whole length of the esophagus. The tumor was removed by parasternocleidomastoidal approach with a stapler. Histopathological examination revealed a well-differentiated liposarcoma (grade I. Well-differentiated liposarcomas are characterised by amplified material of the 12q13–15 chromosomal region, present in the form of giant or ring chromosomes and leading to the overexpression of MDM2 and CDK4 genes. MDM2 and CDK4 proteins can be detected immunhistochemically, which was the case in the reported tumor. Overexpression of these proteins leads to suppression of tumor suppressor genes, leading to increased cell survival.

  7. EARLY RECURRENCE OF WELL-DIFFERENTIATED ENDOMETRIAL CANCER (A CASE REPORT

    Directory of Open Access Journals (Sweden)

    N. E. Levchrnko

    2017-01-01

    Full Text Available Endometrial cancer is the 6-th most common malignancy in women worldwide, accounting for about 4.8 % of all female cancers. The treatment of recurrent endometrial cancer remains a major challenge. Some endometrial cancer recurrences, for example vaginal stump recurrence, are reported to be effectively treated with surgical resection and radiation therapy. Early recurrence of early-stage well-differentiated endometrial cancer is uncommon. Case report. Herein we report a rare case of recurrent well-differentiated endometrial cancer in a 65-year-old woman. The patient had recurrence 10 months after laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Recurrent endometrial tumor with extension into the rectosigmoid colon, urinary bladder and the right ureter manifested itself clinically with severe pain requiring the use of opioids. The recurrent tumor was removed. Resection of the bladder, left ureter and upper ampular rectum was followed by anastomosis. The patient received multiple cycles of chemotherapy. Conclusion. Compliance with the principles of ablastics during the laparoscopic or laparotomic surgery helps to avoid recurrence in patients with prognostically favorable cancer. In case of recurrence, combined operations are the only possible chance of improving survival of patients with locally advanced or recurrent tumors, which are insensitive to chemoradiotherapy.

  8. Well-differentiated fetal adenocarcinoma: A very uncommon malignant lung tumor

    Directory of Open Access Journals (Sweden)

    H. El Ouazzani

    2012-01-01

    Full Text Available Well-differentiated fetal adenocarcinoma (WDFA is a very uncommon malignant tumor originating in the lung. This report describes the case of a 38-year-old woman with a WDFA treated by surgery. The malignancy is low grade and associated with a good prognosis, and so it is important for clinicians to be aware of and to identify this rare variant of adenocarcinoma. Resumo: O adenocarcinoma fetal bem diferenciado (WDFA, de acordo com a sigla em inglês é um tumor maligno no pulmão muito invulgar que tem origem no pulmão. Este relatório descreve o caso de uma mulher de 38 anos com WDFA tratada através de cirurgia. A malignidade é de baixo grau e está associada a um bom prognóstico e, por isso, é importante que os clínicos estejam atentos e identifiquem esta variante rara de adenocarcinoma. Keywords: Well-differentiated fetal adenocarcinoma, Lung, Good prognosis, Palavras-chave: Adenocarcinoma fetal bem diferenciado, pulmão, bom prognóstico

  9. High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123 for Extraskeletal Ewing's Sarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomoya Sakabe

    2011-01-01

    Full Text Available Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123 contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment.

  10. Synchronous multicentric osteosarcoma: the case for metastases

    International Nuclear Information System (INIS)

    Daffner, R.H.; Kennedy, S.L.; Fox, K.R.; Crowley, J.J.; Sauser, D.D.; Cooperstein, L.A.

    1997-01-01

    Objective. There is a current debate whether multicentric osteosarcoma represents synchronous multiple primary osteosarcomas or metastatic disease. The purpose of this report is to evaluate the etiology, presentation, and classification of this entity. Design and patients. Six patients ranging in age from 7 to 29 years were studied. The clinical, radiographic, and pathologic findings are reported. In addition, a review of the literature was undertaken. Results. The clinical courses of our six patients as well as a review of the literature suggest that multicentric osteosarcoma represent one extreme of a continuous scale of metastatic osteosarcoma rather than multiple synchronous primary tumors. The presentation is unusual and the clinical behavior distinctive, but the mechanism of spread remains the same: blood-borne and lymphatic-borne. Conclusions. Our experience with these six patients supports the concept in the recent literature that synchronous osteosarcoma is one extreme of the spectrum of metastatic osteosarcoma. Its unique features are: (1) multiple radiodense lesions that present simultaneously with or without pulmonary metastases; (2) a single ''dominant'' lesion with multiple smaller lesions; and (3) a uniformly rapid, fatal prognosis. Osteosarcoma should be regarded as a metastatic disease, even when only a single primary lesion is found at the initial presentation. (orig.)

  11. Intracranial osteosarcoma after radiosurgery. Case report

    International Nuclear Information System (INIS)

    Sanno, Naoko; Hayashi, Shinkichi; Shimura, Toshiro; Maeda, Shotaro; Teramoto, Akira

    2004-01-01

    A 56-year-old woman presented with an intracranial osteosarcoma at the site of previous radiosurgery, manifesting as sudden onset of headache and left hemiparesis with aphasia. She had a previous history of stereotactic radiosurgery for an intracranial tumor under a diagnosis of falx meningioma. Computed tomography showed intratumoral and peritumoral hemorrhage at the right parietofrontal region. Gross total resection of the tumor with hematoma was performed. The histological diagnosis was osteosarcoma. Sarcomatous change is a rare complication of radiotherapy. This case illustrates that osteosarcoma may develop years after radiosurgery for benign brain neoplasm. (author)

  12. CONTEMPORARY APPROACHES TO LEVOTHYROXINE THERAPY AFTER SURGERY IN PATIENTS WITH WELL-DIFFERENTIATED THYROID CANCER

    Directory of Open Access Journals (Sweden)

    P. O. Rumyantsev

    2013-01-01

    Full Text Available Levothyroxine therapy with purpose to suppress thyroid stimulating hormone (TSH after surgery in patients with well-differentiated thyroid cancer is implemented since 1937. Accumulated results of levothyroxine suppressive therapy (LST application are attesting its heterogeneous efficacy in various risk groups of tumor recurrence: low, medium and high. Similar risk groups are emphasized towards adverse effect risk due to LST. The more intensivity and duration of TSH suppression the higher risk of adverse effects. First, they include osteopenia or osteoporosis and atrial fibrillation. Contemporary approaches to intensivity and duration of LTS are based on accounting of its potential efficiency into various clinical risk groups of tumor recurrence as well as adverse effects risk groups.

  13. Extraskeletal ewing's sarcoma family of tumors in adults. Prognostic factors and clinical outcome

    International Nuclear Information System (INIS)

    Tural, D.; Molinas Mandel, N.; Dervisoglu, S.

    2012-01-01

    The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma. (author)

  14. [A rare extra-skeletal myxoid chondrosarcoma of the lower leg - is amputation absolutely necessary].

    Science.gov (United States)

    Mroczkowski, P; Evert, M; Tautenhahn, J; Meyer, F; Lippert, H

    2010-02-01

    Sarcomas represent less than 2 % of all malignancies. Special challenges are bone sarcomas in extra-skeletal localisation. The aim of this case report is to show the management of an extraordinary extra-skeletal myxoid chondrosarcoma based on a case report with references from the literature. After a delay in diagnostics for 1.5 years, an MRI scan taken in a 42-year-old male patient with progressive swelling of the left calf showed a soft-tissue tumour in the proximal part of the muscle. Histopathological investigation of a percutaneous biopsy revealed a chondrosarcoma. En-bloc-resection (R 0) of the rear superficial compartment was performed (specimen weight 1 370 g; tumour size 11.5 x 9.5 x 8 cm) leading to the definitive diagnosis of an extra-skeletal myxoid chondrosarcoma. The patient was discharged with a bland wound 8 days after surgery. At 4 weeks postoperatively, the patient received adjuvant radiotherapy with a 56-Gy boost. During the follow-up period of 28 months, there have been neither signs of local tumour recurrence nor distant metastases. The myxoid chondrosarcoma is a rare tumour lesion, and according to the literature, only 2 % occur outside of the skeleton. The accurate diagnostic and therapeutic algorithm allowed a precise preparation for surgery and made amputation obsolete. Compartment resection preserving the main neurovascular bundles as well as enabling an early mobilisation resulted in both sufficient radical resection status and adequate postoperative motor function. Intraoperative clip-marking of the former tumour bed is considered a key point for the focused radiotherapy. Each persistent soft tissue swelling must be appropriately diagnosed using adequate imaging and even biopsy (in case of a doubtful finding), which should be performed with definitive surgery in mind. Georg Thieme Verlag Stuttgart, New York.

  15. Extraskeletal Ewing's sarcoma family of tumors in adults: prognostic factors and clinical outcome.

    Science.gov (United States)

    Tural, Deniz; Molinas Mandel, Nil; Dervisoglu, Sergulen; Oner Dincbas, Fazilet; Koca, Sedat; Colpan Oksuz, Didem; Kantarci, Fatih; Turna, Hande; Selcukbiricik, Fatih; Hiz, Murat

    2012-05-01

    The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma.

  16. Retrotracheal Extraskeletal Ewing's Sarcoma: Case Report and Discussion on Airway Management.

    Science.gov (United States)

    Van Der Meer, Graeme; Linkhorn, Hannah; Gruber, Maayan; Mahadevan, Murali; Barber, Colin

    2017-03-01

    Extraskeletal Ewing's sarcoma is a rare tumor, and the management of airway compromise in case of cervical Ewing's sarcoma has not been established. This report describes the case of a patient with retrotracheal Ewing's sarcoma and discusses a successful approach to airway management. A 12-year-old male presented with a 2-week history of sore throat and sleep-disordered breathing and 48 hours of stridor. Imaging confirmed a retrotracheal soft tissue mass with airway compromise. A planned and controlled approach to his airway management resulted in a secure airway prior to definitive treatment.

  17. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    International Nuclear Information System (INIS)

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies

  18. Osteosarcoma in a woma python (Aspidites ramsayi).

    Science.gov (United States)

    Cowan, M L; Monks, D J; Raidal, S R

    2011-12-01

    Osteosarcoma of the axial skeleton in an 18-month-old woma python (Aspidites ramsayi) is described. A subcutaneous mass overlying the costal arches enlarged progressively over a period of 5 months and, in that time, became ulcerated and more invasive of surrounding tissues. A punch biopsy of the lesion under general anaesthesia provided tissue for histopathology and diagnosis of low-grade osteosarcoma. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

  19. Liver heterotopia in the head of a patient with osteosarcoma of the maxilla. A paracrine tumor-induced hepatogenesis?

    Science.gov (United States)

    Corsi, Alessandro; Riminucci, Mara

    2017-02-01

    Heterotopia of liver tissue is uncommon. It has been reported at various sites, more frequently near the orthotopic liver, including gallbladder, hepatic ligaments, omentum, and retroperitoneum, rarely within the diaphragm and the thoracic cavity, and never within the head. We report here a 22-year-old patient surgically treated for a maxillary osteosarcoma in which microscopic liver tissue islands were incidentally detected in the respiratory mucosa of the surgical margin. The islands comprised well-differentiated HepPar-1-positive hepatocytes and were surrounded by cytokeratin-7- and cytokeratin-19-positive bile duct-like structures. This case, which is unique in the medical literature, may suggest an inductive paracrine effect of the osteosarcoma cells by secretion of factors promoting hepatocyte specification of primitive endodermal progenitors and subsequent liver morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Intracortical osteoblastic osteosarcoma with oncogenic rickets

    International Nuclear Information System (INIS)

    Hasegawa, T.; Hirohashi, Setsuo; Shimoda, Tadakazu; Yokoyama, Ryohei; Beppu, Yasuo; Maeda, Shotaro

    1999-01-01

    Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or rickets, is an unusual clinicopathologic entity in which vitamin D-resistant osteomalacia, or rickets, occurs in association with some tumors of soft tissue or bone. We present a case of oncogenic rickets associated with intracortical osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic abnormalities of rickets disappeared and pertinent laboratory data except for serum alkaline phosphatase became normal after surgical resection of the tumor. Histologically, the tumor was an osteosarcoma with a prominent osteoblastic pattern. An unusual microscopic feature was the presence of matrix mineralization showing rounded calcified structures (calcified spherules). Benign osteoblastic tumors, such as osteoid osteoma and osteoblastoma, must be considered in the differential diagnosis because of the relatively low cellular atypia and mitotic activity of this tumor. The infiltrating pattern with destruction or engulfment of normal bone is a major clue to the correct diagnosis of intracortical osteosarcoma. The co-existing radiographic changes of rickets were due to the intracortical osteosarcoma. (orig.)

  1. Intracortical osteoblastic osteosarcoma with oncogenic rickets

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, T.; Hirohashi, Setsuo [Pathology Division, National Cancer Center Research Institute, Tokyo (Japan); Shimoda, Tadakazu [Clinical Laboratory Division, National Cancer Center Hospital, Tokyo (Japan); Yokoyama, Ryohei; Beppu, Yasuo [Orthopedic Division, National Cancer Center Hospital, Tokyo (Japan); Maeda, Shotaro [Department of Pathology, Nippon Medical School Hospital, Tokyo (Japan)

    1999-01-01

    Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or rickets, is an unusual clinicopathologic entity in which vitamin D-resistant osteomalacia, or rickets, occurs in association with some tumors of soft tissue or bone. We present a case of oncogenic rickets associated with intracortical osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic abnormalities of rickets disappeared and pertinent laboratory data except for serum alkaline phosphatase became normal after surgical resection of the tumor. Histologically, the tumor was an osteosarcoma with a prominent osteoblastic pattern. An unusual microscopic feature was the presence of matrix mineralization showing rounded calcified structures (calcified spherules). Benign osteoblastic tumors, such as osteoid osteoma and osteoblastoma, must be considered in the differential diagnosis because of the relatively low cellular atypia and mitotic activity of this tumor. The infiltrating pattern with destruction or engulfment of normal bone is a major clue to the correct diagnosis of intracortical osteosarcoma. The co-existing radiographic changes of rickets were due to the intracortical osteosarcoma. (orig.) With 8 figs., 25 refs.

  2. The effect of radioactive iodine treatment in well differentiated thyroid carcinoma with lymphnode metastasis

    International Nuclear Information System (INIS)

    Liou, M. J.; Lin, J. D.; Chao, T. C.; Wen, H. F.; Ho, Y. S.

    1994-01-01

    Background: To exam the effect of radioactive iodine treatment for thyroid remnant ablation and/or distant metastasis. A total of 134 well-differentiated thyroid cancer patients with cervical lymphnode metastasis at the time of diagnosis were retrospectively reviewed at Chang Gung Medical Center in Taiwan from 1977 to 1995. Methods: Among them, 126 cases were papillary carcinomas and 8 cases were follicular carcinomas. The mean age was 37.0 ± 14.6 years old. After the operation, 127 (95 %) patients received 131 I treatment (mean dose: 146.6 ± 109.5 mCi, range 30 - 550 mCi) and long-term follow-up. The mean follow-up period is 5.9 ± 3.9 yrs. All patients were restage at the end of 1995. Clinical biochemical results were also analyzed. Results: Among 127 cases who received postoperative radioactive iodine treatment, the majority of cases (92.5 % in papillary ca. vs. 57.1 % in follicular ca.) improved to stage I, 11 (8.6 %) cases remained on the same disease and stages. 13 cases (10.2 %, 10 papillary and 3 follicular) deteriorated to stage III or IV. However, in the non-treatment group, only 33.3 % of papillary carcinoma patients improved to stage I and 16.7 % of the patients remained as stage II. There were 5 cases (3.7 %) of mortality. Two cases with stage IV papillary carcinomas died of metastatic or recurrent malignancy, and the other 2 cases with stage I or III papillary carcinomas died of tracheal cancer or valvular heart disease. One patient with stage IV follicular carcinoma died of cerebral vascular accident. Conclusions: Radioactive iodine ( 131 I) treatment plays a significant role in the management of well-differentiated thyroid carcinoma patients with cervical lymphnode metastasis. The effect of postoperative 131 I treatment on papillary carcinoma was better than that on follicular carcinoma. The optimal dosage and frequency of radioactive iodine treatment warrant further study. (author)

  3. Review of Extraskeletal Activity on Tc-99m Methylene Diphosphonate Bone Scintigraphy and Value of Cross-Sectional and SPECT-CT Imaging Correlation.

    Science.gov (United States)

    Bermo, Mohammed; Behnia, Sanaz; Fair, Joanna; Miyaoka, Robert S; Elojeimy, Saeed

    2017-07-31

    Recognizing the different mechanisms and imaging appearance of extraskeletal Tc-99m methylene diphosphonate uptake enhances the diagnostic value of bone scan interpretation. In this article, we present a pictorial review of the different mechanisms of extraskeletal Tc-99m methylene diphosphonate uptake on bone scintigraphy including neoplastic, inflammatory, ischemic, traumatic, excretory, and iatrogenic. We also illustrate through case examples the added value of correlation with cross-sectional and single photon emission computed tomography and computed tomography imaging in localizing and characterizing challenging cases of extraskeletal uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Primary extraskeletal myxoid chondrosarcoma of bone: Report of three cases and review of the literature.

    Science.gov (United States)

    Finos, L; Righi, A; Frisoni, T; Gambarotti, M; Ghinelli, C; Benini, S; Vanel, D; Picci, P

    2017-05-01

    Extraskeletal myxoid chondrosarcoma is a rare neoplasm of soft tissue. The usual location is in deep parts of the proximal extremities and limb girdles in middle-aged adults. The bone location as primary location is extremely rare and few cases are reported. We present three cases arising in bone with molecular confirmation using both RT-PCR and FISH analysis. Patients include two men and one woman with an age of 62, 69 and 73 years old. The mean size of the lesion was 13cm (range 8-18cm). Tumors arose in the iliac bone in two cases and in the proximal humerus in the other case. At time of diagnosis the three cases show bone cortex and soft tissue involvement. On imaging, lesions have a lobular pattern, are purely lytic, but take up contrast medium after injection. Two patients are alive with disease (local recurrence and lung metastasis) after five years and five years and six months, respectively and one patient died of disease two years after the diagnosis. The primary extraskeletal myxoid chondrosarcoma of bone seems to have a more aggressive behavior than the soft tissue counterpart. The molecular confirmation of diagnosis using RT-PCR is necessary to do the differential diagnosis with other entities, in particular with myoepithelioma that shows similar morphological features and EWSR1 and FUS genes rearrangement. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

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    Collins Michael T

    2012-05-01

    Full Text Available Abstract Fibrous dysplasia (FD is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS. The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues. The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

  6. Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

    Science.gov (United States)

    Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

    2011-04-01

    The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

  7. Diagnostic criteria of well differentiated thyroid tumor of uncertain malignant potential; a histomorphological and immunohistochemical appraisal.

    Science.gov (United States)

    Yassin, Fatma El-Zahraa Salah El-Deen

    2015-06-01

    Well differentiated thyroid tumor of uncertain malignant potential (WDT-UMP) represents a true "gray zone" of "follicular patterned" thyroid lesions, that needs to be characterized in order to outright the diagnosis of carcinoma and avoid unnecessary aggressive treatment. To emphasize on the histomorphological criteria for more accurate diagnosis of WDT-UMP. Also to compare the immunohistochemical expression of CK19 of WDT-UMP versus adenoma and papillary thyroid carcinoma (PTC). The study included 60 thyroid specimens; 18 WDT-UMPs, 24 PTC (18 classic variant and 6 follicular variants) and 18 benign thyroid lesions (8 adenoma, 6 Hashimoto's thyroiditis and 4 hyperplastic nodules). H&E stained sections were assessed according to the published major and minor criteria of malignancy in the thyroid. CK 19 immunostaining was examined and evaluated according to the proportion and intensity scores. We could detect the absence of nuclear inclusions, presence of characteristic nuclear groove, nuclear clearing, ovoid nuclei, nuclear crowdness, nuclear enlargement and pleomorphism as important reliable features for diagnosis of WDT-UMP with p value (<0.0001 for each). WDT-UMP showed moderate to strong CK 19 immunostaining with proportion scores 3 and 4; an intermediate expression profile; higher than adenoma and less than papillary carcinoma (p<0.0001). The constellations of both major and minor criteria of malignancy are important clues for WDT-UMP diagnosis which could be ascertained by CK 19 immunostaining. Copyright © 2015. Production and hosting by Elsevier B.V.

  8. Effect of radioiodine therapy on pulmonary metastases from well-differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Yu Yongli; Jin Changqing; Chen Libo; Lu Hankui; Zhu Ruisen

    2002-01-01

    Objective: To investigate effect of radioiodine therapy on pulmonary metastases from well-differentiated thyroid cancer. Methods: Fifty-eight cases of pulmonary metastases were studied utilizing chest X-ray, pulmonary function test and 99 Tc m -DTPA aerosol clearance examination. Results: The data of pulmonary function test were of no difference between groups of various radiation doses cumulation (P > 0.05). The differences of vital capacity (VC), fast vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ) were not remarkable between the two groups of male or female patients (P > 0.05), but the difference of maximal volume ventilation (MVV) was P 99 Tc m -DTPA aerosol clearance rates between various groups were of no difference (P > 0.05). Only for one female, 43 years old who had received an accumulative dose of 51.8 GBq radioiodine over an 8-yr period, her pulmonary function test showed evidence of restrictive lung disease, chest X-ray showed haziness and DTPA half-time clearance was 26.4 min, which is suggestive of interstitial fibrosis. Conclusion: The cumulative dose of radioiodine and gender of the patients had not statistically significant effects on the pulmonary function. Interstitial fibrosis must be carefully watched when the cumulative radioiodine dose is over 37 GBq

  9. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Van Nostrand, D.; Neutze, J.; Atkins, F.

    1986-01-01

    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach

  10. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Van Nostrand, D.; Neutze, J.; Atkins, F.

    1986-10-01

    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach.

  11. CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.

    Directory of Open Access Journals (Sweden)

    Sanghoon Lee

    Full Text Available The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD and dedifferentiated (DD liposarcomas.From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR.There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05. Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7% and MDM2 amplification in 46 cases (95.8%. WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041. High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54 was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012 and multivariate analyses (P = 0.020.Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

  12. Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

    Science.gov (United States)

    Molenaar, Remco J; Sidana, Surbhi; Radivoyevitch, Tomas; Advani, Anjali S; Gerds, Aaron T; Carraway, Hetty E; Angelini, Dana; Kalaycio, Matt; Nazha, Aziz; Adelstein, David J; Nasr, Christian; Maciejewski, Jaroslaw P; Majhail, Navneet S; Sekeres, Mikkael A; Mukherjee, Sudipto

    2017-12-18

    Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

  13. Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

    Science.gov (United States)

    Hendrickson-Rebizant, J; Sigvaldason, H; Nason, R W; Pathak, K A

    2015-08-01

    Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. The age threshold of 55 years was found to be the best for TNM stage grouping. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Quality of life with well-differentiated thyroid cancer: treatment toxicities and their reduction.

    Science.gov (United States)

    Mendoza, April; Shaffer, Brian; Karakla, Daniel; Mason, M Elizabeth; Elkins, David; Goffman, Thomas E

    2004-02-01

    Patients with well-differentiated thyroid cancer have a good prognosis but a significant chance for local recurrence. In the past, limited surgery with postoperative 131I only for extremely high-risk cases or recurrence was not uncommon. As more aggressive surgical and postoperative treatments appear to gain wider acceptance, toxicity and long-term morbidity become more important issues. Our goal is to present the experience of a single institution with emphasis on oral side effects related to 131I as well as acute and chronic symptoms related to this diagnosis and their impact on quality of life. Fifty-seven patients were followed for a median time of 19.3 months. All patients received therapeutic 131I (mean dose, 154.7 mCi) between January 1, 1996 and August 30, 2002. Fifty-four patients (94.7%) were alive at the time of analysis. Sixteen (28.1%) required a second treatment: any sign of persistence resulted in retreatment. Complaints with 131I treatment included altered taste, 26.3%; acute xerostomia, 21.1%; and acute sialoadenitis, 15.8%. Chronic xerostomia occurred in 6 (35.3%) of all patients who received multiple treatments. The incidence of chronic xerostomia was reduced to 1 of 11 (9.1%) with amifostine pretreatment. Other chronic side effects associated with this disease included fatigue 54.4%, weight gain of more than 6 months duration 24.6%, with 12 (27.9%) of those under 60 experiencing an average gain of 2.3 kg from initial diagnosis. Review of treatment-related symptoms prompted policies to reduce toxicity including amifostine pretreatment for 131I therapy and thyrotropin (synthetic TSH) use in place of iatrogenic hypothyroidism for thyroglobulin testing and scanning.

  15. Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny; Wu, Hong Gyun; Youn, Yeo Kyu; Lee, Kyu Eun; Kim, Kwang Hyun; Park, Do Joon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

  16. Radioiodine therapy in skeletal metastases from well-differentiated thyroid cancer: a Johannesburg experience

    Directory of Open Access Journals (Sweden)

    Nalini Sindy Perumal

    2010-03-01

    Full Text Available Aim.The purpose of this study was to examine the outcome of patients with skeletal metastases from well-differentiated thyroid carcinoma and analyse the effect of variables that influence the prognosis of this disease. Method. We retrospectively reviewed 352 patients treated and followed-up at the Charlotte Maxeke Johannesburg Academic Hospital’s thyroid cancer clinic from 1982 - 1999. Findings. Skeletal metastases were diagnosed in 24 (6.8%, 17 at presentation to the thyroid clinic, and 7 at follow-up. Patients’ ages ranged from 30 - 77 years (mean 53.9 years and the female:male ratio was 3.8:1. Based on the original pathology reports from resected tumours, 9 were papillary and 15 were follicular cancers. Twenty-three of the 24 patients underwent thyroid surgery as the initial management – total thyroidectomy in 18, subtotal thyroidectomy in 3, and lobectomy plus neck dissection in one. The diagnosis of thyroid cancer was based on lobectomy in a single subject. Radioactive iodine (RAI was used as part of the original treatment; external radiation therapy (XRT was mainly used to alleviate severe symptoms. Twenty-one patients (87.5% were treated with RAI; 11 (45.8% received radiotherapy. Seven patients died – 4 from neurological disease directly associated with bone metastases. Of the 17 surviving patients, 2 appeared to be disease-free, 8 were asymptomatic despite overt bony disease, and 7 had persistent symptoms which much improved in 5. Bone metastases were uncommon, and follicular cancer predominated in this survey. Conclusion. RAI therapy improves quality of life in most patients. There is a place for XRT.

  17. Pathogenesis of radiation-induced osteosarcomas

    International Nuclear Information System (INIS)

    Luz, A.

    1980-07-01

    Results backed by experiments are presented here for the osteosarcoma induction in mice after incorporation of radium-224 or thorium-227. The dose-response relationship for osteosarcoma induction by short-lived alpha radiation is very much influenced by the time distribution of the applied activity and is thus influenced by the dose rate in the skeleton. In the total dose range investigated the decrease of the dose rate leads to an increase of the ontogenetic effect to a tumour incidence of nearly 100%. If the internal exposure starts after the period of rapid skeletal growth the osteosarcoma risk is not reduced compared with the young animals and the tumour latency period is even shorter. This reducing of the latency period is dependent on the expected osteosarcoma risk. In the case of a lower exogenic risk the date for the clinical tumour manifestations seems to be determined by the date of the manifestation of spontaneous osteosarcomas whereas, in the case of a great exogenic risk, the agent obviously determines when the tumour appears. A spontaneous osteodysplasia in the skeleton of old female mice certainly cannot be defined as the co-factor of osteosarcomagenesis. The non-neoplastic proliferated cells which are morphologically similar to the osteodysplastia are found to a larger extent in the skeleton of female mice with but also in male mice. It is not clear whether this is a real preneoplasia or a parallel phenomenon of the osteosarcomagenesis. (orig./MG) [de

  18. Cyclin D1 in well differentiated thyroid tumour of uncertain malignant potential.

    Science.gov (United States)

    Lamba Saini, Monika; Weynand, Birgit; Rahier, Jacques; Mourad, Michel; Hamoir, Marc; Marbaix, Etienne

    2015-04-18

    Encapsulated follicular tumours with equivocal papillary thyroid carcinoma (PTC) type nuclear features continue to remain a challenge despite the recent attempts to classify these borderline lesions. The term 'well differentiated tumour of uncertain malignant potential (WDT-UMP)' was introduced to classify these tumours. The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19. Thirteen cases of metastatic PTC, papillary microcarcinoma and follicular variant of PTC (FVPTC) were identified from a histological review of 510 cases. In addition, 13 cases of a subset of follicular adenomatoid nodules with focal areas showing nuclear features characteristic of PTC, identified as WDT-UMP, were also analyzed. Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization. All WDT-UMP lesions showed immunolabelling of cyclin D1, Ki67; 11/ 13 cases showed immunolabelling of CK19; 10/13 cases showed immunolabelling of HBME-1 and 4/13 cases showed immunolabelling of galectin-3. Surrounding benign adenomatoid areas showed no to faint focal staining in all thirteen cases of cyclin D1, HBME-1 and galectin-3. A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an

  19. Predicting survival for well-differentiated liposarcoma: the importance of tumor location.

    Science.gov (United States)

    Smith, Caitlin A; Martinez, Steve R; Tseng, Warren H; Tamurian, Robert M; Bold, Richard J; Borys, Dariusz; Canter, Robert J

    2012-06-01

    Although well-differentiated liposarcoma (WD Lipo) is a low grade neoplasm with a negligible risk of metastatic disease, it can be locally aggressive. We hypothesized that survival for WD Lipo varies significantly based on tumor location. We identified 1266 patients with WD Lipo in the Surveillance, Epidemiology, and End Results database from 1988-2004. After excluding patients diagnosed by autopsy only, those lacking histologic confirmation, those lacking data on tumor location, and those with metastatic disease or unknown staging information, we arrived at a final study cohort of 1130 patients. Clinical, pathologic, and treatment variables were analyzed for their association with overall survival (OS) and disease-specific survival (DSS) using Kaplan-Meier analysis and Cox proportional hazards multivariate models. Mean age was 61 y (± 14.6), 72.2% were white, and 60.4% were male. Eighty-one percent of patients were treated with surgical therapy alone, 4.6% were treated with radiotherapy (RT) alone, and 12.9% were treated with both surgery and RT. Extremity location was most common (41.6%), followed by trunk (29%), retroperitoneal/intra-abdominal (RIA, 21.6%), thorax (4.2%), and head/neck (3.6%). With a median follow-up of 45 mo, median OS was 115 mo (95% confidence interval [CI] 92-138 mo) for RIA tumors compared to not reached for other tumor locations (P = 0.002). On multivariate analysis, increasing age and RIA location both predicted worse OS and DSS while tumor size, race, sex, receipt of RT, and Surveillance, Epidemiology, and End Results (SEER) stage did not. Tumor size became a significant predictor of worse DSS, but not OS, only when site, SEER stage, and extent of resection were removed from the multivariate model. Non-RIA locations, including extremity, experienced statistically similar OS, but 5-y DSS for trunk location was intermediate [92.3%, (95% CI 88.5%-96.1%) compared with 98.0% (95% CI, 96.2%-99.8%) for extremity and 86.6 (95% CI 81

  20. Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients.

    Directory of Open Access Journals (Sweden)

    Jonathan Zagzag

    Full Text Available The incidence of well-differentiated thyroid cancer (WDTC is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2 have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients.The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2 and Obese (BMI≥30 kg/m2 groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups.The final study group contained 270 patients, 181(67% of whom were in the Non-obese Group and 89(33% were in the Obese Group. In the Non-obese group, 81(45% of tumors were found by palpation, 72(40% were found by imaging, and 28(16% were found incidentally. In the Obese group, 40(45% were found by palpation, 38(43% were found by imaging, and 11(12% were found incidentally. These differences were not statistically significant (p-value 0.769.We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an

  1. Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia

    Directory of Open Access Journals (Sweden)

    Zhou Qianjun

    2012-08-01

    Full Text Available Abstract Extraskeletal myxoid chondrosarcoma (EMC is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682

  2. Primary extraskeletal myxoid chondrosarcoma in cerebellum: A case report with literature review.

    Science.gov (United States)

    Qin, You; Zhang, Hai-Bo; Ke, Chang-Shu; Huang, Jing; Wu, Bian; Wan, Chao; Yang, Chen-Su; Yang, Kun-Yu

    2017-11-01

    Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm of which intracranial EMC is the rarest. We present an unusual case report of a 41-year-old woman who was sent to the emergency department for a sudden headache and other symptoms related to increased intracranial pressure. Emergent CT revealed an occupying lesion in the left cerebellum with surrounding edema. A complete surgical excision of the lesion through a transcortical approach was performed. After the operation, this patient received adjuvant radiotherapy and temozolomide treatment. Pathology diagnosis was an intracranial EMC. The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival exceeded 20 months. We have reviewed the literature and here summarize the diagnosis and treatment options for intracranial EMC. Diagnosis and treatment options of this rare disease are discussed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  3. Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

    International Nuclear Information System (INIS)

    Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

    1982-01-01

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

  4. The impact of vitamin D in pregnancy on extraskeletal health in children

    DEFF Research Database (Denmark)

    Christesen, Henrik T; Elvander, Claes; Lamont, Ronald F

    2012-01-01

    The impact of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring has become a "hot topic" with a potential for cost-beneficial prevention. The objective of this study was to systematically review the level I and II evidence. PubMed, Embase and Cochrane databases...... were searched using the MeSH terms "vitamin D" AND "pregnancy" until 1 January 2012. The search was limited to randomized controlled trials (evidence level I) and observational studies (evidence level II) in humans and in the English language. Papers reporting on vitamin D supplementation...... no effect in five other studies. In cohort and case-control studies, higher vitamin D intake, or higher 25OHD, was associated with increased birthweight in large studies only, and modified by vitamin D receptor polymorphisms and by race (U-shaped in Caucasians in one unconfirmed study). The risks of HIV...

  5. The role of imaging in the evaluation of extraskeletal Ewing’s sarcoma

    Directory of Open Access Journals (Sweden)

    Pieter Barnardt

    2013-03-01

    Full Text Available Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing’s sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing’s sarcoma (ESS. Computed tomography (CT scanning and magnetic resonance imaging (MRI features of Ewing’s sarcoma are non-specific, and a radiological differential diagnosis should be considered. Ewing’s sarcoma is confirmed by features on histological analysis. In young people who present with soft-tissue tumours, ESS should be considered. In the management of patients with tumours, imaging techniques are useful for biopsy guidance, evaluating the possibility of resection, and tumour response to treatment.

  6. Preoperative and intraoperative irradiation for osteosarcoma

    International Nuclear Information System (INIS)

    Furuya, Kotaro; Amino, Katsuhisa; Kawaguchi, Noriyoshi.

    1980-01-01

    1) 8 cases of osteosarcoma were treated with preoperative massive irradiation, the over 5 years survival rate was 3/8 (37.5%). 7 out of 8 cases (87.5%) metastasized to the lung. From these result, it is considered that tumorspecific immunological effect can not be expected from irradiation. Irradiation therapy is essentially a local treatment, and therefore systemic chemotherapy is necessary to prevent metastasis. 2) Osteosarcoma was considered to be radioresistant tumor previously, however local control can be obtained by direct view irradiation without the damage of surrounding tissue. This irradiation method is indicated only for young adult in whom the primary tumor is localized. 3) In the experimental study on heterotransplanted human osteosarcoma in nude mice, combined treatment with radiation and chemotherapy (HD-MTX, ADM and EDX) was proven to be more effective as compared with radiation alone. (author)

  7. [Expression of IMP3 in osteosarcoma and its clinical significance].

    Science.gov (United States)

    Li, Kang-hua; Huang, Yue-ping; Zhang, Jun; Li, Guo-jun; Li, Si-hong

    2009-05-01

    To analyze the expressional variability of IMP3 between osteosarcoma and osteochondroma and explore its clinical significance. Paraffin sections from 68 patients with osteosarcoma and 20 patients with osteochondroma were examined for the expression of IMP3 by SP immunohistochemistry. The negative, weak positive, moderate positive and strong positive expression rates of IMP3 in 68 patients with osteosarcoma were 4.41% (3/68), 22.06% (15/68), 22.74% (19/68), 45.59% (31/68), respectively, which were significantly higher than those in 20 cases of osteochondroma tissues (P<0.01). The positive expression of IMP3 in osteosarcoma was negative correlation with the 3-year survival rate of osteosarcoma patients after the operation (P<0.01). The results suggest that IMP3 plays important roles in the tumorigenesis, progress and prognosis of osteosarcoma, and the expression of IMP3 may be an important feature of osteosarcoma.

  8. Cell mediated immunity in patients with osteosarcoma

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Henning, C.B.

    1975-01-01

    Because of the difficulty of obtaining suitable material, earlier studies on cell mediated immunity in the radium patients failed to include positive controls. Recently we were fortunate in obtaining samples of lymphocytes from two suitable patients who had had amputations for spontaneous osteosarcoma six months previously. Lymphocytes from both of these patients showed cytotoxicity to cultured cells derived from a human osteogenic sarcoma but not to normal fibroblasts. These results help to validate our test for early detection of osteosarcoma in the radium patients using measurements of cytotoxicity

  9. The genetics of radiation-induced osteosarcoma

    International Nuclear Information System (INIS)

    Rosemann, M.; Kuosaite, V.; Nathrath, M.; Atkinson, M.J.

    2002-01-01

    Individual genetic variation can influence susceptibility to the carcinogenic effects of many environmental carcinogens. In radiation-exposed populations those individuals with a greater genetically determined susceptibility would be at greater risk of developing cancer. To include this modification of risk into radiation protection schemes it is necessary to identify the genes responsible for determining individual sensitivity. Alpha-particle-induced osteosarcoma in the mouse has been adopted as a model of human radiation carcinogenesis, and genome-wide screens have been conducted for allelic imbalance and genetic linkage. These studies have revealed a series of genes involved in determining the sensitivity to radiogenic osteosarcoma formation. (author)

  10. Whole Genome Analyses of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements

    Science.gov (United States)

    Egan, Jan B.; Barrett, Michael T.; Champion, Mia D.; Middha, Sumit; Lenkiewicz, Elizabeth; Evers, Lisa; Francis, Princy; Schmidt, Jessica; Shi, Chang-Xin; Van Wier, Scott; Badar, Sandra; Ahmann, Gregory; Kortuem, K. Martin; Boczek, Nicole J.; Fonseca, Rafael; Craig, David W.; Carpten, John D.; Borad, Mitesh J.; Stewart, A. Keith

    2014-01-01

    Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2. PMID:24505276

  11. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan B Egan

    Full Text Available Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  12. The value of fat-suppressed T2 or STIR sequences in distinguishing lipoma from well-differentiated liposarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Galant, J. [Servicio de Radiodiagnostico, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain); Resonancia Magnetica del Sureste, Murcia (Spain); Marti-Bonmati, L. [Department of Radiology, Hospital Universitario Dr. Peset, Valencia (Spain); Saez, F. [Department of Radiology, Hospital Cruces de Baracaldo, Vizcaya (Spain); Soler, R. [Department of Radiology, Hospital Juan Canalejo, A Coruna (Spain); Alcala-Santaella, R. [Department of Traumatology, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain); Navarro, M. [Servicio de Radiodiagnostico, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain)

    2003-02-01

    The objective of this study was to evaluate the diagnostic value of fat-suppressed T2-weighted (FS-T2) images or short tau inversion recovery (STIR) imaging in distinguishing lipoma from lipoma-like subtype of well-differentiated liposarcoma. Spin-echo T1-weighted and STIR or fat-suppression T2-weighted sequences were performed in 60 lipomas and 32 lipoma-like well-differentiated liposarcomas, histologically proven, looking for thick septa or nodules in T1-weighted images and linear, nodular, or amorphous hyperintensities on FS-T2/STIR sequences. Fourteen lipomas (23.3%) showed thick septa and/or nodules on T1, whereas on FS-T2 or STIR sequences only seven (11.7%) displayed hyperintense nodules and/or septa. All well-differentiated liposarcomas contained these signs on FS-T2 or STIR sequences. The presence of hyperintense septa or nodules in a predominantly lipomatous tumor on FS-T2/STIR sequences helps to differentiate malignant tumors from lipomas. Employing the presence of hyperintense nodules and/or septa as criteria of malignancy specificity was 76.6% and sensitivity 100%. Overdiagnoses of well-differentiated liposarcoma can occur due to the presence of non-lipomatous areas within lipomas. (orig.)

  13. The value of fat-suppressed T2 or STIR sequences in distinguishing lipoma from well-differentiated liposarcoma

    International Nuclear Information System (INIS)

    Galant, J.; Marti-Bonmati, L.; Saez, F.; Soler, R.; Alcala-Santaella, R.; Navarro, M.

    2003-01-01

    The objective of this study was to evaluate the diagnostic value of fat-suppressed T2-weighted (FS-T2) images or short tau inversion recovery (STIR) imaging in distinguishing lipoma from lipoma-like subtype of well-differentiated liposarcoma. Spin-echo T1-weighted and STIR or fat-suppression T2-weighted sequences were performed in 60 lipomas and 32 lipoma-like well-differentiated liposarcomas, histologically proven, looking for thick septa or nodules in T1-weighted images and linear, nodular, or amorphous hyperintensities on FS-T2/STIR sequences. Fourteen lipomas (23.3%) showed thick septa and/or nodules on T1, whereas on FS-T2 or STIR sequences only seven (11.7%) displayed hyperintense nodules and/or septa. All well-differentiated liposarcomas contained these signs on FS-T2 or STIR sequences. The presence of hyperintense septa or nodules in a predominantly lipomatous tumor on FS-T2/STIR sequences helps to differentiate malignant tumors from lipomas. Employing the presence of hyperintense nodules and/or septa as criteria of malignancy specificity was 76.6% and sensitivity 100%. Overdiagnoses of well-differentiated liposarcoma can occur due to the presence of non-lipomatous areas within lipomas. (orig.)

  14. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature

    OpenAIRE

    Vigo, Federica; Ciammella, Patrizia; Valli, Riccardo; Cagni, Elisabetta; Iotti, Cinzia

    2012-01-01

    Abstract Introduction Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. Case presentation A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery w...

  15. Hedgehog Signaling Inhibitors as Anti-Cancer Agents in Osteosarcoma

    International Nuclear Information System (INIS)

    Ram Kumar, Ram Mohan; Fuchs, Bruno

    2015-01-01

    Osteosarcoma is a rare type of cancer associated with a poor clinical outcome. Even though the pathologic characteristics of OS are well established, much remains to be understood, particularly at the molecular signaling level. The molecular mechanisms of osteosarcoma progression and metastases have not yet been fully elucidated and several evolutionary signaling pathways have been found to be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh) pathway. The present review will outline the importance and targeting the hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data also suggest that aberrant Hh signaling has pro-migratory effects and leads to the development of osteoblastic osteosarcoma. Activation of Hh signaling has been observed in osteosarcoma cell lines and also in primary human osteosarcoma specimens. Emerging data suggests that interference with Hh signal transduction by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby preventing osteosarcomagenesis. From this perspective, we outline the current state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh signaling by inhibitors promise to increase the efficacy of osteosarcoma treatment and improve patient outcome

  16. Mast Cells Density in Fibrotic Capsule of Enchondroma and Well-Differentiated Chondrosarcoma: A Method for Histopathologic Differentiation

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Kharazi Fard

    2012-02-01

    Full Text Available Background: An enchondroma is a benign and a well-differentiated chondrosarcoma is an invasive chondroid tumor with high recurrence potential. In spite of biologic differences, these two tumors have very similar histopathologic appearance. It has been shown that the biologic nature of the connective tissue around benign and malignant tumors varies in the number of mast cells. The aim of this study was to study the histopathologic distinction of enchondroma and well-differentiated chondrosarcoma using the density of the mast cells in fibrotic capsule. Methods: Twelve enchondroma and 15 well-differentiated chondrosarcoma were collected from Pathology department of Cancer Institute and Central Pathology department of Imam Khomeini Hospital in Tehran. 3 micron paraffin embedded tissue sections were stained by toluidine blue for mast cells counting. Mast cells were counted in fibrous capsule of all cases. Mast cells counts were accomplished in 10 high power fields .The average number of mast cells in 10HPF was determined as an index for each lesion. Mann-Whitney U test was used for statistical analysis. Results: Mean index in enchondroma and well-differentiated chondrosarcoma groups were 0.1±0.12 and 0.31±0.33 respectively, showing a significant difference between number of mast cells in the fibrotic capsule in these two lesions (p=0.028. Comparison of the corresponding points in ROC curve, showed a cut-off point = 0.15, with positive predictive value of 61%, negative predictive value 71%, specificity of 33.3% and sensitivity of 66.7%, (p=0.025. Conclusion: Average density of the mast cells in the surrounding fibrotic capsules of enchondroma and well-differentiated chondrosarcoma along with other criterions, could be a beneficial factor for histologically differentiation between these two lesions.

  17. Primary osteosarcoma of the cranial vault

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Gabriel Lacerda; Natal, Marcelo Ricardo Canuto; Cruz, Celio Lucio Palha da; Nascif, Rafael Lemos; Tsuno, Niedja Santos Goncalves; Tsuno, Marco Yukio, E-mail: gabriellacerdafernandes@gmail.com [Diagnostico por Imagem, Brasilia, DF, (Brazil); Hospital de Base do Distrito Federal (HBDF), Brasilia, DF (Brazil); Hospital Sao Luiz, Sao Paulo, SP (Brazil); Instituto do Cancer do Estado de Sao Paulo (ICESP), Sao Paulo, SP (Brazil); Imagem e Laboratorio, Brasilia, DF (Brazil)

    2017-07-15

    Only 5-10% of osteosarcomas arise from the craniofacial bones. We report the case of a 14-year-old female patient who presented with headache and a mass that had been growing in the left frontoparietal region for six months. We describe the findings on conventional radiography, computed tomography, and magnetic resonance imaging. (author)

  18. Diagnosis of extraskeletal myxoid chondrosarcoma in the thigh using EWSR1-NR4A3 gene fusion: a case report.

    Science.gov (United States)

    Kobayashi, Hiroki; Kikuta, Kazutaka; Sekita, Tetsuya; Susa, Michiro; Nishimoto, Kazumasa; Sasaki, Aya; Kameyama, Kaori; Sugita, Shintaro; Hasegawa, Tadashi; Nakamura, Masaya; Matsumoto, Morio; Morioka, Hideo

    2016-11-10

    Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma that has unusual ultrastructural and molecular features. However, unlike other soft tissue sarcomas, it does not have specific clinical symptoms or radiological features, which can make its diagnosis difficult. Nevertheless, extraskeletal myxoid chondrosarcoma has a rare gene fusion (EWSR1-NR4A3) that is useful for making a differential diagnosis. A 43-year-old Japanese man presented with a soft tissue mass in his right thigh. A physical examination and radiography revealed a large soft tissue mass. During magnetic resonance imaging, the mass exhibited isointensity on T1-weighted images and high intensity on T2-weighted images, as well as gadolinium enhancement at the side edge of the partition structure. Thus, we considered a possible diagnosis of a malignant myxoid soft tissue tumor, such as myxoid liposarcoma, myxofibrosarcoma, or metastatic carcinomas, including myoepithelial tumor and neuroendocrine tumor, and performed an incisional biopsy to make a definitive diagnosis. The pathological findings revealed a lobulated tumor with a myxoid structure and atypical spindle-shaped cells that created eosinophilic cord-like forms. Immunohistochemistry revealed that the tumor was positive for S-100 and negative for synaptophysin, chromogranin A, and pan keratin (AE1/AE3). The percentage of Ki-67 was 10 % in the hot spot area. Based on these clinicopathological findings, we initially considered the possibility of a myxoid liposarcoma, although we did not observe any lipoblasts. Therefore, we considered the possibility of an extraskeletal myxoid chondrosarcoma. As this tumor is very rare, we searched for the EWSR1-NR4A3 gene fusion using fluorescence in situ hybridization, which confirmed the diagnosis of extraskeletal myxoid chondrosarcoma. Positron emission tomography-computed tomography did not identify any obvious metastases, and we performed radical resection of our patient's vastus medialis and

  19. Polyostotic Chondroblastic Osteosarcoma in a Kestrel ( Falco tinnunculus ).

    Science.gov (United States)

    De Luca Bossa, Luigi Maria; Mennonna, Giuseppina; Meomartino, Leonardo; Paciello, Orlando; Ciccarelli, Francesca; De Biase, Davide; Raia, Pasquale; Caputo, Vincenzo; Fioretti, Alessandro; Dipineto, Ludovico

    2015-12-01

    We report a case of polyostotic chondroblastic osteosarcoma in a kestrel ( Falco tinnunculus ) admitted to the Wildlife Rehabilitation and Rescue Center (Naples, Italy). A consolidated fracture of the left tibiotarsus bone and a deviation of the limb were evident. After radiographic, cytologic, and histopathologic examinations, a diagnosis of polyostotic chondroblastic osteosarcoma was made. To our knowledge, this is the first report on polyostotic chondroblastic osteosarcoma in a kestrel.

  20. A case of radiation-induced osteosarcoma of the maxilla

    International Nuclear Information System (INIS)

    Tanaka, Rie; Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi

    2003-01-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  1. A case of radiation-induced osteosarcoma of the maxilla

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Rie [Shimada City Hospital, Shizuoka (Japan); Asato, Ryo; Tanaka, Shinzo; Hiratsuka, Yasuyuki; Ito, Juichi [Kyoto Univ. (Japan). Faculty of Medicine

    2003-02-01

    Radiation-induced osteosarcoma in the head and neck region is very rare. A 68-year-old female, who had been treated with radiation for malignant lymphoma of the right maxillary sinus, presented with right cheek swelling. Imaging examinations demonstrated a huge mass occupying the right nasal cavity and paranasal sinuses. Total maxillectomy was performed, and the tumor was histologically diagnosed as osteosarcoma. Diagnosis and treatment for radiation-induced osteosarcoma in the head and neck is discussed. (author)

  2. Osteosarcoma with atypical location in an elderly female patient

    Directory of Open Access Journals (Sweden)

    Daniel Cury Ogata

    2011-12-01

    Full Text Available Osteosarcoma most frequently affects long bones, particularly around theknee, and is therefore rare in the forearm. We report the case of a 67-year-oldwoman presenting with progressive lesion of the distal radius. A pathologicaldiagnosis of osteoblastic osteosarcoma was suspected and was confirmed byneedle biopsy. There had been two other cases of osteosarcoma in the samefamily. The patient was treated with neoadjuvant chemotherapy followed byamputation of the arm below the elbow.

  3. The Immunotherapy of Canine Osteosarcoma: A Historical and Systematic Review

    OpenAIRE

    Wycislo, K.L.; Fan, T.M.

    2015-01-01

    Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high?grade osteosarcoma have not changed in the past 20?years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for d...

  4. Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

    Directory of Open Access Journals (Sweden)

    Andrea Montagnani

    2015-11-01

    Full Text Available Vitamin D and calcium are essential for bone health. An adequate calcium-phosphorus product determines a high quality mineralization long lifetime. In older people, both calcium and vitamin D levels may be lower causing osteomalacia and/or osteoporosis with a higher risk of fracture. Epidemiological data have clearly associated serum vitamin D lower levels (deficiency with bone fracture in older people, however, not univocal data exist in regard to a beneficial effect of vitamin D supplementation in general population. Although not systematic, the present review aims to make a narrative synthesis of the most recent published data on vitamin D effect not only on bone, classical target associated with vitamin D studies, but namely on extraskeletal diseases. In fact, recently, there has been an increasing interest on this latter issue with surprising findings. Vitamin D, and in particular its deficiency, seems to have a role in pathophysiological pathways in several diseases involving cardiovascular, central nervous system and neoplastic process. On the other hand, vitamin D supplementation may modify the outcome of a wide range of illnesses. Up to date the data are conflicting mainly because of difficulty to establish a consensus on the threshold of vitamin D deficit. The US Institute of Medicine recommends to distinguish a level of insufficiency [defined as 30-50 nmol/L or 16-25 ng/mL of 25(OHD] and another of deficiency identified by 25(OHD levels lower than 30 nmol/L (or <16 ng/mL. This latter level is considered a minimum level necessary in older adults to minimize the risk of falls, fracture and probably to have some effects of vitamin D supplementation in extraskeletal diseases. Although there are no absolute certainties in such issue, the most recent data suggest that vitamin D deficiency, and its supplementation, may play an important role in a wide range of diseases other than in bone metabolic diseases in older but not in general

  5. DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

    DEFF Research Database (Denmark)

    Conde, Ana R; Martins, Ana P; Brito, Miguel

    2007-01-01

    in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric...... preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.......Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved...

  6. The immunotherapy of canine osteosarcoma: a historical and systematic review.

    Science.gov (United States)

    Wycislo, K L; Fan, T M

    2015-01-01

    Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high-grade osteosarcoma have not changed in the past 20 years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for delaying metastatic progression with cytotoxic agents, exploration of alterative adjuvant therapies for improving management of osteosarcoma micrometastases is clinically justified. Evidence suggests that osteosarcoma is an immunogenic tumor, and development of immunotherapies for the treatment of microscopic lung metastases might improve long-term outcomes. In this review, the history and foundational knowledge of immune interactions to canine osteosarcoma are highlighted. In parallel, immunotherapeutic strategies that have been explored for the treatment of canine osteosarcoma are summarized. With a greater understanding and awareness for how the immune system might be redirected toward combating osteosarcoma metastases, the rational development of diverse immune strategies for managing osteosarcoma holds substantial promise for transforming the therapeutic landscape and improving disease management in both dogs and human beings. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  7. Raman spectroscopy for grading of live osteosarcoma cells.

    Science.gov (United States)

    Chiang, Yi-Hung; Wu, Stewart H; Kuo, Yi-Chun; Chen, How-Foo; Chiou, Arthur; Lee, Oscar K

    2015-04-18

    Osteosarcoma is the most common primary malignant bone tumor, and the grading of osteosarcoma cells relies on traditional histopathology and molecular biology methods, which require RNA extraction, protein isolation and immunohistological staining. All these methods require cell isolation, lysis or fixation, which is time-consuming and requires certain amount of tumor specimen. In this study, we report the use of Raman spectroscopy for grading of malignant osteosarcoma cells. We demonstrate that, based on the detection of differential production of mineral species, Raman spectroscopy can be used as a live cell analyzer to accurately assess the grades of osteosarcoma cells by evaluating their mineralization levels. Mineralization level was assessed by measuring amount of hydroxyapatite (HA), which is highly expressed in mature osteoblasts, but not in poorly differentiated osteosarcoma cell or mesenchymal stem cells, the putative cell-of-origin of osteosarcoma. We found that under Raman spectroscopy, the level of HA production was high in MG-63 cells, which are low-grade. Moreover, hydroxyapatite production was low in high-grade osteosarcoma cells such as 143B and SaOS2 cells (p Raman spectroscopy for the measurement of HA production by the protocol reported in this study may serve as a useful tool to rapidly and accurately assess the degree of malignancy in osteosarcoma cells in a label-free manner. Such application may shorten the period of pathological diagnosis and may benefit patients who are inflicted with osteosarcoma.

  8. Farnesyl diphosphate synthase is involved in the resistance to zoledronic acid of osteosarcoma cells. : resistance of osteosarcoma to nitrogen bisphosphonates

    OpenAIRE

    Ory , Benjamin; Moriceau , Gatien; Trichet , Valérie; Blanchard , Frédéric; Berreur , Martine; Rédini , Françoise; Rogers , Michael; Heymann , Dominique

    2008-01-01

    International audience; We recently demonstrated original anti-tumor effects of zoledronic acid (Zol) on osteosarcoma cell lines independently of their p53 and Rb status. The present study investigated the potential Zol-resistance acquired by osteosarcoma cells after prolonged treatment. After 12 weeks of culture in the presence of 1 microm Zol, the effects of high doses of Zol (10-100 microm) were compared between the untreated rat (OSRGA, ROS) and human (MG63, SAOS2) osteosarcoma cells and ...

  9. Investigation of osteosarcoma genomics and its impact on targeted therapy: an international collaboration to conquer human osteosarcoma

    OpenAIRE

    Yang, Ji-Long

    2014-01-01

    Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults. The lack of progress in managing this devastating disease in the clinic has prompted international researchers to collaborate to profile key genomic alterations that define osteosarcoma. A team of researchers and clinicians from China, Finland, and the United States investigated human osteosarcoma by integrating transcriptome sequencing (RNA-seq), high-density genome-wide array comparat...

  10. Solitary extra-skeletal sinonasal metastasis from a primary skeletal Ewing's sarcoma.

    Science.gov (United States)

    Hayes, S M; Jani, T N; Rahman, S M; Jogai, S; Harries, P G; Salib, R J

    2011-08-01

    Ewing's sarcoma is a rare, malignant tumour predominantly affecting young adolescent males. We describe a unique case of an isolated extra-skeletal metastasis from a skeletal Ewing's sarcoma primary, arising in the right sinonasal cavity of a young man who presented with severe epistaxis and periorbital cellulitis. Histologically, the lesion comprised closely packed, slightly diffuse, atypical cells with round, hyperchromatic nuclei, scant cytoplasm and occasional mitotic figures, arranged in a sheet-like pattern. Immunohistochemical analysis showed positive staining only for cluster of differentiation 99 glycoprotein. Fluorescent in situ hybridisation identified the Ewing's sarcoma gene, confirming the diagnosis. Complete surgical resection was achieved via a minimally invasive endoscopic transnasal approach; post-operative radiotherapy. Ten months post-operatively, there were no endoscopic or radiological signs of disease. Metastatic Ewing's sarcoma within the head and neck is incredibly rare and can pose significant diagnostic and therapeutic challenges. An awareness of different clinical presentations and distinct histopathological features is important to enable early diagnosis. This case illustrates one potential management strategy, and reinforces the evolving role of endoscopic transnasal approaches in managing sinonasal cavity and anterior skull base tumours.

  11. Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach

    Science.gov (United States)

    Varshney, Jyotika; Scott, Milcah C.; Largaespada, David A.; Subramanian, Subbaya

    2016-01-01

    Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and targetable pathways for

  12. Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach

    Directory of Open Access Journals (Sweden)

    Jyotika Varshney

    2016-01-01

    Full Text Available Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and

  13. Serum tumor markers in pediatric osteosarcoma: a summary review

    Directory of Open Access Journals (Sweden)

    Savitskaya Yulia A

    2012-03-01

    Full Text Available Abstract Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine is an attractive concept for regulation of vascularization in pediatric osteosarcoma.

  14. Case report 461: Dedifferentiated parosteal osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, D.D.; Chase, D.R.

    1988-01-01

    A case of parosteal osteosarcoma has been presented. The lesion initially appeared aggressive on the radiographs but very indolent pathologically. The progressive increase in anaplasia, cellularity and aggressive behavior of the tumor reflects dedifferentiation from a pathologically indolent lesion to a high grade sarcoma with metastatic potential. The rapid progression and demise of the patient, once dedifferentiation occurred, stress the need for correct diagnosis and appropriate therapy at the time the patient presents initially. (orig.)

  15. Radiation, chemotherapy and surgery for canine osteosarcoma

    International Nuclear Information System (INIS)

    Powers, B.E.; Withrow, S.J.; La Rue, S.M.; Straw, R.C.; Gillette, E.L.

    1987-01-01

    Spontaneous canine osteosarcomas is an excellent model for of human osterosarcoma. Twenty dogs with obsteorsarcoma were treated with intravenous or intraarterial cisplatin with or without radiation therapy. This treatment was given 3 weeks prior to limb sparing surgery involving excision of the tumor and allograft replacement. The excised tumor specimen was examined for complete removal and percentage of necrotic tumor measured by planimetry. Intraveneous and intraarterial cisplatin and radiation methods were compared. Data discussing rate of disease development and recurrences is given

  16. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Science.gov (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  17. Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma

    NARCIS (Netherlands)

    Tavanti, E.; Sero, V.; Vella, S.; Fanelli, M.; Michelacci, F.; Landuzzi, L.; Magagnoli, G.; Versteeg, R.; Picci, P.; Hattinger, C. M.; Serra, M.

    2013-01-01

    Aurora kinases are key regulators of cell cycle and represent new promising therapeutic targets in several human tumours. Biological relevance of Aurora kinase-A and -B was assessed on osteosarcoma clinical samples and by silencing these genes with specific siRNA in three human osteosarcoma cell

  18. Expression and prognostic relevance of PRAME in primary osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Pingxian; Zou, Changye; Yong, Bicheng [Department of Orthopaedic Surgery, Musculoskeletal Tumor Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Han, Ju [Department of Pathology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Zhang, Longjuan [Surgery Lab. Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Su, Qiao [Experimental Animal Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Yin, Junqiang; Wang, Jin; Huang, Gang [Department of Orthopaedic Surgery, Musculoskeletal Tumor Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Peng, Tingsheng [Department of Pathology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China); Shen, Jingnian, E-mail: shenjingnan@126.com [Department of Orthopaedic Surgery, Musculoskeletal Tumor Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 (China)

    2012-03-23

    Graphical abstract: High PRAME expression was associated with osteosarcoma patients' poor prognosis and lung metastasis. Highlights: Black-Right-Pointing-Pointer We analyzed and verified the role of PRAME in primary osteosarcoma. Black-Right-Pointing-Pointer High PRAME expression in osteosarcoma correlated to poor prognosis and lung metastasis. Black-Right-Pointing-Pointer PRAME siRNA knockdown significantly suppressed the proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. -- Abstract: The preferentially expressed antigen of melanoma (PRAME), a cancer-testis antigen with unknown function, is expressed in many human malignancies and is considered an attractive potential target for tumor immunotherapy. However, studies of its expression and function in osteosarcoma have rarely been reported. In this study, we found that PRAME is expressed in five osteosarcoma cell lines and in more than 70% of osteosarcoma patient specimens. In addition, an immunohistochemical analysis showed that high PRAME expression was associated with poor prognosis and lung metastasis. Furthermore, PRAME siRNA knockdown significantly suppressed the proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. Our results suggest that PRAME plays an important role in cell proliferation and disease progression in osteosarcoma. However, the detail mechanisms of PRAME function in osteosarcoma require further investigation.

  19. Osteosarcoma: A rare cause of painful enlargement of the hallux.

    LENUS (Irish Health Repository)

    Sproule, J A

    2011-12-01

    Malignant osseous and soft-tissue tumors of the foot are rare. We report a case of osteosarcoma in the proximal phalanx of the hallux in a 45-year-old man. In patients with foot-related symptoms, a high index of suspicion for pedal osteosarcoma is required. Delayed or inappropriate diagnosis may compromise limb-sparing surgery and survivorship.

  20. Clinical and molecular features of high-grade osteosarcoma

    NARCIS (Netherlands)

    Anninga, Jakob Klaas

    2013-01-01

    It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective

  1. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    -MDS/AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... years after finishing treatment. We included all children (n=14) who where diagnosed from October 2006 to January 2011 at our department and treated according to the EURAMOS-1 protocol. Four patients relapsed and died before the end of the study period. We found noteworthy changes in MCV, platelets...... for osteosarcoma developed haematological abnormalities similar to early MDS but few developed t-MDS/AML. Close monitoring of patients recovering from osteosarcoma is essential. Keywords: Osteosarcoma, t-MDS/AML, Haematological abnormalities, Children...

  2. Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

    International Nuclear Information System (INIS)

    Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.; Gustafson, Carl; Gupta, Shiv K.; Riester, Scott M.; Maran, Avudaiappan; Galindo, Mario; Wijnen, Andre J. van; Sarkaria, Jann N.; Yaszemski, Michael J.

    2017-01-01

    Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK CS ), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PK CS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK CS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PK CS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PK CS inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively radiosensitizes osteosarcoma cells. • Combining KU60648 with radiation increases G2/M accumulation and DNA damage.

  3. Well-differentiated adenocarcinoma of the gallbladder with intratumoral cystic components due to abundant mucin production: a mimicker of adenomyomatosis

    International Nuclear Information System (INIS)

    Yoshimitsu, Kengo; Irie, Hiroyuki; Aibe, Hitoshi; Tajima, Tsuyoshi; Nishie, Akihiro; Asayama, Yoshiki; Matake, Kunishige; Honda, Hiroshi; Yamaguchi, Kouji; Matsuura, Shuji

    2005-01-01

    The prevalence and etiology of the cystic components within gallbladder carcinomas as seen on MR images were evaluated. A retrospective review of MR images was performed for 35 proven gallbladder carcinomas in search of radiologically detectable intratumoral cystic components. The pathologic specimens were meticulously reviewed to determine the etiology. MR images of 31 adenomyomatoses were also reviewed for comparison to clarify the difference in MR features between these two entities. Three cases out of 35 proven gallbladder carcinomas were found to have intratumoral cystic components. They were all well-differentiated adenocarcinomas, and the cystic components consisted of dilated neoplastic glands filled with abundant mucin pool. Adenomyomatosis tended to have more and rounded cystic components (Rokitansky-Aschoff sinuses) lined in a linear fashion and were flat-elevated in shape, smaller in size and had a regular surface, as compared to the three carcinomas. Although rare, radiologists need to be aware that well-differentiated gallbladder carcinoma with mucin production can have cystic components, which may mimic adenomyomatosis. Careful interpretation of MR images may provide useful information in the differentiation of these two entities. (orig.)

  4. Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: Re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach

    Directory of Open Access Journals (Sweden)

    Yamaguchi Toshikazu

    2005-01-01

    Full Text Available Abstract Background Although the gastric well-differentiated adenocarcinoma in the distal stomach has been thought to develop via a intestinal metaplasia-carcinoma sequence, there are some disproofs from new mucin examinations for minute-size lesions in same type carcinoma. The current study was performed and pointed out the new findings for the solution to the problem according to the point described above. Methods 12 super-minute lesions (less than 1 mm in maximum diameter of well-differentiated adenocarcinoma in distal stomach (SMCa, which were detected from the pathological examinations of 210 surgically resected stomach specimens, and the mucosa adjacent to these carcinoma lesions, were examined by immunohistochemical mucin stainings (MUC2 and CD-10: intestinal phenotype, 45M1 and MUC6: gastric phenotype and p53-overexpression. And the analyses of the replication error of the microsatellites in chromosome 17 related p53 gene (TP53 and D17S786 (RER-p53MS were performed in SMCa lesions, adjacent mucosa to each lesion and other gastric mucosa with intestinal metaplasia, because all SMCa lesions showed p53-overexpression immunohistochemically, decribed below. Results 1. The carcinoma cells in all SMCa lesions were positive for 45M1 and p53. On the other hand, no positive carcinoma cells for MUC6 were seen although the pyloric glands and the remnant pyloric gland in the SMCa lesions in the same slides were positive for MUC6. Ten lesions (83% had intestinal phenotypic mucin (10 lesions: MUC2 (+, 4 lesions: CD10 (+. Two lesions (17% were positive for only 45M1 (gastric phenotypic mucin. 2. All of the mucosa adjacent to SMCa showed intestinal metaplasia (complete type: 7 regions, incomplete type: 5 regions. 3. RER-p53MS was confirmed in 42% (5/12 regions of SMCa, in 42% (5/12 regions of the mucosa adjacent to SMCa and 14% (6/42 regions of the other intestinal metaplasia mucosa. Conclusion Most of the super-minute well-differentiated adenocarcinoma

  5. New Treatment Options for Osteosarcoma - Inactivation of Osteosarcoma Cells by Cold Atmospheric Plasma.

    Science.gov (United States)

    Gümbel, Denis; Gelbrich, Nadine; Weiss, Martin; Napp, Matthias; Daeschlein, Georg; Sckell, Axel; Ender, Stephan A; Kramer, Axel; Burchardt, Martin; Ekkernkamp, Axel; Stope, Matthias B

    2016-11-01

    Cold atmospheric plasma has been shown to inhibit tumor cell growth and induce tumor cell death. The aim of the study was to investigate the effects of cold atmospheric plasma treatment on proliferation of human osteosarcoma cells and to characterize the underlying cellular mechanisms. Human osteosarcoma cells (U2-OS and MNNG/HOS) were treated with cold atmospheric plasma and seeded in culture plates. Cell proliferation, p53 and phospho-p53 protein expression and nuclear morphology were assessed. The treated human osteosarcoma cell lines exhibited attenuated proliferation rates by up to 66%. The cells revealed an induction of p53, as well as phospho-p53 expression, by 2.3-fold and 4.5-fold, respectively, compared to controls. 4',6-diamidino-2-phenylindole staining demonstrated apoptotic nuclear condensation following cold atmospheric plasma treatment. Cold atmospheric plasma treatment significantly attenuated cell proliferation in a preclinical in vitro osteosarcoma model. The resulting increase in p53 expression and phospho-activation in combination with characteristic nuclear changes indicate this was through induction of apoptosis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. The impact of vitamin D in pregnancy on extraskeletal health in children: a systematic review.

    Science.gov (United States)

    Christesen, Henrik T; Elvander, Claes; Lamont, Ronald F; Jørgensen, Jan S

    2012-12-01

    The impact of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring has become a "hot topic" with a potential for cost-beneficial prevention. The objective of this study was to systematically review the level I and II evidence. PubMed, Embase and Cochrane databases were searched using the MeSH terms "vitamin D" AND "pregnancy" until 1 January 2012. The search was limited to randomized controlled trials (evidence level I) and observational studies (evidence level II) in humans and in the English language. Papers reporting on vitamin D supplementation in combination with other supplements, or not reporting on 25OHD or outcomes of the offspring were excluded. Six randomized controlled trials and 24 observational studies were finally included. In randomized controlled studies, vitamin D supplementation resulted in increased birthweight in one study, but showed no effect in five other studies. In cohort and case-control studies, higher vitamin D intake, or higher 25OHD, was associated with increased birthweight in large studies only, and modified by vitamin D receptor polymorphisms and by race (U-shaped in Caucasians in one unconfirmed study). The risks of HIV mother-to-child transmission, rhinitis symptoms and eczema were lower. Data were conflicting on the effect on respiratory infections and wheezing, whereas U-shaped associations to inhalant allergen-specific IgE at five years and to schizophrenia were reported in unconfirmed studies. The risk of type 1 diabetes at 15 years was lower or unchanged. It is concluded that observational studies suggest an effect of vitamin D on several outcomes. U-Shaped associations warrant caution. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  7. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature.

    Science.gov (United States)

    Vigo, Federica; Ciammella, Patrizia; Valli, Riccardo; Cagni, Elisabetta; Iotti, Cinzia

    2012-08-10

    Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not considered feasible due to the extent of the disease. Our patient underwent external-beam radiation therapy using an intensity modulated technique, thus obtaining a persistent complete remission. Our patient has been in continuous complete local remission for 25 months since the end of radiotherapy. The role of radiotherapy is not defined in multiple myeloma with extraskeletal presentation. Our regimen seems to be effective in controlling the disease in this patient.This case report adds to the existing literature as it describes an unusual presentation of the disease and a new therapeutic approach to this rare presentation of multiple myeloma.

  8. Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature

    Directory of Open Access Journals (Sweden)

    Vigo Federica

    2012-08-01

    Full Text Available Abstract Introduction Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. Case presentation A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not considered feasible due to the extent of the disease. Our patient underwent external-beam radiation therapy using an intensity modulated technique, thus obtaining a persistent complete remission. Our patient has been in continuous complete local remission for 25 months since the end of radiotherapy. Conclusion The role of radiotherapy is not defined in multiple myeloma with extraskeletal presentation. Our regimen seems to be effective in controlling the disease in this patient. This case report adds to the existing literature as it describes an unusual presentation of the disease and a new therapeutic approach to this rare presentation of multiple myeloma.

  9. Extraskeletal myxoid chondrosarcoma presenting as an intradural spinal mass: report of a rare clinical presentation with an emphasis on differential diagnostic considerations

    Directory of Open Access Journals (Sweden)

    Priya Rao

    2014-12-01

    Full Text Available Extraskeletal myxoid chondrosarcoma is a rare soft tissue neoplasm that occurs predominantly in the soft tissues of the lower extremities. Herein we present a case of a 29 year old male who presented with bilateral femoral numbness believed to be the result of prior injury to his back. A magnetic resonance imaging revealed a mass in the T4-T5 epidural space compressing the spinal cord. Laminectomy was performed and the lesion removed piecemeal. The pathology specimen consisted of multiple fragments of dura involved by a myxoid neoplasm with a nodular growth pattern. The tumor cells were arranged in anastomosing cords and strands. Individual tumor cells were small, of uniform size and shape, with small hyperchromatic nuclei and scant eosinophilic cytoplasm. Immunohistochemical stains were performed which showed the tumor cells were diffusely positive for vimentin and focally positive for EMA, S-100 protein and cytokeratin, whereas they were negative for CD34 and CD99. Fluorescence in situ hybridization (FISH studies showed a clonal population of cells with re-arrangement of the EWSR1 locus, confirming the histologic impression of extraskeletal myxoid chondrosarcoma. This is the first report of a case of an extraskeletal myxoid chondrosarcoma arising from the dura, confirmed to have rearrangement of the EWSR1 gene by FISH. There have only been two other cases of dural based extraskeletal myxoid chondrosarcoma reported prior to our case. We also briefly review the published literature and discuss differential diagnostic considerations for this rare tumor.

  10. Response of human osteosarcoma in vitro to irradiation

    International Nuclear Information System (INIS)

    Weichselbaum, R.; Little, J.B.; Nove, J.

    1977-01-01

    Osteogenic sarcomas are very difficult to cure by conventional local radiotherapy. An investigation has been carried out into the effects of X-radiation on density-inhibited, slowly-proliferating, plateau-phase cultures of human osteosarcoma cells. Plates were irradiated at room temperature at a dose-rate of 80 rad/min, then returned to the incubator for intervals of up to 24 hours before the cells were trypsinized and replated at low density. Under these growth conditions, osteosarcoma cells have been found to be far more efficient in the repair of potentially-lethal radiation damage than either a human fibroblast strain or other established human cell lines, and the survival fraction of the osteosarcoma cells increased throughout the 24 hour period at all the doses tested. Complete X-ray survival curves for plateau phase osteosarcoma cells showed a marked difference in slope between the survival curve for cells subcultured immediately and that for cells which has been allowed 4 hours repair time. Studies of cellular proliferation kinetics showed that the increased capacity of the osteosarcoma cells for potentially-lethal-damage repair cannot be explained on the bases of a lower turnover rate in plateau-phase cultures. Consideration is given to the relevance of these results to the radiotherapy of osteosarcomas. In addition, osteosarcoma cells have unexpectedly been shown to be considerably more sensitive to killing by UV light than most normal cells. (U.K.)

  11. Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ash Gargya

    2012-01-01

    Full Text Available Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.

  12. Maxillary osteosarcoma in a beef suckler cow

    Directory of Open Access Journals (Sweden)

    Prins Diether G J

    2012-07-01

    Full Text Available Abstract A ten-year-old beef suckler cow was referred to the Scottish Centre for Production Animal Health & Food Safety of the University of Glasgow, because of facial swelling in the region of the right maxilla. The facial swelling was first noticed three months earlier and was caused by a slow growing oral mass which contained displaced, loosely embedded teeth. The radiographic, laboratory and clinicopathological findings are described. Necropsy, gross pathology and histological findings confirmed the mass as a maxillary osteosarcoma.

  13. Concurrence of metaphyseal fibrous defect and osteosarcoma

    International Nuclear Information System (INIS)

    Kyriakos, M.; Murphy, W.A.

    1981-01-01

    The case of a 15-year-old girl with juxtaposition of a femoral metaphyseal fibrous defect (fibrous cortical defect) and an osteosarcoma is reported. Despite the relatively common occurrence of metaphyseal fibrous defects, their reported association with other bone tumors is exceedingly rare. Only two previous acceptable examples of this association were found. Reports of malignant transformation of metaphyseal fibrous defect were reviewed and rejected because they lacked convincing radiologic or histopathologic evidence of a pre-existent benign fibrous lesion. The finding of a malignant bone tumor in association with a metaphyseal fibrous defect appears to be a chance occurrence. (orig.)

  14. YKL-40 protein in osteosarcoma tumor tissue

    DEFF Research Database (Denmark)

    Thorn, Andrea Pohly; Daugaard, Søren; Christensen, Lise Hanne

    2016-01-01

    YKL-40, a cellular glycoprotein isolated from the human osteosarcoma (OS) cell line MG63, is increased in the blood of patients with various types of cancer, and is found as an independent prognostic variable for survival. YKL-40 is also present with variable intensity in the tumor cells of some...... cancer types, but survival results have been conflicting. The aim of this study was to investigate the tissue expression of YKL-40 and its possible role as a predictive marker in patients with OS. Forty-eight patients were included in the study. Diagnostic biopsies were analyzed by immunohistochemistry...

  15. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. Responses of well-differentiated nasal epithelial cells exposed to particles: Role of the epithelium in airway inflammation

    International Nuclear Information System (INIS)

    Auger, Floriane; Gendron, Marie-Claude; Chamot, Christophe; Marano, Francelyne; Dazy, Anne-Catherine

    2006-01-01

    Numerous epidemiological studies support the contention that ambient air pollution particles can adversely affect human health. To explain the acute inflammatory process in airways exposed to particles, a number of in vitro studies have been performed on cells grown submerged on plastic and poorly differentiated, and on cell lines, the physiology of which is somewhat different from that of well-differentiated cells. In order to obtain results using a model system in which epithelial cells are similar to those of the human airway in vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust particles (DEP) and Paris urban air particles (PM 2.5 ). DEP and PM 2.5 (10-80 μg/cm 2 ) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion exclusively towards the basal compartment. In contrast, there was no IL-1β secretion and only weak non-reproducible secretion of TNF-α. IL-6 and GM-CSF were consistently stimulated towards the apical compartment and only when cells were exposed to PM 2.5 . ICAM-1 protein expression on cell surfaces remained low after particle exposure, although it increased after TNF-α treatment. Internalization of particles, which is believed to initiate oxidative stress and proinflammatory cytokine expression, was restricted to small nanoparticles (≤ 40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were more efficient than PM 2.5 . Collectively, our results suggest that airway epithelial cells exposed to particles augment the local inflammatory response in the lung but cannot alone initiate a systemic inflammatory response

  17. Osteosarcoma inheritance in two families of Scottish deerhounds.

    Science.gov (United States)

    Dillberger, John E; McAtee, Sara Ann

    2017-01-01

    Osteosarcoma is the most common neoplastic disease in Scottish Deerhounds. For Deerhounds, a 2007 population-based study concluded that a single dominant genetic factor largely governed disease risk. For Greyhounds, Rottweilers, and Irish Wolfhounds, a 2013 genome-wide association study found multiple genetic markers in each breed, with each marker only weakly associated with the disease. We obtained from two breeders the pedigrees, age (if alive) or age at death, and osteosarcoma status for two families of Scottish Deerhounds, designated Cohorts K and T. A dog was considered unaffected only if it was osteosarcoma-free and at least 8.5 years old. We analyzed the data in two ways, by assuming either a single recessive genetic factor or a single dominant genetic factor with high penetrance. Cohort K contained 54 evaluable dogs representing 12 litters. Cohort T contained 56 evaluable dogs representing eight litters. Osteosarcoma seemed clearly heritable in both cohorts; however, having a parent with osteosarcoma raised a pup's risk of developing osteosarcoma to 38% for Cohort K but 78% for Cohort T, suggesting the possibility of different genetic risk factors in each cohort. In Cohort K, osteosarcoma inheritance fit well with a single, recessive, autosomal risk factor, although we could not rule out the possibility of a single dominant risk factor with incomplete penetrance. In Cohort T, inheritance could be explained well by a single, dominant, autosomal risk factor but was inconsistent with recessive expression. Inheritance of osteosarcoma in two Scottish Deerhound families could be explained well by a single genetic risk factor residing on an autosome, consistent with a 2007 report. In one family, inheritance was consistent with dominant expression, as previously reported. In the other family, inheritance fit better with recessive expression, although the possibility of a dominant genetic factor influenced by one or more other genetic factors could not be ruled

  18. A case report of osteosarcoma occurred in the maxilla

    International Nuclear Information System (INIS)

    Jung, Yun Hwa; Jeon, Seon Doo

    1996-01-01

    Osteosarcoma is the most common malignant tumor of bone, The mean age of occurrence of osteosarcoma in the jaws is around 30, somewhat older than for other sites in the body. These lesions occur about equally in the maxilla and mandible. They most frequently develop in the body in the mandible, and the antrum and the posterior portion of alveolar ridge in the maxilla. We report a case of osteosarcoma in 35 years old female complaining swelling of the left cheek. Radiographic features showed cotton wool appearance in upper left posterior area. Histopathologic findings exhibited pleomorphic malignant osteoblasts and neoplastic osteoid.

  19. Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

    Science.gov (United States)

    Li, Dongqi; Li, Huiling; Ren, Mingyan; Liao, Yedan; Yu, Shunling; Chen, Yanjin; Yang, Yihao; Zhang, Ya

    2016-01-01

    Osteosarcoma is the most common primary bone tumor in children and adolescents. Although combined therapy including surgery and multi-agent chemotherapy have resulted in great improvements in the overall survival of patients, chemoresistance remains an obstacle for the treatment of osteosarcoma. Molecular targets or effective agents that are actively involved in cell death including apoptosis, autophagy and necroptosis have been studied. We summarized how these agents (novel compounds, miRNAs, or proteins) regulate apoptotic, autophagic and necroptotic pathways; and discussed the current knowledge on the role of these new agents in chemotherapy resistance in osteosarcoma. PMID:27007056

  20. Radiation-induced osteosarcoma of the calvaria; Case report

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Yasuo; Shigemori, Minoru; Miyagi, Jun; Ochiai, Satoshi; Lee, Souichi; Watanabe, Toshinori; Abe, Hitoshi; Morimatsu, Minoru [Kurume Univ., Fukuoka (Japan). School of Medicine

    1992-01-01

    The authors report a case of radiation-induced calvarial osteosarcoma. A 58-year-old female received subtotal removal of the pituitary adenoma and 5000 rads postoperative irradiation. Seven years later, an osteoblastic osteosarcoma occurred in the frontotemporal region. She received total tumor removal and chemotherapy. However, computed tomography subsequently revealed multiple small lesions at the margin of the bone flap. A chest x-ray film demonstrated lung metastasis. Local recurrence and lung metastasis require careful attention in radiation-induced osteosarcoma patients. (author).

  1. Expression of Bcl-2 in canine osteosarcoma

    Science.gov (United States)

    Piro, F.; Leonardi, L.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines. PMID:26623359

  2. Expression of Bcl-2 in canine osteosarcoma

    Directory of Open Access Journals (Sweden)

    F. Piro

    2015-03-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines.

  3. Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Sugimoto, M.; Toguchida, J.; Kotoura, Y.; Yamamuro, T.; Utsumi, H.

    1992-01-01

    The response to radiation of seven osteosarcoma cell lines was analysed by in vitro colony-forming assay and compared with that of eight human fibroblast strains. The values of D 0 , the surviving fraction after 2 Gy (S2Gy), and the mean inactivation dose (D-bar) of osteosarcoma cells in log-phase culture were significantly higher than those of fibroblast strains (p<0.01). PLD (potentially lethal damage) repair of osteosarcoma cells evaluated in the plateau phase of growth showed great variation for enhancement of survival, although all of the values were maximised within 12 h after irradiation. In the osteosarcoma, intrinsic radiosensitivity in vitro reflected the clinical response to radiation. However, the capacity for PLD repair might not be a good indicator for predicting the results of radiation therapy. (author)

  4. Primary Osteosarcoma of the Breast: A Case Report

    Directory of Open Access Journals (Sweden)

    Anna Rizzi

    2013-01-01

    Full Text Available Introduction. Primary osteosarcoma of the breast is a rare soft-tissue form of osteosarcoma without involvement of the skeletal system. Due to the rarity of the disease, its clinical features and optimal treatment remain unclear. Case Presentation. This case report deals with a 62-year-old woman with pure osteosarcoma of the breast. Conclusions. The prognosis of primary osteosarcoma of the breast is poor. Recurrence is frequent, and it is often associated with haematogenous spread of the disease to the lung. Treatment follows the model of sarcomas affecting other locations and must be planned in a multidisciplinary fashion. Adjuvant chemotherapy should be considered for patients with tumors showing aggressive features.

  5. Rehabilitation in radiotherapy of osteosarcomas in children and adolescents

    International Nuclear Information System (INIS)

    Bizer, V.A.

    1985-01-01

    Rehabilitation in radiotherapy of osteosarcomas in children and adolescents is manifested in rational planning of radiotherapy and in simplest orthopedic measures carried out simultaneously with irradiation and aimed at removal of contractures in limb joints

  6. Orbital metastasis: A rare manifestation of scapular bone osteosarcoma

    Directory of Open Access Journals (Sweden)

    Mohammad Taher Rajabi

    2014-01-01

    Full Text Available Purpose: To report a case of orbital metastasis from scapular bone osteosarcoma. Case Report: A 55-year-old man who was a known case of scapular bone osteosarcoma, was referred to our clinic with ocular symptoms including acute painful decreased vision, proptosis, conjunctival injection, and chemosis. He had undergone surgical excision of the original tumor and received systemic chemotherapy 4 months before. Imaging studies and incisional biopsy were performed for the orbital lesion, the histopathological examination confirmed the diagnosis of metastatic osteosarcoma. The patient was referred to the oncologist for palliative chemotherapy and further intervention; however, he deceased 2 months later due to sepsis in the context of immunosuppression. Conclusion: Metastatic involvement of the orbit due to osteosarcoma is a rare condition manifesting with orbital mass, pain, diplopia and ocular motility disturbance. Although there is no effective treatment, the combination of modalities such as chemotherapy, radiotherapy, and surgery may delay progression of the disease.

  7. Decreased RECQL5 correlated with disease progression of osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei, E-mail: doctormawei@163.com

    2015-11-27

    Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressed lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.

  8. Decreased RECQL5 correlated with disease progression of osteosarcoma

    International Nuclear Information System (INIS)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei

    2015-01-01

    Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressed lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.

  9. Extraosseous Osteosarcoma of the Esophagus: A Case Report

    Directory of Open Access Journals (Sweden)

    Rodney E. Wegner

    2010-01-01

    Full Text Available Extraosseous osteosarcoma (EOO is a malignant mesenchymal neoplasm that is located in the soft tissues without direct attachment to the skeletal system and that produces osteoid, bone, or chondroid material. EOO is an extremely rare disease, accounting for only 1% of soft tissue sarcomas, and typically presents in either an extremity or the retroperitoneum. This paper presents the case of a 45-year-old Caucasian male with extraosseous osteosarcoma of the esophagus.

  10. CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

    2015-07-15

    To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

  11. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  12. Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

    Science.gov (United States)

    Aktas, G E; Soyluoglu Demir, S; Sarikaya, A

    2016-01-01

    The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Value of whole body 123I scan for detection of metastasis in patients with well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Takahashi, Naoya; Odano, Ikuo; Sugita, Tadashi; Sato, Yoko; Sakai, Kunio

    1995-01-01

    To evaluate the utility of 123 I whole body scan for detection of metastasis in patients with well-differentiated thyroid carcinoma, post-therapy whole body 131 I images in 55 cases were compared with pre-therapy 123 I images using diagnostic dose (74 MBq). The post-therapy studies were performed 7 days after administration of therapeutic doses (3.33-7.77 GBq) of 131 I. The pre-therapy scans showed 30 lesions (71.4%) of 42 lesions which were shown by 131 I post-therapy scans. The diagnostic accuracy of 123 I whole body scans was considered to be nearly the same as the images obtained by 131 I using diagnostic dose. 123 I has short-life and an optimum gamma ray energy for scintigraphy. It makes radiation dose to patients lower than that of 131 I. Therefore, we recommend pre-therapy 131 I image using diagnostic dose is replaced by 123 I image. (author)

  14. Poorly-differentiated colorectal neuroendocrine tumour: CT differentiation from well-differentiated neuroendocrine tumour and poorly-differentiated adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ji Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-09-15

    The differentiation of poorly-differentiated neuroendocrine tumours (PD-NETs), well-differentiated NETs (WD-NETs), and adenocarcinomas (ADCs) is important due to different management options and prognoses. This study is to find the differential CT features of colorectal PD-NETs from WD-NETs and ADCs. CT features of 25 colorectal WD-NETs, 36 PD-NETs, and 36 ADCs were retrospectively reviewed. Significant variables were assessed using univariate and multivariate analyses. Receiver operating characteristics analysis determined the optimal cut-off value of tumour and lymph node (LN) size. Large size, rectum location, ulceroinfiltrative morphology without intact overlying mucosa, heterogeneous attenuation with necrosis, presence of ≥3 enlarged LNs, and metastasis were significant variables to differentiate PD-NETs from WD-NETs (P < 0.05). High attenuation on arterial phase, persistently high enhancement pattern, presence of ≥6 enlarged LNs, large LN size, and wash-in/wash-out enhancement pattern of liver metastasis were significant variables to differentiate PD-NETs from ADCs (P < 0.05). Compared to WD-NETs, colorectal PD-NETs are usually large, heterogeneous, and ulceroinfiltrative mass without intact overlying mucosa involving enlarged LNs and metastasis. High attenuation on arterial phase, presence of enlarged LNs with larger size and greater number, and wash-in/wash-out enhancement pattern of liver metastasis can be useful CT discriminators of PD-NETs from ADCs. (orig.)

  15. Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study.

    Science.gov (United States)

    Xing, Deyin; Banet, Natalie; Sharma, Rajni; Vang, Russell; Ronnett, Brigitte M; Illei, Peter B

    2018-02-01

    Serous ovarian neoplasms can overlap morphologically with peritoneal mesothelial proliferations, including well-differentiated papillary mesothelioma (WDPM) and malignant epithelioid mesothelioma (MM). Accurate histologic classification of these neoplasms is important for clinical management. The Pax-8 protein is commonly used for differentiating peritoneal MM from serous carcinoma, but the diagnostic value of Pax-8 for distinguishing WDPM from borderline or low-grade serous tumors is unknown. We used immunohistochemistry staining to assess Pax-8 expression in 33 WDPMs, 34 peritoneal MMs, 48 pleural MMs, 11 adenomatoid tumors, 5 peritoneal inclusion cysts, and 51 benign/reactive mesothelium specimens. Staining was noted in 20 WDPMs (61%), with 17 showing strong and diffuse nuclear staining and 3 patchy/focal staining. Calretinin was expressed in 33 cases (100%), whereas focal BerEP4 staining was noted in 2 of 29 cases (7%). In contrast, 4 peritoneal MM (12%) were Pax-8 positive (3 diffuse and 1 focal staining). All adenomatoid tumors and peritoneal inclusion cysts were negative for Pax-8. Of the 48 pleural MM cases, 2 (4%) showed focal weak to moderate nuclear labeling for Pax-8, and 2 cases (4%) of reactive mesothelium demonstrated focal and scattered Pax-8 staining. Pax-8 appears to be a useful marker for distinguishing MM from gynecologic malignancies but is not reliable for distinguishing WDPM from borderline or low-grade gynecologic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses

    Science.gov (United States)

    Jazaeri Farsani, Seyed Mohammad; Deijs, Martin; Dijkman, Ronald; Molenkamp, Richard; Jeeninga, Rienk E; Ieven, Margareta; Goossens, Herman; van der Hoek, Lia

    2015-01-01

    Background Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. Method Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. Results Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). Conclusion We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates. PMID:25482367

  17. Cardiovascular involvement by osteosarcoma: an analysis of 20 patients

    Energy Technology Data Exchange (ETDEWEB)

    Yedururi, Sireesha; Morani, Ajaykumar C.; Gladish, Gregory W. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Vallabhaneni, Srilakshmi [Medstar Harbor Hospital, Department of Internal Medicine, Baltimore, MD (United States); Anderson, Peter M. [Levine Children' s Hospital/Levine Cancer Institute, Department of Pediatrics Hematology/Oncology/BMT, Carolinas Healthcare System, Charlotte, NC (United States); Hughes, Dennis; Daw, Najat C. [The University of Texas MD Anderson Cancer Center, Division of Pediatrics, Houston, TX (United States); Wang, Wei-Lien [The University of Texas MD Anderson Cancer Center, Department of Pathology, Houston, TX (United States)

    2016-01-15

    Although hematogenous spread of osteosarcoma is well known, the imaging findings of cardiovascular involvement by osteosarcoma are seldom reported and can be difficult to recognize. The enhanced resolution of modern CT and MRI scanners may lead to better detection of cardiovascular involvement. To describe the key imaging findings and clinical behavior of cardiovascular involvement by osteosarcoma. We retrospectively reviewed the imaging findings and clinical characteristics of 20 patients with cardiovascular involvement by osteosarcoma identified by two pediatric radiologists from a review of imaging studies at our institution from 2007 to 2013. At initial diagnosis, the median age of the patients was 15.1 years (range 4.8-24.6 years), and 7 (35%) patients had detectable metastases. Median time to detection of cardiovascular metastases was 1.8 years (range 0-7.3 years). Sixteen patients died of disease; 4 have survived a median of 7.4 years since initial diagnosis. The sites of cardiovascular involvement were the systemic veins draining the primary and metastatic osteosarcoma, pulmonary arteries, pulmonary veins draining the pulmonary metastases, and heart. A dilated and mineralized terminal pulmonary arteriole is an early sign of metastatic osteosarcoma in the lung. Unfamiliarity with the imaging features resulted in under-recognition and misinterpretation of intravascular tumor thrombus as bland thrombus. Knowledge of imaging findings in the era of modern imaging modalities has enhanced our ability to detect cardiovascular involvement and lung metastases early and avoid misinterpreting tumor thrombus in draining systemic veins or pulmonary arteries as bland thrombus. (orig.)

  18. Telangiectatic osteosarcoma of femur in a young man

    International Nuclear Information System (INIS)

    Mita-Alban, Luis Carlos; Alvarez-Ramirez, Rodrigo; Alvarado-Acosta, Fernando

    2004-01-01

    Telangiectatic osteosarcoma is a rare malignant lesion that is about 2,5 % of all primary osteosarcomas. This osteosarcoma has been associated with a more aggressive course than the conventional osteosarcoma, in large clinical series. By its clinical behavior, radiological and histopathological aspects, it is very similar to other benign tumours, such as aneurysmal bone cyst. A case of a male patient aged 24, healthy, with chronic pain in his left knee as the only symptom is presented. He was diagnosed with this rare form of osteosarcoma and amputated. The patient received a regimen of 6 months of chemotherapy, after which there were found metastases and chest wall. It is important to recognize this variant of osteosarcoma and to differentiate from benign lesions because only resection, treatment, carries a reserved prognosis, while if chemotherapy is added, life expectancy improves. Besides this, also it is important to remember this entity in the differential diagnosis of the painful member in healthy and young people. (author) [es

  19. Cardiovascular involvement by osteosarcoma: an analysis of 20 patients

    International Nuclear Information System (INIS)

    Yedururi, Sireesha; Morani, Ajaykumar C.; Gladish, Gregory W.; Vallabhaneni, Srilakshmi; Anderson, Peter M.; Hughes, Dennis; Daw, Najat C.; Wang, Wei-Lien

    2016-01-01

    Although hematogenous spread of osteosarcoma is well known, the imaging findings of cardiovascular involvement by osteosarcoma are seldom reported and can be difficult to recognize. The enhanced resolution of modern CT and MRI scanners may lead to better detection of cardiovascular involvement. To describe the key imaging findings and clinical behavior of cardiovascular involvement by osteosarcoma. We retrospectively reviewed the imaging findings and clinical characteristics of 20 patients with cardiovascular involvement by osteosarcoma identified by two pediatric radiologists from a review of imaging studies at our institution from 2007 to 2013. At initial diagnosis, the median age of the patients was 15.1 years (range 4.8-24.6 years), and 7 (35%) patients had detectable metastases. Median time to detection of cardiovascular metastases was 1.8 years (range 0-7.3 years). Sixteen patients died of disease; 4 have survived a median of 7.4 years since initial diagnosis. The sites of cardiovascular involvement were the systemic veins draining the primary and metastatic osteosarcoma, pulmonary arteries, pulmonary veins draining the pulmonary metastases, and heart. A dilated and mineralized terminal pulmonary arteriole is an early sign of metastatic osteosarcoma in the lung. Unfamiliarity with the imaging features resulted in under-recognition and misinterpretation of intravascular tumor thrombus as bland thrombus. Knowledge of imaging findings in the era of modern imaging modalities has enhanced our ability to detect cardiovascular involvement and lung metastases early and avoid misinterpreting tumor thrombus in draining systemic veins or pulmonary arteries as bland thrombus. (orig.)

  20. Osteosarcoma primario del corazón

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    Benito Serrano Gomez

    1986-07-01

    Full Text Available Se informa un caso de osteosarcoma primario del corazón localizado en el ventrículo derecho con metástasis al sistema nervioso central, pulmón derecho y a la serosa del fleon. Este es el único tumor maligno primario del corazón en nuestro archivo de 12.230 autopsias realizadas en el Hospital San Juan de Dios en Bogotá entre 1954 y 1986. Se subraya el hecho de que las manifestaciones clínicas puedan obedecer, como ocurrió en este caso, a las metástasis y no a la alteración funcional del órgano afectado par la neoplasia primitiva. Se hace una electiva revisión del tema.

  1. A guise of osteosarcoma: Chondroblastoma-like

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    Aditi Amit Byatnal

    2013-01-01

    Full Text Available Osteosarcoma (OS is a rare tumor arising from immature bone forming cells or through neoplastic differentiation of other immature mesenchymal cells into osteoblasts. Chondroblastoma-like OS is one of the rare forms of OS to be seen in jaw bones. Aggressive clinical behavior, osteolytic areas in the radiograph and histological presentation of chondroblastoma such as cells with grooved nuclei, typical chicken-wire calcification along with areas of tumor osteoid, implied the diagnosis as chondroblastoma-like OS. Use of reticulin stain further confirmed the diagnosis. A case of chondroblastoma-like OS is reported, emphasizing the importance of early diagnosis of aggressive jaw lesions with the help of routine radiography, histopathology, and special stains.

  2. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability

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    Lirong Zhang

    2018-01-01

    Full Text Available Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS. Three main components (naringin, naringenin, and hesperetin were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n=47 and control group (CG, received 20 mg placebo daily, n=48. After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P>0.01. The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  3. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability.

    Science.gov (United States)

    Zhang, Lirong; Xu, Xiaohua; Jiang, Tiechao; Wu, Kunzhe; Ding, Chuanbo; Liu, Zhen; Zhang, Xuanhe; Yu, Tianhua; Song, Changlong

    2018-01-01

    Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium . Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47) and control group (CG, received 20 mg placebo daily, n = 48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group ( P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  4. Targeting chondrosarcoma and osteosarcoma cell metabolism : the IGF pathway and beyond

    NARCIS (Netherlands)

    Peterse, E.F.P.

    2018-01-01

    Thesis explored potential new therapeutic strategies by identifying cellular pathways that are essential for chondrosarcoma and osteosarcoma cell survival. Although clinical trials with IGF1R inhibitors have disappointing results in osteosarcoma, this thesis strengthens the view that the IGF

  5. Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix

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    Ae Lee Won

    2005-05-01

    Full Text Available Abstract Background Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium. Case presentation A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung. Conclusion The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.

  6. CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses.

    Science.gov (United States)

    Sakai, Yasuhiro; Hong, Seung-Mo; An, Soyeon; Kim, Joo Young; Corbeil, Denis; Karbanová, Jana; Otani, Kyoko; Fujikura, Kohei; Song, Ki-Byung; Kim, Song Cheol; Akita, Masayuki; Nanno, Yoshihide; Toyama, Hirochika; Fukumoto, Takumi; Ku, Yonson; Hirose, Takanori; Itoh, Tomoo; Zen, Yoh

    2017-03-01

    The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. NKX2.2, PDX-1 and CDX-2 as potential biomarkers to differentiate well-differentiated neuroendocrine tumors.

    Science.gov (United States)

    Yang, Michelle X; Coates, Ryan F; Ambaye, Abiy; Cortright, Valerie; Mitchell, Jeannette M; Buskey, Alexa M; Zubarik, Richard; Liu, James G; Ades, Steven; Barry, Maura M

    2018-01-01

    Well-differentiated neuroendocrine tumors (NET) most frequently arise from the gastrointestinal tract (GI), pancreas, and lung. Patients often present as metastasis with an unknown primary, and the clinical management and outcome depend on multiple factors, including the accurate diagnosis with the tumor primary site. Determining the site of the NET with unknown primary remains challenging. Many biomarkers have been investigated in primary NETs and metastatic NETs, with heterogeneous sensitivity and specificity observed. We used high-throughput tissue microarray (TMA) and immunohistochemistry (IHC) with antibodies against a panel of transcriptional factors including NKX2.2, PDX-1, PTF1A, and CDX-2 on archived formalin-fixed paraffin-embedded NETs, and investigated the protein expression pattern of these transcription factors in 109 primary GI ( N  = 81), pancreatic ( N  = 17), and lung ( N  = 11) NETs. Differential expression pattern of these markers was observed. In the GI and pancreatic NETs ( N  = 98), NKX2.2, PDX-1, and CDX-2 were immunoreactive in 82 (84%), 14 (14%), and 52 (52%) cases, respectively. PDX-1 was expressed mainly in the small intestinal and appendiceal NETs, occasionally in the pancreatic NETs, and not in the colorectal NETs. All three biomarkers including NKX2.2, PDX-1, and CDX-2 were completely negative in lung NETs. PTF1A was expressed in all normal and neuroendocrine tumor cells. Our findings suggest that NKX2.2 was a sensitive and specific biomarker for the GI and pancreatic neuroendocrine tumors. We proposed that a panel of immunostains including NKX2.2, PDX-1, and CDX-2 may show diagnostic utility for the most common NETs.

  8. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

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    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-12-15

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7{+-}12.3 years) who had HD-RIT (dose 159.1{+-}25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive ({>=}50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62{+-}66.1 dpm in increased one of follow-up UBT, and 153.3{+-}157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection.

  9. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    International Nuclear Information System (INIS)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee

    2009-01-01

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7±12.3 years) who had HD-RIT (dose 159.1±25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive (≥50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62±66.1 dpm in increased one of follow-up UBT, and 153.3±157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection

  10. A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values

    International Nuclear Information System (INIS)

    Jin, Guang-Zhi; Cong, Wen-Ming; Wu, Meng-Chao; Dong, Hui; Yu, Wen-Long; Li, Yan; Lu, Xin-Yuan; Yu, Hua; Xian, Zhi-Hong; Dong, Wei; Liu, Yin-Kun

    2013-01-01

    Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk

  11. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.

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    Rachael L Gerlach

    Full Text Available Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE may differ between seasonal (H1N1 A/BN/59/07 and H1N1pdm isolates from a fatal (A/KY/180/10 and nonfatal (A/KY/136/09 case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi. At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly

  12. CD271+ osteosarcoma cells display stem-like properties.

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    Jiguang Tian

    Full Text Available Cancer stem cell (CSC theory has been proposed and verified in many cancers. The existence of osteosarcoma CSCs has been confirmed for many years and multiple surface markers have been employed to identify them. In this study, we identified CD271(+ subpopulation of osteosarcoma displaying stem-like properties. CD271, known as the neural crest nerve growth factor receptor, is the marker of bone marrow mesenchymal stem cells (MSCs and human melanoma-initiating cells. We discovered that CD271 was expressed differentially in diverse types of human osteosarcoma and stabilized cell lines. CD271(+ osteosarcoma cells displayed most of the properties of CSC, such as self-renewal, differentiation, drug resistance and tumorigenicity in vivo. Nanog, Oct3/4, STAT3, DNA-PKcs, Bcl-2 and ABCG2 were more expressed in CD271(+ cells compared with CD271- cells. Our study supported the osteosarcoma CSC hypothesis and, to a certain extent, revealed one of the possible mechanisms involved in maintaining CSCs properties.

  13. Expression and function of survivin in canine osteosarcoma.

    Science.gov (United States)

    Shoeneman, Jenette K; Ehrhart, E J; Eickhoff, Jens C; Charles, J B; Powers, Barbara E; Thamm, Douglas H

    2012-01-01

    Osteosarcoma has a high mortality rate and remains in need of more effective therapeutic approaches. Survivin is an inhibitor of apoptosis family member protein that blocks apoptosis and drives proliferation in human cancer cells where it is commonly elevated. In this study, we illustrate the superiority of a canine osteosarcoma model as a translational tool for evaluating survivin-directed therapies, owing to the striking similarities in gross and microscopic appearance, biologic behavior, gene expression, and signaling pathway alterations. Elevated survivin expression in primary canine osteosarcoma tissue correlated with increased histologic grade and mitotic index and a decreased disease-free interval (DFI). Survivin attenuation in canine osteosarcoma cells inhibited cell-cycle progression, increased apoptosis, mitotic arrest, and chemosensitivity, and cooperated with chemotherapy to significantly improve in vivo tumor control. Our findings illustrate the utility of a canine system to more accurately model human osteosarcoma and strongly suggest that survivin-directed therapies might be highly effective in its treatment. ©2011 AACR.

  14. High-grade surface osteosarcoma of the hand

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    Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe [Nagasaki University Hospital, Department of Pathology, Nagasaki (Japan); Kumagai, Kenji; Shindo, Hiroyuki [Nagasaki University Graduate School of Biomedical Sciences, Department of Orthopedic Surgery, Nagasaki (Japan); Uetani, Masataka [Nagasaki University Graduate School of Biomedical Sciences, Department of Radiology and Radiation Biology, Nagasaki (Japan); Ishida, Tsuyoshi [National Center of Neurology and Psychiatry, Department of Pathology and Laboratory Medicine, Kohnodai Hospital, Chiba (Japan); Tokyo Medical and Dental University, Department of Molecular Bone and Cartilage Pathology, Hard Tissue Genome Research Center, Tokyo (Japan)

    2007-09-15

    A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

  15. [The importance of conventional radiographs in the diagnosis of osteosarcoma].

    Science.gov (United States)

    Meyer, S; Reinhard, H; Graf, N; Püschel, W; Ziegler, K; Schneider, G

    2002-01-01

    We report about a 12-year-old boy with a history of recurrent patella luxation. Due to persistent pain in the distal left femur a MRI examination was performed in another hospital which suggested a malignant bone tumor. Without validation of the MRI findings by conventional radiographs bone biopsy was performed. Histopathological examination yielded the diagnosis of a chondroblastic osteosarcoma. Before initiating polychemotherapy, plain radiographs for the first time, a nuclear imaging study and an additional MRI examination were performed in our hospital. The results of these studies made the diagnosis of an osteosarcoma unlikely. In particular, plain radiographs did not show any osseous lesion which was characteristic of an osteosarcoma. To establish a definite diagnosis biopsy was repeated with resection of the bone area which showed suspicious changes in MRI studies. An osteosarcoma was ruled out by histopathological examination. The pathologic changes detected in MRI were rated as bone bruise on plain radiographs and seemed to be of traumatic origin. Our case report emphasises the importance of conventional radiographs in establishing the diagnosis of an osteoarcoma respectively bone tumors and tumor-like lesions in general. They still remain the mainstay in diagnosing bone forming tumors. MRI imaging studies may show changes which mimick solid lesions but in deed can be of traumatic origin. Without informing the pathologist about the exact origin of the specimen, histopathological examination may lead to the misdiagnosis of a chondroblastic osteosarcoma if specimen, like in this case report, represents epiphyseal tissue showing cartilaginous areas with reactive bone formation.

  16. The clinical and radiologic consideration of osteosarcoma of the jaws

    International Nuclear Information System (INIS)

    Ko, Gi Young; Kim, Ki Duck; Park, Chang Seo

    1996-01-01

    The purpose of this study was to know the proper diagnosis and to establish the treatment plan of the osteosarcoma in the jaws through the clinical, radiological, and histopathologic considerations. The authors compared and analyzed t he clinicoradiologic features of the six cases of osteosarcoma, diagnosed at the dental college hospital in Yonsei University, Seoul, Korea, during the period from 1975 to 1995. The obtained results were as follows; 1. Osteosarcoma occurred in the mean age, 26.2 years, ranged from 14 to 35 years, and equally in men and women. 2. The swelling was the most common frequent presenting complaints. Other reported symptoms included pain, parasthesia of the lower lip or the lesion. 3. The average interval was seen 3.5 months before the patient had been seen by a doctor. 4. The frequency of the lesions was equally in the maxilla, 3 cases and mandible, 3 cases. 5. Radiologically, osteoblastic osteosarcoma which is seen in the 3 cases was the most frequent histologic type. Chondroblastic osteosarcoma were seen in the 2 cases. there was no correlation between the radiologic appearance and histopathologic type.

  17. High-grade surface osteosarcoma of the hand

    International Nuclear Information System (INIS)

    Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Kumagai, Kenji; Shindo, Hiroyuki; Uetani, Masataka; Ishida, Tsuyoshi

    2007-01-01

    A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

  18. Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

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    Xiang Chen

    2014-04-01

    Full Text Available Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs and copy number alterations (CNAs. To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%–53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.

  19. Angiographic evaluation of response to preoperative chemotherapy in osteosarcoma

    International Nuclear Information System (INIS)

    Carrasco, C.H.; Charnsangavej, C.; Richii, W.; Wallace, S.; Chawla, S.P.; Raymond, A.K.; Murray, J.A.; Benjamin, R.S.

    1986-01-01

    Preoperative chemotherapy for osteosarcoma facilitates local resection for limb salvage and serves as an in vivo chemosensitivity assay. Arteriograms obtained with each intraarterial course of cisplatin in 79 patients with osteosarcoma were evaluated. Complete remission was defined as complete or nearly complete disappearance of tumor vascularity after treatment. A minimal decrease, no change, or an increase in tumor vascularity was not considered a response. If a complete remission is assumed to represent ≥ 90% histologic tumor necrosis which correlates with prolonged disease-free survival, the sensitivity of an angiographic complete remission was 95%, the specificity was 58%, the predictive value of a negative study was 90%, and the predictive value of a positive study was 75%. Angiography is the best clinical technique for evaluating the therapeutic response in osteosarcoma. Results correlate well with the degree of tumor necrosis, particularly in respect to significant residual viable tumor

  20. Establishment and characterization of a novel osteosarcoma cell line: CHOS.

    Science.gov (United States)

    Liu, Yunlu; Feng, Xiaobo; Zhang, Yukun; Jiang, Hongyan; Cai, Xianyi; Yan, Xinxin; Huang, Zengfa; Mo, Fengbo; Yang, Wen; Yang, Cao; Yang, Shuhua; Liu, Xianzhe

    2016-12-01

    Osteosarcoma has a well-recognized bimodal distribution, with the first peak in adolescence and another in the elderly age-group. The elderly patients have different clinical features and a poorer prognosis as compared to adolescents. To better understand the biological features of osteosarcoma in the elderly population, we established a new human osteosarcoma cell line from a 58-year-old man with primary chondroblastic osteosarcoma. After 6 months of continuous culture in vitro for over 50 passages, an immortalized cell line CHOS was established. The cell line was well-characterized by cytogenetic, biomarker, functional, and histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a doubling time of 36 h. Cytogenetic analysis of CHOS cells revealed the loss of chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate. The cell line was highly tumorigenic and maintained the histological characteristics and invasive nature of the original tumor. Furthermore, on immunohistochemical analysis, the xenografts and metastases were found to co-express collagen II, aggrecan, vimentin and S100A4 that resembled the original tumor cells. Our results indicate, the potential of CHOS cell line to serve as a useful tool for further studies on the molecular biology of osteosarcoma, especially in the elderly patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. The effects of sulforaphane on canine osteosarcoma proliferation and invasion.

    Science.gov (United States)

    Rizzo, V L; Levine, C B; Wakshlag, J J

    2017-09-01

    Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN), found in raw cruciferous vegetables, may have utility in chemoprevention, as an antineoplastic agent and as a free radical scavenger. The effects of SFN alone or with doxorubicin on cell viability were examined, as well as cell cycle kinetics, invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17, OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at potentially physiological concentrations (canine osteosarcoma. © 2016 John Wiley & Sons Ltd.

  2. Osteosarcoma: Accelerating Progress Makes for a Hopeful Future

    Directory of Open Access Journals (Sweden)

    Amanda J. Saraf

    2018-01-01

    Full Text Available Patients who develop osteosarcoma in 2017 receive treatment that remains essentially unchanged since the 1970s. Outcomes likewise remain largely unimproved. Large, collaborative, multinational efforts to improve therapy have evaluated strategies leveraging both cytotoxic intensification and immunomodulatory agents. While these have confirmed our capacity to conduct such trials, results have proved largely disappointing. This has motivated efforts to focus on the basic biology of osteosarcoma, where understanding remains poor but has improved significantly. Recent advances have identified characteristic genetic features of osteosarcoma, including profound chromosomal disruption, marked patient-patient heterogeneity, and a paucity of recurrent mutations. Analyses suggest genesis in early catastrophic genetic events, although the nature of the inciting events remains unclear. While p53 and Rb inactivation occurs in most osteosarcomas, the landscape of associated driver mutations has proved extensive. Few mutations recur with high frequency, though patterns continue to emerge that suggest recurrent alterations within specific pathways. Biological pathways implicated in osteosarcoma biology through genetic and other preclinical studies include PI3K/mTOR, WNT/βcatenin, TGFβ, RANKL/NF-κB, and IGF. Unfortunately, clinical studies evaluating targeted agents have to date yielded disappointing results, as have studies examining modern immunotherapeutics. It remains unclear whether this pattern of clinical failures exposes inadequacies of our preclinical models, unrealistic expectations for single-agent responses in heavily pretreated patients, or biology less relevant than suggested. Nearly all patients who succumb to osteosarcoma develop lung metastases, which exhibit marked chemoresistance. Much scientific effort has recently sought to enhance our mechanistic understanding of metastasis biology. This research has potential to reveal novel targets for

  3. Osteoblastoma-like osteosarcoma of the distal tibia

    Energy Technology Data Exchange (ETDEWEB)

    Abramovici, Luigia; Steiner, German C. [Department of Pathology and Laboratory Medicine, Hospital for Joint Diseases, New York, NY (United States); Kenan, Samuel [Department of Orthopaedic Oncology Surgery, Hospital for Joint Diseases, New York, NY (United States); Hytiroglou, Prodromos [Aristotle University, Thessaloniki (Greece); Rafii, Mahvash [Department of Radiology, Hospital for Joint Diseases, New York, NY (United States)

    2002-03-01

    We report a case of a 14-year-old boy with an intracompartmental lytic lesion with poorly defined margins in the right distal tibia that was originally treated with curettage and bone grafting. Histologic examination showed an osteoblastic tumor with unusual features, which was found on consultation to be an osteoblastoma-like osteosarcoma, a rare, low-grade variant of osteosarcoma. Subsequently, the patient underwent en bloc resection of the distal tibia, which was replaced with vascularized bone graft and followed by chemotherapy. Two years later, he is alive with lung metastases. (orig.)

  4. Osteoblastoma-like osteosarcoma of the distal tibia

    International Nuclear Information System (INIS)

    Abramovici, Luigia; Steiner, German C.; Kenan, Samuel; Hytiroglou, Prodromos; Rafii, Mahvash

    2002-01-01

    We report a case of a 14-year-old boy with an intracompartmental lytic lesion with poorly defined margins in the right distal tibia that was originally treated with curettage and bone grafting. Histologic examination showed an osteoblastic tumor with unusual features, which was found on consultation to be an osteoblastoma-like osteosarcoma, a rare, low-grade variant of osteosarcoma. Subsequently, the patient underwent en bloc resection of the distal tibia, which was replaced with vascularized bone graft and followed by chemotherapy. Two years later, he is alive with lung metastases. (orig.)

  5. Modulation of the osteosarcoma expression phenotype by microRNAs.

    Directory of Open Access Journals (Sweden)

    Heidi M Namløs

    Full Text Available BACKGROUND: Osteosarcomas are the most common primary malignant tumors of bone and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs capable of regulating gene expression at the post transcriptional level, and miRNAs and their target genes may represent novel therapeutic targets or biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in osteosarcoma development, global microarray analyses of a panel of 19 human osteosarcoma cell lines was performed. PRINCIPAL FINDINGS: We identified 177 miRNAs that were differentially expressed in osteosarcoma cell lines relative to normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486-5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497 and miR-206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines. All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29 and miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/p85α regulatory subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b, miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR-497 was identified with an intermediate expression level in osteosarcoma clinical samples compared to osteoblasts and bone, which may reflect the differentiation level of osteosarcoma relative to the undifferentiated osteoblast and fully differentiated normal bone. SIGNIFICANCE: This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex

  6. Extra-skeletal Ewing sarcoma of the lumbosacral region in an adult pregnant patient: a case report.

    Science.gov (United States)

    Al Khawaja, Darweesh; Vescovi, Cristina; Dower, Ashraf; Thiruvilangam, Vallapan; Mahasneh, Tamadur

    2017-03-01

    Extra-skeletal Ewing sarcoma in pregnancy is rare. There is thus limited scientific evidence to guide clinicians in its complicated management, particularly within the context of early gestation. We therefore share our successful outcome in a 32-year-old pregnant patient, following a unique management strategy of complete aggressive surgical resection prior to neo-adjuvant therapy. The case involved a 2-month history of right-sided back and gluteal pain, with associated paraesthesia. Lumbosacral magnetic resonance imaging (MRI) revealed an approximate 40×50 mm indeterminate mass in the lower right paraspinal musculature. The mass extended into the first right sacral foramen and the central canal; and also impinged on the S2 exiting nerve. After considering the patients' rapid deterioration, pregnant status and other clinical factors, it was elected to proceed with complete surgical resection prior to any other therapeutic modality. Following surgery, the patient experienced immediate resolution of her pain and by 6 weeks was able to cease the use of all analgesics. At 32-weeks' gestation she underwent an uncomplicated vaginal delivery. At 9 months follow up, she remains disease free and has experienced complete resolution of her back pain and radiculopathy.

  7. MicroRNA-224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1.

    Science.gov (United States)

    Geng, Shuo; Gu, Lina; Ju, Fang; Zhang, Hepeng; Wang, Yiwen; Tang, Han; Bi, ZhengGang; Yang, Chenglin

    2016-09-01

    Osteosarcoma is the most common primary bone tumour in children and adolescents. Accumulating evidence has shown that microRNAs (miRNAs) participate in the development of almost all types of cancer. Here, we investigated the role of miR-224 in the development and progression of osteosarcoma. We demonstrated that miR-224 was down-regulated in osteosarcoma cell lines and tissues. Lower miR-224 levels were correlated with shorter survivalin osteosarcoma patients. Furthermore, overexpression of miR-224 suppressed osteosarcoma cell proliferation, migration and invasion and contributed to the increased sensitivity of MG-63 cells to cisplatin. We identified Rac1 as a direct target gene of miR-224 in osteosarcoma. Rac1 expression was up-regulated in the osteosarcoma cell lines and tissues, and there was an inverse correlation between Rac1 and miR-224 expression in osteosarcoma tissues. Furthermore, rescuing Rac1 expression decreased the sensitivity of miR-224-overexpressing MG-63 cells to cisplatin. We also demonstrated that ectopic expression of Rac1 promoted the proliferation, migration and invasion of miR-224-overexpressing MG-63 cells. These data suggest that miR-224 plays a tumour suppressor role in the development of osteosarcoma and is related to the sensitivity of osteosarcoma to cisplatin. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  8. Expression of nociceptive ligands in canine osteosarcoma.

    Science.gov (United States)

    Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  9. Osteocalcin and Osteonectin Expression in Canine Osteosarcoma.

    Science.gov (United States)

    Wehrle-Martinez, A S; Dittmer, K E; Aberdein, D; Thompson, K G

    2016-07-01

    Osteosarcoma (OSA) is a malignant heterogeneous primary bone tumor responsible for up to 90% of all primary bone tumors in dogs. In this study, osteocalcin (OC) and osteonectin (ON) immunoreactivity was evaluated in 23 canine OSAs, 4 chondrosarcomas, 4 fibrosarcomas, 2 hemangiosarcomas, and 4 histiocytic sarcomas. The effects of three different decalcification agents (ethylenediaminetetraetic acid [EDTA], formic acid and hydrochloric acid [HCl]) on the immunoreactivity for OC and ON was also assessed. Immunoreactivity to OC was present in 19/23 (83%) cases of OSA and all cases of chondrosarcoma. In three OSAs the extracellular matrix showed immunoreactivity to OC. None of the fibrosarcomas, histiocytic sarcomas or hemangiosarcomas showed immunoreactivity to OC. The sensitivity and specificity for OC in canine OSA in this study was 83% and 71% respectively. For ON, 100% of both OSAs (23/23) and non-OSAs (14/14) showed cytoplasmic immunoreactivity to this antibody, giving a sensitivity of 100% but a complete lack of specificity. There were no significant differences in immunoreactivity for OC and ON between the different decalcification agents used. In conclusion, OC showed high sensitivity for identifying OSA but it failed to distinguish between OSA and chondrosarcoma, and the osteoid produced by neoplastic cells in most cases did not show immunoreactivity to OC. These factors may limit the practical utility of OC in the diagnosis of OSA in dogs when chondrosarcoma is a differential diagnosis. ON showed no specificity in detecting OSA and has little practical application for the diagnosis of OSA in dogs. © The Author(s) 2016.

  10. WEE1 inhibition sensitizes osteosarcoma to radiotherapy

    International Nuclear Information System (INIS)

    PosthumaDeBoer, Jantine; Würdinger, Thomas; Graat, Harm CA; Beusechem, Victor W van; Helder, Marco N; Royen, Barend J van; Kaspers, Gertjan JL

    2011-01-01

    The use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G 2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G 2 arrest and could sensitize OS cells to irradiation induced cell death. WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot. WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G 2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G 2 checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS

  11. MiR-598: A tumor suppressor with biomarker significance in osteosarcoma.

    Science.gov (United States)

    Liu, Kai; Sun, Xiaolu; Zhang, Yingang; Liu, Liang; Yuan, Qiling

    2017-11-01

    Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents. Identifying specific and sensitive biomarkers is beneficial to early detection and improvement of life qualities and overall survival rates of osteosarcoma patients. Realtime PCR was used to detect the expression of miR-598. CCK-8 assay was employed to detect the proliferation of osteosarcoma cells, while transwell assays were used to examine the migration and invasion. Tumor xenograft experiments were performed to test the in vivo malignancy of osteosarcoma cells. Co-culture experiment was used to study the relationship between osteosarcoma cells and osteoblast. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. Using a cohort of 20 cases of osteosarcoma and paired adjacent tissue samples, we found that miR-598 expression was decreased in osteosarcoma tissues and serum, as well as the osteosarcoma cell lines. Over expression of miR-598 suppressed the proliferation, migration, and invasion of osteosarcoma cells, while inhibition of miR-598 expression stimulated the proliferation, migration, and invasion. However, MiR-598 had no effect on osteosarcoma cell apoptosis. Data from nude mice further demonstrated the inhibitory role of miR-598 in osteosarcoma progression in vivo. Mechanically, miR-598 played its role by modulating osteoblastic differentiation in the microenvironment and targeting PDGFB and MET. Our findings enrich the knowledge of miR-598 in osteosarcoma progression, and reveal miR-598 as a promising diagnostic, prognostic, therapeutic biomarker for osteosarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma.

    Science.gov (United States)

    Morello, Emanuela; Martano, Marina; Buracco, Paolo

    2011-09-01

    Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The appendicular locations are most frequently involved and large to giant breed dogs are commonly affected, with a median age of 7-8 years. OSA is a locally invasive neoplasm with a high rate of metastasis, mostly to the lungs. Due to similarities in biology and treatment of OSA in dogs and humans, canine OSA represents a valid and important tumour model. Differences between canine and human OSAs include the age of occurrence (OSA is most commonly an adolescent disease in humans), localisation (the stifle is the most common site of localisation in humans) and limited use of neoadjuvant chemotherapy in canine OSA. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Bone mineral density change during adjuvant chemotherapy in pediatric osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ju Hyun Ahn

    2015-09-01

    Full Text Available PurposeOsteoporosis is currently receiving particular attention as a sequela in survivors of childhood osteosarcoma. The aim of this study was to evaluate bone mineral density (BMD changes during methotrexate-based chemotherapy in children and adolescents with osteosarcoma.MethodsNine patients with osteosarcoma were included in this retrospective study and compared with eight healthy controls. BMD of the lumbar spine and unaffected femur neck of patients was serially measured by dual-energy x-ray absorptiometry (DXA before and just after chemotherapy and compared with controls.ResultsFour patients (44% showed decreased lumbar spine BMD and seven patients (78% showed decreased femur neck BMD, while all controls showed increased lumbar and femur BMD (P=0.024 and P=0.023. The femur neck BMD z-scores decreased from -0.49±1.14 to -1.63±1.50 (P=0.032. At the end of therapy, five patients (56% showed femur neck BMD z-scores below -2.0.ConclusionThe bone metabolism is disturbed during therapy in children with osteosarcoma, resulting in a reduced BMD with respect to healthy controls. Since a reduced BMD predisposes to osteoporosis, specific attention and therapeutic interventions should be considered.

  14. RESEARCH Osteosarcoma presentation stages at a tumour unit in ...

    African Journals Online (AJOL)

    Osteosarcoma is the most common malignant primary bone tumour in children and ... in treatment, the diagnosis must be made prior to progression beyond localised .... Typical radiographic findings of an aggressive bone-forming tumour ... however, can often be overlooked or mistaken for benign lesions.12. Table 1. Patient ...

  15. Osteosarcoma in cats: 22 cases (1974-1984)

    International Nuclear Information System (INIS)

    Bitetto, W.V.; Patnaik, A.K.; Schrader, S.C.; Mooney, S.C.

    1987-01-01

    Osteosarcoma was diagnosed in 22 cats. Diagnosis was based on results of physical, radiographic, and histologic findings. Fifteen tumors arose from the appendicular skeleton, 4 from the skull, 2 from the pelvis, and 1 from a rib. Radiography revealed that in 14 of 15 cats (93%) with appendicular tumors, the lesion was metaphyseal, primarily lytic, with a ''moth-eaten'' appearance; absence and presence of periosteal new bone formation were associated with the tumors in 12 and 3 cats, respectively. The remaining 7 cats had axial tumors that were characterized by the presence of periosteal new bone formation in addition to bony lysis. Of the 15 cats with appendicular tumors, 12 were treated by amputation and 3 were euthanatized at the time of diagnosis. Of the cats undergoing amputation for treatment of their appendicular tumors, 6 cats were still alive 64 months after surgery (range, 13 to 64 months); the median survival time of the 5 cats (1 cat was lost to follow-up evaluation) that died was 49.2 months (range, 1 to 122 months). Four of 12 cats (33%) survived greater than or equal to 5 years after diagnosis. Of the cats with axial tumors that were not euthanatized at the time of diagnosis (6 of 7), the median survival time was 5.5 months. Based on these findings, we concluded that cats with appendicular osteosarcoma have a better prognosis than those with axial osteosarcoma, and that amputation is a viable treatment for cats with appendicular osteosarcoma

  16. Osteosarcoma of limb bones: a clinical, radiological and ...

    African Journals Online (AJOL)

    Objectives: To measure the strength of agreement in clinical, radiological and histopathological diagnosis of osteosarcoma in a 5 year study period. Setting: Addis Ababa University, Black-Lion ('Tikur Anbessa') Hospital-BLH, is the country's highest tertiary level referral and teaching hospital. The departments involved in this ...

  17. Multimodal transfer of MDR by exosomes in human osteosarcoma.

    Science.gov (United States)

    Torreggiani, Elena; Roncuzzi, Laura; Perut, Francesca; Zini, Nicoletta; Baldini, Nicola

    2016-07-01

    Exosomes are extracellular vesicles released by both normal and tumour cells which are involved in a new intercellular communication pathway by delivering cargo (e.g., proteins, microRNAs, mRNAs) to recipient cells. Tumour-derived exosomes have been shown to play critical roles in different stages of tumour growth and progression. In this study, we investigated the potential role of exosomes to transfer the multidrug resistance (MDR) phenotype in human osteosarcoma cells. Exosomes were isolated by differential centrifugation of culture media from multidrug resistant human osteosarcoma MG-63DXR30 (Exo/DXR) and MG-63 parental cells (Exo/S). Exosome purity was examined by transmission electron microscopy and confirmed by immunoblot analysis for the expression of specific exosomal markers. Our data showed that exosomes derived from doxorubicin-resistant osteosarcoma cells could be taken up into secondary cells and induce a doxorubicin-resistant phenotype. The incubation of osteosarcoma cells with Exo/DXR decreased the sensitivity of parental cells to doxorubicin, while exposure with Exo/S was ineffective. In addition, we demonstrated that Exo/DXR expressed higher levels of MDR-1 mRNA and P-glycoprotein compared to Exo/S (p=0.03). Interestingly, both MDR-1 mRNA and P-gp increased in MG-63 cells after incubation with Exo/DXR, suggesting this as the main mechanism of exosome-mediated transfer of drug resistance. Our findings suggest that multidrug resistant osteosarcoma cells are able to spread their ability to resist the effects of doxorubicin treatment on sensitive cells by transferring exosomes carrying MDR-1 mRNA and its product P-glycoprotein.

  18. Prognostic factors in canine appendicular osteosarcoma - a meta-analysis.

    Science.gov (United States)

    Boerman, Ilse; Selvarajah, Gayathri T; Nielen, Mirjam; Kirpensteijn, Jolle

    2012-05-15

    Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

  19. Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

    International Nuclear Information System (INIS)

    Erinjeri, Joseph P.; Deodhar, Ajita; Thornton, Raymond H.; Allen, Peter J.; Getrajdman, George I.; Brown, Karen T.; Sofocleous, Constantinos T.; Reidy, Diane L.

    2010-01-01

    Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.

  20. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma.

    Science.gov (United States)

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma.

  1. Chondroblastic and fibroblastic osteosarcoma of the jaws: Report of two cases and review of literature

    Directory of Open Access Journals (Sweden)

    Sudheerkanth Kondamari Peddana

    2017-01-01

    Full Text Available This study aims to report of two variants of gnathic osteosarcoma with highlights on the varied histopathological presentation of osteosarcomas (OS. OS present with diverse histological appearances. Despite significant advances in molecular pathogenesis and biomarkers, clinicopathologic correlation is still considered as the important criteria in diagnosis. Chondroblastic osteosarcoma in a 52-year-old female and fibroblastic osteosarcoma in a 35-year-old female. Osteosarcoma is a relatively rare disease of the oral and maxillofacial region. Regular screening and follow-up is highly recommended, as recurrence rates are higher. Thorough understanding of the histologic spectrum of osteosarcoma reduces the diagnostic difficulties in categorizing the OS and separating these neoplasms from benign bone diseases.

  2. Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

    OpenAIRE

    Pruksakorn, Dumnoensun; Teeyakasem, Pimpisa; Klangjorhor, Jeerawan; Chaiyawat, Parunya; Settakorn, Jongkolnee; Diskul-Na-Ayudthaya, Penchatr; Chokchaichamnankit, Daranee; Pothacharoen, Peraphan; Srisomsap, Chantragan

    2016-01-01

    Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted fro...

  3. MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation

    OpenAIRE

    Baranski, Zuzanna; Booij, Tijmen H.; Kuijjer, Marieke L.; de Jong, Yvonne; Cleton-Jansen, Anne-Marie; Price, Leo S.; van de Water, Bob; Bovée, Judith V. M. G.; Hogendoorn, Pancras C.W.; Danen, Erik H.J.

    2015-01-01

    Conventional high-grade osteosarcoma is the most common primary bone cancer with relatively high incidence in young people. Recurrent and metastatic tumors are difficult to treat. We performed a kinase inhibitor screen in two osteosarcoma cell lines, which identified MEK1/2 inhibitors. These inhibitors were further validated in a panel of six osteosarcoma cell lines. Western blot analysis was performed to assess ERK activity and efficacy of MEK inhibition. A 3D culture system was used to vali...

  4. Lysophosphatidic acid acyltransferase β (LPAATβ promotes the tumor growth of human osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Farbod Rastegar

    2010-12-01

    Full Text Available Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2 in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective

  5. Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

    OpenAIRE

    Marko, Tracy A.; Shamsan, Ghaidan A.; Edwards, Elizabeth N.; Hazelton, Paige E.; Rathe, Susan K.; Cornax, Ingrid; Overn, Paula R.; Varshney, Jyotika; Diessner, Brandon J.; Moriarity, Branden S.; O?Sullivan, M. Gerard; Odde, David J.; Largaespada, David A.

    2016-01-01

    Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 n...

  6. Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma.

    Science.gov (United States)

    Pruksakorn, Dumnoensun; Teeyakasem, Pimpisa; Klangjorhor, Jeerawan; Chaiyawat, Parunya; Settakorn, Jongkolnee; Diskul-Na-Ayudthaya, Penchatr; Chokchaichamnankit, Daranee; Pothacharoen, Peraphan; Srisomsap, Chantragan

    2016-09-01

    Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted from primary cell culture of osteosarcoma (n=7) and osteoblasts of cancellous bone (n=7) were studied. Using 2-DE based proteomics and LC-MS/MS analysis, we successfully determined seven differentially expressed protein spots. Four upregulated proteins and three downregulated proteins were observed in this study in which KH-type splicing regulatory protein (KSRP) was selected for further exploration. KSRP was significantly upregulated in osteosarcoma cells compared to osteoblasts using western blot assay. In addition, immunohistochemistry demonstrated that KSRP was also highly expressed in osteosarcoma tissue of independent cases from the experimental group. More importantly, KSRP silencing of osteosarcoma cell lines significantly decreased cell proliferation, migration ability, as well as implantation and growth ability in chick chorioallantoic membrane assay. Taken together, these findings demonstrate, that KSRP plays important roles in regulatory controls of osteosarcoma pathogenesis and serves as a potentially therapeutic target of osteosarcoma.

  7. CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells

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    Tang Liu

    2018-04-01

    Full Text Available Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.

  8. ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo.

    Science.gov (United States)

    Yin, Gang; Fan, Jin; Zhou, Wei; Ding, Qingfeng; Zhang, Jun; Wu, Xuan; Tang, Pengyu; Zhou, Hao; Wan, Bowen; Yin, Guoyong

    2017-10-10

    mTOR is a valuable oncotarget for osteosarcoma. The anti-osteosarcoma activity by a novel mTOR kinase inhibitor, CZ415, was evaluated. We demonstrated that CZ415 potently inhibited survival and proliferation of known osteosarcoma cell lines (U2OS, MG-63 and SaOs2), and primary human osteosarcoma cells. Further, CZ415 provoked apoptosis and disrupted cell cycle progression in osteosarcoma cells. CZ415 treatment in osteosarcoma cells concurrently blocked mTORC1 and mTORC2 activation. Intriguingly, ERK-MAPK activation could be a major resistance factor of CZ415. ERK inhibition (by MEK162/U0126) or knockdown (by targeted ERK1/2 shRNAs) dramatically sensitized CZ415-induced osteosarcoma cell apoptosis. In vivo , CZ415 oral administration efficiently inhibited U2OS tumor growth in mice. Its activity was further potentiated with co-administration of MEK162. Collectively, we demonstrate that ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo . CZ415 could be further tested as a promising anti-osteosarcoma agent, alone or in combination of ERK inhibition.

  9. Clinicopathologic and radiologic features of extraskeletal myxoid chondrosarcoma: a retrospective study of 40 Chinese cases with literature review.

    Science.gov (United States)

    Shao, Rui; Lao, I Weng; Wang, Lei; Yu, Lin; Wang, Jian; Fan, Qinhe

    2016-08-01

    The aim of this study is to describe the clinicopathologic and radiologic features of 40 cases of extraskeletal myxoid chondrosarcoma (EMC) from China. There were 25 males and 15 females (sex ratio, 1.7:1). Apart from an adolescent, all patients were adults with a median age of 49years. Twenty-four tumors (60%) occurred in the lower limb and limb girdles, especially the thigh, followed by the upper limb and limb girdles (20%) and trunk (10%). Other less commonly involved locations included the head and neck, sacrococcygeal region, and perineum. Tumors ranged in size from 1.5 to 19cm (mean, 7cm). By radiology, they appeared as hypoattenuated or isoattenuated masses on computed tomography with hyperintense signal on T2-weighted magnetic resonance imaging. Intralesional hypointense septa were present in most cases. Of the 40 tumors, 30 belonged to the classic subtype, whereas 9 cases were cellular, and 1 case had a rhabdoid phenotype. Tumor cells showed variable expression of synaptophysin (36%), S-100 protein (29%), epithelial membrane antigen (11%), and neuron-specific enolase (7%). Ki-67 index was remarkably higher in the cellular variant (mean, 30%). EWSR1-related rearrangement was detected in 12 of 14 cases tested by fluorescence in situ hybridization using break-apart probes. The overall 5- and 7-year survival was 71% and 60%, respectively. Awareness of the imaging features may help pathologists in the diagnosis of EMC. Fluorescence in situ hybridization also serves as a useful diagnostic tool for EMC, especially in the distinction from its mimics. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Structuring osteosarcoma knowledge: an osteosarcoma-gene association database based on literature mining and manual annotation.

    Science.gov (United States)

    Poos, Kathrin; Smida, Jan; Nathrath, Michaela; Maugg, Doris; Baumhoer, Daniel; Neumann, Anna; Korsching, Eberhard

    2014-01-01

    Osteosarcoma (OS) is the most common primary bone cancer exhibiting high genomic instability. This genomic instability affects multiple genes and microRNAs to a varying extent depending on patient and tumor subtype. Massive research is ongoing to identify genes including their gene products and microRNAs that correlate with disease progression and might be used as biomarkers for OS. However, the genomic complexity hampers the identification of reliable biomarkers. Up to now, clinico-pathological factors are the key determinants to guide prognosis and therapeutic treatments. Each day, new studies about OS are published and complicate the acquisition of information to support biomarker discovery and therapeutic improvements. Thus, it is necessary to provide a structured and annotated view on the current OS knowledge that is quick and easily accessible to researchers of the field. Therefore, we developed a publicly available database and Web interface that serves as resource for OS-associated genes and microRNAs. Genes and microRNAs were collected using an automated dictionary-based gene recognition procedure followed by manual review and annotation by experts of the field. In total, 911 genes and 81 microRNAs related to 1331 PubMed abstracts were collected (last update: 29 October 2013). Users can evaluate genes and microRNAs according to their potential prognostic and therapeutic impact, the experimental procedures, the sample types, the biological contexts and microRNA target gene interactions. Additionally, a pathway enrichment analysis of the collected genes highlights different aspects of OS progression. OS requires pathways commonly deregulated in cancer but also features OS-specific alterations like deregulated osteoclast differentiation. To our knowledge, this is the first effort of an OS database containing manual reviewed and annotated up-to-date OS knowledge. It might be a useful resource especially for the bone tumor research community, as specific

  11. SMALL CELL VARIANT OF OSTEOSARCOMA AT DIAPHYSIS OF TIBIA : A RARE CASE REPORT WITH REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Venkatalakshmi

    2015-04-01

    Full Text Available Osteosarcoma is the most common primary malignant tumor of bone involving predominantly metaphysis of the long bones. It accounts for 20% of primary bone cancers. Diaphyseal osteosarcoma is a rare form which accounts for approximately 10% of all cases of osteosarcomas. We present a case of Small cell variant of osteosarcoma in a 25 year old female presented in the diaphysis of left tibia

  12. A case of Werner's syndrome associated with osteosarcoma.

    Science.gov (United States)

    Murata, K; Hatamochi, A; Shinkai, H; Ishikawa, Y; Kawaguchi, N; Goto, M

    1999-10-01

    We described a case of Werner's syndrome associated with osteosarcoma. A 37-year-old Japanese man was diagnosed as having Werner's syndrome by the presence of juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, high-pitched voice, characteristic bird-like appearance of the face with beak-shaped nose, thinning of the entire skin and hyperkeratoses on soles, hyperlipemia, hyperuricemia, diabetes melitus, and the mutated responsible gene (WRN). He had a 3-month history of a tumor on his left forearm. Histologically, the tumor included four histological patterns; a malignant fibrous histiocytoma-like, a desmoid-like, a dermatofibrosarcoma protuberans-like, and a chondrosarcoma-like pattern. Tumoral osteoid formation was also found in the tumor. Therefore, the tumor was diagnosed as osteosarcoma.

  13. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    International Nuclear Information System (INIS)

    Brizzi, Maria P; Ferretti, Benedetta; Alabiso, Oscar; Ciuffreda, Libero; Bertetto, Oscar; Papotti, Mauro; Dogliotti, Luigi; Berruti, Alfredo; Ferrero, Anna; Milanesi, Enrica; Volante, Marco; Castiglione, Federico; Birocco, Nadia; Bombaci, Sebastiano; Perroni, Davide

    2009-01-01

    Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m 2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. NCT00953394

  14. Reproducibility determination of WHO classification of endometrial hyperplasia/well differentiated adenocarcinoma and comparison with computerized morphometric data in curettage specimens in Iran

    Directory of Open Access Journals (Sweden)

    Meysamie Ali

    2009-03-01

    Full Text Available Abstract Background Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability. Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases. Methods A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS. Results The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement. Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined. Interobserver agreement was in substantial rate for simple hyperplasia (SH and well differentiated adenocarcinoma (WDA but was in fair limit for complex hyperplasia (CH and atypical hyperplasia (AH. Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH ( D Score ≥ 1 or VPS ≥ 55% and Endometrial Intraepithelial Neoplasia (EIN (D-Score Conclusion It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and

  15. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    Directory of Open Access Journals (Sweden)

    Ciuffreda Libero

    2009-11-01

    Full Text Available Abstract Background Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU infusion plus long-acting release (LAR octreotide in patients with neuroendocrine carcinoma. Methods Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily plus LAR octreotide (20 mg monthly. Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Results Assessment by Response Evaluation Criteria in Solid Tumors (RECIST criteria showed partial response in 7 (24.1%, stable disease in 20 (69.0%, and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A response was observed in 12/25 assessable patients (48.0%; symptom relief was obtained in 9/15 symptomatic patients (60.0%. There was non significant decrease in circulating vascular epithelial growth factor (VEGF over time. Median time to progression was 22.6 months (range, 2.7-68.5; median overall survival was not reached yet. Toxicity was mild and manageable. Conclusion Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. Trial registration NCT00953394

  16. CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment.

    Science.gov (United States)

    Han, Yan; Wu, Chunlei; Wang, Jing; Liu, Na

    2017-05-01

    The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal-regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal-regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.

  17. Primary diaphyseal osteosarcoma in long bones: Imaging features and tumor characteristics

    International Nuclear Information System (INIS)

    Wang, Cheng-Sheng; Yin, Qi-Hua; Liao, Jin-Sheng; Lou, Jiang-Hua; Ding, Xiao-Yi; Zhu, Yan-Bo; Chen, Ke-Min

    2012-01-01

    Objective: This study aims to assess retrospectively the imaging features of diaphyseal osteosarcoma and compare its characteristics with that of metaphyseal osteosarcoma. Materials and methods: Eighteen pathologically confirmed diaphyseal osteosarcomas were reviewed. Images of X-ray (n = 18), CT (n = 12) and MRI (n = 15) were evaluated by two radiologists. Differences among common radiologic findings of X-ray, CT and MRI, and between diaphyseal osteosarcomas and metaphyseal osteosarcomas in terms of tumor characteristics were compared. Results: The common imaging features of diaphyseal osteosarcoma were bone destruction, lamellar periosteal reaction with/without Codman triangle, massive soft tissue mass/swelling, neoplastic bone and/or calcification. CT and MRI had a higher detection rate in detecting bone destruction (P = 0.001) as compared with that of X-ray. X-ray and CT resulted in a higher percentage in detecting periosteal reaction (P = 0.018) and neoplastic bone and/or calcification (P = 0.043) as compared with that of MRI. There was no difference (P = 0.179) in detecting soft tissue mass among three imaging modalities. When comparing metaphyseal osteosarcoma to diaphyseal osteosarcoma, the latter had the following characteristics: a higher age of onset (P = 0.022), a larger extent of tumor (P = 0.018), a more osteolytic radiographic pattern (P = 0.043). Conclusion: As compared with metaphyseal osteosarcoma, diaphysial osteosarcoma is a special location of osteosarcoma with a lower incidence, a higher age of onset, a larger extent of tumor, a more osteolytic radiographic pattern. The osteoblastic and mixed types are diagnosed easily, but the osteolytic lesion should be differentiated from Ewing sarcoma. X-ray, CT and MRI can show imaging features from different aspects with different detection rates.

  18. Possibilities traditional and liquid-based cytology combined with immunocytochemical detection of some molecular markers in the preoperative diagnosis of well-differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Irina S. Berjozkina

    2016-05-01

    Conclusion. The diagnostic accuracy of the method of liquid-based cytology is higher than the traditional method of cytology. ICC expression of Ki-67 method has 81.8% of sensitivity and 100% of specificity for the preoperative diagnosis of thyroid cancer. Conjoint definition HS Ki-67 and liquid-based cytology increases the sensitivity and specificity of the diagnosis of well-differentiated thyroid cancer preoperative to 100%. There no detected relations between the expression of galectin-3, NFM, Ki-67 and the presence an autoimmune process in the thyroid.

  19. Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

    Science.gov (United States)

    Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

    2008-07-01

    To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

  20. Photodynamic action of methylene blue in osteosarcoma cells in vitro.

    Science.gov (United States)

    Guan, Jiemin; Lai, Xiaoping; Wang, Xinna; Leung, Albert Wingnang; Zhang, Hongwei; Xu, Chuanshan

    2014-03-01

    Osteosarcoma is a common malignant bone tumor which threatens the life of young people worldwide. To explore alternative strategy for combating osteosarcoma, a light-emitting diode (LED) that activates methylene blue (MB) was used in the present study to investigate cell death of osteosarcoma-derived UMR106 cells. Photocytotoxicity in UMR106 cells was investigated 24h after photodynamic activation of MB using sulforhodamine B (SRB) assay and light microscopy. Apoptosis induction was observed 24h after photodynamic treatment using a confocal laser scanning microscopy (CLSM) with Hoechst 33342 staining. The change in mitochondrial membrane potential (MMP) was analyzed using a flow cytometry with rhodamine 123 staining. MB under red light irradiation caused a drug-concentration (0-100μM) and light-dose (0-32J/cm(2)) dependent cytotoxicity in UMR106 cells. The SRB assay and light microscopy observed a significant decrease in the number of UMR106 cells attached to the bottom of culture well after LED light-activated MB (100μM, 32J/cm(2)). Nuclear shrinkage, chromatin condensation and fragmentation were found in the treated cells by nuclear staining. In addition, flow cytometry showed that the MMP in UMR106 cells was rapidly reduced by photo-activated MB (100μM, 32J/cm(2)). Photodynamic action of MB under LED irradiation could remarkably kill osteosarcoma cells and induce cell apoptosis as well as MMP collapse. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  1. Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma

    International Nuclear Information System (INIS)

    Kaushik, Shaifali; Smoker, Wendy R.K.; Frable, William J.

    2002-01-01

    A case of malignant transformation of polyostotic fibrous dysplasia into maxillary chondroblastic osteosarcoma is presented. The clinical, radiographic, CT, MR imaging features and pathological findings of polyostotic fibrous dysplasia and its malignant transformation are described. Malignant transformation of fibrous dysplasia is rare and has not previously been described in the English literature in this location in McCune-Albright syndrome and in the absence of radiation treatment. (orig.)

  2. Osteosarcoma target therapy with stem cell transplant: A case review

    International Nuclear Information System (INIS)

    Fawzy, A.

    2005-01-01

    Full text: Radioisotopes with medium-energy beta emission and half life of a few days are attractive option for systemic delivery of targeted irradiation. Samarium-153 ethylene diamine tetra-ethylene phosphonale (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic osseous lesion. The usual dose of Sm-153 in metastatic disease is 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is thrombocytopenia. As local radiotherapy has only a limited therapeutic role in the treatment of osteosarcoma, and some types of the tumour portray an unpredictable response to chemotherapy. High dose Sm-153 (30mCi/Kg) was proposed for the target management of recurrent osteosarcoma, this was followed by stem cell transplant (peripheral-blood progenitor, PBPCs). A female child, 10 years old, with polyostotic osteosarcoma with local recurrence in the right hipbone was chosen for therapy. She had left knee prosthesis, right lower limb dis-articulation, and was given chemotherapy in multiple regions. She was subjected to MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, which showed negative uptake. She received 30mCi/Kg Sm-153 (660mCi in total dose), with no major events occurring in the post-injection period. After 10 days the patient went into pancytopenia, which necessitated haematological support. By day 14, there was minimal radiation in the whole body image and the child received her bone marrow transplant. There was marked improvement in the tumour size after 6 weeks of therapy, with improvement in the alkaline phosphatase level (from 1350Iu, before treatment to 350 post treatment). This was confirmed by serial MDP bone scan. High dose Sm-153 with stem cell transplant is considered view a promising method in the management of osteosarcoma. (author)

  3. Retrospective Analysis of 119 Osteosarcomas in a Single Centre Experience

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    Meral Gunaldi

    2016-01-01

    Full Text Available Aim: Osteosarcomas must be managed by a team which includes pathologists, radiologists, surgeons, radiation therapists, and medical oncologists. Treatment modalities and demographic charasteristics of osteosarcomas were analysed in this study. Material and Method: Primary osteosarcomas treated between 1999-2010 in Cukurova University Medical Faculty Department of Medical Oncology were analysed retrospectively. Results: Of the total 119 patients, 74% were male and 26% female. The median age was 19. The median follow up time was 37 months. The most frequently seen sarcomas were osteoblastic at 82.4%. Localization of the disease was found to be 55% in the lower extremity, 14.1% in the upper extremity, 13% in the head-neck, 6.6% in the thoracic area, and 4.1 % in the pelvic region. Some 6.41% were local stage, 25.64% locally advanced, 15.8% metastatic, and 14.10% were diagnosed with nuks disease. Chemotherapy was administered in 77 of 119 patients. Patients received different treatments: 23.1% were treated with preoperative chemotherapy, 16.67% postoperative, 9.52% palliative, 33.33% preoperative postoperative, 2.38% postoperative palliative, 9.52% preoperative postoperative palliative chemotherapy, and 4.76% of the patients did not receive chemotherapy. Both radical and conservative surgery was performed. The most common metastatic site was the lungs. The overall length of survival was 65 months (95%CI 30-59. The survival rates did not vary between the groups of preoperative, postoperative, preoperative postoperative chemotherapy and other groups (respectively 23 versus 36 versus 28 versus 44 months (p=0.8. No differences were evident for radiotherapy (p=0.06. Discussion: Osteosarcomas can be treated successfully with surgery, chemotherapy, and radiotherapy. There was no cumulative survival difference in results based on the types of chemotherapy used in this study. These results show the importance of a multimodality treatment approach including

  4. Osteosarcoma: A Meta-Analysis and Review of the Literature.

    Science.gov (United States)

    Friebele, Jill C; Peck, Jeffrey; Pan, Xueliang; Abdel-Rasoul, Mahmoud; Mayerson, Joel L

    2015-12-01

    Over the past 30 years, treatment advances and the addition of neoadjuvant chemotherapy have led to improved 5-year survival in patients with osteosarcoma. More recent literature suggests the overall prognosis remains highly variable, with little improvement since the introduction of neoadjuvant chemotherapy. Tumor necrosis is an important predictor of patient prognosis. Necrosis of more than 90% correlates with overall survival (OS) approaching 75%. We reviewed the history of osteosarcoma treatment and survival and performed a meta-analysis of the 2000-2011 literature. Forty articles were included in the study. Five-year OS was 63% (95% confidence interval, 60%-66%) in studies that included patients with metastatic and nonmetastatic disease and 71% (95% confidence interval, 67%-76%) in studies that included only patients with nonmetastatic disease. Fifty percent of the patients in the studies of those with nonmetastatic osteosarcoma achieved 90% necrosis on histology. Five-year OS and number of patients achieving 90% necrosis are consistent with previous reports. Research is needed to improve treatment regimens and patient outcomes.

  5. Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

    International Nuclear Information System (INIS)

    Blattmann, Claudia; Oertel, Susanne; Thiemann, Markus; Dittmar, Anne; Roth, Eva; Kulozik, Andreas E.; Ehemann, Volker; Weichert, Wilko; Huber, Peter E.; Stenzinger, Albrecht; Debus, Jürgen

    2015-01-01

    Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model. Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated. Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21 Waf1/Cip1 , inhibition of proliferation and angiogenesis compared to tumors treated with HIT only. HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials

  6. Fibroblastic osteosarcoma with epithelioid and squamous differentiation in a dog.

    Science.gov (United States)

    Jenkins, Tiffany L; Agnew, Dalen; Rissi, Daniel R

    2018-04-01

    A fibroblastic osteosarcoma with epithelioid and squamous differentiation in the distal femur of a 9-y-old spayed female Greyhound dog is described. Grossly, the tumor consisted of a pale-white, firm-to-hard mass that replaced the medullary and cortical areas of the distal end of the right femur. Histologically, the mass was composed predominantly of spindle cells admixed with areas of mineralized and non-mineralized osteoid matrix that were surrounded by stellate osteoblasts and scattered multinucleate giant cells, consistent with the diagnosis of a fibroblastic osteosarcoma. In addition, well-demarcated clusters of neoplastic epithelioid cells and foci of squamous differentiation with keratin pearls were present throughout the neoplasm. The spindle cells, epithelioid cells, and areas of squamous differentiation expressed cytoplasmic immunostaining for osteocalcin and osteonectin. The spindle cells and epithelioid cells were also immunopositive for vimentin. Epithelioid cells also expressed occasional cytoplasmic immunostaining for pancytokeratin (PCK) Lu-5, and areas of squamous differentiation were immunoreactive for PCK Lu-5 and high molecular weight CK; these areas were inconsistently immunoreactive for CK 5-6 and immunonegative for low molecular weight CK. Foci of squamous differentiation were not located within blood or lymphatic vessels, given that no immunoreactivity for factor VIII-related antigen was observed around these areas. A thorough autopsy and an evaluation of the medical history excluded a primary carcinoma or other neoplasm elsewhere in the dog. The findings were consistent with a diagnosis of fibroblastic osteosarcoma with epithelioid and squamous differentiation.

  7. Piriformis syndrome caused by extraosseous osteosarcoma. Case report

    International Nuclear Information System (INIS)

    Takemoto, Harumasa; Ishizaki, Yoshitaka; Ri, Taishin; Ito, Katsuya; Nagano, Tatsuo; Kitada, Chikara; Tamai, Masamitsu; Morishita, Toru

    2003-01-01

    We experienced a case of extraosseous osteosarcoma in an irradiated area, which showed the same symptom that piriformis syndrome revealed. This is a case report of a patient, forty-nine years old female. She was given radiation therapy in total dose of 50 Gy after total removal of ovarium and uterus with a diagnosis of the uterine cervix. She complained of pain at the lower extremity from early in January, 2002. Because of increase in pain, she consulted Higashiosaka City General Hospital. On examination, sciatic nerve disturbance was shown, X-ray and computed tomography showed ossification on the portion of the piriformis muscle. Removal of the tumor was done, and the pathological diagnosis as extraosseous osteosarcoma. It is considered that this present case is classified into radiation-induced extraosseous osteosarcoma, which was arisen after a relatively long, silent latent period since radiation was followed. Because it developed in a cartilage tissue in front of the piriformis muscle and infiltrated into the sciatic nerve, it is considered that this case is extremely rare as the case that revealed piriformis syndrome. (author)

  8. Convolutional Neural Network for Histopathological Analysis of Osteosarcoma.

    Science.gov (United States)

    Mishra, Rashika; Daescu, Ovidiu; Leavey, Patrick; Rakheja, Dinesh; Sengupta, Anita

    2018-03-01

    Pathologists often deal with high complexity and sometimes disagreement over osteosarcoma tumor classification due to cellular heterogeneity in the dataset. Segmentation and classification of histology tissue in H&E stained tumor image datasets is a challenging task because of intra-class variations, inter-class similarity, crowded context, and noisy data. In recent years, deep learning approaches have led to encouraging results in breast cancer and prostate cancer analysis. In this article, we propose convolutional neural network (CNN) as a tool to improve efficiency and accuracy of osteosarcoma tumor classification into tumor classes (viable tumor, necrosis) versus nontumor. The proposed CNN architecture contains eight learned layers: three sets of stacked two convolutional layers interspersed with max pooling layers for feature extraction and two fully connected layers with data augmentation strategies to boost performance. The use of a neural network results in higher accuracy of average 92% for the classification. We compare the proposed architecture with three existing and proven CNN architectures for image classification: AlexNet, LeNet, and VGGNet. We also provide a pipeline to calculate percentage necrosis in a given whole slide image. We conclude that the use of neural networks can assure both high accuracy and efficiency in osteosarcoma classification.

  9. Ezrin and moesin expression in canine and feline osteosarcoma.

    Science.gov (United States)

    Hlavaty, Juraj; Wolfesberger, Birgitt; Hauck, Marlene; Obermayer-Pietsch, Barbara; Fuchs-Baumgartinger, Andrea; Miller, Ingrid; Walter, Ingrid

    2017-08-01

    Biological features of canine osteosarcomas (OS) differ markedly from those found in feline and resemble more human osteosarcomas, in particular for their high rate of metastasis and poor prognosis. Ezrin, radixin and moesin are members of the ERM protein family and link the actin cytoskeleton with the cell membrane. Ezrin and moesin have been shown to be of prognostic significance in tumor progression due to their role in the metastatic process. The objective of this study was to analyze ezrin and moesin protein expression in a series of dog (n = 16) and cat (n = 8) osteosarcoma samples using immunohistochemistry and western blot techniques. We found that cat OS have a higher moesin expression compared to dog OS, however, the active phosphorylated forms of moesin and ezrin Tyr353 were more abundant in the dog samples. A statistically significant difference was found for the low and high immunohistochemical scores of ezrin and pan-phospho-ERM proteins between cat and dog. Although phospho-ezrin Thr567 was higher in feline OS, the membranous localization in dog OS samples indicates the presence of the biologically active form. Therefore, the observed differences in phosphorylated forms of ezrin and moesin status should be further studied to demonstrate if they are relevant for different biological behavior between dog and cat OS.

  10. Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma.

    Science.gov (United States)

    Ergen, Arzu; Kılıcoglu, Onder; Ozger, Harzem; Agachan, Bedia; Isbir, Turgay

    2011-08-01

    Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined by PCR-RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P=0.015). Besides, PON1 192 wild type QQ genotype (P=0.015) and PON1 55 wild type L allele (P=0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk of developing osteosarcoma.

  11. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability

    OpenAIRE

    Zhang, Lirong; Xu, Xiaohua; Jiang, Tiechao; Wu, Kunzhe; Ding, Chuanbo; Liu, Zhen; Zhang, Xuanhe; Yu, Tianhua; Song, Changlong

    2018-01-01

    Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory f...

  12. MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1

    International Nuclear Information System (INIS)

    Zhang, Shilian; Zhao, Yuehua; Wang, Lijie

    2016-01-01

    Osteosarcoma is an aggressive primary sarcoma of bone and occurs mainly in adolescents and young adults. The prognosis of OS remains poor, and most of them will die due to local relapse or metastases. The discovery of microRNAs provides a new possibility for the early diagnosis and treatment of OS. Thus, the aim of this study was to explore the expression and functions of microRNA-198 (miR-198) in osteosarcoma. The expression levels of miR-198 were determined by qRT-PCR in osteosarcoma tissues and cell lines. Cell proliferation assays, migration and invasion assays were adopted to investigate the effects of miR-198 on tumorous behaviors of osteosarcoma cells. The results showed that miR-198 expression levels were lower in osteosarcoma tissues and cell lines. In addition, low miR-198 expression levels were correlated with TNM stage and distant metastasis. After miR-198 mimics transfection, cell proliferation, migration and invasion were significantly suppressed in the osteosarcoma cells. Furthermore, ROCK1 was identified as a novel direct target of miR-198 in osteosarcoma. These findings suggested that miR-198 may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.

  13. The Surgical Treatment and Outcome of Nonmetastatic Extremity Osteosarcoma with Pathological Fractures

    Directory of Open Access Journals (Sweden)

    Zhi-Ping Deng

    2015-01-01

    Conclusions: Our study suggests that surgically treated patients with pathologic fractures in osteosarcoma have adequate local control and do not have a poorer outcome compared to patients without a fracture. Though osteosarcoma with a pathologic fracture is not a contraindication for limb salvage, appropriate case selection is important when deciding local control options to ensure adequate oncologic clearance.

  14. MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shilian, E-mail: shilian_zhang@126.com; Zhao, Yuehua; Wang, Lijie

    2016-04-08

    Osteosarcoma is an aggressive primary sarcoma of bone and occurs mainly in adolescents and young adults. The prognosis of OS remains poor, and most of them will die due to local relapse or metastases. The discovery of microRNAs provides a new possibility for the early diagnosis and treatment of OS. Thus, the aim of this study was to explore the expression and functions of microRNA-198 (miR-198) in osteosarcoma. The expression levels of miR-198 were determined by qRT-PCR in osteosarcoma tissues and cell lines. Cell proliferation assays, migration and invasion assays were adopted to investigate the effects of miR-198 on tumorous behaviors of osteosarcoma cells. The results showed that miR-198 expression levels were lower in osteosarcoma tissues and cell lines. In addition, low miR-198 expression levels were correlated with TNM stage and distant metastasis. After miR-198 mimics transfection, cell proliferation, migration and invasion were significantly suppressed in the osteosarcoma cells. Furthermore, ROCK1 was identified as a novel direct target of miR-198 in osteosarcoma. These findings suggested that miR-198 may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.

  15. Osteosarcoma and MFH of Bone Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Osteosarcoma and malignant fibrous histiocytoma (MFH) of bone are most successfully treated with a combination of systemic chemotherapy and complete resection of all clinically detectable disease. Get detailed information about the presentation, diagnosis, genomics, prognosis and treatment of osteosarcoma and MFH in this summary for clinicians.

  16. Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Siemann, Dietmar W; Abbott, Jeffrey R; Kiupel, Matti; Salute, Marc E; Milner, Rowan J

    2014-03-01

    Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (Posteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.

  17. Chemotherapy effectiveness and mortality prediction in surgically treated osteosarcoma dogs : A validation study

    NARCIS (Netherlands)

    Schmidt, A F; Nielen, M; Withrow, S J; Selmic, L E; Burton, J H; Klungel, O H; Groenwold, R H H; Kirpensteijn, J

    2016-01-01

    Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month

  18. Primary Osteoblastic Osteosarcoma of the Rib in an Adult: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jung Ah; Kang, Heung Sik [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Ryoo, In Seon [Dept. of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Hyo Ah; Chung, Jin Haeng [Dept. of Patholgy, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Oh, Joo Han [Dept. of Orthopedic Surgery, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2011-12-15

    We report the CT and magnetic resonance (MR) imaging appearances in an adult case of primary osteoblastic osteosarcoma of the rib. Osteosarcoma of the rib presents a diagnostic challenge because of the rarity of the lesion, especially with plain radiographs. The tumor should be suspected if CT and MR images demonstrate mineralization, suggestive of an osteoid matrix.

  19. [gammadelta T cells stimulated by zoledronate kill osteosarcoma cells].

    Science.gov (United States)

    Jiang, Hui; Xu, Qiang; Yang, Chao; Cao, Zhen-Guo; Li, Zhao-Xu; Ye, Zhao-Ming

    2010-12-01

    To investigate the cytotoxicity of human γδT cells from PBMCs stimulated by zoledronate against osteosarcoma cell line HOS in vitro and in vivo and evaluate the relavent pathways. The peripheral blood mononuclear cells (PBMCs)of healthy donors were stimulated by single dose zoledronate and cultured in the present of IL-2 for two weeks, analysising the percentage of γδT cells on a FACSCalibur cytometer.Study the cytotoxicity of γδT cells against the osteosarcoma line HOS using LDH release assay kit. Pre-treatment of γδT cells with anti-human γδTCR antibody, anti-human NKG2D antibody and concanamycin A to bolck the relavent pathways for evaluating the mechenisms of its cytotoxicity. In vivo, BALB/c mice were inoculated subcutaneously osteosarcoma cell HOS for developing hypodermal tumors. And they were randomized into two groups: unteated group, γδT cell therapy group. Tumor volume and weight of the two groups were compared. After two weeks of culture, γδT cells from zoledronate-stimulated PBMCs could reach (95±3)%. When the E:T as 6:1, 12:1, 25:1, 50:1, the percentage of osteosarcoma cell HOS killed by γδT cells was 26.8%, 31.5%, 37.8%, 40.9%, respectively.When anti-huma γδTCR antibody, anti-human NKG2D antibody and concanamycin A blocked the relavent pathways, the percentage was 32.3%, 4.7%, 16.7% ( E:T as 25:1), respectively. In vivo, the tumor inhibition rate of the group of γδT cell therapy was 42.78%. γδT cells derived from PBMCs stimulated by zoledronate can acquired pure γδT cells. And they show strong cytoxicity against osteosarcoma cell line HOS in vitro and in vivo.

  20. Lung cells support osteosarcoma cell migration and survival.

    Science.gov (United States)

    Yu, Shibing; Fourman, Mitchell Stephen; Mahjoub, Adel; Mandell, Jonathan Brendan; Crasto, Jared Anthony; Greco, Nicholas Giuseppe; Weiss, Kurt Richard

    2017-01-25

    Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined. Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72 h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3 T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment. Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3 T3 conditioned medium (p cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased alkaline

  1. Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Morioka, Hideo; Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Takahashi, Mitsuru; Yonemoto, Tsukasa; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Susa, Michiro; Nakayama, Robert; Nishimoto, Kazumasa; Kikuta, Kazutaka; Horiuchi, Keisuke; Kawai, Akira

    2016-01-01

    Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4–not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3–1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4–26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better

  2. Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma.

    Science.gov (United States)

    Morioka, Hideo; Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Takahashi, Mitsuru; Yonemoto, Tsukasa; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Susa, Michiro; Nakayama, Robert; Nishimoto, Kazumasa; Kikuta, Kazutaka; Horiuchi, Keisuke; Kawai, Akira

    2016-07-14

    Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4-not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3-1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4-26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were

  3. Low-grade osteosarcoma arising from cemento-ossifying fibroma: a case report.

    Science.gov (United States)

    Lee, Yong Bin; Kim, Nam-Kyoo; Kim, Jae-Young; Kim, Hyung Jun

    2015-02-01

    Cemento-ossifying fibromas are benign tumors, and, although cases of an aggressive type have been reported, no cases of cemento-ossifying fibroma transforming into osteosarcoma have been documented previously. Low-grade osteosarcoma is a rare type of primary bone tumor, representing 1%-2% of all osteosarcomas. A 45-year-old female patient was diagnosed with cemento-ossifying fibroma, treated with mass excision several times over a period of two years and eight months, and followed up. After biopsy gathered because of signs of recurrence, she was diagnosed with low-grade osteosarcoma. The patient underwent wide excision, segmental mandibulectomy, and reconstruction with fibula free flap. The aim of this report is to raise awareness of the possibility that cemento-ossifying fibroma can transform into osteosarcoma and of the consequent necessity for careful diagnosis and treatment planning.

  4. Experimental tumor growth of canine osteosarcoma cell line on chick embryo chorioallantoic membrane (in vivo studies).

    Science.gov (United States)

    Walewska, Magdalena; Dolka, Izabella; Małek, Anna; Wojtalewicz, Anna; Wojtkowska, Agata; Żbikowski, Artur; Lechowski, Roman; Zabielska-Koczywąs, Katarzyna

    2017-05-12

    The chick embryo chorioallantoic membrane (CAM) model is extensively used in human medicine in preclinical oncological studies. The CAM model has several advantages: low cost, simple experimental approach, time saving and following "3R principles". Research has shown that the human osteosarcoma cell lines U2OS, MMNG-HOS, and SAOS can form tumors on the CAM. In veterinary medicine, this has been described only for feline fibrosarcomas, feline mammary carcinomas and canine osteosarcomas. However, in case of canine osteosarcomas, it has been shown that only non-adherent osteosarcoma stem cells isolated from KTOSA5 and CSKOS cell lines have the ability to form microtumors on the CAM after an incubation period of 5 days, in contrast to adherent KTOSA5 and CSKOS cells. In the presented study, we have proven that the commercial adherent canine osteosarcoma cell line (D-17) can form vascularized tumors on the CAM after the incubation period of 10 days.

  5. Expression and significance of TRAIL and NF-kB in osteosarcoma

    International Nuclear Information System (INIS)

    Du Xiumin; You Murong; Qi Falian; Hu Chengjin

    2005-01-01

    To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

  6. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

    Science.gov (United States)

    2009-01-01

    Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (SLC1A3), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies. PMID:20028558

  7. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

    Directory of Open Access Journals (Sweden)

    Triche Timothy

    2009-12-01

    Full Text Available Abstract Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8 and solute carrier family 1 (glial high affinity glutamate transporter, member 3 (SLC1A3, which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively. Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.

  8. Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jen-Der; Weng Hsiao-Fen; Lu Wen-Tsoung [Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital (Taiwan, Province of China); Kao Pan-Fu; Huang Miau-Ju [Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taiwan (Taiwan, Province of China)

    1998-07-01

    Radioactive iodine ({sup 131}I) has been found to be more sensitive and more specific than thallium-201 for the detection of distant metastases and thyroid remnants in the neck in cases of well-differentiated thyroid carcinoma. {sup 201}Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative {sup 131}I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of {sup 201}Tl imaging in localizing metastases or recurrence in patients with well-differentiated thyroid carcinoma, and (2) evaluate the false-positive and false-negative results of {sup 131}I and {sup 201}Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative {sup 201}Tl and {sup 131}I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. {sup 201}Tl imaging was performed before the {sup 131}I studies. Of the 62 patients who underwent {sup 201}Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the {sup 201}Tl imaging studies tended to be older, were mor often male, had higher Tg levels and had a higher recurrence rate. Of these 24 patients, ten had negative diagnostic or therapeutic {sup 131}I scans. Concurrently, serum Tg levels were less than 5 ng/ml in five of these ten patients. Three patients were deemed false positive by {sup 201}Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative {sup 201}Tl scans, 11 had positive findings on {sup 131}I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on {sup 131}I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative {sup 201}Tl and {sup 131}I

  9. Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lin Jen-Der; Weng Hsiao-Fen; Lu Wen-Tsoung; Kao Pan-Fu; Huang Miau-Ju

    1998-01-01

    Radioactive iodine ( 131 I) has been found to be more sensitive and more specific than thallium-201 for the detection of distant metastases and thyroid remnants in the neck in cases of well-differentiated thyroid carcinoma. 201 Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative 131 I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of 201 Tl imaging in localizing metastases or recurrence in patients with well-differentiated thyroid carcinoma, and (2) evaluate the false-positive and false-negative results of 131 I and 201 Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative 201 Tl and 131 I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. 201 Tl imaging was performed before the 131 I studies. Of the 62 patients who underwent 201 Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the 201 Tl imaging studies tended to be older, were mor often male, had higher Tg levels and had a higher recurrence rate. Of these 24 patients, ten had negative diagnostic or therapeutic 131 I scans. Concurrently, serum Tg levels were less than 5 ng/ml in five of these ten patients. Three patients were deemed false positive by 201 Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative 201 Tl scans, 11 had positive findings on 131 I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on 131 I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative 201 Tl and 131 I scans, 15 had elevated serum Tg levels. Among these, local recurrence followed by lung

  10. Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: A lost cause?

    Science.gov (United States)

    Lamarca, Angela; Elliott, Emma; Barriuso, Jorge; Backen, Alison; McNamara, Mairéad G; Hubner, Richard; Valle, Juan W

    2016-03-01

    Chemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients. Eligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy. The primary end-point was overall-response (OR) rate; secondary end-points were progression-free survival (PFS), overall survival (OS), disease-stabilization (DS) and disease-control (DC) rates. Of 6434 studies screened, 20 were eligible: one randomised phase III trial, 2 randomised phase II studies, 10 single-arm phase II trials and 7 retrospective analyses including a total of 264 patients (median of 11 patients per study, range 6-49); and employing multiple chemotherapy schedules. The mean "median PFS" and "median OS" were 16.9 months (95%-confidence interval (CI) 3.8-30.04) and 32.2 months (95%-CI 10.4-54.2), respectively. The non-weighted mean OR, DS and DC rates were 11.5% (95%-CI 5.8-17.2), 56.5% (95%-CI 38.1-74.9) and 70.7% (95%-CI 54.9-86.5), respectively. In studies including both pNETs and non-pNET patients, meta-analysis showed a lower OR-rate in the non-pNET patients when compared to pNETs [odds ratio (OR) 0.35 (95% CI 0.18-0.66)]; however significance was lost when high-risk bias studies were excluded in a sensitivity analysis [OR 0.45 (95% CI 0.19-1.07); p-value 0.07]. Studies were of evidence level-C with heterogeneous populations and treatments; and small patient numbers. Well-designed, prospective studies are needed to adequately evaluate the role of chemotherapy in this setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Fluorescence In Situ Hybridization for MDM2 Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center

    Directory of Open Access Journals (Sweden)

    Khin Thway

    2015-01-01

    Full Text Available Background. The assessment of MDM2 gene amplification by fluorescence in situ hybridization (FISH has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL in specialist sarcoma units. We describe our experience of its utility at our tertiary institute. Methods. All routine histology samples in which MDM2 amplification was assessed with FISH over a 2-year period were included, and FISH results were correlated with clinical and histologic findings. Results. 365 samples from 347 patients had FISH for MDM2 gene amplification. 170 were positive (i.e., showed MDM2 gene amplification, 192 were negative, and 3 were technically unsatisfactory. There were 122 histologically benign cases showing a histology:FISH concordance rate of 92.6%, 142 WDL/DDL (concordance 96.5%, and 34 cases histologically equivocal for WDL (concordance 50%. Of 64 spindle cell/pleomorphic neoplasms (in which DDL was a differential diagnosis, 21.9% showed MDM2 amplification. Of the cases with discrepant histology and FISH, all but 3 had diagnoses amended following FISH results. For discrepancies of benign histology but positive FISH, lesions were on average larger, more frequently in “classical” (intra-abdominal or inguinal sites for WDL/DDL and more frequently core biopsies. Discrepancies of malignant histology but negative FISH were smaller, less frequently in “classical” sites but again more frequently core biopsies. Conclusions. FISH has a high correlation rate with histology for cases with firm histologic diagnoses of lipoma or WDL/DDL. It is a useful ancillary diagnostic tool in histologically equivocal cases, particularly in WDL lacking significant histologic atypia or DDL without corresponding WDL component, especially in larger tumors, those from intra-abdominal or inguinal sites or core biopsies. There is a significant group of well-differentiated adipocytic neoplasms

  12. The overexpression of MRP4 is related to multidrug resistance in osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Zhonghui He

    2015-01-01

    Full Text Available Doxorubicin (Adriamycin, ADM is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs are members of a superfamily of ATP-binding cassette (ABC transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient′s primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05. In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05. Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells.

  13. Establishment and Characterization of New Canine and Feline Osteosarcoma Primary Cell Lines

    Directory of Open Access Journals (Sweden)

    Florian R. L. Meyer

    2016-06-01

    Full Text Available Osteosarcomas are the most abundant form of bone malignancies in multiple species. Canine osteosarcomas are considered a valuable model for human osteosarcomas because of their similar features. Feline osteosarcomas, on the other hand, are rarely studied but have interesting characteristics, such as a better survival prognosis than dogs or humans, and less likelihood of metastasis. To enable experimental approaches to study these differences we have established five new canine osteosarcoma cell lines out of three tumors, COS_1186h, COS_1186w, COS_1189, and COS_1220, one osteosarcoma-derived lung metastasis, COS_1033, and two new feline osteosarcoma cell lines, FOS_1077 and FOS_1140. Their osteogenic and neoplastic origin, as well as their potential to produce calcified structures, was determined by the markers osteocalcin, osteonectin, tissue unspecific alkaline phosphatase, p53, cytokeratin, vimentin, and alizarin red. The newly developed cell lines retained most of their markers in vitro but only spontaneously formed spheroids produced by COS_1189 showed calcification in vitro.

  14. Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma.

    Science.gov (United States)

    Baranski, Zuzanna; Booij, Tijmen H; Cleton-Jansen, Anne-Marie; Price, Leo S; van de Water, Bob; Bovée, Judith V M G; Hogendoorn, Pancras C W; Danen, Erik H J

    2015-07-01

    Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients

    Directory of Open Access Journals (Sweden)

    Xia WK

    2016-07-01

    Full Text Available Wen-Kai Xia,1 Qing-Feng Lin,2 Dong Shen,2 Zhi-Li Liu,2 Jun Su,2 Wei-Dong Mao2 1Department of Nephrology, 2Department of Oncology, The Affiliated Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu, People’s Republic of China Abstract: Long noncoding RNAs have been documented as having widespread roles in carcinogenesis and cancer progression. However, roles of long noncoding RNAs in osteosarcoma remain unclear. This study is to investigate the clinical relevance and biological functions of long noncoding RNA 91H in osteosarcoma. Herein, we confirmed that 91H expression was notably increased in osteosarcoma patients and cell lines compared to healthy controls and normal human bone cell lines. High expression of 91H was significantly correlated with advanced clinical stage, chemotherapy after surgery, and tumor size >5 cm. Furthermore, 91H was an independent prognostic factor for overall survival in osteosarcoma patients after treatments. Additionally, the knockdown of 91H expression inhibited osteosarcoma cells’ proliferation and promoted their apoptosis in vitro. In summary, these findings indicate that 91H may be a novel biomarker for risk prognostication and also provide a clue to the molecular etiology of osteosarcoma. Keywords: long noncoding RNA, 91H, osteosarcoma, survival

  16. Preliminary evaluation of serum total cholesterol concentrations in dogs with osteosarcoma.

    Science.gov (United States)

    Leeper, H; Viall, A; Ruaux, C; Bracha, S

    2017-10-01

    To determine if total serum cholesterol concentrations were altered in dogs with osteosarcoma. To evaluate association of total serum cholesterol concentration with clinical outcomes in dogs with appendicular osteosarcoma. Retrospective, multi-institutional study on 64 dogs with osteosarcoma. Control population consisted of dogs with traumatic bone fractures (n=30) and healthy patients of similar age and weight as those of the osteosarcoma cases (n=31). Survival analysis was done on 35 appendicular osteosarcoma patients that received the current standard of care. Statistical associations were assessed by univariable and multi-variable analysis. Information about age, sex, primary tumour location, total cholesterol concentration, monocytes and lymphocyte counts and alkaline phosphatase were also included. Total cholesterol was elevated above the reference interval (3·89 to 7·12 mmol/L) (150 to 275 mg/dL) in 29 of 64 (45·3%) osteosarcoma-bearing dogs, whereas similar elevations were found in only 3 of 30 (10%) fracture controls (Posteosarcoma. These results suggest that elevated total cholesterol is associated with canine osteosarcoma and may have prognostic significance. © 2017 British Small Animal Veterinary Association.

  17. Plutonium-induced osteosarcomas in the St. Bernard

    International Nuclear Information System (INIS)

    Taylor, G.N.; Thurman, G.B.; Mays, C.W.; Shabestari, L.; Angus, W.; Atherton, D.R.

    1981-01-01

    Fourteen osteosarcomas were observed among the eight St. Bernards that died following the injection of 239 Pu. Early data tentatively indicate that the St. Bernard is about 5 times more sensitive than the beagle and about 130 times more sensitive than the average person is estimated to be to 239 Pu-induced bone sarcomas. Thus the St. Bernard may be an excellent model in which to study the pathogenesis of bone cancer induction, to evaluate the relationship between spontaneous susceptibility and radiosensitivity, and to determine whether radiosensitivity significantly affects the toxicity ration of 239 Pu/ 226 Ra

  18. Plutonium-induced osteosarcomas in the St. Bernard

    International Nuclear Information System (INIS)

    Taylor, G.N.; Thurman, G.B.; Mays, C.W.; Shabestari, L.; Angus, W.; Eaton, J.; Hitchman, J.

    1978-01-01

    Thirteen osteosarcomas have been observed among the 7 St. Bernards that have died following the injection of 239 Pu. Preliminary data indicate that the St. Bernard is about 6 times more sensitive than the Beagle, and about 150 times more sensitive than the average person is to 239 Pu-induced bone sarcomas. Thus, the St. Bernard may be an excellent model to study the pathogenesis of bone cancer induction, to evaluate the relationship between spontaneous susceptibility and radiosensitivity, and to determine whether or not radiosensitivity significantly affects the toxicity ratio

  19. Metastatic transitional cell carcinoma of the tibia radiologically mimicking osteosarcoma.

    LENUS (Irish Health Repository)

    Cunningham, Laurence Patrick

    2013-01-01

    We report a case of a 73-year-old lady with transitional cell carcinoma and no evidence of metastatic disease presenting with gradual weight loss, pretibial swelling and painful weightbearing. Investigations revealed a lesion of the right tibial diaphysis. The radiological and clinical appearance was that of primary osteosarcoma. Biopsy results revealed metastatic transitional cell carcinoma of the tibia. Intramedullary nailing was performed which relieved pain on weightbearing. The patient declined radiotherapy and was started on a palliative care regimen. This case illustrates the importance of histological diagnosis in the treatment of diaphyseal lesions.

  20. Osteosarcoma of mandible in a 10-year-old girl

    Directory of Open Access Journals (Sweden)

    SVSG Nirmala

    2014-01-01

    Full Text Available Osteosarcoma (OS of the jaws is a relatively rare malignant bone tumor. Like, its counterpart in the long bones, OS affecting the head and neck region shows distinct yet diverse clinical, histologic and prognostic characteristics. Here, we report a rare case of OS of fibroblastic variant in a 10-year-old girl, who came with a bony swelling in the left mandibular posterior region, with a radiographic presentation of sunburst appearance, the histopathological examination confirmed the diagnosis. The patient underwent partial mandibulectomy under general anesthesia followed by prosthodontic rehabilitation and is currently undergoing regular follow-up examination.

  1. Multifocal osteosarcoma as second tumor after childhood retinoblastoma

    International Nuclear Information System (INIS)

    Potepan, P.; Laffranchi, A.; Danesini, G.M.; Spagnoli, I.; Luksch, R.; Sozzi, G.; Testi, A.; Parafioriti, A.; Giardini, R.

    1999-01-01

    We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases. (orig.)

  2. Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma.

    Science.gov (United States)

    Daft, Paul G; Yuan, Kaiyu; Warram, Jason M; Klein, Michael J; Siegal, Gene P; Zayzafoon, Majd

    2013-04-01

    Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca(2+)/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca(2+)-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by short hairpin RNA (shRNA) in MG-63 and 143B cells resulted in decreased proliferation (50% and 41%), migration (22% and 25%), and invasion (95% and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%), and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. ©2013 AACR.

  3. 2-methoxyestradiol-mediated anti-tumor effect increases osteoprotegerin expression in osteosarcoma cells.

    Science.gov (United States)

    Benedikt, Michaela B; Mahlum, Eric W; Shogren, Kristen L; Subramaniam, Malayannan; Spelsberg, Thomas C; Yaszemski, Michael J; Maran, Avudaiappan

    2010-04-01

    Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17beta-estradiol and a tumorigenic estrogen metabolite, 16alpha-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co-treating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment. Copyright 2010 Wiley-Liss, Inc.

  4. Effects of epidermal growth factor receptor kinase inhibition on radiation response in canine osteosarcoma cells.

    Science.gov (United States)

    Mantovani, Fernanda B; Morrison, Jodi A; Mutsaers, Anthony J

    2016-05-31

    Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of life. Epidermal growth factor receptor (EGFR) expression has been documented in canine osteosarcoma and higher EGFR levels have been correlated to a worse prognosis. However, effects of EGFR inhibition on radiation responsiveness in canine osteosarcoma have not been previously characterized. This study examined the effects of the small molecule EGFR inhibitor erlotinib on canine osteosarcoma radiation responses, target and downstream protein expression in vitro. Additionally, to assess the potential impact of treatment on tumor angiogenesis, vascular endothelial growth factor (VEGF) levels in conditioned media were measured. Erlotinib as a single agent reduced clonogenic survival in two canine osteosarcoma cell lines and enhanced the impact of radiation in one out of three cell lines investigated. In cell viability assays, erlotinib enhanced radiation effects and demonstrated single agent effects. Erlotinib did not alter total levels of EGFR, nor inhibit downstream protein kinase B (PKB/Akt) activation. On the contrary, erlotinib treatment increased phosphorylated Akt in these osteosarcoma cell lines. VEGF levels in conditioned media increased after erlotinib treatment as a single agent and in combination with radiation in two out of three cell lines investigated. However, VEGF levels decreased with erlotinib treatment in the third cell line. Erlotinib treatment promoted modest enhancement of radiation effects in canine osteosarcoma cells, and possessed activity as a single agent in some cell lines, indicating a potential role for EGFR inhibition in the treatment of a subset of osteosarcoma patients. The relative radioresistance of

  5. Osteosarcoma with a pathologic fracture in a six-month-old dog

    International Nuclear Information System (INIS)

    Phillips, L.; Hager, D.; Parker, R.; Yanik, D.

    1986-01-01

    This case history report describes the clinical, radiographic, and histopathologic features of an osteosarcoma with an associated pathologic fracture in a 6-month-old dog. A 6-month-old intact male Bloodhound was presented with a primary complaint of a right forelimb lameness of one month's duration. In radiographs, a minimally displaced transverse fracture of the proximal humeral metaphysis was seen. There was extensive cortical bone destruction at the fracture site and minimal periosteal new bone suggestive of a primary bone tumor with a pathologic fracture. Biopsy specimens demonstrated neoplastic mesenchymal cells producing osteoid compatible with a diagnosis of osteosarcoma. This case history report constitutes the youngest reported canine osteosarcoma

  6. Case report 331: Small cell osteosarcoma of the tibia with diffuse metastatic disease

    International Nuclear Information System (INIS)

    Roessner, A.; Miebs, T.; Grundmann, E.; Immenkamp, M.; Hiddemann, W.; Althoff, J.

    1985-01-01

    In summary, the case is presented of a 29-year-old woman who developed a sclerosing small-cell osteosarcoma in the upper end of the tibia. The unique features in this case are reflected both in its morphology and protracted clinical course, while its histological pattern resembles in some features a small cell variant of the highly malignant osteosarcoma described by Sim and Martin. In addition to the unusual clinical course, the failure in response to chemotherapy underscores that this tumor differed in its biological behavior from other highly malignant types of osteosarcoma. The importance of DNA analysis is stressed. (orig./WU)

  7. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

    Science.gov (United States)

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-Hara, Tomoko; Fujita, Naoya

    2014-08-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co-culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho-antibody arrays revealed that co-culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. The addition of supernatants of osteosarcoma-platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated-PDGFR and -Akt. Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet-induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt. Our results suggest that inhibitors that specifically target osteosarcoma-platelet interactions may eradicate osteosarcomas. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  8. Neck and whole-body scanning with 5-mCi dose of (123)I as diagnostic tracer in patients with well-differentiated thyroid cancer.

    Science.gov (United States)

    Gulzar, Z; Jana, S; Young, I; Bukberg, P; Yen, V; Naddaf, S; Abdel-Dayem, H M

    2001-01-01

    To determine whether a 5-mCi dose of 123I can be used as an effective radiotracer for assessing the presence of remnant thyroid tissue and for searching for metastatic lesions in patients with well-differentiated thyroid cancer as well as to attempt to ascertain whether a scan performed only at 4 hours is sufficient for accurate diagnosis and might replace the conventional protocol of scanning at both 4 hours and 24 hours. We prospectively studied 27 patients who had undergone near-total thyroidectomy and had a documented diagnosis of well-differentiated thyroid carcinoma. Patients underwent scanning after receiving a 5-mCi dose of 123I, at a time when they had discontinued thyroid replacement therapy and had a thyrotropin level in excess of 30 mIU/mL. Whole-body images at 4 hours and 24 hours were obtained and were compared with posttherapy scans obtained 5 to 7 days after administration of 131I. Scans were interpreted by two board-certified nuclear medicine physicians. Of the 27 patients, 2 (7.4%) showed discordance between the 123I scan performed at 24 hours and the posttherapy 131I scan. When 4-hour images after administration of 123I were compared with the posttherapy 131I scans, a discordance rate of 14.8% (4 of 27 patients) was noted. In addition, two of these four patients showed lesions on the 24-hour images that were not seen on the 4-hour images (one with new lung metastatic involvement and the other with a local recurrence in the lower neck area). The prognosis and treatment of these two patients were substantially changed by the result of the 24-hour images. On comparison of scans obtained after administration of a 5-mCi dose of 123I with those obtained after 131I therapy, we conclude that 5 mCi of 123I produces images that have excellent quality and resolution and also compare favorably with those obtained after 131I therapy. Furthermore, a decrease in the dose of 123I from 10 mCi to 5 mCi lowered the cost of the study without compromising the

  9. Unusual presentation of primary extra osseous osteosarcoma: As breast abscess

    Directory of Open Access Journals (Sweden)

    N J Nawarathna

    2016-01-01

    Full Text Available Primary extra osseous osteogenic sarcoma is one of the rarest forms of malignant tumor of the breast. It can arise as a result of osseous metaplasia of a preexisting neoplasm or from a none-phylloides sarcoma of a previously normal breast. Due to its rarity, natural history and optimal treatment methods remain unclear. A 60-year-old patient presented to the surgical casualty with large breast abscess. Abscess wall histology revealed an osteosarcoma of the breast. Left total mastectomy with axillary clearance was performed. Histology and subsequent imunohistochemical studies confirmed the diagnosis of osteogenic sarcoma without lymph nodal metastasis. The patient was referred to the oncologist for further management. Rare types of breast tumors can be presented as breast abscess. Incision and drainage together with wall biopsy help to exclude associated sinister pathologies. Diagnosis of primary osteosarcoma of the breast was made using histological and immunohistochemical findings once the possible primary from the sternum and ribs were excluded. Treatment is as for sarcomas affecting other locations and should comprise a multidisciplinary approach.

  10. [Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma].

    Science.gov (United States)

    Marguglio, A; Hoyoux, C; Dresse, M F; Chantraine, J M; Thiry, A; Gillet, P

    1998-03-01

    Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.

  11. Three-dimensional alginate spheroid culture system of murine osteosarcoma.

    Science.gov (United States)

    Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

    2009-11-01

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

  12. Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

    Science.gov (United States)

    Cannon, C M; Pozniak, J; Scott, M C; Ito, D; Gorden, B H; Graef, A J; Modiano, J F

    2015-03-01

    We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted. © 2013 Blackwell Publishing Ltd.

  13. Possible application of boron neutron capture therapy to canine osteosarcoma

    International Nuclear Information System (INIS)

    Takeuchi, Akira

    1985-01-01

    Possibility for successful treatment of canine osteosarcoma by boron neutron capture therapy (BNCT) was demonstrated based upon an uptake study of the boron compound and an experimental treatment by BNCT. In the up take study following intravenous administration of Na 2 B 12 H 11 SH, satisfactorily higher boron concentration with some variation between tumors is likely to be obtained 12 hours after the administration, together with significantly lower boron levels in blood and bone. Based upon these results, osteosarcoma of a mongrel dog was successfully treated by BNCT. The tumor received approximately 3800 rads with single neutron irradiation (approximately 1.4 x 10 13 n./cm 2 ) about 12 hours after intravenous infusion of Na 2 B 12 H 11 SH of 96 % enriched 10 B in the ratio of 50 mg 10 B/kg. Clinical and radiographical improvements were remarkable and no neoplastic cell was found in any part of the original neoplastic lesion and its surrounding tissue at the time of autopsy after 30 days. (author)

  14. New small molecules targeting apoptosis and cell viability in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Doris Maugg

    Full Text Available Despite the option of multimodal therapy in the treatment strategies of osteosarcoma (OS, the most common primary malignant bone tumor, the standard therapy has not changed over the last decades and still involves multidrug chemotherapy and radical surgery. Although successfully applied in many patients a large number of patients eventually develop recurrent or metastatic disease in which current therapeutic regimens often lack efficacy. Thus, new therapeutic strategies are urgently needed. In this study, we performed a phenotypic high-throughput screening campaign using a 25,000 small-molecule diversity library to identify new small molecules selectively targeting osteosarcoma cells. We could identify two new small molecules that specifically reduced cell viability in OS cell lines U2OS and HOS, but affected neither hepatocellular carcinoma cell line (HepG2 nor primary human osteoblasts (hOB. In addition, the two compounds induced caspase 3 and 7 activity in the U2OS cell line. Compared to conventional drugs generally used in OS treatment such as doxorubicin, we indeed observed a greater sensitivity of OS cell viability to the newly identified compounds compared to doxorubicin and staurosporine. The p53-negative OS cell line Saos-2 almost completely lacked sensitivity to compound treatment that could indicate a role of p53 in the drug response. Taken together, our data show potential implications for designing more efficient therapies in OS.

  15. Radiosensitization by histone deacetylase inhibition in an osteosarcoma mouse model

    International Nuclear Information System (INIS)

    Blattmann, C.; University Children's Hospital of Heidelberg; Thiemann, M.; Stenzinger, A.

    2013-01-01

    Background: Osteosarcomas (OS) are highly malignant and radioresistant tumors. Histone deacetylase inhibitors (HDACi) constitute a novel class of anticancer agents. We sought to investigate the effect of combined treatment with suberoylanilide hydroxamic acid (SAHA) and radiotherapy in OS in vivo. Methods: Clonogenic survival of human OS cell lines as well as tumor growth delay of OS xenografts were tested after treatment with either vehicle, radiotherapy (XRT), SAHA, or XRT and SAHA. Tumor proliferation, necrosis, microvascular density, apoptosis, and p53/p21 were monitored by immunohistochemistry. The CD95 pathway was performed by flow cytometry, caspase (3/7/8) activity measurements, and functional inhibition of CD95 death signaling. Results: Combined treatment with SAHA and XRT markedly reduced the surviving fraction of OS cells as compared to XRT alone. Likewise, dual therapy significantly inhibited OS tumor growth in vivo as compared to XRT alone, reflected by reduced tumor proliferation, impaired angiogenesis, and increased apoptosis. Addition of HDACi to XRT led to elevated p53, p21, CD95, and CD95L expression. Inhibition of CD95 signaling reduced HDACi- and XRT-induced apoptosis. Conclusion: Our data show that HDACi increases the radiosensitivity of osteosarcoma cells at least in part via ligand-induced apoptosis. HDACi thus emerge as potentially useful treatment components of OS. (orig.)

  16. Radiosensitization by histone deacetylase inhibition in an osteosarcoma mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Blattmann, C. [Olgahospital, Stuttgart (Germany). Paediatrie 5; University Children' s Hospital of Heidelberg (Germany). Dept. of Pediatric Oncology, Hematology and Immunology; Thiemann, M. [German Cancer Research Center (DKFZ), Heidelberg (Germany). Dept. of Radiotherapy, Molecular- and Translational Radiation Oncology; Stenzinger, A. [Heidelberg Univ. (Germany). Inst. of Pathology; and others

    2013-11-15

    Background: Osteosarcomas (OS) are highly malignant and radioresistant tumors. Histone deacetylase inhibitors (HDACi) constitute a novel class of anticancer agents. We sought to investigate the effect of combined treatment with suberoylanilide hydroxamic acid (SAHA) and radiotherapy in OS in vivo. Methods: Clonogenic survival of human OS cell lines as well as tumor growth delay of OS xenografts were tested after treatment with either vehicle, radiotherapy (XRT), SAHA, or XRT and SAHA. Tumor proliferation, necrosis, microvascular density, apoptosis, and p53/p21 were monitored by immunohistochemistry. The CD95 pathway was performed by flow cytometry, caspase (3/7/8) activity measurements, and functional inhibition of CD95 death signaling. Results: Combined treatment with SAHA and XRT markedly reduced the surviving fraction of OS cells as compared to XRT alone. Likewise, dual therapy significantly inhibited OS tumor growth in vivo as compared to XRT alone, reflected by reduced tumor proliferation, impaired angiogenesis, and increased apoptosis. Addition of HDACi to XRT led to elevated p53, p21, CD95, and CD95L expression. Inhibition of CD95 signaling reduced HDACi- and XRT-induced apoptosis. Conclusion: Our data show that HDACi increases the radiosensitivity of osteosarcoma cells at least in part via ligand-induced apoptosis. HDACi thus emerge as potentially useful treatment components of OS. (orig.)

  17. O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

    Science.gov (United States)

    Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

    2017-07-01

    Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

  18. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

    International Nuclear Information System (INIS)

    Martín-Richard, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Ángel; Quindós, Maria; Maisonobe, Pascal; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta

    2013-01-01

    Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier http://clinicaltrials.gov/show/NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18

  19. Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Min Jeong Kim

    2018-01-01

    Full Text Available Mitotic counts in the World Health Organization (WHO grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs. The mitosis-specific marker phosphohistone H3 (PHH3 can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.

  20. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

    Science.gov (United States)

    Masab, Muhammad; Saif, Muhammad Wasif

    2017-12-01

    Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

  1. Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report.

    Science.gov (United States)

    Okuyama, Kohei; Fujita, Shuichi; Yanamoto, Souichi; Naruse, Tomofumi; Sakamoto, Yuki; Kawakita, Akiko; Omori, Keisuke; Tsuchihashi, Hiroki; Umeda, Masahiro

    2017-09-01

    Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy.

  2. Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

    Science.gov (United States)

    Nanno, Yoshihide; Toyama, Hirochika; Matsumoto, Ippei; Otani, Kyoko; Asari, Sadaki; Goto, Tadahiro; Ajiki, Tetsuo; Zen, Yoh; Fukumoto, Takumi; Ku, Yonson

    The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. Copyright © 2016. Published by Elsevier B.V.

  3. Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: a multifactorial decision-making guide for the Thyroid Cancer Care Collaborative.

    Science.gov (United States)

    Urken, Mark L; Milas, Mira; Randolph, Gregory W; Tufano, Ralph; Bergman, Donald; Bernet, Victor; Brett, Elise M; Brierley, James D; Cobin, Rhoda; Doherty, Gerard; Klopper, Joshua; Lee, Stephanie; Machac, Josef; Mechanick, Jeffrey I; Orloff, Lisa A; Ross, Douglas; Smallridge, Robert C; Terris, David J; Clain, Jason B; Tuttle, Michael

    2015-04-01

    Well-differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web-based repository of a patient's clinical information. Ten clinical decision-making modules (CDMMs) process this information and display individualized treatment recommendations. We conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC. Surgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery. The management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician. © 2014 Wiley Periodicals, Inc.

  4. Whole-body low-dose computed tomography in multiple myeloma staging: Superior diagnostic performance in the detection of bone lesions, vertebral compression fractures, rib fractures and extraskeletal findings compared to radiography with similar radiation exposure.

    Science.gov (United States)

    Lambert, Lukas; Ourednicek, Petr; Meckova, Zuzana; Gavelli, Giampaolo; Straub, Jan; Spicka, Ivan

    2017-04-01

    The primary objective of the present prospective study was to compare the diagnostic performance of conventional radiography (CR) and whole-body low-dose computed tomography (WBLDCT) with a comparable radiation dose reconstructed using hybrid iterative reconstruction technique, in terms of the detection of bone lesions, skeletal fractures, vertebral compressions and extraskeletal findings. The secondary objective was to evaluate lesion attenuation in relation to its size. A total of 74 patients underwent same-day skeletal survey by CR and WBLDCT. In CR and WBLDCT, two readers assessed the number of osteolytic lesions at each region and stage according to the International Myeloma Working Group (IMWG) criteria. A single reader additionally assessed extraskeletal findings and their significance, the number of vertebral compressions and bone fractures. The radiation exposure was 2.7±0.9 mSv for WBLDCT and 2.5±0.9 mSv for CR (P=0.054). CR detected bone involvement in 127 out of 486 regions (26%; Prib fractures compared with CR (188 vs. 47; Pfractures, vertebral compressions and extraskeletal findings, which results in up- or downstaging in 24% patients according to the IMWG criteria. The attenuation of osteolytic lesions can be measured with the avoidance of the partial volume effect.

  5. Isolation of Osteosarcoma-Associated Human Antibodies from a Combinatorial Fab Phage Display Library

    Directory of Open Access Journals (Sweden)

    Carmela Dantas-Barbosa

    2009-01-01

    Full Text Available Osteosarcoma, a highly malignant disease, is the most common primary bone tumor and is frequently found in children and adolescents. In order to isolate antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab library displayed on the surface of phages was used. After three rounds of selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were detected. From these Fabs, five were better characterized, and despite having differences in their VH (heavy chain variable domain and Vκ (kappa chain variable domain regions, they all bound to a protein with the same molecular mass. Further analysis by cell ELISA and immunocytochemistry suggested that the Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in neoplasic cells than in normal tissue. These results suggest that the human Fabs selected in this work are a valuable tool for the study of this neoplasia.

  6. Vitamin A effects on UMR 106 osteosarcoma cells are not mediated by specific cytosolic receptors.

    OpenAIRE

    Oreffo, R O; Francis, J A; Triffitt, J T

    1985-01-01

    Retinol and retinoic acid at 20 microM altered cell morphology and inhibited cell proliferation of UMR 106 osteosarcoma cells in culture. No specific cytosolic binding proteins for retinol could be detected.

  7. Primary breast osteosarcoma mimicking calcified fibroadenoma on screening digital breast tomosynthesis mammogram

    Directory of Open Access Journals (Sweden)

    Debbie Lee Bennett, MD

    2017-12-01

    Full Text Available Primary breast osteosarcoma is a rare malignancy, with mostly case reports in the literature. The appearance of breast osteosarcoma on digital breast tomosynthesis imaging has not yet been described. A 69-year-old woman presents for routine screening mammography and is found to have a calcified mass in her right breast. Pattern of calcification appeared “sunburst” on digital breast tomosynthesis images. This mass was larger than on the previous year's mammogram, at which time it had been interpreted as a benign calcified fibroadenoma. The subsequent workup demonstrated the mass to reflect primary breast osteosarcoma. The patient's workup and treatment are detailed in this case. Primary breast osteosarcoma, although rare, should be included as a diagnostic consideration for breast masses with a sunburst pattern of calcifications, particularly when the mammographic appearance has changed.

  8. Distribution of a boronated porphyrin (BTPP) in osteosarcoma bearing nude mice

    International Nuclear Information System (INIS)

    Takeuchi, Akira; Ojima, N.; Kadosawa, T.; Hatanaka, H.

    1992-01-01

    Osteosarcoma is known as one of the malignant tumor which is highly resistant to the ordinary irradiation therapy, and amputation of the affected limb at an early stage has been a treatment of choice for long years. The authors final goal in this study is to find out a possibility to treat the osteosarcoma conserving the affected limb by irradiating high dose to the tumor specifically using the characteristics of boron-neutron capture therapy (BNCT). For the success of this study, the development of the boron carrier with specific affinity to tumor or osteosarcoma is essential. In this paper, a recently developed boronated derivative, boronotetraphenylporphyrin (BTPP) was studied for its distribution in osteosarcoma bearing nude mice by means of whole body alfa-track autoradiography

  9. Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-01-01

    Conclusions: Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX. An optimal individualized rescue strategy can be created with consideration of gender, age, and C24 h.

  10. A Rare Case Report of Mandible Osteosarcoma in an 8-Year-Old Child

    Directory of Open Access Journals (Sweden)

    Atena Shiva

    2017-09-01

    Full Text Available Introduction: Osteosarcoma of jaw bones is the most common primary malignant bone tumor arising from mesenchymal cells capable of producing steoid; this disorder predominantly occurs in the long bones and rarely involves the maxillofacial region.  Normally, this disease presents in the third and fourth decades of life, is slightly more common in men than women, and affects the mandible and maxilla in the same proportion. Case report: An 8-year-old girl was referred to an oral and maxillofacial surgeon due to tumoral lesions in the posterior mandible in Sari, Iran. After the surgery, histopathological examination of the tumoral lesions revealed fibroblastic osteosarcoma. Further, immunohistochemical markers were evaluated, results of which approved final diagnosis of mandible osteosarcoma. Conclusion: Given that osteosarcoma of jaw bones share the same clinical manifestations with benign lesions, misdiagnosis is highly common and diagnosis is challenging for dentists. Accurate diagnosis and early referral are critical in prognosis and survival of patients.

  11. Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differences in vitro.

    Science.gov (United States)

    Holmes, K E; Thompson, V; Piskun, C M; Kohnken, R A; Huelsmeyer, M K; Fan, T M; Stein, T J

    2015-09-01

    Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumour size, presence of metastatic disease and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behaviour of osteosarcoma cells differ based on serum ALP concentration. Here, we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion or chemosensitivity between cell lines associated with normal or increased serum ALP concentration. © 2013 Blackwell Publishing Ltd.

  12. Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioral differences in vitro

    Science.gov (United States)

    Holmes, Katie E.; Thompson, Victoria; Piskun, Caroline M.; Kohnken, Rebecca A.; Huelsmeyer, Michael K.; Fan, Timothy M.; Stein, Timothy J.

    2013-01-01

    Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumor size, presence of metastatic disease, and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behavior of osteosarcoma cells differ based on serum ALP concentration. Here we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behavior differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP assays were performed to evaluate proliferation, migration, invasion, and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion, or chemosensitivity between cell lines associated normal or increased serum ALP concentration. PMID:23489774

  13. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-01-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors

  14. LncRNA expression and implication in osteosarcoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-11-01

    Full Text Available Ying Wang,1,2,* Yuelong Huang,2,* Peng Xiang,3 Wei Tian2 1Department of Molecular Orthopaedics, Beijing Institute of Traumatology and Orthopaedics, 2Department of Spinal Surgery, Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, 3Department of Urology, Peking University First Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: Osteosarcoma is the most prevalent primary bone tumor in children, adolescents, and older adults, typically presenting with poor survival outcomes. In recent years, ample evidence has shown that many long noncoding RNAs (lncRNAs have been aberrantly expressed in osteosarcoma, demonstrating their potential to serve as prognostic markers. In this study, we performed a meta-analysis on four lncRNAs (TUG1, UCA1, BCAR4, and HULC to systematically evaluate their prognostic value in osteosarcoma.Materials and methods: The eligible articles were systematically searched in PubMed, Web of Science, Embase, and Elsevier ScienceDirect (up to September 22, 2017, and one meta-analysis concerning the association between lncRNA expression and the overall survival (OS of osteosarcoma patients was performed. Survival outcomes were analyzed by OS. Subgroup analyses were performed.Results: A total of 1,361 patients with osteosarcoma and 12 lncRNAs from 16 articles were included in the study. Of the listed lncRNAs, the high expression of 10 lncRNAs indicated worse survival outcomes, while only two lncRNAs were shown to positively affect patients’ OS.Conclusion: This meta-analysis indicated that the abnormally expressed lncRNAs might significantly affect the survival of osteosarcoma patients. Combined use of these lncRNAs may serve as potential novel biomarkers for the indication of clinical outcomes of osteosarcoma patients as well as the selection of adjuvant chemotherapy strategies for clinical treatment of this disease. Keywords: lncRNAs, osteosarcoma

  15. Bmi-1-targeting suppresses osteosarcoma aggressiveness through the NF-κB signaling pathway

    Science.gov (United States)

    Liu, Jiaguo; Luo, Bin; Zhao, Meng

    2017-01-01

    Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full-length antibody targeting Bmi-1 (AbBmi-1) was produced and the preclinical value of Bmi-1-targeted therapy was evaluated in bone carcinoma cells and tumor xenograft mice. The results indicated that the Bmi-1 expression level was markedly upregulated in bone cancer cell lines, and inhibition of Bmi-1 by AbBmi-1 reduced the invasiveness and migration of osteosarcoma cells. Overexpression of Bmi-1 promoted proliferation and angiogenesis, and increased apoptosis resistance induced by cisplatin via the nuclear factor-κB (NF-κB) signal pathway. In addition, AbBmi-1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi-1 blocked NF-κB signaling and reduced MMP-9 expression. Furthermore, Bmi-1 promoted osteosarcoma tumor growth, whereas AbBmi-1 significantly inhibited osteosarcoma tumor growth in vitro and in vivo. Notably, AbBmi-1 decreased the percentages of Ki67-positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in tumors compared with Bmi-1-treated and PBS controls. Notably, MMP-9 and NF-κB expression were downregulated by treatment with AbBmi-1 in MG-63 osteosarcoma cells. In conclusion, the data provides evidence that AbBmi-1 inhibited the progression of osteosarcoma, suggesting that AbBmi-1 may be a novel anti-cancer agent through the inhibition of Bmi-1 via activating the NF-κB pathway in osteosarcoma. PMID:28983587

  16. MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells.

    Directory of Open Access Journals (Sweden)

    Vanita Vanas

    Full Text Available Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

  17. FDG PET/CT appearance of local osteosarcoma recurrences in pediatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Sharp, Susan E.; Gelfand, Michael J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Shulkin, Barry L.; McCarville, M.B. [St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States)

    2017-12-15

    Osteosarcoma is the most common pediatric malignant bone tumor, frequently surgically managed with limb salvage rather than amputation. Local recurrences are seen in up to 9% of osteosarcoma patients, with CT and MRI imaging often limited by metal artifacts. To describe the [F-18]2-fluoro-2-deoxyglucose (FDG) PET/CT appearance of local osteosarcoma recurrences with correlation to findings on other imaging modalities. A retrospective review of pediatric osteosarcoma patients imaged with FDG PET/CT was performed in patients with pathologically proven local recurrences. FDG PET/CT findings were reviewed and correlated with available comparison imaging studies. Ten local osteosarcoma recurrences in eight pediatric osteosarcoma patients were imaged with FDG PET/CT. All eight patients had a local recurrence after limb salvage; two patients had a second local recurrence after amputation. All local recurrences were seen with FDG PET/CT, demonstrating solid (n=5) or peripheral/nodular (n=5) FDG uptake patterns. Maximum standard uptake values (SUVs) ranged from 3.0 to 15.7. In five recurrences imaged with FDG PET/CT and MRI, MRI was limited or nondiagnostic in three. In four recurrences imaged with FDG PET/CT and bone scan, the bone scan was negative in three. Local osteosarcoma recurrences are well visualized by FDG PET/CT, demonstrating either solid or peripheral/nodular FDG uptake with a wide range of maximum SUVs. FDG PET/CT demonstrates the full extent of local recurrences, while MRI can be limited by artifact from metallic hardware. PET/CT appears to be more sensitive than bone scan in detecting local osteosarcoma recurrences. (orig.)

  18. FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Julia Brun

    Full Text Available BACKGROUND: The molecular mechanisms that are involved in the growth and invasiveness of osteosarcoma, an aggressive and invasive primary bone tumor, are not fully understood. The transcriptional co-factor FHL2 (four and a half LIM domains protein 2 acts as an oncoprotein or as a tumor suppressor depending on the tissue context. In this study, we investigated the role of FHL2 in tumorigenesis in osteosarcoma model. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analyses showed that FHL2 is expressed above normal in most human and murine osteosarcoma cells. Tissue microarray analysis revealed that FHL2 protein expression is high in human osteosarcoma and correlates with osteosarcoma aggressiveness. In murine osteosarcoma cells, FHL2 silencing using shRNA decreased canonical Wnt/β-catenin signaling and reduced the expression of Wnt responsive genes as well as of the key Wnt molecules Wnt5a and Wnt10b. This effect resulted in inhibition of osteosarcoma cell proliferation, invasion and migration in vitro. Using xenograft experiments, we showed that FHL2 silencing markedly reduced tumor growth and lung metastasis occurence in mice. The anti-oncogenic effect of FHL2 silencing in vivo was associated with reduced cell proliferation and decreased Wnt signaling in the tumors. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that FHL2 acts as an oncogene in osteosarcoma cells and contributes to tumorigenesis through Wnt signaling. More importantly, FHL2 depletion greatly reduces tumor cell growth and metastasis, which raises the potential therapeutic interest of targeting FHL2 to efficiently impact primary bone tumors.

  19. Canine osteosarcoma karyotypes from an original tumor, its metastasis, and tumor cells in tissue culture

    International Nuclear Information System (INIS)

    Taylor, N.; Shifrine, M.; Wolf, H.G.; Trommershausen-Smith, A.

    1975-01-01

    Radiation-induced osteosarcoma, its metastasis, and cells grown in tissue culture were karyotyped. Both hypodiploid and hyperdiploid stem lines were observed. The hypodiploid line contained 45-55 chromosomes with 10 to 15 abnormal metacentric and submetacentric chromosomes and one subtelocentric marker. The hyperdiploid line contained 90 to 105 chromosomes with 20 to 30 abnormal metacentric and submetacentric chromosomes with two subtelocentric markers. Karyotypic analysis can be used to monitor osteosarcomas maintained in tissue culture

  20. Anticancer Effects of Geopropolis Produced by Stingless Bees on Canine Osteosarcoma Cells In Vitro

    OpenAIRE

    Cinegaglia, Naiara Costa; Bersano, Paulo Ricardo Oliveira; Ara?jo, Maria Jos? Abigail Mendes; B?falo, Michelle Cristiane; Sforcin, Jos? Maur?cio

    2013-01-01

    Geopropolis is produced by indigenous stingless bees from the resinous material of plants, adding soil or clay. Its biological properties have not been investigated, such as propolis, and herein its cytotoxic action on canine osteosarcoma (OSA) cells was evaluated. OSA is a primary bone neoplasm diagnosed in dogs being an excellent model in vivo to study human OSA. spOS-2 primary cultures were isolated from the tumor of a dog with osteosarcoma and incubated with geopropolis, 70% ethanol (geop...

  1. Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

    OpenAIRE

    Di Tommaso, Morena; Rocconi, Francesca; Marruchella, Giuseppe; D?Angelo, Anna Rita; Masci, Stefano; Santori, Domenico; Civitella, Carla; Luciani, Alessia; Boari, Andrea

    2015-01-01

    A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytolo...

  2. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

    OpenAIRE

    Simpson, Siobhan; Dunning, Mark D.; de Brot, Simone; Grau-Roma, Llorenc; Mongan, Nigel P.; Rutland, Catrin S.

    2017-01-01

    Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with th...

  3. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma

    OpenAIRE

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine os...

  4. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Sarver Aaron L

    2013-01-01

    Full Text Available Abstract Background Deregulation of microRNA (miRNA transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma. Methods Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance. Results Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544. Conclusions We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.

  5. Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach

    Science.gov (United States)

    Scott, Milcah C.; Sarver, Aaron L.; Gavin, Katherine J.; Thayanithy, Venugopal; Getzy, David M.; Newman, Robert A.; Cutter, Gary R.; Lindblad-Toh, Kerstin; Kisseberth, William C.; Hunter, Lawrence E.; Subramanian, Subbaya; Breen, Matthew; Modiano, Jaime F.

    2011-01-01

    The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with G2/M transition and DNA damage checkpoint and microenvironment-interaction categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts, with stratification into the two expected groups. Significantly, this restricted signature partially overlapped a previously defined, predictive signature for soft tissue sarcomas, and it unmasked orthologous molecular subtypes and their corresponding natural histories in five independent data sets from human patients with osteosarcoma. Our results indicate that the narrower genetic diversity of dogs can be utilized to group complex human osteosarcoma into biologically and clinically relevant molecular subtypes. This in turn may enhance prognosis and prediction, and identify relevant therapeutic targets. PMID:21621658

  6. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma

    Science.gov (United States)

    2013-01-01

    Background Deregulation of microRNA (miRNA) transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma. Methods Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance. Results Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death) and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs) in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544. Conclusions We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease. PMID:23311495

  7. Radiographic diagnosis of an expansile bone lesion in a dog [osteosarcoma

    International Nuclear Information System (INIS)

    Lamb, C.R.; Berg, J.; Schelling, S.H.

    1993-01-01

    An old dog had an expansile lesion affecting the ulnar diaphysis. The lesion had clinical and radiographic features typical of a bone cyst; however, computed X-ray tomography indicated that the lesion had a tissue content incompatible with a true cyst. The histological diagnosis was osteosarcoma. This report emphasises the highly variable radiological appearance of canine osteosarcoma; biopsy is required to establish the diagnosis because the radiological signs may mimic a lesion of different aetiology

  8. Vertebral metastasis of femur primary osteosarcoma: a case report and literature review

    International Nuclear Information System (INIS)

    Cioni, Claudia Helena; Oliveira, Andrea Alencar de; Neves, Felipe Trentin

    2006-01-01

    We present a case of a 21-year-old patient, bearer of femur primary osteosarcoma, who began with pain in the thoracic column. The metastasis of primary osteosarcoma has greater incidence on lungs, rarely affecting vertebras. We reviewed the literature about this disease and emphasized the image's characteristics on the several methods used (traditional radiographic exams, bone scintigraphy, computed tomography, magnetic resonance) and the main differential diagnostics. (author)

  9. Advances in the management of osteosarcoma [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stefan S. Bielack

    2016-11-01

    Full Text Available Osteosarcoma, a bone cancer most commonly seen in adolescents and young adults, is usually a high-grade malignancy characterized by a very high risk for the development of pulmonary metastases. High-grade osteosarcomas are usually treated by preoperative and postoperative chemotherapy and surgery, with a very limited number of active agents available. Rarer lower-grade variants such as parosteal and periosteal osteosarcoma or low-grade central osteosarcoma are treated by surgery only. Imaging to search for possible metastases focuses on the lung. Computed tomography is the most sensitive method but cannot reliably distinguish small metastases from benign lesions. Advances of local imaging and surgical reconstruction now allow the use of limb-salvage in an ever-increasing proportion of patients. While still troubled by complications, non-invasive endoprosthesis-lengthening mechanisms have led to an increased uptake of limb-salvage, even for young, skeletally immature patients. Radiotherapy is employed when osteosarcomas cannot be removed with clear margins, but very high doses are required, and both proton and carbon-ion radiotherapy are under investigation. Unfortunately, the past 30 years have witnessed few, if any, survival improvements. Novel agents have not led to universally accepted changes of treatment standards. In patients with operable high-grade osteosarcomas, the extent of histological response to preoperative chemotherapy is a significant predictive factor for both local and systemic control. Attempts to improve prognosis by adapting postoperative treatment to response, recently tested in a randomized, prospective setting by the European and American Osteosarcoma Study Group, have not been proven to be beneficial. Many agree that only increased knowledge about osteosarcoma biology will lead to novel, effective treatment approaches and will be able to move the field forward.

  10. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis

    OpenAIRE

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-hara, Tomoko; Fujita, Naoya

    2014-01-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the pro...

  11. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

    Directory of Open Access Journals (Sweden)

    De Divitiis C

    2015-03-01

    Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

  12. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

    2012-02-01

    Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

  13. Application of Long Noncoding RNAs in Osteosarcoma: Biomarkers and Therapeutic Targets

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    Zhihong Li

    2017-07-01

    Full Text Available Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1 are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.

  14. Flavonoids Active Against Osteosarcoma: A Review of the Molecular Mechanisms Involved.

    Science.gov (United States)

    Liu, Hui; Gao, Yutong; Dong, Yonghui; Cheng, Peng; Chen, Anmin; Huang, Hui

    2017-01-01

    Osteosarcoma is the most frequent primitive malignant bone tumor affecting adolescents and young adults worldwide. The tumor exhibits aggressive growth in the primary site and readily metastasizes to other organs. There has been no significant improvement in the 5-year survival rate since the 1970s and the figure remains at 60-70%. In addition, the side effects of chemotherapeutic drugs and resistance to chemotherapy compromise the effects of treatment for osteosarcoma. In recent years, the development of flavonoids drugs inhibiting carcinogenesis is attracting great interest in the scientific community. Flavonoids are one kind of polyphenolic compounds widely found in vegetables and fruits. Moreover, flavonoids have become popular compounds, exhibiting comprehensive antitumor activities, while being safe and inexpensive. Here, the literature on the benefits afforded by flavonoids in terms of osteosarcoma treatment is reviewed and certain flavonoids and their effects on osteosarcoma are discussed. These compounds can perturb the cell cycle, induce apoptosis, inhibit tumor cell invasion and metastasis, potentiate the actions of chemotherapeutic agents, trigger autophagy, and stimulate antitumor activity in vivo. In summary, we highlight the currently well-accepted flavonoid compounds and detail the molecular mechanisms by which flavonoids may treat osteosarcoma, and thus the flavonoids exhibit great promise as anti-osteosarcoma agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. The tumor suppressor role of miR-124 in osteosarcoma.

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    Shuo Geng

    Full Text Available MicroRNAs have crucial roles in development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-124 was down-regulated in many cancers; however, the role of miR-124 in osteosarcoma development is unknown. In this study, we demonstrate that expression of miR-124 is significantly downregulated in osteosarcoma tissues and cell lines, compared to the adjacent tissues. The expression of miR-124 in the metastases osteosarcoma tissues was lower than that in non- metastases tissues. We identified and confirmed Rac1 as a novel, direct target of miR-124 using prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed Rac1 protein expression and attenuated cell proliferation, migration, and invasion and induced apoptosis in MG-63 and U2OS in vitro. Moreover, overexpression of Rac1 in miR-124-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion caused by miR-124. Therefore, our results demonstrate that miR-124 is a tumor suppressor miRNA and suggest that this miRNA could be a potential target for the treatment of osteosarcoma in future.

  16. Inherited germline ATRX mutation in two brothers with ATR-X syndrome and osteosarcoma.

    Science.gov (United States)

    Ji, Jianling; Quindipan, Catherine; Parham, David; Shen, Lishuang; Ruble, David; Bootwalla, Moiz; Maglinte, Dennis T; Gai, Xiaowu; Saitta, Sulagna C; Biegel, Jaclyn A; Mascarenhas, Leo

    2017-05-01

    We report a family in which two brothers had an undiagnosed genetic disorder comprised of dysmorphic features, microcephaly, severe intellectual disability (non-verbal), mild anemia, and cryptorchidism. Both developed osteosarcoma. Trio exome sequencing (using blood samples from the younger brother and both parents) was performed and a nonsense NM_000489.4:c.7156C>T (p.Arg2386*) mutation in the ATRX gene was identified in the proband (hemizygous) and in the mother's peripheral blood DNA (heterozygous). The mother is healthy, does not exhibit any clinical manifestations of ATR-X syndrome and there was no family history of cancer. The same hemizygous pathogenic variant was confirmed in the affected older brother's skin tissue by subsequent Sanger sequencing. Chromosomal microarray studies of both brothers' osteosarcomas revealed complex copy number alterations consistent with the clinical diagnosis of osteosarcoma. Recently, somatic mutations in the ATRX gene have been observed as recurrent alterations in both osteosarcoma and brain tumors. However, it is unclear if there is any association between osteosarcoma and germline ATRX mutations, specifically in patients with constitutional ATR-X syndrome. This is the first report of osteosarcoma diagnosed in two males with ATR-X syndrome, suggesting a potential increased risk for cancer in patients with this disorder. © 2017 Wiley Periodicals, Inc.

  17. Quantitative Assessment of the Association between ABC Polymorphisms and Osteosarcoma Response: a Meta-analysis.

    Science.gov (United States)

    Chen, Xu; Jiang, Min; Zhao, Rui-Ke; Gu, Guo-Hao

    2015-01-01

    ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

  18. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  19. Retrospective Evaluation of Whole Body Computed Tomography for Tumor Staging in Dogs with Primary Appendicular Osteosarcoma.

    Science.gov (United States)

    Talbott, Jessica L; Boston, Sarah E; Milner, Rowan J; Lejeune, Amandine; Souza, Carlos H de M; Kow, Kelvin; Bacon, Nicholas J; Hernandez, Jorge A

    2017-01-01

    To evaluate whole body computed tomography (CT) for staging canine appendicular osteosarcoma. Retrospective case series. Client-owned dogs diagnosed with appendicular osteosarcoma (n=39). Medical records for client-owned dogs diagnosed with appendicular osteosarcoma from August 2008 to July 2014 were reviewed. Dogs were included if they had a confirmed diagnosis of appendicular osteosarcoma and were staged using whole body CT. Data collected included signalment, body weight, primary tumor location, serum alkaline phosphatase (ALP) activity, findings on 3-view thoracic radiographs, cytologic or histologic results, and findings on CT. Thirty-nine dogs (median age 8.5 years; median body weight 37 kg) had osteosarcoma of the distal radius (n=17), proximal humerus (11) and other sites. Serum ALP activity was elevated in 14 dogs. Bone metastasis was not detected in any dog on whole body CT. Pulmonary metastasis was considered definitive on CT based on board certified radiologist assessment in 2/39 dogs (5%). Two additional dogs (2/39, 5%) had soft tissue masses diagnosed on CT, consistent with concurrent, non-metastatic malignancies. Bone metastases were not identified in any dog with whole body CT. Thoracic and abdominal CT detected lung lesions and concurrent neoplasia in dogs with primary appendicular osteosarcoma. Whole body CT may be a useful adjunct to other screening tests for disseminated malignancy. © 2016 The American College of Veterinary Surgeons.

  20. Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma

    International Nuclear Information System (INIS)

    Susa, Michiro; Iyer, Arun K; Ryu, Keinosuke; Hornicek, Francis J; Mankin, Henry; Amiji, Mansoor M; Duan, Zhenfeng

    2009-01-01

    Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOS R2 , U-2OS, and U-2OS R2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma

  1. Osteosarcoma: correlation of T1 map and histology map

    International Nuclear Information System (INIS)

    Suh, Jin Suck; Yun, Mi Jin; Jeong, Eun Kee; Shin, Kyoo Ho; Yang, Woo Ick

    1999-01-01

    To determine whether T1 mapping shows regional differences between viable and necrotic regions of osteosarcomas after anticancer chemotherapy and to assess whether this mapping is able to express the characteristics of various intramural tissue components. Eleven of 20 osteosarcomas were included in this study, while the remaining nine were excluded because the tumor site was inappropriate for comparison of T1 map and tumor macrosection. All patients underwent MR imaging for the purpose of T1 mapping, followed by pre-operative chemotherapy and subsequent limb-salvage surgery. Spin echo pulse sequencing was used with varying TR (100, 200, 400, 800, 1600, and 2400 msec) and a constant TE of 20 msec. Using a C-language software program, T1 relaxation time was calculated on a pixel-by-pixel basis and then a T1 map was generated by using a post-processing program, NIH Image. We attempted correlation of the T1 map and histologic findings, particularly in regions of interest(ROI) if certain areas were different from other regions on either the T1 or histologic map. Value was expressed as an average of the ratio of T1 of ROI and T1 of fat tissue, and this was used as an internal reference for normalization of the measurement. Tumor necrosis was 100 %(Grade IV) in six specimens, and over 90 % (Grade III) in five. Viable tumor cells were found mostly in regions with chondroid matrix and seldom in regions with osteoid matrix. Regardless of cell viability, values ranged from 0.9 to 9.87(mean, 4.02) in tumor necrotic area with osteoid matrices, and from 3.04 to 3.9(mean, 3.55) in areas with chondroid matrices. Other regions with fibrous tissue proliferation, hemorrhage, and fatty necrosis showed values of 2.92-9.83(mean, 7.20), 2.65-5.96(mean,3.59), and 1.43-3.11(mean, 2.68) respectively. The values of various tissues overlapped. No statistically significant difference was found between regions in which tumors were viable and those with tumor necrosis. Although we hypothesized

  2. Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique.

    Science.gov (United States)

    Yu, Zhe; Sun, Honghui; Fan, Qingyu; Long, Hua; Yang, Tongtao; Ma, Bao'an

    2009-05-01

    In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45+/-8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10(5) to 1x10(6) UMR106 cells in 50 microl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10(5) tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat

  3. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro

    OpenAIRE

    Carsten Geiss; Zoltán Kis; Barbara Leuchs; Monika Frank-Stöhr; Jörg R. Schlehofer; Jean Rommelaere; Christiane Dinsart; Jeannine Lacroix

    2017-01-01

    Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts...

  4. Chondroblastic osteosarcoma arising in the maxilla mimicking the radiographic and histological characteristics of cemento-osseous lesions: A case report.

    Science.gov (United States)

    Li, Bin-Bin; Zhang, Jian-Yun; Gao, Yan

    2017-05-01

    Osteosarcomas of the jaw are comparatively rare and represent only 2-10% of all osteosarcomas. We herein present a rare case of an osteosarcoma exhibiting the radiographic and histological characteristics of cemento-osseous lesions in the alveolar ridge of the maxilla. A 53-year-old male patient presented with the complaint of gradual swelling of the left maxilla over 4 years. Radiography revealed an ill-defined radioopaque mass, intimately associated with the apices of the involved teeth, without a periosteal reaction. Microscopically, a cementicle-like structure was identified in the alveolar bone. In addition, the lesion exhibited typical characteristics of chondroblastic osteosarcoma in the body of the maxilla. The tumor contained abundant osteoid and cartilage intimately associated with anaplastic tumor cells. The cartilage displayed malignant-appearing cells in lacunae, and there was crowding at the periphery of the lobule where the spindle cells formed sheets. The differential diagnosis included primary osteosarcoma, concurrent cemento-osseous dysplasia and osteosarcoma, or a secondary osteosarcoma based on a pre-existing cemento-osseous lesion. The presence of the cementicle-like structure in the alveolar bone and the involvement of the periodontal ligament and alveolar bone proper were unique in our case. The general invasive growth pattern and the abundance of the irregular tumor bone helped establish the diagnosis of primary osteosarcoma. This case may represent evidence of the pathogenesis of primary osteosarcoma in the jaw.

  5. Suppression of liver receptor homolog-1 by microRNA-451 represses the proliferation of osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhiyong; Wu, Shuwen; Lv, Shouzheng; Wang, Huili; Wang, Yong; Guo, Qiang, E-mail: qiangguo_gq@163.com

    2015-06-05

    Liver receptor homolog-1 (LRH-1) plays an important role in the onset and progression of many cancer types. However, the role of LRH-1 in osteosarcoma has not been well investigated. In this study, the critical role of LRH-1 in osteosarcoma cells was described. Quantitative polymerase chain reaction and Western blot analysis results revealed that LRH-1 was highly overexpressed in osteosarcoma cells. LRH-1 was knocked down by small interfering RNA (siRNA), and this phenomenon significantly inhibited osteosarcoma cell proliferation. Bioinformatics analysis results showed that LRH-1 contained putative binding sites of microRNA-451 (miR-451); this result was further validated through a dual-luciferase activity reporter assay. miR-451 was overexpressed in osteosarcoma cells through transfection of miR-451 mimics; miR-451 overexpression then significantly inhibited LRH-1 expression and cell proliferation. The loss of LRH-1 by siRNA or miR-451 mimics significantly impaired Wnt/β-catenin activity, leading to G0/G1 cell cycle arrest. Results showed that LRH-1 is implicated in osteosarcoma. Therefore, miR-451-induced suppression of LRH-1 can be a novel therapy to treat osteosarcoma. - Highlights: • LRH-1 was highly overexpressed in osteosarcoma cells. • Knockdown of LRH-1 inhibited osteosarcoma cell proliferation. • miR-451 directly targeted and regulated LRH-1 expression. • Overexpression of miR-451 suppressed Wnt activity.

  6. Extraosseous osteosarcoma in a maned wolf (Chrysocyon brachyurus).

    Science.gov (United States)

    Reid, Heather L; Deem, Sharon L; Citino, Scott B

    2005-09-01

    A 6-yr-old maned wolf (Chrysocyon brachyurus) was diagnosed with an extraosseous osteosarcoma on the lateral aspect of the right thigh. Antemortem radiography revealed a calcified mass with no skeletal involvement. The mass was excised, but visible regrowth of the tumor was evident within 5 wk. Histologic examination and immunohistochemistry, including staining for p53 tumor suppression gene protein, were performed on the excised mass. The maned wolf was euthanized 13 wk after the initial diagnosis. The neoplasm was located in a site commonly used for the delivery of intramuscular injections, including vaccinations. Although no definitive association can be made, it is worth noting this relationship, as vaccine-site neoplasias have been observed in other species, most notably the domestic cat (Felis domesticus).

  7. Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

    Science.gov (United States)

    Armstrong, Jo; Dass, Crispin R

    2018-01-01

    The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain. As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin. Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. T-ray relevant frequencies for osteosarcoma classification

    Science.gov (United States)

    Withayachumnankul, W.; Ferguson, B.; Rainsford, T.; Findlay, D.; Mickan, S. P.; Abbott, D.

    2006-01-01

    We investigate the classification of the T-ray response of normal human bone cells and human osteosarcoma cells, grown in culture. Given the magnitude and phase responses within a reliable spectral range as features for input vectors, a trained support vector machine can correctly classify the two cell types to some extent. Performance of the support vector machine is deteriorated by the curse of dimensionality, resulting from the comparatively large number of features in the input vectors. Feature subset selection methods are used to select only an optimal number of relevant features for inputs. As a result, an improvement in generalization performance is attainable, and the selected frequencies can be used for further describing different mechanisms of the cells, responding to T-rays. We demonstrate a consistent classification accuracy of 89.6%, while the only one fifth of the original features are retained in the data set.

  9. In vitro osteosarcoma biosensing using THz time domain spectroscopy

    Science.gov (United States)

    Ferguson, Bradley S.; Liu, Haibo; Hay, Shelley; Findlay, David; Zhang, Xi-Cheng; Abbott, Derek

    2004-03-01

    Terahertz time domain spectroscopy (THz-TDS) has a wide range of applications from semiconductor diagnostics to biosensing. Recent attention has focused on bio-applications and several groups have noted the ability of THz-TDS to differentiate basal cell carcinoma tissue from healthy dermal tissue ex vivo. The contrast mechanism is unclear but has been attributed to increased interstitial water in cancerous tissue. In this work we investigate the THz response of human osteosarcoma cells and normal human bone cells grown in culture to isolate the cells' responses from other effects. A classification algorithms based on a frequency selection by genetic algorithm is used to attempt to differentiate between the cell types based on the THz spectra. Encouraging preliminary results have been obtained.

  10. Involvement and Clinical Aspects of MicroRNA in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ram Mohan Ram Kumar

    2016-06-01

    Full Text Available Osteosarcoma (OS is the most common primary bone cancer in children and adolescents, but its pathogenesis has been difficult to establish because of its well-known heterogeneous nature. OS has been associated with genetic and cytogenetic abnormalities, which include function-impairing mutations in tumor suppressors and the activation of oncogenes. OS tumorigenesis has been linked to alterations of several genes characterized by a high level of genetic instability and recurrent DNA amplifications and deletions. MicroRNAs (miRNAs, 18–25-nucleotide noncoding RNAs, are critical for various biological processes like differentiation, cell growth and cell death. Dysregulation of miRNA expression leads to phenotypic and genotypic changes in cells, which leads to cancer. Studies on miRNAs have initiated a significant effect in both diagnosis and treatment of cancer. This review focuses on the current knowledge of clinical applications of miRNAs for the better diagnosis and management of OS.

  11. Survivin inhibition via EZN-3042 in canine lymphoma and osteosarcoma.

    Science.gov (United States)

    Shoeneman, J K; Ehrhart, E J; Charles, J B; Thamm, D H

    2016-06-01

    Canine lymphoma (LSA) and osteosarcoma (OS) have high mortality rates and remain in need of more effective therapeutic approaches. Survivin, an inhibitor of apoptosis (IAP) family member protein that inhibits apoptosis and drives cell proliferation, is commonly elevated in human and canine cancer. Survivin expression is a negative prognostic factor in dogs with LSA and OS, and canine LSA and OS cell lines express high levels of survivin. In this study, we demonstrate that survivin downregulation in canine LSA and OS cells using a clinically applicable locked nucleic acid antisense oligonucleotide (EZN-3042, Enzon Pharmaceuticals, Piscataway Township, NJ, USA) inhibits growth, induces apoptosis and enhances chemosensitivity in vitro, and inhibits survivin transcription and protein production in orthotopic canine OS xenografts. Our findings strongly suggest that survivin-directed therapies might be effective in treatment of canine LSA and OS and support evaluation of EZN-3042 in dogs with cancer. © 2014 John Wiley & Sons Ltd.

  12. Expandable Total Humeral Replacement in a Child with Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Eric R. Henderson

    2015-01-01

    Full Text Available Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.

  13. The expression and clinical significance of HDGF in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Chen Z

    2015-09-01

    Full Text Available Zhiguo Chen,1 Shenghai Qiu,2 Xiaofei Lu31Department of Orthopedics, Linyi People’s Hospital, Linyi City, Shandong Province, People’s Republic of China; 2Department of Orthopedics, People’s Hospital of Taiyuan, Taiyuan City, Shanxi Province, People’s Republic of China; 3Department of General Surgery, Jinan Central Hospital affiliated to Shandong University, Jinan City, Shandong Province, People’s Republic of ChinaAim: To investigate the expression of hepatoma-derived growth factor (HDGF in osteosarcoma (OS and the correlation with clinicopathologic factors, prognosis, and tumor progression.Method: HDGF expression in OS tissues was detected by immunohistochemistry. The correlation between HDGF and clinicopathologic factors was analyzed by chi-square test, and the association between HDGF expression and the overall survival rates was evaluated by univariate analysis using Kaplan–Meier method. HDGF concentration in cell medium or cell lysates was detected by enzyme-linked immunosorbent assay method. The effect of extrinsic and intrinsic HDGF on OS cell proliferation was detected by MTT assay after recombinant HDGF stimulation or HDGF knockdown, respectively.Results: Proportion of HDGF high expression was 18.69% (20/107 in OS. HDGF high expression was significantly associated with larger tumor size (P=0.004. With experiments in vitro, we demonstrated that human recombinant HDGF could activate AKT and MAPK signaling pathway, resulting in OS cell proliferation. By knocking down HDGF expression, we proved that intrinsic HDGF was required in OS proliferation.Conclusion: High HDGF expression was significantly associated with larger OS tumor size and could promote OS cell proliferation, indicating that HDGF could be an effective biomarker and a potential drug target in OS treatment.Keywords: hepatoma-derived growth factor, osteosarcoma, tumor size, proliferation, overall survival rate

  14. Staged lengthening arthroplasty for pediatric osteosarcoma around the knee.

    Science.gov (United States)

    Kong, Chang-Bae; Lee, Soo-Yong; Jeon, Dae-Geun

    2010-06-01

    Orthopaedic oncologists often must address leg-length discrepancy after resection of tumors in growing patients with osteosarcoma. There are various alternatives to address this problem. We describe a three-stage procedure: (1) temporary arthrodesis, (2) lengthening by Ilizarov apparatus, and (3) tumor prosthesis. We asked (1) to what extent are affected limbs actually lengthened; (2) how many of the patients who undergo a lengthening procedure eventually achieve joint arthroplasty; and (3) can the three-stage procedure give patients a functioning joint with equalization of limb length? We reviewed 56 patients (younger than 14 years) with osteosarcoma who had staged lengthening arthroplasty between 1991 and 2004. Thirty-five of the 56 patients (63%) underwent soft tissue lengthening, and of these 35, 28 (50% of the original group of 56) had implantation of a mobile joint. Three of the 28 prostheses were later removed owing to infection after arthroplasty. The overall average length gained was 7.8 cm (range, 4-14 cm), and 25 (71%) of the 35 patients had a mobile joint at final followup. The average Musculoskeletal Tumor Society functional score was 23.2 (range, 15-28) and limb-length discrepancy at final followup was 2.6 cm (range, 0-6.5 cm). Although most mobile joints had an acceptable ROM (average, 74.2 degrees ; range, 35 degrees -110 degrees ), extension lag was frequent. Our approach is one option for skeletally immature patients, especially in situations where an expandable prosthesis is not available. However, this technique requires multiple stages and would be inappropriate for patients who cannot accept prolonged functional deficit owing to a limited lifespan or other reasons. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

  15. Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma.

    Science.gov (United States)

    Feng, Jinyi; Lan, Ruilong; Cai, Guanxiong; Lin, Jinluan; Wang, Xinwen; Lin, Jianhua; Han, Deping

    2016-11-24

    The study aimed to explore the correlation between the expression of TREX1 and the metastasis and the survival time of patients with osteosarcoma as well as biological characteristics of osteosarcoma cells for the prognosis judgment of osteosarcoma. The correlation between the expression of TREX1 protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma was analyzed. The CD133 + and CD133 - cell subsets of osteosarcoma stem cells were sorted by the flow cytometry. The tumorsphere culture, clone formation, growth curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were compared between the cell subsets in two groups; the expressions of stem cell-related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and mRNA were compared between the cell subsets in two groups. The data was statistically analyzed. The measurement data between the two groups were compared using t test. The count data between the two groups were compared using χ 2 test and Kaplan-Meier survival analysis. A P value osteosarcoma in the metastasis group was significantly lower than that in the non-metastasis group. The difference was statistically significant (P osteosarcoma CD133 + cell subsets was significantly lower than that in CD133 - cell subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human osteosarcoma CD133 + cell subsets with lower expression of TREX1; the biological characteristics identification experiment showed that human CD133 + cell subsets with low TREX1 expression could form tumorspheres, the number of colony forming was more, the cell proliferation ability was strong, the osteogenic and adipogenic differentiation potential was big, the tumor-forming ability in nude mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was low. The expression of TREX1 may be related to metastasis in

  16. Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Weihai Liu

    2017-09-01

    Full Text Available Background/Aims: Osteosarcoma (OS is the most common primary malignant bone tumor in children and adolescents. However, the molecular mechanisms regulating osteosarcoma tumorigenesis and progression are still poorly understood. Circular RNAs (circRNAs have been identified as microRNA sponges and are involved in many important biological processes. This study aims to investigate the global changes in the expression pattern of circRNAs in osteosarcoma and provide a comprehensive understanding of differentially expressed circRNAs. Methods: Microarray based circRNA expression was determined in osteosarcoma cell lines and compared with hFOB1.19, which was used as the normal control. We confirmed the microarray data by real time-qPCR in both osteosarcoma cell lines and tissues. The circRNA/microRNA/mRNA interaction network was predicted using bioinformatics. Gene Ontology analysis and 4 annotation tools for pathway analysis (KEGG, Biocarta, PANTHER and Reactome were used to predict the functions of differentially expressed circRNAs. Results: We revealed a number of differentially expressed circRNAs and 12 of them were confirmed, which suggests a potential role of circRNAs in OS. Among these differentially expressed circRNAs, hsa_circRNA_103801 was up-regulated in both osteosarcoma cell lines and tissues, while hsa_circRNA_104980 was down-regulated. The most likely potential target miRNAs for hsa_circRNA_103801 include hsa-miR-370-3p, hsa-miR-338-3p and hsa-miR-877-3p, while the most potential target miRNAs of hsa_circRNA_104980 consist of hsa-miR-1298-3p and hsa-miR-660-3p. Functional analysis found that hsa_circRNA_103801 was involved in pathways in cancer, such as the HIF-1, VEGF and angiogenesis pathway, the Rap1 signaling pathway and the PI3K-Akt signaling pathway, while hsa_circRNA_104980 was related to some pathways such as the tight junction pathway. Conclusions: This study has identified the comprehensive expression profile of circRNAs in

  17. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Haug, Alexander; Auernhammer, Christoph J.; Goeke, Burkhard; Waengler, Bjoern; Tiling, Reinhold; Bartenstein, Peter; Poepperl, Gabriele; Schmidt, Gerwin

    2009-01-01

    To compare the diagnostic impact of 68 Ga-DOTA-TATE and 18 F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both 68 Ga-DOTA-TATE and 18 F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for 68 Ga-DOTA-TATE PET and 56% for 18 F-DOPA PET. 68 Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by 18 F-DOPA PET. Overall, 68 Ga-DOTA-TATE was superior to 18 F-DOPA in 13 patients (two patients showed fewer positive tumour regions with 18 F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of 18 F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive 18 F-DOPA uptake. In patients positive for 18 F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study 68 Ga-DOTA-TATE PET proved clearly superior to 18 F-DOPA PET for detection and staging of NET. 18 F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that 18 F-DOPA PET should be employed in patients with NET with negative 68 Ga-DOTA-TATE PET and elevated plasma serotonin. (orig.)

  18. Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer.

    Science.gov (United States)

    Ocak, Meltem; Demirci, Emre; Kabasakal, Levent; Aygun, Aslan; Tutar, Rumeysa O; Araman, Ahmet; Kanmaz, Bedii

    2013-11-01

    Somatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. Thirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. Both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, PDOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.

  19. Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

    Science.gov (United States)

    Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

    2016-03-01

    Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

  20. miR-30a suppresses osteosarcoma proliferation and metastasis by downregulating MEF2D expression

    Directory of Open Access Journals (Sweden)

    Du L

    2018-04-01

    Full Text Available Liuxue Du,* Tianpei Chen,* Kai Zhao,* Dong Yang Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China *These authors contributed equally to this work Abstract: Many studies have revealed that microRNAs (miRNAs play crucial roles in cancer development and progression. miRNA-30a (miR-30a, as a member of the miR-30 family, has been implicated in various cancers. However, the role of miR-30a in osteosarcoma remains unclear. In the current study, we found that miR-30a was significantly downregulated in osteosarcoma tissues and cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR. In addition, miR-30a could inhibit cancer cell growth, migration, and invasion in vitro. Furthermore, bioinformatics of miRNA target prediction and luciferase reporter assay indicated that MEF2D is a direct target of miR-30a. miR-30a was able to reduce the mRNA and protein expression of MEF2D as assessed using RT-PCR and Western blotting assay. Interestingly, overexpression of MEF2D partially reversed the miR-30a-reduced cell proliferation, migration, and invasion of osteosarcoma cell, indicating that miR-30a suppresses osteosarcoma cell proliferation and metastasis partially mediated by inhibition of MEF2D. Overall, our study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in osteosarcoma, providing a promising prognostic biomarker and a therapeutic strategy for osteosarcoma. Keywords: miR-30a, MEF2D, osteosarcoma, proliferation, invasion, migration

  1. Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

    2013-05-01

    Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

  2. MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R

    Directory of Open Access Journals (Sweden)

    Guangnan Chen

    2016-02-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. Methods: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR. The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. Results: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. Conclusion: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.

  3. On the importance of considering disease subtypes: Earliest detection of a parosteal osteosarcoma? Differential diagnosis of an osteosarcoma in an Anglo-Saxon female.

    Science.gov (United States)

    Ferrante di Ruffano, Lavinia; Waldron, Tony

    2016-12-30

    A case of potentially dedifferentiated parosteal osteosarcoma was found in the proximal humerus of an adult female buried in the late Anglo-Saxon cemetery of Cherry Hinton, Cambridgeshire, UK. Key features include a large, dense, lobulated mass attached to the medial metaphysis of the proximal humerus by a broad-based attachment, accompanied by cortical destruction and widespread spiculated periosteal reaction. Radiographic images confirm medullary involvement, lack of continuity between the cortex and external mass, a radiolucent cleavage plane and possible radiolucent zones within the bony masses. Differential diagnoses considered include osteochondroma, myositis ossificans, fracture callus, as well as the primary malignancies of osteosarcoma and chondrosarcoma, and their various subtypes. The macroscopic and radiographic analysis of the tumor is described and discussed within clinical and paleopathological contexts. One of only 19 uncontested examples of osteosarcoma from past human populations, most of which remain unconfirmed, this case represents what we believe to be the earliest, and probably singular, bioarcheological example of parosteal osteosarcoma in human history. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  4. Our experience of high dose I-131 therapy in 75 patients with well differentiated carcinoma thyroid followed up over 5 years

    International Nuclear Information System (INIS)

    Dougall, P.; Kumar, A.; Ashok, P.; Chinwan, B.P.; Khan, B.; Pandey, D.; Joshi, N.D.

    2005-01-01

    Thyroid cancer is the most common endocrine malignancy. The epidemiology of thyroid cancer is variable, depending on the geographic location of the patient population. Well differentiated thyroid cancer (WTC), is responsive to high dose I-131 treatment, and is the most accepted form of therapy, even though the dose administered for ablation of residual thyroid tissue maybe controversial. At our centre, 75 patients of WTC, mean age 42.4 years, 22 males and 53 females (M:F 1:2.4), were treated with high dose oral I-131 therapy with a Total Mean Dose (TMD) of 263.6 mCi, 4 - 6 weeks post thyroidectomy. They were followed up over a period of 6 years. Twenty ( 26.7%) patients had follicular cancer (FC), 47 (62.7%) papillary cancer (PC) and 8 (10.7%) were mixed (MC), on histopathology, at presentation. 38 (50.7%) patients had only residual thyroid tissue (RTT) on I-131 whole body bone scan (WBS) and 37 (49.3%) presented with metastatic disease (MD) at the time of therapy. Of the 37 patients with MD, 21 (56.8%) had metastases to the lymph nodes, 6 (16.2%) to the lungs, 4 (10.8%) to bone, 3 (8.1%) to bone and lung, and 4 (10.8%) to lung plus lymph nodes. Twenty-three patients (7 FC , 13 - PC and 3 MC; 6 RTT, 17 - MD) , received more than one dose of I-131 with a TMD of 422.7 mCi (Range 88 1590 mCi ). 52 patients (13 FC, 34 PC, 5 MC; 20 MD and 32 RTT) received a single TMD of 104.4 (Range 39.5 219 mCi). On follow-up, 3 patients of FC with MD (2 lung metastasis and 1 with extensive lymph node metastasis), died within 3 months 2 years of therapy. 3 patients of MD (2 FC, 1-MC; 2 bone metastasis and 1 bone with lung metastasis) died after 5 .5 years, Of the 6 patients who died, 5 were FC and only 1 was MC. 2 patients with MD to lungs and bone had received a single dose and were lost to follow up. All patients with PC and FC with only RTT, were surviving at the end of 5 years. None of the patients with MD to lymph nodes died at the end of 5 years, either receiving single or

  5. Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis.

    Science.gov (United States)

    Zhang, Qiang; Geng, Pei-Liang; Yin, Pei; Wang, Xiao-Lin; Jia, Jin-Peng; Yao, Jie

    2013-01-01

    To investigate the expression level of TUG1 and one of its transcript variants (n377360) in osteosarcoma cells and assess the role of TUG1 in proliferation and apoptosis in the U2OS cell line. TUG1 and n377360 expression levels in patients with osteosarcomas and the U2OS human osteosarcoma cell line were evaluated using real-time quantitative PCR. U2OS cells were transected with TUG1 and n377360 siRNA or non-targeting siRNA. MTS was performed to assess the cell proliferation and flow cytometry was applied to analyze apoptosis. We found significantly higher TUG1 and n377360 expression levels in osteosarcoma tissues compared with matched non-tumorous tissues. In line with this, suppression of TUG1 and n377360 expression by siRNA significantly impaired the cell proliferation potential of osteosarcoma cells. Furthermore, inhibition of TUG1 expression significantly promoted osteosarcoma cell apoptosis. The overexpression of TUG1 and n377360 in osteosarcoma specimens and the functional role of TUG1 and n377360 regarding cell proliferation and apoptosis in an osteosarcoma cell line provided evidence that the use of TUG1 or n377360 may be a viable but an as yet unexplored therapeutic strategy in tumors that over express these factors.

  6. Low-grade central osteosarcoma in proximal humerus: a rare entity

    Directory of Open Access Journals (Sweden)

    Tang F

    2017-10-01

    Full Text Available Fan Tang,1,2 Li Min,1,2 Yong Zhou,1 Yi Luo,1 Chongqi Tu1 1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA Abstract: Low-grade central osteosarcoma is a rare subtype of tumor with low-grade malignancy. Currently, wide resection with negative resection margin is the standard treatment for this disease. The role of neoadjuvant chemotherapy in low-grade central osteosarcoma was controversial and was mostly considered for tumors containing high-grade focal areas. Local tumor recurrences often exhibited a tumor with higher histologic grade or differentiation with the potential for metastases. In low-grade central osteosarcoma, timely wide resection after definite diagnosis can result in 5-year survival for almost 90%. However, the relatively nonspecific radiological and pathological findings make diagnosis very difficult. MDM2 and CDK4 are specific and provide sensitive markers for the diagnosis of low-grade central osteosarcoma, helping to differentiate low-grade central osteosarcoma from some benign lesions, including fibrous dysplasia, bone giant cell tumor, and chondrosarcoma. Here, we report the case of a 19-year-old woman with low-grade central osteosarcoma located at the proximal humerus. The affected site was rare, but the sensitive biomarkers CDK4 and MDM2 were positive. The patient recovered well after wide tumor resection following a proximal humerus endoprosthesis replacement. Our case highlighted the management strategies in low-grade central osteosarcoma. Being familiar with radiographic features, understanding the biological characteristics, and mastering diagnostic biomarkers can help oncologists avoid embarrassing situations in treatment when this rare tumor is highly suspected, even when located at an uncommon site. The discussion in this report

  7. Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity

    International Nuclear Information System (INIS)

    Nishida, Yoshihiro; Knudson, Warren; Knudson, Cheryl B.; Ishiguro, Naoki

    2005-01-01

    Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion

  8. Involvement of HIF-1α activation in the doxorubicin resistance of human osteosarcoma cells.

    Science.gov (United States)

    Roncuzzi, Laura; Pancotti, Fabia; Baldini, Nicola

    2014-07-01

    Osteosarcoma is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, survival outcomes remain unsatisfactory, particularly in patients with metastatic and/or recurrent disease. Unfortunately, treatment failure is commonly due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. The aim of the present study was to investigate the role of hypoxia-inducible factor 1α (HIF‑1α) and its signalling pathways as mediators of drug-resistance in human osteosarcoma. Toward this aim, we established two osteosarcoma cell lines selected for resistance to doxorubicin, a drug of choice in the treatment of this tumour. Our results showed that the multidrug resistance (MDR) phenotype was also mediated by HIF-1α, the most important regulator of cell adaptation to hypoxia. Our data showed that this transcription factor promoted the outward transport of intracellular doxorubicin by activating the P-glycoprotein (P-gp) expression in osteosarcoma cells maintained in normoxic conditions. In addition, it hindered doxorubicin-induced apoptosis by regulating the expression of c-Myc and p21. Finally, we observed that the doxorubicin-resistant cells maintained for 2 months of continuous culture in a drug-free medium, lost their drug-resistance and this effect was associated with the absence of HIF-1α expression. The emerging role of HIF-1α in osteosarcoma biology indicates its use as a valuable therapeutic target.

  9. Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro.

    Science.gov (United States)

    Fu, Dehao; He, Xianfeng; Yang, Shuhua; Xu, Weihua; Lin, Tao; Feng, Xiaobo

    2011-06-30

    To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro. A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

  10. Genomic instability of osteosarcoma cell lines in culture: impact on the prediction of metastasis relevant genes.

    Science.gov (United States)

    Muff, Roman; Rath, Prisni; Ram Kumar, Ram Mohan; Husmann, Knut; Born, Walter; Baudis, Michael; Fuchs, Bruno

    2015-01-01

    Osteosarcoma is a rare but highly malignant cancer of the bone. As a consequence, the number of established cell lines used for experimental in vitro and in vivo osteosarcoma research is limited and the value of these cell lines relies on their stability during culture. Here we investigated the stability in gene expression by microarray analysis and array genomic hybridization of three low metastatic cell lines and derivatives thereof with increased metastatic potential using cells of different passages. The osteosarcoma cell lines showed altered gene expression during in vitro culture, and it was more pronounced in two metastatic cell lines compared to the respective parental cells. Chromosomal instability contributed in part to the altered gene expression in SAOS and LM5 cells with low and high metastatic potential. To identify metastasis-relevant genes in a background of passage-dependent altered gene expression, genes involved in "Pathways in cancer" that were consistently regulated under all passage comparisons were evaluated. Genes belonging to "Hedgehog signaling pathway" and "Wnt signaling pathway" were significantly up-regulated, and IHH, WNT10B and TCF7 were found up-regulated in all three metastatic compared to the parental cell lines. Considerable instability during culture in terms of gene expression and chromosomal aberrations was observed in osteosarcoma cell lines. The use of cells from different passages and a search for genes consistently regulated in early and late passages allows the analysis of metastasis-relevant genes despite the observed instability in gene expression in osteosarcoma cell lines during culture.

  11. Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro

    Directory of Open Access Journals (Sweden)

    Lin Tao

    2011-06-01

    Full Text Available Abstract Background To study the effects of zoledronic acid (ZA on the vasculogenic mimicry of osteosarcoma cells in vitro. Methods A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. Results ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. Conclusions ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

  12. Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor

    Directory of Open Access Journals (Sweden)

    Noah Federman

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary malignancy of bone in children, adolescents, and adults. Despite extensive surgery and adjuvant aggressive high-dose systemic chemotherapy with potentially severe bystander side effects, cure is attainable in about 70% of patients with localized disease and only 20%–30% of those patients with metastatic disease. Targeted therapies clearly are warranted in improving our treatment of this adolescent killer. However, a lack of osteosarcoma-associated/specific markers has hindered development of targeted therapeutics. We describe a novel osteosarcoma-associated cell surface antigen, ALCAM. We, then, create an engineered anti-ALCAM-hybrid polymerized liposomal nanoparticle immunoconjugate (α-AL-HPLN to specifically target osteosarcoma cells and deliver a cytotoxic chemotherapeutic agent, doxorubicin. We have demonstrated that α-AL-HPLNs have significantly enhanced cytotoxicity over untargeted HPLNs and over a conventional liposomal doxorubicin formulation. In this way, α-AL-HPLNs are a promising new strategy to specifically deliver cytotoxic agents in osteosarcoma.

  13. Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

    Science.gov (United States)

    Story, A L; Boston, S E; Kilkenny, J J; Singh, A; Woods, J P; Culp, W T N; Skorupski, K A; Lu, X

    2017-07-01

    The prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients. (1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma. Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals. Retrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment. A slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival. Weight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma.

    Science.gov (United States)

    Mauchle, Ulrike; Selvarajah, Gayathri T; Mol, Jan A; Kirpensteijn, Jolle; Verheije, Monique H

    2015-08-01

    Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Mori Y

    2017-11-01

    Full Text Available Yuki Mori,1 Toshiharu Shirai,1 Ryu Terauchi,1 Shinji Tsuchida,1 Naoki Mizoshiri,1 Daichi Hayashi,1 Yuji Arai,2 Tunao Kishida,3 Osam Mazda,3 Toshikazu Kubo1 1Department of Orthopaedics, 2Department of Sports and Para-Sports Medicine, 3Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Abstract: There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease. Keywords: pristimerin, osteosarcoma, apoptosis, caspase, Akt 

  16. Stereotactic Body Radiotherapy for Metastatic and Recurrent Ewing Sarcoma and Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Lindsay C. Brown

    2014-01-01

    Full Text Available Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES, in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma (n=19 or ES (n=8. The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions. The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions. Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.

  17. Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

    Science.gov (United States)

    Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

    2017-08-01

    Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P  0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

  18. Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.

    Science.gov (United States)

    York, D; Withers, S S; Watson, K D; Seo, K W; Rebhun, R B

    2017-09-01

    Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity. © 2016 John Wiley & Sons Ltd.

  19. Essential role of RSK2 in c-Fos-dependent osteosarcoma development.

    Science.gov (United States)

    David, Jean-Pierre; Mehic, Denis; Bakiri, Latifa; Schilling, Arndt F; Mandic, Vice; Priemel, Matthias; Idarraga, Maria Helena; Reschke, Markus O; Hoffmann, Oskar; Amling, Michael; Wagner, Erwin F

    2005-03-01

    Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.

  20. Letter regarding Li JS et al. entitled "ERCC polymorphisms and prognosis of patients with osteosarcoma".

    Science.gov (United States)

    Jian, Yuekui; Tian, Xiaobin; Li, Bo; Zhou, Zhuojia; Wu, Xinglin

    2015-05-01

    With great interest, we read the article "ERCC polymorphisms and prognosis of patients with osteosarcoma" (by Li JS et al.), which has reached important conclusions about the relationship between ERCC polymorphisms and osteosarcoma prognosis. Through quantitative analysis, the meta-analysis showed that ERCC2 Lys751Gln (ORGG vs. AA = 0.40 (95%CI = 0.1-0.86), P heterogeneity = 0.502; I (2) = 0 %) and ERCC5 His46His (ORCC vs. TT = 0.37 (95%CI = 0.15-0.93), P heterogeneity = 0.569; I (2) = 0 %) polymorphisms might influence the prognosis of patients with osteosarcoma [1]. The meta-analysis results are encouraging. Nevertheless, some deficiencies still existed that we would like to raise.

  1. Radiation-induced osteosarcoma of the jaw treated with skull base surgery

    International Nuclear Information System (INIS)

    Yamamoto, Misaki; Asato, Ryo; Torii, Hiroko; Kanda, Tomoko; Tamura, Yoshihiro; Hirano, Shigeru; Ito, Juichi; Tanaka, Shinzou

    2009-01-01

    Head and neck osteosarcomas are rare. A 33-year-old woman received radiation therapy for lymphoepithelioma of the epipharynx in her childhood. After twenty-two years, she presented with a swelling of the right cheek. We did a work up, and diagnosed her radiation-induced osteosarcoma of the jaw. We treated her with neoadjuvant chemotherapy, surgery including skull base resection, and adjuvant chemo-therapy. A small skin recurrence developed after one year, but it was resected under local anesthesia, and there have been no recurrences since. We think that skull base surgery with a combined approach is a useful method in therapy for osteosarcomas in the skull base region. (author)

  2. Osteosarcoma of the mandible: A case report with an early radiographic manifestation

    Energy Technology Data Exchange (ETDEWEB)

    Samraj, Lavanya; Venkatapathy, Ramesh; Oza, Nirima [Dept. of Oral Pathology and Microbiology, Mahatma Gandhi Post Graduate Institute of Dental Sciences, Pondicherry (India); Kaliamoorthy, Sriram [Dept. of Oral and Maxillofacial Pathology, Chettinad Dental College and Research Institute, Tamilnadu (India)

    2014-03-15

    Osteosarcoma is a classical malignant bone-forming neoplasm which usually presents with an aggressive clinical course. The current case is presented with the radiographic feature of widening of the periodontal ligament space of the involved teeth, which is considered to be the earliest radiographic manifestation of osteosarcoma involving the jaw bone. The main aim of this case report was to focus on the importance of early diagnosis of this tumor based on clinical and radiographic examinations, and confirmation by histopathology. Considering the rarity of the disease type and particularly taking into account the fast progression and aggressiveness of this neoplasm, it is clear that the presentation of a clinical case represents a major contribution to better understanding of osteosarcomas involving the jaw bone.

  3. Knockdown of Long Noncoding RNA TUG1 Inhibits the Proliferation and Cellular Invasion of Osteosarcoma Cells By Sponging MiR-153.

    Science.gov (United States)

    Wang, Heping; Yu, Yanzhang; Fan, Shuxin; Luo, Leifeng

    2017-04-12

    Long noncoding RNA (lncRNA) Taurine-upregulated gene 1 (TUG1) has been confirmed to be involved in the progression of various cancers, however, its mechanism of action in osteosarcoma has not been well addressed. In our study, TUG1 was overexpressed and miR-153 was downregulated in osteosarcoma tissues and cell lines. Loss-of-function assay showed that TUG1 knockdown suppressed the viability, colony formation, and invasion of osteosarcoma cells in vitro. Moreover, TUG1 was confirmed to be a miR-153 sponge. Ectopic expression of TUG1 reversed the inhibitory effect of miR-153 on the proliferation and invasion of osteosarcoma cells. Further transplantation experiment proved the carcinogenesis of TUG1 in osteosarcoma in vivo. Collectively, our study elucidated that TUG1 contributed to the osteosarcoma development by sponging miR-153. These findings may provide a novel lncRNA-targeted therapy for patients with osteosarcoma.

  4. Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells.

    Science.gov (United States)

    Kotake, Yojiro; Goto, Taiki; Naemura, Madoka; Inoue, Yasutoshi; Okamoto, Haruna; Tahara, Keiichiro

    2017-01-01

    A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G 1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G 1 phase arrest. These results suggest that PANDA promotes G 1 -S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro,; Toshiyuki,; Hayashi, Yasuyuki [Nagasaki Univ. (Japan). School of Medicine

    1992-10-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.).

  6. Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma.

    Science.gov (United States)

    Palmini, Gaia; Zonefrati, Roberto; Mavilia, Carmelo; Aldinucci, Alessandra; Luzi, Ettore; Marini, Francesca; Franchi, Alessandro; Capanna, Rodolfo; Tanini, Annalisa; Brandi, Maria Luisa

    2016-10-14

    The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs.

  7. Morphological and Immunohistochemical Characterization of Canine Osteosarcoma Spheroid Cell Cultures.

    Science.gov (United States)

    Gebhard, C; Gabriel, C; Walter, I

    2016-06-01

    Spheroid cell culture emerges as powerful in vitro tool for experimental tumour research. In this study, we established a scaffold-free three-dimensional spheroid system built from canine osteosarcoma (OS) cells (D17). Spheroids (7, 14 and 19 days of cultivation) and monolayer cultures (2 and 7 days of cultivation) were evaluated and compared on light and electron microscopy. Monolayer and spheroid cultures were tested for vimentin, cytokeratin, alkaline phosphatase, osteocalcin and collagen I by means of immunohistochemistry. The spheroid cell culture exhibited a distinct network of collagen I in particular after 19-day cultivation, whereas in monolayer cultures, collagen I was arranged as a lamellar basal structure. Necrotic centres of large spheroids, as observed in 14- and 19-day cultures, were characterized by significant amounts of osteocalcin. Proliferative activity as determined by Ki-67 immunoreactivity showed an even distribution in two-dimensional cultures. In spheroids, proliferation was predominating in the peripheral areas. Metastasis-associated markers ezrin and S100A4 were shown to be continuously expressed in monolayer and spheroid cultures. We conclude that the scaffold-free spheroid system from canine OS cells has the ability to mimic the architecture of the in vivo tumour, in particular cell-cell and cell-matrix interactions. © 2015 The Authors. Anatomia, Histologia, Embryologia Published by Blackwell Verlag GmbH.

  8. Murine models of osteosarcoma: A piece of the translational puzzle.

    Science.gov (United States)

    Walia, Mannu K; Castillo-Tandazo, Wilson; Mutsaers, Anthony J; Martin, Thomas John; Walkley, Carl R

    2018-06-01

    Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. While our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targets, in addition to testing the role of additional mutations in vivo. Most recently these models have begun to be used for discovery based approaches and screens, which hold significant promise in furthering our understanding of the genetic and therapeutic sensitivities of OS. In this review, we discuss the mouse models of OS that have been reported in the last 3-5 years and newly identified pathways from these studies. Finally, we discuss the preclinical utilization of the mouse models of OS for identifying and validating actionable targets to improve patient outcome. © 2017 Wiley Periodicals, Inc.

  9. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    International Nuclear Information System (INIS)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro; Toshiyuki; Hayashi, Yasuyuki

    1992-01-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.)

  10. Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma.

    Science.gov (United States)

    Kozicki, A R; Robat, C; Chun, R; Kurzman, I D

    2015-09-01

    Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti-tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post-operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease-free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment. © 2013 Blackwell Publishing Ltd.

  11. What do we know about canine osteosarcoma treatment? Review.

    Science.gov (United States)

    Szewczyk, M; Lechowski, R; Zabielska, K

    2015-03-01

    Osteosarcoma (OSA) is the most common type of bone tumors in dogs, which has high metastasis ability. 80 % of dogs with OSA die due to lung metastasis. As a result its treatment is a challenge for veterinary practitioners. The authors discuss the etiology, pathogenesis and the possible risk factors of OSA. The article focuses on literature review and the study of recent advances in OSA treatment. The authors describe therapies which have significantly prolonged the lives of dogs, as well as those that have proven to be ineffective. Advantages and disadvantages of limb amputation and limb-sparing surgery have been described. Authors present also the results of both single agent's therapies with the most commonly used drugs as cisplatin, carboplatin and doxorubicin and compare them to the results obtained using combined chemotherapy. The use of nanotechnology as a new approach in OSA treatment in order to avoid multidrug resistance and reduce negative side effects of cytostatic drugs is presented. The main reasons of the therapies failure are also provided in this article.

  12. Evaluation of P16 expression in canine appendicular osteosarcoma.

    Science.gov (United States)

    Murphy, B G; Mok, M Y; York, D; Rebhun, R; Woolard, K D; Hillman, C; Dickinson, P; Skorupski, K

    2017-06-20

    Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.

  13. Mechanical properties of canine osteosarcoma-affected antebrachia.

    Science.gov (United States)

    Steffey, Michele A; Garcia, Tanya C; Daniel, Leticia; Zwingenberger, Allison L; Stover, Susan M

    2017-05-01

    To determine the influence of neoplasia on the biomechanical properties of canine antebrachia. Ex vivo biomechanical study. Osteosarcoma (OSA)-affected canine antebrachia (n = 12) and unaffected canine antebrachia (n = 9). Antebrachia were compressed in axial loading until failure. A load-deformation curve was used to acquire the structural mechanical properties of neoplastic and unaffected specimens. Structural properties and properties normalized by body weight (BW) and radius length were compared using analysis of variance (ANOVA). Modes of failure were compared descriptively. Neoplastic antebrachia fractured at, or adjacent to, the OSA in the distal radial diaphysis. Unaffected antebrachia failed via mid-diaphyseal radial fractures with a transverse cranial component and an oblique caudal component. Structural mechanical properties were more variable in neoplastic antebrachia than unaffected antebrachia, which was partially attributable to differences in bone geometry related to dog size. When normalized by dog BW and radial length, strength, stiffness, and energy to yield and failure, were lower in neoplastic antebrachia than in unaffected antebrachia. OSA of the distal radial metaphysis in dogs presented for limb amputation markedly compromises the structural integrity of affected antebrachia. However, biomechanical properties of affected bones was sufficient for weight-bearing, as none of the neoplastic antebrachia fractured before amputation. The behavior of tumor invaded bone under cyclic loading warrants further investigations to evaluate the viability of in situ therapies for bone tumors in dogs. © 2017 The American College of Veterinary Surgeons.

  14. Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

    Science.gov (United States)

    Batschinski, K; Dervisis, N G; Kitchell, B E

    2014-12-01

    A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

  15. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Goudarzi, Atta, E-mail: atta.goudarzi@utoronto.ca [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Merico, Daniele [The Centre for Applied Genomics, The Hospital for Sick Children, MaRS Centre-East Tower, 101 College Street Rm.14-701, Toronto, ON M5G 1L7 (Canada); Wunder, Jay S. [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Andrulis, Irene L. [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada)

    2013-04-08

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation.

  16. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

    International Nuclear Information System (INIS)

    Goudarzi, Atta; Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi; Merico, Daniele; Wunder, Jay S.; Andrulis, Irene L.

    2013-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation

  17. Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Marie E. Legare, Jamie Bush, Amanda K. Ashley, Taka Kato, William H. Hanneman

    2011-01-01

    Full Text Available Canine and human osteosarcoma (OSA have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have characterized seven different OSA canine cell lines: Abrams, D17, Grey, Hughes, Ingles, Jarques, and Marisco and compared them to U2, a human OSA cell line, for the following parameters: morphology, growth, contact inhibition, migrational tendencies, alkaline phosphatase staining, heterologous tumor growth, double-strand DNA breaks, and oxidative damage. All results demonstrated the positive characteristics of the Abrams cell line for use in future studies of OSA. Of particular interest, the robust growth of a subcutaneous tumor and rapid pulmonary metastasis of the Abrams cell line in an immunocompromised mouse shows incredible potential for the future use of Abrams as a canine OSA model. Further investigations utilizing a canine cell model of OSA, such as Abrams, will be invaluable to understanding the molecular events underlying OSA, pharmaceutical inhibition of metastasis, and eventual prevention of this devastating disease.

  18. A complex pattern of chemokine receptor expression is seen in osteosarcoma

    International Nuclear Information System (INIS)

    Luettichau, Irene von; Huss, Ralf; Nelson, Peter J; Segerer, Stephan; Wechselberger, Alexandra; Notohamiprodjo, Mike; Nathrath, Michaela; Kremer, Markus; Henger, Anna; Djafarzadeh, Roghieh; Burdach, Stefan

    2008-01-01

    Osteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma. The overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression. Expression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells. Our data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology

  19. Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells.

    Science.gov (United States)

    Paiva-Oliveira, Daniela I; Martins-Neves, Sara R; Abrunhosa, Antero J; Fontes-Ribeiro, Carlos; Gomes, Célia M F

    2018-01-01

    Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin. Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay. Metformin cytotoxicity alone and combined with doxorubicin were evaluated using MTT/BrdU assays. Protein levels of AMPK and AKT were evaluated by Western Blot. Cellular metabolic status was assessed based on [ 18 F]-FDG uptake and lactate production measurements. Sphere-forming efficiency and expression of pluripotency transcription factors analysed by qRT-PCR were tested as readout of Metformin effects on stemness features. Metformin induced a concentration-dependent decrease in the metabolic activity and proliferation of sphere-forming cells and improved doxorubicin-induced cytotoxicity. This drug also down-regulated the expression of master regulators of pluripotency (OCT4, SOX2, NANOG), and decreased spheres' self-renewal ability. Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations. Furthermore, Metformin-induced mitochondrial stress increased [ 18 F]-FDG uptake and lactate production in parental cells but not in the quiescent stem-like cells, suggesting the inability of the latter to cope with the energy crisis induced by metformin. This preclinical study suggests that Metformin may be a potentially useful therapeutic agent and chemosensitizer of osteosarcoma stem-like cells to doxorubicin.

  20. Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, C. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)], E-mail: ferraric@unipv.it; Zonta, C.; Cansolino, L.; Clerici, A.M.; Gaspari, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy); Altieri, S.; Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); Dionigi, P.; Zonta, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)

    2009-07-15

    Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of {sup 10}B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry {sup 10}B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue {sup 10}B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.

  1. Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

    Science.gov (United States)

    Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

    2016-12-01

    Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

    Science.gov (United States)

    Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

    2013-03-01

    To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

  3. Proximal femoral osteosarcoma: Diagnostic challenges translate into delayed and inappropriate management.

    Science.gov (United States)

    Dahan, M; Anract, P; Babinet, A; Larousserie, F; Biau, D

    2017-11-01

    The proximal femuris is an uncommon site of osteosarcoma. The unusual manifestations at this site may lead to diagnostic and therapeutic mistakes. We therefore performed a retrospective study to estimate the proportions of patients with imaging study findings and/or clinical manifestations typical for osteosarcoma and/or inappropriate treatment decisions. Proximal femoral osteosarcoma often produces atypical clinical and radiological presentations. Consecutive patients who underwent surgery at our center to treat proximal femoral osteosarcoma were included. For each patient, we collected the epidemiological characteristics, clinical symptoms, imaging study findings, treatment, and tumor outcome. Proportions were computed with their confidence intervals. Twelve patients had surgery for proximal femoral osteosarcoma between 1986 and 2015. Imaging findings were typical in 1 (8%) patient; they consisted of ill-defined osteolysis in 11/12 (92%) patients, a periosteal reaction in 1/12 (8%) patient, soft tissue involvement in 7/12 (58%) patients, and immature osteoid matrix in 11/12 (92%) patients. No patient had the typical combination of pain with a soft tissue swelling. Management was inappropriate in 2/12 (17%) patients, who did not undergo all the recommended imaging studies before surgery and were treated in another center before the correct diagnosis was established. At last follow-up, 4 patients had died (after a mean of 7 years) and 8 were alive (after a mean of 4 years). Proximal femoral osteosarcoma is uncommon and rarely produces the typical clinical and imaging study findings. The atypical presentation often results in diagnostic errors and inappropriate treatments. Ill-defined osteolysis on standard radiographs should prompt computed tomography or magnetic resonance imaging of the proximal femur. Treatment in a specialized center is imperative. IV, retrospective study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma

    OpenAIRE

    Yun-Bo, Feng; Xiao-Po, Liu; Xiao-Li, Li; Guo-Long, Cao; Pei, Zhang; Fa-Ming, Tian

    2016-01-01

    Abstract Objective: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1) in human osteosarcoma cells. Methods: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection eff...

  5. Characteristics of monolayer culture of bone marrow cells of rats bearing 239Pu-induced osteosarcoma

    International Nuclear Information System (INIS)

    Bukhtoyarova, Z.M.; Lemberg, V.K.

    1984-01-01

    The report is concerned with a monolayer culture of bone marrow cells of rats in which optimal blastogenic dose (92.5 kBq/kg) induced osteosarcoma. The cell culture showed an enhanced rate of fibroblast-like cell proliferation (increased number of mitoses and symplasts and larger colonies of cells), apparent signs of radiation in ury (pathologic mitoses, chromosome aberrations and gaps) as well as an increase in ploidy. Diffusion chamber measurements demonstrated osteogenic precursor-cells in osteosarcoma-bearing rats to be highly capable of bone formation. This relatively high ability seems to occur outside bone marrow as well

  6. HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor

    Directory of Open Access Journals (Sweden)

    Tsukahara Tomohide

    2009-06-01

    Full Text Available Abstract Background To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2. Methods Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201+ patients with osteosarcoma using limiting dilution (LD/mixed lymphocyte peptide culture (MLPC followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by 51Cr release assay. Results Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 × 10-7 to 5 × 10-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2. Conclusion These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.

  7. Hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma in a dog

    International Nuclear Information System (INIS)

    Rahal, S.C.; Mamprim, M.J.; Sequeira, J.L.; Franco, A.P.R.

    2003-01-01

    A 1.8-year-old female German Shepherd dog was presented with lameness, and painful non-edematous swelling of the right front limb. Swelling surrounding soft tissue and periosteal bone formation of the radius, ulna, metacarpals, without evidence of articular involvement were observed in the right front limb by radiographic examinations. Also, pulmonary tumor was observed in radiographic examination. Five months ago, the dog had developed osteosarcoma of the left distal ulna, and the treatment was cisplatin chemotherapy and limb amputation. The final diagnosis was hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma [pt

  8. Major surgery in an osteosarcoma patient refusing blood transfusion: case report.

    Science.gov (United States)

    Dhanoa, Amreeta; Singh, Vivek A; Shanmugam, Rukmanikanthan; Rajendram, Raja

    2010-11-08

    We describe an unusual case of osteosarcoma in a Jehovah's Witness patient who underwent chemotherapy and major surgery without the need for blood transfusion. This 16-year-old girl presented with osteosarcoma of the right proximal tibia requiring proximal tibia resection, followed by endoprosthesis replacement. She was successfully treated with neoadjuvant chemotherapy and surgery with the support of haematinics, granulocyte colony-stimulating factor, recombinant erythropoietin and intraoperative normovolaemic haemodilution. This case illustrates the importance of maintaining effective, open communication and exploring acceptable therapeutic alternative in the management of these patients, whilst still respecting their beliefs.

  9. Isolated brain metastases of osteosarcoma in a patient presenting with a patent foramen ovale

    International Nuclear Information System (INIS)

    Menassa, L.; Haddad, S.; Aoun, N.; Slaba, S.; Atallah, N.

    1997-01-01

    We report the case of a patient in whom brain MR imaging was requested for initial symptoms of intracranial hypertension. The presence of multiple intracranial hemorrhagic lesions suggested brain metastases. Body screening showed periosteal osteosarcoma of the left fibula with no lung metastases, but with a patent foramen ovale which probably allowed neoplastic cells to reach the brain without being filtered through the lungs. The conclusion of this study was that a left-right cardiac communication is to be considered in cases of isolated brain metastases from osteosarcoma. (orig.). With 3 figs

  10. Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

    Science.gov (United States)

    Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

    2013-11-01

    Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

  11. Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha.

    Directory of Open Access Journals (Sweden)

    Jennifer Adamski

    Full Text Available Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1. In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1α stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1α in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1α. Inhibition of the phosphoinositide 3-kinase (PI3K pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target

  12. p53 functions as a cell cycle control protein in osteosarcomas.

    OpenAIRE

    Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

    1990-01-01

    Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfect...

  13. Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

    International Nuclear Information System (INIS)

    Sadikovic, Bekim; Thorner, Paul; Chilton-MacNeill, Susan; Martin, Jeff W; Cervigne, Nilva K; Squire, Jeremy; Zielenska, Maria

    2010-01-01

    Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts. RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma

  14. Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

    Science.gov (United States)

    Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M; Shogren, Kristen L; Lu, Lichun; Yaszemski, Michael J

    2013-09-01

    Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. Copyright © 2012 Wiley Periodicals, Inc.

  15. Evaluation of clinical and histopathologic prognostic factors for survival in canine osteosarcoma of the extracranial flat and irregular bones.

    Science.gov (United States)

    Kruse, M A; Holmes, E S; Balko, J A; Fernandez, S; Brown, D C; Goldschmidt, M H

    2013-07-01

    Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

  16. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro.

    Science.gov (United States)

    Geiss, Carsten; Kis, Zoltán; Leuchs, Barbara; Frank-Stöhr, Monika; Schlehofer, Jörg R; Rommelaere, Jean; Dinsart, Christiane; Lacroix, Jeannine

    2017-10-17

    Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA replication, transcription of viral genes, and translation to viral proteins. After H-1PV infection, release of infectious viral particles from osteosarcoma cells into the supernatant indicated successful viral assembly and egress. Crystal violet staining revealed progressive cytomorphological changes in all osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H-1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a limited capacity for standard H-1PV virus replication. The cytotoxicity of wild-type H-1PV virus towards osteosarcoma cells was compared in vitro with that of two variants, Del H-1PV and DM H-1PV, previously described as fitness variants displaying higher infectivity and spreading in human transformed cell lines of different origins. Surprisingly, wild-type H-1PV displayed the strongest cytostatic and cytotoxic effects in this analysis and thus seems the most promising for the next preclinical validation steps in vivo.

  17. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro

    Directory of Open Access Journals (Sweden)

    Carsten Geiss

    2017-10-01

    Full Text Available Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA replication, transcription of viral genes, and translation to viral proteins. After H-1PV infection, release of infectious viral particles from osteosarcoma cells into the supernatant indicated successful viral assembly and egress. Crystal violet staining revealed progressive cytomorphological changes in all osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H-1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a limited capacity for standard H-1PV virus replication. The cytotoxicity of wild-type H-1PV virus towards osteosarcoma cells was compared in vitro with that of two variants, Del H-1PV and DM H-1PV, previously described as fitness variants displaying higher infectivity and spreading in human transformed cell lines of different origins. Surprisingly, wild-type H-1PV displayed the strongest cytostatic and cytotoxic effects in this analysis and thus seems the most promising for the next preclinical validation steps in vivo.

  18. Genomic instability and telomere fusion of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available Canine osteosarcoma (OSA is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

  19. Aberrant tropoelastin secretion in MG-63 human osteosarcoma cells

    International Nuclear Information System (INIS)

    Curtiss, S.W.

    1989-01-01

    The secretion of newly synthesized tropoelastin, the soluble precursor of the extracellular matrix protein elastin, is not well understood. MG-63 human osteosarcoma cells were found by immunoblot analysis to synthesize 62 kD and 64 kD tropoelastins. Media from 63 cells labelled for five hours with [ 3 H]-valine contain no detectable tropoelastin, unlike media from other tropoelastin-synthesizing cells. Immunoblots of conditioned media and 1Ox-concentrated conditioned media left on the cells for six days also show an absence of tropoelastin from the cell media. No insoluble elastin is associated with the cell layer, as determined by amino acid analysis and electron microscopy of 18-21 day cell cultures. The absence of tropoelastin from the cell medium and elastin from the extracellular matrix indicates that MG63 cells do not secrete tropoelastin as expected, but accumulate it intracellularly. This accumulation is transient: immunoblots and immunofluorescence microscopy show that cells three days after passage have the highest steady-state levels of tropoelastin per cell, that day 8 cells contain lower but still significant amounts of tropoelastin, and that by day 22 tropoelastin is no longer present in the cell cultures. Cell density is a critical factor in the observed pattern of tropoelastin expression. Cells seeded at ten fold their usual initial density have high tropoelastin levels at one day after passage, sooner than cells seeded normally. Tropoelastin also disappears from high density-seeded cells more quickly and is no longer detectable at day 10. Lysosome-like vesicles containing membranous structures appear by immunoelectron microscopy to be the primary site of intracellular tropoelastin localization

  20. Cathepsin K expression and activity in canine osteosarcoma.

    Science.gov (United States)

    Schmit, J M; Pondenis, H C; Barger, A M; Borst, L B; Garrett, L D; Wypij, J M; Neumann, Z L; Fan, T M

    2012-01-01

    Cathepsin K (CatK) is a lysosomal protease with collagenolytic activity, and its secretion by osteoclasts is responsible for degrading organic bone matrix. People with pathologic bone resorption have higher circulating CatK concentrations. Canine osteosarcoma (OS) cells will possess CatK, and its secretion will be cytokine inducible. Circulating CatK concentrations will be increased in dogs with OS, and will be a surrogate marker of bone resorption. Fifty-one dogs with appendicular OS and 18 age- and weight-matched healthy control dogs. In a prospective study, expressions of CatK mRNA and protein were investigated in OS cells. The inducible secretion and proteolytic activity of CatK from OS cells was assessed in vitro. Serum CatK concentrations were quantified in normal dogs and dogs with OS and its utility as a bone resorption marker was evaluated in dogs with OS treated with palliative radiation and antiresorptive agents. Canine OS cells contain preformed CatK within cytoplasmic vesicles. In OS cells, TGFβ1 induced the secretion of CatK, which degraded bone-derived type I collagen in vitro. CatK concentrations were higher in dogs with OS than healthy dogs (11.3 ± 5.2 pmol/L versus 8.1 ± 5.0 pmol/L, P = .03). In a subset of dogs with OS, pretreatment CatK concentrations gradually decreased after palliative radiation and antiresorptive treatment, from 9.3 ± 3.2 pmol/L to 5.0 ± 3.1 pmol/L, P = .03. Canine OS is associated with pathologic bone resorption, and CatK inhibitors might aid in the management of canine OS-related malignant osteolysis. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  1. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology.

    Science.gov (United States)

    Fenger, Joelle M; London, Cheryl A; Kisseberth, William C

    2014-01-01

    Osteosarcoma (OSA) is the most common form of malignant bone cancer in children and dogs, although the disease occurs in dogs approximately 10 times more frequently than in people. Multidrug chemotherapy and aggressive surgical techniques have improved survival; however, new therapies for OSA are critical, as little improvement in survival times has been achieved in either dogs or people over the past 15 years, even with significant efforts directed at the incorporation of novel therapeutic approaches. Both clinical and molecular evidence suggests that human and canine OSA share many key features, including tumor location, presence of microscopic metastatic disease at diagnosis, development of chemotherapy-resistant metastases, and altered expression/activation of several proteins (e.g. Met, ezrin, phosphatase and tensin homolog, signal transducer and activator of transcription 3), and p53 mutations, among others. Additionally, canine and pediatric OSA exhibit overlapping transcriptional profiles and shared DNA copy number aberrations, supporting the notion that these diseases are similar at the molecular level. This review will discuss the similarities between pediatric and canine OSA with regard to histology, biologic behavior, and molecular genetic alterations that indicate canine OSA is a relevant, spontaneous, large animal model of the pediatric disease and outline how the study of naturally occurring OSA in dogs will offer additional insights into the biology and future treatment of this disease in both children and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Jian, Yuekui; Chen, Changqiong; Li, Bo; Tian, Xiaobin, E-mail: drtxb_guiyang@sina.com

    2015-10-23

    Tight junction proteins (TJPs) including Claudins, Occludin and tight junction associated protein Zonula occludens-1 (ZO-1), are the most apical component of junctional complex that mediates cell–cell adhesion in epithelial and endothelial cells. In human malignancies, TJPs are often deregulated and affect cellular behaviors of tumor cells. In this study, we investigated alternations of TJPs and related biological characteristics in human osteosarcoma (OS). Claudin1 was increased in the metastatic OS cells (KRIB and KHOS) compared with the normal osteoblast cells (hFOB1.19) or primary tumor cells (HOS and U2OS), whereas no significant difference was found in Occludin and ZO-1. Immunohistochemistry, immunofluorescence and Western blotting revealed that Claudin1 was initially localized at cell junctions of normal osteoblasts, but substantially delocalized to the nucleus of metastatic OS cells. Phenotypically, inhibition of the nucleus Claudin1 expression compromised the metastatic potential of KRIB and KHOS cells. Moreover, we found that protein kinase C (PKC) but not PKA phosphorylation influenced Claudin1 expression and cellular functions, as PKC inhibitor (Go 6983 and Staurosporine) or genetic silencing of PKC reduced Claudin1 expression and decreased the motility of KRIB and KHOS cells. Taken together, our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. - Highlights: • Claudin1 is increased during the malignant transformation of human OS. • Delocalization of Claudin1 in metastatic OS cells. • Silencing nuclear Claudin1 expression inhibits cell invasion of OS. • Deregulated Claudin1 is regulated by PKC.

  3. Prevalence of 5-lipoxygenase expression in canine osteosarcoma and the effects of a dual 5-lipoxygenase/cyclooxygenase inhibitor on osteosarcoma cells in vitro and in vivo.

    Science.gov (United States)

    Goupil, R C; Bushey, J J; Peters-Kennedy, J; Wakshlag, J J

    2012-09-01

    Canine osteosarcoma is an insidious disease with few effective treatment modalities; therefore, use of pharmacologic intervention to improve mortality or morbidity is constantly sought. The use of cyclooxygenase enzyme inhibitors has been an area of interest with limited efficacy based on retrospective examination of tumor expression and in vivo cell proliferation models. Recently, examination of dual cyclooxygenase and 5-lipoxygenase inhibitors in human and canine oncology suggests that 5-lipoxygenase inhibitors may be an effective approach in vitro and during tumor induction in rodent models. Therefore, the authors decided to examine 5-lipoxygenase expression in primary canine osteosarcoma samples and have shown that approximately 65% of osteosarcomas label positive for cytoplasmic 5-lipoxygenase. Further examination of a cell culture and xenograft model shows similar 5-lipoxygenase expression. Surprisingly, a canine 5-lipoxygenase inhibitor (tepoxalin) significantly reduced cell proliferation at physiologic doses in vitro and diminished xenograft tumor growth in nude mice, suggesting that further investigation is needed. Traditionally, 5-lipoxygense leads to production of lipid mediators, such as leukotriene B(4) and 5-oxo-eicosatetraenoic acid, which, when added back to the media of tepoxalin-treated cells, did not recover cell proliferation. The lack of nuclear staining in primary and xenografted tumors and the lack of response to eicoasanoids suggest that lipid mediator production is not the primary means by which tepoxalin acts to alter proliferation. Regardless of the mechanisms involved in retarding cell proliferation, future investigation is warranted.

  4. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma.

    Science.gov (United States)

    Yun-Bo, Feng; Xiao-Po, Liu; Xiao-Li, Li; Guo-Long, Cao; Pei, Zhang; Fa-Ming, Tian

    2016-01-01

    To examine the expression and function of long non-coding RNA taurine up-regulated 1 ( TUG1 ) in human osteosarcoma cells. Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1 , since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

  5. Doxycyclin induces p53 expression in SaOs (osteosarcoma) cell line ...

    African Journals Online (AJOL)

    The p53 tumour suppressor gene plays an important role in preventing cancer development. This study determined if p53 can be induced in osteosarcoma cell line upon treatment ... represent an important component of the p53 tumor suppressor pathway. Keywords: Tumor suppressor, oncogene, mdm2, cyclinE, apoptosis ...

  6. Short communication: selective cytotoxicity of curcumin on osteosarcoma cells compared to healthy osteoblasts

    Directory of Open Access Journals (Sweden)

    Chang R

    2014-01-01

    Full Text Available Run Chang,1 Linlin Sun,1 Thomas J Webster1,21Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: Curcumin is a natural phenolic compound extracted from the plant Curcuma longa L. In previous studies, curcumin has been shown to have anticancer, antioxidant, and anti-inflammatory effects. In this study, the cytotoxicity of different concentrations (5, 10, 25, 50, 75, and 100 µM of curcumin dissolved in dimethyl sulfoxide was compared between MG-63 osteosarcoma and healthy human osteoblast cells. Consequently, the viability of osteosarcoma cells was less than 50% at a concentration of 10 µM compared to the control sample without curcumin, but healthy osteoblast cells had at least 80% viability throughout all the concentrations tested. The results demonstrated that MG-63 osteosarcoma cells were much more sensitive in terms of cytotoxicity to curcumin, while the healthy human osteoblasts exhibited a higher healthy viability after 24 hours of curcumin treatment. Therefore, this study showed that at the right concentrations (5 µM to 25 µM, curcumin, along with a proper nanoparticle drug delivery carrier, may selectively kill bone cancer cells over healthy bone cells.Keywords: curcumin, osteosarcoma, human osteoblast, viability, bone cancer

  7. Osteosarcoma: a comparison of jaw versus nonjaw localizations and review of the literature

    NARCIS (Netherlands)

    van den Berg, H.; Schreuder, W.H.; de Lange, J.

    2013-01-01

    Purpose. It is assumed that osteosarcomas of the jaws mainly occur at older ages, whereas the most prominent sites, that is, the long bones, are more affected at ages <20. Jaw-localized tumors are less malignant and have lower metastatic spread rates. Patients and Methods. This study analyses the

  8. Osteosarcoma: A Comparison of Jaw versus Nonjaw Localizations and Review of the Literature

    NARCIS (Netherlands)

    van den Berg, H.; Schreuder, W. H.; de Lange, J.

    2013-01-01

    Purpose. It is assumed that osteosarcomas of the jaws mainly occur at older ages, whereas the most prominent sites, that is, the long bones, are more affected at ages <20. Jaw-localized tumors are less malignant and have lower metastatic spread rates. Patients and Methods. This study analyses the

  9. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    International Nuclear Information System (INIS)

    Díaz-Montero, C Marcela; McIntyre, Bradley W

    2005-01-01

    Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well. Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators

  10. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  11. Proteomic approach toward molecular backgrounds of drug resistance of osteosarcoma cells in spheroid culture system.

    Science.gov (United States)

    Arai, Kazuya; Sakamoto, Ruriko; Kubota, Daisuke; Kondo, Tadashi

    2013-08-01

    Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than five cell lines and four species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the upregulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. CD133 expression in osteosarcoma and derivation of CD133⁺ cells.

    Science.gov (United States)

    Li, Ji; Zhong, Xiao-Yan; Li, Zong-Yu; Cai, Jin-Fang; Zou, Lin; Li, Jian-Min; Yang, Tao; Liu, Wei

    2013-02-01

    Cluster of differentiation 133 (CD133) is recognized as a stem cell marker for normal and cancerous tissues. Using cell culture and real‑time fluorescent polymerase chain reaction, CD133 expression was analyzed in osteosarcoma tissue and Saos‑2 cell lines. In addition, cancer stem cell‑related gene expression in the Saos‑2 cell line was determined to explore the mechanisms underlying tumorigenesis and high drug resistance in osteosarcoma. CD133+ cells were found to be widely distributed in various types of osteosarcoma tissue. Following cell culture, cells entered the G2/M and S cell cycle stages from G0/G1. Levels of CD133+ cells decreased to normal levels rapidly over the course of cell culture. Colony forming efficiency was higher in the CD133+ compared with the CD133‑ subpopulation of Saos‑2 cells. Expression levels of stem cell‑related genes, including multidrug resistance protein 1 (MDR1) and sex determining region Y‑box 2 (Sox2) in the CD133+ subpopulation of cells were found to be significantly higher compared with the CD133‑ subpopulation. These observations indicate that CD133+ Saos‑2 cells exhibit stem cell characteristics, including low abundance, quiescence and a high potential to undergo differentiation, as well as expression of key stem cell regulatory and drug resistance genes, which may cause osteosarcoma and high drug resistance.

  13. Expression of intracisternal A-particles in radiation-induced murine osteosarcomas

    International Nuclear Information System (INIS)

    Seidel, E.

    1989-01-01

    The expression of intracisternal A-type particles (IAPs) and the distribution of the corresponding type I and type II genes was investigated in radiation induced osteosarcomas of Balb/c, NMRI and CBA mice. The results can be summarized as follows: 1. Slot blot analysis showed that 9 out of 23 (i.e. 39%) of the examined tumours had enhanced IAP expression as compared to normal tissues. None of the CBA tumours were enhanced in IAP expression - only tumours of the strains Balb/c and NMRI expressed higher levels of IAP RNA. 2. Northern blot analysis of RNA from osteosarcomas revealed that the two IAP transcrips (7.2 kb and 5.4 kb) had the same mobility in these tissues as in normal tissue. Some tumours showed a higher level of expression of the 7.2 kb transcript as compared to normal tissues. This 7.2 kb transcript encodes the major structural protein p 73 of IAPs. 3. Hybridization of Southern blots of mouse DNA using the IAP type I specific probe revealed a unique fragment in three of the investigated Balb/c osteosarcomas. 4. Although it could not directly be shown that IAPs were involved in the genesis of osteosarcomas, the changes in IAP expression and the unique fragments suggest a possible correlation with tumour progression. In this light the level of IAP expression may serve as a marker for the degree of the malignancy of the tumour. (orig.) [de

  14. Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming.

    Science.gov (United States)

    Choong, Pei Feng; Teh, Hui Xin; Teoh, Hoon Koon; Ong, Han Kiat; Choo, Kong Bung; Sugii, Shigeki; Cheong, Soon Keng; Kamarul, Tunku

    2014-01-01

    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.

  15. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Yun-Bo Feng

    2016-01-01

    Full Text Available Objective: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1 in human osteosarcoma cells. Methods: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Results: Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1, since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Conclusion: Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

  16. [Paraosteal osteosarcoma of the tibia treated with the OSS prosthesis. Case report].

    Science.gov (United States)

    Ochoa-Cázares, S; Mancilla, J A; Cuadra-Castillo, M

    2014-01-01

    Parosteal osteosarcoma originates on the surface of long bones and spares the medullary canal. Its peak incidence occurs in the third decade of life and it is more frequent in females than males. The juxtacortical variety of parosteal osteosarcoma is one of the most common ones, accounting for 1-6% of all osteosarcomas. The classical radiographic appearance of osteosarcoma includes high ossification density and a lobed mass, usually in the posterior aspect of the distal femur, sparing the medullary canal. We report herein the case of a 31 year-old male patient with a clinical picture that included left knee pain and who was seen as outpatient. He was started on treatment for enbloc resection of the tumor and implantation of the OSS (Orthopedic Salvage System) prosthesis. Treatment consisted of broad resection of the proximal tibia, of approximately 14 cm, as well as the implantation of a nonconventional modular tibial prosthesis. Both the radiographic and the clinical results were good and appropriate at the three week follow up.

  17. Comparative studies on prognostic markers and signaling pathways for canine and human osteosarcoma

    NARCIS (Netherlands)

    Selvarajah, G.T.

    2011-01-01

    Osteosarcoma is an aggressive bone tumor that occurs naturally mainly in large and medium breed dogs where almost 90% of dogs will develop metastasis predominantly in the lungs. The standard treatments (extirpation of the primary tumor including limb amputation/sparing, post-operative chemotherapy

  18. Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma

    DEFF Research Database (Denmark)

    Colding-Rasmussen, Thomas; Thorn, Andrea Pohly; Horstmann, Peter

    2018-01-01

    BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diag...

  19. Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo.

    Science.gov (United States)

    Mori, Yuki; Shirai, Toshiharu; Terauchi, Ryu; Tsuchida, Shinji; Mizoshiri, Naoki; Hayashi, Daichi; Arai, Yuji; Kishida, Tunao; Mazda, Osam; Kubo, Toshikazu

    2017-01-01

    There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

  20. Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

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    Hai-Yong Ren

    2015-01-01

    Full Text Available Background. Serum alkaline phosphatase (SALP is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and relative risks (RRs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients’ overall survival (OS (HR = 1.82; 95% CI: 1.61–2.06; p<0.001 and event-free survival (EFS (HR = 1.97; 95% CI: 1.61–2.42; p<0.001. Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p=0.006. No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

  1. Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data.

    Science.gov (United States)

    Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

    2015-01-01

    Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61-2.06; p SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61-9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

  2. Heterogeneity of Osteosarcoma Cell Lines Led to Variable Responses in Reprogramming

    Science.gov (United States)

    Choong, Pei Feng; Teh, Hui Xin; Teoh, Hoon Koon; Ong, Han Kiat; Choo, Kong Bung; Sugii, Shigeki; Cheong, Soon Keng; Kamarul, Tunku

    2014-01-01

    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture. PMID:25170299

  3. Differences in the characteristics of cell cultures established from seven human osteosarcomas

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Henning, C.B.; Mackevicius, F.

    1975-01-01

    Cell cultures derived from seven human osteosarcomas have been characterized with respect to their pattern of growth and cell morphology using light microscopy, transmission electron microscopy, and scanning electron microscopy. Other characteristics studied included growth rates, chromosomal abnormalities, and ability to grow in low serum concentrations and on a semisolid substrate. Normal human fibroblasts in culture have also been examined by the same methods. The results show many differences both between individual osteosarcoma cultures and normal fibroblasts. Two of the osteosarcoma cultures were epithelium-like, and five had a more fibroblastic appearance when viewed by the light microscope. Examination by electron microscopy showed a wide variety of cells in each culture. Many of the features exhibited in the fibroblast-like tumor cells were different from those seen with the normal fibroblast cultures. Growth rates differed widely with characteristic doubling times varying between 1 and 7 days from the osteosarcoma cultures, compared to 3 to 4 days for normal fibroblasts. Unlike normal mouse fibroblasts, which grow poorly or not at all in low serum concentrations, the normal human fibroblasts tested grew almost as well in media with 1 percent serum as with 15 percent serum

  4. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

    NARCIS (Netherlands)

    Posthuma de Boer, J.; Witlox, M.A.; Kaspers, G.J.L.; van Royen, B.J.

    2011-01-01

    Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy

  5. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Bajpai, Jyoti; Bakhshi, Sameer [Dr. B. R. A. Institute Rotary Cancer Hospital, Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi (India); Gamnagatti, Shivanand [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India); Kumar, Rakesh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Sreenivas, Vishnubhatla [All India Institute of Medical Sciences, Department of Biostatistics, New Delhi (India); Sharma, Mehar Chand; Safaya, Rajni [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India); Khan, Shah Alam; Rastogi, Shishir [All India Institute of Medical Sciences, Department of Orthopedics, New Delhi (India)

    2011-04-15

    Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response {>=}90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

  6. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

    International Nuclear Information System (INIS)

    Bajpai, Jyoti; Bakhshi, Sameer; Gamnagatti, Shivanand; Kumar, Rakesh; Malhotra, Arun; Sreenivas, Vishnubhatla; Sharma, Mehar Chand; Safaya, Rajni; Khan, Shah Alam; Rastogi, Shishir

    2011-01-01

    Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

  7. Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients

    NARCIS (Netherlands)

    Smeele, L. E.; Kostense, P. J.; van der Waal, I.; Snow, G. B.

    1997-01-01

    To evaluate the possible value of chemotherapy in the treatment of craniofacial osteosarcoma (CFOS). In a systematic review, data of 201 patients (age, 36.6 +/- 19.0 years [mean +/- SD]) from 20 uncontrolled series on CFOS indexed in Medline and Excerpta Medica between 1974 and 1994 were pooled; 180

  8. Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy

    Directory of Open Access Journals (Sweden)

    Wang F

    2018-02-01

    Full Text Available Fen Wang,1,* Jia-Dong Pang,2,* Lei-lei Huang,1 Ran Wang,1 Dan Li,3 Kang Sun,4 Lian-tang Wang,1,* Li-Ming Zhang2,* 1Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 2PCFM Lab and GDHPPC Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 3Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 4School of Engineering, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Nanomedicine, which is the application of nanotechnology in medicine to make medical diagnosis and treatment more accurate, has great potential for precision medicine. Despite some improvements in nanomedicine, the lack of efficient and low-toxic vectors remains a major obstacle. Objective: The aim of this study was to prepare an efficient and low-toxic vector which could deliver astrocyte elevated gene-1 (AEG-1 small interfering RNA (siRNA; siAEG-1 into osteosarcoma cells effectively and silence the targeted gene both in vitro and in vivo. Materials and methods: We prepared a novel polysaccharide derivative by click conjugation of azidized chitosan with propargyl focal point poly (L-lysine dendrons (PLLD and subsequent coupling with folic acid (FA; Cs-g-PLLD-FA. We confirmed the complexation of siAEG-1and Cs-g-PLLD or Cs-g-PLLD-FA by gel retardation assay. We examined the cell cytotoxicity, cell uptake, cell proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in osteosarcoma cells. In osteosarcoma 143B cells tumor-bearing mice models, we established the therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1. Results: Cs-g-PLLD-FA could completely encapsulate siAEG-1 and showed low cytotoxicity in osteosarcoma cells and tumour-bearing mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were capable of transferring siAEG-1 into osteosarcoma cells efficiently, and the knockdown of AEG-1

  9. Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

    Science.gov (United States)

    Boro, Aleksandar; Arlt, Matthias Je; Lengnick, Harald; Robl, Bernhard; Husmann, Maren; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2015-01-01

    Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy.

  10. Comparative proteomic analysis of plasma membrane proteins between human osteosarcoma and normal osteoblastic cell lines

    International Nuclear Information System (INIS)

    Zhang, Zhiyu; Ma, Fang; Cai, Zhengdong; Zhang, Lijun; Hua, Yingqi; Jia, Xiaofang; Li, Jian; Hu, Shuo; Peng, Xia; Yang, Pengyuan; Sun, Mengxiong

    2010-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. However, the knowledge in diagnostic modalities has progressed less. To identify new biomarkers for the early diagnosis of OS as well as for potential novel therapeutic candidates, we performed a sub-cellular comparative proteomic research. An osteosarcoma cell line (MG-63) and human osteoblastic cells (hFOB1.19) were used as our comparative model. Plasma membrane (PM) was obtained by aqueous two-phase partition. Proteins were analyzed through iTRAQ-based quantitative differential LC/MS/MS. The location and function of differential proteins were analyzed through GO database. Protein-protein interaction was examined through String software. One of differentially expressed proteins was verified by immunohistochemistry. 342 non-redundant proteins were identified, 68 of which were differentially expressed with 1.5-fold difference, with 25 up-regulated and 43 down-regulated. Among those differential proteins, 69% ware plasma membrane, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc., and interaction with each other. One protein--CD151 located in net nodes was verified to be over-expressed in osteosarcoma tissue by immunohistochemistry. It is the first time to use plasma membrane proteomics for studying the OS membrane proteins according to our knowledge. We generated preliminary but comprehensive data about membrane protein of osteosarcoma. Among these, CD151 was further validated in patient samples, and this small molecule membrane might be a new target for OS research. The plasma membrane proteins identified in this study may provide new insight into osteosarcoma biology and potential diagnostic and therapeutic biomarkers

  11. An integrative multi-platform analysis for discovering biomarkers of osteosarcoma

    International Nuclear Information System (INIS)

    Li, Guodong; Zhang, Wenjuan; Zeng, Huazong; Chen, Lei; Wang, Wenjing; Liu, Jilong; Zhang, Zhiyu; Cai, Zhengdong

    2009-01-01

    SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry) has become an attractive approach for cancer biomarker discovery due to its ability to resolve low mass proteins and high-throughput capability. However, the analytes from mass spectrometry are described only by their mass-to-charge ratio (m/z) values without further identification and annotation. To discover potential biomarkers for early diagnosis of osteosarcoma, we designed an integrative workflow combining data sets from both SELDI-TOF-MS and gene microarray analysis. After extracting the information for potential biomarkers from SELDI data and microarray analysis, their associations were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. Immuno-blot analysis was then performed to examine whether the expression of the putative biomarkers were indeed altered in serum from patients with osteosarcoma. Six differentially expressed protein peaks with strong statistical significances were detected by SELDI-TOF-MS. Four of the proteins were up-regulated and two of them were down-regulated. Microarray analysis showed that, compared with an osteoblastic cell line, the expression of 653 genes was changed more than 2 folds in three osteosarcoma cell lines. While expression of 310 genes was increased, expression of the other 343 genes was decreased. The two sets of biomarkers candidates were combined by the link-test statistics, indicating that 13 genes were potential biomarkers for early diagnosis of osteosarcoma. Among these genes, cytochrome c1 (CYC-1) was selected for further experimental validation. Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis can accelerate the identification of tumor biomarkers. The result confirmed that CYC-1 may be a promising biomarker for early diagnosis of osteosarcoma

  12. Genomic instability of osteosarcoma cell lines in culture: impact on the prediction of metastasis relevant genes.

    Directory of Open Access Journals (Sweden)

    Roman Muff

    Full Text Available Osteosarcoma is a rare but highly malignant cancer of the bone. As a consequence, the number of established cell lines used for experimental in vitro and in vivo osteosarcoma research is limited and the value of these cell lines relies on their stability during culture. Here we investigated the stability in gene expression by microarray analysis and array genomic hybridization of three low metastatic cell lines and derivatives thereof with increased metastatic potential using cells of different passages.The osteosarcoma cell lines showed altered gene expression during in vitro culture, and it was more pronounced in two metastatic cell lines compared to the respective parental cells. Chromosomal instability contributed in part to the altered gene expression in SAOS and LM5 cells with low and high metastatic potential. To identify metastasis-relevant genes in a background of passage-dependent altered gene expression, genes involved in "Pathways in cancer" that were consistently regulated under all passage comparisons were evaluated. Genes belonging to "Hedgehog signaling pathway" and "Wnt signaling pathway" were significantly up-regulated, and IHH, WNT10B and TCF7 were found up-regulated in all three metastatic compared to the parental cell lines.Considerable instability during culture in terms of gene expression and chromosomal aberrations was observed in osteosarcoma cell lines. The use of cells from different passages and a search for genes consistently regulated in early and late passages allows the analysis of metastasis-relevant genes despite the observed instability in gene expression in osteosarcoma cell lines during culture.

  13. Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

    Science.gov (United States)

    Petrilli, A S; Kechichian, R; Broniscer, A; Garcia, R J; Tanaka, C; Francisco, J; Lederman, H; Odone Filho, V; Camargo, O P; Bruniera, P; Pericles, P; Consentino, E; Ortega, J A

    1999-08-01

    Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma. Copyright 1999 Wiley-Liss, Inc.

  14. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study.

    Directory of Open Access Journals (Sweden)

    Daniela Caronia

    Full Text Available Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response.In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs and 2 Copy Number Variants (CNVs in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10⁻⁵, and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9×10⁻⁵, rs1128503 and rs10276036 (r² = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9×10⁻⁵. Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤ 0.03.Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy.

  15. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-05-09

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  16. Combination of etoposide and fisetin results in anti-cancer efficiency against osteosarcoma cell models.

    Science.gov (United States)

    Ferreira de Oliveira, José Miguel P; Pacheco, Ana Rita; Coutinho, Laura; Oliveira, Helena; Pinho, Sónia; Almeida, Luis; Fernandes, Eduarda; Santos, Conceição

    2018-03-01

    Osteosarcoma chemotherapy is often limited by chemoresistance, resulting in poor prognosis. Combined chemotherapy could, therefore, be used to prevent resistance to chemotherapeutics. Here, the effects of fisetin on osteosarcoma cells were investigated, as well as cytostatic potential in combination with the anti-cancer drug etoposide. For this, different osteosarcoma cell lines were treated with fisetin, with etoposide and with respective combinations. Fisetin was associated with decrease in colony formation in Saos-2 and in U2OS cells but not in MG-63 cells. Notwithstanding, upon evaluation of cellular growth by crystal violet assay, MG-63 and Saos-2 cells showed decreased cell proliferation at 40 and 20 µM fisetin, respectively. Depending on the relative concentrations, fisetin:etoposide combinations showed negative-to-positive interactions on the inhibition of cell proliferation. In addition, fisetin treatment up to 50 µM for 48 h resulted in G2-phase cell cycle arrest. Regardless of the combination, fisetin:etoposide increased % cells in G2-phase and decreased % cells in G1-phase. In addition, mixtures with more positive combined effects induced increased % cells in S-phase. Compared to etoposide treatment, these combinations resulted in decreased levels of cyclins B1 and E1, pointing to the role of these regulators in fisetin-induced cell cycle arrest. In conclusion, these results show that the combination of fisetin with etoposide has higher anti-proliferative effects in osteosarcoma associated with cell cycle arrest, allowing the use of lower doses of the chemotherapeutic agent, which has important implications for osteosarcoma treatment.

  17. Prognostic factors in canine appendicular osteosarcoma – a meta-analysis