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Sample records for well-differentiated extraskeletal osteosarcoma

  1. Well-Differentiated Extraskeletal Osteosarcoma Arising from the Retroperitoneum That Recurred as Anaplastic Spindle Cell Sarcoma

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    Hiromasa Arai; Yasushi Rino; Teppei Nishii; Norio Yukawa; Nobuyuki Wada; Hisashi Oshiro; Tsuyoshi Ishida; Noboru Nakaigawa; Munetaka Masuda

    2010-01-01

    Extraskeletal osteosarcoma is an uncommon high-grade malignant soft tissue sarcoma. Well-differentiated extraskeletal osteosarcoma is thought to have a better prognosis than classical extraskeletal osteosarcoma, but dedifferentiation after recurrence has also been reported. We present a case of a primary retroperitoneal extraskeletal osteosarcoma in a 62-year-old Japanese woman. Abdominal CT revealed a large mass with diffuse calcification in the right retroperitoneal space and tumor resectio...

  2. Pediatric extraskeletal osteosarcoma

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    Beall, Douglas P.; Stapp, Annette M. [Clinical Radiology of Oklahoma, P.O. Box 2814, Edmond, OK (United States); Ly, Justin [Wilford Hall Medical Center, Department of Radiology, San Antonio, TX (United States); Bell, Jayson P.; Babb, Julie C. [University of Oklahoma Health Science Center, College of Medicine, Oklahoma, OK (United States); Parker, Ellen E. [University of Oklahoma Health Science Center, Department of Radiology, Oklahoma, OK (United States); John, Christopher M. [Midwestern University, College of Medicine, Oakbrook Terrace, IL (United States)

    2008-05-15

    Extraskeletal osteosarcoma (ESOS) is a rare malignant tumor composed of mesenchymal cells comprising approximately 1% of soft-tissue sarcomas and 4% of all osteosarcomas. Primary osseous osteosarcomas more commonly develop in children and adolescents, but there are very few reports of ESOS occurring in those younger than 40 years. These variants of high-grade osteosarcoma are often characterized histopathologically by the production of an osteoid matrix and bone from malignant osteoblasts that by definition are present in the soft tissue outside the normal skeletal anatomy. We present a 13-year-old girl with a gradually enlarging, painless left thigh mass. (orig.)

  3. Extraskeletal Osteosarcoma of Penis: A Case Report

    Institute of Scientific and Technical Information of China (English)

    Chuan-zhen Wu; Cheng-mei Li; Song Han; Shuang Wu

    2012-01-01

    Extraskeletal osteosarcoma (EOS) is rare and commonly arises in the retroperitoneum,limbs,head and neck.There is no significant difference between EOS and other malignant tumors in soft tissue.Localized pain and swelling are the common presenting symptoms.Clinical diagnosis of EOS is difficult,imaging techniques may be helpful and careful,and the histopathological analysis is necessary.The common histological variants of EOS include:osteoblastoma,chondroblastoma,and fibroblastoma,and other unusual subtypes were reported occasionally.It should be distinguished with myositis ossificans,malignant mesenchymoma,giant cell tumor and parosteal osteosarcoma.We present an EOS arising in the penis.The primary site and histological category of the tumor were extremely rare.We hope the case will be helpful to the recognition of clinical signs,iconography and histopathology of EOS.

  4. Extraskeletal Osteosarcoma: A case report and review of the literature

    Science.gov (United States)

    Hoch, Michael; Ali, Sayed; Agrawal, Shefali; Wang, Congli; Khurana, Jasvir S.

    2013-01-01

    We report an instructive case of extraskeletal osteosarcoma in a 63-year-old African American male who presented after an episode of recent trauma, with clinical and radiological features characteristic of this neoplasm. Osteosarcoma is the most common primary malignant tumor of bone in young adults, but the extraskeletal variety is very uncommon. The radiological and pathological features of this neoplasm will be discussed, along with a review of the literature. PMID:24421944

  5. Extraskeletal osteosarcoma of the thorax in a goat: case report.

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    Braun, Ueli; Schwarzwald, Colin C; Forster, Eva; Becker-Birck, Mareike; Borel, Nicole; Ohlerth, Stefanie

    2011-09-19

    This report describes the results of clinical, ultrasonographic and computed tomographic examination of a 16-year-old goat with extraskeletal osteosarcoma of the thorax. The lead clinical signs were abnormal condition and demeanour, fever, tachycardia, tachypnoea, dyspnoea and dilated jugular veins. Ultrasonographic examination of the thorax revealed a precardial mass, measuring 16.4 by 11.4 by 14.2 cm. Computed tomographic examination showed dorsocaudal displacement of the trachea, heart and lungs to the right. A tentative diagnosis of mediastinal or pleural neoplasia was made, and the goat was euthanased and necropsied. A definitive diagnosis was based on histological examination of the mass. To our knowledge, this case report is the first description of extraskeletal osteosarcoma of the thorax in goats and serves to broaden the diagnostic spectrum of thoracic diseases in this species. Extraskeletal osteosarcoma should be part of the differential diagnosis in goats with thoracic tumours.

  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. Extraskeletal Osteosarcoma: Analysis of Outcome of a Rare Neoplasm

    Directory of Open Access Journals (Sweden)

    Martin D. McCarter

    2000-01-01

    Full Text Available Purpose. Extraskeletal osteosarcoma represents an unusual soft-tissue sarcoma that historically is reported to carry an exceptionally poor prognosis.The objectives of this study were to use a prospectively gathered sarcoma database to test the prevailing clinical bias and more accurately describe the natural history, characterize the prognostic features, estimate survival and evaluate treatment strategies for this unusual sarcoma.

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

    Directory of Open Access Journals (Sweden)

    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. Dedifferentiated parosteal osteosarcoma with well-differentiated metastases

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    Takeuchi, Katsuhito; Morii, Takeshi; Yabe, Hiroo; Morioka, Hideo; Toyama, Yoshiaki [Keio University, School of Medicine, Department of Orthopaedic Surgery, Shinjuku-ku, Tokyo (Japan); Mukai, Makio [Keio University, School of Medicine, Division of Diagnostic Pathology, Shinjuku-ku, Tokyo (Japan)

    2006-10-15

    Metastases of dedifferentiated sarcoma usually contain a dedifferentiated component. We report a rare case of dedifferentiated parosteal osteosarcoma (dd-POS) with well-differentiated multiple metastases in a 65-year-old woman with a painful firm mass on her thigh. Radiological examination revealed that the mass arose from the surface of her femur without medullary involvement. Multiple intramuscular metastases were detected in her lower leg on MR imaging. Small subcutaneous palpable masses were identified on her left lower leg, buttock, chest wall and head. An open biopsy and above-the-knee amputation were performed, and the mass on her femur was diagnosed as a dd-POS. However, histological examination on the subcutaneous lesions in her lower leg, buttock and head showed low-grade conventional POS without dedifferentiated components. To the best of our knowledge, this is the first report of a dd-POS with multiple metastases that do not contain any dedifferentiated components. (orig.)

  11. Osteosarcoma of breast: A rare case of extraskeletal osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ashwin A Kallianpur

    2013-01-01

    Full Text Available Primary osteogenic sarcomas of the breast are exceptionally uncommon. We describe such a case occurring in a 50 year-old woman who presented with a large painful mass in her left breast. Simple mastectomy of the left breast was performed. Microscopical and immunohistochemical findings established the diagnosis of primary osteogenic sarcoma. Similar to extremity osteosarcoma, adjuvant adriamycin and cisplatin based chemotherapy and external beam radiotherapy was given to the present case. She remained well 57 months later, without tumor recurrence. The current article made a literature search proving the rarity of this lesion type and discusses in detail the diagnostic implications and the treatment of this rare site tumor entity.

  12. Radiation-Associated Low-Grade Extraskeletal Osteosarcoma of the Neck Following Treatment for Thyroid Cancer.

    Science.gov (United States)

    Jones, Martin; Chebib, Ivan; Deshpande, Vikram; Nielsen, G Petur

    2015-08-01

    Low-grade extraskeletal osteosarcoma is a rare tumor that may arise de novo or following radiation therapy. Because of the low-grade histology, it may be misdiagnosed as a benign lesion. We present a case of a 59-year-old man with a past history of radiotherapy for papillary carcinoma of the thyroid, presenting 16 years later with a low-grade extraskeletal osteosarcoma of the neck. The patient was treated with surgical excision and is disease free after 12 months of follow-up. The prognosis for patients with low-grade extraskeletal osteosarcoma is relatively good when compared with high-grade sarcomas. While there is a report of a low-grade extraskeletal osteosarcoma arising following radiotherapy for a benign condition, to the best of our knowledge this is the first reported case of a low-grade extraskeletal osteosarcoma occurring following radiotherapy for thyroid cancer, and the only case reported in the soft tissue of the head and neck region. © The Author(s) 2015.

  13. Treatment of extraskeletal osteosarcoma at a previous injection site resulting in prolonged survival in 1 dog.

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    Selmic, Laura E; Griffin, Lynn R; Rector, Megan H; Lafferty, Mary; Pool, Roy; Ehrhart, Nicole P

    2016-09-01

    A rare presentation of an extraskeletal osteosarcoma at a previous interscapular injection site in a dog is described. Treatment included surgical excision of the tumor followed by 6 rounds of intravenous carboplatin, oral toceranib, and cyclophosphamide. The dog survived for 20.5 months after diagnosis despite early development of pulmonary metastases.

  14. Primary extraskeletal osteosarcoma: a clinicopathological study of 18 cases focusing on MDM2 amplification status.

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    Yamashita, Kyoko; Kohashi, Kenichi; Yamada, Yuichi; Nishida, Yoshihiro; Urakawa, Hiroshi; Oda, Yoshinao; Toyokuni, Shinya

    2017-05-01

    Extraskeletal osteosarcoma (ESOS) is an uncommon malignant neoplasm. Most ESOSs are high grade, although some low-grade cases have been reported. A few cases of ESOS with MDM2 amplification have also been reported, suggesting some similarity to skeletal low-grade osteosarcoma such as parosteal osteosarcoma, where MDM2 is often amplified. However, the frequency of low-grade cases and cases with MDM2 amplification among ESOSs remains unknown, and their relationship is unclear. To clarify this, we examined 18 primary ESOS cases clinically, pathologically, and genetically, focusing on their MDM2 amplification status. Our cases comprised 10 men and 8 women whose mean age was 58.6 years; the most common site of the lesion was the thigh and buttock. There were one histologically low-grade case evaluated by biopsy specimen with an aggressive course and 2 relatively low-grade cases whose lesions were of low grade for the most part. MDM2 amplification status was revealed by fluorescence in situ hybridization in all 18 cases; 2 patients-histologically intermediate- and high-grade cases-were found to have MDM2 amplification. In conclusion, this study indicates that histologically low-grade and relatively low-grade cases of ESOS are not always associated with MDM2 amplification. The ESOS case with MDM2 amplification could be high grade, although MDM2-amplified dedifferentiated liposarcoma with osteogenic differentiation should be ruled out in making the diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 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]. E-mail: flaviomanzi@hotmail.com; 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)

  16. Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients.

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    Longhi, A; Bielack, S S; Grimer, R; Whelan, J; Windhager, R; Leithner, A; Gronchi, A; Biau, D; Jutte, P; Krieg, A H; Klenke, F M; Grignani, G; Donati, D M; Capanna, R; Casanova, J; Gerrand, C; Bisogno, G; Hecker-Nolting, S; De Lisa, M; D'Ambrosio, L; Willegger, M; Scoccianti, G; Ferrari, S

    2017-03-01

    Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis. Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS. Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis. At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival. Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Extraskeletal osteosarcoma in Norway, between 1975 and 2009, and a brief review of the literature.

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    Berner, Kjetil; Bjerkehagen, Bodil; Bruland, Øyvind S; Berner, Aasmund

    2015-04-01

    To evaluate the clinicopathological features of extraskeletal osteosarcoma (ESOS) and its response to multimodal therapy. A nationwide cohort comprising all Norwegian histologically verified ESOS patients between 1975 and 2009 supplemented with clinical reports from all hospitals involved in sarcoma management. Thirty-seven patients were classified as ESOS, mostly elderly people. Seventy-six % had an axial tumour, including nine patients with radiation-induced ESOS. The gender balance was equal. The 5-year sarcoma-specific survival (SSS) was 16 %. Adequate surgical remission had a positive impact on SSS, in contrast to chemotherapy and radiotherapy. Primary metastatic disease, elevated tumour size and elevated serum alkaline phosphatase, serum lactate dehydrogenase and Ki67, respectively, all predicted poor outcome. The relatively poor prognosis of ESOS may relate to both primary chemotherapy resistance and different biologic characteristics of these tumours as compared to conventional osteosarcoma. Hence, new predictive molecular markers and therapeutic approaches for treatment of ESOS are needed. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. 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.

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

  20. Osteosarcoma

    National Research Council Canada - National Science Library

    Ritter, J; Bielack, S S

    2010-01-01

    The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical oncologists, surgeons, pathologists and radiologists...

  1. Malignant chondroblastoma of extraskeletal origin.

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    Duttaluri, Ramu; Sultanpurkar, Guru Prasad; Raorane, Harshvardhan; Vikram, Harsha

    2016-01-01

    Chondroblastoma is a rare benign neoplasm of cartilaginous origin. It typically arises in the epiphysis of a long bone. They occur mostly in the second decade of life and is more common in males. Extraskeletal origin of chondroblastoma is a rarity and virulent behavior by its local aggressive nature or metastasis is reported in very few cases. We hereby, present a case of chondroblastoma in the left popliteal fossa first of its kind in a 62-year-old female, primary tumor extraskeletal in origin which turned locally aggressive and eventually metastasized to lungs. The patient is now on palliative therapy.

  2. 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.)

  3. A Rare Case of Primary osteosarcoma of urinary bladder

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    Jagdeesh Kenthanahalli Siddappa

    2012-01-01

    Full Text Available Extraskeletal osteosarcoma is a malignant mesenchymal soft tissue tumor without attachment to the bone, and is able to produce osteoid or cartilaginous matrix. This entity accounts for 1% of all soft tissue sarcomas. Thus far, less than 35 cases of bladder osteosarcomas have been reported in the literature. These tumors are associated with very poor prognosis. We report a case of primary osteosarcoma of the urinary bladder presenting with intermittent hematuria, dysuria, and right flank pain. Contrast-enhanced computed tomography scan of the abdomen, pelvis, and chest revealed a bladder mass and pulmonary metastases with specks of calcification.

  4. 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

  5. Extraskeletal myxoid chondrosarcoma of the orbit

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    Abdullah M Al-Osaily

    2016-01-01

    Full Text Available Extraskeletal myxoid chondrosarcoma (EMC is a rare soft tissue tumor. Numerous cases of EMC have been reported in different anatomical locations. There is currently only a single case of EMC of the orbit and that was reported in 1985. We report a second case of orbital EMC in a 34-year-old healthy male.

  6. Extraskeletal chondroma casuing carpal tunnel syndrome: A case report

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    Kim, Ok Hwa; Kim, Yeon Hee [Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2014-03-15

    Carpal tunnel syndrome caused by extraskeletal chondroma has been scarcely reported in the literature. Authors report a case of carpal tunnel syndrome as a result of an extraskeletal chondroma arising within the carpal tunnel, and describe the radiological and pathological findings of the mass. We also discuss the differential diagnosis of the calcified space, occupying lesions that may occur in carpal tunnel.

  7. Well-differentiated liposarcoma of esophagus

    Institute of Scientific and Technical Information of China (English)

    YANG Bin; SHI Pei-zhi; LI Xiao; XU Ru-jun

    2006-01-01

    @@ Gastrointestinal liposarcoma is rare, and the esophagus is the. least common location at which this kind of liposarcoma may occur. We reported a patient with a well-differentiated liposarcoma of esophagus, and discussed the diagnostic utility of these imaging techniques in patient management.

  8. 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.)

  9. Recurrent well-differentiated thyroid carcinoma.

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    Magarey, Matthew J R; Freeman, Jeremy L

    2013-07-01

    The incidence of Well-differentiated Thyroid Carcinoma (WDTC) has been increasing over the past several decades. Consequently, so has the incidence of recurrence, which ranges from 15% to 30%. Factors leading to increased risk of recurrence are well described. However, the impact of local and regional recurrence is not well understood, but distant recurrence dramatically reduces 10-year survival to 50%. Recurrent WDTC has several established options for treatment; Observation, Radioactive Iodine (RAI), Surgery and External Beam Radiotherapy (EBRT). Novel treatments such as radiofrequency ablation (RFA) and percutaneous ultrasound-guided ethanol injection (PUEI) are beginning to gain popularity and have promising early results. A review of the current literature, outcome measurements and a strategy for revision surgery within the central neck compartment are discussed within this manuscript.

  10. Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib

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    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.

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

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    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.

  12. Parosteal osteosarcoma.

    Science.gov (United States)

    Hang, Jen-Fan; Chen, Paul Chih-Hsueh

    2014-05-01

    Parosteal osteosarcoma is a rare malignant bone tumor arising from the bone cortical surface. It most commonly occurs in young women over the metaphyseal region, especially the long bones near the knee joint. Patients usually report a slow-growing mass for years. The tumor is characterized by its bland microscopic morphology, prone to be misdiagnosed as other benign tumors. In the absence of dedifferentiation, the prognosis is generally better than that of conventional osteosarcoma. Recent studies demonstrated distinctive cytogenetic abnormality resulting in amplification of the CDK4 and MDM2 genes, which may serve as markers for molecular diagnosis. In this article, we review the clinical, radiologic, and pathologic features of parosteal osteosarcoma and identify some diagnostic pitfalls, discuss the prognostic variables, and update recent molecular advances and their application in the diagnosis.

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

    Science.gov (United States)

    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.

  14. 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.

  15. 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.

  16. Parosteal osteosarcoma dedifferentiating into telangiectatic osteosarcoma: importance of lytic changes and fluid cavities at imaging

    Energy Technology Data Exchange (ETDEWEB)

    Azura, M. [Istituto Ortopedico Rizzoli, Musculoskeletal Oncological Surgery Department, Bologna (Italy); University of Malaya, Department of Orthopaedic Surgery, Kuala Lumpur (Malaysia); Vanel, D. [Radiology, Istituto Ortopedico Rizzoli, Bologna (Italy); Istituti Rizzoli, Anatomia Patologica, Bologna (Italy); Alberghini, M. [Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Picci, P.; Staals, E.; Mercuri, M. [Istituto Ortopedico Rizzoli, Musculoskeletal Oncological Surgery Department, Bologna (Italy)

    2009-07-15

    This study was performed to assess the imaging findings in cases of parosteal osteosarcoma dedifferentiated into telangiectatic osteosarcoma. Parosteal osteosarcoma is a low-grade well-differentiated malignant tumor. Dedifferentiation into a more aggressive lesion is frequent and usually visible on imaging as a central lytic area in a sclerotic mass. Only one case of differentiation into a telangiectatic osteosarcoma has been reported. As it has practical consequences, with a need for aggressive chemotherapy, we looked for this rather typical imaging pattern. Review of 199 cases of surface osteosarcomas (including 86 parosteal, of which 23 were dedifferentiated) revealed lesions suggesting a possible telangiectatic osteosarcoma on imaging examinations in five cases (cavities with fluid). Histology confirmed three cases (the two other only had hematoma inside a dedifferentiated tumor). There were three males, aged 24, 28, and 32. They had radiographs and CT, and two an MR examination. Lesions involved the distal femur, proximal tibia, and proximal humerus. The parosteal osteosarcoma was a sclerotic, regular mass, attached to the cortex. A purely lytic mass, partially composed of fluid cavities was easily detected on CT and MR. It involved the medullary cavity twice, and remained outside the bone once. Histology confirmed the two components in each case. Two patients died of pulmonary metastases and one is alive. Knowledge of this highly suggestive pattern should help guide the initial biopsy to diagnose the two components of the tumor, and guide aggressive treatment. (orig.)

  17. Giant cell-rich osteosarcoma of the parotid gland: An exceptionally rare entity at an unusual site.

    Science.gov (United States)

    Huang, Eric C; Ghazikhanian, Varand; Qian, Xiaohua

    2016-12-01

    Giant cell-rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell-rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62-year-old male who presented with initial right jaw swelling. Radiologic work-up revealed a 6.2 cm mass involving the right parotid gland. Fine-needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell-rich osteosarcoma. Diagn. Cytopathol. 2016;44:1107-1111. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Extraskeletal Chondroma of the Index Finger: A Case Report

    Directory of Open Access Journals (Sweden)

    Masato Saito

    2017-06-01

    Full Text Available Extraskeletal chondroma is defined as a rare, benign, cartilaginous tumor arising from soft tissues such as tendons, tendon sheath synovia, and joint capsules with no continuity to the periosteum or bone cortex. In histopathologic findings, the tumor exhibits many lobular structures and some parts similar to hyaline cartilage. Therefore, it is sometimes difficult to differentiate this tumor from low-grade chondrosarcoma because of their similar histopathologic findings. In order to prevent recurrence, it is necessary to remove the tumor as a whole, including the capsule, so as not to leave any remnants of the tumor. In this article, we report our treatment experience with a case of extraskeletal chondroma in the index finger of a 63-year-old patient.

  19. Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases

    Directory of Open Access Journals (Sweden)

    Kapoor Neena

    2014-09-01

    Full Text Available Background. The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC including initial presentation, recurrence, and metastases.

  20. 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.

  1. Radioiodine therapy in skeletal metastases from well-differentiated ...

    African Journals Online (AJOL)

    with skeletal metastases from well-differentiated thyroid carcinoma ... pathology reports from resected tumours, 9 were papillary and 15 were follicular cancers. ... The diagnosis of thyroid cancer was based on lobectomy in a single subject.

  2. Vitamin D and extra-skeletal health: causality or consequence.

    Science.gov (United States)

    Al Nozha, Omar M

    2016-07-01

    Vitamin D deficiency /insufficiency is widely recognized as a global health problem that is likely to be involved in pathogenesis or progression of many acute and chronic health disorders. Its relation to skeletal health has been clearly demonstrated and thoroughly examined. This review aims to highlight the continuous debate about the relation between vitamin D and extra-skeletal health and whether it is a causality or just an association. Overall, the available evidence does not meet the criteria for establishing cause-and-effect relationships because of the limitations of observational studies to corroborate the causality due to many potential confounders. Moreover, the causal relationship couldn't be established in randomized studies or in many meta-analyses. This may reflect the fact that vitamin D level reduction is just a biomarker of ill health. The inflammatory processes involved in the disease occurrence and the functional limitations of the diseases would have a role in reducing serum 25-hydroxy vitamin D "25 (OH) D" level, which would explain why low vitamin D is reported in a wide range of disorders. This may underscore the possibility of harm instead of benefit of vitamin D supplementation when its exact role is not fully established, thus many guidelines and interest groups are still hesitant toward recommending replacement in extra-skeletal disease. Future directions entails the need for a large well-designed randomized control trials (RCTs) to resolve the active debate on the benefits of vitamin D replacement for extra-skeletal disease, and not only that, future studies should establish specific, clinically relevant effects of vitamin D repletion, provide cut-values for optimal serum levels of 25 (OH) D, and appropriate doses for non-skeletal health benefits.

  3. 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.

  4. 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 culture

  5. 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

  6. [Outcome of "well-differentiated jargon" and related lesions].

    Science.gov (United States)

    Nagai, Chiyoko; Takeda, Takahiro; Yoshizawa, Hiroshi; Iwata, Makoto

    2005-06-01

    We introduce "well-differentiated jargon" as a new type of jargon with two relevant cases. To give a simple and clear framework to a classification of jargon, we define three types of jargon as follows: Under the condition that utterance does not decrease remarkably, (1) If approximately 90% of whole utterance consists of real words and clear syntactic structure though incomprehensible, it is "well-differentiated jargon". (2) If approximately 90% of whole utterance consists of unclear phonemes or phonemes that are not able to divide into words, it is "undifferentiated jargon". (3) If in-comprehensible utterance does not belong to any type of jargon above, it is "moderately-differentiated jargon". In this line of definition, "well-differentiated jargon" is the most highly differentiated jargon. The following cases are the examples of "well-differentiated jargon": Case 1 was a 67-year-old woman with head injury of the left orbital cortex, prefrontal cortex, and temporal pole; Case 2 was a 64-year-old man with brain atrophy in bilateral frontal cortex and bilateral (right dominant) anteroinferior temporal cortex after meningoencephalitis. Within six months after onset, they showed characteristic verbal aspects as follows; transcortical sensory aphasia; utterance with a lot of perseverative error, irrelevant words, unnecessary qualifiers during the naming task; well-preserved syntactic structure in a sentence with a few neologism. One year after the first verbal assessment, the performance of Case 1 improved almost entirely, whereas characteristic utterance was still observed in Case 2. These results suggest that "well-differentiated jargon" can be caused by lesions in anteroinferior temporal cortex and prefrontal cortex with preserved language area, where involve more anterior region than that of classical jargon. These two cases cannot belong to any classical jargon, and then we insist the adoption of new type of jargon, "well-differentiated jargon".

  7. [Clinicopathologic features of primary osteosarcoma in elderly patients].

    Science.gov (United States)

    Ding, Yi; Niu, Xiao-hui; Ding, Yi; Meng, Shu-qin; Liu, Bao-yue; Yang, Fa-jun; Huang, Xia; Huang, Xiao-yuan

    2011-06-01

    To study the clinical manifestations, radiologic findings, pathologic diagnosis and differential diagnosis of primary osteosarcoma in elderly patients. Twelve cases of primary osteosarcoma occurring in patients older than 60 years were encountered during the period from 1985 to 2010. The clinical manifestations, radiologic features and pathologic findings were studied and the follow-up data were analyzed. The sites of involvement included long bones (number = 7), ilium (number = 1), craniofacial bones (number = 2) and soft tissue (number = 2). Radiologic examination showed a mixture of osteosclerotic and osteolytic lesions in 10 patients, soft tissue lesions with high-density areas in 2 patients and soft tissue lesions with periosteal reaction in 8 patients. Histologically, most cases showed features of conventional osteosarcoma. There were 2 cases of malignant fibrous histiocytoma-like osteosarcoma, 2 cases of chondroblastic osteosarcoma and 1 case of well-differentiated intraosseous osteosarcoma. Immunohistochemical study played little role in pathologic diagnosis. Ten patients had undergone amputation, including one patient who had received adjuvant chemotherapy beforehand. Nine patients had follow-up information available. Three of them died of lung metastasis and 1 died of cardiovascular disease. Primary osteosarcoma rarely occurs in elderly patients and can easily be missed. Correlation with clinical, radiologic and histologic features is important for arriving at a correct diagnosis.

  8. Osteosarcoma; clinical aspects and significance of conventional radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Jin Suck; Kim, Eung Jo; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1988-12-15

    The clinical features of 141 patients with osteosarcoma were analysed and conventional radiographs of 92 patients out of 141 patients were reviewed retrospectively in order to assess the distribution of the age, sex, locations and to evaluate the predominant radiographic features. The incidence of tumors occurring in the extremities is 90 percent of total 141 patients. The majority of tumors were located in the metaphases of the long tubular bones. About sixty percent of the patients were in the second decade of life. The increment of the level of serum alkaline phosphatase was observed in 76 (67%) out of 114 patients. It is considered that thoracic CT scan might be helpful for the evaluation of metastases to lungs, because the detection rate of lung metastasis was 20 percent among 30 cases by CT, being disclosed higher than by conventional radiographs. Of the 92 patients available for radiographic analysis, predominantly osteolytic lesions were disclosed in 17 cases (19%). Preoperative radiographic impression was not the osteosarcoma in 8 out of 17 patients with purely osteolytic osteosarcoma. It was meant that the radiographic diagnosis was difficult in each case of predominantly osteolytic lesions. The patterns of periosteal reaction were variable, and there was no evidence of periosteal reaction in seventeen patients (18%). Both the cortical destruction and, the intralesional calcification were observed in 85 percent of 92 patients with osteosarcoma. Extraskeletal tumor shadow was observed in 79 percent of 92 patients with osteosarcoma, but either the calcification of ossification was detected in only 55 patients among 73 patients with soft tissue tumor shadows. Only 7 patients had a pathologic fracture, all in the femur.

  9. "Intercellular bridges" in a case of well differentiated squamous carcinoma.

    Science.gov (United States)

    Nguyen, Michaela; Mikita, Geoffrey; Hoda, Rana S

    2016-02-01

    Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node.

  10. Osteosarcoma of maxilla

    Directory of Open Access Journals (Sweden)

    N M Praveena

    2012-01-01

    Full Text Available Osteosarcoma is the primary malignancy of bone. Osteosarcoma of the jaw (JOS is very rarely encountered in the oral cavity compared to osteosarcomas of long bones. Therefore, general dentist should be aware of the initial clinical and radiographic findings. The chief complaint of patients with long bone osteosarcoma is pain, whereas patients with JOS usually have painless swelling as the first sign. Lack of pain may result in delay of diagnosis. This paper documents one such case of 40-year-old female with an expansile lesion of maxilla, which was completely asymptomatic and later diagnosed as osteosarcoma.

  11. Telangiectatic osteosarcoma.

    Science.gov (United States)

    Colomina, Jordi; Peiro, Ana; Trullols, Laura; Garcia, Isidre

    2013-04-01

    To review records of 8 patients with telangiectatic osteosarcoma (TOS) and determine whether pathologic fractures correlate with recurrence and survival. Records of 4 men and 4 women aged 17 to 44 (mean, 28) years treated for TOS were reviewed. RESULTS; Of the 8 patients, 4 developed a pathologic fracture and 4 did not. In each group, 2 patients underwent limb salvage surgery and 2 underwent amputation. All patients received neoadjuvant and adjuvant chemotherapy with a combination of at least 2 of the following drugs: doxorubicin, methotrexate, cisplatin, and vincristin. After a mean follow-up of 5.6 (range, 2-16) years, all 4 patients with a pathologic fracture and 2 of the 4 patients without a pathologic fracture were still alive and disease-free. For the remaining patients, one died after 31 months from progression of a lung metastasis, and the other was alive with the disease and had had 2 recurrences, a lung metastasis, and an infection with Klebsiella oxytoca that eventually led to an amputation. The presence of a pathologic fracture in patients with TOS was not associated with worse outcome in terms of recurrence and survival.

  12. Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying Wu; Zhong-wu Li; Ji-you Li

    2009-01-01

    Objective: To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance.Methods: Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte(Hep) and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin.Results: Of 64 cases, 33(51.6%) were intestinal type, 3(4.7%) were gastric type, 25(39.1%) were gastrointestinal type and 3(4.7%) were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors (invasion or metastasis). The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes

  13. Osteosarcoma associated with hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Jutte, Paul C. [Istituti Orthopedici Rizzoli, Via Pupilli 1, 40136, Bologna (Italy); University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen (Netherlands); Rosso, Renato [Anatomia Patologica Universita di Pavia, via Forlanini 16, 27100, Pavia (Italy); Paolis, Massimiliano de; Errani, Costatino; Pasini, Elisabetta; Campanacci, Laura; Bacci, Gaetano; Bertoni, Franco; Mercuri, Mario [Istituti Orthopedici Rizzoli, Via Pupilli 1, 40136, Bologna (Italy)

    2004-08-01

    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.)

  14. Postradiation multicentric osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Tillotson, C.; Rosenberg, A.; Gebhardt, M.; Rosenthal, D.I.

    1988-07-01

    The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.

  15. Postradiation multicentric osteosarcoma.

    Science.gov (United States)

    Tillotson, C; Rosenberg, A; Gebhardt, M; Rosenthal, D I

    1988-07-01

    The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.

  16. Osteosarcoma of jaw bone

    Directory of Open Access Journals (Sweden)

    Avani Gandhi Dixit

    2008-01-01

    Full Text Available Osteosarcoma is the most common primary malignant bone tumor in children. Its radiolographic appearances vary considerably. It may show a number of presentations from onion skin or sunburst appearance. Osteosarcoma of maxilla and mandible are distinct from long bone osteosarcoma and shows a distinct clinical, histologic and prognostic characteristic that when diagnosed and treated properly have a better prognosis from the later. The present article reports a case of osteogenic sarcoma of maxillary alveolar ridge and compares it with long bones osteosarcomas.

  17. 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

    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 patie

  18. 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

    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 patie

  19. 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

  20. Extraskeletal myxoid chondrosarcoma metastatic to the pancreas: A case report

    Institute of Scientific and Technical Information of China (English)

    C Fotiadis; A Charalambopoulos; S Chatzikokolis; GC Zografos; M Genetzakis; R Tringidou

    2005-01-01

    Extraskeletal myxoid chondrosarcoma (EMC) is a lowgrade sarcoma characterized by developing metastases and local recurrence in high rate. It is mainly deep seated in the proximal extremities. The most common metastatic sites are the lungs, soft tissues, lymph nodes, bones and the brain. To our knowledge, no case of clearly defined EMC has been reported to date developing a metastasis in the pancreas. We describe a case of a man suffering from EMC who developed a single pancreatic metastasis 20 years after the initial diagnosis. A 49-year-old man was submitted to surgical excision of an EMC, in left thigh, 20 years ago. Fourteen years after the initial diagnosis a local recurrence in left thigh occurred. Multiple lesions of metastatic origin, in both lungs, were excised via thoracotomies until the time being. In 2003, as a part of a periodically performed imaging control, an abdominal CT scan was performed revealing a solid lesion in the pancreas. Distal pancreatectomy was performed. The histopathology of the excised specimen proved to be the one of metastatic lesion of EMC. The above-mentioned case of EMC is, as far as we know, the first one described developing a certain pancreatic metastasis.

  1. Ultrasonographic Evaluation of Osteosarcomas

    Institute of Scientific and Technical Information of China (English)

    KABG Bin; ZENG Hui; TANG Xinyu; XIONG Ao; MA Zetao; LIU Guoping

    2006-01-01

    The ultrasonographic appearances of osteosarcomas and the roles of ultrasonography in the diagnosis and surgical staging of osteosarcomas were investigated. A comparative study was performed on 45 cases of osteosarcomas by ultrasonography and radiography. Bony changes, periosteal reaction and soft tissue mass were evaluated for each lesion. The results showed that ultrasonography revealed a solid mass around bone in 42 patients, bone destruction in 24 patients and periosteal reaction in 16 patients. Plain radiographs showed bony changes in 44 patients and no bony change in remaining one patient, shadowing of soft tissue swelling in 30 patients, and pulmonary metastases in 3patients. Surgical biopsy and pathological examination confirmed osteosarcoma in all 45 patients.Soft tissue mass was confirmed in 42 patients surgically. The diagnostic accuracy of soft tissue masses by ultrasonography and radiography was 100 % (42/42) and 71.4 % (30/42), respectively. The positive rate of ultrasonography and radiography in displaying bony changes was 53.3 % (24/45) and 97.8 % (44/45), respectively. In conclusion, in the detection of soft tissue mass of osteosarcoma, ultrasonography is superior to radiography, and in displaying bony changes of osteosarcomas, radiography is superior to ultrasonography. So it may come to a conclusion that plain radiography combined with ultrasonography can completely display the bony and soft tissue lesion of osteosarcomas.

  2. Three Metachronous Osteosarcomas within 22 Years without Pulmonary Metastases: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ulrike Michaela Pirker-Frühauf

    2013-01-01

    Full Text Available Introduction. We present the extremely rare case of a patient with three metachronous osteosarcomas within 22 years without evident pulmonary manifestation of disease 30 years after first diagnosis. Case Presentation. In 1983, a high-grade osteosarcoma of the left distal femur was diagnosed in an 18-year-old Caucasian male. He received rotationplasty accompanied by pre- and postoperative chemotherapy. Ten years later, an osteoblastic osteosarcoma occurred in TH12. En bloc resection and pre- and postoperative chemotherapy followed. In 2005, the patient developed another high-grade osteosarcoma in his right distal femur. Treatment included a wide resection and reconstruction with a tumour endoprosthesis as well as (neoadjuvant chemotherapy. After the third tumour occurrence, cytogenetic and molecular genetic examinations (p53, rb1 were performed, showing a normal genetic pattern. Screening for metastases never showed clinical evidence of extraskeletal tumour manifestation. Discussion. In patients presenting metachronous osteosarcoma, identification of their lesions clonality (second primary tumour or metastases could lead to a better understanding of tumour development and help to filter patients who need extended long-term followup due to a higher risk of late occurring sarcoma recurrence.

  3. 髓内高分化骨肉瘤1例%A case of intraossous well-differentiated osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    邱乾德; 林达

    2008-01-01

    患者男性,25岁。左侧上臂中上段轻度肿胀4年,疼痛不明显。左侧上臂中上段软组织轻度肿胀,并扪及肿块,质硬,轻度压痛,局部温度无增高(图1)。手术后病理诊断为髓内高分化骨肉瘤。

  4. 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.

  5. Osteosarcoma in young children.

    Science.gov (United States)

    Kozakewich, H; Perez-Atayde, A R; Goorin, A M; Wilkinson, R H; Gebhardt, M C; Vawter, G F

    1991-02-01

    The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented. Only one of six children treated before 1972 is a long-term survivor. Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue. It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents. A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival.

  6. UNUSUAL PRESENTATION OF EXTRASKELETAL MESENCHYMAL CHONDROSARCOMA OF ABDOMEN IN 10 YR OLD GIRL- A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Ramani

    2013-01-01

    Full Text Available ABSTRACT: Mesenchymal chondrosarcoma (MSC is rare form of ch ondrosarcoma which usually arises in bone. Extraskeletal mesenchymal c hondrosarcomas are far less common and accounts approximately 30–50% of all mesenchymal chon drosarcomas. We report a rare case of intra-abdominal extraskeletal MSC in a 10 yr old gi rl who presented with biliary vomitings and abdominal pain. Ultrasound abdomen showed 42x24 mm h ypoechoic mass in right iliac fossa. CT abdomen showed calcified granulomas in spleen, Soft tissue dense lesion in right iliac fossa, suggestive of lymphadenopathy. Histopathology and immu nohistochemistry confirmed the diagnosis of MSC

  7. Tumoral calcinosis mimicking recurrent osteosarcoma

    National Research Council Canada - National Science Library

    Petscavage, Jonelle M; Richardson, Michael L

    2009-01-01

    We report a case of a tumoral calcinosis mimicking the appearance of recurrent osteosarcoma of the left femur and tibia in a 29-year-old woman with a history of osteosarcoma and chronic renal failure...

  8. 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

  9. 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

  10. Cabozantinib-s-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma

    Science.gov (United States)

    2017-09-04

    Metastatic Ewing Sarcoma; Metastatic Osteosarcoma; Recurrent Ewing Sarcoma; Recurrent Osteosarcoma; Stage III Osteosarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Unresectable Ewing Sarcoma; Unresectable Osteosarcoma

  11. Surface osteosarcomas: Diagnosis, treatment and outcome

    Directory of Open Access Journals (Sweden)

    Venkatesan Sampath Kumar

    2014-01-01

    Full Text Available Surface osteosarcomas are a rare form of osteosarcomas accounting for around 3-6% of all osteosarcomas. Three major groups of surface osteosarcomas are parosteal, periosteal and the high grade surface osteosarcomas. Of these, the parosteal osteosarcoma is the most common. Parosteal and periosteal osteosarcomas are distinct clinical entities and it is important to identify the clinicoradiological differences between the two types. Surface osteosarcomas occur at a later age as compared to conventional osteosarcomas. The classical site is the lower end of the femur followed by the upper end of the tibia and upper end of humerus, in that order. The periosteal variant affects the tibia more commonly than the parosteal variety. Neo-adjuvant chemotherapy is the standard of care for high grade surface osteosarcomas. Parosteal osteosarcomas, being low grade lesions, can be treated by upfront wide excision without adjuvant systemic therapy. Controversy prevails over the need for chemotherapy in periosteal osteosarcomas, which are intermediate grade lesions.

  12. Clinicopathological Features of Extraskeletal Myxoid Chondrosarcoma:An Analysis of 9 Cases

    Institute of Scientific and Technical Information of China (English)

    YE Xiu-feng; MI Can; LI Yu; LIU Qiong

    2008-01-01

    Objective:To investigate the Clinicopathological characteristics of extraskeletal myxoid chondrosarcoma(EMC).Methods:Nine cases of extraskeletal myxoid chondrosarcoma were studied.Extensive immunohistochemical analysis was performed in all the cases and ultrastructural studies were done in 2 extraskeletal myxoid chondrosarcomas.Follow-up information was available for seven patients.Results:There were 7 males and 2 females whose ages ranged from 31 to 69 years(median 52.78 years).Local pain or tenderness and the presence of a palpable mass were the main complaints of the patients.The tumors were located mainly in the lower extremities(66.7%).Most tumors were deep-seated.They usually had a distinct multinodular configuration delineated by fibrous connective tissue.The tumor cells were arranged in delicate intersecting strands,rings,and garlands for the most part.The myxoid matrix was abundant in most cases.Immunohistochemical analysis was performed in all the cases and ultrastructural studies were done in 2 extraskeletal myxoid chondrosarcomas.EMC expressed vimentin(100%,9/9),neuron-specific enolase(77.8%,7/9),S-100 protein(66.7%,6/9),synaptophysin and chromogranin A(22.2%,2/9).None of the tumors expressed EMA and desmin.Ultrastructurally:EMC was characterized by distinct cords of cells immersed in a glycosaminoglycan rich matrix.The cells were rich in mitochondria,had well-developed Golgi apparatus and there were numerous smooth vesicles.In many cells,there were also prominent glycogen deposits and lipid droplets.Some tumor cells had intracisternal microtubules.In one of the 2 extraskeletal myxoid chondrosarcomas there were 140-180 nm diameter membrane-bound dense-core secretory granules in cell bodies.Conclusion:Extraskeletal myxoid chondrosarcoma(EMC)is a rare soft tissue sarcoma characterized by distinctive morphological and cytogenetical features.However,the chondroid nature has been a subject of controversy,and its line of differentiation remains to be

  13. Primary osteosarcoma of breast

    Science.gov (United States)

    Gull, Sadaf; Patil, Prashant; Spence, Roy AJ

    2011-01-01

    Primary osteosarcoma of breast is rare. The authors present a case of a 51-year-old female who was admitted with a large necrotising tumour involving the right breast. CT scan confirmed chest wall invasion along with a solitary lung metastasis. She underwent a primary mastectomy with chest wall reconstruction. Unfortunately 3 months later she developed local recurrence. PMID:22688473

  14. 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.

  15. A large extraskeletal chondroma in the hand of an elderly patient--a case report.

    Science.gov (United States)

    Ikeda, Kazuo; Osamura, Naoki; Kasashima, Satomi

    2013-01-01

    This paper examines a case of extraskeletal chondroma in the hand of an 82-year-old female, first noticed about two years ago. Magnetic resonance imaging showed a mass in the carpal tunnel which extended from the wrist to the palm. The tumor was located between the thenar area and the hypothenar area at the palm level. There was no continuity to the carpal bone or radius bone. The entire size of the tumor was 120 mm × 45 mm × 42 mm. Although extraskeletal chondroma is sometimes seen, a large one in the hand is extremely rare. Since the tumor was too large to excise totally because median nerve entrapped it, it was divided into two parts and excised. After the operation, there was no neurological deficit or pain in the median nerve lesion.

  16. Cancer Stem Cells in Osteosarcoma

    OpenAIRE

    Heymann, D; Brown, H K; Tellez-Gabriel, M.

    2017-01-01

    Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and...

  17. The Genetics of Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Jeff W. Martin

    2012-01-01

    Full Text Available Osteosarcoma is a primary bone malignancy with a particularly high incidence rate in children and adolescents relative to other age groups. The etiology of this often aggressive cancer is currently unknown, because complicated structural and numeric genomic rearrangements in cancer cells preclude understanding of tumour development. In addition, few consistent genetic changes that may indicate effective molecular therapeutic targets have been reported. However, high-resolution techniques continue to improve knowledge of distinct areas of the genome that are more commonly associated with osteosarcomas. Copy number gains at chromosomes 1p, 1q, 6p, 8q, and 17p as well as copy number losses at chromosomes 3q, 6q, 9, 10, 13, 17p, and 18q have been detected by numerous groups, but definitive oncogenes or tumour suppressor genes remain elusive with respect to many loci. In this paper, we examine studies of the genetics of osteosarcoma to comprehensively describe the heterogeneity and complexity of this cancer.

  18. Fibroblastic osteosarcoma of the mandible

    Energy Technology Data Exchange (ETDEWEB)

    Daffner, Richard H. [Department of Diagnostic Radiology, Allegheny General Hospital, Pittsburgh, PA (United States); Fox, Karl R. [Department of Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA (United States); Galey, Kent R. [Department of Surgery, Division of Oral and Maxillofacial Surgery, Allegheny General Hospital, Pittsburgh, PA (United States)

    2002-02-01

    Osteosarcoma of the mandible is a rare lesion. We report the case of a 16-year-old male who developed a fibroblastic osteosarcoma at the site of a wisdom tooth extraction. The lesion followed an aggressive course of recurrence and diffuse disseminated osteosarcomatosis. We speculate on the causal factors that resulted in this rapid course. (orig.)

  19. 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.)

  20. Cancer stem cells in osteosarcoma.

    Science.gov (United States)

    Brown, Hannah K; Tellez-Gabriel, Marta; Heymann, Dominique

    2017-02-01

    Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and in some cases metastasis. Recent published work demonstrates evidence of cancer stem cell phenotypes in osteosarcoma with links to drug resistance and tumorigenesis. In this review we will discuss the commonly used isolation techniques for cancer stem cells in osteosarcoma as well as the identified biochemical and molecular markers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. 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.

  2. Radiofrequency Ablation to Treat Loco-Regional Recurrence of Well-Differentiated Thyroid Carcinoma

    OpenAIRE

    Lee, Sun Jin; Jung, So Lyung; Kim, Bum Soo; Ahn, Kook Jin; Choi, Hyun Seok; Lim, Dong Jun; Kim, Min Hee; Bae, Ja Seong; Kim, Min Sik; Jung, Chan Kwon; Chong, Se Min

    2014-01-01

    Objective To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Materials and Methods Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo ...

  3. Breast metastasis in osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Roebuck, D.J.; Sato, J.K.; Fahmy, J. [Children`s Hospital, Los Angeles, California (United States). Department of Radiology

    1999-02-01

    A young girl with a history of chondroblastic osteosarcoma of the tibia developed a pulmonary metastasis which was treated by metastasectomy, chemotherapy and lung irradiation. Three years later, at the age of 15, she developed a breast mass which was excised and which proved to be a poorly differentiated sarcoma. This was almost certainly a metastasis rather than a radiation-induced second primary tumour, in view of the short interval since radiotherapy. The ultrasonographic features of this lesion are presented here and the differential diagnosis is discussed in this context. Copyright (1999) Blackwell Science Pty Ltd 12 refs., 3 figs.

  4. Extraskeletal effects of vitamin D: potential impact on WV disease morbidity and mortality.

    Science.gov (United States)

    Shuler, Franklin D; Lycans, Dana; Salloum, Elias

    2012-01-01

    Vitamin D is an essential nutrient and a secosteroid hormone that regulates many physiologic processes beyond calcium and bone homeostasis. These "extraskeletal" effects are impacted by the circulating levels of the storage form of vitamin D, 25-hydroxyvitamin D3. Levels of vitamin D can be detected after completing a simple 25(OH)D blood test. Vitamin D deficiency (diabetes mellitus, obesity, cardiovascular disease, hypertension, stroke, and asthma. This article explores the association between vitamin D deficiency and the burden of chronic diseases in West Virginia.

  5. Osteosarcoma relapse as pleural metastasis

    OpenAIRE

    Debabrata Saha; Kaushik Saha; Arpita Banerjee; Debraj Jash

    2013-01-01

    Osteosarcoma is the most common primary bone tumor in children and young adults arising from primitive mesenchymal bone-forming cells. The lung is the most common site of metastasis of osteosarcoma. Here, we report a case of a 14-year-old male patient having osteosarcoma of tibia presenting to us for evaluation of left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast-enhanced computed tomography thorax revealed a large, heterogeneous, calcified mass (+277 H.U) at left up...

  6. Osteoblastic and fibroblastic multicentric osteosarcoma

    OpenAIRE

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

    2011-01-01

    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.

  7. Osteoblastic and fibroblastic multicentric osteosarcoma

    Science.gov (United States)

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

    2011-01-01

    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. PMID:22674697

  8. Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma.

    Science.gov (United States)

    Kim, Mi Hyun; Kim, Young Keum; Shin, Dong Hoon; Lee, Hyun Jeong; Shin, Nari; Kim, Arong; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang Hun; Sol, Mee Young

    2015-01-01

    The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Collins, Michael T; Singer, Frederick R; Eugster, Erica

    2012-05-24

    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.

  11. Primary dedifferentiated liposarcoma of the axilla arising in a mixed, well-differentiated and myxoid liposarcoma.

    Science.gov (United States)

    Campbell, Garth S; Lawrence, Thomas J; Porter, Scott E; Rezeanu, Luminita

    2012-01-01

    We describe a case of mixed liposarcoma of the axilla presenting as a high grade undifferentiated sarcoma with areas of well-differentiated and myxoid liposarcoma. MRI demonstrated a lobulated, septated intermuscular mass with marked heterogeneous gadolinium enhancement. A small focus of the tumor demonstrated fat suppressed signal more characteristic of well-differentiated liposarcoma. Pathologic analysis following wide local excision revealed a large, high grade sarcomatous component with highly pleomorphic cells with a thin rim of well-differentiated and myxoid liposarcoma on histologic examination. Dedifferentiated liposarcomas arising outside of the retroperitoneum are very rare, as are dedifferentiated liposarcomas arising from a histologically mixed liposarcoma. In this regard, this case illustrates an unusual combination of tumor location and histology which, to our knowledge, has not previously been reported.

  12. Primary renal osteosarcoma: A case report

    African Journals Online (AJOL)

    C. Ahomadégbé

    Pan African Urological Surgeons' Association. African Journal of ... features of a case of primary renal osteosarcoma in a 56-year-old man with stage IV disease. This is the ..... Osteosarcoma metastatic to the kidneys without lung involvement.

  13. 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.

  14. Osteosarcoma of the jaws: case report on synchronous multicentric osteosarcomas.

    Science.gov (United States)

    Jia, Shengnan; Li, Binbin

    2014-06-01

    Research has shown that osteosarcomas display high potential for metastasis to the lungs, pleurae and bones. Mandible, on the other hand, is an uncommon site for metastatic tumour cell colonization. Nevertheless, a metastatic tumour to mandible might be the first indication of an undiscovered malignancy at a distant site. This case report presents a case of a 61-year-old female patient. An osteosarcoma metastasized to her mandible shortly after the curettage of her jaw cyst. Both the metastatic osteosarcoma and the jaw cyst were confirmed by pathology. Initially, bilateral well-defined radiolucent lesions were shown in her panoramic X-ray image. Also, the diagnosis of a dentigerous cyst was made, based on histology. Two months later, a mixed radiolucent-radio opaque mass, which was confirmed as an osteosarcoma by pathology later, occupied the site of the previously enucleated dentigerous cyst, in her right mandible. Then, an identical osteosarcoma was found in the left pelvis on further doing overall radiological and pathological examinations. The pathologic hypotheses, treatment modality and follow-up of this case have also been presented.

  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...

  16. Osteosarcoma relapse as pleural metastasis

    Directory of Open Access Journals (Sweden)

    Debabrata Saha

    2013-01-01

    Full Text Available Osteosarcoma is the most common primary bone tumor in children and young adults arising from primitive mesenchymal bone-forming cells. The lung is the most common site of metastasis of osteosarcoma. Here, we report a case of a 14-year-old male patient having osteosarcoma of tibia presenting to us for evaluation of left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast-enhanced computed tomography thorax revealed a large, heterogeneous, calcified mass (+277 H.U at left upper and middle lobe along with massive left-sided pleural effusion. Thoracoscopy revealed a lung metastasis in the right upper and middle lobe along with 2-cm diameter mass found on the surface of parietal pleura. Lung tumor was resected and biopsy of the pleural mass was carried out. Histopathological examination from both the masses was suggestive of metastatic osteosarcoma. The case underlines the importance of performing thoracoscopy in patients of osteosarcoma who recur with lung metastasis.

  17. Osteosarcoma of pelvic bones: imaging features.

    Science.gov (United States)

    Park, Se Kyoung; Lee, In Sook; Cho, Kil Ho; Lee, Young Hwan; Yi, Jae Hyuck; Choi, Kyung Un

    The metaphyseal locations of tubular bones with osteoid mineralization in young patients are important diagnostic radiologic features of osteosarcoma. The pelvic bones are an unusual location of osteosarcoma. Although osteosarcoma occurring in pelvic bones is not common, the osteoid matrix may be a critical finding for differentiating osteosarcoma from other common pelvic bone tumors. Therefore, the possibility of osteosarcoma in pelvic bones may be considered in the presence of osteoid matrix even in the old age group. Copyright © 2016. Published by Elsevier Inc.

  18. 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

  19. Primary Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis: a report of an extraordinarily unusual site and a literature review of extraskeletal Ewing's sarcoma.

    Science.gov (United States)

    Ma, Zheng; Brimo, Fadi; Zeizafoun, Nebras

    2013-02-01

    Ewing's sarcomas/primitive neuroectodermal tumors (ES/PNETs) arise from a multipotent progenitor cell and are considered to be of neuroectodermal derivation. Most tumors commonly arise in the skeletal system, which are the classic ES/PNET and occasionally occur in the soft tissue of extraskeletal sites, which are named extraskeletal Ewing's sarcomas (EES/PNET). This study reports a case of a 28-year-old man with primary EES/PNET of the penis.

  20. Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

    Science.gov (United States)

    Kotteas, Elias A; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2016-01-01

    Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. PMID:26929640

  1. [Recurrence of Well Differentiated Intrascrotal Liposarcoma in Retroperitoneum Five Years after Resection : A Case Report].

    Science.gov (United States)

    Yoshinaga, Mitsuhiro; Sekii, Yosuke; Nakazawa, Shigeaki; Nakagawa, Masahiro; Kishikawa, Hidefumi; Nishimura, Kenji

    2017-01-01

    A 68-year-old man underwent an inguinal orchiectomy for a right testicular tumor and the pathological diagnosis was atypical lipomatous tumor. Nine years later, a resection procedure was performed for local recurrence. Five years after that second surgery, abdominal computed tomography (CT) findings revealed a low density mass 40 mm in size on the back side of the right kidney and enlarged fat in the retroperitoneal space. We performed a laparoscopic tumor resection under a diagnosis of lipoma or liposarcoma recurrence, and the pathological diagnosis was well differentiated liposarcoma. Treatment with pazopanib was started, as a CT examination showed that the tumor remained, after which we performed an open nephroureterectomy and resected the remaining tumor portion. Pazopanib treatment was continued and no obvious signs of recurrence were seen at 8 months after the most recent surgery. Although well differentiated liposarcoma usually recurs in the original tumor region, multicentric recurrence in other parts is possible.

  2. Recent trends in the treatment of well-differentiated endocrine carcinoma of the small bowel

    Institute of Scientific and Technical Information of China (English)

    Gilles; Poncet; Jean-Luc; Faucheron; Thomas; Walter

    2010-01-01

    Well-differentiated endocrine carcinomas of the small bowel are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that may cause carcinoid syndrome. However, many are clinically silent until late presentation with major effects. Initial treatment aims to control carcinoid syndrome with somatostatin analogs. Even if there is metastatic spread, surgical resection of the primitive tumor should be discussed in cases of retractile mesenteritis, small bowel ischemi...

  3. DNA methylation profiling of well-differentiated thyroid cancer uncovers markers of recurrence free survival.

    Science.gov (United States)

    Mancikova, Veronika; Buj, Raquel; Castelblanco, Esmeralda; Inglada-Pérez, Lucía; Diez, Anna; de Cubas, Aguirre A; Curras-Freixes, Maria; Maravall, Francisco Xavier; Mauricio, Didac; Matias-Guiu, Xavier; Puig-Domingo, Manel; Capel, Ismael; Bella, María Rosa; Lerma, Enrique; Castella, Eva; Reverter, Jordi Lluis; Peinado, Miguel Ángel; Jorda, Mireia; Robledo, Mercedes

    2014-08-01

    Thyroid cancer is a heterogeneous disease with several subtypes characterized by cytological, histological and genetic alterations, but the involvement of epigenetics is not well understood. Here, we investigated the role of aberrant DNA methylation in the development of well-differentiated thyroid tumors. We performed genome-wide DNA methylation profiling in the largest well-differentiated thyroid tumor series reported to date, comprising 83 primary tumors as well as 8 samples of adjacent normal tissue. The epigenetic profiles were closely related to not only tumor histology but also the underlying driver mutation; we found that follicular tumors had higher levels of methylation, which seemed to accumulate in a progressive manner along the tumorigenic process from adenomas to carcinomas. Furthermore, tumors harboring a BRAF or RAS mutation had a larger number of hypo- or hypermethylation events, respectively. The aberrant methylation of several candidate genes potentially related to thyroid carcinogenesis was validated in an independent series of 52 samples. Furthermore, through the integration of methylation and transcriptional expression data, we identified genes whose expression is associated with the methylation status of their promoters. Finally, by integrating clinical follow-up information with methylation levels we propose etoposide-induced 2.4 and Wilms tumor 1 as novel prognostic markers related to recurrence-free survival. This comprehensive study provides insights into the role of DNA methylation in well-differentiated thyroid cancer development and identifies novel markers associated with recurrence-free survival. © 2013 UICC.

  4. Well-differentiated prostate cancer in core biopsy specimens may be associated with extraprostatic disease

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    José Cury

    Full Text Available CONTEXT AND OBJECTIVE: Accurate determination of the Gleason score in prostate core biopsy specimens is crucial in selecting the type of prostate cancer treatment, especially for patients with well-differentiated tumors (Gleason score 2 to 4. For such patients, an inaccurate biopsy score may result in a therapeutic intervention that is too conservative. We evaluate the role of Gleason score 2-4 in prostate core-needle biopsies for predicting the final pathological staging following radical prostatectomy. DESIGN AND SETTING: Retrospective study at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: We analyzed the medical records of 120 consecutive patients who underwent radical retropubic prostatectomy to treat clinical localized prostate cancer at our institution between December 2001 and July 2006. Thirty-two of these patients presented well-differentiated tumors (Gleason score 2 to 4 in biopsy specimens and were included in the study. The Gleason scores of the core-needle biopsies were compared with the pathological staging of the surgical specimens. RESULTS: Sixteen of the 32 patients (50% presented moderately differentiated tumors (Gleason score 5 to 7 in surgical specimens. Eighteen patients (56% had tumors with involvement of the prostate capsule and ten (31% had involvement of adjacent organs. Evaluating the 16 patients that maintained Gleason scores of 2 to 4 in the pathological staging of the surgical specimens, 11 (68.7% had focal invasion of the prostate capsule and five (31.25% had organ-confined disease. CONCLUSION: Well-differentiated tumors (Gleason score 2 to 4 seen in biopsies are not predictive of organ-confined disease.

  5. Radiofrequency ablation to treat loco-regional recurrence of well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jung, So Lyung; Kim, Bum Soo; Ahn, Kook Jin [Dept. of Radiology, eoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); and others

    2014-12-15

    To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo repeated surgery. Average number of RFA sessions were 1.3 (range 1-3). Post-RFA biopsy and ultrasound were performed. The mean follow-up period was 30 months. Pre- and post-RFA serum thyroglobulin values were evaluated. Thirty-one patients with 33 RTCs were treated with RFA only, whereas 1 patient with 2 RTCs was treated with RFA followed by surgery. At the last follow-up ultrasound, 31 (94%) of the 33 RTCs treated with RFA alone completely disappeared and the remaining 2 (6%) RTCs showed decreased volume. The largest diameter and volume of the 33 RTCs were markedly decreased by 93.2% (from 8.1 +/- 3.4 mm to 0.6 +/- 1.8 mm, p < 0.001) and 96.4% (from 173.9 +/- 198.7 mm{sup 3} to 6.2 +/- 27.9 mm{sup 3}, p < 0.001), respectively. Twenty of the 21 RTCs evaluated with post-RFA biopsies (95%) were negative for malignancy. One (5%) showed remaining tumor that was removed surgically. The serum thyroglobulin was decreased in 19 of 26 patients (73%). Voice change developed immediately after RFA in 6 patients (19%) and was spontaneously recovered in 5 patients (83%). Radiofrequency ablation can be effective in treating loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk.

  6. Well differentiated neuroendocrine tumor of the kidney: Report of a rare case with review of literature

    Directory of Open Access Journals (Sweden)

    Kavita Mardi

    2017-01-01

    Full Text Available Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Renal carcinoids are typically slow-growing tumors and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. We herein report a rare cases of well-differentiated NET (carcinoid in a 39-year-old male along with the immunohistochemical features. The rarity of these tumors poses a diagnostic and therapeutic challenge.

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

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    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.

  8. Advances in targeted therapy for osteosarcoma.

    Science.gov (United States)

    Zhou, Wenya; Hao, Mengze; Du, Xiaoling; Chen, Kexin; Wang, Guowen; Yang, Jilong

    2014-06-01

    Osteosarcoma is an aggressive cancer in skeletal system with unknown molecular mechanisms of etiology and pathogenesis, therefore it remains a challenge for current therapeutic strategies to effectively treat osteosarcoma. The aim of this review is to give an overview of the molecular and mechanistic changes identified in recent years which might be new targets for the treatment of osteosarcoma. These molecules play important roles in different biological and pathological programs of osteosarcoma, including the altered oncogenes and tumor suppressor genes, molecules involved in tumor cell migration and invasion, angiogenesis, apoptosis and proliferation, miRNAs, and molecules involved in osteoclast function and multidrug resistance. Further research on these molecules in osteosarcoma will provide new insights into the target therapy for osteosarcoma.

  9. Rb1 GENE MUTATIONS IN OSTEOSARCOMA

    Institute of Scientific and Technical Information of China (English)

    ZENG Ji-bin; SONG Yue; WANG Yi; SHI Yu-yuan

    1999-01-01

    @@ Genetic alternations, such as mutations caused inactivities of tumor suppressor gene, have been identified in a wide variety of tumors, including osteosarcoma. Osteosarcoma is the most frequent primary malignant bone tumor that occurs in the extremities of young adolescents in most cases. Because of the high frequent occurrence of this type of tumor in hereditary retinoblastoma patients, involvement of the Rb1 gene mutations was suspected in the development of osteosarcoma, and a few reports have shown alternations of the Rb1 gene in osteosarcoma. We studied Rb1 gene mutations in 9 osteosarcoma samples and one cell line (OS 732) to explore the types and mechanism of Rb1 gene mutations in osteosarcoma.

  10. Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma

    OpenAIRE

    Ryuichiro Kimura; Takayoshi Rokkaku; Shinji Takeda; Masachika Senba; Naoki Mori

    2013-01-01

    In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell tran...

  11. Primary osteosarcoma of the breast: case report

    OpenAIRE

    Saber, Boutayeb; Nawal, Ahbeddou; Mohamed, Fetohi; Hassan, Errihani

    2008-01-01

    Mammary sarcomas are very uncommon and make up less than 1% of all primary breast malignancies. Primary osteosarcoma of the breast is extremely rare and represents 12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the bone should be considered in the differential diagnosis. In addition, the absence of a direct connection between the tumour and the underlying skeleton is mandatory for the diagnosis. We report a case of primary osteosarcoma of the breast occurring in ...

  12. 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

  13. Well-differentiated gall bladder hepatoid carcinoma producing alpha-fetoprotein: a case report

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    Kao Ching-Yun

    2009-06-01

    Full Text Available Abstract Introduction Gall bladder carcinoma is rare, and metastatic gall bladder carcinoma from hepatocellular carcinoma has been reported in only a few patients. Case presentation We present a 73-year-old man with a history of hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma. He received transcatheter arterial chemoembolization, and was diagnosed to have an alpha-fetoprotein producing gall bladder tumor with intraluminal growth. Open cholecystectomy was performed. Pathologic examination of the lesion revealed a well-differentiated hepatoid carcinoma. The lesion was thought most likely to be a metastatic lesion from previous hepatocellular carcinoma. His alpha-fetoprotein level dropped to normal levels five months after the surgery. Conclusion This unusual intraluminal growing tumor proved to be a well-differentiated hepatoid carcinoma, most likely a metastatic lesion from previous hepatocellular carcinoma. This case reminds clinicians that in looking for likely hepatocellular carcinoma recurrence, when no detectable hepatic lesion can account for an elevated alpha-fetoprotein level, the gall bladder should be included in the search for the site of metastasis.

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

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    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.

  15. Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ryuichiro Kimura

    2013-10-01

    Full Text Available In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma.

  16. Osteosarcoma of The Maxilla : A Case Report

    Directory of Open Access Journals (Sweden)

    Mandavi S Garud

    2005-01-01

    Full Text Available Osteosarcoma is a common malignant lesion of the long bones and occurs rarely in the jaw. In comparison to the mandible it is a rarity in the maxilla. Diagnosed based on the radiographic and histologic findings, jaw osteosarcoma has an increased 5 year survival rate and low incidence of metastasis as compared to that of the long bones. Patients with jaw osteosarcoma can be remarkably treated with a combination of surgery and chemotherapy. One such case of a maxillary osteosarcoma is presented here.

  17. Osteosarcoma of the jaws: a review of literature and a case report on synchronous multicentric osteosarcomas

    Directory of Open Access Journals (Sweden)

    Nthumba Peter M

    2012-11-01

    Full Text Available Abstract Background In the head and neck region, osteosarcoma is the most common primary malignant bone tumor, representing 23% of total head and neck malignancies. Osteosarcomas of the jaws are nevertheless rare lesions, representing only 2 to 10% of all osteosarcomas. This report reviews a single-center histopathology experience with craniofacial osteosarcomas, and reports the management of unusually large synchronous mandibular and maxillary osteosarcomas in a patient. Patients and methods A search of the hospital pathology database for specimens with a histological diagnosis of osteosarcomas submitted between July 1992 and May 2011 was made. A chart review of a patient with large synchronous maxillary and mandibular osteosarcomas was performed, and is reported. Case presentation A 21-year-old African man with large maxillary and mandibular tumors under palliative care presented with increasing difficulties with eating, speech, and breathing. Surgical debulking was performed, with histology confirming synchronous osteosarcomas of the mandible and maxilla. The patient is well after one year, with no evidence of recurrence, having undergone no further treatment. Conclusion Osteosarcomas of the jaw remain enigmatic, and a number of difficulties related to their diagnosis and treatment are yet to be resolved. True synchronous multicentric osteosarcomas of the jaws are extremely rare but, like other osteosarcomas of the jaws, have a favorable outcome, and palliative resection of such lesions, though challenging, can therefore lead to an enormously improved quality of life and self-image, and may even offer the opportunity for cure.

  18. Sensitizing Osteosarcoma to Radiation Therapy

    Science.gov (United States)

    Mamo, Tewodros Kebede

    Several strategies to enhance the effects of radiation therapy are being explored for various cancers, with multiple molecular pathways and physical approaches suggested to play a role. One approach to improve the effectiveness of radiation therapy in tumors is the use of radiosensitizing molecules. Among the key radiosensitizing molecules being explored in various cancers include pharmacologic inhibitors of DNA repair and gold nanoparticles that physically enhance the amount of radiation deposited inside cancer cells. The main goal of this thesis is to explore the role of DNA repair inhibition as a radiosensitizing strategy for osteosarcoma cells. Additionally, the thesis investigates the effects of particle size in the application of gold nanoparticles in osteosarcoma cells to help identify the key parameters relevant to choosing an effective gold nanoparticle-based radiosensitizer.

  19. 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.

  20. Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yoshiyuki Ueno; Satoshi Sekiguchi; Kazuyuki Ishida; Takehiko Igarashi; Yuta Wakui; Takao Iwasaki; Tooru Shimosegawa

    2009-01-01

    A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives. Radiological diagnostics showed the typical findings of liver cell adenoma (LCA). Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase. The tumor was found to contain fat on magnetic resonance imaging. A benign fat containing liver tumor was suggested. However, radiological findings altered, which caused us to suspect that a welldifferentiated hepatocellular carcinoma (HCC) containing fat was becoming dedifferentiated. Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA. This case was an extremely rare LCA, which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

  1. Low-grade osteosarcoma of the spine: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Chul; Suh, Jin Suck; Kim, Myung In; Choo, Hye Jung; Huh, Yong Min [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-06-15

    Low-grade osteosarcoma is not typically found in the long bone and pelvis. Most primary osteosarcomas that arise in the spine are high-grade malignancies. A low-grade osteosarcoma arising in the spine has not been previously described. We report here the clinical, radiological, and histological findings of a case of low-grade osteosarcoma that arose in the spine.

  2. 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.

  3. Osteosarcoma: A Study of 27 Cases

    Directory of Open Access Journals (Sweden)

    Roland Jong

    2000-01-01

    Full Text Available Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease.The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor.

  4. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling

    2010-10-01

    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  5. 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.

  6. Low-grade osteosarcoma of the ethmoid sinus

    Energy Technology Data Exchange (ETDEWEB)

    Vlychou, M.; Ostlere, S.J. [Nuffield Orthopaedic Centre, Department of Musculoskeletal Radiology, Oxford (United Kingdom); Kerr, R. [Radcliffe Infirmary, Department of Neurosurgery, Oxford (United Kingdom); Athanasou, N.A. [Nuffield Orthopaedic Centre, Department of Pathology, Nuffield Department of Orthopaedic Surgery, Oxford (United Kingdom)

    2007-05-15

    Osteosarcoma uncommonly arises in craniofacial bones and has only rarely been reported to arise in the ethmoid sinus. Most primary osteosarcomas arising in paranasal sinuses are high-grade malignancies. A low-grade osteosarcoma arising in the ethmoid sinus has not previously been described. We report the clinical, radiological and histological findings of a case of low-grade (parosteal osteosarcoma-like) osteosarcoma which arose in the ethmoid sinus. (orig.)

  7. Lipoma-like hibernoma: an atypical lipoma/well-differentiated liposarcoma mimicker

    Directory of Open Access Journals (Sweden)

    Reis-Filho Jorge S.

    2002-01-01

    Full Text Available Hibernomas are benign lipomatous tumors which show differentiation toward brown fat. Recently, unusual variants have been described, including myxoid, spindle cell, and lipoma-like variants. Lipoma-like hibernoma (LLH is characterized by mature univacuolated adipocytic cells with rare admixed multivacuolated brown fat-like cells, which may resemble lipoblasts, leading to a misdiagnosis of atypical lipoma/well-differentiated liposarcoma (AL/WDLS. We herein report a case of LLH arising on the anterior aspect of the left thigh of a 17-year-old female. A marginal excision was performed. The patient was discharged and remains well four months after surgery. Histological examination showed a lobulated neoplasm composed of univacuolated mature adipose cells admixed with small vessels and occasional mast cells. Scattered islands of brown fat-like cells accounting for less than 10% of the neoplasm were found. Sometimes these cells presented indented and scalloped nuclei, resembling lipoblasts. A final diagnosis of LLH was made based on the presence of focal areas with typical hibernoma morphology, and the lack of atypical hyperchromatic stromal cells. Pathologists must be aware of the typical histological findings of LLH, not to confuse it with AL/WDLS.

  8. Comparison of methods for proliferative index analysis for grading pancreatic well-differentiated neuroendocrine tumors.

    Science.gov (United States)

    Goodell, Pamela P; Krasinskas, Alyssa M; Davison, Jon M; Hartman, Douglas J

    2012-04-01

    Assessment of proliferative activity is required for grading well-differentiated pancreatic neuroendocrine tumors. However, a standardized method for obtaining the Ki-67 proliferative index is lacking. This study compared proliferative activity obtained by 3 methods: single-field hot spot (Ki-67 HS) and 10 consecutive field average (Ki-67 CFA) using the Ventana image analysis system (Ventana Medical Systems, Tucson, AZ) and mitotic index (MI). These methods resulted in discrepant grades in 30 (67%) of our 45 cases. With the current Ki-67 cutoff of more than 2% for intermediate-grade tumors, MI, CFA, and HS resulted in specificities of 91%, 94%, and 31%, respectively, for detecting metastasis, with positive predictive values (PPVs) of 25%, 67%, and 31%, respectively. At a higher Ki-67 cutoff of 7.5%, HS analysis resulted in a specificity of 94% and PPV of 71% for predicting metastasis. While single-field HS analysis may be practical and reliable at a higher cutoff, this study emphasizes the variability that can exist when different methods of assessment are used.

  9. Contrast enhanced multi-detector CT and MR findings of a well-differentiated pancreatic vipoma.

    Science.gov (United States)

    Camera, Luigi; Severino, Rosa; Faggiano, Antongiulio; Masone, Stefania; Mansueto, Gelsomina; Maurea, Simone; Fonti, Rosa; Salvatore, Marco

    2014-10-28

    Pancreatic vipoma is an extremely rare tumor accounting for less than 2% of endocrine pancreatic neoplasms with a reported incidence of 0.1-0.6 per million. While cross-sectional imaging findings are usually not specific, exact localization of the tumor by means of either computed tomography (CT) or magnetic resonance (MR) is pivotal for surgical planning. However, cross-sectional imaging findings are usually not specific and further characterization of the tumor may only be achieved by somatostatin-receptor scintigraphy (SRS). We report the case of a 70 years old female with a two years history of watery diarrhoea who was found to have a solid, inhomogeneously enhancing lesion at the level of the pancreatic tail at Gadolinium-enhanced MR (Somatom Trio 3T, Siemens, Germany). The tumor had been prospectively overlooked at a contrast-enhanced multi-detector CT (Aquilion 64, Toshiba, Japan) performed after i.v. bolus injection of only 100 cc of iodinated non ionic contrast media because of a chronic renal failure (3.4 mg/mL) but it was subsequently confirmed by SRS. The patient first underwent a successful symptomatic treatment with somatostatin analogues and was then submitted to a distal pancreasectomy with splenectomy to remove a capsulated whitish tumor which turned out to be a well-differentiated vipoma at histological and immuno-histochemical analysis.

  10. Transformation of prostatic adenocarcinoma to well-differentiated neuroendocrine tumor after hormonal treatment.

    Science.gov (United States)

    Gilani, Syed; Guo, Charles C; Li-Ning, Elsa M; Pettaway, Curtis; Troncoso, Patricia

    2017-06-01

    Carcinoid tumor of the prostate is extremely rare. Here we report a unique case of prostate cancer that underwent complete transformation from conventional adenocarcinoma to carcinoid-like tumor shortly after androgen-deprivation treatment (ADT). The patient was a 59-year-old man who presented with lower urinary tract symptoms. His biopsy specimen demonstrated a high-grade prostatic adenocarcinoma with mixed acinar and ductal features. After ADT for 6months, the patient underwent radical prostatectomy. The post-ADT tumor showed monotonous neoplastic cells with fine granular chromatin forming rosette-like structures, resembling a carcinoid tumor. No residual conventional adenocarcinoma was present. On immunostain, the tumor cells were diffusely positive for synaptophysin and chromogranin and negative for prostate-specific antigen and prostein. Thus, the carcinoid-like tumor represented complete transformation from prostatic adenocarcinoma to well-differentiated neuroendocrine tumor after ADT. This unique case highlights the important role of ADT in neuroendocrine differentiation of prostate cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  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. Well-differentiated hepatocellular carcinoma in a ring-tailed lemur (Lemur catta).

    Science.gov (United States)

    Nemeth, N M; Blas-Machado, U; Cazzini, P; Oguni, J; Camus, M S; Dockery, K K; Butler, A M

    2013-02-01

    A 16-year-old male ring-tailed lemur (Lemur catta) was presented with severe cachexia and an abdominal mass. The encapsulated, multilobular mass replaced the right medial lobe of the liver and compressed the adjacent gall bladder. Multiple haemorrhages and necrotic foci were found within the mass. Microscopically, neoplastic cells formed cords of moderately pleomorphic, polygonal cells with mild to moderate anaplasia. Immunohistochemical markers used for diagnosis of hepatocellular carcinomas in man were used to characterize the neoplastic cells, which expressed hepatocyte-specific antigen, but not glypican-3 or polyclonal carcinoembryonic antigen. Gross, microscopical and immunohistochemical features of the tumour were most consistent with a well-differentiated hepatocellular carcinoma. Although this tumour is common among prosimians, to the authors' knowledge this is the first documented case in a ring-tailed lemur. Hepatocellular carcinomas have been associated with hepatitis virus infections and excessive hepatic iron in man; however, no association was established between this tumour and viral infection or hepatic iron storage disease in the present case. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Well-differentiated papillary mesothelioma: a clinicopathological and immunohistochemical study of 18 cases with additional observation.

    Science.gov (United States)

    Chen, Xiaochen; Sheng, Weiqi; Wang, Jian

    2013-04-01

    To present our experience with 18 cases of well-differentiated papillary mesothelioma (WDPM), with an emphasis on its relationship to adenomatoid tumour and multicystic mesothelioma. Eighteen cases of WDPM were retrieved. Twenty cases of multicystic mesothelioma were selected for comparative study. The WDPM patients comprised 14 females and four males, with age ranging from 18 to 60 years (median 37 years). The tumour involved the abdominal or pelvic peritoneum (14 cases), the pleura (two cases), and the testicular tunica vaginalis (two cases). The majority of WDPMs were incidental findings during surgery for a wide variety of conditions. Histologically, 13 cases were consistent with classical WDPM. Two cases had a combined component of adenomatoid tumour, and three cases contained coexisting areas of multicystic mesothelioma. Among the multicystic mesothelioma cases, four had adenomatoid tumour-like foci present in the stroma. Immunohistochemically, all cases of WDPM and multicystic mesothelioma, as well as the coexisting combined components, were positive for mesothelial markers, with a low Ki67 index. This study also showed that WDPM was negative for epithelial membrane antigen and desmin. The simultaneous occurrence of WDPM, adenomatoid tumour and multicystic mesothelioma in some cases suggested histogenetic relationships among these three less aggressive mesotheliomas. © 2012 Blackwell Publishing Ltd.

  14. Contrast enhanced multi-detector CT and MR findings of a well-differentiated pancreatic vipoma

    Institute of Scientific and Technical Information of China (English)

    Luigi; Camera; Rosa; Severino; Antongiulio; Faggiano; Stefania; Masone; Gelsomina; Mansueto; Simone; Maurea; Rosa; Fonti; Marco; Salvatore

    2014-01-01

    Pancreatic vipoma is an extremely rare tumor accounting for less than 2% of endocrine pancreatic neoplasms with a reported incidence of 0.1-0.6 per million. While cross-sectional imaging findings are usually not specific, exact localization of the tumor by means of either computed tomography(CT) or magnetic resonance(MR) is pivotal for surgical planning. However, cross-sectional imaging findings are usually not specific and further characterization of the tumor may only be achieved bysomatostatin-receptor scintigraphy(SRS). We report the case of a 70 years old female with a two years history of watery diarrhoea who was found to have a solid, inhomogeneously enhancing lesion at the level of the pancreatic tail at Gadolinium-enhanced MR(Somatom Trio 3T, Siemens, Germany). The tumor had been prospectively overlooked at a contrast-enhanced multi-detector CT(Aquilion 64, Toshiba, Japan) performed after i.v. bolus injection of only 100 cc of iodinated non ionic contrast media because of a chronic renal failure(3.4 mg/mL) but it was subsequently confirmed by SRS. The patient first underwent a successful symptomatic treatment with somatostatin analogues and was then submitted to a distal pancreasectomy with splenectomy to remove a capsulated whitish tumor which turned out to be a well-differentiated vipoma at histological and immuno-histochemical analysis.

  15. A New Strategy for the Surgical Management of RLN Infiltrated by Well-Differentiated Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Jan Boucek

    2014-01-01

    Full Text Available Well-differentiated thyroid carcinoma (WDTC represents the most common endocrine malignancy. Despite excellent prognoses exceeding 90% in 10-year follow-up, there are clinically controversial issues. One of these is extrathyroidal tumour extension invading recurrent laryngeal nerve (RLN. The spread outside of the thyroid parenchyma and invasion to the surrounding structures, classified as always T4a, are the most important negative prognostic factor for the WDTC. Conversely, resection of the RLN leads to vocal cord paralysis with hoarseness, possible swallowing problems, and finally decreased quality of life. We propose a new algorithm for intraoperative management based on the MACIS classification, which would allow swift status evaluation pre/intraoperatively and consider a possibility to preserve the infiltrated RLN without compromising an oncological radicality. In the case of a preoperative vocal cord paralysis (VCP and confirmation of the invasive carcinoma, a resection of the RLN and the nerve graft reconstruction are indicated. Preoperatively, unaffected vocal cord movement and intraoperatively detected RLN infiltration by the invasive WDTC require an individual assessment of the oncological risk by the proposed algorithm. Preservation of the infiltrated RLN is oncologically acceptable only in specific groups of patients of a younger age with a minor size of primary tumour.

  16. 骨肉中PTEN蛋白表达及临床意义的研究%Expression and clinical significance of PTEN protein in osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    Yubin Wang; Anmin Chen; Fengjin Guo; Yujun Xia

    2008-01-01

    Objective:To investigate the expression and significance of cancer inhibitory gene PTEN protein in osteosarcoma.To analyze the level of its expression in different histological classification of osteosarcoma.To determine the possibility of taking PTEN protein as a marker gene for diagnosing osteosarcoma.To observe the clinical value of PTEN expression levels as a reference index for osteosarcoma classification.Methods:43 specimens collected from osteosarcoma excision were studied.30 specimens collected during the same period from benign lesion of bone (osteochondroma) operation were taken as the control group.Immunohistochemistry staining (ElivisonTM two steps method) was used to detect the expression of PTEN protein in 43 cases of osteosarcoma.SPSS 10.0 was used in statistical analysis.Results:Immunohistochemistry staining showed that the positive reaction of PTEN protein was all oriented to cytoplasm,which were brown or yellowishbrown granules.By way of X2 test,the significant difference of the positive expressions of PTEN protein between bone benign lesion and osteosarcoma (X2=7.976,P<0.01) was observed.Osteosarcoma with different degrees of histodifferentiation showed different level expression of PTEN protein.There was significant difference between well-differentiated osteosarcoma (grades Ⅰ-Ⅱ) and poorly-differentiated osteosarcoma (grade Ⅲ) statistically (P<0.01).The level of expression of PTEN was negatively correlated to the histological grade of osteosarcoma.There was great significance statistically (rs=-0.4922,P<0.01).Conclusion:PTEN protein may be used as candidate gene of cancer inhibitory gene:PTEN protein is a cancer suppressor gene protein which has expression in bone tumors.It might not only be used in the study of pulmonary carcinoma and neurogliocytoma,but also in the study of bone tumor; the expression of PTEN is related to benignancy or malignancy of bone tumor and their degree of differentiation.The expression of PTEN is

  17. Metastatic well differentiated squamous cell carcinoma in the prepuce of a dog: a report of clinicopathological, immunophenotypic and therapeutic approach

    OpenAIRE

    Auler,P.A.; C.O. Gamba; R.S. Horta; G.E. Lavalle; G.D. Cassali

    2014-01-01

    This report describes a case of a well differentiated squamous cell carcinoma (SCC) of the foreskin of a dog, with metastasis in the regional lymph node. A six-year-old male intact Pit Bull dog presented a preputial ulcerated lesion with an evolution time of one year and enlarged left inguinal lymph node. Surgical resection of the preputial lesion and inguinal lymph nodes was made. The diagnosis of a well differentiated SCC was made following histopathological analysis and immunohistochemistr...

  18. 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.

  19. 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.

  20. Study on Angiogenesis Factor of Human Osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10 000 u molecular weight in the conditioned medium obtained from the cultivation of human osteosarcoma cells were partially purified by ultrafiltration, chromatography and dialysis. The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig aorta thoracic endothelial cells. The results showed that the chromatography fractions of 4 to 6 could significantly promote the proliferation of the endothelial cells. It was suggested that the human osteosarcoma cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000 to 10 000 u.

  1. Risk-Based Therapy for Localized Osteosarcoma.

    Science.gov (United States)

    Venkatramani, Rajkumar; Murray, Jeffrey; Helman, Lee; Meyer, William; Hicks, M John; Krance, Robert; Lau, Ching; Jo, Eunji; Chintagumpala, Murali

    2016-03-01

    The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival. Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (treatment-related deaths. Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival. © 2015 Wiley Periodicals, Inc.

  2. Primary osteosarcoma of the breast: case report

    Science.gov (United States)

    Saber, Boutayeb; Nawal, Ahbeddou; Mohamed, Fetohi; Hassan, Errihani

    2008-01-01

    Mammary sarcomas are very uncommon and make up less than 1% of all primary breast malignancies. Primary osteosarcoma of the breast is extremely rare and represents 12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the bone should be considered in the differential diagnosis. In addition, the absence of a direct connection between the tumour and the underlying skeleton is mandatory for the diagnosis. We report a case of primary osteosarcoma of the breast occurring in young patient with fatal evolution. PMID:18691427

  3. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Science.gov (United States)

    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. PMID:24216993

  4. Dedifferentiated parosteal osteosarcoma with giant cell tumor component

    Energy Technology Data Exchange (ETDEWEB)

    Cardona, Diana M.; Knapik, Jacquelyn A. [University of Florida, College of Medicine, Department of Pathology, Immunology, and Laboratory Medicine, P.O. Box 100275, Gainesville, FL (United States); Reith, John D. [University of Florida, College of Medicine, Department of Pathology, Immunology, and Laboratory Medicine, P.O. Box 100275, Gainesville, FL (United States); University of Florida, College of Medicine, Department of Orthopaedics and Rehabilitation, Gainesville, FL (United States)

    2008-04-15

    Dedifferentiated parosteal osteosarcoma is characterized histologically by the admixture of low-grade fibroblastic osteosarcoma and a high-grade component typically resembling conventional osteosarcoma or malignant fibrous histiocytoma. We report an unusual distal femoral dedifferentiated parosteal osteosarcoma in which the dedifferentiated component resembled a giant cell tumor of bone. This phenotype is rarely described in the dedifferentiated component of a dedifferentiated parosteal osteosarcoma. The clinical, radiographic, and pathologic features of this unusual tumor are described to further expand the histologic spectrum of dedifferentiated parosteal osteosarcoma. (orig.)

  5. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Kosei, E-mail: andokercgv@gmail.com [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Heymann, Marie-Françoise [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France); Stresing, Verena [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Nantes University Hospital, Nantes 44035 (France); Mori, Kanji [Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192 (Japan); Rédini, Françoise; Heymann, Dominique [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France)

    2013-05-24

    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.

  6. Extremely well-differentiated adenocarcinoma of the stomach: Clinicopathological and immunohistochemical features

    Institute of Scientific and Technical Information of China (English)

    Takashi Yao; Takashi Utsunomiya; Masafumi Oya; Kenichi Nishiyama; Masazumi Tsuneyoshi

    2006-01-01

    AIM: Minimal deviation carcinoma of the uterine cervix,otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior.In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA,we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products.METHODS: Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion,lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56mo). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium,mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cells and their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein.CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c

  7. 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

  8. Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group.

    Science.gov (United States)

    Cash, Thomas; McIlvaine, Elizabeth; Krailo, Mark D; Lessnick, Stephen L; Lawlor, Elizabeth R; Laack, Nadia; Sorger, Joel; Marina, Neyssa; Grier, Holcombe E; Granowetter, Linda; Womer, Richard B; DuBois, Steven G

    2016-10-01

    The prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with EES and skeletal ES. Patients had localized ES and were treated on two consecutive protocols using five-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n = 213) or skeletal (n = 826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. Patients with extraskeletal ES (EES) were more likely to have axial tumors (72% vs. 55%; P 8 cm (9% vs. 17%; P rate were independently associated with inferior EFS. Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site. © 2016 Wiley Periodicals, Inc.

  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. NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma.

    NARCIS (Netherlands)

    Flucke, U.; Tops, B.B.J.; Verdijk, M.A.J.; Cleef, P.J. van; Zwam, P.H. van; Slootweg, P.J.; Bovee, J.V.; Riedl, R.G.; Creytens, D.H.; Suurmeijer, A.J.H.; Mentzel, T.

    2012-01-01

    Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15-76 years (mean, 42 years). Tumours were located on

  11. NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma

    NARCIS (Netherlands)

    Flucke, Uta; Tops, Bastiaan B. J.; Verdijk, Marian A. J.; van Cleef, Patricia J. H.; van Zwam, Peter H.; Slootweg, Pieter J.; Bovee, Judith V. M. G.; Riedl, Robert G.; Creytens, David H.; Suurmeijer, Albert J. H.; Mentzel, Thomas

    2012-01-01

    Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15-76 years (mean, 42 years). Tumours were located on

  12. Osteosarcoma metastasis causing ileo-ileal intussusception

    National Research Council Canada - National Science Library

    Abbo, Olivier; Pinnagoda, Kalitha; Micol, Lionel A; Beck-Popovic, Maya; Joseph, Jean-Marc

    2013-01-01

    .... We conclude that, in patients with a history of osteosarcoma lung metastasis, echographic and/or computed tomography scan evidence of a small bowel obstruction with intussusception should lead...

  13. Longitudinal Growth Following Treatment for Osteosarcoma

    Directory of Open Access Journals (Sweden)

    W. Paul Cool

    1998-01-01

    Full Text Available Purpose. The purpose of this study was to analyse the height at diagnosis and growth in 72 skeletally immature children who had been treated for osteosarcoma in the area of the knee.

  14. Initial symptoms and clinical features in osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    Sujia Wu; Xing Shi; Jianling Zhao; Yurong Wang; Jun Zhang; Liwu Zhou; Yuexian Cheng; Guangxin Zhou

    2005-01-01

    Objective: To establish the initial symptoms and physical signs of osteosarcoma from the records of the first medical visit and to identify early characteristics of the diseases to shorten the delay of diagnosis. Methods: A group of patients with osteosarcoma in extremities was identified from Nanjing Jinling Hospital. Records from the first medical visit due to symptoms and physical signs related to the bone tumor were obtained from 71 patients with osteosarcoma. Results: The results of the data recorded about the first medical visit,reasons for consultation, pain,trauma,initial diagnosis,delay in diagnosis were reported respectively. Conclusion: Pair an initial symptom of osteosarcoma, and was intermittent but not frequently felt at night. A history of trauma was common, but the clinical course often diverged from what was expected from trauma. The most important clinical feature was a palpable mass. This finding emphasizes that a thorough physical examination is absolutely necessary.

  15. Activating GNAS mutations in parosteal osteosarcoma.

    Science.gov (United States)

    Carter, Jodi M; Inwards, Carrie Y; Jin, Long; Evers, Barbara; Wenger, Doris E; Oliveira, Andre M; Fritchie, Karen J

    2014-03-01

    Parosteal osteosarcoma is a surface-based osteosarcoma that often exhibits deceptively bland cytologic features, hindering diagnosis in small biopsies or when correlative radiologic imaging is not readily available. A number of benign and malignant fibro-osseous lesions, including fibrous dysplasia (FD) and low-grade central osteosarcoma, fall within the morphologic differential diagnosis of parosteal osteosarcoma. Somatic mutations in GNAS, encoding the α-subunit of the heterotrimeric G protein complex (Gsα), occur in FD and McCune-Albright syndrome but have not been reported in parosteal osteosarcoma. We evaluated GNAS mutational status in parosteal osteosarcoma and several of its histologic mimics to determine its utility in differentiating these entities. Eleven of 14 (79%) FD cases had GNAS mutations within codon 201 (5 R201C and 6 R201H mutations). GNAS mutations were not detected in any cases of adamantinoma or osteofibrous dysplasia. Direct sequencing of 9 parosteal osteosarcomas, including 3 of low grade and 6 with dedifferentiation, revealed activating GNAS mutations in 5 cases (55%), distributed as 4 R201C-mutated tumors and 1 tumor with an R201H mutation. GNAS codon 227 mutations were not detected in any of the cases. There was no association between GNAS mutational status and patient demographics, histologic dedifferentiation, or clinical outcome. To our knowledge, we report the first series of parosteal osteosarcomas harboring activating GNAS mutations. Our data suggest that GNAS mutational status may have limited utility as an ancillary technique in differentiating benign and malignant fibro-osseous lesions of the bone.

  16. Vitronectin significantly influences prognosis in osteosarcoma.

    Science.gov (United States)

    Shi, Kai; Lan, Rui-Long; Tao, Xuan; Wu, Chao-Yang; Hong, Hai-Feng; Lin, Jian-Hua

    2015-01-01

    Vitronectin (Vn), a multifunctional adhesive protein, is found in association with tumor progression, angiogenesis and metastasis in a variety of (human) tumors. But no studies concerning its correlation to osteosarcoma prognosis were found. Hence, we aimed to investigate the prognostic value of Vitronectin (Vn) in osteosarcoma. Here, we studied the expression of VN in the tumor tissues from 67 patients with osteosarcoma and 20 patients with osteochondroma using immunohistochemistry and estimated the effects of VN expression in osteosarcoma on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Increased expression of VN in osteosarcoma tissue compared to no VN expression in osteochondroma tissue was shown in immunohistochemical assay. No associations were observed between VN expression and osteosarcoma patients' gender (P = 0.675), age (P = 0.813), tumor size (P = 0.436), histologic subtype (P = 0.0.543) or tumor location (P = 0.456). Univariate survival analysis demonstrated significant correlations of high VN expression with shorter PFS (P = 0.002) and OS (P = 0.001); multivariate survival analysis revealed high VN expression as a significant independent prognostic indicator for shorter PFS (HR 2.788, P = 0.003) and OS (HR2.817, P = 0.003). In conclusion, the high expression of VN in tumor cells independently indicated poor clinical prognosis in patients with osteosarcoma, other than large tumor size and non-neoadjuvant chemoradiotherapy, suggesting that VN may serve as a potential therapeutic target in osteosarcoma.

  17. 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.

  18. In vivo photoacoustic imaging of osteosarcoma on animal model

    Energy Technology Data Exchange (ETDEWEB)

    Yu Menglei; Hu Jun [Department of Orthopaedics, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041 (China); Ye Fei, E-mail: hjzkm@yahoo.com.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631 (China)

    2011-01-01

    Osteosarcoma is the commonest primary malignant tumor of bone, and the second highest cause of cancer-related death in the paediatric age group. Although there are several methods for osteosarcoma detection, e.g. X-ray, CT, MRI and bone scan, they are not satisfied methods because they can hardly detect osteosarcoma in early stage. Photoacoustic imaging (PAI) is an emerging hybrid imaging modality that is noninvasive, nonionizing, with high sensitivity, satisfactory imaging depth and good temporal and spatial resolution. In order to explore this new method to detect osteosarcoma, we established SD rat models with osteosarcoma and utilized PAI to reconstruct the osteosarcoma image in vivo. This is the first time detecting osteosarcoma in vivo using PAI, and the results suggested that PAI has potential clinical application for detecting osteosarcoma in the early stage.

  19. Pediatric osteosarcoma: An updated review

    Directory of Open Access Journals (Sweden)

    Shachi Jain Taran

    2017-01-01

    Full Text Available Osteosarcoma (OS, the most common type of primary malignant bone tumor, is defined by the presence of malignant mesenchymal cells producing osteoid or immature bone. The peak incidence of the most frequent type of OS, i.e., high-grade central OS, occurs in the second decade of life during the adolescent growth spurt. Most patients suffer from the pain and swelling in the involved region and, usually, seek medical attention. Diagnosis is carried out by conventional radiographs, computed tomography, and magnetic resonance image (MRI. In addition, three-phase bone scans, thallium scintigraphy, dynamic MRI, and positron emission spectroscopy are new innovative promising tools. OS can be treated with surgery, radiotherapy, and chemotherapy. There is a clear need for newer effective agents for patients with OS, especially for patients who afflicted with metastatic and recurrence tumor. Monoclonal antibodies directed against OS may prove useful as treatment, either for drug delivery or for radiopharmaceuticals.

  20. 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

    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 ...

  1. 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.)

  2. 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

    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 ...

  3. 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.

  4. 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.

  5. Osteosarcoma

    Science.gov (United States)

    ... If the tumor has not spread to the lungs (pulmonary metastasis ), long-term survival rates are better. If the ... include: Limb removal Spread of cancer to the lungs Side effects of chemotherapy When to Contact a Medical Professional ... X-ray Osteogenic sarcoma - x-ray Ewing ...

  6. Genetically engineered mouse models and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ng Alvin JM

    2012-10-01

    Full Text Available Abstract Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.

  7. Metachronous osteosarcoma: a report of five cases.

    Science.gov (United States)

    Rodriguez, Edward K; Hornicek, Francis J; Gebhardt, Mark C; Mankin, Henry J

    2003-06-01

    Five patients with primary osteosarcoma who were treated effectively with chemotherapy and resective surgery and in whom a metachronous tumor subsequently developed in another site but who never had evidence of pulmonary metastases are described. The original bone scans of the five patients showed only the primary site as being involved. After diagnosis and treatment of the initial tumor, at intervals ranging from 12 to 78 months (average, 39 months) another osteosarcoma developed in the patients at a distant bony site. After diagnosis and treatment of the second osteosarcoma, followup of these patients for a mean of 77 months (range, 24-96 months) after the appearance of the metachronous tumor and for a mean of 118 months (range, 99-150 months) after the diagnosis of the primary lesion showed that none had pulmonary metastases develop. No recurrences of the local tumors have occurred and four of the patients currently are alive and free of disease. One of the patients had a fatal acute myelogenous leukemia develop 144 months after the discovery of the primary osteosarcoma and 86 months after the appearance of the metachronous disease. At the time of her death, however she had no evidence of osteosarcoma in any site.

  8. Primary osteosarcoma of the distal femur in two consecutive brothers.

    Science.gov (United States)

    Chin, K R; Mankin, H J; Gebhardt, M C

    2001-01-01

    The following report describes two consecutive brothers from a nonimmigrant family, with no identifiable predisposing factors, who presented with osteosarcomas of their distal femurs, one at the age of 18 years and the other at the age of 21 years. Until a cost-effective program is developed to screen for osteosarcoma, a detailed family history should be obtained from every new patient with osteosarcoma and parents should be urged to schedule early evaluations of siblings with complaints of painful extremities. Increased frequency of cytogenetic studies to screen for genetic abnormalities in patients with osteosarcoma is recommended to help elucidate the cause of osteosarcoma.

  9. At-Risk Populations for Osteosarcoma: The Syndromes and Beyond

    Directory of Open Access Journals (Sweden)

    George T. Calvert

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary malignancy of bone. Most cases are sporadic without a known genetic or environmental cause. Heritable genetic predisposition syndromes are associated with a small percentage of osteosarcomas. Study of these rare disorders has provided insight into the molecular pathogenesis of osteosarcoma. Screening of at-risk families and surveillance of affected individuals for these syndromes may permit earlier diagnosis and more effective treatment of osteosarcoma in these populations. This paper reviews the genetic and clinical features of the known osteosarcoma predisposition syndromes.

  10. In vivo photoacoustic imaging of osteosarcoma in a rat model

    Science.gov (United States)

    Hu, Jun; Yu, Menglei; Ye, Fei; Xing, Da

    2011-02-01

    Osteosarcoma is one of the most common primary malignant tumors of the bone and the second leading cause of cancer-related deaths in the pediatric age group. Confirmed diagnosis and prompt treatment of osteosarcoma are critical for effective prognosis. In this study, we investigate the application of photoacoustic imaging (PAI) for the detection of osteosarcoma in an animal model. Cross-section images of a normal rat leg and a tumorous rat leg were successfully reconstructed in vivo. Morphological changes and the development of the implanted osteosarcoma were accurately mapped with time-dependent photoacoustic images. Furthermore, we evaluate the use of gold nanorods as contrast agents for imaging osteosarcoma with PAI. This is the first study that uses PAI to detect osteosarcoma in vivo, and the results suggest that PAI has the potential clinical application for detecting osteosarcoma in the early stage.

  11. Parosteal osteosarcoma of the posterior aspect of the distal part of the femur. Oncological and functional results following a new resection technique.

    Science.gov (United States)

    Lewis, V O; Gebhardt, M C; Springfield, D S

    2000-08-01

    Parosteal osteosarcoma is a low-grade malignant bone tumor that arises from the surface of the metaphysis of long bones. Parosteal osteosarcoma is usually well differentiated and displays a low propensity to metastasize. Wide resection of a parosteal osteosarcoma has been shown to provide a relatively risk-free method of preventing local recurrence. We propose a new method of resection of parosteal osteosarcomas located in the popliteal paraosseous space of the distal part of the femur. This method involves resection of the mass through separate medial and lateral incisions, which allows for wide margins yet limits the amount of dissection of the soft tissues and the neurovascular bundle. Six patients with parosteal osteosarcoma located on the posterior aspect of the distal part of the femur underwent resection of the lesion and reconstruction with a posterior hemicortical allograft through dual medial and lateral incisions. The patients were evaluated with regard to pain, postoperative function, union of the allograft (osteosynthesis), and the prevalence of local recurrence. The average time until the last follow-up assessment was 4.3 years. No metastases developed, and there were no local recurrences. All patients were free of disease at the last follow-up evaluation. Postoperatively, the average range of motion of the knee was 0 to 122 degrees. Five of the six patients were free of pain at the time of the latest follow-up. Five of the six patients returned to their preoperative active functional status. We recommend resection of a parosteal osteosarcoma located on the posterior surface of the femur through separate medial and lateral incisions. This approach provides minimal dissection of the neurovascular bundle but ample exposure for reconstruction with a hemicortical allograft.

  12. Metastatic well differentiated squamous cell carcinoma in the prepuce of a dog: a report of clinicopathological, immunophenotypic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    P.A. Auler

    2014-10-01

    Full Text Available This report describes a case of a well differentiated squamous cell carcinoma (SCC of the foreskin of a dog, with metastasis in the regional lymph node. A six-year-old male intact Pit Bull dog presented a preputial ulcerated lesion with an evolution time of one year and enlarged left inguinal lymph node. Surgical resection of the preputial lesion and inguinal lymph nodes was made. The diagnosis of a well differentiated SCC was made following histopathological analysis and immunohistochemistry technique was used to confirm lymph node metastasis and to determine the histological features of the tumor. Here we demonstrated that immunohistochemistry can be an important complementary diagnostic tool to assess the prognostic features of SCC and to determine the treatment of choice. Also, the combination of COX-2 selective inhibitors in adjuvant therapy is presented as an effective alternative treatment for metastatic SCC in dogs.

  13. Biology and therapeutic advances for pediatric osteosarcoma.

    Science.gov (United States)

    Marina, Neyssa; Gebhardt, Mark; Teot, Lisa; Gorlick, Richard

    2004-01-01

    Osteosarcoma is the most common malignant bone tumor in children and adolescents. Survival for these patients was poor with the use of surgery and/or radiotherapy. The introduction of multi-agent chemotherapy dramatically improved the outcome for these patients and the majority of modern series report 3-year disease-free survival of 60%-70%. This paper describes current strategies for treating patients with osteosarcoma as well as review of the clinical features, radiologic and diagnostic work-up, and pathology. The authors review the state of the art management for patients with osteosarcoma in North America and Europe including the use of limb-salvage procedures and reconstruction as well as discuss the etiologic and biologic factors associated with tumor development. Therapy-related sequelae and future directions in the biology and therapy for these patients are also discussed. Copyright AlphaMed Press

  14. Molecular Alterations Associated with Osteosarcoma Development

    Directory of Open Access Journals (Sweden)

    Kosei Ando

    2012-01-01

    Full Text Available Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.

  15. Primary renal osteosarcoma with systemic dissemination

    Directory of Open Access Journals (Sweden)

    Tarun Puri

    2012-01-01

    Full Text Available Primary renal osteosarcoma is an uncommon disease, which, unlike its skeletal counterpart, presents mostly in adults, and is generally diagnosed late due to its non-specific features and intra-abdominal location. Even if the disease is localized at diagnosis, it follows an aggressive course despite radical surgery and adjuvant treatment. We report a case of renal osteosarcoma in a 65-year-old female, who developed regional recurrence, and lung and bone metastases soon after radical nephrectomy for localized disease. Chemotherapy was ineffective in controlling systemic disease.

  16. Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

    Science.gov (United States)

    Evola, Francesco R.; Costarella, Luciano; Pavone, Vito; Caff, Giuseppe; Cannavò, Luca; Sessa, Andrea; Avondo, Sergio; Sessa, Giuseppe

    2017-01-01

    Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the diagnosis and assist in subtyping bone tumors. Here, we review these markers and discuss their role in the diagnosis and prognosis of the three most frequent malignant bone neoplasms, namely osteosarcoma, chondrosarcoma, and Ewing sarcoma. PMID:28439237

  17. Pediatric Chondromyxoid Fibroma-Like Osteosarcoma.

    Science.gov (United States)

    Stark, Matthew; Heinrich, Stephen D; Sivashanmugam, Raju; Mackey, Dane; Wasilewska, Ewa; Craver, Randall

    2017-04-01

    Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is a low-grade osteosarcoma, often misdiagnosed on initial biopsy as a benign lesion, with five cases previously described. We report a 13-year-old male with an intramedullary lytic CMF-OS of the right tibial proximal metaphysis with cortical destruction and soft tissue extension. Diagnosis was based on malignant new bone formation, increased mitotic figures, lamellar bone permeation with bony destruction, and correlation with imaging studies. There were no metastasis at presentation and the tumor showed good response to standard chemotherapy with >95% necrosis.

  18. Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases

    National Research Council Canada - National Science Library

    Koshkina, Nadezhda V; Kleinerman, Eugenie S

    2005-01-01

    .... We used 2 osteosarcoma lung metastases animal models: human LM7 cells that form lung metastases in mice following intravenous injection and murine LM8 cells, which grows subcutaneously in mice and spontaneously metastasize to the lung...

  19. Primary Metastatic Osteosarcoma: Presentation and Outcome of Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

    National Research Council Canada - National Science Library

    Leo Kager; Andreas Zoubek; Ulrike Pötschger; Ulrike Kastner; Silke Flege; Beate Kempf-Bielack; Detlev Branscheid; Rainer Kotz; Mechthild Salzer-Kuntschik; Winfried Winkelmann; Gernot Jundt; Hartmut Kabisch; Peter Reichardt; Heribert Jürgens; Helmut Gadner; Stefan S. Bielack; for the Cooperative German-Austrian-Swiss Osteosarcoma Study Group

    2003-01-01

    To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation...

  20. PSMC2 is up-regulated in osteosarcoma and regulates osteosarcoma cell proliferation, apoptosis and migration

    Science.gov (United States)

    Song, Mingzhi; Wang, Yong

    2017-01-01

    Proteasome 26S subunit ATPase 2 (PSMC2) is a recently identified gene potentially associated with certain human carcinogenesis. However, the expressional correlation and functional importance of PSMC2 in osteosarcoma is still unclear. Current study was focused on elucidating the significance of PSMC2 on malignant behaviors in osteosarcoma including proliferation, apoptosis, colony formation, migration as well as invasion. The high protein levels of PSMC2 in osteosarcoma samples were identified by tissue microarrays analysis. Besides, its expression in the levels of mRNA and protein was also detected in four different osteosarcoma cell lines by real-time PCR and western blotting separately. Silencing PSMC2 by RNA interference in osteosarcoma cell lines (SaoS-2 and MG-63) would significantly suppress cell proliferation, enhance apoptosis, accelerate G2/M phase and/or S phase arrest, and decrease single cell colony formation. Similarly, pharmaceutical inhibition of proteasome with MG132 would mimic the PSMC2 depletion induced defects in cell cycle arrest, apoptosis and colonies formation. Silencing of PSMC2 was able to inhibit osteosarcoma cell motility, invasion as well as tumorigenicity in nude mice. Moreover, the gene microarray indicated knockdown of PSMC2 notably changed a number of genes, especially some cancer related genes including ITGA6, FN1, CCND1, CCNE2 and TGFβR2, and whose expression changes were further confirmed by western blotting. Our data suggested that PSMC2 may work as an oncogene for osteosarcoma and that inhibition of PSMC2 may be a therapeutic strategy for osteosarcoma treatment. PMID:27888613

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

    Energy Technology Data Exchange (ETDEWEB)

    Ram Kumar, Ram Mohan, E-mail: rkumar@research.balgrist.ch; Fuchs, Bruno [Laboratory for Orthopaedic Research, Balgrist University Hospital, Sarcoma Center-UZH University of Zurich, Zurich 8008 (Switzerland)

    2015-05-13

    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.

  2. CYR61 downregulation reduces osteosarcoma cell invasion, migration, and metastasis.

    Science.gov (United States)

    Fromigue, Olivia; Hamidouche, Zahia; Vaudin, Pascal; Lecanda, Fernando; Patino, Ana; Barbry, Pascal; Mari, Bernard; Marie, Pierre J

    2011-07-01

    Osteosarcoma is the most common primary tumor of bone. The rapid development of metastatic lesions and resistance to chemotherapy remain major mechanisms responsible for the failure of treatments and the poor survival rate for patients. We showed previously that the HMGCoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor statin exhibits antitumoral effects on osteosarcoma cells. Here, using microarray analysis, we identify Cyr61 as a new target of statins. Transcriptome and molecular analyses revealed that statins downregulate Cyr61 expression in human and murine osteosarcoma cells. Cyr61 silencing in osteosarcoma cell lines enhanced cell death and reduced cell migration and cell invasion compared with parental cells, whereas Cyr61 overexpression had opposite effects. Cyr61 expression was evaluated in 231 tissue cores from osteosarcoma patients. Tissue microarray analysis revealed that Cyr61 protein expression was higher in human osteosarcoma than in normal bone tissue and was further increased in metastatic tissues. Finally, tumor behavior and metastasis occurrence were analyzed by intramuscular injection of modified osteosarcoma cells into BALB/c mice. Cyr61 overexpression enhanced lung metastasis development, whereas cyr61 silencing strongly reduced lung metastases in mice. The results reveal that cyr61 expression increases with tumor grade in human osteosarcoma and demonstrate that cyr61 silencing inhibits in vitro osteosarcoma cell invasion and migration as well as in vivo lung metastases in mice. These data provide a novel molecular target for therapeutic intervention in metastatic osteosarcoma. Copyright © 2011 American Society for Bone and Mineral Research.

  3. PERSPECTIVES ON CANCER STEM CELLS IN OSTEOSARCOMA

    Science.gov (United States)

    Basu-Roy, Upal; Basilico, Claudio; Mansukhani, Alka

    2012-01-01

    Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are derived from progenitor cells in the osteoblast lineage that have accumulated mutations to escape cell cycle checkpoints leading to excessive proliferation and defects in their ability to differentiate appropriately into mature bone-forming osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous, consisting of phenotypically distinct cells with features of different stages of differentiation. The cancer stem cell hypothesis posits that tumors are maintained by stem cells and it is the incomplete eradication of a refractory population of tumor-initiating stem cells that accounts for drug resistance and tumor relapse. In this review we present our current knowledge about the biology of osteosarcoma stem cells from mouse and human tumors, highlighting new insights and unresolved issues in the identification of this elusive population. We focus on factors and pathways that are implicated in maintaining such cells, and differences from paradigms of epithelial cancers. Targeting of the cancer stem cells in osteosarcoma is a promising avenue to explore to develop new therapies for this devastating childhood cancer. PMID:22659734

  4. Surface osteosarcoma: Clinical features and therapeutic implications

    Directory of Open Access Journals (Sweden)

    H. Nouri

    2015-12-01

    Conclusion: Histological grade of malignancy is the main point to assess in surface osteosarcoma since it determines treatment and prognosis. Low grade lesions should be treated by wide resection, while high grade lesions need more aggressive surgical approach associated to post operative chemotherapy.

  5. Future directions in the treatment of osteosarcoma.

    Science.gov (United States)

    Bishop, Michael W; Janeway, Katherine A; Gorlick, Richard

    2016-02-01

    Overall survival rates for osteosarcoma have remained essentially unchanged over the past 3 decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in the comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies. Recent results from international collaborative trials have failed to demonstrate an ability to improve outcomes using a design in which the randomized question is dictated based on histologic response to preoperative chemotherapy. Novel prognostic markers assessable at diagnosis are vital to identifying subsets of osteosarcoma. Clinical trials focus has now shifted to serial phase II studies of novel agents to evaluate for activity in recurrent and refractory disease. In-depth analyses have revealed profound genomic instability and heterogeneity across patients, with nearly universal TP53 aberration. Although driver mutational events have not clearly been established, frequent derangements in specific pathways may suggest opportunities for therapeutic exploitation. Genomic complexity may lend support to a role for immune-mediated therapies. Rigorous preclinical investigations are potentially generating novel strategies for the treatment of osteosarcoma that will inform the next generation of clinical trials, with the opportunity to identify agents that will improve survival outcomes.

  6. Experimental model of osteosarcomas in rats

    Energy Technology Data Exchange (ETDEWEB)

    Jasmin, C.; Allouche, M.; Jude, J.G.; Klein, B. (Institut de Cancerologie et d' Immunogenetique, Villejuif (France)); Thiery, J.P.; Perdereau, B.; Gongora, R.; Gongora, G.; Mazabraud, A. (Institut Curie, Paris (France))

    1982-07-08

    Satisfactory experimental models for preclinical prediction in cancerology must answer the following criteria: reproducibility of the method used for inducing tumors; clinical, pathological and kinetic similarity with the corresponding human tumors. We have developed a model of osteosarcoma locally induced by insoluble radioactive cerium chloride (/sup 144/Ce Cl/sub 3/) in Sprague Dawley rats. This method yields over 80% of bone tumors at the injection site, of which approximately half are histologically similar to human tumors. These tumors double their volume fairly slowly (in approximately 20 days); lung metastases occur both early and frequently (80% of animals). A transplantable tumor was developed from an induced osteosarcoma and adapted to the Curie strain. Transplantation in the bone, next to the bone, or under the skin is followed by widespread metastatic dissemination. The kinetics and histological features of the primary tumor are maintained. Tumor /sup 85/strontium uptake is similar to that seen in human osteosarcomas. These new models of osteosarcomas are being used for evaluating new cancer chemotherapeutic agents and interferon, etc.

  7. Risedronate inhibits human osteosarcoma cell invasion

    Directory of Open Access Journals (Sweden)

    Jung Sung

    2009-07-01

    Full Text Available Abstract Background Osteosarcoma is a highly malignant bone tumor and is the most commonly encountered malignant bone tumor in children and adolescents. Furthermore, significant numbers of patients eventually develop pulmonary metastases and succumb to the disease even after conventional multi-agent chemotherapy and surgical excision. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs, and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs, which have a profound effect on bone resorption, are widely used to treat osteoclast-mediated bone diseases. BPs are also known to inhibit tumor growths and metastases in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer. Methods Two osteosarcoma cell lines (SaOS-2 and U2OS were treated with risedronate (0, 0.1, 1, 10 μM for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MMP-9 were analyzed by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MMP-9 protein were analyzed by Westernblot, the activities of MMP-2 and MMP-9 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after risedronate treatment. Results The invasiveness of osteosarcoma cell lines (SaOS-2, U2OS were reduced in a dose dependent manner follow 48 hour treatment of up to 10 μM of the risedronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MMP-9 were also suppressed by increasing risedronate concentrations. Conclusion Given that MMP-2 and MMP-9 are instrumental in tumor cell invasion, our results suggest the risedronate could reduce osteosarcoma cell invasion.

  8. Evaluation of quercetin as a potential drug in osteosarcoma treatment.

    Science.gov (United States)

    Berndt, Kersten; Campanile, Carmen; Muff, Roman; Strehler, Emanuel; Born, Walter; Fuchs, Bruno

    2013-04-01

    Osteosarcoma is the most common malignant bone tumor in children and young adults. Since the introduction of chemotherapy, the 5-year survival rate of patients with non-metastatic osteosarcoma is ~70%. The main problems in osteosarcoma therapy are the occurrence of metastases, severe side-effects and chemoresistance. Antiproliferative and apoptotic effects of quercetin were shown in several types of cancers, including breast cancer and lung carcinoma. The present study investigates the cytotoxic potential of quercetin, a dietary flavonoid, in a highly metastasizing human osteosarcoma cell line, 143B. We found that quercetin induces growth inhibition, G2/M phase arrest, and apoptosis in the 143B osteosarcoma cell line. We also observed impaired adhesion and migratory potential after the addition of quercetin. Since quercetin has already been shown to have low side effects in a clinical phase I trial in advanced cancer patients, this compound may have considerable potential for osteosarcoma treatment.

  9. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t......-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...... 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...

  10. 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.

  11. 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

  12. Osteopontin Upregulates the Expression of Glucose Transporters in Osteosarcoma Cells

    Science.gov (United States)

    Hsieh, I-Shan; Yang, Rong-Sen; Fu, Wen-Mei

    2014-01-01

    Osteosarcoma is the most common primary malignancy of bone. Even after the traditional standard surgical therapy, metastasis still occurs in a high percentage of patients. Glucose is an important source of metabolic energy for tumor proliferation and survival. Tumors usually overexpress glucose transporters, especially hypoxia-responsive glucose transporter 1 and glucose transporter 3. Osteopontin, hypoxia-responsive glucose transporter 1, and glucose transporter 3 are overexpressed in many types of tumors and have been linked to tumorigenesis and metastasis. In this study, we investigated the regulation of glucose transporters by osteopontin in osteosarcoma. We observed that both glucose transporters and osteopontin were upregulated in hypoxic human osteosarcoma cells. Endogenously released osteopontin regulated the expression of glucose transporter 1 and glucose transporter 3 in osteosarcoma and enhanced glucose uptake into cells via the αvβ3 integrin. Knockdown of osteopontin induced cell death in 20% of osteosarcoma cells. Phloretin, a glucose transporter inhibitor, also caused cell death by treatment alone. The phloretin-induced cell death was significantly enhanced in osteopontin knockdown osteosarcoma cells. Combination of a low dose of phloretin and chemotherapeutic drugs, such as daunomycin, 5-Fu, etoposide, and methotrexate, exhibited synergistic cytotoxic effects in three osteosarcoma cell lines. Inhibition of glucose transporters markedly potentiated the apoptotic sensitivity of chemotherapeutic drugs in osteosarcoma. These results indicate that the combination of a low dose of a glucose transporter inhibitor with cytotoxic drugs may be beneficial for treating osteosarcoma patients. PMID:25310823

  13. Precision medicine for diagnosis and treatment of osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    Rui Wang; Freddie H Fu; Bing Wang

    2016-01-01

    Osteosarcoma is one of the most common primary malignant bone tumors, most commonly afecting chil-dren and adolescents. With a low 5-year survival rate, osteosarcoma is among the most dangerous threats to the health and life of young people. In many cases, lung micro-metastases are detected at the time of osteosarcoma diagnosis, which makes it very dificult to save patients’ lives even with very radical treat-ments such as surgical amputation to remove the primary lesion. Patients with osteosarcoma often die of lung metastatic disease. The diagnosis of osteosarcoma at an early stage is therefore very important for disease prognosis. Osteosarcoma shows a remarkable variation in its pathologic presentation between its diferent pathologic sub-types and from patient to patient. Prior to displaying any abnormalities in celular morphology, molecular and biochemical metabolic changes may occur, leading to increases in abnormaly functioning oncoproteins. New evidence from molecular biological and genomic studies provides critical information about the occurrence, development, metastasis, and prognosis of osteosarcoma. The precision medicine approach, which alows for individualized treatment, has improved the prognosis and treatment outcomes for osteosarcoma. This review aims to comprehensively summarize the recent key discoveries in osteosarcoma and to highlight optimal strategies for diagnosis and treatment.

  14. Salinomycin inhibits osteosarcoma by targeting its tumor stem cells.

    Science.gov (United States)

    Tang, Qing-Lian; Zhao, Zhi-Qiang; Li, Jin-Chun; Liang, Yi; Yin, Jun-Qiang; Zou, Chang-Ye; Xie, Xian-Biao; Zeng, Yi-Xin; Shen, Jing-Nan; Kang, Tiebang; Wang, Jin

    2011-12-01

    Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are presumed to drive tumor initiation and tumor relapse or metastasis. Hence, the poor prognosis of osteosarcoma likely results from a failure to target the osteosarcoma stem cells. Here, we have utilized three different methods to enrich TSCs in osteosarcoma and further evaluated whether salinomycin could selectively target TSCs in osteosarcoma. Our results indicated that sarcosphere selection, chemotherapy selection and stem cell marker OCT4 or SOX2 over-expression are all effective in the enrichment of TSCs from osteosarcoma cell lines. Further investigation found that salinomycin inhibited osteosarcoma by selectively targeting its stem cells both in vitro and in vivo without severe side effects, and the Wnt/β-catenin signaling pathway may be involved in this inhibition of salinomycin. Taken together, we have identified that salinomycin is an effective inhibitor of osteosarcoma stem cells, supporting the use of salinomycin for elimination of osteosarcoma stem cells and implying a need for further clinical evaluation.

  15. LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients.

    Science.gov (United States)

    Yong, Bi-Cheng; Lu, Jin-Chang; Xie, Xian-Biao; Su, Qiao; Tan, Ping-Xian; Tang, Qing-Lian; Wang, Jing; Huang, Gang; Han, Ju; Xu, Hong-Wen; Shen, Jing-Nan

    2017-02-01

    Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan-Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan-Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas.

  16. 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.

  17. Aberrant ADAM10 expression correlates with osteosarcoma progression

    Science.gov (United States)

    2014-01-01

    Background Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear. Method Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP). Results Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining. Conclusions Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation. PMID:24548763

  18. Smoothened as a new therapeutic target for human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Nagao Hiroko

    2010-01-01

    Full Text Available Abstract Background The Hedgehog signaling pathway functions as an organizer in embryonic development. Recent studies have demonstrated constitutive activation of Hedgehog pathway in various types of malignancies. However, it remains unclear how Hedgehog pathway is involved in the pathogenesis of osteosarcoma. To explore the involvement of aberrant Hedgehog pathway in the pathogenesis of osteosarcoma, we investigated the expression and activation of Hedgehog pathway in osteosarcoma and examined the effect of SMOOTHENED (SMO inhibition. Results To evaluate the expression of genes of Hedgehog pathway, we performed real-time PCR and immunohistochemistry using osteosarcoma cell lines and osteosarcoma biopsy specimens. To evaluate the effect of SMO inhibition, we did cell viability, colony formation, cell cycle in vitro and xenograft model in vivo. Real-time PCR revealed that osteosarcoma cell lines over-expressed Sonic hedgehog, Indian hedgehog, PTCH1, SMO, and GLI. Real-time PCR revealed over-expression of SMO, PTCH1, and GLI2 in osteosarcoma biopsy specimens. These findings showed that Hedgehog pathway is activated in osteosarcomas. Inhibition of SMO by cyclopamine, a specific inhibitor of SMO, slowed the growth of osteosarcoma in vitro. Cell cycle analysis revealed that cyclopamine promoted G1 arrest. Cyclopamine reduced the expression of accelerators of the cell cycle including cyclin D1, cyclin E1, SKP2, and pRb. On the other hand, p21cip1 wprotein was up-regulated by cyclopamine treatment. In addition, knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo. Conclusions These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma.

  19. 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.

  20. Serum fluoride and sialic acid levels in osteosarcoma.

    Science.gov (United States)

    Sandhu, R; Lal, H; Kundu, Z S; Kharb, S

    2011-12-01

    Osteosarcoma is a rare malignant bone tumor most commonly occurring in children and young adults presenting with painful swelling. Various etiological factors for osteosarcoma are ionizing radiation, family history of bone disorders and cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status of fluoride levels in serum of osteosarcoma is still not clear. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones. The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by Warren's method. Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease.

  1. 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

  2. Mandibular Osteosarcoma in Cat: Case report

    OpenAIRE

    2011-01-01

    The primary malignant bone tumors are uncommon in cats. Osteosarcoma is the most frequently observed in old animals. This tumors affects the appendicular skeleton, however the axial skeleton is also affected, but the bones of the head and pelvis frequent sites of injury. This paper reports a case of a cat with a history of progressive swelling in the left mandible, with follow-up period of four months. The presumptive diagnosis of osteopathy, signed by clinical and radiographic observations w...

  3. Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

    OpenAIRE

    Evola, Francesco R.; Costarella, Luciano; Pavone, Vito; Caff, Giuseppe; Cannavò, Luca; Sessa, Andrea; Avondo, Sergio; Sessa, Giuseppe

    2017-01-01

    Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the d...

  4. 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.

  5. The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene.

    Science.gov (United States)

    Filion, C; Motoi, T; Olshen, A B; Laé, M; Emnett, R J; Gutmann, D H; Perry, A; Ladanyi, M; Labelle, Y

    2009-01-01

    The NR4A3 nuclear receptor is implicated in the development of extraskeletal myxoid chondrosarcoma (EMC), primitive sarcoma unrelated to conventional chondrosarcomas, through a specific fusion with EWSR1 resulting in an aberrant fusion protein that is thought to disrupt the transcriptional regulation of specific target genes. We performed an expression microarray analysis of EMC tumours expressing the EWSR1/NR4A3 fusion protein, comparing their expression profiles to those of other sarcoma types. We thereby identified a set of genes significantly overexpressed in EMC relative to other sarcomas, including PPARG and NDRG2. Western blot or immunohistochemical analyses confirm that PPARG and NDRG2 are expressed in tumours positive for EWSR1/NR4A3. Bioinformatic analysis identified a DNA response element for EWSR1/NR4A3 in the PPARG promoter, and band-shift experiments and transient transfections indicate that EWSR1/NR4A3 can activate transcription through this element. Western blots further show that an isoform of the native NR4A3 receptor lacking the C-terminal domain is very highly expressed in tumours positive for EWSR1/NR4A3, and co-transfections of this isoform along with EWSR1/NR4A3 indicate that it may negatively regulate the activity of the fusion protein on the PPARG promoter. These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours. The specific up-regulation of PPARG by EWSR1/NR4A3 may also have potential therapeutic implications.

  6. Tissue-engineered triphasic ceramic coated hydroxyapatite induced bone formation and vascularization at an extraskeletal site in a rat model

    Indian Academy of Sciences (India)

    Manitha B Nair; H K Varma; P V Mohanan; Annie John

    2011-12-01

    Tissue-engineered bone regeneration has attracted much attention because of its high clinical demand for restoration of injured tissues. In the present study, we have evaluated the capability of bare (without cells) and tissue-engineered (with osteogenic-induced rat Mesenchymal Stem Cells (MSCs)) bioactive ceramics such as hydroxyapatite (HA) and triphasic ceramic-coated hydroxyapatite (HASi) to mediate vascularisation and osteoinduction at an extraskeletal site of rat model. The viability, proliferation and osteogenic differentiation of MSCs on the scaffolds were assessed in vitro and thereby established the capability of HASi in providing a better structural habitat than HA. The vascular invasion was relatively low in bare and tissueengineered HA at 2 and 4 weeks. Interestingly, the implantation site was well vascularised with profuse ingrowth of blood capillaries in HASi groups, with preference for tissue-engineered HASi groups. Similarly, neo-osteogenesis studies were shown only by tissue-engineered HASi groups. The ingrowth of numerous osteoblast-like cells was seen around and within the pores of the material in bare HASi and tissue-engineered HASi groups (very low cellular infiltration in bare HA groups), but there was no osteoid deposition. The positive impact in forming bone in tissue-engineered HASi groups is attributable to the scaffold and to the cells, with the first choice for scaffold because both HA and HASi were engineered simultaneously with the cells from same source and same passage. Thus, highly porous interconnected porous structure and appropriate chemistry provided by HASi in combination with osteogenic-induced MSCs facilitated better vascularisation that lead to neo-osteogenesis.

  7. 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 c

  8. Meningeal chondroblastic osteosarcoma: case report and review of the literature.

    Science.gov (United States)

    Romeo, Emilie; Gisserot, Olivier; de Jaureguiberry, Jean-Pierre; Desse, Nicolas; Souraud, Jean-Baptiste; Salem, Naji; Faivre, Anthony; Bouvier, Corinne; Bertucci, François

    2010-11-01

    Primary meningeal osteosarcomas are exceedingly rare. We report a case of a 51-year-old man with a chondroblastic osteosarcoma treated with pre-operative embolization, surgical removal, followed by adjuvant chemotherapy and radiation therapy. Patient is alive without any recurrence 43 months after diagnosis.

  9. Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells.

    Science.gov (United States)

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

    2017-04-29

    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-PKCS), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PKCS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PKCS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PKCS 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-PKCS inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A systems biology approach to study high-grade osteosarcoma

    NARCIS (Netherlands)

    Kuijjer, Marieke Lydia

    2013-01-01

    High-grade osteosarcoma is a primary bone tumor with complex genetic alterations, for which targeted therapy is lacking. The aim of this thesis was to use high-throughput molecular data analysis of high-grade osteosarcoma specimens and model systems, in order to learn more on osteosarcomagenesis and

  11. 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

  12. 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.

  13. 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.

  14. A systems biology approach to study high-grade osteosarcoma

    NARCIS (Netherlands)

    Kuijjer, Marieke Lydia

    2013-01-01

    High-grade osteosarcoma is a primary bone tumor with complex genetic alterations, for which targeted therapy is lacking. The aim of this thesis was to use high-throughput molecular data analysis of high-grade osteosarcoma specimens and model systems, in order to learn more on osteosarcomagenesis and

  15. Tumor blood vessels formation in osteosarcoma:vasculogenesis mimicry

    Institute of Scientific and Technical Information of China (English)

    蔡宣松; 贾永伟; 梅炯; 汤如勇

    2004-01-01

    Background Osteosarcoma is characterized by high neovascularization and a high propensity for metastasis through bloodstream. This study was to examine whether there is evidence for vasculogenic mimicry in osteosarcoma and to illustrate mechanism of tumor blood vessels formation in osteosarcoma.Methods Osteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type Ⅰ collagen. The structures of the tubular networks were observed with phase contrast microscope and transmission electron microscope (TEM). Morphometric studies using hematoxylin and eosin (HE) stain and CD31 immunohistochemical stain to show tumor-lined channels in human osteosarcoma were also performed.Results Observation with light microscope and TEM showed that highly aggressive osteosarcoma cell lines (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type Ⅰ collagen, in the absence of endothelial cells or fibroblasts. Morphometric observation using HE stain and CD31 immunohistochemical stain showed that tumor cell-lined channels were also detected in vivo in osteosarcoma; by comparison, all vascular areas in the pedicel of osteochondroma or outside osteochondroma were endothelial-lined.Conclusion These observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry.

  16. Increased expression of serum gelsolin in patients with osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    JIN Song; SHEN Jing-nan; PENG Jian-qiang; WANG Jin; HUANG Gang; LI Ming-tao

    2012-01-01

    Background Identification of potential serum biomarkers of osteosarcoma to aid in its early diagnosis and in the discovery of possible therapeutic targets is an area of increasing interest.Methods Two-dimensional difference-in-gel electrophoresis was used to assess multiple serum samples in patients with osteosarcoma.In addition,differential expression of protein biomarkers was characterized in osteosarcoma serum by using matrix-assisted desorption/ionization time-of-flight mass spectrometry coupled with database interrogation.Serum samples from four individuals with osteosarcoma and four age- and sex-matched healthy control subjects were compared.Results Fifty-eight significant protein spot features in the osteosarcoma sera were found.These spot features were excised,digested with trypsin,and analyzed with mass spectrometry.Gelsolin was down-regulated only in osteosarcoma.Furthermore,Western blotting and enzyme linked immunosorbent assay (ELISA) confirmed decreased levels of gelsolin in the osteosarcoma serum samples.Conclusions These results indicated that gelsolin might have great potential as a biomarker of osteosarcoma and as a potential target for gene therapy.

  17. Strategies for the targeted delivery of therapeutics for osteosarcoma.

    Science.gov (United States)

    Hughes, Dennis P M

    2009-12-01

    Conventional therapy for osteosarcoma has reached a plateau of 60 - 70%, a 5-year survival rate that has changed little in two decades, highlighting the need for new approaches. To review the alternative means of delivering effective therapy for osteosarcoma that reach beyond the central venous catheter. Drawing on the author's own experiences providing care to high-risk osteosarcoma patients and reviewing the last two decades of literature describing sarcoma therapy, available information is summarized about potential osteosarcoma treatments that deliver therapy by a less conventional route. Intra-arterial chemotherapy has a limited impact on survival, but may help to achieve a better limb salvage. Intrapleural chemotherapy is important for managing malignant effusions. The development of inhalation therapies, treatments that target new bone formation such as bisphosphonates, chemically targeted radiation and antibody-based therapies all have potential to improve osteosarcoma therapy.

  18. 3D-printed guiding templates for improved osteosarcoma resection

    Science.gov (United States)

    Ma, Limin; Zhou, Ye; Zhu, Ye; Lin, Zefeng; Wang, Yingjun; Zhang, Yu; Xia, Hong; Mao, Chuanbin

    2016-03-01

    Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125.

  19. Tim-3 as a diagnostic and prognostic biomarker of osteosarcoma.

    Science.gov (United States)

    Ge, Wenhui; Li, Jing; Fan, Wenhao; Xu, Delong; Sun, Shangfei

    2017-07-01

    Osteosarcoma is the most frequent primary bone tumor that affects adolescents and children. However, diagnostic and prognostic biomarkers for osteosarcoma remain lacking. (Tim-3) T-cell immunoglobulin domain and mucin domain-3, which negatively regulates T cell helper (Th1) cells and affects cytokine expression, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In this study, we evaluated serum soluble Tim-3 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Serum soluble Tim-3 level was measured with enzyme-linked immunosorbent assay in 120 osteosarcoma patients, 120 benign bone tumors patients and 120 healthy controls, followed by analysis of the correlation with clinic pathological characteristics. Receiver operating curves, Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate the diagnostic and prognostic significance. Serum solubleTim-3 level was remarkably elevated in osteosarcoma patients. Osteosarcoma patients with larger tumor size, late stages and distant metastases were accompanied with higher levels of Tim-3. ROC/AUC analysis indicated thatTim-3 served as a reliable marker to distinguish healthy participants from Tim-3 patients. Osteosarcoma patients with higher Tim-3 had relatively lower survival. Multivariate analyses for overall survival revealed that high serum soluble Tim-3 level was an independent prognostic factor for osteosarcoma. Furthermore, Tim-3 levels of CD8+ and CD4+ T cells were elevated in peripheral circulation of osteosarcoma patients. Therefore, It was indicated in our research that elevated serum soluble Tim-3 level might be a novel potential diagnostic and prognostic biomarker for osteosarcoma patients.

  20. Clinical and biological significance of PIM1 kinase in osteosarcoma.

    Science.gov (United States)

    Liao, Yunfei; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

    2016-07-01

    Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene serine/threonine-protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down-regulation of anti-apoptotic protein Bcl-2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185-1194, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Tenascin-C as a prognostic biomarker in osteosarcoma?

    Institute of Scientific and Technical Information of China (English)

    XIONG Wei; NIU Peng-yan; ZHU Wen-tao; CHEN Jing

    2009-01-01

    Background Treating metastatic osteosarcoma has been challenged in past decades. Extracelluar matrix (ECM) proteins play an important role in the progression of osteosarcoma as they are pivotal components of the tumor microoenvironment. Here, we identified potential genes belonging to the ECM and characterized the roles of these genes in the progression of osteosarcoma and their association with outcomes.Methods Osteosarcoma parental cell line MG63 and its derivative MG63-A1 with a high metastatic potential underwent oligonucleotide microarray analysis. Gene ontology analysis was used to screen deregulated genes between the 2 cell lines which were either upregulated or downregulated by more than 4 fold, particularly focusing on mRNAs encoding extracellular matrix proteins. The expression of resulting candidate genes was then validated by reverse transcription-PCR for mRNA expression as well as Western blotting for protein expression. Immunohistochemistry was performed on 37 osteosarcoma specimens to examine the potential role of the candidate genes in a clinical context.Results Microarray data and gene ontology analysis showed that Tenascin-C, a critical component of the EGM, is significantly down-regulated in the highly metastatic cell line MG63A1 compared with the parental osteosarcoma cell line MG63-wt. This finding was validated at mRNA and protein levels. Immunohistochemical analysis found that Tenascin-C is located in the intercellular space in osteosarcoma specimens. Furthermore, low-grade Tenascin-C expression (less than 20%) in osteosarcoma specimens was associated with poor survival.Conclusions Tenascin-C expression level correlates with the survival of osteosarcoma patients. Its biological functional role and underlying molecular mechanisms in the progression of osteosarcoma needs further investigation.

  2. 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.

  3. 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.)

  4. Multicystic and well-differentiated papillary peritoneal mesothelioma treated by surgical cytoreduction and hyperthermic intra-peritoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Baratti, D; Kusamura, S; Nonaka, D; Oliva, G D; Laterza, B; Deraco, M

    2007-10-01

    Multicystic peritoneal mesothelioma (MPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM) are exceedingly uncommon lesions with uncertain malignant potential and no uniform treatment strategy. The aim of the current study was to review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in these clinical settings. Four women with MPM and eight with WDPPM underwent 13 procedures of cytoreduction and close-abdomen HIPEC with cis-platin and doxorubicin. Seven patients had recurrent disease after previous debulking (one operation in five patients, two in one, four in one). Potential clinicopathological prognostic factors were assessed. Optimal cytoreduction (residual tumor nodules mesothelioma was documented in one patient who died of disease progression following incomplete cytoreduction and HIPEC. Following multimodality treatment, 5-year overall and progression-free survival were 90.0% (standard error = 9.0) and 79.7% (11.9), respectively. Progression-free survival following previous debulking surgery (median 24 months; range 2-87) was statistically worse (P = .0156). Incomplete cytoreduction and poor performance status correlated to both reduced overall and progression-free survival after cytoreduction and HIPEC. MPM and WDPPM are borderline tumors capable of transformation into potentially lethal processes. Definitive tumor eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease recurrence or transition to aggressive malignancies.

  5. Non-functioning well-differentiated neuroendocrine tumor of the extrahepatic bile duct:an unusual suspect?

    Institute of Scientific and Technical Information of China (English)

    Harsheet Sethi; Mansoor Madanur; Parthi Srinivasan; Bernard Portmann; Nigel Heaton; Mohamed Rela

    2007-01-01

    BACKGROUND: Neuroendocrine tumors (NETs) arising in the biliary tree are extremely rare, and 37 cases were identiifed in the English literature. METHODS: A well-differentiated NET was found arising from the junction of the cystic and common hepatic ducts, in a 51-year-old male presenting with pedal edema and weight loss with abnormal liver enzymes and a normal serum bilirubin level. No mass was seen on radiological imaging and biopsy of the liver was suggestive of an early cholangiopathy. A bile leak complicating the liver biopsy led to an ERCP that demonstrated a iflling defect suggestive of a mass in the common bile duct (CBD). RESULTS: He underwent a successful excision of the tumor with a Roux-en-Y hepaticojejunostomy. The diagnosis of NET was made on histological and immunohistochemical analysis of the resected specimen. He remains well and disease free 22 months after surgery. CONCLUSIONS: Recognition of biliary NET continues to be a challenge and an increased awareness of these tumors in rare sites will result in optimal management of these tumors.

  6. Genetically modified T cells targeting interleukin-11 receptor α-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases

    National Research Council Canada - National Science Library

    Huang, Gangxiong; Yu, Ling; Cooper, Laurence J N; Hollomon, Mario; Huls, Helen; Kleinerman, Eugenie S

    2012-01-01

    .... In the current study, we found that interleukin (IL)-11Rα was selectively expressed on 14 of 16 osteosarcoma patients' lung metastases and four different human osteosarcoma cell lines, indicating that IL-11Rα...

  7. Focal adhesion kinase overexpression and its impact on human osteosarcoma

    Science.gov (United States)

    Chen, Yong; Yang, Aizhen; Chen, Hui; Zhang, Jian; Wu, Sujia; Shi, Xin; Wang, Chen; Sun, Xiaoliang

    2015-01-01

    Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various malignancies. We sought to examine the expression patterns of FAK and the activated form, phosphorylated FAK (pFAK), in human osteosarcoma and to investigate the correlation of FAK expression with clinicopathologic parameters and prognosis. In addition, the functional consequence of manipulating the FAK protein level was investigated in human osteosarcoma cell lines. Immunohistochemical staining was used to detect FAK and pFAK in pathologic archived materials from 113 patients with primary osteosarcoma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognoses. The role of FAK in the cytological behavior of MG63 and 143B human osteosarcoma cell lines was studied via FAK protein knock down with siRNA. Cell proliferation, migration, invasiveness and apoptosis were assessed using the CCK8, Transwell and Annexin V/PI staining methods. Both FAK and pFAK were overexpressed in osteosarcoma. There were significant differences in overall survival between the FAK-/pFAK- and FAK+/pFAK- groups (P = 0.016), the FAK+/pFAK- and FAK+/pFAK+ groups (P = 0.012) and the FAK-/pFAK- and FAK+/pFAK+ groups (P osteosarcoma cell proliferation and apoptosis. These results collectively suggest that FAK overexpression and phosphorylation might predict more aggressive biologic behavior in osteosarcoma and may be an independent predictor of poor prognosis. PMID:26393679

  8. Cyr61 silencing reduces vascularization and dissemination of osteosarcoma tumors.

    Science.gov (United States)

    Habel, N; Vilalta, M; Bawa, O; Opolon, P; Blanco, J; Fromigué, O

    2015-06-11

    Osteosarcoma is the most prevalent primary pediatric cancer-related bone disease. These tumors frequently develop resistance to chemotherapy and are highly metastatic, leading to poor outcome. Thus, there is a need for new therapeutic strategies that can prevent cell dissemination. We previously showed that CYR61/CCN1 expression in osteosarcoma cells is correlated to aggressiveness both in vitro and in vivo in mouse models, as well as in patients. In this study, we found that CYR61 is a critical contributor to the vascularization of primary tumor. We demonstrate that silencing CYR61, using lentiviral transduction, leads to a significant reduction in expression level of pro-angiogenic markers such as VEGF, FGF2, PECAM and angiopoietins concomitantly to an increased expression of major anti-angiogenic markers such as thrombospondin-1 and SPARC. Matrix metalloproteinase-2 family member expression, a key pathway in osteosarcoma metastatic capacity was also downregulated when CYR61 was downregulated in osteosarcoma cells. Using a metastatic murine model, we show that CYR61 silencing in osteosarcoma cells results in reduced tumor vasculature and slows tumor growth compared with control. We also find that microvessel density correlates with lung metastasis occurrence and that CYR61 silencing in osteosarcoma cells limits the number of metastases. Taken together, our data indicate that CYR61 silencing can blunt the malignant behavior of osteosarcoma tumor cells by limiting primary tumor growth and dissemination process.

  9. IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα

    Science.gov (United States)

    Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J.

    2016-01-01

    Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activity of IAP antagonists (also known as Smac mimetics) using cells from primary and metastatic osteosarcomas that arose spontaneously in mice engineered to lack p53 and Rb expression in osteoblast-derived cells. The IAP antagonists SM-164, GDC-0152 and LCL161, which efficiently target XIAP and cIAPs, sensitized cells from most osteosarcomas to killing by low levels of TNFα but not TRAIL. RIPK1 expression levels and activity correlated with sensitivity. RIPK3 levels varied considerably between tumors and RIPK3 was not required for IAP antagonism to sensitize osteosarcoma cells to TNFα. IAP antagonists, including SM-164, lacked mutagenic activity. These data suggest that drugs targeting XIAP and cIAP1/2 may be effective for osteosarcoma patients whose tumors express abundant RIPK1 and contain high levels of TNFα, and would be unlikely to provoke therapy-induced cancers in osteosarcoma survivors. PMID:27129149

  10. SIRT1 promotes metastasis of human osteosarcoma cells.

    Science.gov (United States)

    Zhang, Ning; Xie, Tao; Xian, Miao; Wang, Yi-Jie; Li, Heng-Yuan; Ying, Mei-Dan; Ye, Zhao-Ming

    2016-11-29

    Pulmonary metastasis is the leading cause of mortality in patients with osteosarcoma; however, the underlying mechanism remains unclear. The NAD+-dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in carcinogenesis through deacetylation of important regulatory proteins. Here, we report that SIRT1 promotes osteosarcoma metastasis by regulating the expression of metastatic-associated genes. The SIRT1 protein was significantly upregulated in most primary osteosarcoma tumours, compared with normal tissues, and the SIRT1 expression level may be coupled with metastatic risk in patients with osteosarcoma. Moreover, the results of cell migration and wound-healing assays further suggested that higher expression of SIRT1 promoted invasive activity of osteosarcoma cells. Importantly, downregulating SIRT1 with shRNA inhibited the migration ability of osteosarcoma cells in vitro and suppressed tumour lung metastasis in mice. Finally, a gene expression analysis showed that knockdown of SIRT1 profoundly activated translation of its downstream pathway, particularly at migration and invasion. In summary, high levels of SIRT1 may be a biomarker for a high metastatic rate in osteosarcoma patients; inhibiting SIRT1 could be a potent therapeutic intervention for these patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. MDM2 antagonists synergize with PI3K/mTOR inhibition in well-differentiated/dedifferentiated liposarcomas.

    Science.gov (United States)

    Laroche, Audrey; Chaire, Vanessa; Algeo, Marie-Paule; Karanian, Marie; Fourneaux, Benjamin; Italiano, Antoine

    2017-08-15

    Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) are characterized by a consistent amplification of the MDM2 gene. The PI3K/AKT/mTOR pathway has been suggested to play also an important role in their tumorigenesis. Our goal was to determine whether combined MDM2 and PI3K/AKT/mTOR targeting is associated with higher anti-tumor activity than single agent alone in preclinical models of WDLPS/DDLPS. WDLPS/DDLPS cells were exposed to RG7388 (MDM2 antagonist) and BEZ235 (PI3K/mTOR dual inhibitor) after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival. Western blotting, histopathology, and tumor volume evolution were used for the assessment of treatment efficacy. The PI3K/AKT/mTOR was upregulated in up to 81% of the human WDLPS/DDLPS samples analysed. Treatment with RG7388 and BEZ235 resulted in a greater tumor activity than either drug alone with a significant difference in terms of cell viability after 72h of treatment with RG-73888 alone, BEZ235 alone and a combination of both agents. Consistent with these observations, we found a significant increase in apoptosis with the combination versus the single agent treatment alone. We then analysed the in vivo antitumor activity of RG7388 and BEZ235 in a xenograft model of DDLPS. The combination regimen significantly reduced tumor growth rate in comparison with single agent alone. Our results represent the first in vivo evidence of synergy between MDM2 and PI3K/AKT/mTOR antagonists and represent a strong rationale to evaluate the therapeutic potential of such a combination in WDLPS/DDLPS.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Blumenthal, Gideon M; Cortazar, Patricia; Zhang, Jenny J; Tang, Shenghui; Sridhara, Rajeshwari; Murgo, Anthony; Justice, Robert; Pazdur, Richard

    2012-01-01

    On May 20, 2011, the U.S. Food and Drug Administration (FDA) approved sunitinib malate capsules (Sutent®; Pfizer, Inc., New York) for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable locally advanced or metastatic disease. In a phase III randomized trial, 171 patients received either sunitinib (37.5 mg) or placebo once daily. The progression-free survival (PFS) interval was the primary efficacy endpoint. Secondary endpoints included the overall survival (OS) time, objective response rate (ORR), patient-reported outcomes, and safety. Based on early results favoring sunitinib, the independent data monitoring committee recommended trial termination prior to the prespecified interim analysis. This premature analysis may have led to an overestimate of the treatment effect. In the FDA analysis of investigator-assessed PFS times, the median values for the sunitinib and placebo arms were 10.2 months and 5.4 months, respectively. The ORRs were 9.3% and 0% in the sunitinib and placebo arms, respectively. The OS data were not mature at the time of approval and were confounded by 69% crossover. Common adverse reactions in patients receiving sunitinib included diarrhea, nausea, asthenia, fatigue, neutropenia, hypertension, and palmar-plantar erythrodysesthesia syndrome. Two patients on sunitinib died as a result of cardiac failure. The Oncologic Drugs Advisory Committee voted eight to two that, despite residual uncertainty about the magnitude of the PFS effect because of early trial termination, sunitinib demonstrated a favorable benefit-risk profile in pNET patients. The FDA concurred with the committee's assessment and granted sunitinib regular approval for this rare malignancy with few available therapies.

  15. Maxillary osteosarcoma in a beef suckler cow

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    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.

  16. Modular Tumor Resection Prosthesis in Osteosarcoma Treatment

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    Alper Cirakli

    2016-07-01

    Full Text Available Aim: The aim of the study is to evaluate the cases who underwent tumor resection prosthesis due to osteosarcoma. Material and Method: 14 cases who underwent tumor resection prosthesis due to osteosarcoma in our clinic between 2000 and 2012 and who had sufficient follow-ups were evaluated. The cases were examined in terms of gender, age, direction, tumor location, follow-up time, success of the treatment, complication, recurrence, and survival. The data obtained were transferred to the SPSS 15.0 program and analyzed. Normality distributions of the data were analyzed with the Shapiro-Wilk test. Results: 8 of the 14 cases were male, 6 were female, and the average age of the cases was 21.9±7.02. Osteosarcoma was in the distal femur in 9 (64.3% of the patients, in the proximal tibia in 5 (35.7% of the patients, in the right lower extremity in 5 of the patients, and in the left lower extremity in 9 of the patients. Average follow-up time was 33 months (3-144 months range. Average MSTS score was found as 81.9 (53-96 range, perfect results were taken in 11 (78.6% patients while insufficient results were taken in 3 (21.4% patients. As for complications, aseptic softening was observed in 3 cases, peroneal nerve paralysis was observed in 2 cases, skin necrosis was observed in 2 cases, periprostatic fracture was observed in 2 cases, prosthesis infection was observed in 1 case, and local recurrence was observed in 1 case. Except for the two cases with peroneal nerve paralysis, cases with complications recovered without any problems. The patient who developed local recurrence was lost due to lung metastasis. Discussion: Treatment of osteosarcoma through tumor resection prosthesis raises question marks due to possible complications that can affect the survival of the prosthesis in the long term. However, this treatment method is favorable in terms of stability, early load efficiency, and causing less anxiety than osteosynthesis; it is also psychologically

  17. Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma.

    Science.gov (United States)

    Rubin, Elyssa M; Guo, Yi; Tu, Khoa; Xie, Jun; Zi, Xiaolin; Hoang, Bang H

    2010-03-01

    It has been reported that the progression of osteosarcoma was closely associated with the aberrant activation of canonical Wnt signaling. Wnt inhibitory factor-1 (WIF-1) is a secreted Wnt inhibitor whose role in human osteosarcoma remains unknown. In this study, WIF-1 expression in NHOst and osteosarcoma cell lines was determined by real-time reverse transcription-PCR, methylation-specific PCR, and Western blotting analysis. In addition, tissue array from patient samples was examined for WIF-1 expression by immunohistochemistry. Compared with normal human osteoblasts, WIF-1 mRNA and protein levels were significantly downregulated in several osteosarcoma cell lines. The downregulation of WIF-1 mRNA expression is associated with its promoter hypermethylation in these tested cell lines. Importantly, WIF-1 expression was also downregulated in 76% of examined osteosarcoma cases. These results suggest that the downregulation of WIF-1 expression plays a role in osteosarcoma progression. To further study the potential tumor suppressor function of WIF-1 in osteosarcoma, we established stable 143B cell lines overexpressing WIF-1. WIF-1 overexpression significantly decreased tumor growth rate in nude mice as examined by the s.c. injection of 143B cells stably transfected with WIF-1 and vector control. WIF-1 overexpression also markedly reduced the number of lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Together, these data suggest that WIF-1 exerts potent antiosteosarcoma effect in vivo in mouse models. Therefore, the reexpression of WIF-1 in WIF-1-deficient osteosarcoma represents a potential novel treatment and preventive strategy.

  18. Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

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    Avudaiappan Maran

    2016-06-01

    Full Text Available Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin’s therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

  19. Primary cardiac osteosarcoma in a 42-year-old woman

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    Zou Jianyong

    2010-11-01

    Full Text Available Abstract We describe here a 42-year-old woman who was admitted to hospital with a pedunculated mass in her left atrium. She was diagnosed with a primary cardiac osteosarcoma with special immunohistochemical characteristics. Echocardiography and computed tomography can be used to differentiate cardiac osteosarcomas from routine intracardiac tumors. The patient was treated by surgical removal of the mass. Two years later, she has shown no evidence of disease recurrence. We discuss primary osteosarcomas in the cardiac cavity and their management.

  20. Radiological appearances of appendicular osteosarcoma: a comprehensive pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Suresh, S. [Department of Radiology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP (United Kingdom); Saifuddin, A. [Department of Radiology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP (United Kingdom) and Institute of Orthopaedics and Musculoskeletal Sciences, University College London, London (United Kingdom) and London Bone and Soft Tissue Tumour Unit, University College London, London (United Kingdom)]. E-mail: Asaifuddin@aol.com

    2007-04-15

    Osteosarcoma is the most common primary malignant tumour of bone in adolescents and young adults. Hence, a comprehensive knowledge of the common and unusual imaging appearance of this tumour is essential. Correct diagnosis of the various varieties of osteosarcoma is important for optimal clinical management including staging, biopsy, treatment and follow-up of patients. This review article provides a comprehensive approach to the radiological diagnosis of the different types of appendicular osteosarcoma and illustrates the role of CT and MRI in further characterisation.

  1. Minnelide reduces tumor burden in preclinical models of osteosarcoma

    Science.gov (United States)

    Banerjee, Sulagna; Thayanithy, Venugopal; Sangwan, Veena; Mackenzie, Tiffany N.; Saluja, Ashok K.; Subramanian, Subbaya

    2015-01-01

    Osteosarcoma is the most common bone cancer in children and adolescents with a five-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets NF-κB pathway. PMID:23499892

  2. Progress and opportunities for immune therapeutics in osteosarcoma.

    Science.gov (United States)

    Lettieri, Christina K; Appel, Nicole; Labban, Nicole; Lussier, Danielle M; Blattman, Joseph N; Hingorani, Pooja

    2016-10-01

    Survival outcomes for osteosarcoma have plateaued since the 1980s, and patients with relapsed or refractory disease have a particularly dismal outcome. Treatment options for these patients are limited primarily due to the paucity of effective therapeutics. Immune therapies such as tumor vaccines and traditional antigen-targeted monoclonal antibodies have had limited success in solid tumors. The recent discovery of novel immune checkpoint blockade strategies and their success in adult cancers has revitalized the use of immunotherapy strategies for the treatment of solid tumors. This paper summarizes existing data supporting the use of immune therapies in osteosarcoma and the progress of this class of drugs in osteosarcoma therapy.

  3. 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

  4. Primary Osteosarcoma of the Breast Arising in an Intraductal Papilloma

    Directory of Open Access Journals (Sweden)

    Khalefa Ali Alghofaily

    2017-01-01

    Full Text Available Introduction. Primary osteosarcoma of the breast is extremely rare, and an osteosarcoma arising from an intraductal papilloma is exceptional. Case Presentation. A 72-year-old Saudi Arabian woman presented with a solid, bone-containing breast mass that was diagnosed as primary osteosarcoma of the breast on biopsy. She had a history of untreated intraductal papilloma. Treatment was completed with a modified mastectomy after excluding extramammary metastases. However, she subsequently developed multiple recurrent lesions at the same site. Conclusion. Primary osteogenic sarcomas of the breast are very rare. Although the main treatment is resection the optimal management remains uncertain and prognosis is poor.

  5. 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).

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

    Institute of Scientific and Technical Information of China (English)

    Ji-Long Yang

    2014-01-01

    Osteosarcoma is a genetical y 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 comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), Sanger sequencing, cell culture, and molecular biological approaches. Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings, including novel rearrangement hotspots, osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes, VEGF and Wnt signaling pathway alterations, deletion of the WWOX gene, and amplification of the APEX1 and RUNX2 genes. Importantly, these genetic events associate significantly with pathogenesis, prognosis, progression, and therapeutic activity in osteosarcoma, suggesting their potential impact on improved managements of human osteosarcoma. This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.

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

    Science.gov (United States)

    Yang, Ji-Long

    2014-12-01

    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 comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), Sanger sequencing, cell culture, and molecular biological approaches. Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings, including novel rearrangement hotspots, osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes, VEGF and Wnt signaling pathway alterations, deletion of the WWOX gene, and amplification of the APEX1 and RUNX2 genes. Importantly, these genetic events associate significantly with pathogenesis, prognosis, progression, and therapeutic activity in osteosarcoma, suggesting their potential impact on improved managements of human osteosarcoma. This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin.

    Science.gov (United States)

    Wartofsky, Leonard

    2002-07-01

    A multicenter study was undertaken to ascertain prevalence and significance of recombinant human thyrotropin (rhTSH)-stimulated increases in thyroglobulin (Tg) levels in thyroid cancer patients classified to be at low risk for recurrence. Patients were eligible for enrollment if they had undergone near-total or total thyroidectomy and remnant ablation between 1-10 years prior to enrollment and had received thyroxine suppression therapy (THST) with a TSH level of < 0.5 mU/L and Tg level less than or equal to 5 ng/mL within the prior year. Patients with anti-Tg antibodies, distant metastases, or other evidence of residual disease were excluded. Four hundred eighty-six patients were entered into the study, and 300 were considered eligible and comprise the study population. TSH, Tg, and anti-Tg antibody levels were obtained at baseline, followed by intramuscular injection of 0.9 mg of rhTSH on days 1 and 2 and measurement of Tg on day 5. After rhTSH, 53 patients (18%) had elevations in Tg of at least 2 ng/mL, including 33 patients (11%) with increases from baseline of equal to or greater than 5 ng/mL. Patients with an initial advanced stage of disease were more likely to display elevations in Tg after rhTSH. One third of those with stage III disease displayed elevations in Tg of 2 ng/mL or more. Patients within 5 years of thyroidectomy were as likely to display elevations in rhTSH-stimulated Tg as those 5-10 years from surgery. In conclusion, these data suggest rhTSH-stimulated Tg testing without scan may be a useful tool in the follow-up of patients with low-risk thyroid cancer, and may serve to identify patients previously thought free of disease on the basis of undetectable Tg levels while undergoing THST. A strategy is presented for incorporation of this approach into the management of patients with low-risk well-differentiated thyroid cancer.

  10. Establishment and characterization of cell sublines with high and low metastatic potential derived from human osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-bing; CHEN An-ming; CAI Xian-hua; GUO Fen-jing; LIAO Guo-ning; MA Ding

    2005-01-01

    @@ The most frequent cause of death of patients with osteosarcoma is the metastasis of tumour cells. In spite of successful control of the primary tumour, the mortality of the patients due to metastatic spread is more than 30% within 5 years.1 Recent studies about osteosarcoma metastatic mechanism are based on osteosarcoma matrilineal cell lines.2 For further studies of metastatic mechanism of osteosarcoma the establishment of a better metastatic experimental model of osteosarcoma is needed. We isolated and established two cell sublines, with high and low metastatic potentials, respectively, derived from human osteosarcoma MG-63 cell line by cloning in vitro and transplantation in vivo, then analysed and identified their biological characteristics.

  11. Flow cytometric studies of human osteosarcoma.

    Science.gov (United States)

    Mankin, H J; Gebhardt, M C; Springfield, D S; Litwak, G J; Kusazaki, K; Rosenberg, A E

    1991-09-01

    A number of recent studies have emphasized the potential value of flow cytometry as a "marker" to assess the malignity and therefore to help predict the biologic behavior of neoplasms, including bone tumors. Using propidium iodide and a home-built flow cytometer, the authors have studied the DNA distribution in 95 patients with osteosarcoma and determined the percentage of cells in diploidy, S-phase, tetraploidy, and aneuploidy. Using these values and a derived one, mean DNA concentration, it was possible to demonstrate the extent of the abnormalities observed in this group of neoplasms and show their severity as compared with the normal pattern. When the data are compared against disease-free survival and total survival, correlations were noted that, although weak, suggested that some patterns were predictive of increased risk of metastasis and death. The effect of treatment could also be assessed by evaluating the pattern before and after chemotherapy and correlating these with survival. It seems likely that with some improvement in technology, flow cytometry will be of value in the future in assessing the prognosis for osteosarcoma and predicting whether treatment has been effective.

  12. Expression of Bcl-2 in canine osteosarcoma

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    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.

  13. Chondroblastic osteosarcoma of the distal tibia: a rare case report.

    Science.gov (United States)

    Fredj, Aymen Ben; Hassini, Lassaad; Fekih, Aymen; Allagui, Mohamed; Aloui, Issam; Abid, Abderrazek

    2017-01-01

    Chondroblastic osteosarcoma, representing about 25% of osteosarcoma, is a fatal primary malignancy of the skeleton if not diagnosed and treated appropriately. It most commonly occurs in the long bones of the extremities near the metaphyseal growth plates. In this report, we describe the occurrence of chondroblastic osteosarcoma involving the left distal tibia in a 14-year-old male. The diagnosis was confirmed by the histological examination of a surgical biopsy. The patient was treated by both surgery and neoadjuvant chemotherapy. No recurrence was noted at 3 years of follow-up. To our knowledge, only two cases describing chondroblastic osteosarcoma of the distal tibia had been reported through English medical literature. Therefore, the aim of our article is to make the clinician aware of this rare clinical presentation and also to provide a comprehensive review of the literature related to this uncommon malignant tumour.

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

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    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.

  15. Kinetic effects of adriamycin and bleomycin on two osteosarcoma models.

    Science.gov (United States)

    Bell, D F; Bell, R S; Mankin, H J; Gebhardt, M C; Weltie, F; O'Brien, T

    1988-01-01

    Although chemotherapeutic drugs are frequently administered to patients with osteosarcoma, there has been little research into the effect of cytotoxic drugs on osteosarcoma cell biology. The effect of two drugs (Adriamycin and bleomycin) on cell cycle kinetics was investigated in vitro in an established line of human osteosarcoma cells and in vivo using the Dunn osteosarcoma model. The cell cycle changes were consistent with G2 arrest for both drugs in vivo and in vitro. The alteration in cell cycle distribution was correlated with inhibition of 3H-thymidine incorporation in vitro. In vivo, the greater change in cell cycle distribution caused by Adriamycin was reflected in the increased inhibition of tumor growth found with this drug.

  16. Intramedullary Osteosarcoma of the Mandible: A Clinicoradiologic Perspective

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    Bhogisetty Chittaranjan

    2014-01-01

    Full Text Available Osteosarcoma is a non-hematopoietic primary malignant tumor of bone or mesenchymal tissue. Although osteosarcoma is not a common malignant bone tumor, accounting for approximately 20% of sarcomas, tumor of the jaw bone is uncommon, representing only about 4% of osteosarcomas of long bones. We report a case of a 72-year-old female with a swelling on the left side of the mandible and intra-oral swelling on the floor of the mouth. Conventional radiograph and advanced imaging modalities such as computed tomography and magnetic resonance imaging revealed an intramedullary osteosarcoma of the mandible. This report highlights importance of imaging modalities in the diagnosis of malignant tumors of the jaws.

  17. Primary Osteosarcoma of the Breast: A Case Report

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    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.

  18. Osteosarcoma: A rare case report and review of literature

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    Mallika Kishore

    2016-01-01

    Full Text Available Osteosarcoma of the jaws is a rare, aggressive, malignant mesenchymal tumor with an estimated incidence of 5% in 100,000 of the new cases per year. Osteosarcoma of jaws is a very rare disease and may constitute approximately 1% of all head and neck cancers and only 0.14% of intraoral malignancies. Approximately 7% of all osteosarcomas arise in the jawbones. Diagnosis of the tumor is important, especially in early stages for improving prognosis. Here, we report a rare case of osteosarcoma of chondroblastic variant in a 20-year-old girl, who presented with a bony swelling in the right mandibular posterior region, with a radiographic presentation of sunburst appearance, and the histopathological examination confirmed the diagnosis.

  19. Unusual presentation of a pancreatic cyst resulting from osteosarcoma metastasis.

    Science.gov (United States)

    Akpinar, Burcu; Obuch, Joshua; Fukami, Norio; Pokharel, Sajal S

    2015-07-21

    Pancreatic metastases are uncommon. They have been reported in lung cancer, gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma, lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the pancreas is even more rare with few case reports in the literature. However, with the increasing use of computed tomography and magnetic resonance imaging as well as endoscopic ultrasound, more such lesions may be detected. Metastasis to the pancreas from osteosarcoma is highly unusual, but can be seen with the increasing survival of patients with osteosarcoma. We present an extremely rare case of a predominantly cystic lesion of the pancreas, which was diagnosed as metastasis from osteosarcoma. The pathophysiology of the cystic component of the metastasis of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis or pancreatitis secondary to the metastasis with development of associated fluid collection can be considered. Metastasis should remain a differential consideration even for primarily cystic lesions of the pancreas.

  20. General Information about Osteosarcoma and Malignant Fibrous Histiocytoma of Bone

    Science.gov (United States)

    ... to the lung. Bone Metastasis or Bone with Lung Metastasis Osteosarcoma and malignant fibrous histiocytoma may spread to a distant bone and/or the lung. Treatment may include the following: Combination chemotherapy followed ...

  1. Treatment Option Overview (Osteosarcoma and Malignant Fibrous Histiocytoma of Bone)

    Science.gov (United States)

    ... to the lung. Bone Metastasis or Bone with Lung Metastasis Osteosarcoma and malignant fibrous histiocytoma may spread to a distant bone and/or the lung. Treatment may include the following: Combination chemotherapy followed ...

  2. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    Directory of Open Access Journals (Sweden)

    Yalın Dirik

    2014-01-01

    CONCLUSION: Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed.

  3. Human Soluble TRAIL Protein Inducing Apoptosis in Osteosarcoma Cell

    Institute of Scientific and Technical Information of China (English)

    ZHU Shaobo; YU Aixi; ZHANG Zhongning; WU Gang

    2007-01-01

    This study is to examine the effect of human recombinant soluble TRAIL (TNF-related apoptosis-inducing ligand) protein inducing apoptosis in MG-63 human osteosarcoma cells. The inhibitive rates of TRAIL to MG-63 cells were detected by MTT assay. The apoptosis induced by TRAIL in MG-63 human osteosarcoma cells was analyzed with FACS and TUNEL and the apoptotic bodies were observed by transmission electron microscope. MTT assay showed that the inhibitive rates of 500, 1 000,2 000 and 4 000 ng/mL TRAIL for 24 h were 10.1%, 24.3%,50.6% and 97.7% respectively. Flow cytometric analysis showed that after MG-63 cells were treated with 2 μg/mL TRAIL for 6 h,obvious apoptotic peak would immediately appear before diploid peak. Human soluble TRAIL protein can quickly kill MG-63 osteosarcoma cells selectively, and may have potential value for clinical treatment of osteosarcoma.

  4. [Osteosarcoma of the skull base: a case report].

    Science.gov (United States)

    Haddad, H; Benchakroun, N; Sahraoui, S; Benider, A

    2007-12-01

    Osteosarcoma, usually observed in long bones, is the second most frequent primitive malignant bone tumor after myeloma. The skull base is an exceptional localization. We report a case of skull base osteosarcoma managed in our department. A 23-year-old female was admitted for bilateral epistaxis, headache, decreasing visual acuity then blindness. Physical examination revealed bilateral blindness and exophthalmia. Cranial magnetic resonance imaging showed a voluminous mass in the skull base extending to the nasosinusal area. A rhinoseptal surgical approach was used but the tumor was so huge that excision was impossible. The biopsy identified at an osteoblastic osteosarcoma. Search for extension (chest computed tomography and abdominal ultrasonography) was negative. Chemotherapy was to be delivered before combination chemoradiotherapy but the patient died before any treatment could be started. Osteosarcoma of the skull base is very rare. The treatment is based on surgery which should be as complete as possible followed by chemoradiotherapy. Prognosis is poor. Median survival is around six months.

  5. Bio-inspired cisplatin nanocarriers for osteosarcoma treatment

    National Research Council Canada - National Science Library

    Zhou, Haidong; Wang, Gangxiang; Lu, Yiyun; Pan, Zhijun

    2016-01-01

    In this study, cisplatin ( cis -diaminedichloroplatinum, CDDP) nanocarriers with phosphorylcholine surface tailoring were developed to enhance the anti-tumor potential of CDDP for the treatment of osteosarcoma. Poly...

  6. Heat shock transcription factor 1 promotes the proliferation, migration and invasion of osteosarcoma cells.

    Science.gov (United States)

    Zhou, Zhenhua; Li, Yan; Jia, Qi; Wang, Zhiwei; Wang, Xudong; Hu, Jingjing; Xiao, Jianru

    2017-08-01

    Osteosarcoma is the most commonly diagnosed primary malignancy of bone and its overall survival rate is still very low. The molecular mechanisms underlying the progression of osteosarcoma have not been clearly illuminated. Heat shock transcription factor 1 (HSF1) is a key regulator of the heat shock response and also plays important roles in many cancers, but its function in osteosarcoma remains unexplored. In this study, the proliferation of osteosarcoma cells was determined by Cell Counting Kit-8 assays and colony formation assays. Transwell assays were used to demonstrate the migration and invasion abilities of osteosarcoma cells. A tumour formation assay in a nude mouse model was performed to assess the effect of HSF1 on osteosarcoma cell growth in vivo. The protein levels of HSF1 were analysed with immunohistochemical staining in samples from osteosarcoma patients. We demonstrated that knockdown of HSF1 reduced the proliferation, migration and invasion of osteosarcoma cells, while overexpression of HSF1 promoted the proliferation, migration and invasion of osteosarcoma cells. Furthermore, HSF1 promoted the proliferation of osteosarcoma cells in vivo. In addition, high levels of HSF1 were associated with a poor prognosis in osteosarcoma. These data highlight an important role of HSF1 in proliferation, migration and invasion of osteosarcoma cells. Moreover, the expression of HSF1 was associated with prognosis in osteosarcoma. © 2017 John Wiley & Sons Ltd.

  7. Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma.

    Science.gov (United States)

    Roth, Michael; Barris, David M; Piperdi, Sajida; Kuo, Vicky; Everts, Stephanie; Geller, David; Houghton, Peter; Kolb, E Anders; Hawthorne, Thomas; Gill, Jonathan; Gorlick, Richard

    2016-01-01

    Cure rates for children and young adults with osteosarcoma have remained stagnant over the past three decades. Targeting glycoprotein non-metastatic b (GPNMB) with the antibody-drug conjugate glembatumumab vedotin has improved outcomes for patients with melanoma and breast cancer. The potential utility of targeting GPNMB in osteosarcoma was explored. GPNMB protein expression was evaluated by immunohistochemistry in human osteosarcoma tumor samples and by enzyme-linked immunosorbent assay (ELISA) in osteosarcoma cell lines. mRNA expression was measured by quantitative PCR in primary osteosarcoma samples and cell lines. Surface GPNMB expression was evaluated by flow cytometry and correlated with in vitro and in vivo cytotoxicity of glembatumumab vedotin. Sixty seven human osteosarcoma samples were evaluated by immunohistochemistry, including 12 samples from initial biopsy, 38 samples from definitive surgery, and 17 from the time of disease recurrence. GPNMB was expressed in 92.5% (62/67) of osteosarcoma samples. All primary osteosarcoma samples expressed high levels of GPNMB mRNA. Glembatumumab induced cytotoxic effects in 74% (14/19) of osteosarcoma cell lines, and GPNMB protein levels correlated with glembatumumab in vitro cytotoxicity (r = -0.46, P = 0.04). All osteosarcoma cell lines demonstrated surface GPNMB expression. GPNMB is expressed in osteosarcoma and targeting GPNMB with the antibody-drug conjugate glembatumumab vedotin demonstrates osteosarcoma cytotoxic activity. Clinical trials are indicated to assess the efficacy of targeting GPNMB in patients with osteosarcoma. © 2015 Wiley Periodicals, Inc.

  8. 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.

  9. Malignant Transformation of an Aneurysmal Bone Cyst to Fibroblastic Osteosarcoma.

    Science.gov (United States)

    Kansagra, Akash P; Wan, Jennifer J; Devulapalli, Kavi K; Horvai, Andrew E; O'Donnell, Richard J; Link, Thomas M

    Aneurysmal bone cysts are uncommon primary bone tumors typically regarded as histologically and clinically benign. Malignant transformation of these lesions occurs almost exclusively in the context of prior radiation exposure. However, 4 cases of an osteosarcoma developing without prior radiation exposure have been reported. In this article, we report a fifth case of degeneration of an aneurysmal bone cyst to a fibroblastic osteosarcoma. In addition to reviewing the earlier cases, we describe the radiologic, pathologic, and immunohistochemical basis of this diagnosis.

  10. Spontaneous regression of lung metastasis from osteosarcoma: a case report.

    Science.gov (United States)

    Bacci, Gaetano; Palmerini, Emanuela; Staals, Eric L; Ferrari, Stefano; Battaglia, Milva; Longhi, Alessandra; Bertoni, Franco; Briccoli, Antonio

    2008-01-01

    A case of spontaneous regression of a pulmonary metastasis from high-grade osteosarcoma is reported. The metastasis developed 5 years after chemotherapy and amputation for a distal femur osteosarcoma. The sarcomatous nature of the lesion was histologically confirmed. No treatment was attempted owing to the patient's refusal. The patient was followed up every 3 months and a spontaneous regression of the lesion was documented. Seven years after the diagnosis of lung metastases, no pulmonary nodules or other signs of relapse are present.

  11. Evolution and prognosis of breast osteosarcoma: A case report

    OpenAIRE

    Guo, Wanfeng; Cao, Yang; Teng, Guangju; Liu, Jin; Su, Jianbin

    2015-01-01

    Breast osteosarcoma is a rare malignancy of unknown etiology, with no standard adjuvant treatment at present. The prognosis of the disease is poor, and it has a high propensity for recurrence and metastasis. The current report presents the case of a 52-year-old woman, in whom adenomyoepithelioma gradually developed into breast osteosarcoma following three separate surgeries. The patient survived for 41 months from the initial lesion occurrence and resection in the left breast; during this tim...

  12. 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.

  13. Dedifferentiated high-grade osteosarcoma originating from low-grade central osteosarcoma of the fibula

    Energy Technology Data Exchange (ETDEWEB)

    Kenan, Samuel [New York University-Hospital for Joint Diseases, Department of Orthopedic Surgery, New York, NY (United States); Ginat, Daniel T. [New York University, School of Medicine, New York, NY (United States); Steiner, German C. [New York University-Hospital for Joint Diseases, Department of Orthopedic Pathology, New York, NY (United States); Department of Pathology, New York, NY (United States)

    2007-04-15

    Low grade central osteosarcoma is a distinct, rare low grade malignant neoplasm characterized histologically by a spindle cell proliferation associated with trabecular bone formation. This tumor usually carries a good prognosis. However, it has the potential to recur, dedifferentiate, and metastasize subsequent to surgical treatment. In extremely rare occasions, LGCOS presents with areas of dedifferentiation upon initial patient evaluation. In this report we describe one such case affecting the fibula of a 39-year-old female, presenting with pain. Initial biopsy demonstrated a high-grade osteosarcoma. No areas of LGCOS were seen histologically. Following biopsy the patient received 3 months of chemotherapy at a different institution. However, the patient continued to exhibit symptoms. X-rays indicated a very aggressive tumor in the diaphysis of the proximal fibula, MRI revealed soft tissue involvement. The tumor and surrounding soft-tissues were excised en bloc at our institution. Microscopically, the lesion consisted of high-grade osteosarcoma as well as an underlying LGCOS that involved the cortex and medullary cavity of the fibula. The two histological components of the tumor were sharply delineated from one another. No chemotherapy effect was appreciated histologically or clinically. Eight months following the surgery, the patient died from lung metastases. This is the third documented case of dedifferentiated LGCOS at initial presentation. This case reveals that the low-grade component was also evident on preoperative radiographs. (orig.)

  14. Assessment of recombinant human thyrotropin application in following-up patients with well-differentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Rajkovača Zvezdana

    2012-01-01

    Full Text Available Background/Aim. The most sensitive indicators for detecting recurrence of well-differentiated thyroid cancer (DTC are 131I whole body scintigraphy (WBS and measurement of serum thyroglobulin (Tg. In order to perform it, it is necessary to raise the level of endogenous tiroidstimulating hormon (TSH, which can be achieved by Lthyroxine withdrawal for 3-5 weeks or administration of recombinant human thyrotropin (rhTSH without requiring the discontinuation of thyroid hormone therapy. The aim of this study was to assess the effect of rhTSH using in comparison to the traditional thyroid hormone withdrawal in the follow-up of patients with DTC. Methods. This retrospective study included 44 patients, mean age 48.8 years, with DTC divided into 2 groups. The group I consisted of patients (n = 31 in which the analysis in the follow-up (WBS with 131I, TSH, Tg and antiTgAt made in the hypothyroid state, and group II patients (n = 13 in which they made after the administration of rhTSH. The presence of 13 symptoms and signs of hypothyroidism was investigated on the day of giving 131I. Quality of life was evaluated using a modified form: the quality of life scale (SF-36 completed on the day of giving 131I. Results. In both groups, serum TSH reached a very good stimulation level, but significantly higher in the group II (group I 30.3-101.5 µlU/mL, group II 68.6-192.0 µlU/mL, p < 0.05. In both groups, TSHstimulated Tg was higher (group I 0.1-546.0 ng/mL, group II 0.1-7517 ng/mL comapred to value during the Lthyroxine therapy (group I 0.1-495.0 ng/mL, group II 0.1- 2785 ng/mL. There was no difference in technical quality of WBS obtained from both groups. The patients in the group I had attended 8-13 symptoms of hypothyroidism, while patients in group II did not have symptoms of hypothyroidism. The patients after application of rhTSH, showed statistically significantly better quality of life as compared with those who showed to have L-thyroxine withdrawal, (74

  15. Decreased RECQL5 correlated with disease progression of osteosarcoma.

    Science.gov (United States)

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

    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.

  16. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

    Science.gov (United States)

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Gorlick, Richard; Geller, David S.

    2017-01-01

    Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs. PMID:28264040

  17. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis.

    Science.gov (United States)

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Morris, Jonathan; Gorlick, Richard; Geller, David S

    2017-01-01

    Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

  18. 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.)

  19. [The long-term treatment outcomes of adult osteosarcoma].

    Science.gov (United States)

    Ługowska, Iwowa; Pieńkowski, Andrzej; Szumera-Ciećkiewicz, Anna; Koseła-Paterczyk, Hanna; Teterycz, Pawel; Głogowski, Maciej; Kozak, Katarzyna; Klimczak, Anna; Falkowski, Slawomir; Rutkowski, Piotr

    2017-04-21

    Osteosarcoma is the most common primary bone tumor. Treatment of osteosarcoma patients is based on chemotherapy as well as surgical resection of primary tumor and distant metastases. Lung metastases are the primary cause of death in this group of patients. The aim of this study is to summarize the 20 years of osteosarcoma treatment outcomes in the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw. Our analysis included clinical data of 299 osteosarcoma patients aged between 14 and 81 years (median 32) treated in Maria Sklodowska-Curie Memorial Cancer Center between 1998 and 2016. The standard therapeutic protocol included perioperative anthracycline-based chemotherapy and surgical resection of primary tumor and distant metastases. The statistical analysis was performed using Kaplan-Meier estimator, log-rank test and Cox proportional hazards model. In analyzed group 38 (13%) patients had distant metastases at the diagnosis. The tumor size was greater than 8 cm in 61% of cases. In the histopathological assessment the most prevalent subtype was the conventional one (diagnosed in 76% of cases) and histological grade 3 (79%). The 5-year survival rate for patients with localized disease reached 46%. The negative prognostic factors included: distant metastases at diagnosis, axial location of primary tumor, unresectability of the primary lesion, higher histological grade, and older age of patients. The best results of the treatment of osteosarcoma patients are achieved with multidisciplinary treatment, and when the reference center supports other healthcare providers in management of diagnostic and treatment procedures of osteosarcoma patients.

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

    Science.gov (United States)

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

    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.

  1. Extraskeletal problems and amyloid.

    Science.gov (United States)

    Drüeke, T B

    1999-12-01

    The major clinical manifestations of dialysis-associated A beta 2M amyloidosis are chronic arthralgias, destructive arthropathy and the carpal tunnel syndrome. For dialysis patients who have been maintained on renal replacement therapy for more than 10-15 years, this complication may become a major physical handicap. It may even be life-threatening in some instances due to cervical cord compression. Amyloid deposits in joint areas precede clinical symptoms and signs by several years. Systemic deposits may also occur but their clinical manifestations are infrequent. The diagnosis of dialysis arthropathy associated with beta 2-microglobulin-associated (A beta 2M) amyloidosis mostly relies on indirect clinical and radiological evidence. Histologic proof is rarely obtained in vivo. The pathogenesis of the disease is complex. It includes reduced elimination of beta 2M and potentially also as impaired degradation of A beta 2M as well as enhanced production of A beta 2M amyloid fibrils. Non enzymatic modifications of beta 2M probably play a role, including beta 2M protein modification with advanced glycation end-products (AGE) and advanced oxidation protein products. Modified beta 2M, collagen and proteoglycans appear actively involved in the induction of a local inflammatory response and beta 2M amyloid formation. There is also evidence in favor of treatment-related factors such as the type of hemodialysis membrane and the purity of dialysis water. Hopefully, the translation of our improving knowledge of all the factors involved will lead to a better treatment and eventually to the prevention of this dramatic complication of dialysis.

  2. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution

    Science.gov (United States)

    Huh, Jimi; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

    2015-01-01

    Objective To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ≥ 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results Among the 70 patients (mean age, 35.8 ± 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. PMID:26175577

  3. Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy.

    Science.gov (United States)

    Gianferante, D Matthew; Mirabello, Lisa; Savage, Sharon A

    2017-08-01

    Clinical outcomes and treatment modalities for osteosarcoma, the most common primary cancer of bone, have changed very little over the past 30 years. The peak incidence of osteosarcoma occurs during the adolescent growth spurt, which suggests that bone growth and pubertal hormones are important in the aetiology of the disease. Tall stature, high birth weight and certain inherited cancer predisposition syndromes are well-described risk factors for osteosarcoma. Common genetic variants are also associated with osteosarcoma. The somatic genome of osteosarcoma is highly aneuploid, exhibits extensive intratumoural heterogeneity and has a higher mutation rate than most other paediatric cancers. Complex pathways related to bone growth and development and tumorigenesis are also important in osteosarcoma biology. In this Review, we discuss the contributions of germline and somatic genetics, tumour biology and animal models in improving our understanding of osteosarcoma aetiology, and their potential to identify novel therapeutic targets and thus improve the lives of patients with osteosarcoma.

  4. Quality of life in osteosarcoma survivors.

    Science.gov (United States)

    Greenberg, D B; Goorin, A; Gebhardt, M C; Gupta, L; Stier, N; Harmon, D; Mankin, H

    1994-11-01

    Charts of 89 osteosarcoma survivors from Massachusetts General Hospital and The Children's Hospital/Dana Farber Cancer Center, who had received primary treatment more than 1 year previously and had no evidence of disease, were reviewed. Sixty-two patients, mean 12 years from diagnosis, agreed to structured interviews. Rates of psychopathology did not differ significantly from the general population. High distress was noted in 13%. Twenty-three normal progeny had been born postchemotherapy to eight women and the wives of five male patients. One pregnancy was complicated by doxorubicin-induced cardiac toxicity. Only two with previous childhood tumors believed themselves infertile. All felt the effort to save the limb was worthwhile. In most, ongoing pain was mild; phantom pain and neuralgia common. Most survivors were in good mental and physical health with the capacity to bear children.

  5. 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......; YKL-staining scores as well as CD14 and CD163 scores were determined, and survival data were determined statistically. A universal intense immunostaining for YKL-40 was found in all tumor cells, but tumor cell/stroma ratio varied, and this ratio (%) served as staining score. Using 24% as mean score...... to divide the material, patients with tumors of high YKL-40 score had a better survival than patients with low score (p = 0.05). YKL-positive macrophages had no influence on the result. Unexpectedly and contrary to some other findings in cancer tissues, this study has shown a correlation between high YKL-40...

  6. A guise of osteosarcoma: Chondroblastoma-like

    Directory of Open Access Journals (Sweden)

    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.

  7. A guise of osteosarcoma: chondroblastoma-like.

    Science.gov (United States)

    Byatnal, Aditi Amit; Rao, Anuradha C K; Solomon, Monica C; Radhakrishnan, Raghu A

    2013-01-01

    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.

  8. MR Imaging Findings of a Primary Cardiac Osteosarcoma and Its Bone Metastasis with Histopathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Se Jin; Choi, Jung Ah; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of); Chun, Eun Ju; Choi, Sang Il; Chung, Jin Haeng [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Choi, Ho Cheol [Gyeongsang National University Hospital, Jinju (Korea, Republic of)

    2011-02-15

    An osteosarcoma of cardiac origin is extremely rare, and a comprehensive description of MR imaging (MRI) findings of cardiac osteosarcoma and its metastasis in the femur have not been reported in the literature. We present a case of cardiac osteosarcoma in a 47-year-old woman and its metastasis to the femur, focusing on the description of MRI findings of the cardiac and metastatic bony osteosarcoma with a histopathologic correlation

  9. Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Yoshitake Hayashi; Hirotsugu Ikawa; Kenji Ando; Keiji Mita; Shuichi Fuki; Michiie Sakamoto; Yoshihiro Kanbara; Toshiyuki Matsuoka; Masatoshi Kudo

    2007-01-01

    We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepatocellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven.US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia,and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia.Moreover, immunohistochemical staining of cyclaseassociated protein 2, a new molecular marker of well-differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.

  10. Pediatric osteosarcoma: a single institution's experience.

    Science.gov (United States)

    Vijayakumar, Vani; Lowery, Rachel; Zhang, Xu; Hicks, Chindo; Rezeanu, Luminita; Barr, Jennifer; Giles, Henry; Vijayakumar, Srinivasan; Megason, Gail

    2014-11-01

    The aim of the study was to evaluate outcomes with an examination of individual predictors influencing survival at a single institution. This was a retrospective review of the 28 pediatric osteosarcoma patients diagnosed and studied from 2000 through 2012. Twenty-eight patient charts and imaging studies were reviewed for age, race, sex, location, extent of disease at presentation, imaging results, histology, treatment options, and overall survival. Of the 28 patients who were identified, the median age at diagnosis was 14 years. The majority of the patients were male African Americans with the tumor located in the lower long bones and most had conventional osteosarcoma histology. Four patients had metastasis at diagnosis. Of the 28 patients, 16 patients underwent limb salvage surgery, 6 underwent amputation, 4 had biopsy only, 1 had hip disarticulation, and 1 moved out of state and had no information available. All 28 patients received chemotherapy. Four patients received additional radiation therapy. On follow-up, 15 patients were still alive at last clinical contact and 13 died. Of the deceased, the median survival time was 2.3 years. The patient who lived the longest survived 8.3 years. Metastasis at diagnosis was associated with poorer outcome (P = 0.002). The 5-year overall survival rate was 40% (95% confidence interval 18-62) for our entire population of patients. Survival in our patient cohort tended to be at the lower end of the spectrum reported by other contemporary treatment centers of excellence or Surveillance, Epidemiology, and End Results databases probably because of the large number of African American patients with associated poor socioeconomic status. Future studies should be conducted to explore biological and nonbiological factors that may affect the prognosis in this disease.

  11. Quercetin Inhibits Cell Migration and Invasion in Human Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Haifeng Lan

    2017-09-01

    Full Text Available Background/Aims: Osteosarcoma is a malignant tumor associated with high mortality; however, no effective therapies for the disease have been developed. Several studies have focused on elucidating the pathogenesis of osteosarcoma and have aimed to develop novel therapies for the disease. Quercetin is a vital dietary flavonoid that has been shown to have a variety of anticancer effects, as it induces cell cycle arrest, apoptosis, and differentiation and is involved in cell adhesion, metastasis and angiogenesis. Herein, we aimed to investigate the effects of quercetin on osteosarcoma migration and invasion in vitro and in vivo and to explore the molecular mechanisms underlying its effects on osteosarcoma migration and invasion. Methods: Cell viability, cell cycle activity and cell apoptosis were measured using CCK-8 assay and flow cytometry, and cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The mRNA and protein expression levels of several proteins of interest were assessed by real-time quantitative PCR and western blotting, respectively. Moreover, a nude mouse model of human osteosarcoma lung metastasis was established to assess the anti-metastatic effects of quercetin in vivo. Results: We noted no significant differences in cell cycle activity and apoptosis between HOS and MG63 cells and control cells. Treatment with quercetin significantly attenuated cell migration and invasion in HOS and MG63 cells compared with treatment with control medium. Moreover HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels were significantly downregulated in HOS cells treated with quercetin compared with HOS cells treated with controls. Additionally, treatment with quercetin attenuated metastatic lung tumor formation and growth in the nude mouse model of osteosarcoma compared with treatment with controls. Conclusion: Our findings regarding the inhibitory effects of quercetin on cell migration and

  12. miR-10b promotes invasion by targeting KLF4 in osteosarcoma cells.

    Science.gov (United States)

    Wang, Jing; Wang, Bing; Chen, Ling-Qiang; Yang, Jin; Gong, Zhi-Qiang; Zhao, Xue-Ling; Zhang, Chun-Qiang; Du, Kai-Li

    2016-12-01

    Osteosarcoma is a common malignancy with high rate of metastasis. miR-10b has been reported to be expressed in many types of tumors abnormally and be associated with cancer carcinogenesis and progression. But the function of miR-10b in osteosarcoma is still unknown. So this study was aimed to investigate the role of miR-10b in osteosarcoma development. miR-10b expression in osteosarcoma tissues and osteosarcoma cells were detected using real time PCR. The effects of miR-10b on osteosarcoma cells proliferation, apoptosis, migration and invasion were detected using CCK-8 assay, flow cytometry, wound-healing assay and transwell assay, respectively. The relationship between miR-10b and KLF4 was evaluated using dual-luciferase assay, correlation analysis. miR-10b was highly expressed in osteosarcoma tissues and osteosarcoma cells. Furthermore, inhibition of miR-10b in osteosarcoma cells depressed the cells proliferation, migration and invasion but promoted cells apoptosis. In addition, KLF4 was down-regulated by miR-10b and miR-10b expression was negatively related to KLF4 expression in osteosarcoma tissue, miR-10b participated in the process of osteosarcoma cells invasion by regulating KLF4 expression. miR-10b is overexpressed in osteosarcoma and KLF4 is the direct target gene of miR-10b. Furthermore, miR-10b promotes osteosarcoma cells progression by downregulating KLF4 expression. These results suggest that miR-10b functions as an oncomiR and play an important role in osteosarcoma cellular processes at least partially through regulating KLF4; miR-10b may be a therapeutic target for osteosarcoma treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. [Cerebral primitive osteosarcoma, a radiological and histological atypia].

    Science.gov (United States)

    Ahanogbe, K M H; Ibahioin, K; Karkouri, M; Dianka, M B; Akpo, W; El Azhari, A

    2016-10-01

    Osteosarcoma is a malignant mesenchymal tumor including cells that present an osteoblastic differentiation. On the skull, it has often extra-axial development associated with bone reaction. We report an atypical and rare case of intracranial or cerebral osteosarcoma underline the radiological and pathological diagnostic difficulties. Our case concerns a primary osteosarcoma without bone involvement in a 10-year old boy who was admitted for intracranial hypertension with progressive worsening and brachial monoparesis. Subtotal resection was performed but the postoperative course was not favorable. The child died five months after the initial surgery. Its radiological aspect prompted us evoke several diagnoses including glioma or meningioma. On the histological level, osteosarcoma, especially with poorly differentiated cells, can be deceiving with other processes, including a gliosarcoma that was revealed by simple microscopic reading before being confirmed by an immunohistochemical study. In the absence of any bone reaction or known extra-cranial location, it can be difficult to suggest the diagnosis of osteosarcoma based on imagery alone. Immunohistochemistry is essential for an accurate diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Potential mechanisms underlying CDK5 related Osteosarcoma progression.

    Science.gov (United States)

    Bao, Hang-Xing; Bi, Qing; Han, Yong; Zhao, Chen; Zou, Hai

    2017-05-01

    Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed. We demonstrated that tricarboxylic acid (TCA) cycle is activated while antigen presentation is repressed in patients with CDK5 overexpression and poor survival. This results indicated that sufficient energy production and tumor immune escape are important characteristics and potential therapeutic targets for this subgroup of osteosarcoma patients. Furthermore, several critical hub genes that are associated with CDK5 related osteosarcoma progression such as MELK were identified. This study discussed the pro-malignant role of CDK5 and potential mechanisms involved. Further preclinical and clinical studies to develop CDK5 based treatments are warranted.

  15. Hiporfin-mediated photodynamic therapy in preclinical treatment of osteosarcoma.

    Science.gov (United States)

    Sun, Mengxiong; Zhou, Chenghao; Zeng, Hui; Puebla-Osorio, Nahum; Damiani, Elisabetta; Chen, Jian; Wang, Hongsheng; Li, Guodong; Yin, Fei; Shan, Liancheng; Zuo, Dongqing; Liao, Yuxin; Wang, Zhuoying; Zheng, Longpo; Hua, Yingqi; Cai, Zhengdong

    2015-01-01

    This study was carried out to investigate the anti-tumor effect and mechanism of hiporfin-mediated photodynamic therapy (hiporfin-PDT) in osteosarcoma. We found that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time and concentration-dependent manner. Hiporfin-PDT inhibited the proliferation, induced apoptosis and produced cell cycle arrest at G2M in osteosarcoma cell lines. Hiporfin-PDT increased the expression of cleaved-caspase-3, cleaved PARP-1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low concentration of hiporfin increased LC3 conversion. Furthermore, cell death caused by hiporfin-PDT could be rescued by Nec-1 but not by Z-VAD-FMK. Production of reactive oxygen species was increased after hiporfin-PDT. In vivo studies showed a significant decrease in tumor volume and weight after hiporfin-PDT in all three tumor mouse models investigated (subcutaneous and orthotopic). Histological analysis showed widespread cell apoptosis and necrosis after treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and downregulation of Bcl-2 after hiporfin-PDT. These results indicate that hiporfin-PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is associated with apoptosis and necroptosis, while autophagy plays a protective role. All these findings shed light on a potential future clinical use for hiporfin in the treatment of osteosarcoma. © 2015 The American Society of Photobiology.

  16. Hematological Changes Mimicking Myelodysplastic Syndrome Following Treatment for Osteosarcoma.

    Science.gov (United States)

    Løhmann, Ditte J A; Hasle, Henrik

    2015-04-01

    Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a feared long-term complication of pediatric cancer. Few osteosarcoma patients develop t-MDS/AML, but the frequency of hematological abnormalities after therapy is unknown. We reviewed biochemistry from osteosarcoma patients up to 3 years posttreatment. All children diagnosed with osteosarcoma at our department from 2006 to 2012 without relapse 1 month posttherapy were included (n=14). Serial blood counts posttherapy were analyzed. The median increase of mean corpuscular volume (MCV) from baseline was 8 fL 6 months posttherapy and remained >5 throughout follow-up. All posttreatment levels of MCV were above 90 fL in 5 patients. Six months posttherapy, the median difference for platelets, white blood count, and absolute neutrophil count had decreased from baseline. They remained under baseline throughout follow-up. Hemoglobin remained stable. Ferritin level was associated with increased MCV. MDS with monosomy 7 was diagnosed in 1 patient. Hypoplastic refractory cytopenia was found in another patient showing spontaneous normalization of hematologic values. More than a third of patients treated for osteosarcoma developed hematological abnormalities mimicking early MDS, but only 1 developed t-MDS/AML. Close hematological monitoring of patients recovering from osteosarcoma is essential and it is worth noting that hematological abnormalities are frequent and may be transitory.

  17. Drugs in early clinical development for the treatment of osteosarcoma.

    Science.gov (United States)

    Heymann, Marie-Françoise; Brown, Hannah K; Heymann, Dominique

    2016-11-01

    Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

  18. [Survival analysis of 104 cases of osteosarcoma with lung metastases].

    Science.gov (United States)

    Ren, J; Xu, Y F; Kuang, T H; Chen, J; Liu, Y X

    2017-04-23

    Objective: To investigate the prognosis of osteosarcoma patients with lung metastases and its correlated factors. Methods: The clinical data of 104 osteosarcoma patients with lung metastasis from April 2007 to September 2015 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multivariate Cox regression was applied to analyze independent prognostic factor for patient survival. Results: The one-year, two-year and five-year survival rates of the 104 osteosarcoma patients with lung pulmonary metastasis were 93.3%, 61.5% and 11.5%, respectively, and the median survival time was 33 months. The univariate analysis revealed that number of lung metastases, objective response of first-line chemotherapy and therapeutic methods for lung metastases were significant prognostic factors for patient survival, whereas gender, age, time to lung metastasis and time to other metastasis were not (P>0.05). The multivariate analysis indicated that number of lung metastases, objective response of first-line chemotherapy and therapeutic methods for lung metastases were independent significant prognostic factors for patient survival. Conclusions: The prognosis of osteosarcoma patients with advanced lung metastases and active treatment is better. Surgery and adjuvant chemotherapy could effectively prolong survival time for osteosarcoma patients with pulmonary metastasis.

  19. Unusual thoracic CT manifestations of osteosarcoma: review of 16 cases

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Ruchi; Garg, Rachana; Thulkar, Sanjay [All India Institute of Medical Sciences, Department of Radiology, New Delhi (India); Bakhshi, Sameer; Gupta, Ajay [All India Institute of Medical Sciences, Department of Medical Oncology, New Delhi (India)

    2008-05-15

    Pulmonary metastases are common in osteosarcoma and the most common appearance is of multiple well-defined nodules in the lung parenchyma. However, a variety of atypical locations and presentations of osteosarcoma metastasis can occur in the thorax. We present a review of the thoracic CT findings in 16 patients with histopathologically confirmed osteosarcoma with unusual thoracic manifestations. The 16 patients were selected out of a total 136 patients who received a chest CT scan for osteosarcoma during a period of 3 years in a tertiary care hospital. Unusual imaging findings included a solitary large ossified lung mass, ossified mediastinal and hilar lymph nodes, an esophagomediastinal fistula, lymphangitic carcinomatosis, pulmonary artery tumor emboli, a solitary large pleural deposit along the major fissure, multiple pleural deposits, diffuse pleural calcification, pneumothorax, diaphragmatic deposits, an isolated chest wall deposit without lung involvement, and primary osteosarcoma of the rib. Our findings of lymphangitic carcinomatosis in a living patient as well as calcified mediastinal lymphadenopathy leading to esophageal fistula are unique in the literature, and there are only a few case reports of our other findings. (orig.)

  20. Intra-abdominal metastasis in osteosarcoma: survey and literature review.

    Science.gov (United States)

    Rejin, Kebudi; Aykan, Ozgüven A; Omer, Görgün; Ensar, Yekeler; Bilge, Bilgiç; Inci, Ayan; Harzem, Ozger

    2011-10-01

    Extrapulmonary metastasis, particularly abdominal metastasis from osteogenic sarcoma, are rare and generally appear as a solid mass of calcification as the primary tumor. The aim of this case report is to document the incidence, characteristics, treatment, and prognosis of abdominal metastasis in osteosarcomas in a single institution and to review the literature. From September 1989 to December 2002, 94 children ≤16 years of age with osteosarcomas were diagnosed and treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with abdominal metastasis were assessed. Two girls of 94 patients (2.1%) with osteosarcoma developed abdominal metastasis. One had pulmonary metastasis at diagnosis and the other had developed lung metastasis 15 months after diagnosis. They developed abdominal metastasis 4 and 3 years after diagnosis during therapy or relapse at a median duration of 16 months (1-70 months) from initial diagnosis. All patients had metastasis to various sites, mostly lung, at the time the abdominal metastasis were detected. Treatment included surgery, chemotherapy, and radiotherapy in one and only surgery in the other patient. Both patients died at a median time of 4 months (2-6 months) from the time of abdominal metastasis with progressive disease. Abdominal metastasis in osteosarcoma is a rare event, but abdomen should be investigated in case of recurrence from osteosarcoma. The outcome for these patients is dismal in this series and in the literature.

  1. High-grade surface osteosarcoma of the hand

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  2. The Role of RUNX2 in Osteosarcoma Oncogenesis

    Directory of Open Access Journals (Sweden)

    J. W. Martin

    2011-01-01

    Full Text Available Osteosarcoma is an aggressive but ill-understood cancer of bone that predominantly affects adolescents. Its rarity and biological heterogeneity have limited studies of its molecular basis. In recent years, an important role has emerged for the RUNX2 “platform protein” in osteosarcoma oncogenesis. RUNX proteins are DNA-binding transcription factors that regulate the expression of multiple genes involved in cellular differentiation and cell-cycle progression. RUNX2 is genetically essential for developing bone and osteoblast maturation. Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number together with RNA and protein levels are highly elevated in osteosarcoma tumors. The protein is also important for metastatic bone disease of prostate and breast cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone morphogenesis. This paper provides a synopsis of the current understanding of the functions of RUNX2 and its potential role in osteosarcoma and suggests directions for future study.

  3. Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

    Science.gov (United States)

    Okada, Atsushi; Hosaka, Masami; Watanuki, Munenori; Itoi, Eiji

    2009-01-01

    Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies. PMID:19961270

  4. Long-term survival after sporadic and delayed metastases of conventional osteosarcoma: A case report.

    Science.gov (United States)

    Kubo, Tadahiko; Furuta, Taisuke; Johan, Muhammad P; Yoshizuka, Masaaki; Ochi, Mitsuo; Adachi, Nobuo

    2017-05-01

    Histologically conventional osteosarcoma, once metastasized to the lung, generally causes a rapid and fatal outcome. Osteosarcoma metastasis to the gastrointestinal tract is extremely rare.We report herein a case of osteoblastic osteosarcoma with exceptionally unique features: sporadic lung metastases and delayed metastases to the stomach and the jejunum with long-term survival. She received multiple operations and chemotherapies, but consequently died of peritoneal dissemination. A review of the literature on osteosarcoma metastasis to the gastrointestinal tract is presented.This patient was very unusual in terms of a long-term survival and metastatic sites, suggesting the importance of vigilance and thorough follow-up for patients with conventional osteosarcoma.

  5. Primary osteogenic osteosarcoma of the ethmoid sinus in an adolescent: case report.

    Science.gov (United States)

    Gonzalez, Marta E; Raghavan, Prashant; Cho, Benjamin; Muttikkal, Thomas Jose Eluvathingal; Rehm, Patrice K

    2016-02-01

    Osteosarcomas of the craniofacial bones account for fewer than 10% of all osteosarcomas. Primary osteosarcomas of the nasal cavity and paranasal sinus are rare (0.5-8.1% of the osteosarcomas occur in this location). Because of the rarity of this presentation, we report a case of osteogenic osteosarcoma arising de novo from the ethmoid bone in a 13 year old male who presented with discharge from the right eye and headaches. We describe the imaging features of this rare tumor and provide a brief review of the literature.

  6. Downregulation of microRNA-497 is associated with upregulation of synuclein γ in patients with osteosarcoma

    OpenAIRE

    Wang, Liang; Gao, Hongwei; Gong, Ningji; Gong, Mingzhi

    2016-01-01

    The present study aimed to investigate the effects of microRNA (miRNA/miR)-497 expression levels on the expression levels of synuclein γ (SNCG) in serum samples, as well as osteosarcoma and lung-metastatic tissue samples, from patients with osteosarcoma. Between December 2010 and August 2013, fasting peripheral blood was collected from 36 patients with osteosarcoma for serum separation. In addition, osteosarcoma and lung metastatic tissues were resected from 15 osteosarcoma patients with lung...

  7. Qualitative analysis of small (≤2 cm) regenerative nodules, dysplastic nodules and well-differentiated HCCs with gadoxetic acid MRI

    OpenAIRE

    Di Martino, M.; M. Anzidei; Zaccagna, Fulvio; Saba, L; Bosco, S.; M. Rossi; Ginanni Corradini, S.; Catalano, C

    2016-01-01

    $\\textbf{BACKGROUND}$: The characterization of small lesions in cirrhotic patients is extremely difficult due to the overlap of imaging features among different entities in the step-way of the hepatocarcinogenesis. The aim of our study was to evaluate the role of gadoxetic-acid MRI in the differentiation of small (≤2 cm) well-differentiated hepatocellular carcinomas from regenerative and dysplastic nodules. $\\textbf{METHODS}$: Seventy-three cirrhotic patients, with 118 focal liver lesion...

  8. Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma.

    Science.gov (United States)

    Shen, Aidong; Zhang, Yunqing; Yang, Huiguang; Xu, Ruisheng; Huang, Guowei

    2012-06-15

    This study aimed to investigate the expression of ZEB1 in osteosarcoma tissues and to discuss the relationship between ZEB1 expression and osteosarcoma metastasis. Using RT-PCR and Western blotting, the mRNA and protein expressions of ZEB1 in the osteosarcoma and normal bone tissues were detected. Using the RNA interference technique, the expression of ZEB1 in the human osteosarcoma MG-63 cell line was downregulated, and the changes in the invasion of MG-63 cells were examined. The positive mRNA expression rate of ZEB1 in the osteosarcoma tissues was significantly higher than that in normal bone tissue (P lung metastasis was significantly higher than that from patients without lung metastasis (P osteosarcoma may be related to the carcinogenesis and development as well as metastasis and invasion of osteosarcoma. Copyright © 2011 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Primary osteosarcoma of the uterine corpus: A case report.

    Science.gov (United States)

    Tsukasaki, Nanami; Mori, Taisuke; Yasukawa, Satoru; Konishi, Eiichi; Kokabu, Tetsuya; Kitawaki, Jo

    2016-11-01

    Pure osteosarcoma arising from the uterus is extremely rare. Only 15 cases of this type of cancer have been reported to date. Most patients showed local or lung metastasis early after surgery and died within a year of treatment initiation, regardless of multimodality therapy, indicating that this tumor is aggressive with a poor prognosis. Herein, we report the first clinical experience treated with a combination of docetaxel and gemcitabine for local and lung metastasis from primary osteosarcoma of the uterus. Although the disease was considered stable after three cycles of treatment, new metastatic lesions appeared in the lungs after six cycles. The patient was asymptomatic for 13 months; however, she died two months after symptom recurrence. Our case demonstrates that a combined regimen of docetaxel and gemcitabine may be a sound therapeutic option to control primary osteosarcoma of the uterus. © 2016 Japan Society of Obstetrics and Gynecology.

  11. Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

    Directory of Open Access Journals (Sweden)

    Rebecca Sowers

    2011-01-01

    Full Text Available Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored.

  12. Exuberant callus formation misdiagnosed as osteosarcoma: a case report

    Institute of Scientific and Technical Information of China (English)

    Fariba Binesh; Mohammad Sobhan; Reza Nafisi Moghadam; Ali Akhavan

    2013-01-01

    Reactive lesions of bone and soft tissue can appear alarming on histologic examination because they are often cellular and have atypical cytologic features, such as distinct nucleoli, mild hyperchromasia, and mitotic activity. Reactive lesions of bone and periosteum also produce bone and cartilage matrix, resulting in confusion with osteosarcoma or chon-drosarcoma. Careful attention to key cytomorphological features such as the pattern of bone formation, uniform appearance of cells, and absence of atypical mitoses should help identify the reactive nature of a lesion. Correlation with clinical and radiological findings is also imperative to avoid misclassification of the tumor because reactive lesions often arise at sites where osteosarcoma and chondrosarcoma are rare (eg, the hand) and lack aggressive radiological features. Here we pres-ent a case of exuberant callus formation after avulsion fracture of tibia in a three year-old Iranian girl which misdiagnosed as osteosarcoma.

  13. A Novel Drug Delivery System for Osteosarcoma Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A thermo-responsive chitosan hydrogel system (TRCHS) was prepared by chitosan ( CS ) andβ- glycerophosphate ( β- GP ) to deliver Adriamycin (ADM) locally for curing osteosarcoma . Release property was investigated by release experiments in vitro and results show that it can be applied to local drug release because it is able to release drug at high concentration for 17 days. The treatment effect was studied by injecting intratumorally to osteosarcoma tumors ( CRL- 1427) implanted subcutaneously on Specific Pathogen-free (SPF) mice. The statistical analytical results show that TRCHS delivering ADM is more efficacious than saline intratumoral injection,which loads the same quantity of ADM , but is less poisonous. Based on the analysis above, this novel biodegradable polymer implant is an effective and safe vehicle for sustained local delivery of ADM, and is supposed to be applied in neoadjuvant chemotherapy for osteosarcoma.

  14. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

    Science.gov (United States)

    Anderson, Peter M; Wiseman, Gregory A; Erlandson, Linda; Rodriguez, Vilmarie; Trotz, Barbara; Dubansky, Stephen A; Albritton, Karen

    2005-10-01

    Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of 1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

  15. A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.

    Science.gov (United States)

    Guérin, Maxime; Thariat, Juliette; Ouali, Mounia; Bouvier, Corinne; Decouvelaere, Anne-Valérie; Cassagnau, Elisabeth; Aubert, Sébastien; Lepreux, Sébastien; Coindre, Jean-Michel; Valmary-Degano, Séverine; Larousserie, Frédérique; Meilleroux, Julie; Projetti, Fabrice; Stock, Nathalie; Galant, Christine; Marie, Béatrice; Peyrottes, Isabelle; de Pinieux, Gonzague; Gomez-Brouchet, Anne

    2016-04-01

    In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/α subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement

  16. 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.

  17. Involvement and targeted intervention of dysregulated Hedgehog signaling in osteosarcoma.

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    Lo, Winnie W; Wunder, Jay S; Dickson, Brendan C; Campbell, Veronica; McGovern, Karen; Alman, Benjamin A; Andrulis, Irene L

    2014-02-15

    During development, the Hedgehog pathway plays important roles regulating the proliferation and differentiation of chondrocytes, providing a template for growing bone. In this study, the authors investigated the components of dysregulated Hedgehog signaling as potential therapeutic targets for osteosarcoma. Small-molecule agonists and antagonists that modulate the Hedgehog pathway at different levels were used to investigate the mechanisms of dysregulation and the efficacy of Hedgehog blockade in osteosarcoma cell lines. The inhibitory effect of a small-molecule Smoothened (SMO) antagonist, IPI-926 (saridegib), also was examined in patient-derived xenograft models. An inverse correlation was identified in osteosarcoma cell lines between endogenous glioma-associated oncogene 2 (GLI2) levels and Hedgehog pathway induction levels. Cells with high levels of GLI2 were sensitive to GLI inhibition, but not SMO inhibition, suggesting that GLI2 overexpression may be a mechanism of ligand-independent activation. In contrast, cells that expressed high levels of the Hedgehog ligand gene Indian hedgehog (IHH) and the target genes patched 1 (PTCH1) and GLI1 were sensitive to modulation of both SMO and GLI, suggesting ligand-dependent activation. In 2 xenograft models, active autocrine and paracrine, ligand-dependent Hedgehog signaling was identified. IPI-926 inhibited the Hedgehog signaling interactions between the tumor and the stroma and demonstrated antitumor efficacy in 1 of 2 ligand-dependent models. The current results indicate that both ligand-dependent and ligand-independent Hedgehog dysregulation may be involved in osteosarcoma. It is the first report to demonstrate Hedgehog signaling crosstalk between the tumor and the stroma in osteosarcoma. The inhibitory effect of IPI-926 warrants additional research and raises the possibility of using Hedgehog pathway inhibitors as targeted therapeutics to improve treatment for osteosarcoma. © 2013 American Cancer Society.

  18. [Clinical features and comprehensive treatment of skull base osteosarcoma].

    Science.gov (United States)

    Hu, Ke; Wan, Jinghai; Ni, Song; Li, Xueji; Liu, Shaoyan; Meng, Xiaoli; Qian, Haipeng

    2015-05-01

    To analyze the clinical features and treatment of skull base osteosarcoma. The clinical data of 18 patients with skull base osteosarcoma, who were admitted to the CAMS Cancer Hospital from January 2005 to November 2013, were retrospectively analyzed. The patients were followed up by telephone, outpatient review and other means. Fifteen patients were followed up, 4 cases received surgery only, and 11 cases received surgery with adjuvant chemotherapy and/or radiotherapy. Kaplan-Meier survival curve analysis was used to analyze the clinical data and Log rank method was used for verification. Nine patients died among the 15 patients who were followed up for 3-103 months (mean 25.0 months): seven patients died of local recurrence, and two patients died of distant metastasis, and six patients were still alive. Four patients received surgery only, with a median survival time of 25.0 months, and 11 patients received comprehensive treatment, with a median survival time of 47.0 months (P = 0.02). Five patients received sub-total resection, with a mean survival time of 47.0 months, and 10 patients received total resection, with a mean survival time of 45.0 months (P = 0.37). The 1- and 2-year recurrence rates were 46.6% and 68.9%, respectively. The overall 1-, 2-, 3- and 5-year survival rates were 82.4%, 61.8%, 36.0% and 36.0%, respectively, with a median survival time of 30.0 months. To compare the long bone and head and neck osteosarcoma with skull base osteosarcoma, the skull base osteosarcoma has a lower total resection rate, a higher recurrence rate, and a poorer prognosis. Radical surgery and comprehensive treatment are appropriate for skull base osteosarcoma.

  19. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma.

    Science.gov (United States)

    Dirik, Yalın; Çınar, Arda; Yumrukçal, Feridun; Eralp, Levent

    2014-01-01

    We report a case with lymph node metastasis of osteosarcoma, which is a rare entity in comparison to hematogeneous lung or bone metastasis. Twenty-seven years old male patient referred to our clinic complaining of ongoing left knee pain and swelling since one month without a history of prior trauma. Magnetic resonance imaging (MRI) revealed a mass of malignant nature which causes more prominent expansion and destruction of the bone distally with periosteal reaction. A lymphadenomegaly 16mm×13mm in diameter was also present in the popliteal fossa having the same signal pattern with the primary lesion. Thirteen weeks following the first referral of the patient, wide resection and reconstruction with modular tumor prosthesis was performed. Popliteal lymph node was excised through the same incision. Pathologic examination of the resected speciman reported osteoblastic osteosarcoma. The lymph node extirpated from the popliteal fossa was reported to be a metastasis of the primary tumor. Osteosarcoma of the long bones is the most common primary malignant bone neoplasm of both childhood and adulthood. Osteosarcomas commonly metastasize hematogeneously to the lungs and bones. Lymph node metastasis is a rare entity. Similar studies report rates between 2.3% and 4%. It is not clearly explained, how lymph node metastasis in osteosarcoma occurs despite lack of lymphatic drainage in normal cortical and spongious bone. Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. JNK pathway in osteosarcoma: pathogenesis and therapeutics.

    Science.gov (United States)

    Li, Yu-Sheng; Deng, Zhen-Han; Zeng, Chao; Lei, Guang-Hua

    2016-10-01

    The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein-1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients.

  1. Radiation induced osteosarcoma of the chest wall

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    Sugimoto, Tsutomu; Yuki, Yoshihiro; Oizumi, Hiroyuki; Iijima, Yoshiyuki; Fujishima, Tsukasa; Shimazaki, Yasuhisa [Yamagata Univ. (Japan). School of Medicine

    1996-11-01

    We report a successful resection of an osteosarcoma in the chest wall developed 25 years after irradiation. A 74-year-old woman was admitted to our hospital for her swelling in the left chest wall at August 24, 1995. At 49-year-old, she had undergone an operation and postoperative irradiation for left breast cancer. A computed tomography demonstrated a mass in the left chest wall that destructed the first rib, extending into the pleural space and invaded into the left common carotid and subclavian arteries. We planned a radical resection of the mass after repeated CT scannings, since it was histopathologically diagnosed as a chondrosarcoma and showed a rapid growth. The tumor was completely removed with radical transmediastinal forequarter amputation of the partial chest wall and total left upper extremity. The left common carotid artery was partially replaced with 6 mm EPTFE vascular prosthesis. The chest wall was reconstructed with Marlex-mesh prosthesis and a myocutaneous flap. She was discharged uneventfully and has not shown any evidence of recurrence. (author)

  2. Prognostic implications of Kindlin proteins in human osteosarcoma

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    Ning K

    2017-02-01

    Full Text Available Kai Ning,* Haoshaqiang Zhang,* Zhigang Wang, Kun Li Department of Orthopedics Surgery Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both P<0.01, but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<0.05, than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both P=0.01, presence of metastasis (both P=0.006, recurrence (both P=0.006 and poor response to chemotherapy (both P=0.02. Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01 and disease-free (P=0.02 and 0.01, respectively survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients’ prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function

  3. Timing of chemotherapy and surgery in a murine osteosarcoma model.

    Science.gov (United States)

    Bell, R S; Roth, Y F; Gebhardt, M C; Bell, D F; Rosenberg, A E; Mankin, H J; Suit, H D

    1988-10-01

    The sequential use of chemotherapy and surgery in the treatment of osteosarcoma developed in an empirical fashion without the benefit of investigations in animal models. The MGH-OGS murine osteosarcoma is a transplantable tumor that resembles the human disease with respect to histology, local invasiveness, metastatic characteristics, tumor ploidy, and its response to chemotherapy. We have used this tumor model to investigate the efficacy of preoperative, perioperative, and postoperative chemotherapy on the development of pulmonary metastases in three different experimental protocols. In each experimental design, perioperative chemotherapy demonstrated a significant advantage in preventing systemic relapse.

  4. Chondroblastoma-like osteosarcoma: a case report and review.

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    Aycan, Osman Emre; Vanel, Daniel; Righi, Alberto; Arikan, Yavuz; Manfrini, Marco

    2015-06-01

    Chondroblastoma-like osteosarcomas are extremely rare malignancies having varying clinical, radiological and histological features. Their rarity causes challenges in both diagnosis and clinical management. They are often misdiagnosed as benign lesions. Their accurate diagnosis is important because they require adequate treatment. Misdiagnosed lesions or undertreatment may result in recurrences. We report a case of chondroblastoma-like osteosarcoma arising in the left first metatarsal bone with tarsometatarsal joint involvement in a 10-year-old boy for whom surgery with an original technique was planned after a multidisciplinary diagnostic review.

  5. Telangiectatic osteosarcoma of the skull. A post-Paget case.

    Science.gov (United States)

    Donato, G; Lavano, A; Volpentesta, G; Chirchiglia, D; Veraldi, A; De Rose, F; Iannello, A N; Stroscio, C; Signorelli, C D

    1997-01-01

    We report a case of post-Paget telangiectatic osteosarcoma of the skull in a 75-year-old woman. Such a neoplasia is a rare variant of osteosarcoma, a tumor rare in the cranic bones. The patient was submitted for a careful analysis by the following procedures: technetium scintigram, X-rays, CT scan, and MRI. After the surgical procedure, pathological examination confirmed the diagnosis. Both radiological and pathological pattern of this tumor are discussed in relation to the differential diagnosis. Our report shows that benign lesions may represent a possible cause of diagnostic errors. They must be excluded by histological analysis.

  6. miR-218 expression in osteosarcoma tissues and its effect on cell growth in osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    Hong-Tai Wang; Ai-Gang Liu; Dao-Shu Luo; Zhang-Nan Zhou; Hong-Guang Lin; Rong-Zi Chen; Jin-Shui He; Kun Chen

    2014-01-01

    Objective:To investigate the expression of miR-218 and its clinical significance in osteosarcoma tissues and explore its effect on proliferation and apoptosis in osteosarcoma cells.Methods:miR-218 expression was detected in76 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR).MiR-218 was over-expressed by exogenous miR-218 plasmids inSaos-2 cells, and thenBrdU cell proliferation assay and flow cytometry were used to determine cell proliferation and apoptosis.Results:The expression of miR-218 in osteosarcoma tissues was significantly lower than those in normal tumor-adjacent tissues(t=8.735,P<0.001).MiR-218 expression in tumor tissues was significantly correlated with tumor size(χ2=5.380,P=0.020), clinical stage (χ2=6.692,P=0.010) and distant metastasis(χ2=4.180,P=0.041).MiR-218 was obviously over-expressed by exogenous miR-218 plasmids(t=19.42,P<0.001), and miR-218 overexpression significantly reduced cell proliferation(t=9.045,P<0.001) and induced apoptosis(t=12.38, P<0.001) inSaos-2 cells.Conclusions:The low-expression of miR-218 is correlated with the poor clinicopathological features in osteosarcoma.Moreover, miR-218 overexpression reduces cancer cell proliferation and induces apoptosis inSaos-2 cells, suggesting that miR-218 may play a key role in the progression of human osteosarcoma.

  7. Modulation of the osteosarcoma expression phenotype by microRNAs.

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    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

  8. Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription.

    Science.gov (United States)

    Chen, Fenyong; Mo, Jiadong; Zhang, Li

    2016-10-01

    Despite great advances have been made in the understanding of biology of osteosarcoma, the molecular mechanisms involved in osteosarcoma tumorigenesis and progression are still largely unknown. Long noncoding RNA (lncRNA) is a new type of RNA molecule, which plays pivotal roles in many tumors. lncRNA BCAR4 has been identified as an oncogenetic lncRNA involved in the progression of breast cancer. However, the functions and clinical significances of BCAR4 in osteosarcoma are unknown now. In this study, we found that BCAR4 was significantly upregulated in osteosarcoma tissues. Increased expression of BCAR4 was significantly correlated with large tumor size, advanced Enneking stage, lung metastasis, and poor prognosis. Functional experiments demonstrated that knockdown of BCAR4 inhibits the proliferation and migration of osteosarcoma cell in vitro. Consistently, knockdown of BCAR4 inhibits osteosarcoma tumorigenesis and lung metastasis in vivo. Chromatin isolation by RNA purification assay showed that BCAR4 physically associates with the promoters of GLI2 target genes. The depletion of BCAR4 inhibits the expression of GLI2 target genes and GLI2 reporter luciferase activity in a dose-dependent manner. The expression of BCAR4 and GLI2 target genes is significantly correlated in osteosarcoma tissues. Depletion of DLI2 abolished the effects of BCAR4 on osteosarcoma. Taken together, these findings demonstrated that BCAR4 promotes osteosarcoma progression via activating GLI2-dependent gene transcription and serves as a potential prognostic biomarker and a therapeutic target of osteosarcoma.

  9. Cytogenetic aberrations in osteosarcomas. Nonrandom deletions, rings, and double-minute chromosomes.

    Science.gov (United States)

    Fletcher, J A; Gebhardt, M C; Kozakewich, H P

    1994-10-01

    Relatively few karyotypes have been reported from short-term cultures and/or direct harvests of osteosarcomas. We describe clonal aberrations in 17 high-grade osteosarcoma specimens and in one low-grade osteosarcoma. The high-grade osteosarcomas were karyotyped after direct harvest (four cases) or after short-term culture periods of osteosarcoma and two lung metastases, were from the same patient and shared a number of clonal aberrations. No consistent chromosome translocations were identified in the overall group of high-grade osteosarcomas, but potential nonrandom deletions involved 6q21-->qter, 9p21-->pter, chromosome 10, chromosome 13, 17p12-pter, and chromosome 20. Ring chromosomes were detected in three cases, and double-minute (dmin) chromosomes were detected in six. All high-grade osteosarcomas had numerous nonclonal chromosome aberrations superimposed on complex clonal events. The single low-grade osteosarcoma was characterized by a balanced, nonconstitutional, t(5;10) (p13;p14-15), together with an addition to the short arm of chromosome X. This is the first translocation reported in low-grade osteosarcoma, and the simplicity of the karyotype contrasts strikingly with those in the high-grade osteosarcomas.

  10. HMGB1 promotes cellular proliferation and invasion, suppresses cellular apoptosis in osteosarcoma.

    Science.gov (United States)

    Meng, Qingbing; Zhao, Jie; Liu, Hongbing; Zhou, Guoyou; Zhang, Wensheng; Xu, Xingli; Zheng, Minqian

    2014-12-01

    Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-binding protein high-mobility group box 1 (HMGB1) was associated with the development of cancer. This study aimed to explore the expression of HMGB1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the role of HMGB1 in the development of osteosarcoma. The results from RT-PCR and Western blot showed that the expression rate of HMGB1 messenger RNA (mRNA) and the expression of HMGB1 in the osteosarcoma tissues were significantly higher than those in normal bone tissue (p lung metastasis were significantly higher than those without lung metastasis (p osteosarcoma, the expression of HMGB1 in the human osteosarcoma MG-63 cell line was downregulated by the technique of RNA interference. Western blot results showed that the protein expression of HMGB1 was significantly decreased in the MG-63 cells from HMGB1-siRNA transfection group (p osteosarcoma might be related to the tumorigenesis, invasion, and metastasis of osteosarcoma, which might be a potential target for the treatment of osteosarcoma.

  11. GLI2 is a novel therapeutic target for metastasis of osteosarcoma.

    Science.gov (United States)

    Nagao-Kitamoto, Hiroko; Nagata, Masahito; Nagano, Satoshi; Kitamoto, Sho; Ishidou, Yasuhiro; Yamamoto, Takuya; Nakamura, Shunsuke; Tsuru, Arisa; Abematsu, Masahiko; Fujimoto, Yusuke; Yokouchi, Masahiro; Kitajima, Shinichi; Yoshioka, Takako; Maeda, Shingo; Yonezawa, Suguru; Komiya, Setsuro; Setoguchi, Takao

    2015-03-15

    Aberrant activation of the Hedgehog (Hh) pathway has been reported in several malignancies. We previously demonstrated that knockdown of GLI2 inhibited proliferation of osteosarcoma cells through regulation of the cell cycle. In this study, we analyzed the function of GLI2 in the pathogenesis of osteosarcoma metastasis. Immunohistochemical studies showed that GLI2 was overexpressed in patient osteosarcoma specimens. Knockdown of GLI2 inhibited migration and invasion of osteosarcoma cells. In contrast, the forced expression of constitutively active GLI2 in mesenchymal stem cells promoted invasion. In addition, xenograft models showed that knockdown of GLI2 decreased lung metastasis of osteosarcomas. To examine clinical applications, we evaluated the efficacy of arsenic trioxide (ATO), which is a Food and Drug Administration-approved antitumor drug, on osteosarcoma cells. ATO treatment suppressed the invasiveness of osteosarcoma cells by inhibiting the transcriptional activity of GLI2. In addition, the combination of Hh inhibitors including ATO, vismodegib and GANT61 prevented migration and metastasis of osteosarcoma cells. Consequently, our findings suggested that GLI2 regulated metastasis as well as the progression of osteosarcomas. Inhibition of the GLI2 transcription may be an effective therapeutic method for preventing osteosarcoma metastasis. © 2014 UICC.

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

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    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

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

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    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

  14. Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue.

    Science.gov (United States)

    Inyang, Alero; Thomas, Dafydd G; Jorns, Julie

    2016-05-01

    Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well-differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS-like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis.

  15. WEE1 inhibition sensitizes osteosarcoma to radiotherapy

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    Helder Marco N

    2011-04-01

    Full Text Available Abstract Background 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 G2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G2 arrest and could sensitize OS cells to irradiation induced cell death. Methods 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. Results 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 G2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. Conclusion We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G2 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.

  16. Allograft Arthrodesis of the Knee in High-grade Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Teng-Le Huang

    2005-09-01

    Conclusion: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or “back-up” reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.

  17. The role of pharmacogenetics in the treatment of osteosarcoma

    NARCIS (Netherlands)

    Vos, H.I.; Coenen, M.J.H.; Guchelaar, H.J.; Loo, D.M.W.M. te

    2016-01-01

    In osteosarcoma, large variation is observed in the efficacy and toxicity of chemotherapeutic drugs among similarly treated patients. Treatment optimization using predictive factors or algorithms is of importance, because there has been a lack of improvement of treatment outcome and survival for

  18. Osteosarcoma: Current Treatment and a Collaborative Pathway to Success

    Science.gov (United States)

    Isakoff, Michael S.; Bielack, Stefan S.; Meltzer, Paul; Gorlick, Richard

    2015-01-01

    Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor. PMID:26304877

  19.  Telangiectatic osteosarcoma: a review of literature

    Directory of Open Access Journals (Sweden)

    Liu J

    2013-05-01

    Full Text Available Jun-jian Liu,1* Shen Liu,2* Jian-guang Wang,1 Wei Zhu,1 Ying-qi Hua,1 Wei Sun,1 Zheng-dong Cai1 1Department of Orthopedic Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Orthopedics, the Sixth Affiliated People’s Hospital, Shanghai Jiaotong University Schoolof Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this workAbstract: Telangiectatic osteosarcoma is a rare variant of osteosarcoma and hence its occurrence, presentation, and prognosis are poorly understood. With advancements in technology and available treatment options, the scenario of its diagnosis, management, and outcome has changed. Chemotherapy with surgery was challenged previously, but has now been proved to be beneficial. We reviewed the available literature and compared results to define the characteristics of the disease, its presentation, radiographic and pathologic features, optimal treatment, and prognosis.Keywords: telangiectatic osteosarcoma, osteosarcoma, radiology

  20. Sonographic Hair-on-end Sign in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Norman Loberant

    2015-01-01

    Full Text Available This report is a case of osteosarcoma in a young female whose initial examination was sonography. This examination demonstrated a femoral tumor and included a unique finding corresponding to the radiographic hair-on-end sign of malignant new bone formation.

  1. Osteosarcoma telangiectásico en un lactante

    Directory of Open Access Journals (Sweden)

    María de los Ángeles Cepeda

    2017-01-01

    Conclusiones: El osteosarcoma telangiectásico en la edad pediátrica es poco común. A la fecha, la paciente ha presentado buena respuesta al tratamiento, aunque se desconoce el pronóstico y la supervivencia de este padecimiento.

  2. Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.

    Science.gov (United States)

    Isakoff, Michael S; Bielack, Stefan S; Meltzer, Paul; Gorlick, Richard

    2015-09-20

    Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor. © 2015 by American Society of Clinical Oncology.

  3. Acridine orange inhibits pulmonary metastasis of mouse osteosarcoma.

    Science.gov (United States)

    Satonaka, Haruhiko; Kusuzaki, Katsuyuki; Akeda, Koji; Tsujii, Masaya; Iino, Takahiro; Uemura, Takeshi; Matsubara, Takao; Nakamura, Tomoki; Asanuma, Kunihiro; Matsumine, Akihiko; Sudo, Akihiro

    2011-12-01

    Although the survival of patients with osteosarcoma has improved following development of chemotherapy and surgery, the presence of pulmonary metastases indicate a poor prognosis. We developed photodynamic and radiodynamic therapies with acridine orange (AO-PDT and AO-RDT) for minimally invasive surgery to treat musculoskeletal sarcomas and reported a good clinical outcome of local control and limb function. We investigated the effect of AO-PDT using flash-wave light (FWL) on pulmonary metastasis of mouse osteosarcoma. In in vitro and in vivo studies, AO alone and AO-PDT significantly inhibited cell invasion and the growth of pulmonary metastases from primary mouse osteosarcoma. AO may have a specific metastasis-inhibitory effect, different from the effect of AO-PDT. The fluorovisualization effect on pulmonary metastases following intravenous AO administration showed that pulmonary metastases localized on the lung surface were recognized as brilliant green lesions. In conclusion, AO-PDT using FWL inhibited cell invasion and pulmonary metastases in mouse osteosarcoma; therefore, this treatment modality might be applicable for treating pulmonary metastasis from malignant musculoskeletal tumors in humans.

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

    African Journals Online (AJOL)

    regimens and surgical techniques.2,4,6,8 To benefit from these advances in treatment, the ... osteosarcoma were managed at our orthopaedic tumour unit. After complete ... (Table 1); metastasis to the lung was the most common site in 12/16.

  5. Recurrent cardiac metastasis of primary femoral osteosarcoma: a case report.

    Science.gov (United States)

    Iyigun, Taner; Ciloglu, Ufuk; Ariturk, Cem; Civelek, Ali; Tosun, Remzi

    2010-10-01

    A 17-year-old female patient with a history of surgery for primary femoral and metastatic lung osteosarcoma was admitted to our clinic with palpitations. Upon evaluation, a metastatic osteosarcoma in the left ventricle was diagnosed. Based on the collaborative decision of the oncology and cardiovascular surgery clinics, surgery was performed and the patient was discharged without any problems. According to the recommendation of the oncology clinic, chemotherapy was postponed for 6 months after surgery. Five months postoperatively, however, she had a recurrence with 2 tumors. Based on the collaborative decision, chemotherapy was initiated and in 2 months the size of the recurrent tumors had diminished. The patient is still under the care of the oncology and cardiovascular surgery clinics and continuing her chemotherapy regimen. Osteosarcomas have a high mortality. Metastatic tumors of the heart are not common. The location of the metastasis and the characteristics of the primary tumor determine the treatment modality. In some previously published reports, various treatment choices have been described. In the present case report, we present a rare case with metastatic cardiac osteosarcoma.

  6. [Low grade parosteal osteosarcoma. Clinical and oncological outcomes].

    Science.gov (United States)

    Albergo, José I; Farfalli, Germán L; Ayerza, Miguel A; Muscolo, Domingo L; Aponte-Tinao, Luis A

    2015-01-01

    The objective of the study was to analyze a group of patients with low grade parosteal osteosarcoma treated with limb salvage surgery and reconstructed with bone allograft. A retrospective review from our oncologic data base between 1980 and 2010 was done and all patients with diagnosis of low grade parosteal osteosarcoma, treated with limb salvage surgery and reconstructed with allograft were included. Twenty-two patients were included for the analysis. The mean age was 32±11 years (10-59) y the mean follow-up 93±69 months (8-237). Ten year overall survival of the series was 91% (95% CI: 79-100). Four patients developed local recurrence, 2 of them histological classified after the resection dedifferentiated parosteal osteosarcoma. Two patients developed distant recurrence, being the lung the only site of metastasis. Ten year limb salvage reconstruction survival was 65% (95% CI: 44-86). Long term survival rate in low grade parosteal osteosarcoma is over 90%. Surgical resection wide margin should be the elective treatment and biological limb salvage reconstruction is a good alternative.

  7. Kissing pleural metastases from metastatic osteosarcoma of the lung.

    Science.gov (United States)

    Mori, Takeshi; Yoshioka, Masakazu; Iwatani, Kazunori; Kobayashi, Hironori; Yoshimoto, Kentaro; Nomori, Hiroaki

    2006-04-01

    Two patients with osteosarcoma lung metastases of which migrated to the parietal pleura due to contact are reported. The first patient was a 16-year-old male who had a pleural metastasis in the diaphragm within an area in contact with a single lung metastasis. Both of the tumors were resected, followed by systemic chemotherapy. Nine months after the resection of the first metastases, two other lung metastases were found which were resected after chemotherapy. The patient is alive without recurrence 84 months after the first resection of the metastases. The second patient was an 11-year-old female with a pleural metastasis of osteosarcoma which was within an area in contact with a single lung metastasis, which had been resected 4 months before. We concluded (1) that a lung metastasis of osteosarcoma occasionally metastasizes to the pleura due to contact; and (2) that because this kissing metastases of osteosarcoma could be cured by a complete resection, the intrathoracic cavity should be thoroughly observed.

  8. Osteosarcoma of the jaws. An analytical study of 13 cases

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, T.; Horiuchi, J.; Shibuya, H.; Suzuki, S. (Tokyo Medical and Dental Univ. (Japan). School of Medicine); Takeda, M.

    1982-03-01

    The clinical features and roentgenographic findings were analyzed in a series of 13 cases of osteosarcoma of the jaws treated at Tokyo Medical and Dental University Hospital during a period of 14 years from 1962 to 1975. In contrast with osteosarcomas located elsewhere, the ages in the present series were distributed from 23 to 59 years, with an average of 35.8 years. There seemed to be no predilection for sex distribution. Some patients had complaints of numbness in lips and odontalgia. Regional lymph node metastasis as well as lung metastasis could not be observed in 12 cases at the first visit to the hospital but metastasis to submandibular lymph node from osteosarcoma of mandible was noted in the remaining case. Three of 13 cases were classified as osteosclerotic, 6 osteolytic and 4 mixed type by roentgenographic findings of the jaws. Four among 13 cases were treated by surgical removal alone and the other 9 cases were treated by a combination of surgery and radiation therapy. Good results were obtained in the cases treated by surgery with or without preoperative irradiation. Two-year, 5-year and 10-year survival rates of all 13 cases were 69%, 69% and 44%, respectively. Local control may provide a reasonable chance of curing patients with osteosarcoma of jaws, since metastasis, especially hematogenous, is much less frequent in the group of jaws than other sites.

  9. Osteosarcoma of the mandible with exuberant sunburst periosteal ...

    African Journals Online (AJOL)

    McRoy

    occur at an older age with pain and swelling. ... tooth loss. She complained of difficulty in opening mouth since last two weeks. ... osteosarcoma, they present in 3rd to 4th decade and carry a ... department of maxillofacial surgery for further.

  10. MicroRNAs and potential targets in osteosarcoma: review

    Directory of Open Access Journals (Sweden)

    Valerie B. Sampson

    2015-08-01

    Full Text Available Osteosarcoma is the most common bone cancer in children and young adults. Surgery and multi-agent chemotherapy are the standard treatment regimens for this disease. New therapies are being investigated to improve overall survival in patients. Molecular targets that actively modulate cell processes such as cell-cycle control, cell proliferation, metabolism and apoptosis, have been studied, but it remains a challenge to develop novel, effective targeted therapies to treat this heterogeneous and complex disease. MicroRNAs (miRNAs are small noncoding RNAs that play critical roles in regulating cell processes including growth, development and disease. miRNAs function as oncogenes or tumor suppressors to regulate gene and protein expression. Several studies have demonstrated the involvement of miRNAs in the pathogenesis of osteosarcoma with the potential for development in disease diagnostics and therapeutics. In this review, we discuss the current knowledge on the role of miRNAs and their target genes and evaluate their potential use as therapeutic agents in osteosarcoma. We also summarize the efficacy of inhibition of oncogenic miRNAs or expression of tumor suppressor miRNAs in preclinical models of osteosarcoma. Recent progress on systemic delivery as well as current applications for miRNAs as therapeutic agents has seen the advancement of miR-34a in clinical trials for adult patients with non-resectable primary liver cancer or metastatic cancer with liver involvement. We suggest a global approach to the understanding of the pathogenesis of osteosarcoma may identify candidate miRNAs as promising biomarkers for this rare disease.

  11. Vasculogenic mimicry: a new prognostic sign of human osteosarcoma.

    Science.gov (United States)

    Ren, Ke; Yao, Nan; Wang, Guangye; Tian, Lei; Ma, Jie; Shi, Xin; Zhang, Lei; Zhang, Jian; Zhou, Xing; Zhou, Guangxin; Wu, Sujia; Sun, Xiaoliang

    2014-10-01

    Vasculogenic mimicry (VM), a formation of nonendothelial microvascular channels, has been generally recognized as a new pattern of neovascularization in aggressive malignancies. However, whether VM is present and clinically significant in osteosarcoma remains unknown. We identified VM by CD34/periodic acid-Schiff double staining of osteosarcoma specimens before chemotherapy and investigated its prognostic implications. Tumors were also immunohistochemically stained for focal adhesion kinase (FAK) and migration inducing gene 7 (Mig-7) to determine whether these markers are associated with the occurrence of VM. VM was found in 15 of 66 osteoblastic-type osteosarcoma samples (22.7%), and the incidence of VM did not differ with respect to patient sex, age, tumor size, tumor site, surgical type, or histologic response to preoperative chemotherapy. However, Kaplan-Meier survival analysis determined that the presence of VM and the tumor necrosis rate after preoperative chemotherapy are associated with both the overall survival (P = .011 and P = .040, respectively) and metastasis-free survival (P = .002 and P = .045, respectively). Furthermore, Cox proportional hazards analysis showed that the presence of VM and the histologic response to preoperative chemotherapy were independent indicators for both poor overall survival (P = .007 and P = .024, respectively) and poor metastasis-free survival (P = .002 and P = .027, respectively). The expression level of FAK and Mig-7 were higher in the VM group than the non-VM group (P = .017 and P = .021, respectively). These results demonstrate the presence of VM in osteoblastic osteosarcoma and suggest that VM is an unfavorable prognostic factor with FAK and Mig-7 expressions as a potential mechanism of VM formation in osteosarcoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail.

    Science.gov (United States)

    Fang, Shuo; Yu, Ling; Mei, Hongjun; Yang, Jian; Gao, Tian; Cheng, Anyuan; Guo, Weichun; Xia, Kezhou; Liu, Gaiwei

    2016-12-01

    More than 30% of patients with osteosarcoma succumb to pulmonary metastases. Epithelial-mesenchymal transition (EMT) is a biological process by which tumor cells gain an increased capacity for invasiveness and metastasis. A previous study confirmed the phenomenon of EMT in osteosarcoma, a mesenchymal-derived tumor. However, whether chemotherapy affects EMT remains to be elucidated. In the present study, the osteosarcoma cells were exposed to a sublethal dose of cisplatin, and any surviving cells were assumed to be more resistant to cisplatin. In addition, these cells exhibited a more mesenchymal phenotype. Immunofluorescence analysis revealed that the cisplatin treated cells had an increased long/short axis ratio and increased expression of N-cadherin compared with control cells. A panel of EMT-associated genes was subsequently assessed by quantitative PCR and western blot analysis, and they were observed to be significantly upregulated in the cisplatin treated cells. The in vitro wound healing and Transwell assay indicated that the cisplatin treated cells were more prone to migrate and invade. An in vivo assay showed that the cisplatin-treated xenograft had increased expression of EMT-associated genes, and exhibited increased pulmonary lesions compared with the control, which indicated an elevated capacity to metastasize. The expression of Snail was knocked down by specific small interfering RNA, and it was observed that Snail inhibition promoted cisplatin sensitivity, and cisplatin-induced EMT was significantly blocked. Taken together, the results of the present study supported that idea that Snail participates in cisplatin-induced EMT in osteosarcoma cells, and targeting EMT-transcription factors may offer promise for the therapeutics of osteosarcoma.

  13. Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

    Science.gov (United States)

    Correale, P; Sciandivasci, A; Intrivici, C; Pascucci, A; Del Vecchio, M T; Marsili, S; Savelli, V; Voltolini, L; Di Bisceglie, M; Guarnieri, A; Gotti, G; Francini, G

    2007-01-01

    We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m−2) and etoposide (100 mg m−2) on days 1–3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours. PMID:17437022

  14. Elevated expression of serine/threonine phosphatase type 5 correlates with malignant proliferation in human osteosarcoma.

    Science.gov (United States)

    Han, Kun; Gan, Zhihua; Lin, Shuchen; Hu, Haiyan; Shen, Zan; Min, Daliu

    2017-01-01

    Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells. Moreover, FACS analysis showed that knockdown of PP5 expression induced a significant arrest in the G0/G1 phase of the cell cycle, which was associated with the inhibition of cell proliferation. Therefore, knockdown of PP5 is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

  15. Expression of Survivin Gene and Its Relationship with Clinical Multidrug Resistance in Osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    NIETao; DAIMin; ZONGShizhang

    2005-01-01

    Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.

  16. Osteosarcoma condroblástico maxilar: Presentación de un caso Chondroblastic osteosarcoma of the maxilla: A case report

    Directory of Open Access Journals (Sweden)

    E. Álvarez Martínez

    2012-10-01

    Full Text Available Los osteosarcomas son neoplasmas caracterizados por la presencia de células mesenquimales que producen tejido osteoide. Las manifestaciones clínicas en la cavidad bucal comprenden dolor, inflamación, desplazamiento de los dientes, espasmos, parestesias y obstrucción nasal. Este artículo presenta un osteosarcoma condroblástico avanzado en el maxilar superior. El examen histológico evidenció proliferación neoplásica extensamente cartilaginosa, con áreas pequeñas en la que se identificó formación osteoide y hueso no laminar, rodeado por células neoplásicas. El tratamiento consistió en maxilectomía y vaciamiento bilateral de cuello. Además, se colocó férula quirúrgica obturadora con el fin de sellar el defecto de la comunicación oronasosinusal. Aun cuando el osteosarcoma de los maxilares presenta un mejor pronóstico que el osteosarcoma de los huesos largos, los pacientes con osteosarcoma maxilar pueden presentar tumores avanzados, principalmente cuando no se realiza el diagnóstico adecuado.Osteosarcomas are neoplasms characterized by the presence of mesenchymal cells that produce osteoid. The clinical manifestations in the oral cavity include pain, swelling, teeth displacement, twitching, paresthesia, and nasal obstruction. This paper presents an advanced chondroblastic osteosarcoma in the maxilla. Histological examination showed extensive cartilaginous neoplastic proliferation, with small areas in which osteoid formation was identified and non-lamellar bone, surrounded by neoplastic cells. The treatment consisted in maxillectomy and bilateral neck dissection. In addition, sealing stents were placed to seal the defect orosinonasal communication. Although osteosarcoma of the jaw has a better prognosis than osteosarcoma of long bones, jaw osteosarcoma patients with advanced tumors can occur, especially when the proper diagnosis is not appropriate.

  17. Long-term survival after sporadic and delayed metastases of conventional osteosarcoma

    OpenAIRE

    Kubo, Tadahiko; Furuta, Taisuke; Johan, Muhammad P.; Yoshizuka, Masaaki; Ochi, Mitsuo; Adachi, Nobuo

    2017-01-01

    Abstract Histologically conventional osteosarcoma, once metastasized to the lung, generally causes a rapid and fatal outcome. Osteosarcoma metastasis to the gastrointestinal tract is extremely rare. We report herein a case of osteoblastic osteosarcoma with exceptionally unique features: sporadic lung metastases and delayed metastases to the stomach and the jejunum with long-term survival. She received multiple operations and chemotherapies, but consequently died of peritoneal dissemination. A...

  18. A case of parosteal osteosarcoma with a rare complication of myositis ossificans

    OpenAIRE

    Spinelli Maria Silvia; Perisano Carlo; Rocca Carlo Della; Hardes Jendrick; Barone Carlo; Fabbriciani Carlo; Maccauro Giulio

    2012-01-01

    Abstract We report the case of a parosteal osteosarcoma of the distal ulna, treated with wide resection without reconstruction. The patient developed lung metastasis and a mass in the interosseus membrane of the forearm proximally to the osteotomy. The lung mass was found to be a metastasis from parosteal osteosarcoma and the biopsy of the forearm mass revealed a myositis ossificans. The suspicion of a recurrence of parosteal osteosarcoma, already metastatic, led to a second wide resection wi...

  19. Stereotactic Body Radiotherapy for Metastatic and Recurrent Ewing Sarcoma and Osteosarcoma

    OpenAIRE

    Brown, Lindsay C.; Lester, Rachael A.; Grams, Michael P.; Haddock, Michael G.; Olivier, Kenneth R.; Arndt, Carola A S; Rose, Peter S.; Laack, Nadia N.

    2014-01-01

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Farbod Rastegar

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  1. The ARF Tumor Suppressor Regulates Bone Remodeling and Osteosarcoma Development in Mice

    Science.gov (United States)

    Harding, John C.; Deng, Hongju; Shea, Lauren K.; Eagleton, Mark C.; Niewiesk, Stefan; Lairmore, Michael D.; Piwnica-Worms, David; Rosol, Thomas J.; Weber, Jason D.; Ratner, Lee; Weilbaecher, Katherine N.

    2010-01-01

    The ARF tumor suppressor regulates p53 as well as basic developmental processes independent of p53, including osteoclast activation, by controlling ribosomal biogenesis. Here we provide evidence that ARF is a master regulator of bone remodeling and osteosarcoma (OS) development in mice. Arf-/- mice displayed increased osteoblast (OB) and osteoclast (OC) activity with a significant net increase in trabecular bone volume. The long bones of Arf-/- mice had increased expression of OB genes while Arf-/- OB showed enhanced differentiation in vitro. Mice transgenic for the Tax oncogene develop lymphocytic tumors with associated osteolytic lesions, while Tax+Arf-/- mice uniformly developed spontaneous OS by 7 months of age. Tax+Arf-/- tumors were well differentiated OS characterized by an abundance of new bone with OC recruitment, expressed OB markers and displayed intact levels of p53 mRNA and reduced Rb transcript levels. Cell lines established from OS recapitulated characteristics of the primary tumor, including the expression of mature OB markers and ability to form mineralized tumors when transplanted. Loss of heterozygosity in OS tumors arising in Tax+Arf+/- mice emphasized the necessity of ARF-loss in OS development. Hypothesizing that inhibition of ARF-regulated bone remodeling would repress development of OS, we demonstrated that treatment of Tax+Arf-/- mice with zoledronic acid, a bisphosphonate inhibitor of OC activity and repressor of bone turnover, prevented or delayed the onset of OS. These data describe a novel role for ARF as a regulator of bone remodeling through effects on both OB and OC. Finally, these data underscore the potential of targeting bone remodeling as adjuvant therapy or in patients with genetic predispositions to prevent the development of OS. PMID:21209895

  2. CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models

    Science.gov (United States)

    Zhang, Shui-Jun; Zhao, Chen; Qiu, Bin-Song; Gu, Hai-Feng; Hong, Jian-Fei; Cao, Li; Chen, Yu; Xia, Bing; Bi, Qin; Wang, Ya-Ping

    2015-01-01

    Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells. In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor. PMID:26093091

  3. Synchronous multifocal osteosarcoma with small cell histological variant: A double rarity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2016-01-01

    Full Text Available Multifocal osteosarcoma (MFOS, osteosarcoma involving multiple sites, is a rare variant of osteosarcoma. When the lesions appear within 6 months of initial presentation of the tumor, it is known as synchronous MFOS. Synchronous MFOS has an incidence of 1%–3% only. Moreover, the histological variant of small cell osteosarcoma is even rarer. A case of 14-year-old male with synchronous MFOS of small cell type involving frontal and mandibular bone simultaneously is being reported here. It poses a dilemma to both the clinician and the pathologist to diagnose whether it represents multiple primary tumor or metastatic disease.

  4. miR-486 suppresses the development of osteosarcoma by regulating PKC-δ pathway.

    Science.gov (United States)

    He, Ming; Wang, Guangbin; Jiang, Linlin; Qiu, Chuang; Li, Bin; Wang, Jiashi; Fu, Yonghui

    2017-05-01

    Osteosarcoma is one of the most highly malignant types of cancer in adolescents and young adults with a high mortality rate. Despite advances in surgery, radiation therapy and chemotherapy, the prognosis for patients with osteosarcoma has not significantly improved over the past several decades. It is necessary to find new indicators of prognosis and therapeutic targets of osteosarcoma. Through the analysis of 40 osteosarcoma tissues, we found that the expression of miR‑486 was low and the expression of PKC‑δ was high in osteosarcoma. Median survival of patients with low expression of miR-486 (30 months) was shorter than the patients with higher expression of miR‑486 (40 months). We further found that miR-486 can inhibit the targeting of PKC‑δ signaling pathways, and this inhibition can inhibit the growth and invasion of osteosarcoma cells. After transfection of miR‑486 for 24 h, the proliferation of osteosarcoma cells was inhibited by ~20%, and the migration was inhibited by ~15%. In the present investigation, we demonstrated that miR‑486 is negatively associated with the expression of PKC-δ and could regulate the development of osteosarcoma. miR-486 may be a potential target for the treatment of osteosarcoma.

  5. Elevated expression of matrix metalloproteinase-3 in human osteosarcoma and its association with tumor metastasis.

    Science.gov (United States)

    Huang, Jie-Feng; Du, Wen-Xi; Chen, Jun-Jie

    2016-01-01

    Matrix metalloproteinase-3 (MMP-3) is one of the several MMPs that is associated with malignant tumors of breast, colon, cervix and lung, where its expression has been correlated with tumor invasion and metastasis. However, the role of MMP-3 in metastasis of osteosarcoma has not yet been explored. MMP-3 expression in 15 primary and metastatic osteosarcomas with case-matched adjacent non-tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. Further, MMP-3 mRNA and protein levels were also determined in osteoblast and osteosarcoma cell lines. Additionally, migration and invasion assays were performed in MMP-3 knockdown cells. MMP-3 was expressed in 86.6% (13/15) of the osteosarcoma patients and its expression was significantly higher in metastatic tumors as compared to the primary osteosarcoma tumor tissues. Furthermore, osteosarcoma cell lines showed higher MMP-3 expression as compared to osteoblast cell lines. siRNA-mediated MMP-3 knockdown in osteosarcoma cell lines significantly inhibited their migration and invasion properties. Our results demonstrated that MMP-3 expression is deregulated in osteosarcomas and this potentially contributes to metastasis and might be a promising marker for the prognosis and therapy of metastatic osteosarcoma.

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

    Science.gov (United States)

    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

    2016-12-14

    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 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2. Proliferation, migration, and anchorage independent growth were evaluated. RNA sequencing and immunohistochemistry of human osteosarcoma tissue samples were used to further evaluate the potential role of the Slit-Robo pathway in osteosarcoma. The effects of Srgap2 expression modulation in the murine OS cell lines support the hypothesis that SRGAP2 may have a role as a suppressor of metastases in osteosarcoma. Additionally, SRGAP2 and other genes in the Slit-Robo pathway have altered transcript levels in a subset of mouse and human osteosarcoma, and SRGAP2 protein expression is reduced or absent in a subset of primary tumor samples. SRGAP2 and other axon guidance proteins likely play a role in osteosarcoma metastasis, with loss of SRGAP2 potentially contributing to a more aggressive phenotype.

  7. Childhood osteosarcoma of greater wing of sphenoid: case report and review of literature.

    Science.gov (United States)

    Meel, Rachna; Thulkar, Sanjay; Sharma, Mehar Chand; Jagadesan, Pandjatcharan; Mohanti, Bidhu Kalyan; Sharma, Suresh Chandra; Bakhshi, Sameer

    2012-03-01

    Primary osteosarcoma of skull base is extremely rare. We present a case of primary osteosarcoma arising in greater wing of sphenoid in a child. Our patient had an incomplete excision after which he received adjuvant chemotherapy and radiotherapy. There was good response to adjuvant chemoradiotherapy and the patient is disease free at a follow-up of 18 months. Treatment of skull base osteosarcomas is difficult, as complete excision is often not possible. To the best of our knowledge, this is the first case of sphenoid wing osteosarcoma in childhood to be reported in literature.

  8. Intrinsic resistance to chemotherapeutic agents in murine osteosarcoma cells.

    Science.gov (United States)

    Takeshita, H; Kusuzaki, K; Ashihara, T; Gebhardt, M C; Mankin, H J; Hirasawa, Y

    2000-07-01

    There are two general categories of drug resistance: acquired and intrinsic. The mechanisms involved in acquired drug resistance have been extensively studied, and several mechanisms have been described. However, the mechanisms responsible for intrinsic drug resistance have not been elucidated, to our knowledge. The purpose of the present study was to investigate the cytological and biochemical differences between acquired and intrinsic drug resistance in osteosarcoma cells. We previously isolated a clonal cell line (MOS/ADR1) to study acquired resistance in osteosarcoma by exposure of parental murine osteosarcoma cells (MOS) to doxorubicin. In the present study, we cloned a new, intrinsically resistant cell line (MOS/IR1) by single-cell culture of MOS cells and we investigated the differences in cell phenotype and the mechanisms of resistance in both of these resistant clones. The MOS/ADR1 and MOS/IR1 cells were sevenfold and fivefold more resistant to doxorubicin than the parental murine osteosarcoma cells. Morphologically, the MOS/ADR1 cell line was composed of polygonal cells, whereas the MOS/IR1 cell line consisted of plump spindle cells with long cytoplasmic processes. The MOS/IR1 cells showed a much lower level of alkaline phosphatase activity than did the MOS/ ADR1 and MOS cells. There were no substantial differences in the cellular DNA content or the doubling time among these three lines. Overexpression of the P-glycoprotein involved in the function of an energy-dependent drug-efflux pump was detected in the MOS/ADR1 cells but not in the MOS/ IR1 cells. After the cells were incubated with doxorubicin for one hour, the two resistant lines had less accumulation of the drug than did the parent line (p osteosarcoma may include multiple chemotherapeutic agents, such as doxorubicin, cisplatin, and methotrexate. These drugs exhibit different cytotoxic actions and, thus, the mechanisms of resistance to individual drugs vary. Clinical resistance to multidrug

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Hypoxia-inducible microRNA-488 regulates apoptosis by targeting Bim in osteosarcoma.

    Science.gov (United States)

    Zhou, Chusong; Tan, Wei; Lv, Hai; Gao, Fei; Sun, Jin

    2016-10-01

    Osteosarcoma is a malignant bone cancer of which the survival rate is still low. One reason for this low survival rate is drug resistance. In the past, it has been shown that microRNAs may play critical roles in osteosarcoma development and drug resistance. The mechanisms by which osteosarcoma cells acquire this resistance have, however, remained largely unknown. Here, we aimed at assessing the role of microRNA-488 in the acquisition of drug resistance by osteosarcoma cells. Quantitative RT-PCR was used to measure the expression of microRNA-488 in primary osteosarcoma samples and in osteosarcoma-derived cells, whereas microRNA-488 mimics and inhibitors were used to modify its expression in these cells. Luciferase reporter, Western blotting, cell viability, apoptosis and ChIP assays were used to assess the various effects of modified microRNA-488 expression in osteosarcoma-derived cells. We found that microRNA-488 is over-expressed in primary osteosarcoma tissues and osteosarcoma-derived cells and that hypoxia can induce microRNA-488 expression via binding to the hypoxia response element (HRE) in its promoter. We also found that exogenous over-expression of microRNA-488 promotes the proliferation, reduces the apoptosis and decreases the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the tumor suppressor Bim, which is a mediator of apoptosis. In contrast, we found that transfection of a microRNA-488 inhibitor resulted in an increase in both apoptosis and drug sensitivity, and a decrease in proliferation. Our data suggest that miRNA-488 may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-Sheng, E-mail: wangchsh2011@hotmail.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China); Yin, Qi-Hua, E-mail: 843003910@qq.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China); Liao, Jin-Sheng, E-mail: liaojinsheng850929@163.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China); Lou, Jiang-Hua, E-mail: loujianghua1985@163.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China); Ding, Xiao-Yi, E-mail: dxyrj@hotmail.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China); Zhu, Yan-Bo, E-mail: zhuyanbo11@hotmail.com [Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai 200025 (China); Chen, Ke-Min, E-mail: chenkemin1@hotmail.com [Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025 (China)

    2012-11-15

    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.

  16. Inhibition of casein kinase 2 prevents growth of human osteosarcoma.

    Science.gov (United States)

    Takahashi, Kengo; Setoguchi, Takao; Tsuru, Arisa; Saitoh, Yoshinobu; Nagano, Satoshi; Ishidou, Yasuhiro; Maeda, Shingo; Furukawa, Tatsuhiko; Komiya, Setsuro

    2017-02-01

    High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2α and CK2β by western blot analysis, and performed WST-1 assays using CK2α and CK2β siRNA or CX-4945. Flow cytometry and western blot analyses were performed to evaluate apoptotic cell death. Xenograft models were used to examine the effect of CX-4945 in vivo. Western blot analysis revealed upregulation of CK2α and CK2β in human osteosarcoma cell lines compared with human osteoblast cells or mesenchymal stem cells. WST assay showed that knockdown of CK2α or CK2β by siRNA inhibited the proliferation of human osteosarcoma cells. Treatment with 3 µM of CX-4945 inhibited osteosarcoma cell proliferation; however, the same concentration of CX-4945 did not affect the proliferation of human mesenchymal stem cells. Additionally, treatment with CX-4945 inhibited the proliferation of human osteosarcoma cells in a dose-dependent manner. Western blot and flow cytometry analyses showed that treatment with CX-4945 promoted apoptotic death of osteosarcoma cells. The xenograft model showed that treatment with CX-4945 significantly prevented osteosarcoma growth in vivo compared with control vehicle treatment. Our findings indicate that CK2 may be an attractive therapeutic target for treating osteosarcoma.

  17. Fibroblastic Type Osteosarcoma of the Ulna: a Case Report of a Tumor in a Rare Location with Atypical Imaging Findings

    Science.gov (United States)

    Joo, Ijin; Chung, Jin-Haeng; Oh, Joo Han; Hong, Sung Hwan; Kang, Heung Sik

    2009-01-01

    The ulna is a rare site of origin for osteosarcoma, and purely osteolytic osteosarcomas are uncommonly noted on conventional radiographs. We present a patient with a lytic lesion of the distal ulna for which imaging findings suggested an aneurysmal bone cyst. The lesion was histologically confirmed to be a fibroblastic osteosarcoma. PMID:19182508

  18. Fibroblastic Type Osteosarcoma of the Ulna: a Case Report of a Tumor in a Rare Location with Atypical Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Joo, I Jin; Choi, Jung Ah; Hong, Sung Hwan; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of); Chung, Jin Haeng; Oh, Joo Han [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2009-02-15

    The ulna is a rare site of origin for osteosarcoma, and purely osteolytic osteosarcomas are uncommonly noted on conventional radiographs. We present a patient with a lytic lesion of the distal ulna for which imaging findings suggested an aneurysmal bone cyst. The lesion was histologically confirmed to be a fibroblastic osteosarcoma.

  19. Aberrant Hedgehog Signaling and Clinical Outcome in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Winnie W. Lo

    2014-01-01

    Full Text Available Despite the importance of Hedgehog signaling in bone development, the relationship between Hedgehog pathway expression and osteosarcoma clinical characteristics and outcome has not been investigated. In this study of 43 high-grade human osteosarcoma samples, we detected high expression levels of the Hedgehog ligand gene, IHH, and target genes, PTCH1 and GLI1, in most samples. Further analysis in tumors of patients with localized disease at diagnosis identified coexpression of IHH and PTCH1 exclusively in large tumors. Higher levels of IHH were observed more frequently in males and patients with higher levels of GLI1 were more responsive to chemotherapy. Subgroup analysis by tumor size and IHH expression indicated that the well-known association between survival and tumor size was further refined when IHH levels were taken into consideration.

  20. The Partial Purification of Angiogenesis Factor of Human Osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    WUHua; DENGZhongduan; 等

    2002-01-01

    Objective To partially purify the angiogenesis factor of human osteosarcoma(HuOs) and study its biological features. Methods The active peptide with a molecular weight of 8000-10000 Da in the conditioned medium obtained from the cultivation of Hu-Os cells(osteoblastic osteosarcoma) was partially purified by ultrafiltration, chromatography and dialysis.The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig thoracic aorta endothelial cells. Results The chromatography fractions 4-6 could significantly promote the proliferation of the endothelial cells.Conclusion The HuOs cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000-10000 Da.

  1. Scintigraphy of lower extremity cadaveric bone allografts in osteosarcoma patients.

    Science.gov (United States)

    Bar-Sever, Z; Connolly, L P; Gebhardt, M C; Treves, S T

    1997-08-01

    To describe scintigraphic characteristics of bone allografts used in limb salvage reconstruction after resection of lower extremity osteosarcoma. The authors reviewed 85 skeletal scintigrams of 20 pediatric patients followed up for 0.5-5.7 years after resection of lower extremity osteosarcoma and allograft reconstruction. Uptake in the allograft and adjacent host tissues was assessed visually. Lack of tracer uptake in the allografts was seen in 99% of the studies and a faint rim of tracer localization outlining the allograft's periphery was seen in 95% of the studies. Increased uptake was noted at the allograft-host bone junction in 78% of the studies. Uptake was increased in the joint surfaces of native bones articulating with allografts (97% of studies), including the patella (93% of studies) when the knee was involved. These findings were stabilized as time passed. Cadaveric bone allografts have a characteristic scintigraphic appearance in this selected patient group that reflects the physiology of their incorporation process.

  2. 'Bubble-like' lung metastases in osteosarcoma patients

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    Briccoli, Antonio; Rocca, Michele; Salone, Maria Cristina [General Surgery, Rizzoli Orthopaedic Institute, Bologna (Italy); Di Fiore, Maria [Anaesthesiology, izzoli Orthopaedic Institute, Bologna (Italy); Vanel, Daniel [Research in Imaging, Rizzoli Orthopaedic Institute, Bologna (Italy)], E-mail: vanel@igr.fr; Balladelli, Alba [Laboratory Oncology Research, Rizzoli Orthopaedic Institute, Bologna (Italy); Alberghini, Marco [Pathology, Rizzoli Orthopaedic Institute, Bologna (Italy)

    2009-07-15

    Purpose: Cavitation of pulmonary metastases have been reported by several authors either as a spontaneous phenomenon or as a consequence of chemotherapy. We present two cases, with this type of image in follow-up, and 20-45 months after the end of treatment. This was the first sign of pulmonary metastases. Results: Two patients with osteogenic sarcoma developed radiological evidence of pulmonary 'bubble-like' cavitation several years following completion of chemotherapy. In one patient the 'bubble-like' cavitation transformed into a solid nodule. Both patients had surgical resections of all pulmonary lesions, and histology confirmed presence of viable osteosarcoma metastases. Conclusion: The two cases suggest that onset of 'bubble-like' cavitation in lung parenchyma of osteosarcoma patients may be the first sign of pulmonary metastases.

  3. Percutaneous intra-arterial chemotherapy of osteosarcoma with cisplatin

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    Lim, Duk; Byun, Hong Sik; Kim, Kie Hwan; Chin, Soo Yil; Chung, Jin Youb; Lee, Soo Yong [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1990-04-15

    Intra-arterial Chemotherapy (IAC) was performed to the 34 patients with non metastatic osteosarcoma using Cisplatin and surgery was done in 26 cases out of 34. We analysed the therapeutic effect of IAC in the view of local control rate and distant metastasis for two and half years. Local control rate was 94% on the base of the radiologic studies including simple X-ray, angiography and CT. No variable cells were observed in 50% of the cases on the pathologic examination of the surgical specimens. Distant metastasis developed in 14 cases (41%), mainly in the lung. No significant complications occurred except each case of acute renal failure, congestive heart failure and peripheral embolism, which were improved by proper management. IAC is one of the most effective methods in controlling the regionally confined osteosarcoma, but it may be incorporated with other adjuvant protocols to decrease the chance of delayed metastasis.

  4. Rotationplasty for patients with osteosarcoma around the knee joint.

    Directory of Open Access Journals (Sweden)

    Kawai,Akira

    1995-08-01

    Full Text Available The results of rotationplasty for patients with osteosarcoma around the knee joint are presented. After an average observation period of 13.3 months, there has been no local recurrence or metastasis. The ankle joints (the new knee joints of the patients were able to support their body weight with an average range of motion of 75 degrees. All patients could walk well without crutches and without risk of the giving way phenomenon. The average rate of the functional evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0-86.7%. No patient had psychological trouble in accepting the shortened and rotated extremity. The results show that rotationplasty is a useful reconstructive method for the treatment of osteosarcoma around the knee joint.

  5. Imaging in primary osteosarcomas; Bildgebung beim primaeren Osteosarkom

    Energy Technology Data Exchange (ETDEWEB)

    Davies, A.M. [MRI Centre, Royal Orthopaedic Hospital, Birmingham (United Kingdom)

    1998-06-01

    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.) [Deutsch] Das Osteosarkom ist abgesehen vom Myelom der haeufigste primaere boesartige Knochentumor. Die ueberwiegende Mehrzahl der Osteosarkome kommen innerhalb des Knochens vor und werden `konventionelle Osteosarkome` genannt. Die im Knochen vorkommenden Varianten beinhalten

  6. 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.

  7. Re-calculating! Navigating through the osteosarcoma treatment roadblock.

    Science.gov (United States)

    McGuire, J; Utset-Ward, T J; Reed, D R; Lynch, C C

    2017-03-01

    The survival rates for patients with osteosarcoma have remained almost static for the past three decades. Current standard of care therapy includes chemotherapies such as doxorubicin, cisplatin, and methotrexate along with complete surgical resection and surgery with or without ifosfamide and etoposide for relapse, though outcomes are hoped to be improved through clinical trials. Additionally, increased understanding of the genetics, signaling pathways and microenvironmental factors driving the disease have led to the identification of promising agents and potential paths towards translation of an exciting array of novel targeted therapies. Here, we review the mechanism of action of these emerging therapies and how, with clinical translation, they can potentially improve the survival rates for osteosarcoma patients in the near future.

  8. 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

  9. Endobronchial metastasis of parosteal osteosarcoma: a case report

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    Jung, Gyoo Sik; Huh, Jin Do; Kwon, Sam Ok; Oh, Kyung Seung; Kim, Jong Min; Joh, Young Duk [Kosin Medical College, Busan (Korea, Republic of)

    1995-06-15

    Endobronchial metastasis from extrapulmonary carcinoma, both clinically and radiologically similar in appearance to a primary lung cancer, is rare. We present a case of endobronchial metastasis from parosteal osteosarcoma. The first abnormality noted on the chest radiography was tramline calcification with branching pattern along the right upper lobe bronchus and intermediate bronchus. This lesion progressed into a solid calcified nodule which increased in size. Another lesion with same pattern was also observed in the left lower lung zone.

  10. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    OpenAIRE

    Dirik, Yalın; Çınar, Arda; Yumrukçal, Feridun; Eralp, Levent

    2014-01-01

    INTRODUCTION: We report a case with lymph node metastasis of osteosarcoma, which is a rare entity in comparison to hematogeneous lung or bone metastasis. PRESENTATION OF CASE: Twenty-seven years old male patient referred to our clinic complaining of ongoing left knee pain and swelling since one month without a history of prior trauma. Magnetic resonance imaging (MRI) revealed a mass of malignant nature which causes more prominent expansion and destruction of the bone distally with perioste...

  11. Measurement of bone alkaline phosphatase and relative study with osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    YANG Zhiping; HUO Yanqing; SUN Guangzhi; LI Jianmin; LI Xin

    2007-01-01

    The objective of this paper is to explore the value of bone alkaline phosphatase (BALP) for diagnosing osteosarcoma,evaluating the effect of the chemotherapy,judging the prognosis and supervising the relapse and metastasis.The immunoassay was used to check the BALP of the blood serum that was from 42 primary osteosarcoma patients.Alkaline phosphatase (ALP) in blood serum was checked with auto biochemistry equipment.The biopsy tissue and the lesion resected in operation were treated with pathology and histological response was counted.The patients were followed up from five months to 49 months with an average of 24.3 months.Eighteen cases relapsed and transferred,among which,16 of them were dead,and others were survival to the end of the follow-up.BALP was more sensitive than ALP in diagnosing osteosarcoma (P = 0.015).Fifteen cases decreased to normal value in ALP after preoperative chemotherapy,and 34 cases decreased in BALP.Both ALP and BALP in all cases decreased to normal value in postoperative.There was significant difference in positive correlation between the decrease of BALP and the increase of histological response (P = 0.001,r = 0.642).In the followup,there was significant difference in BALP between the group of relapse and transfer and the group of free disease survival (P=0.000).As a check marker in blood serum,BALP,reflecting the process of ossification,has a higher sensitivity than ALP.It has applied value in the diagnosis of osteosarcoma,reflection of the effect of chemotherapy and forecast the prognosis.

  12. Morphologic characterization of osteosarcoma growth on the chick chorioallantoic membrane

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    Gosheger Georg

    2010-03-01

    Full Text Available Abstract Background The chick chorio-allantoic membrane (CAM assay is a commonly used method for studying angiogenic or anti-angiogenic activities in vivo. The ease of access allows direct monitoring of tumour growth by biomicroscopy and the possibility to screen many samples in an inexpensive way. The CAM model provides a powerful tool to study effects of molecules, which interfere with physiological angiogenesis, or experimental tumours derived from cancer cell lines. We therefore screened eight osteosarcoma cell lines for their ability to form vascularized tumours on the CAM. Findings We implanted 3-5 million cells of human osteosarcoma lines (HOS, MG63, MNNG-HOS, OST, SAOS, SJSA1, U2OS, ZK58 on the CAM at day 10 of embryonic development. Tumour growth was monitored by in vivo biomicroscopy at different time points and tumours were fixed in paraformaldehyde seven days after cell grafting. The tissue was observed, photographed and selected cases were further analyzed using standard histology. From the eight cell lines the MNNG-HOS, U2OS and SAOS were able to form solid tumours when grafted on the CAM. The MNNG-HOS tumours showed the most reliable and consistent growth and were able to penetrate the chorionic epithelium, grow in the CAM stroma and induce a strong angiogenic response. Conclusions Our results show that the CAM assay is a useful tool for studying osteosarcoma growth. The model provides an excellent alternative to current rodent models and could serve as a preclinical screening assay for anticancer molecules. It might increase the speed and efficacy of the development of new drugs for the treatment of osteosarcoma.

  13. Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Kaushik, Shaifali [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (United States); Department of Radiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (United States); Smoker, Wendy R.K. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (United States); Frable, William J. [Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (United States)

    2002-02-01

    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.)

  14. Limb salvage surgery for osteosarcoma- Early results in Indian patients

    Directory of Open Access Journals (Sweden)

    Akshay Tiwari

    2014-01-01

    Full Text Available Background: While limb salvage surgery has long been established as the standard of care for osteosarcoma, large studies from Indian centers are few. Given the diverse socio economic milieu of our patients, it becomes significant to determine the feasibility and outcome of management of osteosarcoma in our population. We analyzed the early outcome of limb salvage surgery with multimodality treatment of osteosarcoma of the extremity/girdle bones at a tertiary North Indian Cancer Centre. Materials and Methods: A total of 51 limb salvage surgeries performed during the months between November 2008 and November 2012 were studied. Neoadjuvant/adjuvant chemotherapy was given by the pediatric/adult medical oncology teams as applicable. The mean followup was 19.45 months (range 2-50 months. The oncological outcome was correlated with age, sex, size of tumor, stage at presentation, site, histological subtype, type of chemotherapy protocol followed and necrosis seen on postoperative examination of resected specimen. The functional outcome of the patients was evaluated using the musculoskeletal tumor society (MSTS scoring system. Results: Out of a total of 37 males and 14 females with an average age of 18.8 years, the 3 year overall survival was 66% and 3 year event free survival was 61.8%. In this group of patients with a short followup, a better oncological outcome was associated with good postoperative tumor necrosis, nonchondroblastic histology and age <14 years. The average MSTS score was highest in patients with proximal or distal femur prosthesis and the lowest in patients undergoing a knee arthrodesis. Conclusion: The present study shows oncological and functional outcomes of limb salvage combined with chemotherapy in Indian patients with osteosarcoma comparable to those in world literature. Larger studies on Indian population with longer followup are recommended.

  15. SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN OSTEOSARCOMA

    Science.gov (United States)

    ZUMÁRRAGA, JUAN PABLO; BAPTISTA, ANDRÉ MATHIAS; ROSA, LUIS PABLO DE LA; CAIERO, MARCELO TADEU; CAMARGO, OLAVO PIRES DE

    2016-01-01

    ABSTRACT Objective: To study the relationship between the pre and post chemotherapy (CT) serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) found in specimens after the pre surgical CT in patients with osteosarcoma. Methods: Series of cases with retrospective evaluation of patients diagnosed with osteosarcoma. Participants were divided into two groups according to serum values of both enzymes. The values of AP and LDH were obtained before and after preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens of each patient was also included. Results: One hundred and thirty seven medical records were included from 1990 to 2013. Both the AP as LDH decreased in the patients studied, being the higher in pre CT than post CT. The average LHD decrease was 795.12U/L and AP decrease was 437.40 U/L. The average TN was 34.10 %. There was no statistically significant correlation between the serums values and the percentage of tumoral necrosis. Conclusion: The serum levels values of AP and LDH are not good predictors for the chemotherapy-induced necrosis in patients with osteosarcoma. Level of Evidence IV, Case Series. PMID:27217815

  16. Role of glutathione in cisplatin resistance in osteosarcoma cell lines.

    Science.gov (United States)

    Komiya, S; Gebhardt, M C; Mangham, D C; Inoue, A

    1998-01-01

    This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin-glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione-cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2-induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.

  17. Osteosarcoma of the jaws: demographic and CT imaging features

    Science.gov (United States)

    Wang, S; Shi, H; Yu, Q

    2012-01-01

    Objective The aim of this study was to evaluate the patient demographic and CT imaging findings of primary osteosarcoma of the jaws. Methods 88 primary osteosarcomas of the jaws histopathologically diagnosed during 1997–2007 were reviewed. 21 cases of CT images were reviewed. Results Of 88 patients, 51 (58%) had tumours in the mandible and 37 (42%) in the maxilla. The mean age was 37.8 years (range 9–80 years). The male-to-female ratio was 1.32:1. The mean age of patients with mandibular lesions was 41.04 years and in those with maxillary lesions it was 33.3 years. CT imaging findings were available in 21 patients. In the maxilla (n = 9), all tumours (100%) arose from the alveolar ridge. In the mandible (n = 12), most tumours (9 cases, 75%), arose from the ramus and/or condyle. All except two lesions had the epicentrum within the medullary cavity of the involved bone. The presence of periosteal reaction was demonstrated in 13 cases (62%). Soft-tissue extension was present in 18 lesions (86%), with calcification identified in 13 (72%). Conclusions This study provides age, sex distribution, location and CT imaging features of primary osteosarcoma of the jaws. PMID:22074870

  18. Altered matrix mineralization in a case of a sclerosing osteosarcoma.

    Science.gov (United States)

    Hofstaetter, Jochen G; Roschger, Andreas; Puchner, Stephan E; Dominkus, Martin; Sulzbacher, Irene; Windhager, Reinhard; Klaushofer, Klaus; Roschger, Paul

    2013-04-01

    Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma. We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol. Data were compared to recently published normative reference data for young individuals. Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space). The BMDD was shifted tremendously towards higher matrix mineralization (CaMean +18.5%, CaPeak +22.5%, CaHigh +100 fold) compared to normal bone. Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth +40%). In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix. We also found an altered BMDD of the patient's normal bone when compared with the reference BMDD of young individuals. In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density. Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover. The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.

  19. [Osteosarcoma lung metastases. Survival after chemotherapy and surgery].

    Science.gov (United States)

    Farfalli, Germán L; Albergo, José I; Lobos, Pablo A; Smith, David E; Streitenberger, Patricia D; Pallotta Rodríguez, María G; Aponte-Tinao, Luis A

    2015-01-01

    Five years overall survival in osteosarcoma patients is around 70%, although in patients with metastatic disease it is only 10-30%. The objective of this study was to analyze overall survival and prognostic factors in a group of patients with metastatic osteosarcoma treated with surgical removal of the lung metastases. A retrospective review from our oncology data base revealed 38 patients treated between 1992 and 2006. The mean age at diagnosis was 18 ± 9.4 years (3-45) and mean follow-up was 57 ± 53.8 months (12-231). All patients were treated with chemotherapy and oncologic resection of the primary tumor and surgical removal of the lung metastases. We analyzed overall survival and prognostic factors: age, gender, site, time of metastasis, local recurrences, number of lung metastasis and chemotherapy response (necrosis). Overall survival of the entire series was 29% at 5 years (CI 95%: 14.5-43.5) and 26% at 10 years (CI 95%: 12-40). Significant difference in 5 year overall survival was found between good and bad responders to chemotherapy, 53% (IC 95%: 28-78) vs. 8% (IC 95%: 0-20) (p = 0.0008). No statistically significant relationship between other prognostic factors analyzed was observed. Five and ten years overall survival rates in osteosarcoma patients with lung metastasis treated with chemotherapy and surgically resection is poor. Patients with good response to chemotherapy have better prognosis.

  20. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms.

    Science.gov (United States)

    Basturk, Olca; Yang, Zhaohai; Tang, Laura H; Hruban, Ralph H; Adsay, Volkan; McCall, Chad M; Krasinskas, Alyssa M; Jang, Kee-Taek; Frankel, Wendy L; Balci, Serdar; Sigel, Carlie; Klimstra, David S

    2015-05-01

    The 2010 World Health Organization (WHO) classification recommends that pancreatic neuroendocrine tumors (PanNETs) be graded on the basis of the mitotic rate and Ki67 index, with grade 2 (G2) PanNETs defined as having a mitotic rate of 2 to 20 mitotic figures/10 high-power fields or a Ki67 index of 3% to 20%. Grade 3 (G3) pancreatic neuroendocrine carcinoma (NEC) is defined as having >20 mitotic figures/10 high-power fields or a Ki67 index of >20%. However, some PanNETs show discordance between the mitotic rate and Ki67 index, usually having a Ki67 index in the G3 range but a mitotic rate suggesting G2, prompting us to examine the clinical significance of the Ki67 index in a large series of clinically well-characterized mitotic G2 PanNETs. Mitotic G2 well differentiated PanNETs, surgically resected at our institutions were reviewed. Of those, 19 cases had a Ki67>20% and were selected as the study group of grade-discordant (mitotic count G2/Ki67 index G3) PanNETs. For comparison, 53 grade-concordant (both mitotic count and Ki67 index G2) PanNETs matched for presenting stage with the discordant group as well as 43 morphologically poorly differentiated (either small cell or large cell type) pancreatic NECs were also included. The percentage of Ki67-positive neoplastic cells was quantified by manual counting of at least 500 cells on printed photographic images of "hot spots." The mean Ki67 index for grade-concordant and grade-discordant PanNETs and poorly differentiated NECs were 8.1% (range, 3% to 20%), 40% (range, 24% to 80%), and 70% (range, 40% to 98%), respectively. Overall, patients with grade-discordant PanNETs had significantly longer survival time compared with the patients with poorly differentiated NEC (median survival of 54.1 vs. 11 mo and 5 y survival of 29.1% vs. 16.1%; P=0.002). In addition, the survival time of the patients with grade-discordant PanNETs was shorter than that of the patients with grade-concordant PanNETs (median survival of 67.8 mo and 5

  1. Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system.

    Science.gov (United States)

    Feng, Yong; Sassi, Slim; Shen, Jacson K; Yang, Xiaoqian; Gao, Yan; Osaka, Eiji; Zhang, Jianming; Yang, Shuhua; Yang, Cao; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2015-02-01

    Osteosarcoma is the most common type primary malignant tumor of bone. Patients with regional osteosarcoma are routinely treated with surgery and chemotherapy. In addition, many patients with metastatic or recurrent osteosarcoma show poor prognosis with current chemotherapy agents. Therefore, it is important to improve the general condition and the overall survival rate of patients with osteosarcoma by identifying novel therapeutic strategies. Recent studies have revealed that CDK11 is essential in osteosarcoma cell growth and survival by inhibiting CDK11 mRNA expression with RNAi. Here, we apply the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system, a robust and highly efficient novel genome editing tool, to determine the effect of targeting endogenous CDK11 gene at the DNA level in osteosarcoma cell lines. We show that CDK11 can be efficiently silenced by CRISPR-Cas9. Inhibition of CDK11 is associated with decreased cell proliferation and viability, and induces cell death in osteosarcoma cell lines KHOS and U-2OS. Furthermore, the migration and invasion activities are also markedly reduced by CDK11 knockout. These results demonstrate that CRISPR-Cas9 system is a useful tool for the modification of endogenous CDK11 gene expression, and CRISPR-Cas9 targeted CDK11 knockout may be a promising therapeutic regimen for the treatment of osteosarcoma.

  2. Case report 529: Osteosarcoma of calcaneus with Rothmund-Thompson syndrome (RTS)

    Energy Technology Data Exchange (ETDEWEB)

    Baro, P.R.; Bastart, F.M.; Bartrina, J.R.; Mateo, J.M.; Vidal, M.T.R.

    1989-04-01

    A new case of Rothmund Thomson syndrome (RTS) diagnosed at infancy is described. This patient developed a lesion in the calcaneus classified histologically as an osteosarcoma. Twelve months later she developed metastasic lesions in a rib and in the lungs. This case is the fourth reported osteosarcoma in a patient with the RTS syndrome. (orig./GDG).

  3. Evaluation of P-glycoprotein (Pgp) expression in human osteosarcoma by high-throughput tissue microarray.

    Science.gov (United States)

    Gao, Yan; Liao, Yunfei; Shen, Jacson K; Feng, Yong; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2016-09-01

    Survival of osteosarcoma patients is currently limited by the development of metastases and multidrug resistance (MDR). A well-established cause of MDR involves overexpression of P-glycoprotein (Pgp) in tumor cells. However, some discrepancies still exist as to the clinical significance of Pgp in osteosarcoma. We sought to elucidate further whether the Pgp expression correlated with clinical behavior in a series of patients with osteosarcoma via high-throughput tissue microarray (TMA) analysis. Immunohistochemical analysis of Pgp expression in a TMA of 114 specimens with a retrospective review of 70 osteosarcoma patients admitted to the Massachusetts General Hospital (MGH) was performed. High Pgp expression was correlated with metastasis development and poor response to pre-operative chemotherapy in osteosarcoma patients. Eighteen of the fifty-seven patients initially admitted with primary osteosarcoma showed high Pgp expression. Among these 18 patients with high Pgp expression, 13 of 18 (72%) patients eventually developed metastases. There was no significant clinical relevance between Pgp expression and osteosarcoma survival. These results support that high expression of Pgp is important, but cannot be assigned as, an individual predictor in the development of human osteosarcoma. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1606-1612, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. 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 mo

  5. Knockdown of DDX46 Inhibits the Invasion and Tumorigenesis in Osteosarcoma Cells.

    Science.gov (United States)

    Jiang, Feng; Zhang, Dengfeng; Li, Guojun; Wang, Xiao

    2017-03-13

    DDX46, a member of the DEAD-box (DDX) helicase family, is involved in the development of several tumors. However, the exact role of DDX46 in osteosarcoma and the underlying mechanisms in tumorigenesis remain poorly understood. Thus, in the present study, we explored the role of DDX46 in osteosarcoma and the underlying mechanisms. Our results demonstrated that the expression levels of DDX46 in both mRNA and protein were greatly elevated in human osteosarcoma tissues and cell lines. Knockdown of DDX46 obviously inhibited osteosarcoma cell proliferation and tumor growth in vivo. In addition, knockdown of DDX46 also significantly suppressed migration and invasion in osteosarcoma cells. Furthermore, knockdown of DDX46 substantially downregulated the phosphorylation levels of PI3K and Akt in SaOS2 cells. In summary, the present results have revealed that DDX46 plays an important role in osteosarcoma growth and metastasis. Knockdown of DDX46 inhibited osteosarcoma cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Therefore, DDX46 may be a potential therapeutic target for the treatment of osteosarcoma.

  6. Matrix metalloproteinase 9 expression and survival of patients with osteosarcoma: a meta-analysis.

    Science.gov (United States)

    Liu, Y; Wang, Y; Teng, Z; Chen, J; Li, Y; Chen, Z; Li, Z; Zhang, Z

    2017-01-01

    Several studies have evaluated the effect of matrix metalloproteinase-9 (MMP-9) expression on the overall survival of patients with osteosarcoma, but the results remain conflicting. To examine the prognostic significance of MMP-9 expression in osteosarcoma risk, we conducted this meta-analysis to systematically review the published studies. We searched the commonly used electronic databases updated to September 2013 for relevant studies which evaluated the correction between MMP-9 expression and survival of patients with osteosarcoma. Overall, a total of eight studies including 437 cases were screened out. No significant heterogeneity was observed between studies. The MMP-9 was expressed in 73.9% (323/437) of cases, and the results showed that MMP-9 expression was associated with increased mortality rate of osteosarcoma during the follow-up (risk ratio = 2.79, 95% confidence interval, CI = 1.96-3.97, P osteosarcoma risk among Asian and non-Asian population (P osteosarcoma. In conclusion, this meta-analysis indicated that MMP-9 expression might be a biomarker of poor prognosis for patients with osteosarcoma. However, the prognostic value of MMP-9 on survival of osteosarcoma patients still needs further large-scale trials to be clarified. © 2015 John Wiley & Sons Ltd.

  7. A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

    Science.gov (United States)

    Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

    2015-01-01

    Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

  8. Correlations of Ezrin Expression with Pathological Characteristics and Prognosis of Osteosarcoma: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Da-Hang Zhao

    2014-01-01

    Full Text Available We conducted a meta-analysis to comprehensively evaluate the correlations of ezrin expression with pathological characteristics and the prognosis of osteosarcoma. The MEDLINE (1966–2013, the Cochrane Library Database, EMBASE, CINAHL, Web of Science (1945–2013, and the Chinese Biomedical Database were searched without language restrictions. Meta-analyses conducted using STATA software were calculated. Ten studies met the inclusion criteria, including 459 patients with osteosarcoma. Meta-analysis results illustrated that ezrin expression may be closely associated with the recurrence of osteosarcoma or metastasis in osteosarcoma. Our findings also demonstrated that patients with grade III-IV osteosarcoma showed a higher frequency of ezrin expression than those with histological grade I-II osteosarcoma. Furthermore, we found that patients with positive expression of ezrin exhibited a shorter overall survival than those with negative ezrin expression. The results also indicated that positive ezrin expression was strongly correlated with poorer metastasis-free survival. Nevertheless, no significant relationships were observed between ezrin expression and clinical variables (age and gender. In the current meta-analysis, our results illustrated significant relationships of ezrin expression with pathological characteristics and prognosis of osteosarcoma. Thus, ezrin expression could be a promising marker in predicting the clinical outcome of patients with osteosarcoma.

  9. MicroRNA-379 suppresses osteosarcoma progression by targeting PDK1.

    Science.gov (United States)

    Li, Zheng; Shen, Jianxiong; Chan, Matthew T V; Wu, William Ka Kei

    2017-02-01

    Osteosarcoma is the most common primary bone tumour. Increasing evidence has demonstrated the pathogenic role of microRNA (miRNAs) dysregulation in tumour development. miR-379 was previously reported to function as an oncogenic or tumour-suppressing miRNA in a tissue-dependent manner. However, its function in osteosarcoma remains unknown. In this study, we found that the expression of miR-379 was downregulated in osteosarcoma tissues and cell lines. Further functional characterization revealed that miR-379 suppressed osteosarcoma cell proliferation and invasion in vitro and retarded the growth of osteosarcoma xenografts in vivo. Mechanistically, PDK1 was identified as the direct target of miR-379 in osteosarcoma, in which PDK1 expression was up-regulated and showed inverse correlation with miR-379. Enforced expression of PDK1 promoted osteosarcoma cell proliferation and rescued the anti-proliferative effect of miR-379. These data suggest that miR-379 could function as a tumour-suppressing miRNA via targeting PDK1 in osteosarcoma. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. 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.

  11. Mir-150 Up-Regulates Glut1 and Increases Glycolysis in Osteosarcoma Cells

    Science.gov (United States)

    Yuan, Guangke; Zhao, Yanqing; Wu, Dongjin; Gao, Chunzheng

    2017-04-01

    Objective: Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Many studies have shown that microRNAs play a critical role in proliferation and metastasis with this tumour type. However, whether aberrant expression might contribute to a metabolism switch in osteosarcoma cases is not clearly understood. In this study, we explored expression and function of miR-150 in osteosarcoma cells. Materials and methods: Expression of miR-150 was assessed by real-time PCR in cell lines and human patient tissues. Scramble siRNA, miR-150 inhibitor, and miR-150 mimics were transfected into osteosarcoma cells to determine their effects on proliferation rate, glucose uptake and lactate secretion. Finally, the relationship between Glut1 and the miR-150 level was explored by luciferase reporter assay and western blotting. Result: miR-150 was consistently decreased in cell lines and osteosarcoma tissues as compared to osteoblast cells and normal bone. Ectopic overexpression of miR-150 inhibited osteosarcoma cell proliferation and suppressed glucose uptake and lactate secretion. Loss of function of miR-150, on the other hand, enhanced osteosarcoma cell proliferation and increased glucose uptake and lactate secretion. Western blot and luciferase reporter assays showed that miR-150 may function by regulating Glut1 expression. Conclusion: These data suggest that miR-150 is involved in regulation of glycolysis in osteosarcoma cells by influencing Glut1 expression. Creative Commons Attribution License

  12. IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling.

    Science.gov (United States)

    Lu, Jinchang; Song, Guohui; Tang, Qinglian; Zou, Changye; Han, Feng; Zhao, Zhiqiang; Yong, Bicheng; Yin, Junqiang; Xu, Huaiyuan; Xie, Xianbiao; Kang, Tiebang; Lam, YingLee; Yang, Huiling; Shen, Jingnan; Wang, Jin

    2015-05-01

    Osteosarcoma is a common malignant bone tumor with a propensity to metastasize to the lungs. Epigenetic abnormalities have been demonstrated to underlie osteosarcoma development; however, the epigenetic mechanisms that are involved in metastasis are not yet clear. Here, we analyzed 2 syngeneic primary human osteosarcoma cell lines that exhibit disparate metastatic potential for differences in epigenetic modifications and expression. Using methylated DNA immunoprecipitation (MeDIP) and microarray expression analysis to screen for metastasis-associated genes, we identified Iroquois homeobox 1 (IRX1). In both human osteosarcoma cell lines and clinical osteosarcoma tissues, IRX1 overexpression was strongly associated with hypomethylation of its own promoter. Furthermore, experimental modulation of IRX1 in osteosarcoma cell lines profoundly altered metastatic activity, including migration, invasion, and resistance to anoikis in vitro, and influenced lung metastasis in murine models. These prometastatic effects of IRX1 were mediated by upregulation of CXCL14/NF-κB signaling. In serum from osteosarcoma patients, the presence of IRX1 hypomethylation in circulating tumor DNA reduced lung metastasis-free survival. Together, these results identify IRX1 as a prometastatic gene, implicate IRX1 hypomethylation as a potential molecular marker for lung metastasis, and suggest that epigenetic reversion of IRX1 activation may be beneficial for controlling osteosarcoma metastasis.

  13. Chemotherapy for osteosarcoma - where does it come from? What is it? Where is it going?

    Science.gov (United States)

    Yamamoto, Norio; Tsuchiya, Hiroyuki

    2013-11-01

    Although chemotherapy is currently indispensable for the treatment of osteosarcoma, chemotherapy for this rare cancer has not been developed based on multicentre randomised prospective trials with many subjects. The therapeutic outcomes of chemotherapy have been improved in large part through the efforts and innovation of physicians who treated patients with osteosarcoma and conducted detailed examinations of a small number of subjects. It is important to understand how chemotherapy for osteosarcoma has changed to achieve further development. This article discusses the changes in chemotherapy for osteosarcoma, including adjuvant and neoadjuvant chemotherapy, and focuses on four key anticancer drugs: methotrexate, adriamycin, cisplatin, and ifosfamide. This article also discusses the problems of research on osteosarcoma treatment, from the perspective of osteosarcoma as a rare disease, and the challenges to be addressed. Approximately 30 years have passed since the key anticancer drugs were introduced. The development of new therapeutic drugs for osteosarcoma has stagnated. Given that osteosarcoma is a rare cancer, it would be difficult to expect that drug development will be led by pharmaceutical companies. Thus, it is very important to create a system for more efficient drug development based on innovations from various academic and medical institutions.

  14. Effect of miR-143 on the apoptosis of osteosarcoma cells.

    Science.gov (United States)

    Liu, Hao; Wang, Hongliang; Liu, Haichun; Chen, Yunzhen

    2015-01-01

    As one common malignant bone cancer, osteosarcoma is mainly occurred in young people with increasing incidences. Current treatment of osteosarcoma includes surgery and chemo-/radio-therapy. Due to the unclear pathogenesis mechanism, the overall treatment efficacy is still not satisfactory. As anti-apoptotic molecule Bcl-2 has been suggested to be related with osteosarcoma and is regulated by miR-143, we thus investigated the correlation between miR-143 and Bcl-2 in osteosarcoma patients, in an attempt to elucidate the role of miR-143 in cancer occurrence. Real-time fluorescent RT-PCR was used to quantify expression levels of miR-143 and Bcl-2 from a total of 5 osteosarcoma patients, along with protein contents determination by Western blotting. In vitro study was also performed to detect Bcl-2 expression and cell apoptosis via silencing or over-expressing miR-143 in cultured osteosarcoma cells. MiR-143 showed down-regulation in osteosarcoma tissues. Bcl-2, however, had elevated expression in cancer cells when compared to adjacent tissues (Posteosarcoma cells, and mediate the apoptotic process, thereby playing a critical role in the pathogenesis of osteosarcoma.

  15. miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma.

    Science.gov (United States)

    Zhou, Shuguang; Wang, Bing; Hu, Jun; Zhou, Yucheng; Jiang, Mengzhen; Wu, Mingyu; Qin, Liming; Yang, Xuming

    2016-07-01

    MicroRNAs (miRNAs) are a new class of prognostic and diagnostic biomarkers for many cancers. Recent studies have shown that miRNAs are highly stable in plasma/serum. The aim of this study was to investigate the role of miR-421 in osteosarcoma. We found that the serum expression levels of miR-421 were significantly higher in osteosarcoma patients than those in healthy volunteers. Moreover, miR-421 expression was significantly higher in osteosarcoma tissues compared with that in the adjacent normal tissues. Meanwhile, the expression of miR-421 was upregulated in 90 % (36/40) osteosarcoma tissues compared to non-tumor tissues. More importantly, the expression levels of miR-421 in osteosarcoma tissues were correlated with those in patients' serum. In addition, patients with high miR-421 expression had shorter overall survival (OS) than those with low expressions. We also found that overexpression of miR-421 promoted osteosarcoma cell line MG-63 proliferation, migration, and invasion. In conclusion, miR-421 expression levels were upregulated in osteosarcoma tissue and serum and it may be a useful marker for diagnosis of osteosarcoma.

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

    Science.gov (United States)

    Zhang, Shilian; 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.

  17. Expression and prognostic relevance of centromere protein A in primary osteosarcoma.

    Science.gov (United States)

    Gu, Xiao-Min; Fu, Jie; Feng, Xiao-Jun; Huang, Xue; Wang, Shou-Mei; Chen, Xin-Feng; Zhu, Ming-Hua; Zhang, Shu-Hui

    2014-04-01

    Centromere protein A (CENP-A) is one of the fundamental components of the human active kinetochore and plays important roles in cell-cycle regulation, cell survival, and genetic stability. The aim of the present study was to explore the expression and prognostic significance of CENP-A in osteosarcoma. The results of real-time quantitative PCR and Western blotting analysis revealed an enhanced expression of CENP-A in osteosarcomas relative to adjacent non-tumorous bone tissues at both mRNA and protein levels. Immunohistochemically, 72 of the 123 osteosarcoma specimens (58.5%) had high expression of CENP-A. CENP-A overexpression was significantly correlated with tumor size (P=0.002), poor response to neoadjuvant chemotherapy (P=0.016), local recurrence/lung metastasis (P=0.001), high Ki-67 index (P=0.004), and P53 positivity (P=0.005). Median overall and recurrence-free survival time was significantly shorter in patients with high-CENP-A osteosarcomas than in those with low-CENP-A osteosarcomas. Multivariate analysis identified CENP-A as an independent poor prognostic factor for osteosarcoma. In conclusion, our results demonstrate that elevated CENP-A expression is significantly associated with osteosarcoma progression and has an independent prognostic value in predicting overall and recurrence-free survival for patients with osteosarcoma.

  18. 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.

  19. Expression of Leptin and Sirtuin-1 is associated with poor prognosis in patients with osteosarcoma.

    Science.gov (United States)

    Feng, Helin; Guo, Peng; Wang, Jin; Xu, Jianfa; Xie, Congcong; Gao, Fulu

    2016-04-01

    Sirtuin-1 (SIRT1) is a downstream target of Leptin, and its inhibition promotes p53-mediated apoptosis. This study aimed to evaluate the expression and prognostic significance of Leptin and SIRT1 in osteosarcoma. Leptin and SIRT1 levels in osteosarcoma samples from 89 patients were evaluated by immunohistochemical staining. The correlations between Leptin and SIRT1 expression with clinical parameters were analyzed by Spearman's test and Pearson's chi-squared test. Prognostic factors were identified by Univariate and multivariate Cox regression analysis. We found that Leptin and SIRT1 expression was low in 23.6% and 20.2%; moderate in 25.8% and 24.7%; and high in 50.5% and 55.1% of patients with osteosarcoma, respectively. Both Leptin and SIRT1 expression were significantly associated with the Enneking stage, distant metastasis and neo-adjuvant chemotherapy. Leptin expression and SIRT1 expression were significantly correlated and they were significantly associated with shorter overall survival. Among osteosarcoma patients who received neo-adjuvant chemotherapy, both Leptin and SIRT1 expression were significantly associated with overall survival of osteosarcoma patients in univariate analysis, but only SIRT1 expression was significantly associated with overall survival of osteosarcoma patients in multivariate analysis. In conclusion, Leptin and SIRT1 expressions are significantly associated with shorter overall survival of osteosarcoma patients, and SIRT1 expression is a significant independent prognostic indicator in patients with osteosarcoma.

  20. 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.

  1. Small cell osteosarcoma of a toe phalanx: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Bras Johannes

    2010-06-01

    Full Text Available Abstract This report describes the radiological and histological findings of a small cell osteosarcoma of a toe phalanx in a 38 year old man. This man presented with pain, swelling and redness of the left third toe. Medical history revealed an osteomyelitis of this toe eight years prior. Based on clinical findings and medical history the lesion was diagnosed as an osteomyelitis. However, peroperatively the lesion had a malignant aspect. Histological examination revealed a small cell osteosarcoma of the proximal phalanx. Osteosarcoma of the foot and especially of the tubular bones is rare. Moreover small cell osteosarcoma is a rare subtype of osteosarcoma. This case demonstrates that medical history and clinical examination can be misleading. In patients with apparent bone destruction, a malignancy must always be excluded prior to treatment. It emphasises the care that should be taken in the process of formulating a diagnosis.

  2. Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma

    Science.gov (United States)

    Liu, Ju-Fang; Tsao, Ya-Ting; Hou, Chun-Han

    2015-01-01

    Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression. PMID:26503469

  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. EXPRESSION AND SIGNIFICANCE OF ONCOPROTEIN p16 AND FOS IN OSTEOSARCOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate p16, c-fos protein expression and theirrelationships in osteosarcoma. Methods: Immuno-histochemical technique (SABC) was used to detect p16 and C-fos protein expression in 41 cases of osteosarcoma. Results: The positive rates of p16 and C-fos protein expres-sion were 51.2% and 82.9% respectively. Their expression was not correlated to pathological subtype, but correlated to clinic grade, and the latter was associated with tumor metastasis. There was a negative correlation between p16 and C-fos protein expression. Conclusion: The alteration of p16 and C-fos protein expression may be related to the tumorigenesis and development of osteosarcoma, and C-fos proteins may take part in osteosarcoma metastasis. These data will offer useful helpness to determine the prognosis of osteosarcoma.

  5. p21WAF1/CIP1 gene DNA sequencing and its expression in human osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    廖威明; 张春林; 李佛保; 曾炳芳; 曾益新

    2004-01-01

    Background Mutation and expression change of p21WAF1/CIP1 may play a role in the growth of osteosarcoma. This study was to investigate the expression of the p21WAF1/CIP1 gene in human osteosarcoma, p21WAF1/CIP1 gene DNA sequence change and their relationships with the phenotype and clinical prognosis.Methods p21WAF1/CIP1 gene in 10 normal people and the tumours of 45 osteosarcoma patients were examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with silver staining. The PCR product with an abnormal strand was sequenced directly. The p21WAF1/CIP1 gene mRNA and P21 protein of 45 cases of osteosarcoma were investigated by using in situ hybridization and immunohistochemistry, respectively. Results The occurrence of P21 protein in osteosarcoma was 17.78% (8/45), and p21WAF1/CIP1 mRNA expression in osteosarcoma was 42.22% (19/45). The p21WAF1/CIP1 gene DNA sequencing of amplified production showed that in p21WAF1/CIP1 gene exon 3 of 36 cases of human osteosarcoma, there were 17 cases (47.22%) with C→T at position 609; 10 normal blood samples' DNA sequence analysis yielded 8 cases (80.00%) with C→T at the same position. Conclusions Along with the increase of malignancy, the expression of p21WAF1/CIP1mRNA and P21 protein in osteosarcoma tends to decrease. It is uncommon for the p21WAF1/CIP1 gene mutation to occur in human osteosarcoma. As a result, the possible existence of tumour subtypes of p21WAF1/CIP1 gene mutation should be investigated. Our research leads to the location of p21WAF1/CIP1 gene polymorphism of Chinese osteosarcoma patients, which can provide a basis for further research.

  6. Telomere length and variation in telomere biology genes in individuals with osteosarcoma.

    Science.gov (United States)

    Mirabello, Lisa; Richards, Elliott G; Duong, Linh M; Yu, Kai; Wang, Zhaoming; Cawthon, Richard; Berndt, Sonja I; Burdett, Laurie; Chowdhury, Salma; Teshome, Kedest; Douglass, Chester; Savage, Sharon A

    2011-01-01

    Osteosarcoma, the most common primary bone tumor, occurs most frequently in adolescents. Chromosomal aneuploidy is common in osteosarcoma cells, suggesting underlying chromosomal instability. Telomeres, located at chromosome ends, are essential for genomic stability; several studies have suggested that germline telomere length (TL) is associated with cancer risk. We hypothesized that TL and/or common genetic variation in telomere biology genes may be associated with risk of osteosarcoma. We investigated TL in peripheral blood DNA and 713 single nucleotide polymorphisms (SNPs) from 39 telomere biology genes in 98 osteosarcoma cases and 69 orthopedic controls. For the genotyping component, we added 1363 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer ScreeningTrial. Short TL was not associated with osteosarcoma risk overall (OR 1.39, P=0.67), although there was a statistically significant association in females (OR 4.35, 95% Cl 1.20-15.74, P=0.03). Genotype analyses identified seven SNPs in TERF1 significantly associated with osteosarcoma risk after Bonferroni correction by gene. These SNPs were highly linked and associated with a reduced risk of osteosarcoma (OR 0.48-0.53, P=0.0001-0.0006). We also investigated associations between TL and telomere gene SNPs in osteosarcoma cases and orthopedic controls. Several SNPs were associated with TL prior to Bonferroni correction; one SNP in NOLA2 and one in MEN1 were marginally non-significant after correction (P(adj)=0.057 and 0.066, respectively). This pilot-study suggests that females with short telomeres may be at increased risk of osteosarcoma, and that SNPs in TERF1 are inversely associated with osteosarcoma risk.

  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. PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

    Science.gov (United States)

    Liang, Shoulei; Ren, Zhiwu; Han, Xiuxin; Yang, Jilong; Shan, Luling; Li, Lin; Wang, Binying; Zhang, Qianyi; Mu, Tianyang; Chen, Kexin; Xiong, Shunbin; Wang, Guowen

    2015-01-01

    Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis. Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors. Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P valuesmetastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values metastasis-free survival (both P values osteosarcoma patients for predicting the development of metastases and poor survival.

  9. Wnt Inhibitory Factor 1 (WIF-1) decreases tumorigenesis and metastasis in osteosarcoma

    Science.gov (United States)

    Rubin, Elyssa M.; Guo, Yi; Tu, Khoa; Xie, Jun; Zi, Xiaolin; Hoang, Bang H.

    2010-01-01

    It has been reported that the progression of osteosarcoma was closely associated with aberrant activation of canonical Wnt signaling. Wnt inhibitory factor-1 (WIF-1) is a secreted Wnt inhibitor whose role in human osteosarcoma remains unknown. In this study, WIF-1 expression in normal human osteoblast and osteosarcoma cell lines was determined by real-time RT-PCR, methylation-specific PCR (MSP), and Western blotting analysis. In addition, tissue array from patient samples was examined for WIF-1 expression by immunohistochemistry. Compared to normal human osteoblasts, WIF-1 mRNA and protein levels were significantly down-regulated in several osteosarcoma cell lines. The downregulation of WIF-1 mRNA expression is associated with its promoter hypermethylation in these tested cell lines. Importantly, WIF-1 expression was also downregulated in 76% of examined osteosarcoma cases. These results suggest that the downregulation of WIF-1 expression plays a role in osteosarcoma progression. To further study the potential tumor suppressor function of WIF-1 in osteosarcoma, we established stable 143B cell lines overexpressing WIF-1. WIF-1 overexpression significantly decreased tumor growth rate in nude mice as examined by subcutaneous injection of 143B cells stably transfected with WIF-1 and vector control. WIF-1 overexpression also markedly reduced the number of lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Together, these data suggest that WIF-1 exerts potent anti-osteosarcoma effect in vivo in mouse models. Therefore, re-expression of WIF-1 in WIF-1 deficient osteosarcoma represents a potential novel treatment and preventive strategy. PMID:20197388

  10. TRAF4 enhances osteosarcoma cell proliferation and invasion by Akt signaling pathway.

    Science.gov (United States)

    Yao, Weitao; Wang, Xin; Cai, Qiqing; Gao, Songtao; Wang, Jiaqiang; Zhang, Peng

    2014-01-01

    TRAF4, or tumor necrosis factor receptor-associated factor 4, is overexpressed in several cancers, suggesting a specific role in cancer progression. However, its functions in osteosarcoma are unclear. This study aimed to explore the expression of TRAF4 in osteosarcoma tissues and cells, the correlation of TRAF4 to clinical pathology of osteosarcoma, as well as the role and mechanism of TRAF4 in osteosarcoma metastasis. The protein expression levels of TRAF4 in osteosarcoma tissues and three osteosarcoma cell lines, MG-63, HOS, and U2OS, were assessed. Constructed TRAF4 overexpression vectors and established TRAF4 overexpression of the U2OS cell line. Cell proliferation, cell invasion, protein levels, and TRAF4 phosphorylations were assessed following TRAF4 transfection, as well as the effects of TRAF4 siRNA on cell proliferation and invasion. The results show that TRAF4 protein levels in osteosarcoma tissues were significantly higher than that in normal bone tissues. Importantly, an obvious upregulation of TRAF4 was found in carcinoma tissues from patients with lung metastasis compared with patients without lung metastasis. Consistently, a similar increase in TRAF4 mRNA and protein was also demonstrated in the osteosarcoma cell lines MG-63, HOS, and U2OS compared to normal bone cells, hFOB1.19. When TRAF4 was overexpressed in U2OS cells, cell proliferation was significantly enhanced, accompanied by an increase in Ki67 expression and colony formation. Compared with the control and vector-treated groups, TRAF4 transfection increased the invasion potential of U2OS cells (p osteosarcoma cell proliferation and invasion partially by the Akt pathway. This work suggests that TRAF4 might be an important target in osteosarcoma.

  11. PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

    Directory of Open Access Journals (Sweden)

    Shoulei Liang

    Full Text Available Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases, and immunohistochemistry (IHC staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05 than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02. Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03.This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.

  12. MiR-133b Is Down-Regulated in Human Osteosarcoma and Inhibits Osteosarcoma Cells Proliferation, Migration and Invasion, and Promotes Apoptosis

    Science.gov (United States)

    Zhao, Huafu; Li, Mei; Li, Lihua; Yang, Xiaoming; Lan, Guobo; Zhang, Yu

    2013-01-01

    MicroRNAs (miRNAs) decrease the expression of specific target oncogenes or tumor suppressor genes and thereby play crucial roles in tumorigenesis and tumor growth. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. In this study, the miRNA microarray assay and hierarchical clustering analysis were performed in human osteosarcoma samples. In comparison with normal human skeletal muscle, 43 miRNAs were significantly differentially expressed in human osteosarcomas (fold change ≥2 and p≤0.05). Among these miRNAs, miR-133a and miR-133b expression was decreased by 135 folds and 47 folds respectively and the decreased expression was confirmed in both frozen and paraffin-embedded osteosarcoma samples. The miR-133b precursor expression vector was then transfected into osteosarcoma cell lines U2-OS and MG-63, and the stable transfectants were selected by puromycin. We found that stable over-expression of miR-133b in osteosarcoma cell lines U2-OS and MG-63 inhibited cell proliferation, invasion and migration, and induced apoptosis. Further, over-expression of miR-133b decreased the expression of predicted target genes BCL2L2, MCL-1, IGF1R and MET, as well as the expression of phospho-Akt and FAK. This study provides a new insight into miRNAs dysregulation in osteosarcoma, and indicates that miR-133b may play as a tumor suppressor gene in osteosarcoma. PMID:24391788

  13. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis.

    Directory of Open Access Journals (Sweden)

    Huafu Zhao

    Full Text Available MicroRNAs (miRNAs decrease the expression of specific target oncogenes or tumor suppressor genes and thereby play crucial roles in tumorigenesis and tumor growth. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. In this study, the miRNA microarray assay and hierarchical clustering analysis were performed in human osteosarcoma samples. In comparison with normal human skeletal muscle, 43 miRNAs were significantly differentially expressed in human osteosarcomas (fold change ≥2 and p≤0.05. Among these miRNAs, miR-133a and miR-133b expression was decreased by 135 folds and 47 folds respectively and the decreased expression was confirmed in both frozen and paraffin-embedded osteosarcoma samples. The miR-133b precursor expression vector was then transfected into osteosarcoma cell lines U2-OS and MG-63, and the stable transfectants were selected by puromycin. We found that stable over-expression of miR-133b in osteosarcoma cell lines U2-OS and MG-63 inhibited cell proliferation, invasion and migration, and induced apoptosis. Further, over-expression of miR-133b decreased the expression of predicted target genes BCL2L2, MCL-1, IGF1R and MET, as well as the expression of phospho-Akt and FAK. This study provides a new insight into miRNAs dysregulation in osteosarcoma, and indicates that miR-133b may play as a tumor suppressor gene in osteosarcoma.

  14. Actin-like protein 6A is a novel prognostic indicator promoting invasion and metastasis in osteosarcoma.

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    Sun, Wei; Wang, Wanchun; Lei, Jian; Li, Hui; Wu, Yi

    2017-04-01

    Osteosarcoma harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. Actin-like protein 6A (ACTL6A) regulates cell proliferation, migration and differentiation. However, the biologic role of ACTL6A in osteosarcoma remains unknown. In this study, the results showed that, by analysis of frozen fresh primary tumor tissues, matched non-cancerous bone tissues (NCBTs) and biopsy lung metastatic nodule tissues from 30 osteosarcoma patients after radical surgical resection, ACTL6A was overexpressed in osteosarcoma tissues compared with matched NCBTs, and its expression level was associated with osteosarcoma metastasis. Immunohistochemical analyses of osteosarcoma tissue samples from two independent cohorts of formaldehyde-fixed, paraffin-embedded osteosarcoma tissue samples from total of 186 osteosarcoma patients showed that high ACTL6A expression correlated with malignant clinicopathological features such as larger tumor size, high Ennecking grade, high histologic grade, and advanced tumor node metastasis stage. High ACTL6A expression was associated with poor prognosis for patients with osteosarcoma, and an independent and significant risk factor for disease-free survival and overall survival after radical tumor resection. Both in vitro and in vivo assays showed that ACTL6A overexpression promoted osteosarcoma cell invasion and metastasis, whereas knockdown of ACTL6A expression reduced osteosarcoma cell malignant behavior such as invasion and metastasis. Furthermore, we proved that ACTL6A promoted osteosarcoma cells of metastasis through facilitating epithelial-mesenchymal transition (EMT). In conclusion, data from the present study demonstrated that ACTL6A was associated with poor survival and promoted osteosarcoma cell metastasis through EMT, suggesting that ACTL6A may be a novel prognostic biomarker and therapeutic target for osteosarcoma.

  15. Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells

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    Wimbauer Fritz

    2012-03-01

    Full Text Available Abstract Background Osteosarcoma is a bone tumor that often affects children and young adults. Although a combination of surgery and chemotherapy has improved the survival rate in the past decades, local recurrence and metastases still develop in 40% of patients. A definite therapy is yet to be determined for osteosarcoma. Anti- tumor compound and a metabolite of estrogen, 2-methoxyestradiol (2-ME induces cell death in osteosarcoma cells. In this report, we have investigated whether interferon (IFN pathway is involved in 2-ME-induced anti-tumor effects in osteosarcoma cells. Methods 2-ME effects on IFN mRNA levels were determined by Real time PCR analysis. Transient transfections followed by reporter assays were used for investigating 2-ME effects on IFN-pathway. Western blot analyses were used to measure protein and phosphorylation levels of IFN-regulated eukaryotic initiation factor-2 alpha (eIF-2α. Results 2-ME regulates IFN and IFN-mediated effects in osteosarcoma cells. 2 -ME induces IFN gene activity and expression in osteosarcoma cells. 2-ME treatment induced IFN-stimulated response element (ISRE sequence-dependent transcription and gamma-activated sequence (GAS-dependent transcription in several osteosarcoma cells. Whereas, 2-ME did not affect IFN gene and IFN pathways in normal primary human osteoblasts (HOB. 2-ME treatment increased the phosphorylation of eIF-2α in osteosarcoma cells. Furthermore, analysis of osteosarcoma tissues shows that the levels of phosphorylated form of eIF-2α are decreased in tumor compared to normal controls. Conclusions 2-ME treatment triggers the induction and activity of IFN and IFN pathway genes in 2-ME-sensitive osteosarcoma tumor cells but not in 2-ME-resistant normal osteoblasts. In addition, IFN-signaling is inhibited in osteosarcoma patients. Thus, IFN pathways play a role in osteosarcoma and in 2-ME-mediated anti-proliferative effects, and therefore targeted induction of IFN signaling could lead

  16. Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?

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    Lassalle, Sandra; Hofman, Véronique; Ilie, Marius; Bonnetaud, Christelle; Puisségur, Marie-Pierre; Brest, Patrick; Loubatier, Céline; Guevara, Nicolas; Bordone, Olivier; Cardinaud, Bruno; Lebrigand, Kévin; Rios, Géraldine; Santini, Joseph; Franc, Brigitte; Mari, Bernard; Al Ghuzlan, Abir; Vielh, Philippe; Barbry, Pascal; Hofman, Paul

    2011-10-01

    The term 'thyroid tumors of uncertain malignant potential' (TT-UMP) was coined by surgical pathologists to define well-differentiated tumors (WDT) showing inconclusive morphological evidence of malignancy or benignity. We have analyzed the expression of microRNA (miRNA) in a training set of 42 WDT of different histological subtypes: seven follicular tumors of UMP (FT-UMP), six WDT-UMP, seven follicular thyroid adenomas (FTA), 11 conventional papillary thyroid carcinomas (C-PTC), five follicular variants of PTC (FV-PTC), and six follicular thyroid carcinomas (FTC), which led to the identification of about 40 deregulated miRNAs. A subset of these altered miRNAs was independently validated by qRT-PCR, which included 18 supplementary TT-UMP (eight WDT-UMP and ten FT-UMP). Supervised clustering techniques were used to predict the first 42 samples. Based on the four possible outcomes (FTA, C-PTC, FV-PTC, and FTC), about 80% of FTA and C-PTC and 50% of FV-PTC and FTC samples were correctly assigned. Analysis of the independent set of 18 WDT-UMP by quantitative RT-PCR for the selection of the six most discriminating miRNAs was unable to separate FT-UMP from WDT-UMP, suggesting that the miRNA signature is insufficient in characterizing these two clinical entities. We conclude that considering FT-UMP and WDT-UMP as distinct and specific clinical entities may improve the diagnosis of WDT of the thyroid gland. In this context, a small set of miRNAs (i.e. miR-7, miR-146a, miR-146b, miR-200b, miR-221, and miR-222) appears to be useful, though not sufficient per se, in distinguishing TT-UMP from other WDT of the thyroid gland.

  17. Qualitative analysis of small (≤2 cm) regenerative nodules, dysplastic nodules and well-differentiated HCCs with gadoxetic acid MRI.

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    Di Martino, Michele; Anzidei, Michele; Zaccagna, Fulvio; Saba, Luca; Bosco, Sandro; Rossi, Massimo; Ginanni Corradini, Stefano; Catalano, Carlo

    2016-11-11

    The characterization of small lesions in cirrhotic patients is extremely difficult due to the overlap of imaging features among different entities in the step-way of the hepatocarcinogenesis. The aim of our study was to evaluate the role of gadoxetic-acid MRI in the differentiation of small (≤2 cm) well-differentiated hepatocellular carcinomas from regenerative and dysplastic nodules. Seventy-three cirrhotic patients, with 118 focal liver lesions (≤2 cm) were prospectively recruited. MRI examination was performed with a 3T magnet and the study protocol included T1 - and T2-weighted pre-contrast sequences and T1 -weighted gadoxetic-acid enhanced post-contrast sequences obtained during the arterial, venous, late dynamic and hepatobiliary phases. All lesions were pathologically confirmed. Two radiologists blinded to clinical and pathological information evaluated two imaging datasets; another radiologist analysed the signal intensity characteristics of each lesion. Sensitivity, specificity and diagnostic accuracy were considered for statistical analysis. Good agreement was reported between the two readers (κ 0.70). Both readers reported a significantly improved sensitivity (57.7 and 66.2 vs 74.6 and 83.1) and diagnostic accuracy (0.717 and 0.778 vs 0.843 and 0.901) with the adjunction of the hepatobiliary phase 57.7 vs 74.6 and 66.2 vs 83.1 (p ≤ 0.04). Gadoxetic-acid MRI is a reliable tool for the characterization of HCC and lesions at high risk to further develop.

  18. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

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    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

  19. Differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma: utility of p16 in combination with MDM2 and CDK4 immunohistochemistry.

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    Kammerer-Jacquet, Solène-Florence; Thierry, Sixte; Cabillic, Florian; Lannes, Morgane; Burtin, Florence; Henno, Sébastien; Dugay, Frédéric; Bouzillé, Guillaume; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine; Stock, Nathalie

    2017-01-01

    The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization for MDM2 and CDK4 amplification. We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20). In the differential diagnosis of ALT-WDLPS, p16 had a sensitivity of 89.5% but a specificity of 68.2%, which was impaired by false-positive lipomas with secondary changes, especially in biopsies. Likewise, in the differential diagnosis of DDLPS, p16 had a sensitivity of 94.4% and a specificity of 70%, which hampered its use as a single marker. However, adding p16 to MDM2 and/or CDK4 increased diagnostic specificity. Indeed, MDM2+/p16+ tumors were all ALT-WDLPS, and MDM2-/p16- tumors were all benign adipocytic tumors. Moreover, all MDM2+/CDK4+/p16+ tumors were DDLPS, and the MDM2-/CDK4-/p16- tumor was an undifferentiated sarcoma. Although the use of p16 as a single immunohistochemical marker is limited by its specificity, its combination with MDM2 and CDK4 IHC may help discriminate ALT-WDLPS/DDLPS.

  20. Treatment with octreotide in patients with well-differentiated neuroendocrine tumors of the ileum: prognostic stratification with Ga-68-DOTA-TATE positron emission tomography.

    Science.gov (United States)

    Koch, Walter; Auernhammer, Christoph J; Geisler, Julia; Spitzweg, Christine; Cyran, Clemens C; Ilhan, Harun; Bartenstein, Peter; Haug, Alexander R

    2014-01-01

    We investigated the use of Ga-68-DOTA-Tyr3-octreotate (Ga-68-DOTA-TATE) positron emission tomography (PET) and standardized uptake values (SUVs) to predict the effectiveness of treatment with the somatostatin analogue octreotide acetate (Sandostatin LAR) in patients with neuroendocrine tumors (NETs). Thirty patients with well-differentiated NETs of the ileum (grades G1 and G2) were studied with Ga-68-DOTA-TATE. The average SUV of a 50% isocontour volume of interest covering the lesion with maximum uptake (SUV mean) and the maximum SUV (SUV max) were determined. Patients were followed up, and the time to progression was recorded. Twenty-one patients showed progressive disease at the end of the study; nine patients had stable disease. The median progression-free survival (PFS) was 51.0 weeks (95% confidence interval [CI] 26.4-75.6). A cutoff for the SUV max of 29.4 and for the SUV mean of 20.3 could separate between patients with a long PFS (69.0 weeks; 95% CI 9.8-128.2) and a short PFS (26.0 weeks; 95% CI 8.7-43.3) response to octreotide acetate therapy. Patients with high radiotracer uptake had significantly higher PFS with a 2.9-fold higher chance for stable disease after 45 weeks; however, the prognostic performance of SUV max on an individual basis was poor, with a sensitivity of 75% and a specificity of 64%. SUV max and SUV mean of NET tumor lesions in Ga-68-DOTA-TATE PET are important prognostic indices for predicting the response to therapy with octreotide acetate.

  1. The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

    Science.gov (United States)

    Kulkarni, K; Van Nostrand, D; Atkins, F; Aiken, M; Burman, K; Wartofsky, L

    2006-10-01

    The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

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

    Science.gov (United States)

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

    2013-09-20

    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 NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

  3. MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4.

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    Chen, Bingpeng; Liu, Jingjing; Qu, Ji; Song, Yang; Li, Yuxiang; Pan, Su

    2017-07-01

    Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.

  4. Epiphyseal osteosarcoma revisited: four illustrative cases with unusual histopathology and literature review.

    Science.gov (United States)

    Chow, Louis Tsun Cheung; Wong, Simon Kwok Chuen

    2015-01-01

    Osteosarcomas arising in the epiphysis are extremely rare and easily missed in the diagnostic consideration of epiphyseal tumors. It is the purpose of this study to delineate the clinical pathological characteristics of 'epiphyseal osteosarcoma' under the definition of 'a solitary long bone osteosarcoma radiographically considered an epiphyseal tumor for which the main radiologic differential diagnosis would encompass giant cell tumor, chondroblastoma and clear cell chondrosarcoma'. Four such cases with unusual histopathology were retrieved among 110 cases of osteosarcoma. Their clinical, radiological and pathological features, together with all 10 reported cases, were analyzed. The radiographic diagnoses of our four cases include two giant cell tumors, one chondroblastoma and one clear cell chondrosarcoma but turn out to be fibroblastic, giant cell rich, telangiectatic and epithelioid variant of epiphyseal osteosarcoma. Including our patients, the 14 reported epiphyseal osteosarcomas comprise 8 males and 6 females, the age at presentation ranges from 11 to 39 years, two-third in the second decade, 71.4% affect the femur. Due to their epiphyseal locations, many carry benign radiological diagnoses notably giant cell tumor and chondroblastoma. Epiphyseal osteosarcomas may not only masquerade as benign radiological bony lesions but also assume many histological patterns; orthopedic surgeons, radiologists and pathologists should be aware of such possibility. Their behavior and prognosis are dictated by the histologic types, grading and staging rather than location. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  5. ZD6474, a new treatment strategy for human osteosarcoma, and its potential synergistic effect with celecoxib.

    Science.gov (United States)

    Liu, Jiani; Wu, Jiangxue; Zhou, Ling; Pan, Changchuan; Zhou, Yi; Du, Wuying; Chen, Jie-Min; Zhu, Xiaofeng; Shen, Jingnan; Chen, Shuai; Liu, Ran-Yi; Huang, Wenlin

    2015-08-28

    ZD6474, a small molecule VEGFR and EGFR tyrosine kinase inhibitor, has been considered as a promising tumor-targeted drug in various malignancies. EGFR and cyclooxygenase-2 (COX-2) were found overexpressed in osteosarcoma in previous reports, so here we tried to explore the anti-osteosarcoma effect of ZD6474 alone or combination with celecoxib, a COX-2 inhibitor. The data demonstrated that ZD6474 inhibited the growth of osteosarcoma cells, and promoted G1-phase cell cycle arrest and apoptosis by inhibiting the activity of EGFR tyrosine kinase, and consequently suppressing its downstream PI3k/Akt and MAPK/ERK pathway. Additionally, daily administration of ZD6474 produced a dose-dependent inhibition of tumor growth in nude mice. Celecoxib also significantly inhibited the growth of osteosarcoma cells in dose-dependent manner, while combination of ZD6474 and celecoxib displayed a synergistic or additive antitumor effect on osteosarcoma in vitro and in vivo. The possible molecular mechanisms to address the synergism are likely that ZD6474 induces the down-regulation of COX-2 expression through inhibiting ERK phosphorylation, while celecoxib promotes ZD6474-directed inhibition of ERK phosphorylation. In conclusion, ZD6474 exerts direct anti-proliferative effects on osteosarcoma cells, and the synergistic antitumor effect of the combination of ZD6474 with celecoxib may indicate a new strategy of the combinative treatment of human osteosarcoma.

  6. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

    Science.gov (United States)

    Li, Yongning; Zhou, Qi; Hu, Zheng; Yang, Bin; Li, Qingsong; Wang, Jianhua; Zheng, Jinhua; Cao, Wenwu

    2015-01-01

    Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro. The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined. Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (Ptreatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (posteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (posteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  7. Identification of CBX3 and ABCA5 as Putative Biomarkers for Tumor Stem Cells in Osteosarcoma

    Science.gov (United States)

    Saini, Vaibhav; Hose, Curtis D.; Monks, Anne; Nagashima, Kunio; Han, Bingnan; Newton, Dianne L.; Millione, Angelena; Shah, Jalpa; Hollingshead, Melinda G.; Hite, Karen M.; Burkett, Mark W.; Delosh, Rene M.; Silvers, Thomas E.; Scudiero, Dominic A.; Shoemaker, Robert H.

    2012-01-01

    Recently, there has been renewed interest in the role of tumor stem cells (TSCs) in tumorigenesis, chemoresistance, and relapse of malignant tumors including osteosarcoma. The potential exists to improve osteosarcoma treatment through characterization of TSCs and identification of therapeutic targets. Using transcriptome, proteome, immunophenotyping for cell-surface markers, and bioinformatic analyses, heterogeneous expression of previously reported TSC or osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4), NANOG, SOX2, and aldehyde dehydrogenase, among others, was observed in vitro. However, consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed. In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma cultures was identified. ABCA5 was identified as a putative biomarker of TSCs and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic (5-azacytidine), anti-microtubule (vincristine), and anti-telomerase (3,11-difluoro-6,8,13-trimethyl- 8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4)-targeted therapeutic agents as candidates for TSC ablation in osteosarcoma. PMID:22870217

  8. RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis

    Directory of Open Access Journals (Sweden)

    Tomohiro Fujiwara

    2014-01-01

    Full Text Available Drug resistance and metastasis are lethal characteristics of tumors. We previously demonstrated that silencing of ribophorin II (RPN2, which is part of the N-oligosaccharyl transferase complex, efficiently induced apoptosis and reduced resistance to docetaxel in human breast cancer cells. Here, we report the clinical and functional correlations of RPN2 expression in osteosarcoma. Immunohistochemical evaluation of 35 osteosarcoma patient biopsies revealed that RPN2 was moderately to highly expressed in all specimens, and higher RPN2 mRNA expression was significantly correlated with poor prognosis. To investigate whether lethal phenotypes of osteosarcoma could be reduced by regulating the expression of RPN2, we conducted a study of RNAi-induced RPN2 knockdown in highly metastatic human osteosarcoma cells. The results indicated that RPN2 silencing reduced cell proliferation, sphere formation, cell invasion, and sensitized drug response in vitro. Mice bearing RPN2-silenced highly metastatic osteosarcoma xenografts showed reduced tumor growth and lung metastasis, and survived longer than mice bearing control tumor xenografts. Taken together, our data suggest that RPN2 silencing contributes to regulation of lethal osteosarcoma phenotypes and could be a novel target for RNAi-based therapeutics against osteosarcoma.

  9. MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1.

    Science.gov (United States)

    Duan, Guoqing; Ren, Chunfeng; Zhang, Yuanmin; Feng, Shiqing

    2015-08-01

    Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.

  10. 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.

  11. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    2016-01-01

    Full Text Available Several research groups have examined the association between TP53 mutations and prognosis in human osteosarcoma. However, the results were controversial. The purpose of this study was to evaluate the prognostic value of TP53 mutations in osteosarcoma patients. A meta-analysis was conducted with all eligible studies which quantitatively evaluated the relationship between TP53 mutations and clinical outcome of osteosarcoma patients. Eight studies with a total of 210 patients with osteosarcoma were included in this meta-analysis. The risk ratio (RR with a 95% confidence interval (95% CI was calculated to assess the effect of TP53 mutations on 2-year overall survival. The quantitative synthesis of 8 published studies showed that TP53 mutations were associated with 2-year overall survival in osteosarcoma patients. These data suggested that TP53 mutations had an unfavorable impact on 2-year overall survival when compared to the counterparts with wild type (WT TP53 (RR: 1.79; 95% CI: 1.12 to 2.84; P=0.01; I2=0%. There was no between-study heterogeneity. TP53 mutations are an effective prognostic marker for survival of patients with osteosarcoma. However, further large-scale prospective trials should be performed to clarify the prognostic value of TP53 mutations on 3- or 5-year survival in osteosarcoma patients.

  12. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data.

    Science.gov (United States)

    Chen, Zhe; Guo, Jiayi; Zhang, Kun; Guo, Yanxing

    2016-01-01

    Several research groups have examined the association between TP53 mutations and prognosis in human osteosarcoma. However, the results were controversial. The purpose of this study was to evaluate the prognostic value of TP53 mutations in osteosarcoma patients. A meta-analysis was conducted with all eligible studies which quantitatively evaluated the relationship between TP53 mutations and clinical outcome of osteosarcoma patients. Eight studies with a total of 210 patients with osteosarcoma were included in this meta-analysis. The risk ratio (RR) with a 95% confidence interval (95% CI) was calculated to assess the effect of TP53 mutations on 2-year overall survival. The quantitative synthesis of 8 published studies showed that TP53 mutations were associated with 2-year overall survival in osteosarcoma patients. These data suggested that TP53 mutations had an unfavorable impact on 2-year overall survival when compared to the counterparts with wild type (WT) TP53 (RR: 1.79; 95% CI: 1.12 to 2.84; P = 0.01; I (2) = 0%). There was no between-study heterogeneity. TP53 mutations are an effective prognostic marker for survival of patients with osteosarcoma. However, further large-scale prospective trials should be performed to clarify the prognostic value of TP53 mutations on 3- or 5-year survival in osteosarcoma patients.

  13. Genetic polymorphisms in COL18A1 influence the development of osteosarcoma.

    Science.gov (United States)

    Guo, Zhihao; Zhang, Tianji; Wu, Juntao; Wang, Hongwei; Liu, Xiaotan; Tian, Linqiang

    2015-01-01

    We conducted a case-control study to investigate the association of COL18A1 D104N polymorphism in the development of osteosarcoma in a Chinese population. Between May 2012 and May 2014, 141 patients with pathologically proven osteosarcoma and 341 were selected into this study. Genotyping of COL18A1 D104N was analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, we found that individuals with the NN genotype of COL18A1 D104N were significantly associated with an increased risk of osteosarcoma when compared with the DD genotype (OR=20.97, 95% CI=2.74-933.42). In dominant model, the NN+DN genotype of COL18A1 D104N had a 1.99 fold risk of osteosarcoma when compared with the DD genotype. Moreover, the NN genotype was correlated with a 20.45 fold risk of osteosarcoma when compared with the DN+DD genotype in recessive model. However, we did not find significant interaction between COL18A1 D104N polymorphism and Enneking stage, histological subtype, tumor metastasis and tumor location of patients with osteosarcoma. In conclusion, our study suggests that the homozygous DN and NN genotypes of COL18A1 D104N were associated with the risk of osteosarcoma.

  14. Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma.

    Science.gov (United States)

    Saini, Vaibhav; Hose, Curtis D; Monks, Anne; Nagashima, Kunio; Han, Bingnan; Newton, Dianne L; Millione, Angelena; Shah, Jalpa; Hollingshead, Melinda G; Hite, Karen M; Burkett, Mark W; Delosh, Rene M; Silvers, Thomas E; Scudiero, Dominic A; Shoemaker, Robert H

    2012-01-01

    Recently, there has been renewed interest in the role of tumor stem cells (TSCs) in tumorigenesis, chemoresistance, and relapse of malignant tumors including osteosarcoma. The potential exists to improve osteosarcoma treatment through characterization of TSCs and identification of therapeutic targets. Using transcriptome, proteome, immunophenotyping for cell-surface markers, and bioinformatic analyses, heterogeneous expression of previously reported TSC or osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4), NANOG, SOX2, and aldehyde dehydrogenase, among others, was observed in vitro. However, consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed. In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma cultures was identified. ABCA5 was identified as a putative biomarker of TSCs and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic (5-azacytidine), anti-microtubule (vincristine), and anti-telomerase (3,11-difluoro-6,8,13-trimethyl- 8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4)-targeted therapeutic agents as candidates for TSC ablation in osteosarcoma.

  15. Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Vaibhav Saini

    Full Text Available Recently, there has been renewed interest in the role of tumor stem cells (TSCs in tumorigenesis, chemoresistance, and relapse of malignant tumors including osteosarcoma. The potential exists to improve osteosarcoma treatment through characterization of TSCs and identification of therapeutic targets. Using transcriptome, proteome, immunophenotyping for cell-surface markers, and bioinformatic analyses, heterogeneous expression of previously reported TSC or osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4, NANOG, SOX2, and aldehyde dehydrogenase, among others, was observed in vitro. However, consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed. In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma cultures was identified. ABCA5 was identified as a putative biomarker of TSCs and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic (5-azacytidine, anti-microtubule (vincristine, and anti-telomerase (3,11-difluoro-6,8,13-trimethyl- 8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4-targeted therapeutic agents as candidates for TSC ablation in osteosarcoma.

  16. ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells

    Science.gov (United States)

    Valabrega, G; Fagioli, F; Corso, S; Madon, E; Brach del Prever, A; Biasin, E; Linari, A; Aglietta, M; Giordano, S

    2003-01-01

    Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT–PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker. PMID:12569382

  17. 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.

  18. An assay to measure adriamycin binding in osteosarcoma cells.

    Science.gov (United States)

    Gebhardt, M C; Kusuzaki, K; Mankin, H J; Springfield, D S

    1994-09-01

    Adjuvant chemotherapy is currently employed in the treatment of patients with osteosarcoma, but the drug regimens, although effective in improving disease-free survival, are unsuccessful in 20-40% of patients and very toxic. It would be useful to know whether tumor cells are sensitive to a given drug prior to its use. To this end, we developed a method of assessing Adriamycin (doxorubicin) binding to tumor nuclei as a possible means of detecting sensitivity to the drug. Adriamycin-sensitive murine osteosarcoma cells were used to develop the assay. The in vitro conditions (drug concentration, duration of incubation, and temperature) were optimized with use of the murine osteosarcoma cells in culture. After the cells had been incubated with Adriamycin, cell viability was determined and Adriamycin fluorescence intensity was measured with a cytofluorometer. The optimal parameters for Adriamycin binding were found to be a 30-minute incubation in a 10 micrograms/ml concentration of Adriamycin at 37 degrees C; the frequency of cells that emitted Adriamycin fluorescence from the nucleus compared with the total number of living cells reached 100% under these conditions. In a murine leukemia cell line with known sensitivity to Adriamycin, the cells emitted red fluorescence from the nucleus and cytoplasm, whereas in a resistant line the cells emitted Adriamycin fluorescence from only the cytoplasm. We demonstrated that it is possible to differentiate nuclear from cytoplasmic concentration of Adriamycin in a tumor cell with use of a fluorescent microscope and that resistant cell lines can be distinguished from sensitive cell lines by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Polyploidization induced by acridine orange in mouse osteosarcoma cells.

    Science.gov (United States)

    Kusuzaki, K; Takeshita, H; Murata, H; Gebhardt, M C; Springfield, D S; Mankin, H J; Ashihara, T; Hirasawa, Y

    2000-01-01

    This study was undertaken to clarify the in vitro effect of acridine orange (AO) on the cell kinetics of mouse osteosarcoma cells, as well as the mechanism of cell growth inhibition induced by AO. A mouse osteosarcoma cell line (MOS), established from a radiation-induced mouse osteosarcoma, was cultured under exposure to 0.05, 0.5, 5, and 50 micrograms/ml of AO, either continuously or for 10 minutes. The cell kinetic analysis was performed using the following parameters: tumor cell growth by trypan blue exclusion test, mitotic activity, DNA synthetic activity by BrdU labeling and DNA ploidy by cytofluorometry. The results showed that continuous exposure to 5 and 50 micrograms/ml of AO or 10 minute exposure to 50 micrograms/ml of AO quickly killed the tumor cells within 12 hours, whereas continuous exposure to 0.5 microgram/ml of AO or 10 minute exposure to 5 micrograms/ml of AO gradually inhibited tumor cell growth. Under the latter conditions, mitotic activity was rapidly and completely inhibited within 48 hours but DNA synthetic activity was not completely inhibited even after 96 hours. DNA ploidy analysis demonstrated that most of the tumor cells arrested at the S-G2 phase after 12 hours, followed by G2 phase arrest after 24 hours and progressive DNA synthesis to a higher DNA ploidy class after 48 to 96 hours. We therefore concluded that a high concentration of AO has a strong cytocidal effect due to cytotoxicity whilst a moderate concentration of AO induces progressive and synchronous polyploidization by mitotic inhibition without DNA damage in MOS cells. We presume that this in vitro effect on MOS cells may be caused by protein synthetic inhibition after transfer RNA inactivation caused by AO binding.

  20. Review of mifamurtide in the treatment of patients with osteosarcoma

    Directory of Open Access Journals (Sweden)

    Leo Kager

    2010-06-01

    Full Text Available Leo Kager1, Ulrike Pötschger2, Stefan Bielack31St. Anna Children’s Hospital, Vienna, Austria; 2Children’s Cancer Research Institute, Vienna, Austria; 3Klinikum Stuttgart, Olgahospital, Pediatrics 5 – Oncology, Hematology, Immunology, Stuttgart, GermanyAbstract: Osteosarcoma is the most common primary malignant tumor of bone. The disease, however, is very rare with less than 2,000 expected patients at all age groups per year within the European Union and the United States of America. With multimodal therapy, which combines multiagent chemotherapy and complete resection of all macroscopically detectable tumors, about 60%–70% of patients with localized osteosarcoma can be cured. The prognosis, however, is still poor for patients with synchronous or metachronous metastatic or nonresectable primary disease, with reported 5-year event-free survival (EFS rates of less than 30%. Overall, the EFS rate has been rather stable since the introduction of combination chemotherapy including doxorubicin, cisplatin, high-dose methotrexate with leukovorin rescue, and/or ifosfamide. Mifamurtide, a modulator of innate immunity, which activates macrophages and monocytes, which in turn release chemicals with potential tumoricidal effects, may help to control microscopic metastatic disease and has been safely given together with standard adjuvant chemotherapy to patients with high-grade osteosarcoma. Results of the recently published intergroup study 0133 trial from the Children’s Cancer and Pediatric Oncology Groups suggest that mifamurtide is a medicine that deserves further investigation in this orphan disease.Keywords: orphan drug, orphan disease, outcome innate immunity, immunotherapy

  1. 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.

  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

    2013-01-01

    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 alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-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 cell lines (HOS, MG-63, 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 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%), while α-CaMKII overexpression resulted in tumor formation in a previously non-tumor 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. PMID:23364534

  3. Efficacy of glycogen synthase kinase-3β targeting against osteosarcoma via activation of β-catenin

    Science.gov (United States)

    Yamamoto, Norio; Nishida, Hideji; Hayashi, Katsuhiro; Kimura, Hiroaki; Takeuchi, Akihiko; Miwa, Shinji; Igarashi, Kentaro; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Hirose, Mayumi; Hoffman, Robert M; Minamoto, Toshinari; Tsuchiya, Hiroyuki

    2016-01-01

    Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3β in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3β inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of β-catenin in osteosarcoma cells following GSK-3β inhibition. Expression of the active form of GSK- 3β (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3β-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3β reduced phosphorylation at GSK- 3β-phospho-acceptor sites in β-catenin and increased β-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3β inhibitors is associated with activation of β-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3β in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma. PMID:27780915

  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. Long noncoding RNA MALAT1 as a potential therapeutic target in osteosarcoma.

    Science.gov (United States)

    Cai, Xianyi; Liu, Yunlu; Yang, Wen; Xia, Yun; Yang, Cao; Yang, Shuhua; Liu, Xianzhe

    2016-06-01

    Recent studies have revealed that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in the development of several solid tumors. However, the function of MALAT1 in the tumorigenesis of osteosarcoma remains unknown. In the present study, levels of MALAT1 in human osteosarcoma cell lines and tissues were detected by quantitative real-time polymerase chain reaction (RT-PCR). The roles of MALAT1 in osteosarcoma were investigated by using in vitro and in vivo assays. We observed that MALAT1 expression was up-regulated in human osteosarcoma cell lines and tissues. In vitro knockdown of MALAT1 by siRNA significantly inhibited cell proliferation and migration, and induced cell cycle arrest and apoptosis in osteosarcoma cells. In addition, MALAT1 knockdown markedly suppressed the formation of tubular network structures and caused breakage of stress fibers in osteosarcoma cell lines U2OS and MNNG/HOS. Furthermore, MALAT1 knockdown delayed tumor growth in an osteosarcoma xenograft model. Specifically, we found that administration of MALAT1 siRNA decreased the protein levels of RhoA and its downstream effectors Rho-associated coiled-coil containing protein kinases (ROCKs). Taken together, these findings suggest that MALAT1 plays an oncogenic role in osteosarcoma and may be a promising therapeutic target for the treatment of osteosarcoma patients. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:932-941, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. The expression and function of miRNA-106 in pediatric osteosarcoma.

    Science.gov (United States)

    Xu, M; Zhang, Y-Y; Wang, H-F; Yang, G-S

    2017-02-01

    This study is to investigate the expression and biological function of miRNA-106b in osteosarcoma. Freshly resected osteosarcoma tissues and the corresponding para-carcinoma tissues were collected from 54 patients. Then miR-106b level in the carcinoma tissues was detected by real-time PCR. To test the function of miR-106b, osteosarcoma cell line U2-OS was transfected with miR-106b inhibitor in vitro. Then, the proliferation, cell cycle, invasion and metastasis of U2-OS cells were detected by CCK-8 assay, flow cytometry, and transwell respectively. The PI3K/AKT signaling pathway activity after treatment was detected by Western blot. miR-106b level was significantly higher in osteosarcoma, and its expression was positively correlated with the lung metastasis and the clinical stages. In vitro experiments showed that the proliferation, invasion, and migration of U2-OS osteosarcoma cells were inhibited after miR-106b inhibition. The transition from G1 to S phase of U2-OS osteosarcoma cells was inhibited after miR-106b inhibition. The Western blot analysis demonstrated that both the AKT phosphorylation in PI3K/AKT pathway and the PI3Kp100 expression were significantly reduced when the expression of miR-106b was down-regulated. miR-106b level was significantly up-regulated in osteosarcoma, which was positively correlated with the lung metastasis and clinical stages. The down-regulation of miR-16b inhibited the proliferation, invasion, and migration of osteosarcoma cells; thus, it may function as an oncogene to promote osteosarcoma proliferation and invasion through the PI3K/AKT signaling pathway.

  7. Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression.

    Science.gov (United States)

    Tsuru, A; Setoguchi, T; Matsunoshita, Y; Nagao-Kitamoto, H; Nagano, S; Yokouchi, M; Maeda, S; Ishidou, Y; Yamamoto, T; Komiya, S

    2015-03-31

    Activation of the Notch pathway has been reported in various types of cancers. However, the role of the hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) in osteosarcoma is unknown. We examined the function of HEY1 in osteosarcoma. Expression of HEY1 was studied in human osteosarcoma. The effects of HEY1 in osteosarcoma were evaluated in vitro and in a xenograft model. Moreover, we examined the function of matrix metallopeptidase 9 (MMP9) as a downstream effector of HEY1. HEY1 was upregulated in human osteosarcoma. Knockdown of HEY1 inhibited the invasion of osteosarcoma cell lines. In contrast, the forced expression of HEY1 increased the invasion of mesenchymal stem cell. In addition, lung metastases were significantly inhibited by the knockdown of HEY1. We found that MMP9 was a downstream effector of HEY1 that promotes the invasion of osteosarcoma cells. Knockdown of HEY1 decreased the expression of MMP9. Addition of MMP9 rescued the invasion of osteosarcoma cells that had been rendered less invasive by knockdown of HEY1 expression. Our findings suggested that HEY1 augmented the metastasis of osteosarcoma via upregulation of MMP9 expression. Therefore, inhibition of HEY1 may be a novel therapeutic strategy for preventing osteosarcoma metastasis.

  8. Periosteal osteosarcoma arising from the rib and scapula: Imaging features in two cases

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jae Beom; Cho, Kil Ho; Choi, Joon Hyuk [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2014-06-15

    Periosteal osteosarcoma is an extremely rare chondroblastic osteosarcoma in the flat bone. There were authors reporting of two cases of periosteal osteosarcoma in the highly unusual sites. One of them arose from the rib, in a 17-year-old male, which appeared as a hypodense juxtacortical mass with periosteal reaction on CT. The other one arose from the scapula, in a 17-year-old female, which showed the intermediate signal intensity (SI) on T1-weighted image (WI), heterogeneous high SI on T2WI, and rim-enhancement on contrast-enhanced T1WI with cortical destruction on MRI.

  9. Osteoblastoma-like Osteosarcoma of the Proximal Tibia: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Soon Young; Kim, Mi Sung; Park, Noh Hyuck; Park, Chan Sub [Dept. of Radiology, Myoungji Hospital, Kwandong University College of Medicine, Goyang (Korea, Republic of); Park, Hee Jin [Dept. of Radiology, Kangbuk Samsung, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Yi, Sng Yeop [Dept. of Pathology, Myoungji Hospital, Kwandong University College of Medicine, Goyang (Korea, Republic of); Kim, Hyung Soo [Dept. of Orthpedic Surgery, Myoungji Hospital, Kwandong University College of Medicine, Goyang (Korea, Republic of)

    2011-05-15

    Osteoblastoma-like osteosarcoma is a rare, low-grade variant of osteosarcoma that may resemble osteoblastoma clinically, radiographically and histologically. We report a case of osteoblastoma-like osteosarcoma in the right proximal tibia in a 17-year-old woman. Plain radiography revealed an irregular osteolytic lesion in the metaepiphysis of the right proximal tibia and transverse fracture line of the metaphysic through an osteolytic lesion. MRI showed well-defined mass confined to the medullary space with cortical disruption and pathologic fracture. The MR signals were low on T1-weighted image and intermediate on T2-weighted image.

  10. Periosteal osteosarcoma arising from the rib and scapula: imaging features in two cases.

    Science.gov (United States)

    Hong, Jae Beom; Cho, Kil-Ho; Choi, Joon Hyuk

    2014-01-01

    Periosteal osteosarcoma is an extremely rare chondroblastic osteosarcoma in the flat bone. There were authors reporting of two cases of periosteal osteosarcoma in the highly unusual sites. One of them arose from the rib, in a 17-year-old male, which appeared as a hypodense juxtacortical mass with periosteal reaction on CT. The other one arose from the scapula, in a 17-year-old female, which showed the intermediate signal intensity (SI) on T1-weighted image (WI), heterogeneous high SI on T2WI, and rim-enhancement on contrast-enhanced T1WI with cortical destruction on MRI.

  11. 18F-NaF PET/CT Images of Cardiac Metastasis From Osteosarcoma.

    Science.gov (United States)

    Chou, Yi-Hsien; Ko, Kuan-Yin; Cheng, Mei-Fang; Chen, Wei-Wu; Yen, Ruoh-Fang

    2016-09-01

    Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Cardiac osteosarcoma metastasis is rare. We described a 17-year-old boy who had right distal femoral osteosarcoma with lung metastases. During follow-up, right ventricular (RV) metastasis was noted and confirmed by histopathological examination of the surgical specimen. F-NaF PET/CT was then arranged 1 month after debulking surgery for residual tumor survey. The images showed intense F-NaF uptake at RV region, suggestive of residual cardiac metastases.

  12. Lung metastasis 21 years after initial diagnosis of osteosarcoma: a case report

    Directory of Open Access Journals (Sweden)

    Montgomery Sam

    2009-11-01

    Full Text Available Abstract Introduction To the best of our knowledge, this case report describes the longest disease-free interval between primary diagnosis and metastatic recurrence of an osteosarcoma. Case presentation A 35-year-old Caucasian American man presented with asymptomatic lung metastases 21 years after being diagnosed and treated for lower extremity osteosarcoma. He underwent curative lung resection, but 2 years thereafter developed metastatic disease in the scapula and tibia and, after resection and chemotherapy, is in remission 1 year later. Conclusion This case highlights the importance of long follow-up periods and continued surveillance of osteosarcoma patients after initial curative treatment.

  13. MicroRNA-143 Regulates Human Osteosarcoma Metastasis by Regulating Matrix Metalloprotease-13 Expression

    OpenAIRE

    Osaki, Mitsuhiko; Takeshita, Fumitaka; Sugimoto, Yui; Kosaka, Nobuyoshi; Yamamoto, Yusuke; Yoshioka, Yusuke; Kobayashi,Eisuke; Yamada, Tesshi; Kawai, Akira; Inoue, Toshiaki; Ito, Hisao; Oshimura, Mitsuo; Ochiya, Takahiro

    2011-01-01

    Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell p...

  14. Calcaneal osteosarcoma: a rare cause of heel pain in the paediatric population.

    Science.gov (United States)

    Taslakian, Bedros; Issa, Ghada; Saab, Raya; Jabbour, Mark N; Khoury, Nabil J

    2013-02-04

    Osteosarcoma is the most common primary non-haemopoietic malignant bone tumour in children and adolescents. However, it rarely occurs in the calcaneus with only a few case reports in the literature. We report a case of a 14-year-old boy with calcaneal osteosarcoma, who presented with heel pain followed by swelling. The pain was initially thought to be related to a benign process and treated with analgesics, delaying the diagnosis. We discuss the clinical presentation, the differential diagnosis, multi-imaging and pathological findings of a calcaneal osteosarcoma, its clinical outcome and the importance of early diagnosis to improve outcome.

  15. Analysis of SDF-1/CXCR4 pathway function in osteosarcoma and the regulating effect of exogenous SDF-1 on osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    Ding-Tian Liang; Quan-Wang Li

    2016-01-01

    Objective:To study SDF-1/CXCR4 pathway function in osteosarcoma and the regulating effect of exogenous SDF-1 on osteosarcoma cells.Methods: Osteosarcoma tissue and adjacent tissue were collected to detect mRNA contents of SDF-1, CXCR4, Wnt,β-catenin, TCF and LEF; osteosarcoma MG63 cell lines were cultured, treated with SDF-1 and transfected with CXCR4-siRNA, and cell migration rate, number of invasive cells as well as mRNA contents of Wnt,β-catenin, TCF, LEF, c-myc, cyclinD1, MMP2, MMP9 and VEGF were detected. Results:mRNA contents of SDF-1, CXCR4, Wnt,β-catenin, TCF and LEF in osteosarcoma tissue were significantly higher than those in adjacent tissue; cell migration rate, number of invasive cells as well as mRNA contents of Wnt,β-catenin, TCF, LEF, c-myc, cyclinD1, MMP2, MMP9 and VEGF of SDF-1 treatment group were higher than those of control group; cell migration rate, number of invasive cells as well as mRNA contents of Wnt,β-catenin, TCF, LEF, c-myc, cyclinD1, MMP2, MMP9 and VEGF of SDF-1+CXCR4 interference group were lower than those of SDF-1 treatment group.Conclusion:SDF-1/CXCR4 pathway function in osteosarcoma is enhanced, and exogenous SDF-1 can promote osteosarcoma cell migration and invasion and activate Wnt/β-catenin pathway through CXCR4.

  16. Extraskeletal Effects of Vitamin D

    Directory of Open Access Journals (Sweden)

    V.V. Povoroznyuk

    2014-05-01

    Thus, the condition of deficiency or a failure of VD gains the predictor importance of a wide range of pathological states development, and also promotes increase in indexes both of total mortality and lethality from cardiovascular pathology, oncopathology and respiratory organs diseases.

  17. 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.

  18. Correlation between the expression of vegf and survival in osteosarcoma.

    Science.gov (United States)

    Baptista, André Mathias; Camargo, André Ferrari De França; Filippi, Renée Zon; Oliveira, Cláudia Regina Gomes Cardim Mendes De; Azevedo Neto, Raymundo Soares De; Camargo, Olavo Pires De

    2014-01-01

    To present a series of 50 consecutive patients with non-metastatic extremity osteosarcoma, and attempt to correlate expression of the vascular endothelial growth factor (VEGF) protein in biopsy tissue to their prognosis regarding overall survival, disease-free survival and local recurrence. Fifty cases of non-metastatic osteosarcoma of the extremities treated between 1986 and 2006 at Instituto de Ortopedia e Traumatologia da Universidade de São Paulo, São Paulo, Brasil, were evaluated regarding expression of the VEGF protein. There were 19 females and 31 males. The mean age was 16 years old (range 5-28 years old) and the mean follow-up was 60.6 months (range 25-167 months). The variables studied were age, gender, anatomic location, type of surgery, surgical margins, tumor size, post chemotherapy necrosis, local recurrence, pulmonary metastasis and death. Thirty-six patients showed VEGF expression on 30% or less cells (low), and the remaining 14 cases had VEGF expression above 30% (high). Among the 36 patients with low VEGF expression, nine developed pulmonary metastasis and four died (11.1%). Among the 14 patients with high VEGF expression, six developed pulmonary metastasis and three died (21.4%). There was no statistically significant correlation between the expression of VEGF and any of the variables studied. Level of Evidence IV, Therapeutic Study.

  19. Bilateral synchronous tibial periosteal osteosarcoma with familial incidence.

    Science.gov (United States)

    Maheshwari, Aditya V; Jelinek, James S; Seibel, Nita L; Meloni-Ehrig, Aurelia M; Kumar, Dhruv; Henshaw, Robert M

    2012-08-01

    Multifocal or multicentric osteosarcoma (OS) has been described as tumor occurrence at two or more sites in a patient without visceral metastasis. These may be synchronous (more than one lesion at presentation) or metachronous (new tumor developing after the initial treatment). The incidence of multifocal OS has ranged from 1.5 to 5.4% in large series, with the synchronous type being rarer. Similarly, periosteal OS is another rare subtype of surface OS and constitutes less than 2% of all OS. An 11-year-old female was diagnosed with bilateral synchronous tibial periosteal OS, which were confirmed by CT-guided biopsies. After neoadjuvant chemotherapy, the patient underwent a staged wide local resection of the tumors. The defect was reconstructed with a proximal tibial replacement on the left side and autologous bone grafting on the right side. The patient did well after surgery and is free of disease at 5.5 years of follow-up. However, her brother also developed a right tibial periosteal osteosarcoma 4 years after her index surgery. Genetic analysis of blood sample from both patients showed a similar missense mutation in at least one allele of TP53 gene (exon 8). To the best of our knowledge, a case of bilateral 'synchronous' periosteal OS with a familial incidence has not been reported before.

  20. Genetically Modified T-Cell Therapy for Osteosarcoma

    Science.gov (United States)

    DeRenzo, Christopher

    2015-01-01

    T-cell immunotherapy may offer an approach to improve outcomes for patients with osteosarcoma, who fail current therapies. In addition, it has the potential to reduce treatment-related complications for all patients. Generating tumor-specific T cells with conventional antigen presenting cells ex vivo is time consuming and often results in T-cell products with a low frequency of tumor-specific T cells. In addition, the generated T cells remain sensitive to the immunosuppressive tumor microenvironment. Genetic modification of T cells is one strategy to overcome these limitations. For example, T cells can be genetically modified to render them antigen specific, resistant to inhibitory factors, or increase their ability to home to tumor sites. Most genetic modification strategies have only been evaluated in preclinical models, however early phase clinical trials are in progress. In this chapter we review the current status of gene-modified T-cell therapy with special focus on osteosarcoma, highlighting potential antigenic targets, preclinical and clinical studies, and strategies to improve current T-cell therapy approaches. PMID:24924183

  1. 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.)

  2. Osteosarcoma de huesos del pie con alto grado de malignidad

    Directory of Open Access Journals (Sweden)

    Alain Martínez Milián

    2015-05-01

    Full Text Available El osteosarcoma es la neoplasia primaria del hueso más frecuente, los hombres son los más afectados en una relación 1,2 - 1,5 por cada mujer y con una tasa de mortalidad cercana a 0,15/100.000 habitantes/año. Se reporta el caso de una paciente femenina de 57 años de edad, con dolor, aumento de volumen e impotencia funcional de aproximadamente seis meses de evolución, los exámenes diagnósticos utilizados fueron radiografía de pie, tomografía axial computarizada de miembro inferior y biopsia de hueso. Se tuvo la confirmación diagnóstica de osteosarcoma de alto grado de malignidad por anatomía patológica. El tratamiento realizado fue quirúrgico, practicándose la amputación del miembro inferior, pudiendo así mejorar la supervivencia y extendiéndole la vida a la paciente. El motivo de la presentación del caso está dado por la poca frecuencia de este tipo de tumor óseo en los huesos del pie en pacientes femeninas

  3. Pathologic fracture in osteosarcoma : prognostic importance and treatment implications.

    Science.gov (United States)

    Scully, Sean P; Ghert, Michelle A; Zurakowski, David; Thompson, Roby C; Gebhardt, Mark C

    2002-01-01

    The presence of a pathologic fracture in an osteosarcoma has been considered a poor prognostic factor and an indication for immediate amputation. The purpose of the present study was to determine, in the current era of neoadjuvant chemotherapy, whether a pathologic fracture in an osteosarcoma has prognostic importance and whether limb salvage can be safely performed in such patients without compromising clinical outcome. In a cooperative effort of the Musculoskeletal Tumor Society, members from eight institutions provided retrospective data on fifty-two patients with osteosarcoma who had a pathologic fracture and on fifty-five patients with osteosarcoma who had not had a pathologic fracture and had been followed for at least two years or until disease recurrence, metastasis, or death. The two groups were matched for patient age and tumor location. Outcomes examined were survival and local recurrence. A subgroup analysis was performed to assess differences in outcome within the group with the pathologic fracture. The five-year estimated survival rates were 55% for the group with a pathologic fracture and 77% for the group without a fracture (p = 0.02). The rate of survival without a local recurrence at five years was 75% for the group with a fracture and 96% for the group without a fracture (p = 0.007). In the group with a fracture, seven (23%) of the thirty patients managed with limb salvage and four (18%) of the twenty-two managed with an amputation had a local recurrence (p = 0.75). Eleven (37%) of the thirty patients with a fracture who were managed with limb salvage and ten (45%) of the twenty-two patients with a fracture who were managed with an amputation died of the disease (p = 0.50). Five patients underwent open reduction and internal fixation followed by limb-salvage surgery. Two of them had a local recurrence and died at an average of eight months postoperatively. The remaining three patients were alive at an average of 6.1 years postoperatively. Local

  4. Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

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    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.

  5. Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?

    Science.gov (United States)

    Tamamyan, Gevorg; Dominkus, Martin; Lang, Susanna; Diakos, Christopher; Mittheisz, Edda; Horcher, Ernst; Holter, Wolfgang; Zoubek, Andreas; Bielack, Stefan; Kager, Leo

    2015-03-01

    The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses. © 2014 Wiley Periodicals, Inc.

  6. Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma.

    Science.gov (United States)

    Shaikh, Atik Badshah; Li, Fangfei; Li, Min; He, Bing; He, Xiaojuan; Chen, Guofen; Guo, Baosheng; Li, Defang; Jiang, Feng; Dang, Lei; Zheng, Shaowei; Liang, Chao; Liu, Jin; Lu, Cheng; Liu, Biao; Lu, Jun; Wang, Luyao; Lu, Aiping; Zhang, Ge

    2016-04-06

    Osteosarcoma (OS) is a bone cancer mostly occurring in pediatric population. Current treatment regime of surgery and intensive chemotherapy could cure about 60%-75% patients with primary osteosarcoma, however only 15% to 30% can be cured when pulmonary metastasis or relapse has taken place. Hence, novel precise OS-targeting therapies are being developed with the hope of addressing this issue. This review summarizes the current development of molecular mechanisms and targets for osteosarcoma. Therapies that target these mechanisms with updated information on clinical trials are also reviewed. Meanwhile, we further discuss novel therapeutic targets and OS-targeting drug delivery systems. In conclusion, a full insight in OS pathogenesis and OS-targeting strategies would help us explore novel targeted therapies for metastatic osteosarcoma.

  7. 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.

  8. 骨肉瘤的靶向治疗%Targeted therapies for osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    田大为; 蔡林

    2014-01-01

    As a kind of malignant tumor derived from mesenchymal tissues, osteosarcoma is harmful to adolescent health and may cause death, with a higher grade of malignancy and metastasis and worse treatment outcomes and prognosis. Chemotherapy, especially neoadjuvant chemotherapy, plays a very important role in the treatment of osteosarcoma. However, because of the deifciency of treatment speciifcity, the antineoplastic drug will do harm to normal cells and organs and meanwhile kill osteosarcoma cells. Depending on selective functions of the oriented part, targeted therapies will selectively act on target locations and toxic reactions will also be reduced for normal organs. Different mechanisms of targeted therapies will be used on different target points. The key examples of target identiifcation in osteosarcomas is highlighted in this review. The drug doses and side effects can be reduced and the treatment effects can be improved, with potential clinical values in the future.

  9. EXPRESSION OF CYCLIN D1 AND CDK4 IN OSTEOSARCOMA OF THE JAWS

    Institute of Scientific and Technical Information of China (English)

    司晓辉; 刘正

    2001-01-01

    Objective: To analyze cyclin D1 and cyclin- dependent kinase 4 (CDK4) expression and their significance in osteosarcoma of the jaws. Methods: Immunohistochemical ABC method was used to detect the expression of cyclin D1 and CDK4 in 20 cases of osteosarcoma and 8 cases of osteochondroma of the jaws. Results: The positive rates of cyclin D1 and CDK4 were 65% (13/20) and 60% (12/20), respectively. There was significant positive correlation between cyclin D1 and CDK4 expression (gs=0.48, P<0.05). Both cyclin D1 and CDK4 were present in 1/8 (12.5%) osteochondroma. The positive rate was remarkably different between osteosarcoma and osteochondroma (P<0.05). Conclusion: Cyclin D1 and CDK4 are overexpressed in osteosarcoma of the jaws and closely related to its occurrence and development.

  10. The osteosarcoma of the great poet Arthur Rimbaud (1854-1891).

    Science.gov (United States)

    Androutsos, G

    2005-01-01

    Thanks to Arthur Rimbaud's excellent medical auto-observation, which is included in his correspondance, we can diagnose, post-mortem, an osteosarcoma in the right knee, a disease which turned out to be fatal for him.

  11. Palliative approach in advanced pelvic osteosarcoma: a single centre experience of a rare disease

    Directory of Open Access Journals (Sweden)

    Ritesh Kumar

    2014-01-01

    Conclusions: Pelvic osteosarcomas are rare neoplasms with aggressive growth patterns. Survival results are poor in view of advanced stage of presentation and difficult surgical approaches. The combined modality approach is needed to improve the results.

  12. How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize.

    Science.gov (United States)

    Hughes, Dennis P M

    2009-01-01

    Controlling metastasis is the key to improving outcomes for osteosarcoma patients; yet our knowledge of the mechanisms regulating the metastatic process is incomplete. Clearly Fas and Ezrin are important, but other genes must play a role in promoting tumor spread. Early developmental pathways are often recapitulated in malignant tissues, and these genes are likely to be important in regulating the primitive behaviors of tumor cells, including invasion and metastasis. The Notch pathway is a highly conserved regulatory signaling network involved in many developmental processes and several cancers, at times serving as an oncogene and at others, behaving as a tumor suppressor. In normal limb development, Notch signaling maintains the apical ectodermal ridge in the developing limb bud and regulated size of bone and muscles. Here, we examine the role of Notch signaling in promoting metastasis of osteosarcoma, and the underlying regulatory processes that control Notch pathway expression and activity in the disease. We have shown that, compared to normal human osteoblasts and non-metastatic osteosarcoma cell lines, osteosarcoma cell lines with the ability to metastasize have higher levels of Notch 1, Notch 2, the Notch ligand DLL1 and the Notch-induced gene Hes1. When invasive osteosarcoma cells are treated with small molecule inhibitors of gamma-secretase, which blocks Notch activation, invasiveness is abrogated. Direct retroviral expression has shown that Hes1 expression was necessary for osteosarcoma invasiveness and accounted for the observations. In a novel orthotopic murine xenograft model of osteosarcoma pulmonary metastasis, blockade of Hes1 expression and Notch signaling eliminated spread of disease from the tibial primary tumor. In a sample of archival human osteosarcoma tumor specimens, expression of Hes1 mRNA was inversely correlated with survival (n=16 samples, p=0.04). Expression of the microRNA 34 cluster, which is known to downregulate DLL1, Notch 1 and

  13. Misdiagnosis of osteosarcoma as cementoblastoma from an atypical mandibular swelling: A case report

    OpenAIRE

    2016-01-01

    Cementoblastoma is a form of benign odontogenic tumor, with the preferred treatment consisting of tooth extraction and follow-up examinations, while in certain cases, follow-up examinations without surgery are performed. Osteosarcoma of the jaw is a rare, malignant, mesenchymal tumor, associated with a high mortality rate and low incidence of metastasis. Cementoblastoma and osteosarcoma of the jaw are dissimilar in terms of their histological type and prognosis; however, there are a number of...

  14. FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo.

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    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.

  15. Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway.

    Science.gov (United States)

    Yu, Gui-Hua; Li, Ai-Min; Li, Xiang; Yang, Zhong; Peng, Hao

    2017-06-01

    Osteosarcoma is one of the most lethal malignancies, and the prognosis remains dismal due to the paucity of effective therapeutic targets. Bmi-1 and TRIM-14 are associated with the initiation and progression of osteosarcoma, which could promote angiogenesis, invasion, and apoptotic resistance in bone cancer tissue. In this study, we constructed a bispecific antibody of BsAbBmi/TRIM targeting Bmi-1 and TRIM-14 and investigated the therapeutic value in bone carcinoma cells and xenograft mice. Our results showed that Bmi-1 and TRIM-14 expression levels were markedly upregulated correlated with nuclear factor-κB nuclear translocation in bone cancer cells and clinical carcinoma tissues. Results have demonstrated that overexpression of Bmi-1 and TRIM-14 promoted growth, proliferation, aggressiveness, and apoptosis resistance of osteosarcoma cells. BsAbBmi/TRIM administration significantly inhibited nuclear factor-κB expression derived by matrix metalloproteinase-9 promoter. BsAbBmi/TRIM administration inhibited growth of osteosarcoma cells and downregulated Bmi-1 and TRIM-14 expression levels. Data also demonstrated that migration and invasion of osteosarcoma cells were also inhibited by BsAbBmi/TRIM. In addition, results illustrated that BsAbBmi/TRIM inhibited tumor growth and tumorigenicity by blockaded sensor expression in nuclear factor-κB signal pathway. Furthermore, in vivo study showed that BsAbBmi/TRIM treatment markedly inhibited the tumorigenicity and growth of osteosarcoma cells compared to either AbBmi-1 or AbTRIM-14 treatment. Notably, survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy.

  16. 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

  17. Extraosseous osteosarcoma presenting with intestinal hemorrhage: case report and literature review.

    Science.gov (United States)

    Nojima, T; Gebhardt, M C; Mankin, H J; Schiller, A L

    1986-01-01

    A 23-year-old man presented with intestinal bleeding due to an extraosseous osteosarcoma of the jejunum. A lesion was also found in the deltoid muscle, and other metachronous soft tissue sites developed subsequently. The presence of malignant osteoid was documented by immunohistochemical studies of one of the lesions. The patient died of metastatic disease 19 months after diagnosis, despite surgical resections and adjuvant chemotherapy. This unique presentation is discussed, and the literature concerning extraosseous osteosarcoma is reviewed.

  18. 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.

  19. PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway

    Science.gov (United States)

    Li, Lin; Liang, Shoulei; Wasylishen, Amanda R.; Zhang, Yanqin; Yang, Xueli; Zhou, Bingzheng; Shan, Luling; Han, Xiuxin; Mu, Tianyang; Wang, Guowen; Xiong, Shunbin

    2016-01-01

    The prognosis of metastatic osteosarcoma is dismal and a better understanding of the mechanisms underlying disease progression is essential to improve treatment options and patient outcomes. We previously demonstrated Pla2g16 overexpression in mouse osteosarcoma contributes to metastasis phenotypes and increased expression of PLA2G16 is associated with metastasis and poor prognosis in human tumors. To further examine the mechanisms through which PLA2G16 contributes to human osteosarcoma metastasis and explore the potential of PLA2G16 as a therapeutic target in osteosarcoma, we generated a panel of human osteosarcoma cell lines expressing different levels of PLA2G16. The functional analyses of these cell lines demonstrated high levels of PLA2G16 expression increased osteosarcoma cell migration, invasion, clonogenic survival, and anchorage-independent colony formation. Importantly, this activity was dependent on the phospholipase activity of PLA2G16. Additionally, PLA2G16 overexpression decreased the sensitivity of cells to a panel of chemotherapeutic agents. Analysis of downstream pathways revealed the pro-metastasis functions of PLA2G16 were mediated through the MAPK pathway, as knockdown of PLA2G16 decreased ERK1/2 phosphorylation and pharmacological inhibition of MEK significantly repressed PLA2G16 mediated cell migration and clonogenic survival. Furthermore, PLA2G16 overexpression promoted xenograft tumor growth in vivo, and these tumors exhibit increased ERK1/2 phosphorylation. Lastly, the expression of PLA2G16 is strongly correlated with the increased ERK1/2 phosphorylation in human osteosarcoma samples, and the combined lesions are associated with reduced overall and metastasis-free survival. Collectively, these results demonstrate increased PLA2G16 expression activates the MAPK pathway to enhance osteosarcoma metastasis and may be a novel therapeutic target for these cancers. PMID:26933804

  20. Fatty acid synthase expression in osteosarcoma and its correlation with pulmonary metastasis

    OpenAIRE

    Liu, Zhi Li; Wang, Gao; Peng, Ai Fen; LUO, QING FENG; Zhou, Yang; Huang, Shan Hu

    2012-01-01

    Previous experimental evidence has suggested that fatty acid synthase (FASN) may be involved in cancer metastasis. However, its role has been poorly evaluated in osteosarcoma. The aim of this study was to investigate the correlation of FASN expression with pulmonary metastasis and the correlation of FASN expression with the Ki-67 antigen, a proliferation marker, in patients with osteosarcoma of the extremities. The expression of FASN protein and Ki-67 was detected by immunohistochemistry of b...