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Sample records for primary pulmonary osteosarcoma

  1. Imaging in primary osteosarcomas

    International Nuclear Information System (INIS)

    Davies, A.M.

    1998-01-01

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

  2. Primary renal osteosarcoma: A case report

    African Journals Online (AJOL)

    C. Ahomadégbé

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

  3. Retrospective Evaluation of Whole Body Computed Tomography for Tumor Staging in Dogs with Primary Appendicular Osteosarcoma.

    Science.gov (United States)

    Talbott, Jessica L; Boston, Sarah E; Milner, Rowan J; Lejeune, Amandine; Souza, Carlos H de M; Kow, Kelvin; Bacon, Nicholas J; Hernandez, Jorge A

    2017-01-01

    To evaluate whole body computed tomography (CT) for staging canine appendicular osteosarcoma. Retrospective case series. Client-owned dogs diagnosed with appendicular osteosarcoma (n=39). Medical records for client-owned dogs diagnosed with appendicular osteosarcoma from August 2008 to July 2014 were reviewed. Dogs were included if they had a confirmed diagnosis of appendicular osteosarcoma and were staged using whole body CT. Data collected included signalment, body weight, primary tumor location, serum alkaline phosphatase (ALP) activity, findings on 3-view thoracic radiographs, cytologic or histologic results, and findings on CT. Thirty-nine dogs (median age 8.5 years; median body weight 37 kg) had osteosarcoma of the distal radius (n=17), proximal humerus (11) and other sites. Serum ALP activity was elevated in 14 dogs. Bone metastasis was not detected in any dog on whole body CT. Pulmonary metastasis was considered definitive on CT based on board certified radiologist assessment in 2/39 dogs (5%). Two additional dogs (2/39, 5%) had soft tissue masses diagnosed on CT, consistent with concurrent, non-metastatic malignancies. Bone metastases were not identified in any dog with whole body CT. Thoracic and abdominal CT detected lung lesions and concurrent neoplasia in dogs with primary appendicular osteosarcoma. Whole body CT may be a useful adjunct to other screening tests for disseminated malignancy. © 2016 The American College of Veterinary Surgeons.

  4. Expression and prognostic relevance of PRAME in primary osteosarcoma

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    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.

  5. Primary Osteosarcoma of the Breast: A Case Report

    Directory of Open Access Journals (Sweden)

    Anna Rizzi

    2013-01-01

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

  6. Primary osteosarcoma of the cranial vault

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

    2017-07-15

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

  7. Primary mesenteric extraskeletal osteosarcoma in the pelvic cavity

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  8. Primary mesenteric extraskeletal osteosarcoma in the pelvic cavity

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  9. Hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma in a dog

    International Nuclear Information System (INIS)

    Rahal, S.C.; Mamprim, M.J.; Sequeira, J.L.; Franco, A.P.R.

    2003-01-01

    A 1.8-year-old female German Shepherd dog was presented with lameness, and painful non-edematous swelling of the right front limb. Swelling surrounding soft tissue and periosteal bone formation of the radius, ulna, metacarpals, without evidence of articular involvement were observed in the right front limb by radiographic examinations. Also, pulmonary tumor was observed in radiographic examination. Five months ago, the dog had developed osteosarcoma of the left distal ulna, and the treatment was cisplatin chemotherapy and limb amputation. The final diagnosis was hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma [pt

  10. Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine.

    Science.gov (United States)

    Gordon, Nancy; Koshkina, Nadezhda V; Jia, Shu-Fang; Khanna, Chand; Mendoza, Arnulfo; Worth, Laura L; Kleinerman, Eugenie S

    2007-08-01

    Pulmonary metastases continue to be a significant problem in osteosarcoma. Apoptosis dysfunction is known to influence tumor development. Fas (CD95, APO-1)/FasL is one of the most extensively studied apoptotic pathways. Because FasL is constitutively expressed in the lung, cells that express Fas should be eliminated by lung endothelium. Cells with low or no cell surface Fas expression may be able to evade this innate defense mechanism. The purpose of these studies was to evaluate Fas expression in osteosarcoma lung metastases and the effect of gemcitabine on Fas expression and tumor growth. Using the K7M2 murine osteosarcoma model, Fas expression was quantified using immunohistochemistry. High levels of Fas were present in primary tumors, but no Fas expression was present in actively growing lung metastases. Blocking the Fas pathway using Fas-associated death domain dominant-negative delayed tumor cell clearance from the lung and increased metastatic potential. Treatment of mice with aerosol gemcitabine resulted in increased Fas expression and subsequent tumor regression. We conclude that corruption of the Fas pathway is critical to the ability of osteosarcoma cells to grow in the lung. Agents such as gemcitabine that up-regulate cell surface Fas expression may therefore be effective in treating osteosarcoma lung metastases. These data also suggest that an additional mechanism by which gemcitabine induces regression of osteosarcoma lung metastases is mediated by enhancing the sensitivity of the tumor cells to the constitutive FasL in the lung.

  11. Whole lung computed tomography for detection of pulmonary metastasis of osteosarcoma confirmed at thoracotomy

    International Nuclear Information System (INIS)

    Ishida, Itsuro; Fukuma, Seigo; Sawada, Kinya; Seki, Yasuo; Tanaka, Fumitaka

    1980-01-01

    Whole lung computed tomography (CT) was performed in patients with osteosarcoma of bone to evaluate its diagnostic efficacy in comparison to that in conventional chest radiography and in whole lung tomography to detect metastatic nodules in the lung. In 11 of the 12 patients with osteosarcoma, CT detected pulmonary nodules and in 6 of the 11 patients pulmonary nodules were detected by CT, conventional chest radiography and whole lung tomography, respectively, and 22 pulmonary nodules were resected at thoracotomy and proved to be metastatic lesions. Nineteen nodules of the 22 nodules resected were detected by CT and nine of the 22 nodules were discovered only by CT, while only 10 of 22 nodules were recognized by the conventional chest radiography and the whole lung tomography. Two pulmonary nodules, measuring 1 mm and 2 mm in diameter, respectively, were not detected by any of these three methods. In three nodules that showed to be false positive in CT in the two patients, two nodules were histologically suture granulomas induced by the previous operation, and a deformed protuberance of the chest wall was erroneously interpreted to be a subpleural and intrapulmonary nodule in the remaining. We conclude that CT is the most efficient method to detect pulmonary nodules in the patients with osteosarcoma, but that the minimal size of the detectable nodule by CT is 3 mm in diameter. But a smaller nodule having a tendency to ossify can be detected by CT. (author)

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

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    N J Nawarathna

    2016-01-01

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

  13. Pulmonary metastasis in osteosarcoma in bone scintigraphy: 2 case reports poster

    International Nuclear Information System (INIS)

    Grobocopatel, D.; Silva, N.J.; Hunsche, A.; Fernandes, D.D.; Berdichevski, E.H.; Cembrani, L.; Anselmi, C.E.; Anselmi, O.E.

    2004-01-01

    Full text: Osteosarcoma is considered the most common malignant primary bone tumour in children and adolescents. The lungs are the common sites of metastasis, which, if present, are associated with poor prognosis. Imaging workup includes x-ray, computed tomography, nuclear resonance imaging and bone scintigraphy in order to diagnose, help to choose appropriate treatment and prognosticate this disease. Chemotherapy is used to increase survival rate and to control the occurrence of lung metastasis. CASE 1: ELWS, male, 6 years old. The patient had a left knee trauma followed by increase in size and pain over 15 days. Knee x-ray showed a voluminous lesion and densely calcified tissue in the left knee, with soft tissue involvement. Chest x-ray showed multiple nodular dense lesions diffusely involving the lungs. Left knee MRI showed a neoplasm involving the distal epiphysis of the femur with extension from the bone marrow to the trochanteric region. Biopsy diagnosed small cell osteosarcoma. Chest computed tomography showed multiple opacities in the parenchyma of both lungs, most with calcification, predominantly in the cortical region. Bone scintigraphy showed intense uptake of the radiopharmaceutical in the distal half of the left femur and focal areas of increased uptake in the skull, left humerus, right scapula, thoracic soft tissue (mostly in the right side, in the same place as the pulmonary metastasis seen in the chest computed tomography), 12th thoracic vertebra, 4th lumbar vertebra and in the pelvis. CASE 2: ACD, male 20 years old. The patient presented pain and increase in size of the right knee starting 5 months ago. Right knee x-ray: insufflating bony lesion in the proximal epiphysis of the right tibia compatible with osteosarcoma; increase in volume in soft tissue around the knee. Right knee MRI: voluminous expansive osteoblastic lesion hypointense in T1 and heterogeneous in T2, diffusely enhanced by the use of gadolinium-DTPA; the lesion involved almost

  14. Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8

    International Nuclear Information System (INIS)

    Aizawa, Junichi; Sakayama, Kenshi; Kamei, Setsuya; Kidani, Teruki; Yamamoto, Haruyasu; Norimatsu, Yoshiaki; Masuno, Hiroshi

    2010-01-01

    Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ) is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group) or ethanol (control group) on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2) within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD) within the tumor was determined by immunohistochemistry for CD34. TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the control group. Inhibition of Akt signaling by

  15. Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8

    Directory of Open Access Journals (Sweden)

    Kidani Teruki

    2010-02-01

    Full Text Available Abstract Background Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. Methods LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group or ethanol (control group on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2 within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD within the tumor was determined by immunohistochemistry for CD34. Results TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the

  16. 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.

  17. A mouse model of pulmonary metastasis from spontaneous osteosarcoma monitored in vivo by Luciferase imaging.

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    Silvia Miretti

    Full Text Available BACKGROUND: Osteosarcoma (OSA is lethal when metastatic after chemotherapy and/or surgical treatment. Thus animal models are necessary to study the OSA metastatic spread and to validate novel therapies able to control the systemic disease. We report the development of a syngeneic (Balb/c murine OSA model, using a cell line derived from a spontaneous murine tumor. METHODOLOGY: The tumorigenic and metastatic ability of OSA cell lines were assayed after orthotopic injection in mice distal femur. Expression profiling was carried out to characterize the parental and metastatic cell lines. Cells from metastases were propagated and engineered to express Luciferase, in order to follow metastases in vivo. PRINCIPAL FINDINGS: Luciferase bioluminescence allowed to monitor the primary tumor growth and revealed the appearance of spontaneous pulmonary metastases. In vivo assays showed that metastasis is a stable property of metastatic OSA cell lines after both propagation in culture and luciferase trasduction. When compared to parental cell line, both unmodified and genetically marked metastatic cells, showed comparable and stable differential expression of the enpp4, pfn2 and prkcd genes, already associated to the metastatic phenotype in human cancer. CONCLUSIONS: This OSA animal model faithfully recapitulates some of the most important features of the human malignancy, such as lung metastatization. Moreover, the non-invasive imaging allows monitoring the tumor progression in living mice. A great asset of this model is the metastatic phenotype, which is a stable property, not modifiable after genetic manipulation.

  18. CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF.

    Science.gov (United States)

    Zhang, Peng; Dong, Ling; Yan, Kang; Long, Hua; Yang, Tong-Tao; Dong, Ming-Qing; Zhou, Yong; Fan, Qing-Yu; Ma, Bao-An

    2013-10-01

    Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis. CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2), which has a high tumorigenic ability and potential for spontaneous pulmonary metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the tumor stroma and promote metastasis. However, mechanisms underlying the promotion of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our study co-injected the human MSCs and F5M2 cells into the caudal vein of nude mice. The total number of tumor nodules per lung was significantly increased in the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100 decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels of VEGF as determined by immunohistochemistry, western blotting and ELISA, respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly increased in the co-culture system. Additionally, VEGF increased the proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4-mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs through VEGF.

  19. Vertebral metastasis of femur primary osteosarcoma: a case report and literature review

    International Nuclear Information System (INIS)

    Cioni, Claudia Helena; Oliveira, Andrea Alencar de; Neves, Felipe Trentin

    2006-01-01

    We present a case of a 21-year-old patient, bearer of femur primary osteosarcoma, who began with pain in the thoracic column. The metastasis of primary osteosarcoma has greater incidence on lungs, rarely affecting vertebras. We reviewed the literature about this disease and emphasized the image's characteristics on the several methods used (traditional radiographic exams, bone scintigraphy, computed tomography, magnetic resonance) and the main differential diagnostics. (author)

  20. Primary breast osteosarcoma mimicking calcified fibroadenoma on screening digital breast tomosynthesis mammogram

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    Debbie Lee Bennett, MD

    2017-12-01

    Full Text Available Primary breast osteosarcoma is a rare malignancy, with mostly case reports in the literature. The appearance of breast osteosarcoma on digital breast tomosynthesis imaging has not yet been described. A 69-year-old woman presents for routine screening mammography and is found to have a calcified mass in her right breast. Pattern of calcification appeared “sunburst” on digital breast tomosynthesis images. This mass was larger than on the previous year's mammogram, at which time it had been interpreted as a benign calcified fibroadenoma. The subsequent workup demonstrated the mass to reflect primary breast osteosarcoma. The patient's workup and treatment are detailed in this case. Primary breast osteosarcoma, although rare, should be included as a diagnostic consideration for breast masses with a sunburst pattern of calcifications, particularly when the mammographic appearance has changed.

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

    OpenAIRE

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

    2015-01-01

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

  2. Synchronous multicentric osteosarcoma: the case for metastases

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  3. Primary Osteosarcoma of the Sternum: A case Report and Review of the Literature

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    Masoud Pezeshki Rad

    2014-10-01

    Full Text Available Osteosarcoma (osteogenic sarcoma: OS is the most common primary malignant bone tumor of long bones, whereas primary osteosarcoma of chest wall, especially in sternum, is extremely rare. We report a 57-year-old man with an immobile slow growing mass located in the middle of the sternum. The patient had no significant pain or tenderness and the past medical history was not remarkable. CT-scan showed a large densely sclerotic sternal mass and MRI revealed an extensive central signal loss within the tumor because of necrosis. We performed a CT-guided needle biopsy, but it was inconclusive. After an incisional biopsy, a high-grade osteosarcoma of the sternum was diagnosed. The patient underwent subtotal sternal resection and reconstruction using synthetic mesh and bone cement followed by chemotherapy and external beam radiotherapy. After one year of follow-up, the patient is back to normal life and is doing the daily activities without problem. By this time, focal recurrence or metastatic disease did not occur.

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

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    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.)

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

    Wycislo, K L; Fan, T M

    2015-01-01

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

  7. Primary osteosarcoma of the breast presenting as a large breast abscess

    Directory of Open Access Journals (Sweden)

    Nadeesha J Nawarathna

    2016-01-01

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

  8. RANK and RANK ligand expression in primary human osteosarcoma

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    Daniel Branstetter

    2015-09-01

    Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79 of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.

  9. When a pulmonary embolism is not a pulmonary embolism: a rare case of primary pulmonary leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Nargiz Muganlinskaya

    2015-12-01

    Full Text Available Arterial leiomyosarcomas account for up to 21% of vascular leiomyosarcomas, with 56% of arterial leiomyosarcomas occurring in the pulmonary artery. While isolated cases of primary pulmonary artery leiomyosarcoma document survival up to 36 months after treatment, these uncommon, aggressive tumors are highly lethal, with 1-year survival estimated at 20% from the onset of symptoms. We discuss a rare case of a pulmonary artery leiomyosarcoma that was originally diagnosed as a pulmonary embolism (PE. A 72-year-old Caucasian female was initially diagnosed with ‘saddle pulmonary embolism’ based on computerized tomographic angiography of the chest 2 months prior to admission and placed on anticoagulation. Dyspnea escalated, and serial computed tomography scans showed cardiomegaly with pulmonary emboli involving the right and left main pulmonary arteries with extension into the right and left upper and lower lobe branches. An echocardiogram on admission showed severe pulmonary hypertension with a pulmonary artery pressure of 82.9 mm Hg, and a severely enlarged right ventricle. Respiratory distress and multiorgan failure developed and, unfortunately, the patient expired. Autopsy showed a lobulated, yellow mass throughout the main pulmonary arteries measuring 13 cm in diameter. The mass extended into the parenchyma of the right upper lobe. On microscopy, the mass was consistent with a high-grade primary pulmonary artery leiomyosarcoma. Median survival of patients with primary pulmonary artery leiomyosarcoma without surgery is one and a half months, and mortality is usually due to right-sided heart failure. Pulmonary artery leiomyosarcoma is a rare but highly lethal disease commonly mistaken for PE. Thus, we recommend clinicians to suspect this malignancy when anticoagulation fails to relieve initial symptoms. In conclusion, early detection and suspicion of pulmonary artery leiomyosarcoma should be considered in patients refractory to anticoagulation

  10. Perfusion lung scintigraphy in primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Ogawa, Yoji; Nishimura, Tsunehiko; Kumita, Shin-ichirou; Hayashida, Kohei; Uehara, Toshiisa; Shimonagata, Tsuyoshi; Ohno, Akira

    1991-01-01

    Fifteen cases with primary pulmonary hypertension (PPH) were classified into two groups by using the perfusion lung scan pattern. Eight cases had multiple, small, ill-defined defects (mottled pattern), and remaining seven cases had no mottled pattern. These two groups were compared with mean pulmonary arterial pressure (mean PAP), right ventricular ejection fraction (RVEF), blood gas at room air (PaO 2 ), and alveolar-arterial O 2 difference (A-aDo 2 ). The cases with mottled pattern showed a significant increase in mean PAP. There were no significant differences in RVEF, PaO 2 , and A-aDo 2 , between the groups. The survival rate of the patients with mottled pattern was significantly lower than that without mottled pattern (p<0.05). We concluded that perfusion lung scan is very useful for evaluation of the prognosis in primary pulmonary hypertension. (author)

  11. CT differential diagnosis of primary pelvic osteosarcoma, chondrosarcoma and Ewing's sarcoma

    International Nuclear Information System (INIS)

    Heller, M.; Heyer, D.; Spielmann, R.P.; Buecheler, E.

    1990-01-01

    The value of CT for the differential diagnosis of primary malignant tumours in the pelvis was investigated in the case of three types of tumour: Osteosarcomas, chondrosarcomas and Ewing's sarcomas. A total of 78 CT examinations in 29 patients was used. The results show that CT, using suitable techniques (high resolution etc.) constitutes a valuable diagnostic method for differentiating these bone tumours. This applies not only for the localisation of the tumour and for defining its extent, but also for showing the morphology of intra- and extra-osseous soft tissue components and their patterns of calcification. It is possible to recognise patterns of growth and of tissue destruction that are typical of individual tumours. (orig.) [de

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  13. Vertebral metastasis of femur primary osteosarcoma: a case report and literature review; Metastase vertebral de osteossarcoma primario de femur: relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, Claudia Helena [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Radiologia Pediatrica; Francisco, Marina Celli; Lederman, Henrique Manoel [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem]. E-mail: nana_celli@hotmail.com; Francisco, Fabiano Celli [Hospital de Caridade Sao Braz, Porto Uniao, SC (Brazil); Oliveira, Andrea Alencar de [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Oncologia Pediatrica; Neves, Felipe Trentin [Hospital Ipiranga, Sao Paulo, SP (Brazil). Cirurgia Geral

    2006-10-15

    We present a case of a 21-year-old patient, bearer of femur primary osteosarcoma, who began with pain in the thoracic column. The metastasis of primary osteosarcoma has greater incidence on lungs, rarely affecting vertebras. We reviewed the literature about this disease and emphasized the image's characteristics on the several methods used (traditional radiographic exams, bone scintigraphy, computed tomography, magnetic resonance) and the main differential diagnostics. (author)

  14. Cardiovocal syndrome – A rare presentation of primary pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Om Shankar

    2014-05-01

    Full Text Available Primary pulmonary hypertension is a well known entity with characteristic features more common in females presenting commonly with dyspnea. However primary pulmonary hypertension presenting as hoarseness of voice is rare occurring most likely due to compression of left recurrent laryngeal nerve between normal aorta and dilated tense pulmonary artery. Here we are presenting a case of 19 year old boy with primary pulmonary hypertension who presented with hoarseness of voice as predominant symptom.

  15. 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.

  16. CT findings in primary pulmonary lymphomas

    International Nuclear Information System (INIS)

    Cardinale, Luciano; Allasia, Marco; Cataldi, Aldo; Ferraris, Fabrizio; Fava, Cesare; Parvis, Guido

    2005-01-01

    Purpose. To describe the CT findings of pathologically confirmed primary pulmonary lymphomas. Materials and methods. The CT examinations of 11 patients with pathologically proven primary pulmonary lymphoma (9 BALT lymphomas and 2 non-BALT lymphomas) were retrospectively reviewed by three radiologists. Evaluated findings included morphology (consolidation, mass, nodule), number and distribution of lesions. Other CT findings such as air bronchogram, lymphadenopathy atelectasis and pleural effusion were also assessed. Results. Pulmonary lesions were depicted as air-space consolidation (pneumonia-like) in 5 patients (45%), tumour-like rounded opacity in 4 (36%), and nodules in 4 (36%). Multiple and bilateral long lesions were seen in 3 patients (27%). Air bronchogram was present in 7 patients (63%), lymphadenopathy in 3 (27%), atelectasis in 4 (36%) and pleural effusion in only 1 (9%). Conclusions. Our results agree with previous studies regarding lesion patterns and their relative frequency. A smaller number of nodules and of multiple lesions were found compared with some previous studies. The most frequent pattern was airspace consolidation [it

  17. Primary Pulmonary Amebiasis Complicated with Multicystic Empyema

    Directory of Open Access Journals (Sweden)

    Ali Zakaria

    2016-01-01

    Full Text Available Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid for E. histolytica cysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease.

  18. Perfusion lung scintigraphy in primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Ogawa, Y.; Hayashida, K.; Uehara, T.; Shimonagata, T.; Nishimura, T.; Osaka Univ., Suita

    1993-01-01

    15 cases of primary pulmonary hypertension were classified into two groups by patterns of perfusion lung scintigraphy. Perfusion scintigrams showed multiple, small, ill-defined defects (mottled + ve) pattern in eight cases, and the remaining seven cases had a normal (mottled - ve) pattern. The mean pulmonary arterial pressure in patients with a mottled pattern (54 ± 10 mmHg) was higher than in those with a normal pattern (42 ± 9 mmHg, p < 0.05). There were no significant differences between the two groups in right ventricular ejection fraction, partial pressures of oxygen in the arterial blood or alveolo-arterial oxygen difference. All the patients with a mottled pattern died within 2 years following the lung scintigraphy. There was a significant difference in the survival curves between the two groups. (author)

  19. Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension.

    Science.gov (United States)

    Castelain, V; Hervé, P; Lecarpentier, Y; Duroux, P; Simonneau, G; Chemla, D

    2001-03-15

    The purpose of this time-domain study was to compare pulmonary artery (PA) pulse pressure and wave reflection in chronic pulmonary thromboembolism (CPTE) and primary pulmonary hypertension (PPH). Pulmonary artery pressure waveform analysis provides a simple and accurate estimation of right ventricular afterload in the time-domain. Chronic pulmonary thromboembolism and PPH are both responsible for severe pulmonary hypertension. Chronic pulmonary thromboembolism and PPH predominantly involve proximal and distal arteries, respectively, and may lead to differences in PA pressure waveform. High-fidelity PA pressure was recorded in 14 patients (7 men/7 women, 46 +/- 14 years) with CPTE (n = 7) and PPH (n = 7). We measured thermodilution cardiac output, mean PA pressure (MPAP), PA pulse pressure (PAPP = systolic - diastolic PAP) and normalized PAPP (nPAPP = PPAP/MPAP). Wave reflection was quantified by measuring Ti, that is, the time between pressure upstroke and the systolic inflection point (Pi), deltaP, that is, the systolic PAP minus Pi difference, and the augmentation index (deltaP/PPAP). At baseline, CPTE and PPH had similar cardiac index (2.4 +/- 0.4 vs. 2.5 +/- 0.5 l/min/m2), mean PAP (59 +/- 9 vs. 59 +/- 10 mm Hg), PPAP (57 +/- 13 vs. 53 +/- 13 mm Hg) and nPPAP (0.97 +/- 0.16 vs. 0.89 +/- 0.13). Chronic pulmonary thromboembolism had shorter Ti (90 +/- 17 vs. 126 +/- 16 ms, p PPAP (0.26 +/- 0.01 vs. 0.09 +/- 0.07, p < 0.01). Our study indicated that: 1) CPTE and PPH with severe pulmonary hypertension had similar PA pulse pressure, and 2) wave reflection is elevated in both groups, and CPTE had increased and anticipated wave reflection as compared with PPH, thus suggesting differences in the pulsatile component of right ventricular afterload.

  20. High-grade primary pulmonary leiomyosarcoma

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    Rodrigo Afonso da Silva Sardenberg

    2011-12-01

    Full Text Available Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

  1. Primary bronchial carcinoma or pulmonary metastases

    International Nuclear Information System (INIS)

    Hasse, J.

    1987-01-01

    Operative treatment offers the best chance for long term survival in lung cancer of early stage. In the same way surgery may be the most efficient treatment of lung metastases from tumors of extrapulmonary site. The preoperative investigations have to prove that in case of lung cancer this is restricted to one hemithorax and in lung metastases that these are restricted to the lungs exclusively. They also have to prove that the lung function allows adequate resection. This is mainly lobectomy and pneumonectomy, sometimes sleeve resection and rarely segmentectomy for primary lung cancers. Resection of metastases preferably is by wedge excision or enucleation. In bilateral lesions median sternotomy is the favoured approach to both lungs in a single session. Long term results in primary lung cancer depend on the tumor stage. As a rule of thumb by each step of tumor stage the 5-year-survival rate is cut to half. In regard to histology small cell undifferentiated carcinomas are considered surgical indications only in the very early stage and need to be treated by adjuvant chemotherapy. The operative mortality is correlated to the extent of resection and by average is higher for primary carcinoma of the lung because of the usually higher age level and additional pulmonary damage. Patients operated for pulmonary metastases, however, are in lower age range and due to less functional risks, the operative mortality in most series is between 0 and 3%. Early detection of lung cancer, i.e., immediate and expert exploration of suspicious X-ray findings or respiratory symptoms particularly in smokers and with asbestos exposed individuals will contribute to an increasing efficacy of surgical treatment. (orig.) [de

  2. Primary pulmonary neoplasia in the dog and cat

    International Nuclear Information System (INIS)

    Mehlhaff, C.J.; Mooney, S.

    1985-01-01

    This article covers the pertinent clinical, physical, and radiographic findings in dogs and cats with primary pulmonary neoplasia. Diagnostic and treatment recommendations are made. Although primary pulmonary neoplasia is rare in both the dog and cat, it appears to be diagnosed with increasing frequency. Early detection and surgical treatment of carefully selected cases can prolong a good quality of life

  3. New approaches to therapy of primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Konopleva, L.F.; Karpenko, V.V.; Shamaev, A.N.

    1990-01-01

    Application of hemocarboperfusion, plasmapheresis and UV-irradiated blood autotransfusion were studied in patients with primary pulmonary hypertension. The immediate and long-term outcomes of the therapy were analysed. Indications were defined for the usage of extracorporeal techniques in the multimodulity treatment of patients with primary pulmonary hypertension

  4. Tumour microembolism presenting as "primary pulmonary hypertension"

    OpenAIRE

    Hibbert, M.; Braude, S.

    1997-01-01

    Pulmonary tumour microembolism is a rare cause of pulmonary hypertension. A case of rapidly progressive pulmonary hypertension in a patient with a past history of breast carcinoma is presented. Despite active consideration and investigation for malignancy as a cause, correct diagnosis was only made at necropsy. 




  5. Primary prevention of chronic obstructive pulmonary disease in primary care.

    Science.gov (United States)

    van der Molen, Thys; Schokker, Siebrig

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is a prevalent disease, with cigarette smoking being the main risk factor. Prevention is crucial in the fight against COPD. Whereas primary prevention is targeted on whole populations, patient populations are the focus of primary care; therefore, prevention in this setting is mainly aimed at preventing further deterioration of the disease in patients who present with the first signs of disease (secondary prevention). Prevention of COPD in primary care requires detection of COPD at an early stage. An accurate definition of COPD is crucial in this identification process. The benefits of detecting new patients with COPD should be determined before recommending screening and case-finding programs in primary care. No evidence is available that screening by spirometry results in significant health gains. Effective treatment options in patients with mild disease are lacking. Smoking cessation is the cornerstone of COPD prevention. Because cigarette smoking is not only a major cause of COPD but is also a major cause of many other diseases, a decline in tobacco smoking would result in substantial health benefits.

  6. Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

    International Nuclear Information System (INIS)

    Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

    1985-01-01

    Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism

  7. Osteosarcoma Overview.

    Science.gov (United States)

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

    2017-06-01

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

  8. Primary mediastino pulmonary tuberculosis in infancy

    International Nuclear Information System (INIS)

    Bourliere-Najean, B.; Boespflug, M.D.; Dubus, J.C.; Roybet, D.; Panuel, M.; Faure, F.; Kervella, H.; Devred, P.

    1995-01-01

    Primary mediastino pulmonary tuberculosis in infancy is increasing in France. Bacteriological diagnosis is difficult. The aim of the study is to assess the value of chest radiograph and CTscan for diagnosis of tuberculosis. We studied 15 infants, 3 month old to 18 month old, between November 1990 and June 1992. On plain film, lymphadenopathies were present in 13 cases and parenchymal disease in 10 cases, parenchymal nodular densities in 6 cases and pleural effusion in one case, displacement of the trachea in 6 cases. We found CTscan to be useful in delineating the lymphadenopathies and parenchymal changes. In 2 cases lymphadenopathies and in 2 cases alveolar condensation were discovered on CT scan as plain film was normal. In all cases lymphadenopathies were present in CTscan, often in right side and in al cases, lymphadenopathies were hypodense with peripheral enhancement. In conclusion, the association of right paratracheal nodes with displacement of trachea and alveolar consolidation is common in tuberculosis in infants. These findings when seen on chest radiographs must lead to perform a CTscan and suggest the diagnosis. (Authors). 19 refs., 5 figs., 4 tabs

  9. Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

    International Nuclear Information System (INIS)

    Hiraki, T.; Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

    2004-01-01

    A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred

  10. CT diagnosis of primary lung cancer coexisting with pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Kim, Sun Joo; Kim, Young Sook; Oh, Jae Hee; Kim, Eun Kyoung; Kim, Young Chul

    1992-01-01

    When bronchogenic carcinoma is coexisting with pulmonary tuberculosis, it is difficult to differentiate bronchogenic carcinoma from pulmonary tuberculosis radiographically. Thus, the object of this study is to define differential diagnosis of bronchogenic carcinoma by computed tomography. We analyzed CT scans of 27 patients with radiologic findings of pulmonary tuberculosis and mass of which twelve cases were pulmonary tuberculosis and fifteen cases were primary lung cancer. The location of parenchymal infiltration and the mass was the same in 60%(9/15) of the primary lung cancer in cases and 83%(10/12) of the pulmonary tuberculosis cases. The common location of the mass was the both upper lobes in 92%(11/12) of the pulmonary tuberculosis cases and 53%(8/15) of the primary lung cancer cases. The common locations of the mediastinal lymphadenopathy were 4R, 2R of the pulmonary tuberculosis cases and 4R, 10R of the primary lung cancer cases. In the feature of post enhanced lymph nodes, homogenous increased density was more frequent in primary lung cancer. Measurements of the maximum thickness part of the cavity wall was not a reliable indication of malignancy

  11. Histoplasmosis lung. Primary pulmonary infection: histoplasmoma

    International Nuclear Information System (INIS)

    Massaro C Maurizio; Diaz Pacheco, Carlos; Roldan, Miguel

    2005-01-01

    Histoplasmosis is a primarily pulmonary originated mycosis which is acquired by inhalation. In the majority of the cases infection goes unnoticed or gets manifested by slight respiratory symptoms. Histoplasmoma is a relatively common form of acute lung histoplasmosis, in form of nodules, which is generally accompanied by calcification that can increase in size and simulate a lung neoplasia. This article describes a case of an immunocompromised patient with this kind of pulmonary mycosis

  12. Diagnostic Value of Ex-Vivo Three-Dimensional Micro-Computed Tomography Imaging of Primary Nonhematopoietic Human Bone Tumors: Osteosarcoma versus Chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Langheinrich, A. C.; Stolle, C.; Kampschulte, M.; Lommel, D.; Rau, W. S.; Bassaly, B. (Depts. of Radiology and Pathology, Univ. of Giessen, Giessen (Germany))

    2008-10-15

    Background: Osteosarcoma and chondrosarcoma are the most common nonhematopoietic primary malignancies of bone. However, unusual radiographic appearances can lead to delay in diagnosis and confusion with benign diseases. Purpose: To evaluate the feasibility of micro-computed tomography (CT) for the analysis of primary, nonhematopoietic human bone tumors ex vivo. Material and Methods: Samples from 12 human bone specimens (osteosarcoma, n=6; chondrosarcoma, n=6) obtained for diagnostic purposes were scanned using industrial X-ray film without amplifier foil and scanned with micro-CT (7- and 12-mum-cubic voxels). Trabecular bone CT 'density' and tumor matrix CT 'density' were determined, and results were compared with those obtained from a detailed conventional histopathologic analysis of corresponding cross-sections. The significance of differences in grayscale measurements was tested with analysis of variance. Results: Micro-CT provided quantitative information on bone morphology equivalent to histopathological analysis. We established grayscale measurements by which tumor matrices of chondrosarcoma and osteosarcoma could be radiographically categorized following histological classifications (P<0.001). Conclusion: Micro-CT is feasible for the analysis and differentiation of human osteosarcoma and chondrosarcoma

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

    Science.gov (United States)

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

    2015-04-01

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

  14. Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a.

    Science.gov (United States)

    Chang, Yuewen; Zhao, Yongfang; Gu, Wei; Cao, Yuelong; Wang, Shuqiang; Pang, Jian; Shi, Yinyu

    2015-01-01

    Osteosarcoma (OS) is the second leading cause of cancer-related death in children and young adults. Chemoresistance is the most important cause of treatment failure in OS, largely resulting from presence of cancer stem cells (CSCs). However, CSCs isolated from cancer cell lines do not necessarily represent those from primary human tumors due to accumulation of genetic aberrations that increase with passage number. Therefore, studies on CSCs from primary OS may be more important for understanding the mechanisms driving the chemoresistance of CSCs in OS. We established a primary culture of OS cells, known as C1OS, from freshly resected tumor tissue. We further isolated CSCs from C1OS cells (C1OS-CSCs). We analyzed the effects of bufalin, a traditional Chinese medicine, on the stemness of C1OS-CSCs. We also analyzed the microRNA (miR) targets of bufalin on the stemness of C1OS-CSCs. Moreover, we examined these findings in the OS specimen. Bufalin inhibited the stemness of C1OS-CSCs. Moreover, we found that miR-148a appeared to be a target of bufalin, and miR-148a further regulated DNMT1 and p27 to control the stemness of OS cells. This mechanism was further confirmed in OS specimen. Our data suggest that bufalin may be a promising treatment for OS, and its function may be conducted through regulation of miR-148a. © 2015 S. Karger AG, Basel.

  15. Osteosarcoma (Osteogenic sarcoma

    Directory of Open Access Journals (Sweden)

    Picci Piero

    2007-01-01

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

  16. The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.

    Science.gov (United States)

    Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui

    2017-05-10

    This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.

  17. High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

    Science.gov (United States)

    Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

    2014-08-01

    Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. Primary pulmonary adenocarcinoma in a 16-year-old boy

    DEFF Research Database (Denmark)

    Måreng, Ane Stillits; Langer, Seppo W; Bodtger, Uffe

    2016-01-01

    -old boy who presented with metastatic primary pulmonary adenocarcinoma (T3N3M1a) and was treated aggressively, including radiation therapy for local and distant recurrence. He had complete remission, had completed his education, was employed full-time, and suffered only from mild side effects to treatment....

  19. Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Mohammad Taheri

    2010-01-01

    Full Text Available Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

  20. Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a

    Directory of Open Access Journals (Sweden)

    Yuewen Chang

    2015-06-01

    Full Text Available Background/Aims: Osteosarcoma (OS is the second leading cause of cancer-related death in children and young adults. Chemoresistance is the most important cause of treatment failure in OS, largely resulting from presence of cancer stem cells (CSCs. However, CSCs isolated from cancer cell lines do not necessarily represent those from primary human tumors due to accumulation of genetic aberrations that increase with passage number. Therefore, studies on CSCs from primary OS may be more important for understanding the mechanisms driving the chemoresistance of CSCs in OS. Methods: We established a primary culture of OS cells, known as C1OS, from freshly resected tumor tissue. We further isolated CSCs from C1OS cells (C1OS-CSCs. We analyzed the effects of bufalin, a traditional Chinese medicine, on the stemness of C1OS-CSCs. We also analyzed the microRNA (miR targets of bufalin on the stemness of C1OS-CSCs. Moreover, we examined these findings in the OS specimen. Results: Bufalin inhibited the stemness of C1OS-CSCs. Moreover, we found that miR-148a appeared to be a target of bufalin, and miR-148a further regulated DNMT1 and p27 to control the stemness of OS cells. This mechanism was further confirmed in OS specimen. Conclusion: Our data suggest that bufalin may be a promising treatment for OS, and its function may be conducted through regulation of miR-148a.

  1. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Paolo Pazzi

    2013-04-01

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

  3. Bronchoplasty for Primary Broncho-Pulmonary Tumors

    International Nuclear Information System (INIS)

    ABDEL RAHMAN, A.M.

    2010-01-01

    Parenchyma-sparing procedures are widely used in patients with low-grade malignancies of the airway when anatomically suited lesions exist. This study was conducted to evaluate the short-term and the long-term results of bronchoplastic procedures for patients with centrally located primary bronchopulmonary tumors. Methods: Between 2000 and 2009, 36 patients with primary lung tumors required bronchoplasty were retrospectively analyzed. Preoperative assessment included computed tomography (CT) of the chest, bronchoscopy, and spirometry. Pre operative diagnosis was achieved by bronchoscopy for all patients, mediastinoscopy was done for patients with primary lung cancer. Neo adjuvant chemotherapy was given for 6 patients with non small cell lung cancer (NSCLC). Results: We had 15 males and 21 female, the mean age was 37 years and the mean hospital stay was 7.2 days. Operative procedures performed were:Sleeve lobectomy in 30 patients (13 right, 17 left), partial sleeve right pneumonectomy in 3 and bronchial resection with re-anastomosis in 3 (2 left, 1 right). Twelve patients (33.3%) suffered post-operative problems. There was one operative related mortality. Post operative pathology revealed: 27 patients with typical carcinoid, 2 with atypical carcinoid, 4 with squamous cell carcinoma, 2 with adenocarcifioma and one with hamartoma. Pathological TNM staging revealed: 17 patients with stage 1A, 11 with IB, 5 with IIA and 2 with stage IIIA. Follow-up data were available for all patients except two. Two patients died with disseminated disease 1.5 year and 2 years after surgery. The patient with hamartoma developed local recurrence 5 years later and re-excision was done. One patient with lung cancer developed bone metastases and was alive with disease, while the remaining 30 patient's were alive and disease free. The overall 5 years survival was 83.3%. Conclusion: Bronchoplastic resections achieve local control and long-term survival comparable to the standard resections in

  4. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

    Science.gov (United States)

    Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2012-09-19

    Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  5. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases

    Directory of Open Access Journals (Sweden)

    Gong Li

    2012-09-01

    Full Text Available Abstract Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  6. Tomographic findings of lobar consolidation in primary pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Pereira, Bruno Alberto Falcao; Macedo, Solange Goncalves David de; Penna, Claudia Renata Rezende

    2009-01-01

    Objective: To describe tomographic findings of lobar consolidation as early manifestation of primary pulmonary tuberculosis. Materials and methods: The present study was developed at Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2002 and 2006, retrospectively evaluating tomographic findings in four children aged from 3 to 14 months with lobar consolidation as an early manifestation of primary pulmonary tuberculosis. Results: The most frequently found radiological pattern was lobar consolidation with calcifications, cavitation and intermingle necrotic areas, associated with bulging fissure. Signs of bronchogenic dissemination and lymph node enlargement were observed in all of the four children. Consolidation with a pseudotumor aspect and masslike effect was observed in one case. Conclusion: The cases included in the present study have demonstrated that primary pulmonary tuberculosis manifested as lobar consolidation presents typical tomographic images such as cavitation, hypodense areas and calcifications intermingled with consolidation. The association with lymph node enlargement with central necrosis and signs of bronchogenic dissemination reinforce the diagnosis of tuberculosis. (author)

  7. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.

    Science.gov (United States)

    Robl, Bernhard; Botter, Sander Martijn; Boro, Aleksandar; Meier, Daniela; Neri, Dario; Fuchs, Bruno

    2017-06-01

    The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2-derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs) as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF-dependent attraction of pulmonary CD4 + , CD8 + , and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4 + or CD8 + cells or F4/80 + and Ly6G + myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G + myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Bernhard Robl

    2017-06-01

    Full Text Available The targeted delivery of tumor necrosis factor-α (TNF-α with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2–derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF–dependent attraction of pulmonary CD4+, CD8+, and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4+ or CD8+ cells or F4/80+ and Ly6G+ myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G+ myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases.

  9. Outcomes of Pulmonary Valve Replacement for Correction Pulmonary Insufficiency after Primary Repair of Tetralogy of Fallot (TOF)

    OpenAIRE

    Mohammad Abbassi Teshnisi; Aliasghar Moeinipour; Hamid Hoseinikhah; Seyedeh Zahra Aemmi; Shahla Shirin Bahador; Nahid Zirak

    2016-01-01

    Background Total correction of Tetralogy of Fallot (TOF) anomaly in early childhood has been practiced in many centers with good results, but in some of patients after few years sever Pulmonary valve insufficiency occurred. Materials and Methods At a cross- sectional study from January 2015 to January 2016, 10 patients who had history of primary repair of TOF with free pulmonary insufficiency (PI) that underwent of pulmonary valve replacement (PVR) with bioprosthetic valves were evaluated. Re...

  10. 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.

  11. Thallium-201 myocardial scintigram in primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Fujii, Isao; Handa, Shunnosuke; Yamazaki, Hajime; Nakamura, Yoshiro

    1984-01-01

    Right heart catheterization is needed for the diagnosis of pulmonary hypertension in patients with primary pulmonary hypertension (PPH), though the procedure was reported to have an unusually high risk. We examined the usefulness of thallium-201 myocardial scintigraphy for the evaluation of right ventricular overloading in patients with PPH. This study includes 5 patients with PPH, diagnosed by the clinical criteria of research committee of PPH in the Ministry of Health and Welfare in Japan (1976). Autopsy was done and diagnosis was confirmed in 4 cases. The right ventricular (RV) free wall was visualized in all cases. They were divided into 2 groups by the degree of visualization. The cases with heavier visualization had a higher pulmonary arterial resistence. The shape of the interventricular septum was deformed in all cases. It was straight in 3 cases and convex to the left ventricle (LV) in 3. In the later group, a systolic LV-RV pressure difference was less than 25 mmHg. One of these 3 cases showed reversed pressure difference. We concluded that thallium-201 myocardial scintigraphy could non-invasively assess the degree of RV overloading in PPH. (author)

  12. Pulmonary embolism as the primary presenting feature of nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Pallavi Periwal

    2016-01-01

    Full Text Available A 36-year-old previously healthy male presented with subacute onset of shortness of breath and chest pain. He was diagnosed with bilateral extensive pulmonary embolism (PE. In the absence of any predisposing factors, an extensive workup for unprovoked thrombophilia was done. During the course of his illness, the patient developed anasarca and was diagnosed to be suffering from nephrotic syndrome (NS, secondary to membranous glomerulopathy. Although, thrombotic complications are commonly associated with NS, it is unusual for PE to be the primary presenting feature in these patients.

  13. Perfusion lung scintigraphy in primary broncho-pulmonary cancer

    International Nuclear Information System (INIS)

    Lapergue, Paul.

    1976-01-01

    Research on primary broncho-pulmonary cancer has called extensively on scintigraphy and it seemed interesting to weigh up the pros and cons of the technique in this particular case. Our intention is to sum up objectively from recent documents the applications of scintigraphy in the study of primary broncho-pulmonary cancers and to attempt, on the basis of the results compiled, to show what benefits have been gained from this technique and to find out whether it has any pre-surgical value and of what kind. The technique was invariable; the tracer consists of human albumin macro-aggregates labelled with technetium 99m which by its short half-life and slight penetration enables four exposures to be taken during the same examination (front, back, right and left profiles), thus reducing the risks of mistaken diagnoses due to the use of a single incidence. Similarly the detection method was always the scintillation camera which explores the whole organ at once, considerably shortening the examination time. Lung scintigraphy by perfusion of labelled human albumin macro-aggregates offers the great advantage of being simple to use and harmless. It is easy to understand the important place it has taken in the range of methods available for lung circulation exploration [fr

  14. Early Detection of Chronic Obstructive Pulmonary Disease in Primary Care.

    Science.gov (United States)

    Kobayashi, Seiichi; Hanagama, Masakazu; Yanai, Masaru

    2017-12-01

    Objective To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan. Methods Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device. Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography. Results A total of 111 patients with possible COPD were referred for close examination. Among these patients, 27 patients were newly diagnosed with COPD. The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients. COPD patients also had more comorbid conditions. A diagnosis of COPD was significantly associated with a high COPD-PS score (pearly detection of undiagnosed COPD in primary care.

  15. Pleiotropic effects of bisphosphonates on osteosarcoma.

    Science.gov (United States)

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

    2014-06-01

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

  16. BNCT of canine osteosarcoma

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  17. Primary pulmonary sarcoma metastasising to the skin during pregnancy.

    Science.gov (United States)

    Arikan, Ilker; Barut, Aykut; Harma, Muge; Harma, Mehmet Ibrahim; Erdem, Zuhal; Gezer, Sener

    2012-12-01

    Lung cancer during pregnancy is a rare situation which is being increasingly reported during the past two decades due to a rising trend of cigarette smoking among young women and the tendency to delay pregnancy to a later age in life. We describe the case of a 32-year-old woman with primary pulmonary sarcoma, diagnosed at 31st week of pregnancy. X-ray chest and thoracic magnetic resonance imaging revealed a 9 x 6 cm mass in the left mediastinum, with tracheal shift, and pleural effusion. Biopsy performed during broncoscopy, was reported as mesenchymal tumour. She delivered a baby by Caesarean section at the 32nd week of gestation due to the development of superior vena cava syndrome. A skin biopsy taken 3 weeks later from the nodular lesion at the periumblical region was reported as a tumour metastasis. She received radiotherapy for 10 days, but died in the intensive care unit. Malignancies, even those as uncommon as a pulmonary sarcoma, should be considered in the differential diagnosis of pleural effusion during pregnancy.

  18. Acute hemodynamic response to vasodilators in primary pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Kulkarni H

    1996-01-01

    Full Text Available Acute hemodynamic effects of high flow oxygen (O2 inhalation, sublingual isosorbide dinitrate (ISDN, intravenous aminophylline (AMN and sublingual nifedipine (NIF were studied in 32 patients with primary pulmonary hypertension (PPH. In 30 out of 32 patients the basal ratio of pulmonary to systemic vascular resistance (Rp/Rs was > 0.5 (mean = 0.77 +/- 0.20. Oxygen caused significant decrease in the mean resistance ratio to 0.68 +/- 0.20 (p = 0.005. ISDN, AMN and NIF caused increase in the resistance ratio to 0.79 +/- 0.26; 0.78 +/- 0.26; and 0.80 +/- 0.23 respectively. O2, ISDN, AMN and NIF caused a fall of Rp/Rs in 21 (65.6%, 10 (31.2%, 10(31.2% and 9(28.1% patients respectively. Thus, of the four drugs tested high flow O2 inhalation resulted in fall of Rp/Rs in two thirds of patients whereas ISDN, AMN and NIF caused a mean rise in Rp/Rs. One third of patients did respond acutely to the latter three drugs. Acute hemodynamic studies are useful before prescribing vasodilators in patients with PPH since more of the commonly used drugs like ISDN, AMN, NIF could have detrimental hemodynamic responses in some patients. However, great caution should be exercised before performing hemodynamic study as the procedure has definite mortality and morbidity.

  19. Adjuvant chemotherapy for osteosarcoma.

    Science.gov (United States)

    Eilber, F R; Rosen, G

    1989-08-01

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

  20. Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis

    International Nuclear Information System (INIS)

    Berteloot, Laureline; Emond-Gonsard, Sophie; Mamou-Mani, Tania; Lambot, Karen; Grevent, David; Taam, Rola Abou; Le Bourgeois, Muriel; Elie, Caroline; Delacourt, Christophe; Blic, Jacques de; Brunelle, Francis

    2014-01-01

    Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of periodic acid-schiff-positive lipoproteinaceous material in the alveoli. Early diagnosis allows setting up of therapeutic lung lavages, which reduces the need for oxygen supplementation and weight gain. To provide a description of radiological features by CT at the onset of primary PAP in children. The clinical and radiological data of 24 patients, including 16 boys and 8 girls (median age: 12 months), diagnosed with a primary form of PAP between April 1992 and May 2012 in a tertiary referral hospital, were retrospectively reviewed. CT images were examined for the presence of alveolar and interstitial elementary lesions. Correlation between clinical and radiological findings was assessed. The types of elementary lesions detected were: ground-glass opacities (n = 24), intralobular lines (n = 24), thickened interlobular septa (n = 22), thickened fissures (n = 21), airspace consolidation (n = 16), hyperinflation (n = 16), cystic lesions (n = 2) and micronodules (n = 1). A crazy-paving pattern was found in 92% of cases. Consolidation and hyperinflation were especially detected in younger children (median age, 8 months, P < 0.01). A density dependent gradient was found. The distribution of the lesions was symmetrical. There was no correlation between radiological and clinical data of severity of the disease. CT findings are suggestive of diagnosis of PAP in immunocompetent children with chronic respiratory failure. (orig.)

  1. Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Berteloot, Laureline; Emond-Gonsard, Sophie; Mamou-Mani, Tania; Lambot, Karen; Grevent, David [Hopital Necker Enfants-Malades, Department of Pediatric Radiology, Paris (France); Taam, Rola Abou; Le Bourgeois, Muriel [Hopital Necker Enfants-Malades, Department of Pediatric Pneumology and Allergology, Paris (France); Elie, Caroline [Hopital Necker Enfants-Malades, Department of Biostatistics, Paris (France); Paris Descartes University, Paris (France); Delacourt, Christophe; Blic, Jacques de [Hopital Necker Enfants-Malades, Department of Pediatric Pneumology and Allergology, Paris (France); Paris Descartes University, Paris (France); Brunelle, Francis [Hopital Necker Enfants-Malades, Department of Pediatric Radiology, Paris (France); Paris Descartes University, Paris (France)

    2014-07-15

    Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of periodic acid-schiff-positive lipoproteinaceous material in the alveoli. Early diagnosis allows setting up of therapeutic lung lavages, which reduces the need for oxygen supplementation and weight gain. To provide a description of radiological features by CT at the onset of primary PAP in children. The clinical and radiological data of 24 patients, including 16 boys and 8 girls (median age: 12 months), diagnosed with a primary form of PAP between April 1992 and May 2012 in a tertiary referral hospital, were retrospectively reviewed. CT images were examined for the presence of alveolar and interstitial elementary lesions. Correlation between clinical and radiological findings was assessed. The types of elementary lesions detected were: ground-glass opacities (n = 24), intralobular lines (n = 24), thickened interlobular septa (n = 22), thickened fissures (n = 21), airspace consolidation (n = 16), hyperinflation (n = 16), cystic lesions (n = 2) and micronodules (n = 1). A crazy-paving pattern was found in 92% of cases. Consolidation and hyperinflation were especially detected in younger children (median age, 8 months, P < 0.01). A density dependent gradient was found. The distribution of the lesions was symmetrical. There was no correlation between radiological and clinical data of severity of the disease. CT findings are suggestive of diagnosis of PAP in immunocompetent children with chronic respiratory failure. (orig.)

  2. 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

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

    Science.gov (United States)

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

    2009-11-01

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

  4. High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.

    Science.gov (United States)

    Boye, Kjetil; Del Prever, Adalberto Brach; Eriksson, Mikael; Saeter, Gunnar; Tienghi, Amelia; Lindholm, Paula; Fagioli, Franca; Skjeldal, Sigmund; Ferrari, Stefano; Hall, Kirsten Sundby

    2014-05-01

    Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT. The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. © 2013 Wiley Periodicals, Inc.

  5. Primary pulmonary tuberculosis in infancy: A resurgent disease in the urban United States

    International Nuclear Information System (INIS)

    Amodio, J.; Abramson, S.; Berdon, W.

    1986-01-01

    Primary pulmonary tuberculosis in infancy still exists in the urban United States, reflecting new immigrations from less developed areas. The clinical diagnosis may be difficult and routine chest radiographs may be confusing. We found magnification high KV filtered radiography to be very useful in delineating the primary complex and its effect on the tracheobronchial tree. Twelve infants and small children with primary pulmonary tuberculosis were seen in the years 1978-1984. (orig.)

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

    International Nuclear Information System (INIS)

    Ram Kumar, Ram Mohan; Fuchs, Bruno

    2015-01-01

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

  7. Nocardia brasiliensis primary pulmonary nocardiosis with subcutaneous involvement in an immunocompetent patient.

    Science.gov (United States)

    Amatya, R; Koirala, R; Khanal, B; Dhakal, S S

    2011-01-01

    This is a report of an unusual case of Nocardia brasiliensis causing primary pulmonary nocardiosis with disseminated subcutaneous lesions in an immunocompetent patient. This case highlights the importance of considering nocardiosis as a differential diagnosis in patients with pulmonary and cutaneous lesions and the need for vigorous management for complete cure.

  8. Nocardia brasiliensis primary pulmonary nocardiosis with subcutaneous involvement in an immunocompetent patient

    Directory of Open Access Journals (Sweden)

    R Amatya

    2011-01-01

    Full Text Available This is a report of an unusual case of Nocardia brasiliensis causing primary pulmonary nocardiosis with disseminated subcutaneous lesions in an immunocompetent patient. This case highlights the importance of considering nocardiosis as a differential diagnosis in patients with pulmonary and cutaneous lesions and the need for vigorous management for complete cure.

  9. [Jaw osteosarcomas].

    Science.gov (United States)

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

    2011-11-01

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

  10. Use of routine histopathology and factor VIII-related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs.

    Science.gov (United States)

    Giuffrida, M A; Bacon, N J; Kamstock, D A

    2017-12-01

    Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII-RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA. © 2016 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    M.A. Lima

    1998-03-01

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

  12. Osteosarcoma associated with hyperparathyroidism

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  13. Raman spectroscopy for grading of live osteosarcoma cells.

    Science.gov (United States)

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

    2015-04-18

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

  14. Primary pulmonary mucoepidermoid carcinoma: an analysis of 21 cases

    Directory of Open Access Journals (Sweden)

    Xi Jun-jie

    2012-11-01

    Full Text Available Abstract Background The optimal treatment for pulmonary mucoepidermoid carcinoma (MEC, a rare type of tumor, has not been established yet. This study analyzed the survival of pulmonary MEC patients and attempted to find clues for optimal treatment. Methods A total of 21 patients with pulmonary MEC from November 2004 to January 2011 were included in the investigation. Immunohistochemistry, epidermal growth factor receptor (EGFR mutation, and survival were retrospectively studied. Results Among the 21 pulmonary MEC patients, 17 were diagnosed with low-grade malignancy and 4 with high-grade malignancy through pathological examination. The prognosis was found to be poor in the presence of lymph nodes. The expression rates of EGFR and HER2 were 28.6% and 0%, respectively, which correlated with neither grade nor prognosis. The mutation rate of EGFR was 0. Log-rank test results indicated that age, grade, lymph node metastasis, and tumor-node-metastasis stage were prognostic factors. Conclusion Age, grade, lymph node metastasis and tumor-node-metastasis stage correlate with the survival of pulmonary MEC patients. Trial registration This study was approved and registered by the Ethics Committee of Zhongshan Hospital. Written informed consent was obtained from all participants prior to treatment.

  15. Outcomes of Pulmonary Valve Replacement for Correction Pulmonary Insufficiency after Primary Repair of Tetralogy of Fallot (TOF

    Directory of Open Access Journals (Sweden)

    Mohammad Abbassi Teshnisi

    2016-09-01

    Full Text Available Background Total correction of Tetralogy of Fallot (TOF anomaly in early childhood has been practiced in many centers with good results, but in some of patients after few years sever Pulmonary valve insufficiency occurred. Materials and Methods At a cross- sectional study from January 2015 to January 2016, 10 patients who had history of primary repair of TOF with free pulmonary insufficiency (PI that underwent of pulmonary valve replacement (PVR with bioprosthetic valves were evaluated. Results Themean age of patients was 6.5 + 0.753 years old (ranged 8-12 years old and male to female ratio was 6/4. The mean of Intensive care unit (ICU stay and Hospital stay was 4.5+ 0.712 days (ranged 3-8 and 11.5+ 0.357 days (ranged 9- 16. Mean of cardiopulmonary bypass time and operation time was 45 + 0.684 min (ranged 32-60 and 83 + 0.317 min (ranged 65-112. In this study we did not find any mortality and ventricular arrhythmia and Heart block. There was only one case (10% with superficial wound infection that was controlled. At 6 months follow up, all of patients were alive, but Echocardiography sign of Right Ventricular (RV failure was present in 2 patients (20% recently. Conclusion Although for Pulmonary insufficiency after primary TOF repair there is controversial in studies, but we had good results of PVR with Bioprosthesis in TOF patients.

  16. 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

  17. Primary Pulmonary Synovial Sarcoma: A Case with Unique and Impressive Computed Tomography Findings

    Directory of Open Access Journals (Sweden)

    Jaspreet S Kambo

    2015-01-01

    Full Text Available Primary pulmonary synovial sarcoma (PPSS is a rare malignancy. Its etiology, imaging features and optimal treatment are not well understood. Pulmonary pseudoaneurysms and lymphadenopathy are rare complications of synovial sarcomas. A 40-year-old woman with mild hemoptysis and thoracic back pain underwent a computed tomography scan that revealed multiple pulmonary lesions, paraesophageal lymphadenopathy and incidental bilateral pulmonary emboli. A diagnosis of PPSS was made through the identification of an SS18 translocation by fluorescence in situ hybridization. She was started on adriamycin, ifosfamide and mesna chemotherapy. Over the subsequent two months, she developed three pulmonary artery pseudoaneurysms, ultimately requiring endovascular coiling. Seven months after starting treatment, the patient was asymptomatic. The lesions and lymphadenopathy decreased in size. The present case highlights complications of a rare malignancy and demonstrates positive response to ifosfamide-based chemotherapy in the setting of PPSS.

  18. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  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. Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report.

    Science.gov (United States)

    Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Watanabe, Koji; Miwa, Shinji; Tsuchiya, Hiroyuki

    2015-12-07

    In a previous report, we described a method of reconstruction using tumor-bearing autograft treated by liquid nitrogen for malignant bone tumor. Here we present the first case of bone deformity correction following a tumor-bearing frozen autograft via three-dimensional computerized reconstruction after multiple surgeries. A 16-year-old female student presented with pain in the left lower leg and was diagnosed with a low-grade central tibial osteosarcoma. Surgical bone reconstruction was performed using a tumor-bearing frozen autograft. Bone union was achieved at 7 months after the first surgical procedure. However, local tumor recurrence and lung metastases occurred 2 years later, at which time a second surgical procedure was performed. Five years later, the patient developed a 19° varus deformity and underwent a third surgical procedure, during which an osteotomy was performed using the Taylor Spatial Frame three-dimensional external fixation technique. A fourth corrective surgical procedure was performed in which internal fixation was achieved with a locking plate. Two years later, and 10 years after the initial diagnosis of tibial osteosarcoma, the bone deformity was completely corrected, and the patient's limb function was good. We present the first report in which a bone deformity due to a primary osteosarcoma was corrected using a tumor-bearing frozen autograft, followed by multiple corrective surgical procedures that included osteotomy, three-dimensional external fixation, and internal fixation.

  1. X-ray appearance of the heart in primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Matveeva, L.S.; Kitaeva, I.T.; Efimova, L.G.

    1980-01-01

    Roentgenological picture of heart in 36 patients with primary pulmonary hypertension is studied. The diagnosis has been reaffirmed using catheterization of cavities of the heart and pulmonary artery and in a number of cases in autopsy. Variability of the form and the size of the heart depending on different degrees of hypertrophy and dilatation of the right ventricle with possible relative insufficiency of the tricuspid valve and on different degree of ecstasia of the pulmonary arterial trunk and functional state of myocardium. All this to a certain degree is dependent on the patient age, duration and the character of the disease

  2. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

    NARCIS (Netherlands)

    Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

    2005-01-01

    Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

  3. Primary lung cancer coexisting with active pulmonary tuberculosis.

    Science.gov (United States)

    Varol, Y; Varol, U; Unlu, M; Kayaalp, I; Ayranci, A; Dereli, M S; Guclu, S Z

    2014-09-01

    Lung cancer and pulmonary tuberculosis (TB) comorbidity is a clinical problem that presents a challenge for the diagnosis and treatment of both diseases. To clarify the clinical and survival characteristics of cases with both lung cancer and active pulmonary TB. From 2008 to 2013, 3350 TB patients admitted to the TB Department of the Chest Diseases Hospital of Izmir, Turkey, were evaluated. In 38 (1.1%) male patients, lung cancer and TB were found to coexist. Almost all of the patients were diagnosed at Stage III (n = 14, 36.8%) or IV (n = 17, 44.7%) lung cancer, whereas four (10.6%) had Stage II and three (7.9%) had Stage I disease. Squamous cell lung cancer was the predominant histology (n = 23, 60.7%). The median overall survival among patients was 13.4 months (95%CI 8.09-18.8). One-year survival rates for patients with Stages I, II, III and IV were respectively 100%, 75%, 57% and 40%. The present study demonstrates that lung cancer combined with active pulmonary TB most frequently presents as squamous cell carcinoma, with a male predominance. The overall survival of lung cancer patients did not change even with concomitant active TB.

  4. Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach

    Science.gov (United States)

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

    2016-01-01

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

  5. 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

  6. 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.

  7. Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Koji; Sasaki, Tomoaki; Nabaa, Basim; Aburano, Tamio (Department of Radiology, Asahikawa Medical University and Hospital, Asahikawa (Japan)), Email: taka1019@asahikawa-med.ac.jp; Beek, Edwin Jr. von (Clinical Research Imaging Centre, Queen' s Medical Research Institute, University of Edinburgh, Edinburgh (United Kingdom)); Stanford, William (Department of Radiology, University of Iowa College of Medicine, Iowa City (United States))

    2012-03-15

    Background. In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity. Purpose. To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery. Material and Methods. We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups. Results. Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = -0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter (P <0.01). Conclusion. Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent

  8. Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis

    International Nuclear Information System (INIS)

    Takahashi, Koji; Sasaki, Tomoaki; Nabaa, Basim; Aburano, Tamio; Beek, Edwin Jr. von; Stanford, William

    2012-01-01

    Background. In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity. Purpose. To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery. Material and Methods. We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups. Results. Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = -0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter (P <0.01). Conclusion. Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent

  9. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in the detection of primary pulmonary angiosarcomas

    International Nuclear Information System (INIS)

    Krishnamurthy, Arvind; Nayak, Deepika; Ramshankar, Vijayalakshmi; Majhi, Urmila

    2015-01-01

    Angiosarcoma is a malignant vascular tumor that originates from the mesenchymal cells which have undergone angioblastic differentiation. Pulmonary angiosarcomas are invariably (>90%) metastatic tumors form primaries of the skin, bone, liver, breast, or heart. Primary pulmonary angiosarcomas are exceedingly rare, with just about 20 cases being reported in the literature. We report an additional case with a brief review of the literature of a primary pulmonary angiosarcoma in a 26-year-old lady who presented with intractable hemoptysis. In addition, we highlight the potential of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography as an important diagnostic tool in the evaluation of this tumor and thus contribute to the existing sparse literature on this fascinating yet devastating disease

  10. Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis

    Directory of Open Access Journals (Sweden)

    Anna Hirano

    2017-01-01

    Full Text Available We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks with concomitant ruxolitinib administration, but the pulmonary lesions progressed. Subsequently, the patient was treated with voriconazole (300 mg daily for 3 weeks, but the lesions worsened further. The administration of ruxolitinib was therefore discontinued, and the dosage of voriconazole was increased to 400 mg daily. Three months later, the pulmonary lesions diminished in size. The present case of pulmonary cryptococcosis occurred in a patient treated with ruxolitinib. Treatment of pulmonary cryptococcosis with concomitant JAK inhibitor administration may result in poor treatment efficacy. It might be better to stop administration of JAK inhibitors, if possible, in patients being treated for pulmonary cryptococcosis.

  11. Primary Pulmonary Ewing’s Sarcoma: Rare Cause of Superior Vena Cava Syndrome in Children

    OpenAIRE

    Mehra, Shibani; Atwal, Swapndeep Singh; Garga, Umesh Chandra

    2014-01-01

    Ewing’s sarcoma is a common malignant bone tumour presenting in children and young adults. Rarely extra- skeletal soft tissues and visceral organs can also be the site of origin of Ewing’s sarcoma. Primary pulmonary Ewing’s sarcoma is an extremely rare malignancy which occurs in the paediatric population. We report an unusual case of primary pulmonary Ewing’s sarcoma in a nine year old girl who presented with features of superior vena cava syndrome in the emergency department. The diagnosis w...

  12. Primary Pulmonary Ewing's Sarcoma: Rare Cause of Superior Vena Cava Syndrome in Children.

    Science.gov (United States)

    Mehra, Shibani; Atwal, Swapndeep Singh; Garga, Umesh Chandra

    2014-08-01

    Ewing's sarcoma is a common malignant bone tumour presenting in children and young adults. Rarely extra- skeletal soft tissues and visceral organs can also be the site of origin of Ewing's sarcoma. Primary pulmonary Ewing's sarcoma is an extremely rare malignancy which occurs in the paediatric population. We report an unusual case of primary pulmonary Ewing's sarcoma in a nine year old girl who presented with features of superior vena cava syndrome in the emergency department. The diagnosis was confirmed pathologically both by light microscopy and immunohistochemistry. The patient was put on chemotherapy and surgery was planned but the patient expired within three days of starting chemotherapy.

  13. Preoperative and intraoperative irradiation for osteosarcoma

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  14. Clinical study of pulmonary infection caused by mycobacterium avium complex. Evaluation of radiographic features on the primary pulmonary infection

    International Nuclear Information System (INIS)

    Harada, Yasuko; Harada, Susumu; Kitahara, Yoshinari; Kajiki, Akira; Maruyama, Masao; Takamoto, Masahiro; Ishibashi, Tsuneo

    1996-01-01

    During the 13 year period of 1982 to 1994 we had 103 patients with pulmonary Mycobacterium avium complex (MAC) infections. All met the criteria of atypical mycobacteriosis (Japanese Mycobacteriosis Research Group of the National Chest Hospitals). Of 103 patients 70 had no underlying pulmonary diseases and classified as primary type. Radiographic features of chest X-rays or computed tomography (CT) of primary infection were evaluated. Results obtained were as follows: Primary infection of MAC was classified into two types. One was localized type. This type was further classified into three patterns; tuberculosis-like pattern, pneumonia pattern in the lingual and/or middle lobe and pneumonia pattern in other lobes. Another one was diffuse type. Tuberculosis-like pattern was most common in males. On the other hand, the pneumonia pattern and the diffuse type were most common in females. Four characteristic features were seen as follows (Type 1-4) in the chest CT examination of diffuse pattern. Type 1: Nodules near the pleura. Type 2: Nodules with subpleural thickening. Type 3: Bronchial wall thickening and ectatic change of the draining bronchi. Type 4: Cystic bronchiectatic change associated with atelectasis of the segment or the lobe. Bronchiectatic changes became severe and widespreaded in all lung fields as the disease progressed slowly. These findings were more prevalent in the lingual and/or middle lobe than the other lobes. (author)

  15. Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images.

    Science.gov (United States)

    Murray, T I; Boxt, L M; Katz, J; Reagan, K; Barst, R J

    1994-01-01

    The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 +/- 0.8 cm) was significantly larger than the control MPA (2.9 +/- 0.3 cm, p = 0.02); the PPH MPAI (2.8 +/- 0.7 cm/M2) was significantly greater than the control MPA (1.7 +/- 0.2 cm/M2, p < 0.0001). Control AO (2.2 +/- 0.3 cm) was significantly greater than PPH AO (1.6 +/- 0.4 cm, p < 0.0001); there was no significant difference between control AOI (1.3 +/- 0.2 cm/M2) and PPH AOI (1.2 +/- 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 +/- 0.6) was significantly greater than the control MPA/AO (1.3 +/- 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

  16. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    DEFF Research Database (Denmark)

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

    2010-01-01

    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo...

  17. Primary Sjogrens syndrome, with lymphocytic interticial pneumonia and cystic pulmonary disease

    International Nuclear Information System (INIS)

    Vallejo, Jimi Mejia; Bayona, Jorge Carrillo; Iglesias Gamarra, Antonio; Rondon Federico Sanchez Contreras Alvaro, Restrepo Jose Felix

    2007-01-01

    The primary Sjogrens syndrome (PSS) is a chronic autoimmune exocrinopathy characterized by lymphocytic infiltration of glandular and extraglanduIar tissue, the lung involvement is heterogeneous; the aim of this study is report the first case in Colombia of PSS with Iymphocytic intersticiaI pneumonia and cystic pulmonary disease discuss differential diagnosis and the initial diagnostic and therapeutic work up

  18. 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

  19. 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

  20. Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

    Directory of Open Access Journals (Sweden)

    Alida Filippini

    2015-01-01

    Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

  1. Tonsillar tuberculosis, with primary pulmonary focus: A Case Report

    Directory of Open Access Journals (Sweden)

    Juan Antonio Lugo Machado

    2015-09-01

    Full Text Available Tuberculosis is an infectious disease that affects various organs and tissues, with greater tropism for lung disease, gastrointestinal and central nervous system tissue and even bone. However isolated cases of affection to other structures have been reported, just like this patient who came with symptoms in the tonsils and subsequently, lung involvement became apparent. The tonsillar infection in this case was considered a secondary tuberculosis with primary focus in the lungs.

  2. Primary pulmonary immunity to a soluble antigen in the dog

    International Nuclear Information System (INIS)

    Weissman, D.N.; Bice, D.E.; Muggenburg, B.A.; Schuyler, M.R.

    1988-01-01

    In order to study primary lung immunity to soluble antigen, Beagle dogs underwent trans-bronchoscopic instillation of 10 mg keyhole limpet hemocyanin (KLH) into the right cardiac lobe and saline into the left cardiac lobe. Over the next 3 wk, specific immune responses were monitored in blood and bronchoalveolar lavage (BAL) fluids obtained from immunized and control lung lobes. Primary lung immunization of dogs with KLH resulted in easily measurable specific IgG, IgM, and IgA responses in blood and bronchoalveolar lavage fluids. Important class differences were noted to exist for these responses. Levels of specific IgG and IgA in BAL remained elevated at 21 days after immunization, while BAL-specific IgM levels fell to control values by 12 days after immunization. In unimmunized lung lobes, specific antibody levels in BAL and production of specific antibody by bronchoalveolar lavage cells was far greater for IgG than for IgM or IgA. Finally, despite easily detectable specific IgA in serum and BAL fluid, production of specific IgA by peripheral blood mononuclear cells or bronchoalveolar lavage cells after primary lung immunization with KLH could not be demonstrated, suggesting that specific IgA was produced by a compartment of cells poorly sampled in blood and BAL. (author)

  3. Primary pulmonary immunity to a soluble antigen in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Weissman, D N; Bice, D E; Muggenburg, B A; Schuyler, M R

    1988-12-01

    In order to study primary lung immunity to soluble antigen, Beagle dogs underwent trans-bronchoscopic instillation of 10 mg keyhole limpet hemocyanin (KLH) into the right cardiac lobe and saline into the left cardiac lobe. Over the next 3 wk, specific immune responses were monitored in blood and bronchoalveolar lavage (BAL) fluids obtained from immunized and control lung lobes. Primary lung immunization of dogs with KLH resulted in easily measurable specific IgG, IgM, and IgA responses in blood and bronchoalveolar lavage fluids. Important class differences were noted to exist for these responses. Levels of specific IgG and IgA in BAL remained elevated at 21 days after immunization, while BAL-specific IgM levels fell to control values by 12 days after immunization. In unimmunized lung lobes, specific antibody levels in BAL and production of specific antibody by bronchoalveolar lavage cells was far greater for IgG than for IgM or IgA. Finally, despite easily detectable specific IgA in serum and BAL fluid, production of specific IgA by peripheral blood mononuclear cells or bronchoalveolar lavage cells after primary lung immunization with KLH could not be demonstrated, suggesting that specific IgA was produced by a compartment of cells poorly sampled in blood and BAL. (author)

  4. Chronic obstructive pulmonary disease (COPD) rehabilitation at primary health‐care centres – the KOALA project

    DEFF Research Database (Denmark)

    Godtfredsen, Nina Skavlan; Grann, Ove; Larsen, Hanne Bormann

    2012-01-01

    Background:  Implementation of pulmonary rehabilitation in primary health care in Denmark is a new challenge in the management of patients with chronic obstructive pulmonary disease (COPD). Objectives:  To assess the feasibility of introducing a nationwide web-based tool for data recording...... not meet the criteria for pulmonary rehabilitation in terms of dyspnoea upon exertion at the baseline visit. Furthermore, information on severity of COPD is missing for 18% of the attendants. The majority of the referred patients have moderate COPD, which is in accordance with the intentions...... and quality assurance in the rehabilitation programmes and to evaluate whether patients are referred correctly according to Danish guidelines for community based COPD rehabilitation. Methods:  Participation in the KOALA project has been offered to the municipalities since October 2007. As of October 2010, 62...

  5. Primary pulmonary sarcoma in a rhesus monkey after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    Hahn, F.F.; Brooks, A.L.; Mewhinney, J.A.

    1987-01-01

    A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis 9 years after inhalation of plutonium-239 dioxide and with a radiation dose to lung of 1400 rad (14 Gy). It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular pulmonary arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi (10 kBq) which is equivalent to approximately 500 times the maximum permissible lung burden for man on a radioactivity per unit body weight basis. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide and died with lung tumors

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  8. Oesophageal perforation as a complication of primary pulmonary tuberculous lymphadenopathy in children

    International Nuclear Information System (INIS)

    Erlank, Anita; Andronikou, Savvas; Ackermann, Christelle; Parsons, Jaco; Greyling, Jaco; Goussard, Pierre; Gie, Robert; Sidler, Daniel

    2007-01-01

    Involvement of the oesophagus by tuberculosis is rare, and erosion and perforation of the oesophagus by tuberculous lymphadenopathy is an unusual complication of primary pulmonary tuberculosis. There are very few reports describing both CT and contrast swallow appearances of these lesions. To describe the CT and contrast swallow appearances of oesophageal erosion and perforation by lymphadenopathy as a complication of primary pulmonary tuberculosis in children. Imaging of three children with confirmed pulmonary tuberculosis and oesophageal perforation was retrospectively reviewed. Tuberculosis was confirmed by culture in all three patients. Contrast swallow demonstrated a contained leak in two patients and a tracheo-oesophageal fistula in one. Two patients had mediastinal air and one patient had a mediastinal collection on CT. All patients had features diagnostic of pulmonary tuberculosis on CT. The imaging features comprise leakage of contrast medium with or without fistula formation on contrast swallow, large low-density lymph nodes on CT, and mediastinal air. The use of retrievable stents is a promising idea in this condition. (orig.)

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

    Science.gov (United States)

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

    2016-09-01

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

  10. Can historical controls be used in current clinical trials in osteosarcoma. Metastases and survival in a historical and a concurrent group

    International Nuclear Information System (INIS)

    Brostroem, L.A.; Aparisi, T.; Ingimarsson, S.; Lagergren, C.; Nilsonne, U.; Strander, H.; Soederberg, G.

    1980-01-01

    A historical group consisting of 35 patients with osteosarcoma was compared to a concurrent group of 23 patients. The treatment for the primary tumors differed only slghtly in the two groups. A more active approach was adopted for treatment of pulmonary metastases in the concurrent group. The percentage of patients not developing metastases and the survival rate in the historical group were approximately one half those for the concurrent group. An analysis of prognostic factors disclosed differences between the two groups as regards the size and histological type of the tumor. The results of the study cast doubt on the suitability of historical controls in current clinical trials conducted to ascertain the effectiveness of adjuvant therapy for osteosarcoma

  11. Identification of genuine primary pulmonary NK cell lymphoma via clinicopathologic observation and clonality assay.

    Science.gov (United States)

    Gong, Li; Wei, Long-Xiao; Huang, Gao-Sheng; Zhang, Wen-Dong; Wang, Lu; Zhu, Shao-Jun; Han, Xiu-Juan; Yao, Li; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2013-08-19

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual reaction to treatment or an unusual prognosis, it is wise to differentiate NK from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and the clonal status was determined using female X-chromosomal inactivation mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion showed the typical histopathologic characteristics and immunohistochemical features of NK/T cell lymphoma. However, the sample was negative for TCR gene rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It is concluded that this is the first recorded case of genuine primary pulmonary NK cell lymphoma. The purpose of the present work is to recommend that pathologists carefully investigate the whole lesion to reduce the likelihood that primary pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In addition, TCR gene rearrangement and clonal analysis, which is based on female X-chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor (AR) loci, were found to play important roles in differentiating NK cell lymphoma from T cell lymphoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

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

    Science.gov (United States)

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

    2017-11-01

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

  13. Diagnostic value of multi-tumor markers protein biochip detection for primary pulmonary cancer

    International Nuclear Information System (INIS)

    Xu Fengpo; Wu Yiwei; Li Qingru; Fa Yihua

    2005-01-01

    To evaluate the diagnostic value of multi-tumor markers protein biochip detection for primary pulmonary cancer, 12 tumor markers including AFP, CEA, NSE, CA125, CA15-3, CA242, CA19-9, PSA, f-PSA, FER, β-HCG and HGH were measured by the protein biochip in the serum of 45 primary pulmonary cancer patients. Positive rate of tumor markers was FER (42.2%), CEA (35.6%), CA125 (24.4%), CA15-3 (17.8%), CA242 (13.3%), CA19-9 (11.1%), β-HCG(8.9%), HGH(6.7%), NSE(4.4%), AFP (0), f-PSA (0) and PSA (0), respectively. The rate of patients with one abnorma indicator was 57.8% except FER. The positive rate using multi-tumor markers protein biochip detection was significantly higher than that of single tumor marker detective method, and this detection can be used for the diagnosis of patients with primary pulmonary cancer. (authors)

  14. Primary pulmonary hepatoid carcinoma: Report of a case and review of the literature

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    Shiou-Fu Lin

    2013-09-01

    Full Text Available Hepatoid carcinoma is a rare malignancy defined as extrahepatic primary alpha-fetoprotein-producing carcinoma morphologically resembling hepatocellular carcinoma. It is extremely rare in the lungs, with ambiguous pathological descriptions and variable prognosis. Herein, we present the case of a 66-year-old man with a primary pulmonary hepatoid carcinoma in his right upper lung who received complete curative surgical resection and adjuvant chemotherapy. No signs of recurrence or distant metastasis have been observed for 57 months postoperation. In addition, the literature is reviewed and the pathological diagnostic pitfalls are discussed.

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

    Science.gov (United States)

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

    2014-03-01

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

  16. Primary intimal sarcoma of the pulmonary artery 1 case report and retrospective analysis of 20 cases published in China

    International Nuclear Information System (INIS)

    Guo Lingchuan; Chen Yanbin

    2012-01-01

    Objective: To explore the clinical and histopathological features of primary, intimal sarcoma of the pulmonary artery. Methods: One case of primary intimal sarcoma of the pulmonary artery diagnosed in our hospital and 20 cases published openly in China were analysed retrospectively. Results: The clinical presentation of primary intimal sarcoma of the pulmonary artery was progressive dyspnea, cough, chest pain, syncope, bloody phlegm, fever and fatigue. From the radiological finding, its signs were of pulmonary, artery dilation, reduced pulmonary vasculature and cardiomegaly, soft tissue mass near the right ventricle outflow tract. Histological examination of intimal sarcoma of the pulmonary artery revealed a poorly differentiated mesenchymal tumor of fibroblastic or myofibroblastic differentiation, consisting of mildly atypical spindle cells with atypia, mitosis, and nuclear polymorphism. Immunohistochemical analysis showed positive staining with antibodies against vimentin, alpha-smooth muscle actin, while negative for desmin. Conclusion: Primary, intimal sarcoma of the pulmonary artery has atypical clinical and radiological manifestation with poor prognosis, its definite diagnosis depends on histopathology. (authors)

  17. Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma in 41 patients

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    Ma, Huali; Wu, Yaopan [Department of Radiology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Lin, Yongbin [Department of Thoracic Surgery, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Cai, Qingqing [Department of Medical Oncology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Ma, Guowei [Department of Thoracic Surgery, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Liang, Ying, E-mail: liangying@sysucc.org.cn [Department of Medical Oncology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China)

    2013-08-15

    Purpose: To assess the computed tomography (CT) findings of primary pulmonary lymphoepithelioma-like carcinoma (LELC). Materials and methods: Clinical information and CT findings of 41 patients with pulmonary LELC were reviewed. CT images of 2 or 5 mm thickness were obtained with a pre-treatment CT and were jointly evaluated by two radiologists. Results: Thirty central tumors and 11 peripheral tumors with diameters ranging from 1.0 to 8.7 cm (mean, 4.1 ± 1.9 cm) were identified. Central tumors appeared to be larger than peripheral tumors (P = 0.017). Tumors occurred more frequently in right middle lobe (31.7%) and left lower lobe (29.3%). CT findings of patients with early stage were similar to those observed in patients with advanced stage except that lymphadenopathy was significantly more common in patients with advanced stage. CT findings of pulmonary LELC consisted of well defined border (63.4%), lobulation (78.0%), vascular or bronchial encasement (43.9%), obstructive pneumonia (41.5%), pleural effusion (12.2%) and calcification (4.9%). On contrast-enhanced CT scans, inhomogeneously enhanced tumors were significantly larger than homogeneously enhanced tumors (P < 0.001). Lymphadenopathy was seen in 28 patients, and lymph nodes with homogeneous enhancement were observed in 24/28 patients. Enlarged lymph nodes were more frequently occurred in peribronchial or hilar nodes (53.7%), subcrinal nodes (39.0%), right lower paratracheal nodes (31.7%) and right upper paratracheal nodes (22.0%). Conclusion: Pulmonary LELC usually appeared as a large, central, well defined and lobulated tumor with vascular or bronchial encasement and obstructive pneumonia. Calcification was rare in pulmonary LELC. Lymphadenopathy was common, usually with homogeneous enhancement.

  18. Excavated pulmonary nodules: an unusual clinical presentation of lung metastasis in two cases

    Directory of Open Access Journals (Sweden)

    Lalya Issam

    2010-06-01

    Full Text Available Abstract Background Excavated pulmonary metastasis are rare. We present two cases of excavated pulmonary nodules proved to be metastases from osteosarcoma and gallblader lymphoma. Case presentation The first one is 39-year-old man in whom cholecystectomy made the diagnosis of primary non-Hodgkin's lymphoma of the gallbladder. He presented in chest CT scan excavated nodules that had been biopsied and confirmed the diagnosis of non hodgkin lymphoma. He underwent 8 courses of chemotherapy CHOP 21 with complete remission. The second one is an 21 years old man who presented a right leg osteoblastic osteosarcoma with only excavated pulmonary nodules in extension assessment. He had 3 courses of polychemotherapy API (doxorubicin, platinum, and ifosfamide with partial response. Unfortunately, he died following a septic shock. Review of the literature shows that excavated pulmonary nodules as metastasis are rare but we should consider this diagnosis every time we are in front of a cancer. Chest computed tomography is the best diagnosis imaging that could make this diagnosis. Differential diagnosis between benign and malignant bullous lesions is important because surgical excision affects survival in some malignancies. Conclusions Although pulmonary nodules are the most common cancer metastasis, a differential diagnosis of a concurrent primary malignancy should always be considered every time we have excavated lesions, even in patients with known malignant disease. Thorough chest evaluation is important, as multiple primary malignancies may occur concomitantly.

  19. Primary pulmonary cryptococcosis: evaluation of CT characteristics in 26 immunocompetent Chinese patients

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    Qu, Yanjuan; Liu, Guobing; Ghimire, Prasanna; Liao, Meiyan; Xu, Liying [Dept. of Radiology, Zhongnan Hospital of Wuhan Univ., Wuhan (China)], E-mail: leometeor123@gmail.com; Shi, Heshui [Dept. of Radiology, Union Hospital affiliated to Tongji Medical College of Huazhong Univ. of Science and Technology, Wuhan (China); Yang, Guifang [Dept. of Pathology, Zhongnan Hospital of Wuhan Univ., Wuhan (China); Wang, Guanliang [Dept. of Radiology, Taizhou Hospital of Zhejiang Province, Taizhou (China)

    2012-07-15

    Background. Discrepancies still exist in the diagnosis of primary pulmonary cryptococcosis in immunocompetent patients. Purpose. To describe and evaluate radiological manifestations of pulmonary cryptococcosis in immunocompetent patients. Material and Methods. Twenty-six histopathologically confirmed cases of pulmonary cryptococcosis were analyzed for clinical, pathological, and CT characteristics. Necessary statistical tests for differences in CT presentations and correlation analysis between clinical and CT characteristics were performed. Results. The patients' ages ranged from 24 to 79 years, with 20 men and six women. Eighteen patients were symptomatic, with cough as the most common symptom (n = 14, 53.8%). Nodules (n = 21, 80.8%) were the most common CT findings. Eight cases presented with solitary and nine with multiple nodules, while 13 cases presented with irregular and 19 with ill-defined nodules. The halo sign was demonstrated, encompassing nodules in 14 of the 21 patients. Lesions were mainly localized in the lower lobes of the lungs (n = 15, 57.7%) with peripheral distribution (n = 18, 69.2%). Ground-glass opacities (GGOs) were more easily detected in older patients (66.7%, P <0.01). No significant differences in CT abnormalities were found between male and female patients. Conclusion. Primary pulmonary cryptococcosis in immunocompetent patients exhibits certain CT characteristics. The typical presentation includes multiple nodules with the halo sign scattered in the peripheral field in the lower lobes of the bilateral lungs. This could contribute to diagnosis of the disease entity. However, vigilance should be exercised when facing GGOs, with or without nodules, in older patients.

  20. Telangiectatic osteosarcoma of femur in a young man

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Farbod Rastegar

    2010-12-01

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

  2. Periosteal osteosarcoma: A case report

    Directory of Open Access Journals (Sweden)

    Errol U. Hutagalung

    2003-09-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2017-10-10

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

  5. Mean pulmonary 99mTc-pertechnetate passage time. Its correlation with hemodynamic parameters in primary and secondary pulmonary hypertension

    International Nuclear Information System (INIS)

    Sinitsyn, V.E.; Sergienko, V.B.; Ostroumov, E.N.; Mareev, V.Yu.

    1991-01-01

    Diagnostic value of mean pulmonary 99m Tc-pertechnetate passage time was studied in 27 patients with different types of hypertension disturbances. It was shown that the parameters of mean indicator passage time can be used for noninvasive determination of diastolic pressure in pulmonary artery

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

    Science.gov (United States)

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Triche Timothy

    2009-12-01

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

  8. Pulmonary rehabilitation in COPD – available resources and utilization in Swedish primary and secondary care

    Directory of Open Access Journals (Sweden)

    Sundh J

    2017-06-01

    Full Text Available Josefin Sundh,1 Helena Lindgren,2 Mikael Hasselgren,2 Scott Montgomery,3–5 Christer Janson,6 Björn Ställberg,7 Karin Lisspers7 1Department of Respiratory Medicine, School of Medical Sciences, 2Medical Programme, School of Medical Sciences, 3Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, 4Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Epidemiology and Public Health, University College, London, UK; 6Department of Medical Sciences, Respiratory, Allergy and Sleep Research, 7Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden Introduction: Pulmonary rehabilitation is effective in all stages of COPD. The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden. Materials and methods: Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers. Multivariable logistic regression examined associations with having received rehabilitation in the previous year. Results: In primary care, nurse-based asthma/COPD clinics were common (87%, with additional separate access to other rehabilitation professionals. In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%. In total, 36% of the patients met an asthma/COPD nurse in the previous year. Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%, occupational therapists (3% vs 10%, nutritionists (5% vs 13%, and counselors (1% vs 4%. A higher COPD Assessment Test score

  9. Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differences in vitro.

    Science.gov (United States)

    Holmes, K E; Thompson, V; Piskun, C M; Kohnken, R A; Huelsmeyer, M K; Fan, T M; Stein, T J

    2015-09-01

    Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumour size, presence of metastatic disease and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behaviour of osteosarcoma cells differ based on serum ALP concentration. Here, we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion or chemosensitivity between cell lines associated with normal or increased serum ALP concentration. © 2013 Blackwell Publishing Ltd.

  10. Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioral differences in vitro

    Science.gov (United States)

    Holmes, Katie E.; Thompson, Victoria; Piskun, Caroline M.; Kohnken, Rebecca A.; Huelsmeyer, Michael K.; Fan, Timothy M.; Stein, Timothy J.

    2013-01-01

    Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumor size, presence of metastatic disease, and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behavior of osteosarcoma cells differ based on serum ALP concentration. Here we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behavior differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP assays were performed to evaluate proliferation, migration, invasion, and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion, or chemosensitivity between cell lines associated normal or increased serum ALP concentration. PMID:23489774

  11. Epiphyseal osteoblastoma-like osteosarcoma

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    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.)

  12. Chest Radiographic Findings in Primary Pulmonary Tuberculosis: Observations from High School Outbreaks

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    Koh, Won Jung; Kwon, O Jung; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Jeong, Yeon Joo [Pusan National University School of Medicine, Pusan National University Hospital, Busan (Korea, Republic of); Kim, Hee Jin; Lew, Woo Jin [Korean Institute of Tuberculosis, Seoul (Korea, Republic of); Cho, En Hi [4Korea Centers for Disease Control and Prevention, Seoul (Korea, Republic of)

    2010-12-15

    To describe the radiographic findings of primary pulmonary tuberculosis (TB) in previously healthy adolescent patients. The Institutional Review Board approved this retrospective study, with a waiver of informed consent from the patients. TB outbreaks occurred in 15 senior high schools and chest radiographs from 58 students with identical strains of TB were analyzed by restriction fragment length polymorphism analysis by two independent observers. Lesions of nodule(s), consolidation, or cavitation in the upper lung zones were classified as typical TB. Mediastinal lymph node enlargement; lesions of nodule(s), consolidation, or cavitation in lower lung zones; or pleural effusion were classified as atypical TB. Inter-observer agreement for the presence of each radiographic finding was examined by kappa statistics. Of 58 patients, three (5%) had normal chest radiographs. Cavitary lesions were present in 25 (45%) of 55 students. Lesions with upper lung zone predominance were observed in 27 (49%) patients, whereas lower lung zone predominance was noted in 18 (33%) patients. The remaining 10 (18%) patients had lesions in both upper and lower lung zones. Pleural effusion was not observed in any patient, nor was the mediastinal lymph node enlargement. Hilar lymph node enlargement was seen in only one (2%) patient. Overall, 37 (67%) students had the typical form of TB, whereas 18 (33%) had TB lesions of the atypical form. The most common radiographic findings in primary pulmonary TB by recent infection in previously healthy adolescents are upper lung lesions, which were thought to be radiographic findings of reactivation pulmonary TB by remote infection

  13. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

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    Goudarzi, Atta, E-mail: atta.goudarzi@utoronto.ca [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Merico, Daniele [The Centre for Applied Genomics, The Hospital for Sick Children, MaRS Centre-East Tower, 101 College Street Rm.14-701, Toronto, ON M5G 1L7 (Canada); Wunder, Jay S. [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Andrulis, Irene L. [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada)

    2013-04-08

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation.

  14. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

    International Nuclear Information System (INIS)

    Goudarzi, Atta; Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi; Merico, Daniele; Wunder, Jay S.; Andrulis, Irene L.

    2013-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation

  15. Clinical Characteristics of 118 Cases of Chronic Obstructive Pulmonary Disease Complicated with Primary Bronchopulmonary Carcinoma

    Directory of Open Access Journals (Sweden)

    Songlin ZHAO

    2017-08-01

    Full Text Available Background and objective The aim of this study is to investigate the clinical characteristics of patients with primary bronchopulmonary carcinoma complicated with chronic obstructive pulmonary disease (COPD, and to optimize the early diagnoses in the coexistence of COPD and primary bronchopulmonary carcinoma. Methods The clinical data of 118 patients with COPD complicated with primary bronchopulmonary carcinoma were analyzed retrospectively, including age, sex, smoking history, smoking index, clinical symptoms and signs, pathological type, staging, metastasis site and lung function index. 120 patients with simple COPD were selected as control. Results The smoking rate (55.1% and smoking index ≥400 branch /year (90.8% of the patients with COPD complicated with primary bronchopulmonary carcinoma were higher than the simple COPD group (20.8%, 48.0%. The difference between the two groups was statistically significant (P0.05, while the incidence of hemoptysis, weight loss, chest pain, hoarseness, pleural effusion and atelectasis were significantly higher than those in simple COPD group (P0.05, but the diffusing capacity of carbon monoxide (DLCO of COPD patients complicated with primary bronchopulmonary carcinoma was lower than that of simple COPD patients (P<0.05 . In the COPD patients with primary bronchopulmonary carcinoma, squamous cell carcinoma was the most common pathological type (51.7%. Male patients were mainly squamous cell carcinoma (60.7%, while female patients with adenocarcinoma (69.0%. Conclusion COPD combined with primary bronchopulmonary carcinoma occurs in male smokers more. There is higher incidence of squamous cell carcinoma. When they are first diagnosed, most of them are advanced or located late, due to no specific clinical symptoms at the early stages. Periodic chest CT examination for COPD patients can help early diagnoses of primary bronchopulmonary carcinoma.

  16. Chondroblastic osteosarcoma arising in the maxilla mimicking the radiographic and histological characteristics of cemento-osseous lesions: A case report.

    Science.gov (United States)

    Li, Bin-Bin; Zhang, Jian-Yun; Gao, Yan

    2017-05-01

    Osteosarcomas of the jaw are comparatively rare and represent only 2-10% of all osteosarcomas. We herein present a rare case of an osteosarcoma exhibiting the radiographic and histological characteristics of cemento-osseous lesions in the alveolar ridge of the maxilla. A 53-year-old male patient presented with the complaint of gradual swelling of the left maxilla over 4 years. Radiography revealed an ill-defined radioopaque mass, intimately associated with the apices of the involved teeth, without a periosteal reaction. Microscopically, a cementicle-like structure was identified in the alveolar bone. In addition, the lesion exhibited typical characteristics of chondroblastic osteosarcoma in the body of the maxilla. The tumor contained abundant osteoid and cartilage intimately associated with anaplastic tumor cells. The cartilage displayed malignant-appearing cells in lacunae, and there was crowding at the periphery of the lobule where the spindle cells formed sheets. The differential diagnosis included primary osteosarcoma, concurrent cemento-osseous dysplasia and osteosarcoma, or a secondary osteosarcoma based on a pre-existing cemento-osseous lesion. The presence of the cementicle-like structure in the alveolar bone and the involvement of the periodontal ligament and alveolar bone proper were unique in our case. The general invasive growth pattern and the abundance of the irregular tumor bone helped establish the diagnosis of primary osteosarcoma. This case may represent evidence of the pathogenesis of primary osteosarcoma in the jaw.

  17. 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.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  19. Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fernanda Amary, M; Ye, Hongtao; Berisha, Fitim; Khatri, Bhavisha; Forbes, Georgina; Lehovsky, Katie; Frezza, Anna M; Behjati, Sam; Tarpey, Patrick; Pillay, Nischalan; Campbell, Peter J; Tirabosco, Roberto; Presneau, Nadège; Strauss, Sandra J; Flanagan, Adrienne M

    2014-01-01

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors

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

    International Nuclear Information System (INIS)

    Zhang, Shilian; Zhao, Yuehua; Wang, Lijie

    2016-01-01

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

  1. 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.

  2. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G

    2014-01-01

    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  3. Primary pulmonary lymphoma mimicking a refractory lung abscess: A case report.

    Science.gov (United States)

    Matsumoto, Takeshi; Otsuka, Kojiro; Funayama, Yuki; Imai, Yukihiro; Tomii, Keisuke

    2015-04-01

    The current study presents a case of primary pulmonary lymphoma (PPL) mimicking refractory lung abscess that was diagnosed at autopsy. An 80-year-old male with clinically inapparent aspiration presented with a large cavitated mass and pleural effusion. A lung abscess and empyema was diagnosed, therefore, antibiotics were administered and the pleural effusion was drained. Various examinations, including a biopsy, yielded no specific diagnosis. The lesion was considered inoperable due to the poor general condition of the patient. Subsequently, the mass that had been diagnosed as a refractory lung abscess became enlarged and a repeat biopsy resulted in a diagnosis of diffuse large B-cell lymphoma. The patient succumbed to sudden respiratory failure, and the final diagnosis of PPL was confirmed at autopsy. PPL is a rare disease that accounts for 0.45% of all pulmonary malignant tumors and is difficult to diagnose in inoperable cases. Therefore, patients with PPL who do not undergo surgery can be misdiagnosed and consequently treated inappropriately. PPL should therefore be considered in the differential diagnosis of a refractory lung abscess.

  4. Expression and function of survivin in canine osteosarcoma.

    Science.gov (United States)

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

    2012-01-01

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

  5. Asymptomatic Primary Isolated Pulmonary Vein Stenosis in an Adult: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun; Lee, Ho Sung; Choi, Jae Sung; Na, Ju Ock; Kim, Yong Hoon; Jou, Sung Shick; Seo, Ki Hyun [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2010-08-15

    A 31-year-old man without respiratory symptoms was transferred to our clinic with incidentally detected small nodular densities in both the upper lung zones on chest radiography. Chest computed tomography and pulmonary angiography demonstrated that the entrance of the right inferior pulmonary vein to the left atrium was completely blocked, and the venous return of the right lower lobe was achieved through the right superior pulmonary vein with a tortuous venous collateral complex in the venous phase. With echocardiography, mild pulmonary hypertension was detected. Here, we present an asymptomatic adult with isolated stenosis of the pulmonary vein with chronic compensation by venous collateral circulation in spite of mild pulmonary hypertension

  6. Asymptomatic Primary Isolated Pulmonary Vein Stenosis in an Adult: A Case Report

    International Nuclear Information System (INIS)

    Kim, Ji Hyun; Lee, Ho Sung; Choi, Jae Sung; Na, Ju Ock; Kim, Yong Hoon; Jou, Sung Shick; Seo, Ki Hyun

    2010-01-01

    A 31-year-old man without respiratory symptoms was transferred to our clinic with incidentally detected small nodular densities in both the upper lung zones on chest radiography. Chest computed tomography and pulmonary angiography demonstrated that the entrance of the right inferior pulmonary vein to the left atrium was completely blocked, and the venous return of the right lower lobe was achieved through the right superior pulmonary vein with a tortuous venous collateral complex in the venous phase. With echocardiography, mild pulmonary hypertension was detected. Here, we present an asymptomatic adult with isolated stenosis of the pulmonary vein with chronic compensation by venous collateral circulation in spite of mild pulmonary hypertension

  7. Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular Opacity: Report of a Case.

    Science.gov (United States)

    Yoshino, Naoyuki; Hirata, Tomomi; Takeuchi, Chie; Usuda, Jitsuo; Hosone, Masaru

    2017-01-01

    Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

  8. Quantitation of right and left ventricular volume with MR imaging in patients with primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Boxt, L.M.; Katz, J.; Kolb, T.; Czegledy, F.P.; Barst, R.J.

    1990-01-01

    This paper tests the utility of MR imaging in quantitating changes in ventricular volume and function in patients with primary pulmonary hypertension (PPH). Right ventricular (RV) and left ventricular (LV) end-diastolic (ED) and end-systolic (ES) volumes were determined in six patients with PPH and in eight controls. Short-axis images were obtained from the cardiac apex to the base at ED and ES, and the ventricular cavities were planimetered. Volumes were computed by summing the areas of the cavities times the thickness of the sections (12-14 mm). The intersection gap (1-3 mm) was averaged between adjacent sections. Results were indexed to the subject's body surface area. This technique was verified by comparison of results obtained by this method with the water displacement volumes of ventricular casts of eight excised bovine hearts and six water-filled balloons. Linear regression and the unpaired Students t test were used to test significance

  9. A Primary Pulmonary Glomus Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yasushi Ariizumi

    2012-01-01

    Full Text Available A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35, but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.

  10. Anticancer Effects of Geopropolis Produced by Stingless Bees on Canine Osteosarcoma Cells In Vitro

    OpenAIRE

    Cinegaglia, Naiara Costa; Bersano, Paulo Ricardo Oliveira; Ara?jo, Maria Jos? Abigail Mendes; B?falo, Michelle Cristiane; Sforcin, Jos? Maur?cio

    2013-01-01

    Geopropolis is produced by indigenous stingless bees from the resinous material of plants, adding soil or clay. Its biological properties have not been investigated, such as propolis, and herein its cytotoxic action on canine osteosarcoma (OSA) cells was evaluated. OSA is a primary bone neoplasm diagnosed in dogs being an excellent model in vivo to study human OSA. spOS-2 primary cultures were isolated from the tumor of a dog with osteosarcoma and incubated with geopropolis, 70% ethanol (geop...

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

    African Journals Online (AJOL)

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

  12. Spirometry use: detection of chronic obstructive pulmonary disease in the primary care setting

    Science.gov (United States)

    Barnes, Thomas A; Fromer, Len

    2011-01-01

    Objective: To describe a practical method for family practitioners to stage chronic obstructive pulmonary disease (COPD) by the use of office spirometry. Methods: This is a review of the lessons learned from evaluations of the use of office spirometry in the primary care setting to identify best practices using the most recent published evaluations of office spirometry and the analysis of preliminary data from a recent spirometry mass screening project. A mass screening study by the American Association for Respiratory Care and the COPD Foundation was used to identify the most effective way for general practitioners to implement office spirometry in order to stage COPD. Results: A simple three-step method is described to identify people with a high pre-test probability in an attempt to detect moderate to severe COPD: COPD questionnaire, measurement of peak expiratory flow, and office spirometry. Clinical practice guidelines exist for office spirometry basics for safety, use of electronic peak flow devices, and portable spirometers. Conclusion: Spirometry can be undertaken in primary care offices with acceptable levels of technical expertise. Using office spirometry, primary care physicians can diagnose the presence and severity of COPD. Spirometry can guide therapies for COPD and predict outcomes when used in general practice. PMID:21472091

  13. Importance of immunohistochemistry and application of TTF-1 and napsin A in differential diagnosis of primary pulmonary adenocarcinomas and pulmonary metastases of extrapulmonary origins

    International Nuclear Information System (INIS)

    Mikulakova, A.; Hribikova, Z.

    2017-01-01

    The differential diagnosis between primary and secondary pulmonary adenocarcinomas is daily requisition for pathologist. Lungs are the most common site of metastases from various primary and primary pulmonary adenocarcinomas are one of the most common worldwide malignancies. Immunohistochemistry is useful method to determine the origin of tumor in case when histomorphology alone is insufficient in poor differentiated carcinomas. Accordingly, presence of enteric, clear cell, spindle cell and signet-ring cell features complicates determining of origin of adenocarcinomas. The most common and long-used lung specific immunohistochemical marker is TTF-1, but specificity and sensitivity is not 100%. Use of TTF-1 has pitfalls that complicate its routine use. TTF-1 alone is insufficient marker for determining of origin of adenocarcinoma in the lung. Newly used immunohistochemical marker is napsin A. According to many authors is sensitivity and specificity for napsin A higher than TTF-1. Use of TTF-1 and napsin A simultaneously increases sensitivity up to 85% for primary lung adenocarcinomas. Both immunohistochemical l markers can be expressed in various tumours of extrapulmonary origin that can metastasize to lung, thus specificity is not 100%. In cases of surgical resection of tumor wider panels of immunohistochemical antibodies are used. Small biopsies and cytological material is quantitative restricted and sometimes qualitatively deficient. It is sometimes complicated and even impossible for pathologist to determine primary origin of tumor. (author)

  14. Ruling out pulmonary embolism in primary care : Comparison of the diagnostic performance of “gestalt” and the wells rule

    NARCIS (Netherlands)

    Hendriksen, Janneke M T; Lucassen, Wim A M; Erkens, Petra M G; Stoffers, Henri E J H; van Weert, Henk C P M; Büller, Harry R.; Hoes, Arno W.; Moons, Karel G M; Geersing, Geert Jan

    2016-01-01

    PURPOSE Diagnostic prediction models such as the Wells rule can be used for safely ruling out pulmonary embolism (PE) when it is suspected. A physician’s own probability estimate (“gestalt”), however, is commonly used instead. We evaluated the diagnostic performance of both approaches in primary

  15. Ruling Out Pulmonary Embolism in Primary Care: Comparison of the Diagnostic Performance of "Gestalt" and the Wells Rule

    NARCIS (Netherlands)

    Hendriksen, Janneke M. T.; Lucassen, Wim A. M.; Erkens, Petra M. G.; Stoffers, Henri E. J. H.; van Weert, Henk C. P. M.; Büller, Harry R.; Hoes, Arno W.; Moons, Karel G. M.; Geersing, Geert-Jan

    2016-01-01

    Diagnostic prediction models such as the Wells rule can be used for safely ruling out pulmonary embolism (PE) when it is suspected. A physician's own probability estimate ("gestalt"), however, is commonly used instead. We evaluated the diagnostic performance of both approaches in primary care.

  16. Osteoblastic and fibroblastic multicentric osteosarcoma.

    Science.gov (United States)

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

    2011-11-21

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

  17. 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.

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

    Science.gov (United States)

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

    2015-07-01

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

  19. The primary experimental study of self-made percutaneous catheterized thrombectomy device for acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Zhao Shijun; Ma Junshan; Yang Jianping

    2008-01-01

    Objective: To evaluate efficacy, feasibility and safety of the self-made percutaneous catheterized thrombectomy divice in animal model for thrombus removal. Methods: Seven dogs were selected, with acute massive pulmonary embolism animal models created by injecting thrombi into the pulmonary arterial trunk via percutaneous femoral vein approach. After half an hours the catheter sheath was inserted into the occluded pulmonary artery through right femoral vein in 5 dogs, left femoral vein in 1 dog and right internal jugular vein in another one. The procedure began to remove the thrombi with simultaneous recording the thrombectomy time and the blood volume drainage. Blood gass was tested before and after embolization together with those of thrombi removement, continuously monitored pulmonary arterial pressure and intermittently performed angiography. The mean time form vascular recanalization to euthanasia was 2 hours, and then the lung specimens were resected for histological examination. Results: One animal died of pulmonary arterial penetration during thrombi removal, but others were all alive by the end of the test. Mean time of removing thrombi was 2.4 minutes with mean volume blood drainage of 84 ml. Angiograms showed the approximately complete patency of the pulmonary arterial trunk after reopening of occlusion but still with remnont thrombi within distal branches and arterial pressure with blood gas returned to normal level. Pathology revealed the recanalization of pulmonary arterial trunk but with thromi still staying in the distal branches, and effusion around the arteries. Conclusions: The self-made percutaneous catheterized thrombectomy device is effective, feasible and comparatively safe in the treatment of acute massive pulmonary embolism in this primary test. (authors)

  20. Impact of exercise pulmonary hypertension on postoperative outcome in primary mitral regurgitation.

    Science.gov (United States)

    Magne, Julien; Donal, Erwan; Mahjoub, Haifa; Miltner, Beatrice; Dulgheru, Raluca; Thebault, Christophe; Pierard, Luc A; Pibarot, Philippe; Lancellotti, Patrizio

    2015-03-01

    The management of asymptomatic patients with mitral regurgitation (MR) remains controversial. Exercise-induced pulmonary hypertension (ExPHT) was recently reported as a strong predictor of rapid onset of symptoms. We hypothesised that ExPHT is a predictor of postoperative cardiovascular events in patients with primary MR. One hundred and two patients with primary MR, no or mild symptoms (New York heart association (NYHA) ≤2), and no LV dysfunction/dilatation, were prospectively recruited in 3 centres and underwent exercise-stress echocardiography. The presence of ExPHT was defined as an exercise systolic pulmonary arterial pressure >60 mm Hg. All patients were closely followed up and operated on when indication for surgery was reached. Postoperative events were defined as the occurrence of atrial fibrillation (AF), stroke, cardiac-related hospitalisation or death. Among the 102 patients included, 59 developed ExPHT (58%). These patients were significantly older than those without ExPHT (p=0.01). During a mean postoperative follow-up of 50±23 months, 28 patients (26%) experienced a predefined cardiovascular event. Patients with ExPHT had significantly higher rate of postoperative events (39% vs 12%, p=0.005); the rate of events was still higher in these patients (32% vs 9%, p=0.013), even when excluding early postoperative AF (ie, within 48 h). Event-free survival was significantly lower in the ExPHT group (all events: 5-year: 60±8% vs 88±5%, p=0.007, events without early AF: 5-year: 67±7% vs 90±4%, p=0.02). Using Cox multivariable analysis, ExPHT remained independently associated with higher risk of postoperative events in all models (all p≤0.04). ExPHT is associated with increased risk of adverse cardiac events following mitral valve surgery in patients with primary MR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma: Analysis of prognostic factors

    Science.gov (United States)

    Kwon, Jong-Bum; Park, Khun; Kim, Young-Du; Seo, Jong-Hee; Moon, Seok-Whan; Cho, Deog-Gon; Kim, Yong-Whan; Kim, Dong-Goo; Yoon, Seung-Kew; Lim, Hyeon-Woo

    2008-01-01

    AIM: To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors. METHODS: Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS: There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ± 28.2 (range: 1-99 mo), and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma (HCC), and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan-Meier analysis revealed that liver transplantation as a treatment for the primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox’s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC. CONCLUSION: A metastasectomy should be performed before other treatments in selected patients. Although not significant, patients with liver transplantation of a primary HCC survived longer. Liver transplantation might be the most beneficial modality that can offer patients better survival. A multi-institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis. PMID:18837090

  2. Intravascular pulmonary metastases

    International Nuclear Information System (INIS)

    Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

    1988-01-01

    The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

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

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    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.

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

    Science.gov (United States)

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

    2013-04-01

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

  5. 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.

  6. Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach.

    Science.gov (United States)

    Mesquita, Luis; Mortier, Jeremy; Ressel, Lorenzo; Finotello, Riccardo; Silvestrini, Paolo; Piviani, Martina

    2017-06-01

    A 10-year-old, female spayed mixed-breed or cross-bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog. © 2017 American Society for Veterinary Clinical Pathology.

  7. Pulmonary Metastasis from Rectal Cancer on Chest CT Is Correlated with 3T MRI Primary Tumor Location

    International Nuclear Information System (INIS)

    Han, Na Yeon; Kim, Min Ju; Park, Beon Jin; Sung, Deuk Jae; Chung, Kyoo Byung; Oh, Yu Whan

    2011-01-01

    To evaluate the association between the incidence of pulmonary metastasis on chest CT and the location of the primary tumor on rectal MRI. One hundred and nine consecutive patients with rectal adenocarcinoma underwent chest CT and 3T rectal MRI. Two radiologists classified the tumor on MRI as an upper (> 10 cm from the anal verge), mid (5-10 cm), or lower rectal tumor (< 5 cm) by consensus. All chest CT scans were retrospectively reviewed for the presence of metastasis. We used Fisher's exact test to evaluate the correlation between the incidence of pulmonary metastasis with the location of the rectal cancer and the Mantel-Haenszel test to control for local tumor stage. We only included the 60 patients with upper (n = 26) or lower (n = 34) rectal cancer, because of the complicated venous drainage system of the mid rectum. Among these, 9 (15%) showed evidence of pulmonary metastasis on chest CT and almost all (89%, 8/9) patients had lower rectal cancer. The incidence of pulmonary metastasis between the two groups was statistically different (p < 0.05) when local tumor stage was controlled. The incidence of pulmonary metastasis was significantly higher for lower than upper rectal cancers when the T-stage of the tumor was accounted for.

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

    Science.gov (United States)

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

    2017-10-01

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

  9. Expression of Bcl-2 in canine osteosarcoma

    Science.gov (United States)

    Piro, F.; Leonardi, L.

    2015-01-01

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

  10. Expression of Bcl-2 in canine osteosarcoma

    Directory of Open Access Journals (Sweden)

    F. Piro

    2015-03-01

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

  11. The occurrence of primary pulmonary neoplasms in rats after inhalation of 147Pm in fused aluminosilicate particles

    International Nuclear Information System (INIS)

    Herbert, R.A.; Scott, B.R.; Hahn, F.F.; Newton, G.J.; Snipes, M.B.; Damon, E.G.; Boecker, B.B.

    1988-01-01

    To determine the biological response following low-energy, beta irradiation of the lung, F344/Crl rats were exposed to aerosols of promethium-147 in fused aluminosilicate particles and observed for their life spans. Radiation pneumonitis and pulmonary fibrosis caused the majority of deaths during the first year after exposure with cumulative doses to the lungs of 210 to 630 Gy. Primary pulmonary neoplasms were responsible for the majority of deaths that occurred beyond 1 yr after exposure and in rats receiving lower cumulative doses to the lung. Hemangiosarcomas and squamous cell carcinomas were the most prevalent pulmonary neoplasms. Three adenocarcinomas were found. The uncorrected crude incidence of primary lung tumors increased with increasing dose to the lung for cumulative doses less than 140 Gy. With higher doses, the incidence declined. Adjusting the data for competing risks eliminated the turnover in the dose-response curve. The times of onset of pulmonary tumors and median survival times were dose-dependent. Rats with higher accumulated radiation doses developed fatal lung tumors at earlier times after exposure. (author)

  12. Primary pulmonary lymphoepithelioma-like carcinoma on FDG PET/CT

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    Aktas, Gul Ege; Can, Nuray; Demir, Selin Soyluglu; Sarika, Ali [Trakya University Medical Faculty, Edirne (Turkmenistan)

    2017-03-15

    A 69-year-old male smoker was referred to 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) with the indication of a suspicious solitary pulmonary nodule. FDG PET/CT determined a 2.5 × 2-cm soft-tissue lesion (SUV{sub ma{sub x}}, 16.2) with spiculated margins in the hilum of the right lung. A 1-cm diameter lymphadenopathy on the right hilum with an SUV{sub max} of 3.2 was also determined. Transbronchial biopsy of the right hilar lymphadenopathy did not reveal any malignant features in histopathologic examination, and it was determined to be reactive. The patient underwent a right upper lobe segmentectomy, and the histopathologic evaluation revealed that the tumor was a primary lymphoepithelioma-like carcinoma (LELC) of the lung with negative Epstein-Barr virus (EBV) on in situ hybridization studies. In this case report, we mainly focus on the FDG avidity of this very rare kind of tumor comparatively with previous reports and possible explanations of discordancy in FDG avidity in relation to histopathologic characteristics.

  13. Clinicopathologic analysis of resected primary lung cancer with idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Hirami, Yuji; Nakata, Masao; Maeda, Ai; Yukawa, Takuro; Shimizu, Katsuhiko

    2010-01-01

    The aim of the present study was to define the clinicopathological features and operative prognosis of patients with primary lung cancer with idiopathic pulmonary fibrosis (IPF). Of the patients who underwent surgery for non-small cell lung cancer from January 2006 to January 2008 in our hospital, 94 patients who had been preoperatively evaluated with high resolution computed tomography (HRCT) were enrolled in this study. We retrospectively analyzed 9 patients (9.6%) who were given a diagnosis of IPF based on HRCT findings. The patients with IPF consisted of 8 men and 1 woman with an average age of 74.7 years. All 9 patients had a smoking history. Patients with IPF had tumors located adjacent to the pleura significantly more frequently than in 85 patients without IPF (77.8% vs 36.5%; P=0.02). Pathologically, squamous cell carcinoma, and moderately or poorly differentiated tumors were detected significantly more frequently in patients with IPF than without IPF (55.6% vs 20.0%; P=0.05, 88.9% vs 42.4%; P=0.01). The standardized uptake value (SUV) of F-18 fluorodeoxyglucose (FDG) on positron emission tomography (PET) of patients with IPF showed a high average value of 11.1 (range, 3.4-31.6). The Ki-67 labeling index also showed a high average value of 46.1%. Up-staging migration from the clinical stage to the pathological stage was noticed in 4 cases due to underestimation of the tumor diameter in 3 cases and intrapulmonary metastasis in 1 case. Recurrences were observed in 4 of 9 cases. Local recurrence was observed in 2 cases (hilar lymph nodes and mediastinal lymph nodes), and distant recurrence was in 2 cases. As primary lung cancer with IPF seems to have a high potential for malignancy and the preoperative T factor can be often underestimated, we should be cautious selecting limited resection as a curative procedure. (author)

  14. Detection of Chronic Obstructive Pulmonary Disease by student nurses in primary health care: a pilot study

    Directory of Open Access Journals (Sweden)

    Kleoniki Linariti

    2016-12-01

    Full Text Available Introduction: Early detection of Chronic Obstructive Pulmonary Diseases (COPD is the key for its control and management in Primary Health Care. Nurses could significantly contribute to the early detection of COPD if they receive appropriate training and develop skills such as performing spirometry tests and assess early COPD’s signs and symptoms. Aim: To assess the ability of nursing students to detect undiagnosed cases of COPD through a designed spirometry program. Methods: Participants were approached following an open invitation by the local municipal authorities during January-June 2015 in 4 primary health care centres of the island of Crete, Greece. A screening program was conducted using two different diagnostic methods of COPD. All participants completed the ‘International Primary Care Airways Guidelines’ (IPAG questionnaire, a validated instrument for COPD cases identification and performed a spirometry, a gold standard method for the diagnosis of COPD. Nursing students were trained for one month.Two different diagnoses of COPD were given using the interpretations of the spirometry tests and IPAG results for each individual participant (IPAG & GOLD standards. Diagnosis of COPD was based on the spirometry values using the GOLD recommendations (fixed ratio FEV1/FVC<70%. The capacity of nursing students in detecting COPD was based on the degree of agreement (Kappa test and ROC curve between the two diagnoses of COPD (IPAG & GOLD. P-values <0.05 were considered statistically significant. Results: The mean age of the 390 participants was 55.6 (12.7 years old and 46.9% were male. The prevalence of COPD was 20% (78 cases according to IPAG questionnaire and 12.1% (47 cases according to spirometry. However, 31 cases of COPD that were detected using the IPAG, were classified as normal in spirometry, showing middle level of agreement (Kappa=0.71, p<0.001, 47/78 cases. Consequently, a sensitivity and specificity analysis was performed reported

  15. Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective Multicenter Analysis.

    Science.gov (United States)

    Tirtei, Elisa; Asaftei, Sebastian D; Manicone, Rosaria; Cesari, Marilena; Paioli, Anna; Rocca, Michele; Ferrari, Stefano; Fagioli, Franca

    2017-05-01

    Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

  16. Comparison of the Influence of Phospholipid-Coated Porous Ti-6Al-4V Material on the Osteosarcoma Cell Line Saos-2 and Primary Human Bone Derived Cells

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    Axel Deing

    2016-03-01

    Full Text Available Biomaterial surface functionalization remains of great interest in the promotion of cell osteogenic induction. Previous studies highlighted the positive effects of porous Ti-6Al-4V and phospholipid coating on osteoblast differentiation and bone remodeling. Therefore, the first objective of this study was to evaluate the potential synergistic effects of material porosity and phospholipid coating. Primary human osteoblasts and Saos-2 cells were cultured on different Ti-6Al-4V specimens (mirror-like polished or porous specimens and were coated or not with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE for three weeks or five weeks. Selected gene expressions (e.g., classical bone markers: alkaline phosphatase, osteocalcin, osteoprotegerin (OPG, receptor activator of nuclear factor kappa-β ligand (RANKL and runt-related transcription factor 2 were estimated in vitro. Furthermore, the expressions of osteocalcin and osteopontin were examined via fluorescent microscopy at five weeks (immunocytochemistry. Consequently, it was observed that phospholipid coating potentiates preferences for low and high porosities in Saos-2 and primary cells, respectively, at the gene and protein levels. Additionally, RANKL and OPG exhibited different gene expression patterns; primary cells showed dramatically increased RANKL expression, whereas OPG expression was decreased in the presence of POPE. A synergistic effect of increased porosity and phospholipid coating was observed in primary osteoblasts in bone remodeling. This study showed the advantage of primary cells over the standard bone cell model.

  17. Chondroblastic osteosarcoma mimicking periapical abscess.

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2012-05-15

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

  19. Small-cell osteosarcoma

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  20. Tomographic findings of lobar consolidation in primary pulmonary tuberculosis; Aspectos tomograficos da consolidacao lobar na tuberculose pulmonar primaria

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    Pereira, Bruno Alberto Falcao [Hopital Europeen Georges Pompidou, Paris (France); Macedo, Solange Goncalves David de [Hospital Municipal Jesus, Rio de Janeiro, RJ (Brazil). Setor de Pneumologia; Nogueira, Renata do Amaral [Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil). Setor de Pediatria; Castiel, Lola Celeste Pantoja [Clinica Radiologica Dr. Samuel Castiel, Porto Velho, RO (Brazil); Penna, Claudia Renata Rezende [Hospital Municipal Jesus, Rio de Janeiro, RJ (Brazil). Servico de Radiologia Pediatrica], e-mail: cr-penna@uol.com.br

    2009-03-15

    Objective: To describe tomographic findings of lobar consolidation as early manifestation of primary pulmonary tuberculosis. Materials and methods: The present study was developed at Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2002 and 2006, retrospectively evaluating tomographic findings in four children aged from 3 to 14 months with lobar consolidation as an early manifestation of primary pulmonary tuberculosis. Results: The most frequently found radiological pattern was lobar consolidation with calcifications, cavitation and intermingle necrotic areas, associated with bulging fissure. Signs of bronchogenic dissemination and lymph node enlargement were observed in all of the four children. Consolidation with a pseudotumor aspect and masslike effect was observed in one case. Conclusion: The cases included in the present study have demonstrated that primary pulmonary tuberculosis manifested as lobar consolidation presents typical tomographic images such as cavitation, hypodense areas and calcifications intermingled with consolidation. The association with lymph node enlargement with central necrosis and signs of bronchogenic dissemination reinforce the diagnosis of tuberculosis. (author)

  1. Modulation of the osteosarcoma expression phenotype by microRNAs.

    Directory of Open Access Journals (Sweden)

    Heidi M Namløs

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

  2. Osteosarcoma: Evolution of Treatment Paradigms

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    Norman Jaffe

    2013-01-01

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

  3. Isolation of Osteosarcoma-Associated Human Antibodies from a Combinatorial Fab Phage Display Library

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    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.

  4. A Rare Case Report of Mandible Osteosarcoma in an 8-Year-Old Child

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    Atena Shiva

    2017-09-01

    Full Text Available Introduction: Osteosarcoma of jaw bones is the most common primary malignant bone tumor arising from mesenchymal cells capable of producing steoid; this disorder predominantly occurs in the long bones and rarely involves the maxillofacial region.  Normally, this disease presents in the third and fourth decades of life, is slightly more common in men than women, and affects the mandible and maxilla in the same proportion. Case report: An 8-year-old girl was referred to an oral and maxillofacial surgeon due to tumoral lesions in the posterior mandible in Sari, Iran. After the surgery, histopathological examination of the tumoral lesions revealed fibroblastic osteosarcoma. Further, immunohistochemical markers were evaluated, results of which approved final diagnosis of mandible osteosarcoma. Conclusion: Given that osteosarcoma of jaw bones share the same clinical manifestations with benign lesions, misdiagnosis is highly common and diagnosis is challenging for dentists. Accurate diagnosis and early referral are critical in prognosis and survival of patients.

  5. Assessment of a primary and tertiary care integrated management model for chronic obstructive pulmonary disease

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    Peiro Meritxell

    2009-02-01

    Full Text Available Abstract Background The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care. This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD. The new model will be evaluated in terms of 1 improvement in the rational utilization of health-care services and 2 benefits reflected in improved health status and quality of life for patients. Methods/Design A quasi-experimental study of the effectiveness of a COPD management model called COPD PROCESS. The patients in the study cohorts will be residents of neighborhoods served by two referral hospitals in Barcelona, Spain. One area comprises the intervention group (n = 32,248 patients and the other the control group (n = 32,114 patients. The study will include pre- and post-intervention assessment 18 months after the program goes into effect. Analyses will be on two datasets: clinical and administrative data available for all patients, and clinical assessment information for a cohort of 440 patients sampled randomly from the intervention and control areas. The main endpoints will be the hospitalization rates in the two health-care areas and quality-of-life measures in the two cohorts. Discussion The COPD PROCESS model foresees the integrated multidisciplinary management of interventions at different levels of the health-care system through coordinated routine clinical practice. It will put into practice diagnostic and treatment procedures that are based on current evidence, multidisciplinary consensus, and efficient use of available resources. Care pathways in this model are defined in terms of patient characteristics, level of disease severity and the presence or absence of exacerbation. The protocol covers the full range of care from primary prevention to treatment of

  6. MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

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    Fen Zhu

    Full Text Available INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19 resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC, and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC. The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001 and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively. Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023 or disease-free survival (p = 0.027 as well as correlation between FLT1 and overall survival (p = 0.009. CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

  7. 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.

  8. Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

    2013-05-01

    Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

  9. Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma.

    Science.gov (United States)

    Feng, Jinyi; Lan, Ruilong; Cai, Guanxiong; Lin, Jinluan; Wang, Xinwen; Lin, Jianhua; Han, Deping

    2016-11-24

    The study aimed to explore the correlation between the expression of TREX1 and the metastasis and the survival time of patients with osteosarcoma as well as biological characteristics of osteosarcoma cells for the prognosis judgment of osteosarcoma. The correlation between the expression of TREX1 protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma was analyzed. The CD133 + and CD133 - cell subsets of osteosarcoma stem cells were sorted by the flow cytometry. The tumorsphere culture, clone formation, growth curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were compared between the cell subsets in two groups; the expressions of stem cell-related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and mRNA were compared between the cell subsets in two groups. The data was statistically analyzed. The measurement data between the two groups were compared using t test. The count data between the two groups were compared using χ 2 test and Kaplan-Meier survival analysis. A P value osteosarcoma in the metastasis group was significantly lower than that in the non-metastasis group. The difference was statistically significant (P osteosarcoma CD133 + cell subsets was significantly lower than that in CD133 - cell subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human osteosarcoma CD133 + cell subsets with lower expression of TREX1; the biological characteristics identification experiment showed that human CD133 + cell subsets with low TREX1 expression could form tumorspheres, the number of colony forming was more, the cell proliferation ability was strong, the osteogenic and adipogenic differentiation potential was big, the tumor-forming ability in nude mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was low. The expression of TREX1 may be related to metastasis in

  10. Chondroblastic osteosarcoma mimicking periapical abscess

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    Fernanda Paula YAMAMOTO-SILVA

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

  11. Application of Long Noncoding RNAs in Osteosarcoma: Biomarkers and Therapeutic Targets

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    Zhihong Li

    2017-07-01

    Full Text Available Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1 are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.

  12. Flavonoids Active Against Osteosarcoma: A Review of the Molecular Mechanisms Involved.

    Science.gov (United States)

    Liu, Hui; Gao, Yutong; Dong, Yonghui; Cheng, Peng; Chen, Anmin; Huang, Hui

    2017-01-01

    Osteosarcoma is the most frequent primitive malignant bone tumor affecting adolescents and young adults worldwide. The tumor exhibits aggressive growth in the primary site and readily metastasizes to other organs. There has been no significant improvement in the 5-year survival rate since the 1970s and the figure remains at 60-70%. In addition, the side effects of chemotherapeutic drugs and resistance to chemotherapy compromise the effects of treatment for osteosarcoma. In recent years, the development of flavonoids drugs inhibiting carcinogenesis is attracting great interest in the scientific community. Flavonoids are one kind of polyphenolic compounds widely found in vegetables and fruits. Moreover, flavonoids have become popular compounds, exhibiting comprehensive antitumor activities, while being safe and inexpensive. Here, the literature on the benefits afforded by flavonoids in terms of osteosarcoma treatment is reviewed and certain flavonoids and their effects on osteosarcoma are discussed. These compounds can perturb the cell cycle, induce apoptosis, inhibit tumor cell invasion and metastasis, potentiate the actions of chemotherapeutic agents, trigger autophagy, and stimulate antitumor activity in vivo. In summary, we highlight the currently well-accepted flavonoid compounds and detail the molecular mechanisms by which flavonoids may treat osteosarcoma, and thus the flavonoids exhibit great promise as anti-osteosarcoma agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma

    International Nuclear Information System (INIS)

    Susa, Michiro; Iyer, Arun K; Ryu, Keinosuke; Hornicek, Francis J; Mankin, Henry; Amiji, Mansoor M; Duan, Zhenfeng

    2009-01-01

    Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOS R2 , U-2OS, and U-2OS R2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma

  14. LncRNA expression and implication in osteosarcoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-11-01

    Full Text Available Ying Wang,1,2,* Yuelong Huang,2,* Peng Xiang,3 Wei Tian2 1Department of Molecular Orthopaedics, Beijing Institute of Traumatology and Orthopaedics, 2Department of Spinal Surgery, Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, 3Department of Urology, Peking University First Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: Osteosarcoma is the most prevalent primary bone tumor in children, adolescents, and older adults, typically presenting with poor survival outcomes. In recent years, ample evidence has shown that many long noncoding RNAs (lncRNAs have been aberrantly expressed in osteosarcoma, demonstrating their potential to serve as prognostic markers. In this study, we performed a meta-analysis on four lncRNAs (TUG1, UCA1, BCAR4, and HULC to systematically evaluate their prognostic value in osteosarcoma.Materials and methods: The eligible articles were systematically searched in PubMed, Web of Science, Embase, and Elsevier ScienceDirect (up to September 22, 2017, and one meta-analysis concerning the association between lncRNA expression and the overall survival (OS of osteosarcoma patients was performed. Survival outcomes were analyzed by OS. Subgroup analyses were performed.Results: A total of 1,361 patients with osteosarcoma and 12 lncRNAs from 16 articles were included in the study. Of the listed lncRNAs, the high expression of 10 lncRNAs indicated worse survival outcomes, while only two lncRNAs were shown to positively affect patients’ OS.Conclusion: This meta-analysis indicated that the abnormally expressed lncRNAs might significantly affect the survival of osteosarcoma patients. Combined use of these lncRNAs may serve as potential novel biomarkers for the indication of clinical outcomes of osteosarcoma patients as well as the selection of adjuvant chemotherapy strategies for clinical treatment of this disease. Keywords: lncRNAs, osteosarcoma

  15. MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells.

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    Vanita Vanas

    Full Text Available Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

  16. Transplantation of canine osteosarcoma into nude mice

    International Nuclear Information System (INIS)

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

    1975-01-01

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

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

    Science.gov (United States)

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

    1998-03-01

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

  18. Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

    DEFF Research Database (Denmark)

    Modrzynska, Justyna; Berthing, Trine; Ravn-Haren, Gitte

    2018-01-01

    Background Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during...

  19. Usefulness of pulmonary scintigraphy in primary lung cancer patients treated by radiotherapy

    International Nuclear Information System (INIS)

    Mitomo, Osamu

    1994-01-01

    To assess the pulmonary function of lung cancer patients treated by radiotherapy, we tried qualitative and semiquantitative analysis of pulmonary scintigrams using 133 Xe and 99m Tc-MAA. Individual scores for ventilation, perfusion and the ventilation-perfusion ratio of tumor-bearing lungs were calculated on the basis of healthy control cases in order to analyze whether, and to what degree, the tumor-bearing lung was functionally impaired. The score was proportional to the severity of impairment, and when the ventilation and perfusion of tumor-bearing lungs had a score of one or greater than one, the tumor-bearing lung was functionally defined as an 'impaired lung'. Impaired lungs were demonstrated in 68% of tumor-bearing lungs. Hilar and left hilar-type cancers, clinically more advanced cancers, patients whose tumors were confirmed by bronchofiberscopy, small-cell and epidermoid cancers, etc., had higher rates of impairment and more severe impairment. Many patients with impaired lungs had a worse prognosis, but patients in whom scintigraphy showed improvement after radiotherapy had a better prognosis. It can be concluded that pulmonary scintigraphy scoring is capable of semiquantitatively indicating the degree of pulmonary impairment and is useful in deciding on a radiotherapeutic plan and predicting the outcome in pre- and post-radiotherapy lung cancer patients. (author)

  20. Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

    Science.gov (United States)

    Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

    2018-05-01

    Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  1. In vitro cultivation of canine osteosarcoma

    International Nuclear Information System (INIS)

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

    1975-01-01

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

  2. Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

    International Nuclear Information System (INIS)

    Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho; Suk, Eun Ha

    2013-01-01

    Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

  3. The cost-effectiveness of a structured education pulmonary rehabilitation programme for chronic obstructive pulmonary disease in primary care: the PRINCE cluster randomised trial.

    Science.gov (United States)

    Gillespie, Paddy; O'Shea, Eamon; Casey, Dympna; Murphy, Kathy; Devane, Declan; Cooney, Adeline; Mee, Lorraine; Kirwan, Collette; McCarthy, Bernard; Newell, John

    2013-11-25

    To assess the cost-effectiveness of a structured education pulmonary rehabilitation programme (SEPRP) for chronic obstructive pulmonary disease (COPD) relative to usual practice in primary care. The programme consisted of group-based sessions delivered jointly by practice nurses and physiotherapists over 8 weeks. Cost-effectiveness and cost-utility analysis alongside a cluster randomised controlled trial. 32 general practices in Ireland. 350 adults with COPD, 69% of whom were moderately affected. Intervention arm (n=178) received a 2 h group-based SEPRP session per week over 8 weeks delivered jointly by a practice nurse and physiotherapist at the practice surgery or nearby venue. The control arm (n=172) received the usual practice in primary care. Incremental costs, Chronic Respiratory Questionnaire (CRQ) scores, quality-adjusted life years (QALYs) gained estimated using the generic EQ5D instrument, and expected cost-effectiveness at 22 weeks trial follow-up. The intervention was associated with an increase of €944 (95% CIs 489 to 1400) in mean healthcare cost and €261 (95% CIs 226 to 296) in mean patient cost. The intervention was associated with a mean improvement of 1.11 (95% CIs 0.35 to 1.87) in CRQ Total score and 0.002 (95% CIs -0.006 to 0.011) in QALYs gained. These translated into incremental cost-effectiveness ratios of €850 per unit increase in CRQ Total score and €472 000 per additional QALY gained. The probability of the intervention being cost-effective at respective threshold values of €5000, €15 000, €25 000, €35 000 and €45 000 was 0.980, 0.992, 0.994, 0.994 and 0.994 in the CRQ Total score analysis compared to 0.000, 0.001, 0.001, 0.003 and 0.007 in the QALYs gained analysis. While analysis suggests that SEPRP was cost-effective if society is willing to pay at least €850 per one-point increase in disease-specific CRQ, no evidence exists when effectiveness was measured in QALYS gained. Current Controlled Trials ISRCTN52 403 063.

  4. [Value of preoperative pulmonary artery diastolic pressure on predicting primary graft dysfunction after bilateral lung transplantation for patients with idiopathic pulmonary fibrosis].

    Science.gov (United States)

    Zhang, Feng; Xu, Hongyang; Jiang, Shuyun; Li, Jiaqiong; Lu, Shunmei; Wang, Dapeng; Zang, Zhidong; Pan, Hong; Chen, Jingyu

    2017-05-01

    To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF). A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation. Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGD group, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non

  5. Bifocal sclerosing osteosarcoma: unusual presentation and course

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  6. Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Weihai Liu

    2017-09-01

    Full Text Available Background/Aims: Osteosarcoma (OS is the most common primary malignant bone tumor in children and adolescents. However, the molecular mechanisms regulating osteosarcoma tumorigenesis and progression are still poorly understood. Circular RNAs (circRNAs have been identified as microRNA sponges and are involved in many important biological processes. This study aims to investigate the global changes in the expression pattern of circRNAs in osteosarcoma and provide a comprehensive understanding of differentially expressed circRNAs. Methods: Microarray based circRNA expression was determined in osteosarcoma cell lines and compared with hFOB1.19, which was used as the normal control. We confirmed the microarray data by real time-qPCR in both osteosarcoma cell lines and tissues. The circRNA/microRNA/mRNA interaction network was predicted using bioinformatics. Gene Ontology analysis and 4 annotation tools for pathway analysis (KEGG, Biocarta, PANTHER and Reactome were used to predict the functions of differentially expressed circRNAs. Results: We revealed a number of differentially expressed circRNAs and 12 of them were confirmed, which suggests a potential role of circRNAs in OS. Among these differentially expressed circRNAs, hsa_circRNA_103801 was up-regulated in both osteosarcoma cell lines and tissues, while hsa_circRNA_104980 was down-regulated. The most likely potential target miRNAs for hsa_circRNA_103801 include hsa-miR-370-3p, hsa-miR-338-3p and hsa-miR-877-3p, while the most potential target miRNAs of hsa_circRNA_104980 consist of hsa-miR-1298-3p and hsa-miR-660-3p. Functional analysis found that hsa_circRNA_103801 was involved in pathways in cancer, such as the HIF-1, VEGF and angiogenesis pathway, the Rap1 signaling pathway and the PI3K-Akt signaling pathway, while hsa_circRNA_104980 was related to some pathways such as the tight junction pathway. Conclusions: This study has identified the comprehensive expression profile of circRNAs in

  7. The HDAC inhibitor Vorinostat diminishes the in vitro metastatic behavior of Osteosarcoma cells.

    Science.gov (United States)

    Mu, Xiaodong; Brynien, Daniel; Weiss, Kurt R

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC) inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS.

  8. The HDAC Inhibitor Vorinostat Diminishes the In Vitro Metastatic Behavior of Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2015-01-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS.

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

    Science.gov (United States)

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

    2018-04-01

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

  10. 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

  11. Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

    Science.gov (United States)

    Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

    2016-03-01

    Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

  12. Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension

    NARCIS (Netherlands)

    van Beers, Eduard J.; van Eck-Smit, Berthe L. F.; Mac Gillavry, Melvin R.; van Tuijn, Charlotte F. J.; van Esser, Joost W. J.; Brandjes, Dees P. M.; Kappers-Klunne, Mies C.; Duits, Ashley J.; Biemond, Bart J.; Schnog, John-John B.

    2008-01-01

    Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown.

  13. Primary pulmonary low-grade angiosarcoma characterized by mismatch between {sup 18}F-FDG FET and dynamic contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    KIm, Eun Young; Lee, Ho Yun; Han, Joung Ho; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an {sup 18}F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.

  14. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

    DEFF Research Database (Denmark)

    Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

    2009-01-01

    Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

  15. D-dimer testing for safe exclusion and risk stratification in patients with acute pulmonary embolism in primary care

    Directory of Open Access Journals (Sweden)

    Zhou Yin

    2015-01-01

    Full Text Available Background: Safe exclusion and risk stratification are currently recommended for the initial management of patients with acute pulmonary embolism (APE. The aim of this study was to assess the safe exclusion and risk stratification value of D-dimer (DD for APE when tested at the beginning of admission. Materials and Methods: All consecutive Chinese APE patients and controls were recruited from January 2010 to December 2012. All measurements of serum indexes were made in duplicate and blinded to the patients′ status. All the 40 patients with the first episode of APE were confirmed by multi-detector computed tomographic pulmonary angiography. The plasma prothrombin time (PT, activated partial thromboplastin time, thrombin time, fibrinogen, and DD levels were measured within 24 h of admission. We used the Mann-Whitney U-test to determine the differences between groups and drew receiver operator characteristic curve to evaluate the indexes′ value in the APE screening. Results: The PT and DD in the APE group were significantly higher than those in the disease control group (P 1820 μg/L as cut-off value, the sensitivity, specificity, positive and negative predictive value was 82.5%, 75.2%, 56.9%, and 91.6%, respectively. Conclusion: The patients with APE showed significant higher DD levels compared with disease controls, suggesting a negative qualitative DD test result can safely and efficiently exclude APE in primary care.

  16. Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

    International Nuclear Information System (INIS)

    Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

    2009-01-01

    Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

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

    Science.gov (United States)

    Morello, Emanuela; Martano, Marina; Buracco, Paolo

    2011-09-01

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

  18. Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care

    Directory of Open Access Journals (Sweden)

    Carl Llor

    2008-10-01

    moderate patients in primary care.Keywords: exacerbation, chronic obstructive pulmonary disease, randomised controlled trial, amoxycillin, primary care, amoxycillin/clavulanate

  19. Involvement of HIF-1α activation in the doxorubicin resistance of human osteosarcoma cells.

    Science.gov (United States)

    Roncuzzi, Laura; Pancotti, Fabia; Baldini, Nicola

    2014-07-01

    Osteosarcoma is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, survival outcomes remain unsatisfactory, particularly in patients with metastatic and/or recurrent disease. Unfortunately, treatment failure is commonly due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. The aim of the present study was to investigate the role of hypoxia-inducible factor 1α (HIF‑1α) and its signalling pathways as mediators of drug-resistance in human osteosarcoma. Toward this aim, we established two osteosarcoma cell lines selected for resistance to doxorubicin, a drug of choice in the treatment of this tumour. Our results showed that the multidrug resistance (MDR) phenotype was also mediated by HIF-1α, the most important regulator of cell adaptation to hypoxia. Our data showed that this transcription factor promoted the outward transport of intracellular doxorubicin by activating the P-glycoprotein (P-gp) expression in osteosarcoma cells maintained in normoxic conditions. In addition, it hindered doxorubicin-induced apoptosis by regulating the expression of c-Myc and p21. Finally, we observed that the doxorubicin-resistant cells maintained for 2 months of continuous culture in a drug-free medium, lost their drug-resistance and this effect was associated with the absence of HIF-1α expression. The emerging role of HIF-1α in osteosarcoma biology indicates its use as a valuable therapeutic target.

  20. Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor

    Directory of Open Access Journals (Sweden)

    Noah Federman

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary malignancy of bone in children, adolescents, and adults. Despite extensive surgery and adjuvant aggressive high-dose systemic chemotherapy with potentially severe bystander side effects, cure is attainable in about 70% of patients with localized disease and only 20%–30% of those patients with metastatic disease. Targeted therapies clearly are warranted in improving our treatment of this adolescent killer. However, a lack of osteosarcoma-associated/specific markers has hindered development of targeted therapeutics. We describe a novel osteosarcoma-associated cell surface antigen, ALCAM. We, then, create an engineered anti-ALCAM-hybrid polymerized liposomal nanoparticle immunoconjugate (α-AL-HPLN to specifically target osteosarcoma cells and deliver a cytotoxic chemotherapeutic agent, doxorubicin. We have demonstrated that α-AL-HPLNs have significantly enhanced cytotoxicity over untargeted HPLNs and over a conventional liposomal doxorubicin formulation. In this way, α-AL-HPLNs are a promising new strategy to specifically deliver cytotoxic agents in osteosarcoma.

  1. Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma.

    Science.gov (United States)

    Mauchle, Ulrike; Selvarajah, Gayathri T; Mol, Jan A; Kirpensteijn, Jolle; Verheije, Monique H

    2015-08-01

    Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Clinical value of measurement of pulmonary radioaerosol mucociliary clearance in the work up of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Nielsen, Kim Gjerum; Mortensen, Jann

    2015-01-01

    BACKGROUND: We aimed to evaluate and define the general clinical applicability and impact of pulmonary radioaerosol mucociliary clearance (PRMC) on the work up of patients suspected of having primary ciliary dyskinesia (PCD). In addition, we wanted to evaluate the accuracy of the reference values...... primarily to results from nasal ciliary function testing, to electron microscopic (EM) examination of the ultrastructure of the cilia, and to the final clinical diagnosis. RESULTS: Of the 239 patients, 27 ended up with a final clinical diagnosis of definitive PCD. No patients with a PRMC test...... of the entire lung. Its greatest strength is its ability to reject a suspected PCD diagnosis with great certainty. In our material, this accounted for 2/3 of referred patients. In addition, the test has a high rate of conclusive results. According to our analyses, reference equations on children would benefit...

  3. Intracranial osteosarcoma after radiosurgery. Case report

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  4. Cutaneous osteosarcoma arising from a burn scar

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  5. p53 functions as a cell cycle control protein in osteosarcomas.

    OpenAIRE

    Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

    1990-01-01

    Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfect...

  6. Radio-isotope scanning using labelled bleomycin in positive and differential diagnosis of primary and secondary malignant pulmonary lesions

    International Nuclear Information System (INIS)

    Robert, J.; Bertrand, A.; Nouel, J.P.; Witz, H.

    1975-01-01

    A lung scan using bleomycin labelled with cobalt 57 was carried out in 308 patients representing 191 primary malignant tumours, 48 pulmonary metastases and 69 benign lesions. The primary and secondary malignant lesions always gave rise to a hyperactive focus except in 8 cases of primary lung tumour. The negative examination may be explained, either by the small size of the lesion or by radiotherapy in progress. Among the benign lesions, only advanced tuberculosis and very inflammatory lung diseases frequently took up labelled bleomycin (15 hyperactive foci out of 69 benign lesions). Quantitative measurements, i.e. ratio of the lesional activity/activity of healthy lung tissue, were carried out in all patients. The malignant lesions were usually more active than the benign lesions. There was no definite correlation between the uptake of labelled bleomycin and the histological nature of the lesion. However, undifferentiated and anaplastic carcinomas were often more active. One should emphasize that these results show that a hyperactive focus has a 94% chance of being a carcinoma. The absence of bleomycin uptake means that there is a 92% chance of a benign lesion [fr

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

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  8. Comparative studies on prognostic markers and signaling pathways for canine and human osteosarcoma

    NARCIS (Netherlands)

    Selvarajah, G.T.

    2011-01-01

    Osteosarcoma is an aggressive bone tumor that occurs naturally mainly in large and medium breed dogs where almost 90% of dogs will develop metastasis predominantly in the lungs. The standard treatments (extirpation of the primary tumor including limb amputation/sparing, post-operative chemotherapy

  9. Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma

    DEFF Research Database (Denmark)

    Colding-Rasmussen, Thomas; Thorn, Andrea Pohly; Horstmann, Peter

    2018-01-01

    BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diag...

  10. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

    NARCIS (Netherlands)

    Posthuma de Boer, J.; Witlox, M.A.; Kaspers, G.J.L.; van Royen, B.J.

    2011-01-01

    Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy

  11. Using canine osteosarcoma as a model to assess efficacy of novel therapies: can old dogs teach us new tricks?

    Science.gov (United States)

    Rodriguez, Carlos O

    2014-01-01

    Since its domestication more than 10,000 years ago, the dog has been the animal that most intimately shares our work and homelife. Interestingly, the dog also shares many of our diseases including cancer such as osteosarcoma. Like the human, osteosarcoma is the most common bone malignancy of the dog and death from pulmonary metastasis is the most common outcome. The incidence of this spontaneous bone neoplasm occurs ten times more frequently that it does so in children with about 8,000-10,000 cases estimated to occur in dogs in the USA. Because there is no "standard of care" in veterinary medicine, the dog can also serve us by being a model for this disease in children. Although the most common therapy for the dog with osteosarcoma is amputation followed by chemotherapy, not all owners choose this route. Consequently, novel therapeutic interventions can be attempted in the dog with or without chemotherapy that could not be done in humans with osteosarcoma due to ethical concerns. This chapter will focus on the novel therapies in the dog that have been reported or are in veterinary clinical trials at the author's institution. It is hoped that collaboration between veterinary oncologists and pediatric oncologists will lead to the development of novel therapies for (micro- or macro-) metastatic osteosarcoma that improve survival and might ultimately lead to a cure in both species.

  12. Lung cells support osteosarcoma cell migration and survival.

    Science.gov (United States)

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

    2017-01-25

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

  13. 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.

  14. 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.

  15. Chronic obstructive pulmonary disease and heart failure: research and clinical practice in primary care

    Directory of Open Access Journals (Sweden)

    Francesco Chiumeo

    2015-12-01

    Full Text Available The treatment of chronic obstructive pulmonary disease (COPD and comorbidities, increasing with age, is the challenge that nowadays health care systems are facing to better care treat these patients. For this reason a clinical trial was conducted in the province of Trento by a group of 30 volunteer general practitioners members of SNAMID (Scientific Society for Continuing Medical Education of General Practitioners. The objectives were to identify: i prevalence of COPD in patients (65-98 years in the province of Trento; ii presence and incidence of heart failure (HF in COPD patients; iii early detection of other chronic diseases; and iv improving electronic medical records (EMR as an innovation way of professional care management. From May 2011 to October 2013, 17 doctors completed the two-year work using the EMR. The studied patients were men and women (65-98 years, suffering from COPD; the considered data included: anthropometric information, smoking status, International Classification of Diseases (ICD-9 diagnosis of COPD, HF and chronic diseases, specific blood and instrumental tests. The extracted results were then linked with data of sentinel therapies, collected by the EMR. The database obtained identified patients with COPD or HF not previously recognized with ICD-9 diagnosis. The study identified the sentinel drugs chosen for COPD and HF, excluding other drugs not selective for the study or confusing for a proper statistical evaluation.

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

    Science.gov (United States)

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

    2011-12-01

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

  17. Galangin inhibits human osteosarcoma cells growth by inducing transforming growth factor-β1-dependent osteogenic differentiation.

    Science.gov (United States)

    Liu, Chunhong; Ma, Mingming; Zhang, Junde; Gui, Shaoliu; Zhang, Xiaohai; Xue, Shuangtao

    2017-05-01

    Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo. These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  19. Critical role of heat shock protein 27 in bufalin-induced apoptosis in human osteosarcomas: a proteomic-based research.

    Directory of Open Access Journals (Sweden)

    Xian-biao Xie

    Full Text Available Bufalin is the primary component of the traditional Chinese herb "Chan Su". Evidence suggests that this compound possesses potent anti-tumor activities, although the exact molecular mechanism(s is unknown. Our previous study showed that bufalin inhibited growth of human osteosarcoma cell lines U2OS and U2OS/MTX300 in culture. Therefore, this study aims to further clarify the in vitro and in vivo anti-osteosarcoma effects of bufalin and its molecular mechanism of action. We found bufalin inhibited both methotrexate (MTX sensitive and resistant human osteosarcoma cell growth and induced G2/M arrest and apoptosis. Using a comparative proteomics approach, 24 differentially expressed proteins following bufalin treatment were identified. In particular, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27, decreased remarkably. The down-regulation of Hsp27 and alterations of its partner signaling molecules (the decrease in p-Akt, nuclear NF-κB p65, and co-immunoprecipitated cytochrome c/Hsp27 were validated. Hsp27 over-expression protected against bufalin-induced apoptosis, reversed the dephosphorylation of Akt and preserved the level of nuclear NF-κB p65 and co-immunoprecipitated Hsp27/cytochrome c. Moreover, bufalin inhibited MTX-resistant osteosarcoma xenograft growth, and a down-regulation of Hsp27 in vivo was observed. Taken together, bufalin exerted potent anti-osteosarcoma effects in vitro and in vivo, even in MTX resistant osteosarcoma cells. The down-regulation of Hsp27 played a critical role in bufalin-induced apoptosis in osteosarcoma cells. Bufalin may have merit to be a potential chemotherapeutic agent for osteosarcoma, particularly in MTX-resistant groups.

  20. Intracortical osteoblastic osteosarcoma with oncogenic rickets

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  1. Intracortical osteoblastic osteosarcoma with oncogenic rickets

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-01-01

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

  2. On the importance of considering disease subtypes: Earliest detection of a parosteal osteosarcoma? Differential diagnosis of an osteosarcoma in an Anglo-Saxon female.

    Science.gov (United States)

    Ferrante di Ruffano, Lavinia; Waldron, Tony

    2016-12-30

    A case of potentially dedifferentiated parosteal osteosarcoma was found in the proximal humerus of an adult female buried in the late Anglo-Saxon cemetery of Cherry Hinton, Cambridgeshire, UK. Key features include a large, dense, lobulated mass attached to the medial metaphysis of the proximal humerus by a broad-based attachment, accompanied by cortical destruction and widespread spiculated periosteal reaction. Radiographic images confirm medullary involvement, lack of continuity between the cortex and external mass, a radiolucent cleavage plane and possible radiolucent zones within the bony masses. Differential diagnoses considered include osteochondroma, myositis ossificans, fracture callus, as well as the primary malignancies of osteosarcoma and chondrosarcoma, and their various subtypes. The macroscopic and radiographic analysis of the tumor is described and discussed within clinical and paleopathological contexts. One of only 19 uncontested examples of osteosarcoma from past human populations, most of which remain unconfirmed, this case represents what we believe to be the earliest, and probably singular, bioarcheological example of parosteal osteosarcoma in human history. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  3. A complex pattern of chemokine receptor expression is seen in osteosarcoma

    International Nuclear Information System (INIS)

    Luettichau, Irene von; Huss, Ralf; Nelson, Peter J; Segerer, Stephan; Wechselberger, Alexandra; Notohamiprodjo, Mike; Nathrath, Michaela; Kremer, Markus; Henger, Anna; Djafarzadeh, Roghieh; Burdach, Stefan

    2008-01-01

    Osteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma. The overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression. Expression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells. Our data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology

  4. Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells.

    Science.gov (United States)

    Paiva-Oliveira, Daniela I; Martins-Neves, Sara R; Abrunhosa, Antero J; Fontes-Ribeiro, Carlos; Gomes, Célia M F

    2018-01-01

    Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin. Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay. Metformin cytotoxicity alone and combined with doxorubicin were evaluated using MTT/BrdU assays. Protein levels of AMPK and AKT were evaluated by Western Blot. Cellular metabolic status was assessed based on [ 18 F]-FDG uptake and lactate production measurements. Sphere-forming efficiency and expression of pluripotency transcription factors analysed by qRT-PCR were tested as readout of Metformin effects on stemness features. Metformin induced a concentration-dependent decrease in the metabolic activity and proliferation of sphere-forming cells and improved doxorubicin-induced cytotoxicity. This drug also down-regulated the expression of master regulators of pluripotency (OCT4, SOX2, NANOG), and decreased spheres' self-renewal ability. Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations. Furthermore, Metformin-induced mitochondrial stress increased [ 18 F]-FDG uptake and lactate production in parental cells but not in the quiescent stem-like cells, suggesting the inability of the latter to cope with the energy crisis induced by metformin. This preclinical study suggests that Metformin may be a potentially useful therapeutic agent and chemosensitizer of osteosarcoma stem-like cells to doxorubicin.

  5. Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, C. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)], E-mail: ferraric@unipv.it; Zonta, C.; Cansolino, L.; Clerici, A.M.; Gaspari, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy); Altieri, S.; Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); Dionigi, P.; Zonta, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)

    2009-07-15

    Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of {sup 10}B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry {sup 10}B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue {sup 10}B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.

  6. Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

    Science.gov (United States)

    Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

    2016-12-01

    Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Resection of pulmonary metastases from colon and rectal cancer: factors to predict survival differ regarding to the origin of the primary tumor.

    Science.gov (United States)

    Meimarakis, G; Spelsberg, F; Angele, M; Preissler, G; Fertmann, J; Crispin, A; Reu, S; Kalaitzis, N; Stemmler, M; Giessen, C; Heinemann, V; Stintzing, S; Hatz, R; Winter, H

    2014-08-01

    The purpose of the present study was to determine differences in prognostic factors for survival of patients with pulmonary metastases resected in curative intent from colon or rectum cancer. Between 1980 and 2006, prognostic factors after resection of pulmonary metastases in 171 patients with primary rectum or colon tumor were evaluated. Survival of patients after surgical metastasectomy was compared with that of patients receiving standard chemotherapy by matched-pair analysis. Median survival after pulmonary resection was 35.2 months (confidence interval 27.3-43.2). One-, 3-, and 5-year survival for patients following R0 resection was 88.8, 52.1, and 32.9 % respectively. Complete metastasectomy (R0), UICC stage of the primary tumor, pleural infiltration, and hilar or mediastinal lymph node metastases are independent prognostic factors for survival. Matched-pair analysis confirmed that pulmonary metastasectomy significantly improved survival. Although no difference in survival for patients with pulmonary metastases from lower rectal compared to upper rectal or colon cancer was observed, factors to predict survival are different for patients with lower and middle rectal cancer (R0, mediastinal and/or hilar lymph nodes, gender, UICC stage) compared with patients with upper rectal or colon cancer (R0, number of metastases). Our results indicate that distinct prognostic factors exist for patients with pulmonary metastases from lower rectal compared with upper rectal or colon cancer. This supports the notion that colorectal cancer should not be considered as a single-tumor entity. Metastasectomy, especially after complete resection resulted in a dramatic improvement of survival compared with patients treated with chemotherapy alone.

  8. The effectiveness of a structured education pulmonary rehabilitation programme for improving the health status of people with moderate and severe chronic obstructive pulmonary disease in primary care: the PRINCE cluster randomised trial.

    Science.gov (United States)

    Casey, Dympna; Murphy, Kathy; Devane, Declan; Cooney, Adeline; McCarthy, Bernard; Mee, Lorraine; Newell, John; O'Shea, Eamon; Scarrott, Carl; Gillespie, Paddy; Kirwan, Collette; Murphy, Andrew W

    2013-10-01

    To evaluate the effectiveness of a structured education pulmonary rehabilitation programme on the health status of people with chronic obstructive pulmonary disease (COPD). Two-arm, cluster randomised controlled trial. 32 general practices in the Republic of Ireland. 350 participants with a diagnosis of moderate or severe COPD. Experimental group received a structured education pulmonary rehabilitation programme, delivered by the practice nurse and physiotherapist. Control group received usual care. Health status as measured by the Chronic Respiratory Questionnaire (CRQ) at baseline and at 12-14 weeks postcompletion of the programme. Participants allocated to the intervention group had statistically significant higher mean change total CRQ scores (adjusted mean difference (MD) 1.11, 95% CI 0.35 to 1.87). However, the CI does not exclude a smaller difference than the one that was prespecified as clinically important. Participants allocated to the intervention group also had statistically significant higher mean CRQ Dyspnoea scores after intervention (adjusted MD 0.49, 95% CI 0.20 to 0.78) and CRQ Physical scores (adjusted MD 0.37, 95% CI 0.14 to 0.60). However, CIs for both the CRQ Dyspnoea and CRQ Physical subscales do not exclude smaller differences as prespecified as clinically important. No other statistically significant differences between groups were seen. A primary care based structured education pulmonary rehabilitation programme is feasible and may increase local accessibility to people with moderate and severe COPD. ISRCTN52403063.

  9. Outcomes of Adolescent and Adult Patients with Lung Metastatic Osteosarcoma and Comparison of Synchronous and Metachronous Lung Metastatic Groups.

    Directory of Open Access Journals (Sweden)

    Ayse Gok Durnali

    Full Text Available Osteosarcomas with lung metastases are rather heterogenous group. We aimed to evaluate the clinicopathological characteristics and outcomes of osteosarcoma patients with lung metastases and to compare the synchronous and metachronous lung metastatic groups. A total of 93 adolescent and adult patients with lung metastatic osteosarcoma, from March 1995 to July 2011, in a single center, were included. Sixty-five patients (69.9% were male. The median age was 19 years (range, 14-74. Thirty-nine patients (41.9% had synchronous lung metastases (Group A and 54 patients (58.1% had metachronous lung metastases (Group B. The 5-year and 10-year post-lung metastases overall survival (PLM-OS was 17% and 15%, respectively. In multivariate analysis for PLM-OS, time to lung metastases (p = 0.010, number of metastatic pulmonary nodules (p = 0.020, presence of pulmonary metastasectomy (p = 0.007 and presence of chemotherapy for lung metastases (p< 0.001 were found to be independent prognostic factors. The median PLM-OS of Group A and Group B was 16 months and 9 months, respectively. In Group B, the median PLM-OS of the patients who developed lung metastases within 12 months was 6 months, whereas that of the patients who developed lung metastases later was 16 months. Time to lung metastases, number and laterality of metastatic pulmonary nodules, chemotherapy for lung metastatic disease and pulmonary metastasectomy were independent prognostic factors for patients with lung metastatic osteosarcoma. The best PLM-OS was in the subgroup of patients treated both surgery and chemotherapy. The prognosis of the patients who developed lung metastases within 12 months after diagnosis was worst.

  10. 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.

  11. Osteocalcin and Osteonectin Expression in Canine Osteosarcoma.

    Science.gov (United States)

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

    2016-07-01

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

  12. Asthma, chronic obstructive pulmonary disease, or both? Diagnostic labeling and spirometry in primary care patients aged 40 years or more

    Science.gov (United States)

    Melbye, Hasse; Drivenes, Elin; Dalbak, Lene G; Leinan, Tone; Høegh-Henrichsen, Svein; Østrem, Anders

    2011-01-01

    Aims To describe symptoms and lung function in patients registered with asthma or chronic obstructive pulmonary disease (COPD) in primary care and to examine how spirometry findings fit with general practitioners’ (GPs) diagnoses. Methods Patients aged ≥40 years with a diagnosis of asthma or COPD registered in the electronic medical record during the previous 5 years were recruited at seven GP offices in Norway in 2009–2010. Registered diagnosis, spirometry results, comorbidity, and reported symptoms were compared. Results Among 376 patients, 62% were women. Based on Global Initiative for Chronic Obstructive Lung Diseases criteria, a spirometry diagnosis of COPD could be made in 68.1% of the patients with a previous COPD diagnosis and in 17.1% of those diagnosed with asthma only (P spirometry was 0.50. A restrictive spirometry pattern was found in 19.4% and more frequently in patients diagnosed with both asthma and COPD (23.9%) than in patients diagnosed with COPD only (6.8%, P = 0.003). Conclusion The ability of GPs to differentiate between asthma and COPD seems to have considerably improved during the last decade, probably due to the dissemination of spirometry and guidelines for COPD diagnosis. A diagnosis of COPD that cannot be confirmed by spirometry represents a challenge in clinical practice, in particular when a restrictive pattern on spirometry is found. PMID:22135492

  13. Correlation between Either Cupriavidus or Porphyromonas and Primary Pulmonary Tuberculosis Found by Analysing the Microbiota in Patients' Bronchoalveolar Lavage Fluid.

    Science.gov (United States)

    Zhou, Yuhua; Lin, Feishen; Cui, Zelin; Zhang, Xiangrong; Hu, Chunmei; Shen, Tian; Chen, Chunyan; Zhang, Xia; Guo, Xiaokui

    2015-01-01

    Pulmonary tuberculosis (TB) has gained attention in recent decades because of its rising incidence trend; simultaneously, increasing numbers of studies have identified the relationship between microbiota and chronic infectious diseases. In our work, we enrolled 32 patients with primary TB characterised by unilateral TB lesion formation diagnosed by chest radiographic exam. Bronchoalveolar lavage fluid was taken from both lungs. Twenty-four healthy people were chosen as controls. Pyrosequencing was performed on the V3 hypervariable region of 16S rDNA in all bacterial samples and used as a culture-independent method to describe the phylogenetic composition of the microbiota. Through pyrosequencing, 271,764 amplicons were detected in samples and analysed using tools in the Ribosomal Database Project (RDP) and bioinformatics. These analyses revealed significant differences in the microbiota in the lower respiratory tract (LRT) of TB patients compared with healthy controls; in contrast, the microbiota of intra/extra-TB lesions were similar. These results showed that the dominant bacterial genus in the LRT of TB patients was Cupriavidus and not Streptococcus, which resulted in a significant change in the microbiota in TB patients. The abundance of Mycobacteria and Porphyromonas significantly increased inside TB lesions when compared with non-lesion-containing contralateral lungs. From these data, it can be concluded that Cupriavidus plays an important role in TB's secondary infection and that in addition to Mycobacteria, Porphyromonas may also be a co-factor in lesion formation. The mechanisms underlying this connection warrant further research.

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

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

    2018-03-01

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

  15. Bone scintigraphy for metastasis detection in canine osteosarcoma

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  16. Asthma, chronic obstructive pulmonary disease, or both? Diagnostic labeling and spirometry in primary care patients aged 40 years or more

    Directory of Open Access Journals (Sweden)

    Melbye H

    2011-11-01

    Full Text Available Hasse Melbye1, Elin Drivenes1, Lene G Dalbak2, Tone Leinan1, Svein Høegh-Henrichsen2, Anders Østrem21General Practice Research Unit, Department of Community Medicine, University of Tromsø, 2General Practice Research Unit, Department of Health and Society, University of Oslo, NorwayAims: To describe symptoms and lung function in patients registered with asthma or chronic obstructive pulmonary disease (COPD in primary care and to examine how spirometry findings fit with general practitioners’ (GPs diagnoses.Methods: Patients aged ≥40 years with a diagnosis of asthma or COPD registered in the electronic medical record during the previous 5 years were recruited at seven GP offices in Norway in 2009–2010. Registered diagnosis, spirometry results, comorbidity, and reported symptoms were compared.Results: Among 376 patients, 62% were women. Based on Global Initiative for Chronic Obstructive Lung Diseases criteria, a spirometry diagnosis of COPD could be made in 68.1% of the patients with a previous COPD diagnosis and in 17.1% of those diagnosed with asthma only (P < 0.001. The κ agreement between last clinical diagnosis of COPD and COPD based on spirometry was 0.50. A restrictive spirometry pattern was found in 19.4% and more frequently in patients diagnosed with both asthma and COPD (23.9% than in patients diagnosed with COPD only (6.8%, P = 0.003.Conclusion: The ability of GPs to differentiate between asthma and COPD seems to have considerably improved during the last decade, probably due to the dissemination of spirometry and guidelines for COPD diagnosis. A diagnosis of COPD that cannot be confirmed by spirometry represents a challenge in clinical practice, in particular when a restrictive pattern on spirometry is found.Keywords: asthma, COPD, diagnosis, primary care

  17. Pathogenesis of radiation-induced osteosarcomas

    International Nuclear Information System (INIS)

    Luz, A.

    1980-07-01

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

  18. [Pulmonary carcinoma nowadays: notes on epidemiology, primary prevention, and therapeutic planning].

    Science.gov (United States)

    Motta, G

    1995-01-01

    Among the solid malignancies, lung cancer is today the most common cancer in the world (850,000 new cases during 1990). Moreover, with an estimated increase of about 5 percent a year, it now represents the first cause of mortality for cancer in both sexes. The evidence of a close relationship between lung cancer and cigarette smoking was first pointed out by E. Graham in 1950. Since then, the responsibility of active cigarette smoking in determining lung cancer as well as that of nicotine causing addictiveness, have been assessed clearly. Nevertheless primary prevention, mainly through the campaign against cigarette smoking, has always faced great difficulties because it clashes with the economic power and interests of tobacco companies. Moreover the epidemiologic trends show a progressive increase of the disease with a silent epidemic-like worldwide diffusion, in close similarity to AIDS. So, more than 5 million new cases a year of lung cancer are expected to appear at the beginning of 2000. The primary prevention against the major factor of risk-the cigarette-is mainly based, in developed countries, through the following official measures: i) a heavy taxation on the finished goods; ii) the conversion of the tobacco growing to other crops and iii) the package-based health information for all tobacco products. On the other side, while waiting for new effective chemoprevention methods, the need of getting a true early clinical diagnosis of tumor is emphasised. Only by this means is it indeed possible to improve the rate of cure through performing conventional resections of those cancers which could be discovered in still limited clinical stage. In the same time, a strong effort for radically operating Stage III locally advanced cancers, is also attempted through the newer tracheobronchoplastic procedures as well as the other over extended resections done directly in the mediastinal area. The neoadjuvant radio and/or chemotherapy combined treatments preceding surgery

  19. Studies on pulmonary ventilation-perfusion scintigraphy with Xe-133 in primary lung cancer, 1

    International Nuclear Information System (INIS)

    Oshibuchi, Masao

    1984-01-01

    Regional lung ventilation-perfusion scintigraphy by xenon gas was performed on 14 normal cases (normal group) and 86 cases of primary lung cancer (lung cancer group). The patients were measured in a sitting position using a scintillation camera. In normal group, the value of V, Q was higher in the lower lung field than in the upper lung field, the value of MTT was rather delayed in the upper lung field than in the lower lung field, proving to that lung clearance was better in the lower lung field than in the upper lung field. In lung cancer group, VQ match (pattern I, II) was 61 cases (71%) and VQ mismatch (pattern III, IV) was 25 cases (29%). The pattern II (VQ matched defect) accounted for 63% in lung cancer group. In this pattern, the region of disorder of V and Q was corresponded respectively, but disorder grade was not always accorded. The pattern III (normal V and disordered Q) was mainly seen in AH group (hilar type) and D group (lymph node swelling type). The V/Q in lung cancer group was widely distributed to the range of 0 to 5.8. The value of MTT was rather delayed in all cases of lung cancer group than in the normal group, because delayed MTT in focal lesion was markedly affected to whole lung. (author)

  20. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Science.gov (United States)

    Pang, Lisa Y; Gatenby, Emma L; Kamida, Ayako; Whitelaw, Bruce A; Hupp, Ted R; Argyle, David J

    2014-01-01

    Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  1. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Directory of Open Access Journals (Sweden)

    Lisa Y Pang

    Full Text Available Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs, which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05, and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  2. Wnt/β-catenin expression does not correlate with serum alkaline phosphatase concentration in canine osteosarcoma patients.

    Directory of Open Access Journals (Sweden)

    Caroline M Piskun

    Full Text Available Osteosarcoma is an aggressive malignancy of the bone and an increase in serum alkaline phosphatase concentration has clinical prognostic value in both humans and canines. Increased serum alkaline phosphatase concentration at the time of diagnosis has been associated with poorer outcomes for osteosarcoma patients. The biology underlying this negative prognostic factor is poorly understood. Given that activation of the Wnt signaling pathway has been associated with alkaline phosphatase expression in osteoblasts, we hypothesized that the Wnt/β-catenin signaling pathway would be differentially activated in osteosarcoma tissue based on serum ALP status. Archived canine osteosarcoma samples and primary canine osteosarcoma cell lines were used to evaluate the status of Wnt/β-catenin signaling pathway activity through immunohistochemical staining, western immunoblot analyses, quantitative reverse-transcription polymerase chain reaction, and a Wnt-responsive promoter activity assay. We found no significant difference in β-catenin expression or activation between OSA populations differing in serum ALP concentration. Pathway activity was mildly increased in the primary OSA cell line generated from a patient with increased serum ALP compared to the normal serum ALP OSA cell line. Further investigation into the mechanisms underlying differences in serum ALP concentration is necessary to improve our understanding of the biological implications of this negative prognostic indicator.

  3. Video-assisted microwave ablation for the treatment of a metastatic lung lesion in a dog with appendicular osteosarcoma and hypertrophic osteopathy.

    Science.gov (United States)

    Mazzaccari, Kaitlyn; Boston, Sarah E; Toskich, Beau B; Bowles, Kristina; Case, J Brad

    2017-11-01

    To describe video-assisted microwave ablation (VAMA) for the treatment of a metastatic lung lesion secondary to right forelimb osteosarcoma in a dog. Case report. A 10-year-old female spayed mixed breed dog with a metastatic lung lesion secondary to appendicular osteosarcoma. An osteosarcoma of the right distal scapula and proximal humerus that was suspected to be a radiation-induced osteosarcoma was treated with limb amputation and carboplatin chemotherapy. The patient developed pulmonary metastatic lesions and hypertrophic osteopathy (HO). VAMA of a metastatic lesion in the right caudal lung lobe was performed 227 days after amputation. The procedure was performed without complication. Follow-up information with the referring veterinarian 40 days after VAMA indicated that the patient was stable and that the clinical signs of HO had resolved. Thoracic radiographs taken by the referring veterinarian (RDVM) at monthly intervals showed that the previously treated metastatic lesion was stable. At 134 days from VAMA, the patient presented to the RDVM for lethargy and dyspnea and was transferred to an emergency clinic. The patient arrested and died 136 days from the VAMA procedure while hospitalized. A postmortem was not performed. VAMA for pulmonary metastatic lesions is technically feasible and allows for the treatment of symptoms associated with HO and minimally invasive management of pulmonary metastases in the case reported. © 2017 The American College of Veterinary Surgeons.

  4. Evaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia.

    Science.gov (United States)

    Pifferi, Massimo; Bush, Andrew; Pioggia, Giovanni; Caramella, Davide; Tartarisco, Gennaro; Di Cicco, Maria; Zangani, Marta; Chinellato, Iolanda; Maggi, Fabrizio; Tezza, Giovanna; Macchia, Pierantonio; Boner, Attilio

    2012-11-01

    In primary ciliary dyskinesia (PCD) lung damage is usually evaluated by high-resolution CT (HRCT). To evaluate whether HRCT abnormalities and Pseudomonas aeruginosa infection were better predicted by spirometry or plethysmography. A cross-sectional study performed in consecutive patients with PCD who underwent sputum culture, spirometry, plethysmography and HRCT within 48 h. Principal component analysis and soft computing were used for data evaluation. Fifty patients (26 children) were studied. P aeruginosa infection was found in 40% of the patients and bronchiectasis in 88%. There was a correlation between infection with P aeruginosa and extent of bronchiectasis (p=0.009; r =0.367) and air-trapping (p=0.03; r =0.315). Moreover, there was an association between infection with P aeruginosa and residual volume (RV) values >150% (p=0.04) and RV/total lung capacity (TLC) ratio >140% (p=0.001), but not between infection with P aeruginosa and forced expiratory volume in 1 s (FEV(1))<80%, or forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%))<70% or FEV(1)/FVC<70% (<80% in children). Severity of the total lung impairment on chest HRCT directly correlated with RV when expressed as per cent predicted (p=0.003; r =0.423), and RV/TLC (p<0.001; r =0.513) or when expressed as z scores (p=0.002, r =0.451 and p<0.001, r =0.536 respectively). Principal component analysis on plethysmographic but not on spirometry data allowed recognition of different severities of focal air trapping, atelectasis and extent of bronchiectasis. Plethysmography better predicts HRCT abnormalities than spirometry. Whether it might be a useful test to define populations of patients with PCD who should or should not have HRCT scans requires further longitudinal studies.

  5. Primary care physician perceptions on the diagnosis and management of chronic obstructive pulmonary disease in diverse regions of the world

    Directory of Open Access Journals (Sweden)

    Aisanov Z

    2012-04-01

    Full Text Available Zaurbek Aisanov1,*, Chunxue Bai2,*, Otto Bauerle3,*, Federico D Colodenco4,*, Charles Feldman5,6,*, Shu Hashimoto7,*, Jose Jardim8,*, Christopher KW Lai9,*, Rafael Laniado-Laborin10,*, Gilbert Nadeau11,*, Abdullah Sayiner12,*, Jae Jeong Shim13,*, Ying Huang Tsai14,*, Richard D Walters11,*, Grant Waterer15,* 1Pulmonology Research Institute, Moscow, Russia; 2Department of Pulmonary Medicine, Fudan University, Shanghai, People's Republic of China; 3Centro Médico de las Américas, Mérida, Yucatán, Mexico; 4Hospital de Rehabilitación Respiratoria "María Ferrer," Buenos Aires, Argentina; 5Department of Internal Medicine, Charlotte Maxeke Johannesburg Hospital, Johannesburg, South Africa; 6Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 7Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 8Federal University of São Paulo, São Paulo, Brazil; 9Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; 10Faculty of Medicine, Universidad Autónoma de Baja California, Tijuana, Baja California, Mexico; 11Medical Affairs, GlaxoSmithKline, Brentford, UK; 12Department of Chest Diseases, Ege University Medical School, Izmir, Turkey; 13Department of Pulmonology, Guro Hospital, Korea University Medical Center, Seoul, South Korea; 14Department of Respiratory Care Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan; 15School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia*ICON group (International COPD Network, listed in alphabetical orderAbstract: Chronic obstructive pulmonary disease (COPD is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality. Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little

  6. Prevalence of 5-lipoxygenase expression in canine osteosarcoma and the effects of a dual 5-lipoxygenase/cyclooxygenase inhibitor on osteosarcoma cells in vitro and in vivo.

    Science.gov (United States)

    Goupil, R C; Bushey, J J; Peters-Kennedy, J; Wakshlag, J J

    2012-09-01

    Canine osteosarcoma is an insidious disease with few effective treatment modalities; therefore, use of pharmacologic intervention to improve mortality or morbidity is constantly sought. The use of cyclooxygenase enzyme inhibitors has been an area of interest with limited efficacy based on retrospective examination of tumor expression and in vivo cell proliferation models. Recently, examination of dual cyclooxygenase and 5-lipoxygenase inhibitors in human and canine oncology suggests that 5-lipoxygenase inhibitors may be an effective approach in vitro and during tumor induction in rodent models. Therefore, the authors decided to examine 5-lipoxygenase expression in primary canine osteosarcoma samples and have shown that approximately 65% of osteosarcomas label positive for cytoplasmic 5-lipoxygenase. Further examination of a cell culture and xenograft model shows similar 5-lipoxygenase expression. Surprisingly, a canine 5-lipoxygenase inhibitor (tepoxalin) significantly reduced cell proliferation at physiologic doses in vitro and diminished xenograft tumor growth in nude mice, suggesting that further investigation is needed. Traditionally, 5-lipoxygense leads to production of lipid mediators, such as leukotriene B(4) and 5-oxo-eicosatetraenoic acid, which, when added back to the media of tepoxalin-treated cells, did not recover cell proliferation. The lack of nuclear staining in primary and xenografted tumors and the lack of response to eicoasanoids suggest that lipid mediator production is not the primary means by which tepoxalin acts to alter proliferation. Regardless of the mechanisms involved in retarding cell proliferation, future investigation is warranted.

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

    Science.gov (United States)

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

    2009-05-01

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

  8. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-05-09

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  9. Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

    Science.gov (United States)

    2012-01-01

    Background Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. Results A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Conclusions Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma. PMID:22587466

  10. Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

    Directory of Open Access Journals (Sweden)

    Boerman Ilse

    2012-05-01

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

  11. Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

    International Nuclear Information System (INIS)

    Bacci, Gaetano; Longhi, Alessandra; Forni, Cristiana R.N.; Fabbri, Nicola; Briccoli, Antonio; Barbieri, Enza; Mercuri, Mario; Balladelli, Alba B.A.; Ferrari, Stefano; Picci, Piero

    2007-01-01

    Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01)

  12. Inhibition of polo-like kinase 1 leads to the suppression of osteosarcoma cell growth in vitro and in vivo.

    Science.gov (United States)

    Liu, Xianzhe; Choy, Edwin; Harmon, David; Yang, Shuhua; Yang, Cao; Mankin, Henry; Hornicek, Francis J; Duan, Zhenfeng

    2011-06-01

    Osteosarcoma is the most common type of primary bone cancer in children and adolescents. Treatment options for osteosarcoma may include surgery, chemotherapy, and radiotherapy. Unfortunately, many patients eventually relapse, resulting in an unsatisfactory outcome. The serine/threonine-specific polo-like kinase 1 (PLK1) is a kinase that plays an important role in mitosis and the maintenance of genomic stability. PLK1 has been found to be highly expressed in the malignant cells of osteosarcoma. Here, we describe the in-vitro and in-vivo effects of BI 2536, a small-molecule inhibitor of PLK1, which through inhibiting PLK1 enzymatic activity, causes mitotic arrest and eventually induces cancer cell apoptosis. In this study, we show that the PLK1 inhibitor, BI 2536, inhibits proliferation and induces apoptosis in two-dimensional and three-dimensional cultures of osteosarcoma cell lines, KHOS and U-2OS. A proliferation assay performed both in two-dimensional and three-dimensional culture showed that the growth of both cell lines was inhibited by BI 2536. Cell cycle analysis showed that the cells treated with BI 2536 were mainly arrested in the G2/M phase. Immunofluorescence and western blotting analysis confirmed that the administration of BI 2536 led to significant decrease of PLK1 and Mcl-1 protein expression levels in dose-dependent and time-dependent manners. Furthermore, BI 2536-induced apoptosis in the osteosarcoma cell lines was shown by poly (ADP-ribose) polymerase cleavage and caspase assay. Finally, in mouse osteosarcoma xenografts, BI 2536-treated mice had significantly smaller tumors compared with the control mice. These findings offer evidence of the potential role for targeting PLK1 in osteosarcoma therapy.

  13. Survival rate and prognostic factors of conventional osteosarcoma in Northern Thailand: A series from Chiang Mai University Hospital.

    Science.gov (United States)

    Pruksakorn, Dumnoensun; Phanphaisarn, Areerak; Arpornchayanon, Olarn; Uttamo, Nantawat; Leerapun, Taninnit; Settakorn, Jongkolnee

    2015-12-01

    Osteosarcoma is a common and aggressive primary malignant bone tumor occurring in children and adolescents. It is one of the most aggressive human cancers and the most common cause of cancer-associated limb loss. As treatment in Thailand has produced a lower survival rate than in developed countries; therefore, this study identified survival rate and the poor prognostic factors of osteosarcoma in Northern Thailand. The retrospective cases of osteosarcoma, diagnosis between 1 January 1996 and 31 December 2013, were evaluated. Five and ten year overall survival rates were analyzed using time-to-event analysis. Potential prognostic factors were identified by multivariate regression analysis. There were 208 newly diagnosed osteosarcomas during that period, and 144 cases met the criteria for analysis. The majority of the osteosarcoma cases (78.5%) were aged 0-24 years. The overall 5- and 10-year survival rates were 37.9% and 33.6%, respectively. Presence of metastasis at initial examination, delayed and against treatment co-operation, and axial skeletal location were identified as independent prognostic factors for survival, with hazard ratios of 4.3, 2.5 and 3.8, and 3.1, respectively. This osteosarcoma cohort had a relatively poor overall survival rate. The prognostic factors identified would play a critical role in modifying survival rates of osteosarcoma patients; as rapid disease recognition, a better treatment counselling, as well as improving of chemotherapeutic regimens were found to be important in improving the overall survival rate in Thailand. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

    Science.gov (United States)

    Palmerini, E; Jones, R L; Marchesi, E; Paioli, A; Cesari, M; Longhi, A; Meazza, C; Coccoli, L; Fagioli, F; Asaftei, S; Grignani, G; Tamburini, A; Pollack, S M; Picci, P; Ferrari, S

    2016-04-20

    Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

  15. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

    International Nuclear Information System (INIS)

    Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

    2016-01-01

    Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m 2 d 1, 8; D 75 mg/m 2 d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8–71), 26 (51 %) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49 %) patients had metastases limited to lungs, 26 (51 %) multiple sites. Histology: 40 (78 %) osteosarcoma, 11 (22 %) HGS. Eight (16 %) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46 %, and significantly better for patients with ECOG 0 (ECOG 0: 54 % vs ECOG 1: 43 % vs ECOG 2: 0 %; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75 % vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56 % vs HGS 18 %; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13 %) patients had a partial response (PR), 20 (43 %) had stable disease (SD) and 20 (43 %) had progressive disease (PD). The 1-year OS was 30 %: 67 % for PR, 54 % for SD and 20 % for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma

  16. Notch Signaling Is Associated With ALDH Activity And An Aggressive Metastatic Phenotype In Murine Osteosarcoma Cells

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    Xiaodong eMu

    2013-06-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone, and pulmonary metastatic disease accounts for nearly all mortality. However, little is known about the biochemical signaling alterations that drive the progression of metastatic disease. Two murine OS cell populations, K7M2 and K12, are clonally related but differ significantly in their metastatic phenotypes and therefore represent excellent tools for studying metastatic OS molecular biology. K7M2 cells are highly metastatic, whereas K12 cells display limited metastatic potential. Here we report that the expression of Notch genes (Notch1, 2, 4 are up-regulated, including downstream targets Hes1 and Stat3, in the highly metastatic K7M2 cells compared to the less metastatic K12 cells, indicating that the Notch signaling pathway is more active in K7M2 cells. We have previously described that K7M2 cells exhibit higher levels of aldehyde dehydrogenase (ALDH activity. Here we report that K7M2 cell ALDH activity is reduced with Notch inhibition, suggesting that ALDH activity may be regulated in part by the Notch pathway. Notch signaling is also associated with increased resistance to oxidative stress, migration, invasion, and VEGF expression in vitro. However, Notch inhibition did not significantly alter K7M2 cell proliferation. In conclusion, we provide evidence that Notch signaling is associated with ALDH activity and increased metastatic behavior in OS cells. Both Notch and ALDH are putative molecular targets for the treatment and prevention of OS metastasis.

  17. ΔNp63 mediates cellular survival and metastasis in canine osteosarcoma.

    Science.gov (United States)

    Cam, Maren; Gardner, Heather L; Roberts, Ryan D; Fenger, Joelle M; Guttridge, Denis C; London, Cheryl A; Cam, Hakan

    2016-07-26

    p63 is a structural homolog within the 53 family encoding two isoforms, ΔNp63 and TAp63. The oncogenic activity of ΔNp63 has been demonstrated in multiple cancers, however the underlying mechanisms that contribute to tumorigenesis are poorly characterized. Osteosarcoma (OSA) is the most common primary bone tumor in dogs, exhibiting clinical behavior and molecular biology essentially identical to its human counterpart. The purpose of this study was to evaluate the potential contribution of ΔNp63 to the biology of canine OSA. As demonstrated by qRT-PCR, nearly all canine OSA cell lines and tissues overexpressed ΔNp63 relative to normal control osteoblasts. Inhibition of ΔNp63 by RNAi selectively induced apoptosis in the OSA cell lines overexpressing ΔNp63. Knockdown of ΔNp63 upregulated expression of the proapoptotic Bcl-2 family members Puma and Noxa independent of p53. However the effects of ΔNp63 required transactivating isoforms of p73, suggesting that ΔNp63 promotes survival in OSA by repressing p73-dependent apoptosis. In addition, ΔNp63 modulated angiogenesis and invasion through its effects on VEGF-A and IL-8 expression, and STAT3 phosphorylation. Lastly, the capacity of canine OSA cell lines to form pulmonary metastasis was directly related to expression levels of ΔNp63 in a murine model of metastatic OSA. Together, these data demonstrate that ΔNp63 inhibits apoptosis and promotes metastasis, supporting continued evaluation of this oncogene as a therapeutic target in both human and canine OSA.

  18. Cell mediated immunity in patients with osteosarcoma

    International Nuclear Information System (INIS)

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

    1975-01-01

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

  19. The genetics of radiation-induced osteosarcoma

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  20. Expression of nociceptive ligands in canine osteosarcoma.

    Science.gov (United States)

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

    2015-01-01

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

  1. WEE1 inhibition sensitizes osteosarcoma to radiotherapy

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  2. Ação da adenosina na circulação pulmonar de pacientes com hipertensão pulmonar primária Effect of adenosine on pulmonary circulation in patients with primary pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Rogerio Souza

    2005-02-01

    . Although its effect on the pulmonary arteries is well known, its influence on capillaries and veins has yet to be described. OBJECTIVE: To evaluate the pre- and post-administration effects of adenosine on arterial and venous resistance in the pulmonary circulation of patients with primary pulmonary hypertension. METHOD: The study involved 7 patients with primary pulmonary hypertension and presenting a positive response to adenosine on the acute test. Before and after adenosine administration, arterial and venous resistances were determined by estimating pulmonary capillary pressure through analysis of pulmonary artery pressure decay curves. RESULTS: Following adenosine administration, there was an increase in the cardiac index (from 1.71 ± 0.23 to 2.72 ± 0.74 L/min-1/m-2 and a decrease in pulmonary vascular resistance (from 2924 ± 1060 to 1975 ± 764 dynes/s/cm-5/m-2 with no significant variations in mean pulmonary artery pressure (pre: 75.6 ± 16.8 mmHg; post: 78.1 ± 18.8 mmHg, pulmonary wedge pressure (pre: 15.3 ± 1.5 mmHg; post: 15.4 ± 1.9 mmHg and pulmonary capillary pressure (pre: 43.8 ± 5.8 mmHg; post: 44.5 ± 4.9 mmHg. The ratio between arterial resistance and total pulmonary vascular resistance also presented a less than significant variation (pre: 50 ± 15%; post: 49 ± 17%. These findings suggest that adenosine affects the capillaries and veins as well as the arteries. CONCLUSION: We can conclude that the adenosine mechanism is not restricted to the arterial aspect of the pulmonary circulation, and that analysis of pulmonary capillary pressure could prove useful in the study of various drugs that affect the pulmonary circulation.

  3. 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

  4. Micro-computed tomography derived anisotropy detects tumor provoked deviations in bone in an orthotopic osteosarcoma murine model.

    Directory of Open Access Journals (Sweden)

    Heather A Cole

    Full Text Available Radiographic imaging plays a crucial role in the diagnosis of osteosarcoma. Currently, computed-tomography (CT is used to measure tumor-induced osteolysis as a marker for tumor growth by monitoring the bone fractional volume. As most tumors primarily induce osteolysis, lower bone fractional volume has been found to correlate with tumor aggressiveness. However, osteosarcoma is an exception as it induces osteolysis and produces mineralized osteoid simultaneously. Given that competent bone is highly anisotropic (systematic variance in its architectural order renders its physical properties dependent on direction of load and that tumor induced osteolysis and osteogenesis are structurally disorganized relative to competent bone, we hypothesized that μCT-derived measures of anisotropy could be used to qualitatively and quantitatively detect osteosarcoma provoked deviations in bone, both osteolysis and osteogenesis, in vivo. We tested this hypothesis in a murine model of osteosarcoma cells orthotopically injected into the tibia. We demonstrate that, in addition to bone fractional volume, μCT-derived measure of anisotropy is a complete and accurate method to monitor osteosarcoma-induced osteolysis. Additionally, we found that unlike bone fractional volume, anisotropy could also detect tumor-induced osteogenesis. These findings suggest that monitoring tumor-induced changes in the structural property isotropy of the invaded bone may represent a novel means of diagnosing primary and metastatic bone tumors.

  5. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

    OpenAIRE

    Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

    2016-01-01

    Background Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods Patients receiving G 900?mg/m2 d 1, 8; D 75?mg/m2 d 8, every 21?days were eligible. Primary end-point: progression-free survival (PFS) at 4?months; secondary end-point: overall survival (OS) and response rate. Results Fifty-one patients w...

  6. Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.

    Science.gov (United States)

    Babu, K Anand; Supraja, K; Singh, Raj B

    2014-01-01

    Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

  7. A prospective study of whether radiation pneumonitis is influenced by low-dose irradiated lung volume in primary lung cancer with chronic pulmonary disease

    International Nuclear Information System (INIS)

    Niibe, Yuzuru; Hayakawa, Kazushige; Masuda, Noriyuki; Yoshimura, Hirokuni

    2007-01-01

    The current study prospectively investigated the optimal dose-volume condition in cases of lung cancer with chronic pulmonary disease compared to those without chronic pulmonary disease. Cases of primary lung cancer treated with intended curative radiation therapy were registered in the current study. Their fraction size was limited to 2-3 Gy, so-called standard fractionation. They were prescribed a total dose of 60 Gy for non-small cell lung cancer (NSCLC; n=17) and a total dose of 54 Gy for small cell lung cancer (SCLC; n=4). Of the 21 patients enrolled in this study, 4 had chronic pulmonary disease (study arm), and the others had no chronic pulmonary disease (control arm). Seven received chemotherapy. Symptomatic radiation pneumonitis occurred in 5. Of the four patients in the study arm, two (50%) experienced symptomatic radiation pneumonitis; only 3 of the 17 patients in the control arm (17.6%) experienced symptomatic radiation pneumonitis. Furthermore, the median V 20 of patients who experienced symptomatic radiation pneumonitis in the study arm was 14%, which was higher than that of patients with no symptomatic radiation pneumonitis in the study arm, 5.8%. On the other hand, in the control arm, the median V 20 of patients with symptomatic radiation pneumonitis was 14.2%, about the same as that of patients with no symptomatic radiation pneumonitis in the control arm, 15.1%. The current study suggested that, as much as 15% of V 20 , might play an important role in cases of lung cancer with chronic pulmonary disease. (author)

  8. Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

    Science.gov (United States)

    Boro, Aleksandar; Arlt, Matthias Je; Lengnick, Harald; Robl, Bernhard; Husmann, Maren; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2015-01-01

    Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy.

  9. Comparative proteomic analysis of plasma membrane proteins between human osteosarcoma and normal osteoblastic cell lines

    International Nuclear Information System (INIS)

    Zhang, Zhiyu; Ma, Fang; Cai, Zhengdong; Zhang, Lijun; Hua, Yingqi; Jia, Xiaofang; Li, Jian; Hu, Shuo; Peng, Xia; Yang, Pengyuan; Sun, Mengxiong

    2010-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. However, the knowledge in diagnostic modalities has progressed less. To identify new biomarkers for the early diagnosis of OS as well as for potential novel therapeutic candidates, we performed a sub-cellular comparative proteomic research. An osteosarcoma cell line (MG-63) and human osteoblastic cells (hFOB1.19) were used as our comparative model. Plasma membrane (PM) was obtained by aqueous two-phase partition. Proteins were analyzed through iTRAQ-based quantitative differential LC/MS/MS. The location and function of differential proteins were analyzed through GO database. Protein-protein interaction was examined through String software. One of differentially expressed proteins was verified by immunohistochemistry. 342 non-redundant proteins were identified, 68 of which were differentially expressed with 1.5-fold difference, with 25 up-regulated and 43 down-regulated. Among those differential proteins, 69% ware plasma membrane, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc., and interaction with each other. One protein--CD151 located in net nodes was verified to be over-expressed in osteosarcoma tissue by immunohistochemistry. It is the first time to use plasma membrane proteomics for studying the OS membrane proteins according to our knowledge. We generated preliminary but comprehensive data about membrane protein of osteosarcoma. Among these, CD151 was further validated in patient samples, and this small molecule membrane might be a new target for OS research. The plasma membrane proteins identified in this study may provide new insight into osteosarcoma biology and potential diagnostic and therapeutic biomarkers

  10. Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

    Science.gov (United States)

    Petrilli, A S; Kechichian, R; Broniscer, A; Garcia, R J; Tanaka, C; Francisco, J; Lederman, H; Odone Filho, V; Camargo, O P; Bruniera, P; Pericles, P; Consentino, E; Ortega, J A

    1999-08-01

    Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma. Copyright 1999 Wiley-Liss, Inc.

  11. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study.

    Directory of Open Access Journals (Sweden)

    Daniela Caronia

    Full Text Available Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response.In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs and 2 Copy Number Variants (CNVs in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10⁻⁵, and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9×10⁻⁵, rs1128503 and rs10276036 (r² = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9×10⁻⁵. Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤ 0.03.Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy.

  12. Pulmonary carcinosarcoma initially presenting as invasive aspergillosis: a case report of previously unreported combination

    Directory of Open Access Journals (Sweden)

    Van Thien

    2010-01-01

    Full Text Available Abstract Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for diagnosis, and mortality rate is high. We describe a case of primary carcinosarcoma of the lung concurrently occurring with invasive pulmonary aspergillosis in a 66-year old patient.

  13. Unusual sites of metastatic recurrence of osteosarcoma detected on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

    International Nuclear Information System (INIS)

    Kabnurkar, Rasika; Agrawal, Archi; Rekhi, Bharat; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2015-01-01

    Osteosarcoma (OS) is the most common nonhematolymphoid primary bone malignancy characterized by osteoid or new bone formation. Lungs and bones are the most common sites of metastases. We report a case where unusual sites of the soft tissue recurrence from OS were detected on restaging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan done post 6 years of disease free interval

  14. Pulmonary edema

    Science.gov (United States)

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

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

    Science.gov (United States)

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

    2015-12-01

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

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-02-01

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

  18. 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.

  19. Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

    Science.gov (United States)

    Armstrong, Jo; Dass, Crispin R

    2018-01-01

    The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain. As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin. Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Involvement and Clinical Aspects of MicroRNA in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ram Mohan Ram Kumar

    2016-06-01

    Full Text Available Osteosarcoma (OS is the most common primary bone cancer in children and adolescents, but its pathogenesis has been difficult to establish because of its well-known heterogeneous nature. OS has been associated with genetic and cytogenetic abnormalities, which include function-impairing mutations in tumor suppressors and the activation of oncogenes. OS tumorigenesis has been linked to alterations of several genes characterized by a high level of genetic instability and recurrent DNA amplifications and deletions. MicroRNAs (miRNAs, 18–25-nucleotide noncoding RNAs, are critical for various biological processes like differentiation, cell growth and cell death. Dysregulation of miRNA expression leads to phenotypic and genotypic changes in cells, which leads to cancer. Studies on miRNAs have initiated a significant effect in both diagnosis and treatment of cancer. This review focuses on the current knowledge of clinical applications of miRNAs for the better diagnosis and management of OS.

  1. [Usefulness of stratigraphy and computerized tomography in the initial staging of osteosarcoma of the extremities. Retrospective study of 217 cases].

    Science.gov (United States)

    Pelotti, P; Ciminari, R; Bacci, G; Avella, M; Briccoli, A

    1988-01-01

    The value of stratigraphy and pulmonary CT in the initial work-up of osteosarcoma of the extremities is assessed with reference to 217 patients encountered in the Bone Tumour Centre of Rizzoli Orthopaedic Institute in May 1983-May 1986. Stratigraphy revealed lung metastases not identified by standard radiography in 4 patients (1.8%), while CT revealed metastases not identified by either standard X-rays or stratigraphy in a further 6 cases (2.7%). It is concluded that the increase in the percentage of cures (about 30%) reported in the last 10 years in osteosarcoma cases given adjuvant chemotherapy cannot be explained by any difference in initial selection due to the use of these techniques that were not adopted in the historical series.

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

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

    Yang, Ji-Long

    2014-01-01

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

  4. Evaluation of P16 expression in canine appendicular osteosarcoma.

    Science.gov (United States)

    Murphy, B G; Mok, M Y; York, D; Rebhun, R; Woolard, K D; Hillman, C; Dickinson, P; Skorupski, K

    2017-06-20

    Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.

  5. Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Marie E. Legare, Jamie Bush, Amanda K. Ashley, Taka Kato, William H. Hanneman

    2011-01-01

    Full Text Available Canine and human osteosarcoma (OSA have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have characterized seven different OSA canine cell lines: Abrams, D17, Grey, Hughes, Ingles, Jarques, and Marisco and compared them to U2, a human OSA cell line, for the following parameters: morphology, growth, contact inhibition, migrational tendencies, alkaline phosphatase staining, heterologous tumor growth, double-strand DNA breaks, and oxidative damage. All results demonstrated the positive characteristics of the Abrams cell line for use in future studies of OSA. Of particular interest, the robust growth of a subcutaneous tumor and rapid pulmonary metastasis of the Abrams cell line in an immunocompromised mouse shows incredible potential for the future use of Abrams as a canine OSA model. Further investigations utilizing a canine cell model of OSA, such as Abrams, will be invaluable to understanding the molecular events underlying OSA, pharmaceutical inhibition of metastasis, and eventual prevention of this devastating disease.

  6. The Association of Endothelin-1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma.

    Science.gov (United States)

    Neumann, Z L; Pondenis, H C; Masyr, A; Byrum, M L; Wycislo, K L; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin-1-mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression. The endothelin-1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities. 45 dogs with appendicular OS. The expressions of endothelin-1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin-1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity. Canine OS cells express endothelin-1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities. Canine OS cells express endothelin-1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin-1 signaling or excessive osteoproduction within the localized bone microenvironment. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  7. Spontaneous conventional osteosarcoma transformation of a chondroblastoma: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Prashant Narhari

    2018-01-01

    Full Text Available Chondroblastomas are a primary benign cartilaginous tumor that accounts for approximately 1% of all benign bone tumors. Primarily they are treated by curettage. The patient presented 4 years after a successfully treated chondroblastoma (curettage and Bone cement. Wide resection of the proximal tibia with endoprosthesis replacement was done. Lung CT showed multiple lung metastasis and despite starting chemotherapy, he succumbed to the disease. We discuss regarding the possibilities of “aggressive” chondroblastoma and more recently termed chondroblastoma-like osteosarcoma which is a separate entity from chondroblastoma. Aggressiveness in chondroblastoma can be 1 of 3 types as follows: 1. benign chondroblastoma with lung metastasis. 2. malignant chondroblastoma. 3. subsequent malignant transformation of benign chondroblastoma. We have attempted to review the literature and describe the “aggressive” chondroblastoma and chondroblastoma-like osteosarcoma in this report.

  8. p53 functions as a cell cycle control protein in osteosarcomas.

    Science.gov (United States)

    Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

    1990-11-01

    Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

  9. p53 functions as a cell cycle control protein in osteosarcomas.

    Science.gov (United States)

    Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

    1990-01-01

    Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae. Images PMID:2233717

  10. Anticancer Effects of Geopropolis Produced by Stingless Bees on Canine Osteosarcoma Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Naiara Costa Cinegaglia

    2013-01-01

    Full Text Available Geopropolis is produced by indigenous stingless bees from the resinous material of plants, adding soil or clay. Its biological properties have not been investigated, such as propolis, and herein its cytotoxic action on canine osteosarcoma (OSA cells was evaluated. OSA is a primary bone neoplasm diagnosed in dogs being an excellent model in vivo to study human OSA. spOS-2 primary cultures were isolated from the tumor of a dog with osteosarcoma and incubated with geopropolis, 70% ethanol (geopropolis solvent, and carboplatin after 6, 24, 48, and 72 hours. Cell viability was analyzed by the crystal violet method. Geopropolis was efficient against canine OSA cells in a dose- and time-dependent way, leading to a distinct morphology compared to control. Geopropolis cytotoxic action was exclusively due to its constituents since 70% ethanol (its solvent had no effect on cell viability. Carboplatin had no effect on OSA cells. Geopropolis exerted a cytotoxic effect on canine osteosarcoma, and its introduction as a possible therapeutic agent in vivo could be investigated, providing a new contribution to OSA treatment.

  11. Anticancer effects of geopropolis produced by stingless bees on canine osteosarcoma cells in vitro.

    Science.gov (United States)

    Cinegaglia, Naiara Costa; Bersano, Paulo Ricardo Oliveira; Araújo, Maria José Abigail Mendes; Búfalo, Michelle Cristiane; Sforcin, José Maurício

    2013-01-01

    Geopropolis is produced by indigenous stingless bees from the resinous material of plants, adding soil or clay. Its biological properties have not been investigated, such as propolis, and herein its cytotoxic action on canine osteosarcoma (OSA) cells was evaluated. OSA is a primary bone neoplasm diagnosed in dogs being an excellent model in vivo to study human OSA. spOS-2 primary cultures were isolated from the tumor of a dog with osteosarcoma and incubated with geopropolis, 70% ethanol (geopropolis solvent), and carboplatin after 6, 24, 48, and 72 hours. Cell viability was analyzed by the crystal violet method. Geopropolis was efficient against canine OSA cells in a dose- and time-dependent way, leading to a distinct morphology compared to control. Geopropolis cytotoxic action was exclusively due to its constituents since 70% ethanol (its solvent) had no effect on cell viability. Carboplatin had no effect on OSA cells. Geopropolis exerted a cytotoxic effect on canine osteosarcoma, and its introduction as a possible therapeutic agent in vivo could be investigated, providing a new contribution to OSA treatment.

  12. A approach for differential diagnosis of primary lung cancer and breast cancer relapse presenting as a solitary pulmonary nodule in patients after breast surgery

    International Nuclear Information System (INIS)

    Fujita, Takashi; Iwata, Hiroharu; Yatabe, Yasushi

    2009-01-01

    The differential diagnosis of primary lung cancer from metastatic breast cancer is crucial in patients presenting with a solitary pulmonary nodule after breast surgery. However definitive diagnosis of these nodules is often difficult due to similar radiological and pathological features in primary lung and metastatic breast cancer nodules. We assessed the feasibility of our diagnostic approach for these nodules by morphopathological and immunohistochemical examination (thyroid transcription factor-1 (TTF-1), surfactant pro-protein B (SPPB), estrogen receptor (ER), mammaglobin-1 (MGB1)), and estimated the frequency of primary lung cancer occurrence in 23 breast cancer patients. Biopsy specimens were obtained using CT-guided needle biopsy (NB) and transbronchial lung biopsy (TBLB) in 21 patients (91.3%). Surgical resection was performed for diagnosis and treatment in two patients. Differential diagnosis was obtained by morphopathological methods alone in 17 patients (73.9%, primary lung cancer: 6 cases, metastatic breast cancer: 11 cases) and by immunohistochemical examination in the remaining 6 (26.1%, primary lung cancer: 1 case, metastatic breast cancer: 5 cases). Our results show the clinical feasibility of our approach to the differential diagnosis of breast cancer relapse and primary lung cancer presenting as a solitary nodule in breast cancer patients. (author)

  13. A low-grade extraskeletal osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-03-01

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

  14. Extraskeletal osteosarcoma arising in myositis ossificans

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-01-01

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

  15. Extraskeletal osteosarcoma arising in myositis ossificans

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  16. Case report 461: Dedifferentiated parosteal osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

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

  17. Radiation, chemotherapy and surgery for canine osteosarcoma

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  18. 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.

  19. Practical surrogate marker of pulmonary dysanapsis by simple spirometry: an observational case-control study in primary care.

    Science.gov (United States)

    Shiota, Satomi; Ichikawa, Masako; Suzuki, Kazuhiro; Fukuchi, Yoshinosuke; Takahashi, Kazuhisa

    2015-03-26

    We see patients who present with spirometry airflow limitation despite their forced expiratory volume in one second (FEV1) as well as forced vital capacity (FVC) to be supernormal (FEV1/FVC spirometry conditions (results measured with spirometry) could be suitably used as a practical surrogate marker of pulmonary dysanapsis: the condition of disproportionate but physiologically normal growth between airways and lung parenchyma. We compared the conventional surrogate marker of dysanapsis, maximum mid-expiratory flow to FVC (MMF/FVC), in SUBJECTS (FEV1/FVC spirometry results with SUBJECTS) (n = 55), and in CONTROLS (age- and height- matched, normal spirometry results) (n = 25). Next we added imaging analysis to evaluate the relationship between the cross sectional airway luminal area (X-Ai) and the lung volume results among the three groups. The MMF/FVC was significantly lower in SUBJECTS and in EMPHYSEMA compared to CONTROLS. However, percent predicted peak expiratory flow (%PEFR) was significantly lower only in SUBJECTS and not in EMPHYSEMA compared to CONTROLS. The ratio of the X-Ai of the trachea and right apical bronchus to lung volume was significantly lower in SUBJECTS compared to CONTROLS. The simple spirometry conditions in SUBJECTS are highly suggestive of practical surrogate marker of pulmonary dysanapsis. Awareness of this concept would help to attenuate the risk of overdiagnosis of obstructive pulmonary disease.

  20. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

    International Nuclear Information System (INIS)

    Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

    2010-01-01

    Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas

  1. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

    Directory of Open Access Journals (Sweden)

    Dirksen Uta

    2010-07-01

    Full Text Available Abstract Background Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor. Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. Methods HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. Results 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Conclusions Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

  2. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

    Science.gov (United States)

    Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

    2010-07-16

    Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  4. 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.

  5. 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

  6. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

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

  7. Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  8. Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma.

    Science.gov (United States)

    Koh, Young Wha; Chun, Sung-Min; Park, Young-Soo; Song, Joon Seon; Lee, Geon Kook; Khang, Shin Kwang; Jang, Se Jin

    2016-08-01

    Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

  9. 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.

  10. Anesthetic management of right atrial mass removal and pulmonary artery thrombectomy in a patient with primary antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Rawat SKS

    2010-01-01

    Full Text Available Antiphospholipid antibody syndrome (APLAS characterises a clinical condition of arterial and venous thrombosis associated with phospholipids directed antibodies. APLAS occurs in 2% of the general population. However, one study demonstrated that 7.1% of hospitalised patients were tested positive for at least one of the three anticardiolipin antibody idiotype. Antiphospholipid antibodies often inhibit phospholipids dependent coagulation in vitro and interfere with laboratory testing of hemostasis. Therefore, the management of anticoagulation during cardiopulmonary bypass can be quite challenging in these patients. Here, we present a case of right atrial mass removal and pulmonary thrombectomy in a patient of APLAS.

  11. A review of targeted therapies evaluated by the Pediatric Preclinical Testing Program for osteosarcoma

    Directory of Open Access Journals (Sweden)

    Valerie eSampson

    2013-05-01

    Full Text Available Osteosarcoma, the most common malignant bone tumor of childhood, is a high grade primary bone sarcoma that occurs mostly in adolescence. Standard treatment consists of surgery in combination with multi-agent chemotherapy regimens. The development and approval of imatinib for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL in children and the fully human monoclonal antibody, anti-GD2, as part of an immune therapy for high-risk neuroblastoma patients have established the precedent for use of targeted inhibitors along with standard chemotherapy backbones. However, few targeted agents tested have achieved traditional clinical end points for osteosarcoma. Many biological agents demonstrating anti-tumor responses in preclinical and early phase clinical testing have failed to reach response thresholds to justify randomized trials with large numbers of patients. The development of targeted therapies for pediatric cancer remains a significant challenge. To aid in the prioritization of new agents for clinical testing, the Pediatric Preclinical Testing Program (PPTP has developed reliable and robust preclinical pediatric cancer models to rapidly screen agents for activity in multiple childhood cancers and establish pharmacological parameters and effective drug concentrations for clinical trials. In this article, we examine a range of standard and novel agents that have been evaluated by the PPTP, and we discuss the preclinical and clinical development of these for the treatment of osteosarcoma. We further demonstrate that committed resources for hypothesis-driven drug discovery and development are needed to yield clinical successes in the search for new therapies for this pediatric disease.

  12. Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma.

    Science.gov (United States)

    Kundu, Anup K; Iyer, Swathi V; Chandra, Sruti; Adhikari, Amit S; Iwakuma, Tomoo; Mandal, Tarun K

    2017-01-01

    The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency. Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent. This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.

  13. Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Anup K Kundu

    Full Text Available The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line.The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency.Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent.This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.

  14. Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy.

    Science.gov (United States)

    Asling, Jonathan; Morrison, Jodi; Mutsaers, Anthony J

    2016-11-01

    Heat shock proteins (HSPs) are molecular chaperones subdivided into several families based on their molecular weight. Due to their cytoprotective roles, these proteins may help protect cancer cells against chemotherapy-induced cell death. Investigation into the biologic activity of HSPs in a variety of cancers including primary bone tumors, such as osteosarcoma (OSA), is of great interest. Both human and canine OSA tumor samples have aberrant production of HSP70. This study assessed the response of canine OSA cells to inhibition of HSP70 and GRP78 by the ATP-mimetic VER-155008 and whether this treatment strategy could sensitize cells to doxorubicin chemotherapy. Single-agent VER-155008 treatment decreased cellular viability and clonogenic survival and increased apoptosis in canine OSA cell lines. However, combination schedules with doxorubicin after pretreatment with VER-155008 did not improve inhibition of cellular viability, apoptosis, or clonogenic survival. Treatment with VER-155008 prior to chemotherapy resulted in an upregulation of target proteins HSP70 and GRP78 in addition to the co-chaperone proteins Herp, C/EBP homologous transcription protein (CHOP), and BAG-1. The increased GRP78 was more cytoplasmic in location compared to untreated cells. Single-agent treatment also revealed a dose-dependent reduction in activated and total Akt. Based on these results, targeting GRP78 and HSP70 may have biologic activity in canine osteosarcoma. Further studies are required to determine if and how this strategy may impact the response of osteosarcoma cells to chemotherapy.

  15. Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration

    Directory of Open Access Journals (Sweden)

    Jinyang Wang

    2018-05-01

    Full Text Available Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR positively correlates with TNM (tumor-node-metastasis stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.

  16. Evaluation of a tailored implementation strategy to improve the management of patients with chronic obstructive pulmonary disease in primary care: a study protocol of a cluster randomized trial.

    Science.gov (United States)

    Godycki-Cwirko, Maciek; Zakowska, Izabela; Kosiek, Katarzyna; Wensing, Michel; Krawczyk, Jaroslaw; Kowalczyk, Anna

    2014-04-04

    Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking. Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable. We have developed a tailored implementation strategy for enhancing general practitioners' adherence to the disease management guidelines. The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners' adherence to guidelines. A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care. The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD. The nine control practices will provide usual care without any interventions. Tailored interventions to implement four recommendations will be delivered in the remaining nine practices. At follow-up after nine months, data will be collected for all 18 general practices. The primary outcome measure is physicians' adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use. This measurement will be based on data extracted from identified patients' records. Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care. The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care. This trial has been registered with Clinical Trials Protocol Registration System. NCT01893476.

  17. Retrospective evaluation of toceranib (Palladia) treatment for canine metastatic appendicular osteosarcoma.

    Science.gov (United States)

    Kim, Changseok; Matsuyama, Arata; Mutsaers, Anthony J; Woods, J Paul

    2017-10-01

    This retrospective study evaluated the outcomes of dogs with macroscopic pulmonary metastasis of appendicular osteosarcoma (OSA) treated with toceranib. Medical records of 20 dogs with macroscopic pulmonary metastasis of OSA that received toceranib were reviewed. The median dose and duration of toceranib administration were 2.52 mg/kg (range: 2.12 to 2.72 mg/kg) and 60 days (range: 17 to 231 days). The median progression free survival (PFS) and overall survival (OS) were 36 days (range: 17 to 231 days) and 90 days (range: 17 to 433 days), respectively. The clinical benefit rate was 10% (2/20; 1 partial response and 1 stable disease). The longest length of initial pulmonary nodules had significant impact on both PFS ( P = 0.01) and OS ( P = 0.02). The prognosis for dogs with metastatic OSA was poor with only 10% of dogs showing clinical benefit from toceranib. These results suggest that toceranib may not improve outcome in dogs with macroscopic pulmonary metastasis of OSA.

  18. Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyunjin; Bergeron, Eric; Senta, Helena; Guillemette, Kim [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Beauvais, Sabrina [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Blouin, Richard [Universite de Sherbrooke, Department of Biology, Canada J1K 2R1 (Canada); Sirois, Joel [Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Faucheux, Nathalie, E-mail: Nathalie.Faucheux@Usherbrooke.ca [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada)

    2010-08-27

    Research highlights: {yields} We show for the first time the effect of sanguinarine (SA) on MG63 and SaOS-2 cells. {yields} SA altered osteosarcoma cell viability in a concentration and time dependent manner. {yields} SA induced osteosarcoma cell apoptosis and increased caspase-8 and -9 activities. {yields} SA decreased dose dependently the Bcl-2 protein level only in MG63 cells. {yields} SaOS-2 which are osteoblast-derived, seemed more resistant to SA than MG63. -- Abstract: The quaternary benzo[c]phenanthridine alkaloid sanguinarine inhibits the proliferation of cancerous cells from different origins, including lung, breast, pancreatic and colon, but nothing is known of its effects on osteosarcoma, a primary malignant bone tumour. We have found that sanguinarine alters the morphology and reduces the viability of MG-63 and SaOS-2 human osteosarcoma cell lines in concentration- and time-dependent manner. Incubation with 1 {mu}mol/L sanguinarine for 4 and 24 h killed more efficiently MG-63 cells than SaOS-2 cells, while incubation with 5 {mu}mol/L sanguinarine killed almost 100% of both cell populations within 24 h. This treatment also changed the mitochondrial membrane potential in both MG-63 and SaOS-2 cells within 1 h, caused chromatin condensation and the formation of apoptotic bodies. It activated multicaspases, and increased the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These data highlight sanguinarine as a novel potential agent for bone cancer therapy.

  19. The effect of taurine chloramine on human osteosarcoma cell-lines

    International Nuclear Information System (INIS)

    Pilz, M.

    2010-01-01

    Osteosarcoma is the most frequent nonhaematogenic primary malignant tumor of the bone. The rather rare tumour occurs mainly in children and adolescents. This osteogenic tumour is a high-aggressive mesenchymal neoplasm typically producing osteoid. The surgical resection of the complete tumour must be carried out with wide or radical margins to prevent recurrence. Even though the combination of surgery with chemotherapy has noticeably improved the survival rate of osteosarcoma patients, the application of anticancer drugs is still associated with significant adverse reactions, for example the common acquisition of drug-resistant phenotypes, indicating the need of new chemotherapeutical substances. Taurine is a sulfur-containing β-amino acid, which is present in high concentrations in mammalian cells and plasma, in granulocytes and lymphocytes. Large quantities of taurine are released by stimulated neutrophiles and rapidly chlorinated by the reaction with hypochlorous acid (HOCl) generating taurine monochloramine (NCT). NCT is noted to play quite a few roles in the modulation of the immune response and sizeably decreases the production of plenty proinflammatory mediators from adherent as well as non-adherent leucocytes. NCT inhibits the intracellular transcription of nitric-oxide synthase and the production of nitric oxide and switches cell death from the less advantageous necrosis to the more physiologically beneficial apoptosis. Aim of this study was to research, if different concentrations of NCT are capable to induce apoptosis in the human osteosarcoma cell lines HOS, MG-63 and SAOS-2. Therefore the cell proliferation assay EZ4U, a fluorescence staining with acridine-orange, an ELISA for the detection of DNA-fragments and a JC-1 mitochondrial FACS-analysis were performed. The results of these four independent experiments show, that NCT has a pro-apoptotic effect on these osteosarcoma cell lines. (author) [de

  20. HYPOXIA-ACTIVATED PRO-DRUG TH-302 EXHIBITS POTENT TUMOUR SUPPRESSIVE ACTIVITY AND COOPERATES WITH CHEMOTHERAPY AGAINST OSTEOSARCOMA

    Science.gov (United States)

    Liapis, Vasilios; Labrinidis, Agatha; Zinonos, Irene; Hay, Shelley; Ponomarev, Vladimir; Panagopoulos, Vasilios; DeNichilo, Mark; Ingman, Wendy; Atkins, Gerald J.; Findlay, David M.; Zannettino, Andrew CW.; Evdokiou, Andreas

    2015-01-01

    Tumour hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumour hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumours. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS. PMID:25444931

  1. Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma.

    Science.gov (United States)

    Liapis, Vasilios; Labrinidis, Agatha; Zinonos, Irene; Hay, Shelley; Ponomarev, Vladimir; Panagopoulos, Vasilios; DeNichilo, Mark; Ingman, Wendy; Atkins, Gerald J; Findlay, David M; Zannettino, Andrew C W; Evdokiou, Andreas

    2015-02-01

    Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumor hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumors. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

  2. A support vector machine and a random forest classifier indicates a 15-miRNA set related to osteosarcoma recurrence

    Directory of Open Access Journals (Sweden)

    He Y

    2018-01-01

    Full Text Available Yunfei He,1,2,* Jun Ma,1,* An Wang,1,3,* Weiheng Wang,1 Shengchang Luo,1 Yaoming Liu,2 Xiaojian Ye1 1Department of Orthopaedics, Changzheng Hospital Affiliated with Second Military Medical University, Shanghai, 2Department of Orthopaedics, Lanzhou General Hospital of Lanzhou Military Command Region, Lanzhou, 3Department of Orthopaedics, Shanghai Armed Police Force Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Osteosarcoma, which originates in the mesenchymal tissue, is the prevalent primary solid malignancy of the bone. It is of great importance to explore the mechanisms of metastasis and recurrence, which are two primary reasons accounting for the high death rate in osteosarcoma. Data and methods: Three miRNA expression profiles related to osteosarcoma were downloaded from GEO DataSets. Differentially expressed miRNAs (DEmiRs were screened using MetaDE.ES of the MetaDE package. A support vector machine (SVM classifier was constructed using optimal miRNAs, and its prediction efficiency for recurrence was detected in independent datasets. Finally, a co-expression network was constructed based on the DEmiRs and their target genes. Results: In total, 78 significantly DEmiRs were screened. The SVM classifier constructed by 15 miRNAs could accurately classify 58 samples in 65 samples (89.2% in the GSE39040 database, which was validated in another two databases, GSE39052 (84.62%, 22/26 and GSE79181 (91.3%, 21/23. Cox regression showed that four miRNAs, including hsa-miR-10b, hsa-miR-1227, hsa-miR-146b-3p, and hsa-miR-873, significantly correlated with tumor recurrence time. There were 137, 147, 145, and 77 target genes of the above four miRNAs, respectively, which were assigned to 17 gene ontology functionally annotated terms and 14 Kyoto Encyclopedia of Genes and Genomes pathways. Among them, the “Osteoclast differentiation” pathway contained a total of seven target genes and was

  3. Pulmonary tuberculosis

    Science.gov (United States)

    TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

  4. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-01-01

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  5. Response of human osteosarcoma in vitro to irradiation

    International Nuclear Information System (INIS)

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

    1977-01-01

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

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

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    Sheila Thampi

    2014-01-01

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

  7. S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical applications

    International Nuclear Information System (INIS)

    Parashar, Surabhi; Cheishvili, David; Arakelian, Ani; Hussain, Zahid; Tanvir, Imrana; Khan, Haseeb Ahmed; Szyf, Moshe; Rabbani, Shafaat A

    2015-01-01

    Osteosarcoma (OS) is an aggressive and highly metastatic form of primary bone cancer affecting young children and adults. Previous studies have shown that hypomethylation of critical genes is driving metastasis. Here, we examine whether hypermethylation treatment can block OS growth and pulmonary metastasis. Human OS cells LM-7 and MG-63 were treated with the ubiquitous methyl donor S-adenosylmethionine (SAM) or its inactive analog S-adenosylhomocystine (SAH) as control. Treatment with SAM resulted in a dose-dependent inhibition of tumor cell proliferation, invasion, cell migration, and cell cycle characteristics. Inoculation of cells treated with 150 μmol/L SAM for 6 days into tibia or via intravenous route into Fox Chase severe combined immune deficient (SCID) mice resulted in the development of significantly smaller skeletal lesions and a marked reduction in pulmonary metastasis as compared to control groups. Epigenome wide association studies (EWAS) showed differential methylation of several genes involved in OS progression and prominent signaling pathways implicated in bone formation, wound healing, and tumor progression in SAM-treated LM-7 cells. Real-time polymerase chain reaction (qPCR) analysis confirmed that SAM treatment blocked the expression of several prometastatic genes and additional genes identified by EWAS analysis. Immunohistochemical analysis of normal human bone and tissue array from OS patients showed significantly high levels of expression of one of the identified gene platelet-derived growth factor alpha (PDGFA). These studies provide a possible mechanism for the role of DNA demethylation in the development and metastasis of OS to provide a rationale for the use of hypermethylation therapy for OS patients and identify new targets for monitoring OS development and progression

  8. Maxillary osteosarcoma in a beef suckler cow

    Directory of Open Access Journals (Sweden)

    Prins Diether G J

    2012-07-01

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

  9. Concurrence of metaphyseal fibrous defect and osteosarcoma

    International Nuclear Information System (INIS)

    Kyriakos, M.; Murphy, W.A.

    1981-01-01

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

  10. YKL-40 protein in osteosarcoma tumor tissue

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  11. The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens

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    Branden A. Smeester

    2013-01-01

    Full Text Available Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3 beginning at postimplantation day 3 (PID 3. Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7, starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA’s potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

  12. Osteosarcoma inheritance in two families of Scottish deerhounds.

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    Dillberger, John E; McAtee, Sara Ann

    2017-01-01

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

  13. A case report of osteosarcoma occurred in the maxilla

    International Nuclear Information System (INIS)

    Jung, Yun Hwa; Jeon, Seon Doo

    1996-01-01

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

  14. 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).

  15. Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

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    Muhammad Nazirul Mubin Aziz

    2018-01-01

    Full Text Available Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z-3-hydroxy-1-(2-hydroxyphenyl-3-phenylprop-2-en-1-one (DK1. In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC, cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines.

  16. Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

    Science.gov (United States)

    de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

    2017-03-01

    An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

  17. Primary pulmonary lymphoma-role of fluoro-deoxy-glucose positron emission tomography-computed tomography in the initial staging and evaluating response to treatment - case reports and review of literature

    International Nuclear Information System (INIS)

    Agarwal, Krishan Kant; Dhanapathi, Halanaik; Nazar, Aftab Hasan; Kumar, Rakesh

    2016-01-01

    Primary pulmonary lymphoma (PPL) is an uncommon entity of non-Hodgkin lymphoma, which accounts for <1% of all cases of lymphoma. We present two rare cases of PPL of diffuse large B-cell lymphoma, which underwent 18 fluorine fluoro-deoxy-glucose positron emission tomography-computed tomography for initial staging and response evaluation after chemotherapy

  18. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Stine H Kresse

    Full Text Available BACKGROUND: Osteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression using a recurrence threshold of 6/19 (>30% cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between

  19. Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines

    International Nuclear Information System (INIS)

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

    1992-01-01

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

  20. Rehabilitation in radiotherapy of osteosarcomas in children and adolescents

    International Nuclear Information System (INIS)

    Bizer, V.A.

    1985-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Taher Rajabi

    2014-01-01

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

  2. Interdisciplinary model of care (RADICALS) for early detection and management of chronic obstructive pulmonary disease (COPD) in Australian primary care: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Liang, Jenifer; Abramson, Michael J; Zwar, Nicholas; Russell, Grant; Holland, Anne E; Bonevski, Billie; Mahal, Ajay; Hecke, Benjamin van; Phillips, Kirsten; Eustace, Paula; Paul, Eldho; Petrie, Kate; Wilson, Sally; George, Johnson

    2017-09-18

    Up to half of all smokers develop clinically significant chronic obstructive pulmonary disease (COPD). Gaps exist in the implementation and uptake of evidence-based guidelines for managing COPD in primary care. We describe the methodology of a cluster randomised controlled trial (cRCT) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aimed at reducing the burden of smoking and COPD in Australian primary care settings. A cRCT is being undertaken to evaluate an interdisciplinary model of care (RADICALS - Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers). General practice clinics across Melbourne, Australia, are identified and randomised to the intervention group (RADICALS) or usual care. Patients who are current or ex-smokers, of at least 10 pack years, including those with an existing diagnosis of COPD, are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD. Handheld lung function devices are being used to facilitate case-finding. RADICALS includes individualised smoking cessation support, home-based pulmonary rehabilitation and home medicines review. Patients at control group sites receive usual care and Quitline referral, as appropriate. Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life, abstinence rates, health resource utilisation, symptom severity and lung function. The primary outcome is change in St George's Respiratory Questionnaire score of patients with COPD at 6 months from baseline. This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee (CF14/1018 - 2014000433). Results of the study will be disseminated in peer-reviewed journals and research conferences. If the intervention is successful, the RADICALS programme could potentially be integrated into general practices across Australia and sustained over time. ACTRN

  3. How do informal self-care strategies evolve among patients with chronic obstructive pulmonary disease managed in primary care? A qualitative study.

    Science.gov (United States)

    Apps, Lindsay D; Harrison, Samantha L; Williams, Johanna E A; Hudson, Nicky; Steiner, Michael; Morgan, Mike D; Singh, Sally J

    2014-01-01

    There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care. This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors. Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention. Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia). Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD. Self-care activities evolved spontaneously as participants experienced symptoms of COPD. However, there was a lack of awareness about whether these strategies would impact upon symptoms. Perceptions of COPD by family members posed a challenge to self-care for some participants. Health care professionals should elicit patients' prior disease experiences and utilize spontaneous attempts at disease management in future self-management. These findings have implications for promoting self-management and enhancing quality of life.

  4. Decreased RECQL5 correlated with disease progression of osteosarcoma

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    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.

  5. Decreased RECQL5 correlated with disease progression of osteosarcoma

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. 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.

  7. [Effectiveness of an educational program for respiratory rehabilitation of Chronic Obstructive Pulmonary Disease patients in Primary Care in improving the quality of life, symptoms, and clinical risk].

    Science.gov (United States)

    Blánquez Moreno, Cristina; Colungo Francia, Cristina; Alvira Balada, M Carme; Kostov, Belchin; González-de Paz, Luis; Sisó-Almirall, Antoni

    2017-10-04

    To determine the impact of an educational program to improve the management of chronic obstructive pulmonary disease (COPD) that contributes to an increase of the quality of life, exercise capacity, level of dyspnoea, and clinical risk. Intervention study without controls. Primary Healthcare Centre. 193 patients with COPD were invited, 73 accepted and 55 participated in the educational program. Respiratory rehabilitation educational program with basic concepts of pulmonary and respiratory pathophysiology, respiratory physiotherapy exercises, practical workshop on the use of the most frequent inhalation devices, understanding of chronic disease and self-care measures in case of exacerbation. The quality of life (the COPD assessment test), exercise tolerance (the Six-Minute Walk Test), rating of perceived exertion (Borg Dyspnoea Score) and clinical risk (BODE index) were assessed by means of validated questionnaires in Spanish. A total of 43 (78.2%) participants completed the program. An improvement in the quality of life by a mean of 3.3 points was observed (95%CI; 1.76-4.84). Just over half (53.5%) of the participants obtained a clinically relevant improvement. Participants also improved their physical exercise capacity at post-intervention by increasing the distance that they walked in 6min by a mean of 20.76m (95%CI; 2.57-38.95). Improvements in the level of dyspnoea and clinical risk were also observed. The educational program shows a statistically significant and clinically relevant improvement in the quality of life, fatigue, symptomatology, exercise capacity, level of dyspnoea, and clinical risk. The program is adaptable to the health care routine of healthcare centres. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Choi Chan

    2007-05-01

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

  9. A CASE OF IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION IN MALE

    OpenAIRE

    Poongavanam Paranthaman; Ramani Bala Subra Manian; Thenrajan Balaji; Jayakrishnan Jayakumar; Govindaraj Ranjani

    2016-01-01

    Primary Pulmonary Hypertension is a rare disease occurring in 1-2 per million population. It is 2-4 times more common in female. Idiopathic or primary pulmonary hypertension is defined as a disorder with no identifiable cause in which resting mean pulmonary artery pressure in adults is above 25 mmHg and 30 mmHg with exercise. Idiopathic or primary pulmonary hypertension is diagnosed after ruling out all the possible secondary causes of pulmonary hypertension. We are presenting a ...

  10. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

    International Nuclear Information System (INIS)

    Franzius, Ch.; Eckardt, J.; Sciuk, J.; Schober, O.; Bielack, S.; Flege, S.; Juergens, H.

    2001-01-01

    Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors. (orig.)

  11. Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma.

    Science.gov (United States)

    Palmini, Gaia; Zonefrati, Roberto; Mavilia, Carmelo; Aldinucci, Alessandra; Luzi, Ettore; Marini, Francesca; Franchi, Alessandro; Capanna, Rodolfo; Tanini, Annalisa; Brandi, Maria Luisa

    2016-10-14

    The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs.

  12. Multicenter study of the COPD-6 screening device: feasible for early detection of chronic obstructive pulmonary disease in primary care?

    Science.gov (United States)

    Kjeldgaard, Peter; Lykkegaard, Jesper; Spillemose, Heidi; Ulrik, Charlotte Suppli

    2017-01-01

    Early detection of COPD may reduce the future burden of the disease. We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV 1 and FEV 6 ) facilitates early detection of COPD in primary care. In primary care, individuals at high risk of COPD (ie, age ≥35 years, relevant exposure, and at least one respiratory symptom) and no previous diagnosis of obstructive lung disease were examined with a COPD-6 screening device. In prioritized order, the criteria for proceeding to confirmatory spirometry were FEV 1 /FEV 6 COPD regardless of test result (medical doctor's [MD] decision). Based on spirometry, including bronchodilator (BD) reversibility test, individuals were classified as COPD (post-BD FEV 1 /FVC COPD-6 screening to confirmative spirometry based on the following criteria: 510 (54%) FEV 1 /FEV 6 COPD (51%), asthma (3%), and no obstructive lung disease (45%). COPD was diagnosed in 487 (16%) of the enrolled subjects in whom confirmative spirometry was performed in 69% based on FEV 1 /FEV 6 COPD-6 device showed acceptable specificity for the selection of subjects for diagnostic spirometry and is likely to be a useful alternative to current practice in primary care.

  13. PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma.

    Science.gov (United States)

    Hirahata, Mio; Osaki, Mitsuhiko; Kanda, Yusuke; Sugimoto, Yui; Yoshioka, Yusuke; Kosaka, Nobuyoshi; Takeshita, Fumitaka; Fujiwara, Tomohiro; Kawai, Akira; Ito, Hisao; Ochiya, Takahiro; Okada, Futoshi

    2016-05-01

    Despite recent improvements in the therapy for osteosarcoma, 30-40% of osteosarcoma patients die of this disease, mainly due to its lung metastasis. We have previously reported that intravenous injection of miR-143 significantly suppresses lung metastasis of human osteosarcoma cells (143B) in a mouse model. In this study, we examined the biological role and mechanism of miR-143 in the metastasis of human osteosarcoma cells. We identified plasminogen activator inhibitor-1 (PAI-1) as a direct target gene of miR-143. To determine the role of PAI-1 in human osteosarcoma cells, siRNA was transfected into 143B cells for knockdown of PAI-1 expression. An in vitro study showed that downregulation of PAI-1 suppressed cell invasion activity, but not proliferation. Moreover, injection of PAI-1 siRNA into a primary lesion in the osteosarcoma mouse model inhibited lung metastasis compared to control siRNA-injected mice, without influencing the proliferative activity of the tumor cells. Subsequent examination using 143B cells revealed that knockdown of PAI-1 expression resulted in downregulation of the expression and secretion of matrix metalloproteinase-13 (MMP-13), which is also a target gene of miR-143 and a proteolytic enzyme that regulates tumor-induced osteolysis. Immunohistochemical analysis using clinical samples showed that higher miR-143 expressing cases showed poor expression of PAI-1 in the primary tumor cells. All such cases belonged to the lung metastasis-negative group. Moreover, the frequency of lung metastasis-positive cases was significantly higher in PAI-1 and MMP-13 double-positive cases than in PAI-1 or MMP-13 single-positive or double-negative cases (P target gene of miR-143, regulates invasion and lung metastasis via enhancement of MMP-13 expression and secretion in human osteosarcoma cells, suggesting that these molecules could be potential therapeutic target genes for preventing lung metastasis in osteosarcoma patients. © 2016 The Authors. Cancer

  14. Osteosarcoma primario del corazón

    Directory of Open Access Journals (Sweden)

    Benito Serrano Gomez

    1986-07-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Lirong Zhang

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    NARCIS (Netherlands)

    Peterse, E.F.P.

    2018-01-01

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

  19. Prediction of post-operative pulmonary function after lobectomy for primary lung cancer: A comparison among counting method, effective lobar volume, and lobar collapsibility using inspiratory/expiratory CT

    Energy Technology Data Exchange (ETDEWEB)

    Yabuuchi, Hidetake, E-mail: h-yabu@med.kyushu-u.ac.jp [Department of Health Sciences, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Kawanami, Satoshi, E-mail: kawanami_01@mac.com [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Kamitani, Takeshi, E-mail: kamitani@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Yonezawa, Masato, E-mail: ymasato@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Yamasaki, Yuzo, E-mail: yyama@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Yamanouchi, Torahiko, E-mail: tora0228jp@yahoo.co.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Nagao, Michinobu, E-mail: minagao@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Okamoto, Tatsuro, E-mail: tatsuro@surg2.med.kyushu-u.ac.jp [Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan); Honda, Hiroshi, E-mail: honda@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences, Fukuoka (Japan)

    2016-11-15

    Highlights: • ΔFEV{sub 1.0} and ppoΔFEV{sub 1.0} using lobar collapsibility were strongly correlated. • ΔVC and ppoΔVC using effective lobar volume were strongly correlated. • Counting method was inferior to lobar collapsibility for prediction of ppoFEV{sub 1.0}. • Inspiratory/expiratory CT is useful to predict post-operative pulmonary function. - Abstract: Purpose: To compare the predictabilities of postoperative pulmonary function after lobectomy for primary lung cancer among counting method, effective lobar volume, and lobar collapsibility. Methods: Forty-nine patients who underwent lobectomy for primary lung cancer were enrolled. All patients underwent inspiratory/expiratory CT and pulmonary function tests 2 weeks before surgery and postoperative pulmonary function tests 6–7 months after surgery. Pulmonary function losses (ΔFEV{sub 1.0} and ΔVC) were calculated from the pulmonary function tests. Predictive postoperative pulmonary function losses (ppoΔFEV{sub 1.0} and ppoΔVC) were calculated using counting method, effective volume, and lobar collapsibility. Correlations and agreements between ΔFEV{sub 1.0} and ppoFEV{sub 1.0} and those between ΔVC and ppoΔVC were tested among three methods using Spearman’s correlation coefficient and Bland-Altman plots. Results: ΔFEV{sub 1.0} and ppoΔFEV{sub 1.0insp-exp} were strongly correlated (r = 0.72), whereas ΔFEV{sub 1.0} and ppoΔFEV{sub 1.0count} and ΔFEV{sub 1.0} and Pred. ΔFEV{sub 1.0eff.vol.} were moderately correlated (r = 0.50, 0.56). ΔVC and ppoΔVC{sub eff.vol.} (r = 0.71) were strongly correlated, whereas ΔVC and ppoΔVC{sub count}, and ΔVC and ppoΔVC {sub insp-exp} were moderately correlated (r = 0.55, 0.42). Conclusions: Volumetry from inspiratory/expiratory CT data could be useful to predict postoperative pulmonary function after lobectomy for primary lung cancer.

  20. Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres.

    Science.gov (United States)

    Chang, Run; Sun, Linlin; Webster, Thomas J

    2015-01-01

    Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane) has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs) with diameters of 10-20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective cytotoxicity against MG-63 osteosarcoma cells when compared with normal osteoblasts. We have demonstrated for the first time that APNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and curcumin-loaded APNPs could be an innovative treatment

  1. p16(INK4A) inhibits the pro-metastatic potentials of osteosarcoma cells through targeting the ERK pathway and TGF-β1.

    Science.gov (United States)

    Silva, Gabriela; Aboussekhra, Abdelilah

    2016-05-01

    Extracellular signal-regulated kinase (ERK) is a downstream component of the evolutionarily conserved mitogen-activated protein kinase-signaling pathway, which controls the expression of a plethora of genes implicated in various physiological processes. This pathway is often hyper-activated by mutations or abnormal extracellular signaling in different types of human cancer, including the most common primary malignant bone tumor osteosarcomas. p16(INK4A) is an important tumor suppressor gene frequently lost in osteosarcomas, and is associated with the progression of these malignancies. We have shown, here, that the ERK1/2 protein kinase is also activated by p16(INK4A) down-regulation in osteosarcoma cells and normal human as well as mouse cells. This inhibitory effect is associated with the suppression of the upstream kinase MEK1/2, and is mediated via the repression of miR-21-5p and the consequent up-regulation of the MEK/ERK antagonist SPRY2 in osteosarcoma cells. Furthermore, we have shown that p16(INK4) inhibits the migration/invasion abilities of these cells through miR-21-5p-dependent inhibition of ERK1/2. In addition, we present clear evidence that p16(INK4) represses the paracrine pro-migratory effect of osteosarcoma cells on stromal fibroblasts through the inhibition of the TGF-β1 expression/secretion. This effect is also ERK1/2-dependent, indicating that in addition to their cell-autonomous actions, p16(INK4) and ERK1/2 have also non-cell-autonomous cancer-related functions. Together, these results indicate that the tumor suppressor p16(INK4) protein represses the carcinogenic process of osteosarcoma cells not only as a cell cycle regulator, but also as a negative regulator of pro-carcinogenic/-metastatic pathways. This indicates that targeting the ERK pathway is of utmost therapeutic value. © 2015 Wiley Periodicals, Inc.

  2. Effectiveness of computerized clinical decision support systems for asthma and chronic obstructive pulmonary disease in primary care: a systematic review.

    Science.gov (United States)

    Fathima, Mariam; Peiris, David; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol Lyn

    2014-12-02

    The use of computerized clinical decision support systems may improve the diagnosis and ongoing management of chronic diseases, which requires recurrent visits to multiple health professionals, disease and medication monitoring and modification of patient behavior. The aim of this review was to systematically review randomized controlled trials evaluating the effectiveness of computerized clinical decision systems (CCDSS) in the care of people with asthma and COPD. Randomized controlled trials published between 2003 and 2013 were searched using multiple electronic databases Medline, EMBASE, CINAHL, IPA, Informit, PsychINFO, Compendex, and Cochrane Clinical Controlled Trials Register databases. To be included, RCTs had to evaluate the role of the CCDSSs for asthma and/or COPD in primary care. Nineteen studies representing 16 RCTs met our inclusion criteria. The majority of the trials were conducted in patients with asthma. Study quality was generally high. Meta-analysis was not conducted because of methodological and clinical heterogeneity. The use of CCDSS improved asthma and COPD care in 14 of the 19 studies reviewed (74%). Nine of the nineteen studies showed statistically significant (p < 0.05) improvement in the primary outcomes measured. The majority of the studies evaluated health care process measures as their primary outcomes (10/19). Evidence supports the effectiveness of CCDSS in the care of people with asthma. However there is very little information of its use in COPD care. Although there is considerable improvement in the health care process measures and clinical outcomes through the use of CCDSSs, its effects on user workload and efficiency, safety, costs of care, provider and patient satisfaction remain understudied.

  3. Pulmonary Hypertension and Pulmonary Vasodilators.

    Science.gov (United States)

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    Science.gov (United States)

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

  5. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

  6. Osteosarcoma of the spheno-temporo-orbital bone: Imaging aspects of such unusual location

    Directory of Open Access Journals (Sweden)

    ABDEL ILAH RAYAN ALAOUI BOUARRAQUI

    2018-05-01

    Full Text Available Osteosarcoma of the spheno-temporo-orbital bone is a very rare tumor. Despite the fact that primary osteogenic sarcomas are the most common bone neoplasm, their location in the skull bone is uncommon representing less than 2% of all skull tumors. We report the case of a 41-year-old woman, who has experienced periorbital pain with exophthalmos and left eye vision loss. Neuroimaging analysis including both brain computed tomography (CT-scan and Magnetic resonance imaging (MRI were performed. Although radiographic features of skull bone osteosarcomas are not specific, the combination of several radiographic features could lead to this diagnosis in such rare location. The final diagnosis was established by a trans-temporal biopsy with immunohistochemical study. Neurosurgical resection of the primary tumor was not possible given the important extent of the tumor and the involvement of adjacent structures, so the patient underwent conformational radiotherapy. The evolution was marked by local and metastatic progression. The patient received palliative chemotherapy and died few months later. The purpose of presenting this case is not only to report an uncommon malignancy of the skull bone, but also to provide imaging aspects of this rare location and to raise awareness among radiologists in order to consider this radiological entity as a differential diagnosis when a skull bone process is identified.

  7. Genomic instability and telomere fusion of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available Canine osteosarcoma (OSA is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

  8. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiguang Tian

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

  11. 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.)

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

    Science.gov (United States)

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

    2002-01-01

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

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  14. High-grade surface osteosarcoma of the hand

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  16. Primary bone neoplasms in dogs: 90 cases

    Directory of Open Access Journals (Sweden)

    Maria E. Trost

    2012-12-01

    Full Text Available A retrospective study of necropsy and biopsy cases of 90 primary bone tumors (89 malignant and one benign in dogs received over a period of 22 years at the Laboratório de Patologia Veterinária, Universidade Federal de Santa Maria, was performed. Osteosarcoma was the most prevalent bone tumor, accounting for 86.7% of all malignant primary bone neoplasms diagnosed. Most cases occurred in dogs of large and giant breeds with ages between 6 and 10-years-old. The neoplasms involved mainly the appendicular skeleton, and were 3.5 times more prevalent in the forelimbs than in the hindlimbs. Osteoblastic osteosarcoma was the predominant histological subtype. Epidemiological and pathological findings of osteosarcomas are reported and discussed.

  17. Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2017-11-01

    Full Text Available Background/Aims: Osteosarcoma (OS is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. Methods: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. Results: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. Conclusion: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

  18. 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.

  19. Angiographic evaluation of response to preoperative chemotherapy in osteosarcoma

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  20. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cappadone, C., E-mail: concettina.cappadone@unibo.it [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Stefanelli, C. [Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini (Italy); Malucelli, E. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Zini, M. [Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy); Onofrillo, C. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Locatelli, A.; Rambaldi, M.; Sargenti, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Merolle, L. [ELETTRA–Sincrotrone Trieste S.C.p.A., Trieste (Italy); Farruggia, G. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy); Graziadio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Montanaro, L. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy)

    2015-11-13

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  1. Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma.

    Science.gov (United States)

    Meyer, F R L; Steinborn, R; Grausgruber, H; Wolfesberger, B; Walter, I

    2015-10-01

    The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    International Nuclear Information System (INIS)

    Cappadone, C.; Stefanelli, C.; Malucelli, E.; Zini, M.; Onofrillo, C.; Locatelli, A.; Rambaldi, M.; Sargenti, A.; Merolle, L.; Farruggia, G.; Graziadio, A.; Montanaro, L.; Iotti, S.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  3. Digital angiography in pulmonary embolism

    International Nuclear Information System (INIS)

    Bjoerk, L.

    1986-01-01

    Pulmonary digital subtraction angiography was diagnostic in 98.3% of patients with possible acute pulmonary embolism. The procedure was well tolerated even in severely ill patients. A large image intensifier made simultaneous imaging of both lungs possible reducing the number of contrast injections necessary. Small volumes of low iso-osmolar concentration of modern contrast media were used. There was no need for catherization of the pulmonary artery. Theoretical considerations and our limited experience indicate that this will reduce the number of complications compared with conventional pulmonary angiography. The procedure is rapidly performed and the diagnostic accuracy high. This makes digital subtraction angiography cost effective. Digital pulmonary angiography can be recommended as the primary diagnostic method in most patients with possible pulmonary embolism. (orig.)

  4. Detection of alkaline phosphatase in canine cells previously stained with Wright-Giemsa and its utility in differentiating osteosarcoma from other mesenchymal tumors.

    Science.gov (United States)

    Ryseff, Julia K; Bohn, Andrea A

    2012-09-01

    Osteosarcoma (OSA) is a common primary bone tumor in dogs. Demonstration of alkaline phosphatase (ALP) reactivity by tumor cells on unstained slides is useful in differentiating osteosarcoma from other types of sarcoma. However, unstained slides are not always available. The objectives of this study were to evaluate the diagnostic utility of detecting ALP expression in differentiating osteosarcoma from other sarcomas in dogs using cytologic material previously stained with Wright-Giemsa stain and to assess the sensitivity and specificity of ALP expression for diagnosing osteosarcoma using a specific protocol. Archived aspirates of histologically confirmed sarcomas in dogs that had been previously stained with Wright-Giemsa stain were treated with 5-bromo, 4-chloro, 3-indolyl phosphate/nitroblue tetrazolium (BCIP/NBT) as a substrate for ALP. Cells were evaluated for expression of ALP after incubation with BCIP/NBT for 1 hour. Sensitivity and specificity of ALP expression for diagnosis of OSA were calculated. In samples from 83 dogs, cells from 15/17 OSAs and from 4/66 tumors other than OSA (amelanotic melanoma, gastrointestinal stromal tumor, collision tumor, and anaplastic sarcoma) expressed ALP. Sensitivity and specificity of ALP expression detected using BCIP/NBT substrate applied to cells previously stained with Wright-Giemsa stain for OSA were 88 and 94%, respectively. ALP expression detected using BCIP/NBT substrate applied to previously stained cells is useful in differentiating canine OSA from other mesenchymal neoplasms. © 2012 American Society for Veterinary Clinical Pathology.

  5. Strengthening the delivery of asthma and chronic obstructive pulmonary disease care at primary health-care facilities: study design of a cluster randomized controlled trial in Pakistan

    Directory of Open Access Journals (Sweden)

    Muhammad Amir Khan

    2015-11-01

    Full Text Available Background: Respiratory diseases, namely asthma and chronic obstructive pulmonary disease (COPD, account for one-fourth of the patients at the primary health-care (PHC facilities in Pakistan. Standard care practices to manage these diseases are necessary to reduce the morbidity and mortality rate associated with non-communicable diseases in developing countries. Objective: To develop and measure the effectiveness of operational guidelines and implementation materials, with sound scientific evidence, for expanding lung health care, especially asthma and COPD through PHC facilities already strengthened for tuberculosis (TB care in Pakistan. Design: A cluster randomized controlled trial with two arms (intervention and control, with qualitative and costing study components, is being conducted in 34 clusters; 17 clusters per arm (428 asthma and 306 COPD patients, in three districts in Pakistan from October 2014 to December 2016. The intervention consists of enhanced case management of asthma and COPD patients through strengthening of PHC facilities. The main outcomes to be measured are asthma and COPD control among the registered cases at 6 months. Cluster- and individual-level analyses will be done according to intention to treat. Residual confounding will be addressed by multivariable logistic and linear regression models for asthma and COPD control, respectively. The trial is registered with ISRCTN registry (ISRCTN 17409338. Conclusions: Currently, only about 20% of the estimated prevalent asthma and COPD cases are being identified and reported through the respective PHC network. Lung health care and prevention has not been effectively integrated into the core PHC package, although a very well-functioning TB program exists at the PHC level. Inclusion of these diseases in the already existent TB program is expected to increase detection rates and care for asthma and COPD.

  6. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

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

    Science.gov (United States)

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

    2017-09-01

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

  8. Osteosarcoma: Accelerating Progress Makes for a Hopeful Future

    Directory of Open Access Journals (Sweden)

    Amanda J. Saraf

    2018-01-01

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

  9. Osteoblastoma-like osteosarcoma of the distal tibia

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-03-01

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

  10. Osteoblastoma-like osteosarcoma of the distal tibia

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  11. Aberrant tropoelastin secretion in MG-63 human osteosarcoma cells

    International Nuclear Information System (INIS)

    Curtiss, S.W.

    1989-01-01

    The secretion of newly synthesized tropoelastin, the soluble precursor of the extracellular matrix protein elastin, is not well understood. MG-63 human osteosarcoma cells were found by immunoblot analysis to synthesize 62 kD and 64 kD tropoelastins. Media from 63 cells labelled for five hours with [ 3 H]-valine contain no detectable tropoelastin, unlike media from other tropoelastin-synthesizing cells. Immunoblots of conditioned media and 1Ox-concentrated conditioned media left on the cells for six days also show an absence of tropoelastin from the cell media. No insoluble elastin is associated with the cell layer, as determined by amino acid analysis and electron microscopy of 18-21 day cell cultures. The absence of tropoelastin from the cell medium and elastin from the extracellular matrix indicates that MG63 cells do not secrete tropoelastin as expected, but accumulate it intracellularly. This accumulation is transient: immunoblots and immunofluorescence microscopy show that cells three days after passage have the highest steady-state levels of tropoelastin per cell, that day 8 cells contain lower but still significant amounts of tropoelastin, and that by day 22 tropoelastin is no longer present in the cell cultures. Cell density is a critical factor in the observed pattern of tropoelastin expression. Cells seeded at ten fold their usual initial density have high tropoelastin levels at one day after passage, sooner than cells seeded normally. Tropoelastin also disappears from high density-seeded cells more quickly and is no longer detectable at day 10. Lysosome-like vesicles containing membranous structures appear by immunoelectron microscopy to be the primary site of intracellular tropoelastin localization

  12. Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Jian, Yuekui; Chen, Changqiong; Li, Bo; Tian, Xiaobin, E-mail: drtxb_guiyang@sina.com

    2015-10-23

    Tight junction proteins (TJPs) including Claudins, Occludin and tight junction associated protein Zonula occludens-1 (ZO-1), are the most apical component of junctional complex that mediates cell–cell adhesion in epithelial and endothelial cells. In human malignancies, TJPs are often deregulated and affect cellular behaviors of tumor cells. In this study, we investigated alternations of TJPs and related biological characteristics in human osteosarcoma (OS). Claudin1 was increased in the metastatic OS cells (KRIB and KHOS) compared with the normal osteoblast cells (hFOB1.19) or primary tumor cells (HOS and U2OS), whereas no significant difference was found in Occludin and ZO-1. Immunohistochemistry, immunofluorescence and Western blotting revealed that Claudin1 was initially localized at cell junctions of normal osteoblasts, but substantially delocalized to the nucleus of metastatic OS cells. Phenotypically, inhibition of the nucleus Claudin1 expression compromised the metastatic potential of KRIB and KHOS cells. Moreover, we found that protein kinase C (PKC) but not PKA phosphorylation influenced Claudin1 expression and cellular functions, as PKC inhibitor (Go 6983 and Staurosporine) or genetic silencing of PKC reduced Claudin1 expression and decreased the motility of KRIB and KHOS cells. Taken together, our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. - Highlights: • Claudin1 is increased during the malignant transformation of human OS. • Delocalization of Claudin1 in metastatic OS cells. • Silencing nuclear Claudin1 expression inhibits cell invasion of OS. • Deregulated Claudin1 is regulated by PKC.

  13. Acute exacerbation of subclinical idiopathic pulmonary fibrosis triggered by hypofractionated stereotactic body radiotherapy in a patient with primary lung cancer and slightly focal honeycombing

    International Nuclear Information System (INIS)

    Takeda, Atsuya; Sanuki, Naoko; Enomoto, Tatsuji; Takeda, Toshiaki; Kunieda, Etsuo; Nakajima, Takeshi; Sayama, Koichi

    2008-01-01

    Hypofractionated stereotactic body radiotherapy (SBRT) for pulmonary lesions provides a high local control rate, allows completely painless ambulatory treatment, and is not associated with adverse reactions in most cases. Here we report a 70-year-old lung cancer patient with slight focal pulmonary honeycombing in whom subclinical idiopathic pulmonary fibrosis was exacerbated by SBRT. This experience has important implications for the development of selection criteria prior to SBRT for pulmonary lesions. For SBRT candidates with lung tumors, attention must be paid to the presence of co-morbid interstitial pneumonia even if findings are minimal. Such patients must be informed of potential risks, and careful decision-making must take place when SBRT is being considered. (author)

  14. 17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines.

    Science.gov (United States)

    Massimini, M; Palmieri, C; De Maria, R; Romanucci, M; Malatesta, D; De Martinis, M; Maniscalco, L; Ciccarelli, A; Ginaldi, L; Buracco, P; Bongiovanni, L; Della Salda, L

    2017-05-01

    Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 μM, 1 μM) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy, and mitophagy were assessed by transmission electron microscopy, flow cytometry, and immunofluorescence. A simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

  15. Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.

    Science.gov (United States)

    Zarcone, Maria C; van Schadewijk, Annemarie; Duistermaat, Evert; Hiemstra, Pieter S; Kooter, Ingeborg M

    2017-01-28

    Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied. Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5). PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation. ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air. Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression. DE alone induced an increase in markers of oxidative stress (HMOX1, 50-100-fold) and of the integrated stress response (CHOP, 1.5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls. Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold). Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP. Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls. Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response. DE reduced the NTHi-induced expression of S100A7. These data suggest that DE exposure may cause adverse health effects in part by

  16. Pulmonary agenesis

    OpenAIRE

    Oyola, Mercedes; Pontificia Universidad Javeriana; Gordillo, Gisel; Pontificia Universidad Javeriana; García, Carlos A.; Pontificia Universidad Javeriana; Torres, David; Pontificia Universidad Javeriana

    2009-01-01

    Pulmonary agenesis is an infrequent pathology which occurs predominantly among females with no lateral preference. We report on the case of a newborn male diagnosed with prenatal diaphragm hernia though at birth seemed more likely either to be a congenital cystic adenomatoid malformation (congenital pulmonary airway malformation) or pulmonary agenesis. The patient died six days after birth and necropsy confirmed pulmonary agenesis. La agenesia pulmonar es una alteración poco frecuente, con...

  17. Tuberculosis pulmonar y tabaquismo en la Atención Primaria de Salud Pulmonary tuberculosis and Smoking in Primary Health Care

    Directory of Open Access Journals (Sweden)

    Margarita González Tapia

    2012-10-01

    descriptive, cross-sectional study was carried out from January 2010 to December 2011 in Pinar del Rio municipality. The target group involved the total of patients having the diagnosis of pulmonary tuberculosis in Pinar del Rio municipality during 2010-2011. The sample was comprised of 45 patients. Clinical charts of patients, epidemiological surveys recorded in the Statistics Department of the "Municipal Hygiene and Epidemiology Unit" in Pinar del Rio were reviewed. A survey that constituted the primary source of information was applied which included qualitative and quantitative variables. Results: the most affected group of ages was from 25-59 years old, prevailing male sex. Predominant symptoms included cough and expectoration for more than 14 days. All of the cases were new, 9 of them smokers; observing a delay in the disappearance of symptoms for these patients. Conclusions: knowledge of tuberculosis behavior and its association with smoking should be increased in Pinar del Rio municipality.

  18. Self-management behaviour and support among primary care COPD patients: cross-sectional analysis of data from the Birmingham Chronic Obstructive Pulmonary Disease Cohort.

    Science.gov (United States)

    Khan, Ainee; Dickens, Andrew P; Adab, Peymane; Jordan, Rachel E

    2017-07-20

    Self-management support for chronic obstructive pulmonary disease (COPD) patients is recommended by UK national guidelines, but extent of implementation is unknown. We aimed to describe self-management behaviour and support among COPD patients and explore behaviour associated with having a self-management plan. We undertook cross-sectional analysis of self-reported data from diagnosed COPD patients in the Birmingham COPD Cohort study. Questionnaire items relevant to self-management behaviour, knowledge of COPD, receipt of self-management plans and advice from healthcare professionals were examined. Multiple regression models were used to identify behaviour associated with having a self-management plan. One-thousand seventy-eight participants (676 males, 62.7%, mean age 69.8 (standard deviation 9.0) years) were included. The majority reported taking medications as instructed (940, 94.0%) and receiving annual influenza vaccinations (962, 89.2%). Only 400 (40.4%) participants had self-management plans, 538 (49.9%) reported never having received advice on diet/exercise and 110 (42.7%) current smokers had been offered practical help to stop smoking in the previous year. General knowledge about COPD was moderate (mean total Bristol COPD Knowledge Questionnaire score: 31.5 (standard deviation 10.7); max score 65), corresponding to 48.5% of questions answered correctly. Having a self-management plan was positively associated with self-reported adherence to medication (odds ratio 3.10, 95% confidence interval 1.43 to 6.72), attendance at a training course (odds ratio 2.72, 95% confidence interval 1.81 to 4.12), attendance at a support group (odds ratio 6.28, 95% confidence interval 2.96 to 13.35) and better disease knowledge (mean difference 4.87, 95% confidence interval 3.16 to 6.58). Primary care healthcare professionals should ensure more widespread implementation of individualised self-management plans for all patients and improve the lifestyle advice provided. CALL FOR

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

    Directory of Open Access Journals (Sweden)

    Ju Hyun Ahn

    2015-09-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    African Journals Online (AJOL)

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

  2. Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

    Directory of Open Access Journals (Sweden)

    Chang R

    2015-05-01

    Full Text Available Run Chang,1 Linlin Sun,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective

  3. The lncRNA PCAT1 is correlated with poor prognosis and promotes cell proliferation, invasion, migration and EMT in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Zhang X

    2018-01-01

    Full Text Available Xuedong Zhang,1,2 Yakui Zhang,2 Yong Mao,2 Xinlong Ma1 1Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 2Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China Introduction: Osteosarcoma is a malignant primary bone cancer and is lethal to children and adolescents. Recently, the dysregulation of long noncoding RNAs (lncRNAs has been shown in various types of cancers.Aim: The present study aimed to examine the role of the lncRNA prostate cancer-associated transcript 1 (PCAT1 in osteosarcoma progression.Materials and methods: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time polymerase chain reaction. Cell proliferation, invasion and migration were examined by CCK-8 assay, transwell invasion and migration assay, respectively. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by Western blot.Results: Our results showed that PCAT1 was upregulated in osteosarcoma tissues when compared to normal bone tissues. PCAT1 was also upregulated in osteosarcoma cell lines when compared to normal bone cell line. The upregulation of PCAT1 was significantly associated with advanced clinical stage, tumor metastasis and shorter overall survival in patients with osteosarcoma. In vitro studies showed that overexpression of PCAT1 in MG-63 cells enhanced cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT; decreased cell apoptotic rate; and also caused an increase in cell population at S phase with a decrease in cell population at G0/G1 phase. Knockdown of PCAT1 in U2OS cells suppressed cell proliferation, cell invasion and migration, and EMT; increased cell apoptotic rate; and caused an increase in the cell population at G0/G1 phase with a decrease in cell population at S phase.Conclusion: Taken together, our results suggest the

  4. Bioinformatics prediction of miR-30a targets and its inhibition of cell proliferation of osteosarcoma by up-regulating the expression of PTEN

    Directory of Open Access Journals (Sweden)

    Biao Zhong

    2017-11-01

    Full Text Available Abstract Background MiRNAs are frequently abnormally expressed in the progression of human osteosarcoma. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN is one of the tumor suppressors in various types of human cancer. In the present study, we detected how hsa-miR-30a-3p regulated PTEN and further tested the role of hsa-miR-30a-3p in the cell proliferation of osteosarcoma cells. Methods The levels of miR-30a were determined by real time PCR. The expression of PTEN was tested by western blotting analysis. Cell distribution of PTEN was observed with confocal laser scanning microscope. Cell viability was determined by MTT assay. Results The expression of miR-30a and PTEN was obviously decreased in MG-63, 143B and Saos-2 cells compared with primary osteoblasts. TargetScan analysis data showed miR-30a might bind with position 30-57 of 3’UTR of PTEN. Transfection with miR-30a-3p increased the level of PTEN in MG-63 cells, while transfection with miR-30a-3p inhibitor significantly decreased the expression of PTEN in osteosarcoma cells. Transfection with miR-30a-3p significantly inhibited cell proliferation of osteosarcoma cells, while miR-30a inhibitor obviously promoted cell viability of MG63 cells and Saos-2 cells. Inhibition of PTEN eliminated the proliferation inhibitory effect of miR-30a-3p. Conclusion Thus, all these findings revealed the anti-tumor effects of miR-30a in human osteosarcoma cells, which could be mediated by regulating the level of PTEN.

  5. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8.

    Science.gov (United States)

    Nakamura, Atsushi; Aizawa, Junichi; Sakayama, Kenshi; Kidani, Teruki; Takata, Tomoyo; Norimatsu, Yoshiaki; Miura, Hiromasa; Masuno, Hiroshi

    2012-09-26

    One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine (BrdU) incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E). The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells. Treatment of LM8 cells with genistein induced morphological

  6. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8

    Directory of Open Access Journals (Sweden)

    Nakamura Atsushi

    2012-09-01

    Full Text Available Abstract Background One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. Methods LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2’-deoxyuridine (BrdU incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E. The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR. Results Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells

  7. Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

    International Nuclear Information System (INIS)

    Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

    1984-01-01

    The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries

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

    Science.gov (United States)

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

    2016-07-01

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

  9. Preliminary studies of pulmonary perfusion scanning in patients with pulmonary hypertension

    International Nuclear Information System (INIS)

    Shi Rongfang; Liu Xiujie; Wang Yanqun

    1986-01-01

    A comparative analysis of pulmonary perfusion scanning through cardiac catheterization of 57 patients including 32 patients with congenital heart disease, 8 patients with chronic pulmonary thromboembolism and 7 patients with primary pulmonary hypertension is reported. The lung scintigram obtained with In-113m or Tc-99m-MAA represents the distribution of pulmonary blood. It has been found that the lung scintigram was abnormal in patients of congenital heart disease with pulmonary hypertension (i. e. pulmonary artery pressure between 41-80 mmHg) and the extent of radoiactive regional defects is proportional to the level of pulmonary hypertension. The results of the analysis indicated that pulmonary perfusion scanning being a noninvasive technique would be a useful method in evaluating the level of pulmonary hypertension in patients with left to right shunt before and after surgical operation

  10. Chronicle pulmonary histoplasmosis

    International Nuclear Information System (INIS)

    Llanos, Elkin; Ojeda, Paulina

    2004-01-01

    Histoplasmosis is an acquired mycotic disease produced by the histoplasma capsulatum very frequent in Colombia, primarily affecting lungs. The pathogenesis of the histoplasmosis is similar to the one of tuberculosis. From the clinical point of view, this disease has several manifestations including the primary acute and chronic pulmonary forms. Histoplasmoma pulmonary disseminated histoplasmosis, mediastinal compromise due to granulomatosis and fibrosis, as well as ocular histoplasmosis. A clinical case of a 33-year old man is presented who consults for dry coughing of one year of evolution, without any other symptomatology, with a normal chest x-ray and after several studies including chest cat and fiber-bronchoscopy. A pulmonary histoplasmosis was determined by histopathology

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sudheerkanth Kondamari Peddana

    2017-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  14. Femoral mesenchymal chondrosarcoma with secondary aneurysmal bone cysts mimicking a small-cell osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Amukotuwa, Shalini A. [St. Vincent' s Hospital, Melbourne (Australia); Choong, Peter F.M.; Powell, Gerard J. [St. Vincent' s Hospital, Department of Orthopaedics, Melbourne (Australia); Smith, Peter J.; Schlicht, Stephen M. [St. Vincent' s Hospital, Department of Medical Imaging, Melbourne (Australia); Thomas, David [Peter MacCallum Cancer Centre, Ian Potter Centre for Cancer Genomics and Predictive Medicine, Melbourne (Australia)

    2006-05-15

    Mesenchymal chondrosarcoma is a rare but aggressive, high-grade malignancy of primitive cartilage-forming mesenchyme that arises most commonly from skeletal sites. Although there are radiological findings suggestive of the diagnosis, imaging features often overlap with those of other skeletal sarcomas. The definitive diagnosis relies on the histological finding of a typical bimorphic appearance, consisting of nests of small, round, poorly differentiated cells and more mature cartilaginous tissue. To highlight this, we present the case of a 21-year-old man who was referred to our institution with a history of right knee pain. Initial imaging and histological evaluation of a core biopsy of the lesion suggested osteosarcoma of the distal right femur; after review, however, the correct diagnosis of mesenchymal chondrosarcoma was made. Adequate tissue sampling and thorough histological evaluation of biopsy specimens is vital for the accurate diagnosis of primary bone malignancies, especially those of chondroid origin. (orig.)

  15. A Case Report of Osteosarcoma of the Mandible as Peripheral Tumor Like Lesion

    Directory of Open Access Journals (Sweden)

    H.R. Abdolsamadi

    2014-04-01

    Full Text Available Introduction: Osteosarcoma(OS is primary malignant bone tumor in which mesenchymal cell produce osteoid. OS of jawbones is uncommon, representing 4-8% of all OS. Case Report: This paper reports the case of a- 29 year-old female with an OS in mandibular first molar as exophitic lesion with smooth surface during 1 year. Based on the patient's symptoms, differential diagnosis was lymphoma and malignant meshenshymal tumors. Exci-sional biopsy was done and histopatholigic feature proved to be OS. Conclusion: Postoperatively, the patient was referred to the oncology department of Tehran Imam Khomeini hospital for further evaluation and treatment. (Sci J Hamadan Univ Med Sci 2014; 21 (1:80-84

  16. Lung cancer, analysis of the most frequent tomographic findings and histopathological correlation, in patients with primary pulmonary neoplasia diagnosed during the years 2011 and 2012, at the Hospital San Juan de Dios

    International Nuclear Information System (INIS)

    Cruz Romero, Cinthia

    2013-01-01

    Tomographic images, specifically the contrasted chest tomographies, were examined in patients diagnosed in patients diagnosed with lung cancer at the Hospital San Juan de Dios during the years 2011 and 2012. The primitive tomographic behavior of lung cancer was evaluated in order to determine and characterize its presentation pattern. Each histological type of lung cancer was determined. The stage of lung cancer was classified according to the International System of Staging Tumor, Node and Metastasis. An analysis of the incidence and stage of lung cancer at the time of diagnosis was made, evidencing the fundamental role of chest tomography in the screening, diagnosis, management and control of patients with primary pulmonary neoplasia [es

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

    Directory of Open Access Journals (Sweden)

    Tang Liu

    2018-04-01

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

  18. Primary bone tumours in infants

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

    1985-09-01

    Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

  19. Pulmonary atresia

    Science.gov (United States)

    ... another type of congenital heart defect called a patent ductus arteriosus (PDA). Pulmonary atresia may occur with ... known way to prevent this condition. All pregnant women should get routine prenatal care. Many congenital defects ...

  20. Pulmonary Embolism

    Science.gov (United States)

    ... increase the risk for PE, such as: Being bedridden or unable to move around much Having surgery ... of pulmonary embolism (PE) include unexplained shortness of breath, problems breathing, chest pain, coughing , or coughing up ...

  1. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA. Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17 expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

  2. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

    Science.gov (United States)

    Shahi, Mehdi Hayat; York, Daniel; Gandour-Edwards, Regina; Withers, Sita S; Holt, Roseline; Rebhun, Robert B

    2015-01-01

    BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

  3. Ipsilateral vascularised ulnar transposition autograft for limb-sparing surgery of the distal radius in 2 dogs with osteosarcoma : clinical communication

    Directory of Open Access Journals (Sweden)

    G.S. Irvine-Smith

    2006-06-01

    Full Text Available Canine osteosarcoma is the most commonly diagnosed primary bone tumour in the dog, affecting mainly large and giant breed dogs with the predilection site being the metaphysis of long bones, specifically the distal radius, proximal humerus, distal femur and proximal tibia and fibula. Treatment options are either palliative or curative intent therapy, the latter limb amputation or limb-sparing surgery together with chemotherapy. This article describes the use of an ipsilateral vascularised ulnar transposition autograft as well as chemotherapy in 2 dogs with osteosarcoma of the distal radius. Both dogs showed minimal complications with the technique and both survived over 381 days following the surgery. Complications seen were loosening of the screws and osteomyelitis. The procedure was well tolerated with excellent limb use. This technique is indicated for use in cases with small tumour size that have not broken through the bone cortex.

  4. 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.

  5. Small cell extraskeletal osteosarcoma: a rare case report

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

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

    Science.gov (United States)

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

    2008-07-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  9. Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma

    International Nuclear Information System (INIS)

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

    2002-01-01

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

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

    International Nuclear Information System (INIS)

    Fawzy, A.

    2005-01-01

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

  11. CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Taslakian, Bedros, E-mail: bedros.taslakian@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Latson, Larry A., E-mail: larry.latson@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Truong, Mylene T., E-mail: mtruong@mdanderson.org [Department of Radiology, University of Texas, MD Anderson Cancer Center, TX (United States); Aaltonen, Eric, E-mail: Eric.Aaltonen@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Shiau, Maria C., E-mail: Maria.Shiau@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Girvin, Francis, E-mail: Francis.Girvin@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Alpert, Jeffrey B., E-mail: Jeffrey.Alpert@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Wickstrom, Maj, E-mail: Maj.Wickstrom@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Ko, Jane P., E-mail: Jane.Ko@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States)

    2016-11-15

    Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

  12. CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

    International Nuclear Information System (INIS)

    Taslakian, Bedros; Latson, Larry A.; Truong, Mylene T.; Aaltonen, Eric; Shiau, Maria C.; Girvin, Francis; Alpert, Jeffrey B.; Wickstrom, Maj; Ko, Jane P.

    2016-01-01

    Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

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

    Science.gov (United States)

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

    2015-12-01

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

  14. Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  15. Piriformis syndrome caused by extraosseous osteosarcoma. Case report

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  16. Convolutional Neural Network for Histopathological Analysis of Osteosarcoma.

    Science.gov (United States)

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

    2018-03-01

    Pathologists often deal with high complexity and sometimes disagreement over osteosarcoma tumor classification due to cellular heterogeneity in the dataset. Segmentation and classification of histology tissue in H&E stained tumor image datasets is a challenging task because of intra-class variations, inter-class similarity, crowded context, and noisy data. In recent years, deep learning approaches have led to encouraging results in breast cancer and prostate cancer analysis. In this article, we propose convolutional neural network (CNN) as a tool to improve efficiency and accuracy of osteosarcoma tumor classification into tumor classes (viable tumor, necrosis) versus nontumor. The proposed CNN arc